Cancrum Oris: A Single Stage Correction of Ankylosis of Jaw and Cheek Fistula Defect

Abstract

A 55-year-old lady presented with trismus and full thickness oral defect exposing upper and lower row of teeth. This was a sequel of the cancrum oris that she had had in the childhood. The operative intervention consisted of radical excision of scar tissue, release of bony block of right temporo-mandibular joint ankylosis and the cheek fistula defect was corrected in two layers by bipaddled island pectoralis major myocutaneous flap. The correction of jaw ankylosis and the flap cover was done in a single stage and is presented in details.

INTRODUCTION

Cancrum oris is an acute gangrenous disease affecting the face. The condition usually affects young, poorly nourished children and occurs as a complication of measles and other childhood illnesses. Malnutrition is a predisposing factor and the presence of erupted teeth appears necessary for the onset.¹ It is also known as Noma (from the Greek meaning, "to devour"), which aptly describes the process which usually starts as a pustule on the buccal mucosa. The mortality in the acute phase is unknown. The patient usually presents with gross scarring which prevents movement of the mandible, leading on to secondary ankylosis of the jaw and often, there is a large oro-cutaneous fistula with varying degrees of destruction of soft tissue, cartilage and bony framework of face.

CASE REPORT

A 55-year old presented with a 5x4 cm oro-cutaneous fistula in the right cheek, exposing the upper and lower row of teeth (Fig.1 & 2). She had trismus with mouth opening of less than 3 mm. There was extensive scarring around the defect which she had since childhood. An orthopantomogram revealed ankylosis between the temporal bone and the condyle and coronoid process of the mandible. The anaemia was corrected by haematinics and diet counseling. After the pre-anaesthetic checkup, she was admitted for the corrective surgery.
At surgery under general anaesthesia, the dense scar tissue around the oral defect was excised. As the soft tissue release was not sufficient for the mouth opening, the temporo-mandibular area was accessed through the check fistula. The bony block was wide and deep and extended between the ramus and the upper articular surface, completely replacing the architecture of the joint. 1.5cm x 4cm block of bone was excised beneath the zygomatic arch. Once the bony block was removed, the mouth opening achieved was 6cm.
Though the apparent defect in the cheek was of 5 cm x 4 cm, the real defect after the excision of the scar was larger and required an inner lining of 6cm x 5 cm and outer cover of 7cm x 5.5cm. This was provided by a bipaddled pectoralis major myo-cutaneous flap (Fig 3). One of the skin paddles was outlined on the medial aspect of the breast skin over the para-sternal area. The second paddle was outlined over the infra-mammary area, extending a little beyond the pectoralis major muscle but over the rectus fascia. The skin paddles were incised. The dermis of the skin paddle was sutured to the muscle fascia with several interrupted sutures. Care was taken to enter the space deep to the subpectoral fascia. Once the pectoralis major muscle was elevated, the thoraco-acromial pedicle was clearly identified. The muscle pedicle was dissected on either side parallel to the vascular pedicle diretly up to the clavicle. The flap was then tunneled under the neck skin. The bridge of skin between the two paddles was de-epithelised and the flap was folded upon itself and sutured to the margins. The lady had an uneventful post-operative period. She is on regular follow up (eleven months since surgery) and doing well (Fig. 4).

DISCUSSION

Mr. Michael N. Tempest in his paper on Cancrum oris in 1966 presented a detailed study of 250 children with Cancrum oris in Nigeria. This was followed in 1983 by a further series of 140 cases presented by Adekeye and Ord, again from Nigeria.

The basic principles of treatment of the established case of cancrum oris have remained the same, viz.: a) to release the ankylosis if present and b) to carry out reconstruction of the facial defect. To undertake the latter before achieving the former is disastrous for the patient.
A 5-cm of inter-incisor mouth opening in adults is considered to be a good result after release of ankylosis. This patient too, after surgery, has a mouth opening of 6 cm. Adekeye and Ord stressed that lower success rates were achieved in patients with a soft tissue defect.

Since the classic paper of Tempest, there have been significant advances in the knowledge of skin flaps and it is in this area that there have been the most changes. The forehead flap is no longer the first choice for either inner or outer lining on account of the cosmetic deformity of the donor site on the forehead. Other options are the cervical turnover flap, tongue flap, deltopectoral flap, pectoralis major myocutneous flap and free flaps. The cervical and tongue flaps do not provide adequate tissue in large defects. The deltopectoral flap is a versatile flap but it requires a second stage for flap detachment and complete insetting. Unfortunately, free flaps remain an unrealistic option in most of the developing countries, where the demand for reconstructive surgery is growing.

The pectoralis major myocutaneous flap has been the work-horse for head and neck reconstruction. It provides good quality chest skin for cover and / or check lining with minimal morbidity and an acceptable donor site. The greatest advantage lies in the fact that the pectoralis major island flap allows insetting in a single stage procedure. The double paddle technique provides excellent primary reconstruction for full thickness cheek defects, alleviating the need for elevating two different flaps. However, in women, the dissection of pectoralis major flaps is cumbersome because of the overlying breast, and the perforators which are sheared are likely to get damaged while traversing the breast to reach the overlying skin. The reconstructed cheek now has a pin-cushion effect due to circular shape of the pectoralis major flap. This will be corrected subsequently by z-plasty.
As in so many other tropical diseases, the ultimate cure is prevention by raising socio-economic standards. However, in established cases, it is now possible to achieve a reasonable functional and cosmetic by using modern technique of reconstructive surgery.

REFERENCES

1. Adekeye EO, Ord RA. Cancrum oris: principles of management and reconstructive surgery. J Maxillofac Surg 1983; 11:160.
2. Tempest MN. Cancrum oris. Br J Surg 1966; 53: 949.
3. Juri, J. and Juri, C. Advancement and rotation of a large cervicofacial flap for cheek repairs. Plast Reconstr Surg. 1979;61:692.
4. Bakamjian VY, Poole M. Maxillofacial and palatal reconstruction with the deltopectoral flap. Br J Plast Surg. 1977;30:17
5. Ariyan S. Further experiences with the pectoralis major myocutaneous flap for the immediate repair of defects from excision of head and neck cancers. Plast Reconstr Surg 1979;64:605.
6. Coleman JJ, Jurkiewicz MJ, Nahai F, et al. The platysma musculocutaneous flap: experience with 24 cases. Plast Reconstr Surg. 1983;72:315
7. Sharzer LA, Kalisman M, Silver CE, et al. The parasternal paddle: a modification of the pectoralis major myocutaneous flap. Plast Reconstr Surg 1981; 67:753.
8. Back SM, Lawson W, Biller HF. An analysis of 133 pectoralis major myocutaneous flaps. Plast Reconstr Surg 1982;69:460.

Life Events as Risk Factors for Myocardial Infarction: A Pilot Case-control Study in Kolkata, India

ABSTRACT

This case-control study was conducted in the Cardiology Department of Medical College, Kolkata, India, during 2000-2001, to explore the link between stressful life events and subsequent myocardial infarction (MI). One hundred consecutive confirmed MI patients were selected as a case group. One hundred age-, sex- and income-matched controls were selected from visitors other than relatives who attended these patients. The subjects were interviewed and asked to rate 61 life events with a number between 0 and 20. They also noted which of these they had experienced in the last one year. The main exposure variables included life events as per E.S. Paykel, smoking, alcohol consumption, chewing of tobacco, marital status, literacy, employment, and monthly per-capita income. The results showed that an MI patient was likely to experience 4.16 stressful life events, which were twice as much as the control group (2.24). The total stress score was the highest for serious personal illness followed by illness of family members and unemployment for the MI patients. For the controls, conflict between husband and wife, death of friends, and personal illness had the highest total stress score. The mean stress score for the MI patients was 35.5 compared to 17.35 among the controls. The MI subjects were more likely to have experienced stressful life events than the controls.

Introduction

Although coronary artery disease (CAD) is registering a downswing in its incidence in developed countries, it is assuming near-epidemic proportions in the Indian subcontinent (1). Myocardial infarction (MI) is one of the major causes of death in the world. Proportional mortality from diseases of the circulatory system is 45.6% in developed countries and 24.5% in developing countries (2).

Factors, such as hypertension, smoking, and elevated plasma cholesterol, have been studied as risk factors for CAD and MI. Psychosocial factors, such as anxiety and social isolation, have also been shown to contribute to cardiovascular-related morbidity and mortality (3).

Stressful life events, type 'A' behaviour, and prediction of cardiovascular-associated and total mortality over six years have been shown among 12,866 men participating in the multiple risk factor-intervention trial (4). Researchers have presented a life events and difficulties schedule (LEDS), with a perspective on psychodynamic aetiology, emphasizing the specificity of crucial links between life events and subsequent illness (5). The role of psychosocial stressors in the aetiology of acute MI has been studied (6).

Marital stress leads to a poor prognosis in women aged 30-65 years with coronary heart disease (CHD) (7). Increased risk of CHD for women in the lower occupational classes has been shown (8). Mental stress during daily life triggers myocardial ischaemia (9). The relevant link between stressful life events and mental disorders shows that the significance of life events is more important than the volume (10-12).

The impact of emotions on the heart has been shown conclusively in the West (13-15), but few studies have been conducted in developing countries to link stress with CHD. Hence, the present study was designed to show a correlation between stress and MI by life-event research in an Indian population.

Materials and Methods

This pilot case-control study was conducted among 100 (86 males and 14 females) confirmed consecutive MI patients admitted to a teaching hospital (Medical College) in Kolkata, India, during June 2000_May 2001. One hundred controls were selected randomly from visitors other than relatives who visited these patients. They were matched for age, sex, and monthly per-capita income. Since this was a pilot study, the number of cases and controls was chosen ad hoc.

The main exposure variables included the following:

a. Life events as per E.S. Paykel (16).
b. Smoker was defined as a person smoking more than seven cigarettes per day for at least the last five years.
c. Alcoholic was defined as a person consuming more than 200 mL of alcohol every day for more than one year.
d. Tobacco chewer was taken as one chewing tobacco three times every day for more than one year.
e. Marital status was categorized as currently married, or widowed, or single.
f. A literate person was defined as one who could read and write any language.
g. Employment was categorized as unskilled work, skilled work, or professional.
h. Per-capita income of less than Rs 500 was consi-dered as being low-, Rs 500-800 as middle-, and over Rs 800 as high-income groups (17).

Tools and techniques

Data were collected through a pre-designed and pre-tested schedule by interviewing patients and controls. Interview was conducted only after 72 hours of admission or when patients were clinically stable.

The 100 confirmed MI patients and 100 matched controls rated 61 life events presented on the E.S. Paykel scale (16,18) with local Bangla translation. The Bangla translation was validated by three experts in linguistics and cardiology, back-translated into English, and pre-tested with 20 MI patients. The respondents rated each event with a number between 0 (minimum stress) to 20 (maximum stress) to indicate how stressful in general is that event, not how stressful to them personally. They also noted which of these stressful events they experienced during the last one year.

Statistical analysis

The mean scores for each life event were arranged in descending order, separately for the case and the control group. The total stress score was calculated as the product of mean perceived stress and frequency of occurrence for each event. This was used for ranking the most important stressful events for both the groups. Spear-man's rank correlation coefficient was calculated to com-pare with ranks in the control group.

The summation of the total stress scores for the MI patients was divided by 61 (the numbers of events) to find the mean stress score. The same procedure was followed for the control group. A t-test was done to examine the difference in the mean stress scores between the MI patients and the controls. Chi-square tests were also done to show the association between smoking and MI and also between alcohol consumption and MI. Alpha error was taken at 5% level everywhere, except for the chi-square test in Table 1.

The difference between the mean number of life events experienced by the MI patients and the controls was examined using a t-test, taking a normal approximation of study distributions and a one-sided p value.

Results

Table 1 shows that only 8 patients and 10 controls were in the age group of 26-40 years. The rest were in the age groups of 41-55 and 56-70 years. Eighteen controls were female compared to 14 MI patients. Of the 100 MI patients, 87 were currently married, 5 widowed, and 8 were single. Of the 100 controls, 91 were married, 7 widowed, and 2 were single.

Ten percent of the patients and 9% of the controls were illiterate. A comparatively higher percentage (31%) of MI was found among persons performing skilled and semi-skilled work. Moreover, 91% of the patients were of low socioeconomic status having a per-capita income of less than Rs 500 per month compared to 82% of the controls.

Fifty-six percent of the patients were smokers compared to 32% of the controls, and this difference was statistically significant (c2= 11.69 with Yates'correction,p<0.001). Fourteen percent of the patients were alcoholic, while only one person was alcoholic among the control group, and this difference was also statistically significant (c2= 11.68 with Yates'correction,p<0.05). No one admitted to taking drugs in either the patient or the control group. Thirty-four percent of the MI patients consumed betel leaf with tobacco, while 14% of the controls did the same. Fifty-five percent of the MI patients had hypertension and 16% had diabetes compared to 21% and 5% among the controls respectively.

Table 2 shows that the patients' perceptions of stressful events were serious personal illness (rank 5), financial loss/bankruptcy (rank 9), serious illness of family members (rank 15), remaining unemployed for one month despite being fit for work (rank 16), and marriage of children against parent's will (rank 22), whereas among the control group, these ranks were 44, 2, 29, 28, and 46 respectively. Spearman's rank correlation coefficient (rs) was 0.98, i.e. the ranks followed similar trends among patients as in the control group, although the ranks were consistently higher among the case group.

Table 3 shows the product of the mean stress value and actual frequency of occurrence in both MI patients and control group for 15 important life events. Serious personal illness had a product of >1,057 among the MI patients compared to about 55 among the controls. The highest product among the controls was for conflict between husband and wife (81.36) for which the patients had a product of <40. Another major life event for the MI patients was serious illness of family members for which the total score was 333.2 compared to 45.32 among the controls. Unemployment had a product above 300 among the MI patients, but 0 among the controls.

Seven MI patients had experienced substantial financial loss during the past year, while there was none in the control group with similar experience. Family members of 28 MI patients suffered from a serious illness during the past year, whereas only four controls reported a similar incidence. Twenty-seven MI patients were unemployed for one month despite being fit for work, but none among the controls had a similar experience. Sixty-eight MI patients suffered from serious personal illness compared to six among the controls. Fifteen MI patients took huge loans amounting to more than half of their annual income, whereas only three controls were compelled to do the same.

The MI patients experienced an average of 4.16 life events during the past year compared to 2.24 among the controls. This difference was statistically significant (t= 12.4,p<0.001). The mean stress score for each MI patient was 35.3, whereas it was only 17.35 for each control, and this difference was also statistically significant (t= 14.21,p<0.001).

Discussion

Epidemics of CHD began at different times in different countries. In the United States, the epidemic started in the early 1920s, in Britain in the 1930s (19), and in several European countries thereafter. Epidemics have now commenced in developing countries, and countries where an epidemic began earlier are now showing a decline.

This hospital-based case-control study has shown that MI occurred more frequently among males and in older (40 years and above) age groups. The majority (56%) of the patients were regular smokers. More alcoholics were found among the patients than among the controls. Statistical control for age and gender differences was not done, although lack of age and gender differences between the patients and the controls make it unlikely that their effect would be significant.

When CHD emerged as a modern epidemic, it was the disease of higher social classes in most affluent societies, but recently there is a strong inverse relationship between social class and CHD in developed countries (19). A similar finding was also observed in our present study where most (91%) patients were of low socioeconomic status (per-capita income of less than Rs 500 per month) based on the modified Kuppuswamy scale (17).

It was observed in the present study that the control individuals were likely to have experienced an average of two (2.24) stressful life events during the past year without suffering from any adverse physical or psycho- logical disturbance, whereas an MI patient is likely to have experienced an average of four (4.16) stressful life events during the past year.

The above findings corroborated the findings of Singh and colleagues who found that individuals in our society are likely to experience two stressful life events during the past year and 10 events in a life time without suffering from any adverse physical or psychological disturbances (20). The occurrence of major life events signals a period of increased risk when supportive interventions may prevent illness (21). Frasure-Smith has shown that depression after MI can raise the likelihood of subsequent mortality (22).

Geyer and others have compared data from three life-event studies among depressives, MI patients, and industrial workers (23). They showed that the number of events and severity ratings were positively correlated with measures of depression.

Indeed, there should be a social support network to prevent depression due to experiences of extreme and negative life events from leading to psychosomatic problems, including MI (24). Assessment of mental health and timely counselling by trained personnel in this field may be useful tools to enhance mental functioning before the development of such illnesses.

The limitations of the study include an inadequate sample size and a cross-sectional design that allows conclusions about association rather than causes.

The link between stress and MI should be confirmed through longitudinal studies, making adjustments for bias and confounders. Then, coping with stress would have important public-health implications for healthcare providers and policy-makers.

Acknowledgements

This paper is based on the dissertation of Dr. Subhashish Saha as part of D.P.H. training under the guidance of Dr. Anima Haldar with continuous support and encouragement rendered by Professor G.C. Das, Department of Cardiology, Calcutta National Medical College, Park Circus. The authors are also thankful to Dr. Moloy Ghosal, RMO-Cum-Clinical Tutor, Department of Psychiatry, Medical College, Kolkata, College Street, for his continuous help in the present study. The authors are grateful to all the subjects included in the study. They are also indebted to all four reviewers of the paper for their keen interest and suggestions.

References

1. Banerjee A. Coronary artery disease and its problems in management (editorial). J Indian Med Assoc 2001;99:474-5.
2. World Health Organization. The world health report, 1997: conquering suffering, enriching humanity; report of the Director-General. Geneva: World Health Organization, 1997. 162 p.
3. Patronek GJ, Glickman LT. Pet ownership protects against the risks and consequences of coronary heart disease. Med Hypotheses 1993;40:245-9.
4. Hollis JF, Connett JE, Stevens VJ, Greenlick MR. Stressful life events, type A behavior, and the prediction of cardiovascular and total mortality over six years. J Behav Med 1990;13:263-80.
5. Brown GW, Harris TO. Life events and illness. New York: Guilford Press, 1989. 496 p.
6. Mittleman MA. Epidemiologic perspective on the role of psychosocial factors. Ital Heart J 2001;2: 887-9.
7. Orth-Gomér K, Wamala SP, Horsten M, Schenck-Gustafsson K, Schneiderman N, Mittleman MA. Marital stress worsens prognosis in women with coronary heart disease: the Stockholm female coronary risk study. JAMA 2000;284:3008-14.
8. Wamala SP, Mittleman MA, Horsten M, Schenck-Gustafsson K, Orth-Gomér K. Job stress and the occupational gradient in coronary heart disease risk in women: the Stockholm female coronary risk study. Soc Sci Med 2000;51:481-9.
9. Mittleman MA, Maclure M. Mental stress during daily life triggers myocardial ischemia. JAMA 1997; 277:1558-9.
10. Amiel-Lebigre F. [Life events, risk factor or risk indicator?] Acta Psychiatr Belg 1986;86:425-30.
11. Cooke DJ, Hole DJ. The aetiological importance of stressful life events. Br J Psychiatr 1983;143: 397-400.
12. Tennant C, Smith A, Bebbington P, Hurry J. The contextual threat of life events: the concept and its reliability. Psychol Med 1979;9:525-8.
13. Verrier RL, Mittleman MA. The impact of emotions on the heart. Prog Brain Res 2000;122:369-80.
14. Fredrikson M, Matthews KA. Cardiovascular res-ponses to behavioral stress and hypertension: a meta-analytic review. Ann Behav Med 1990;12:30-9.
15. Yan LL, Liu K, Matthews KA, Daviglus ML, Ferguson TF, Kiefe CI. Psychosocial factors & risk of hypertension: the coronary artery risk development in young adults (CARDIA) study. JAMA 2003;290:2138-48.
16. Paykel ES. The interview for recent life events. Psychol Med 1997;27:301-10.
17. Kuppuswamy B. Manual of socio-economic status scale 1981. New Delhi: Ministry of Health and Family Welfare, Government of India, 1981:17.
18. Paykel ES, Prusoff BA, Uhlenhuth EH. Scaling of life events. Arch Gen Psychiatry 1971;25:340-7.
19. World Health Organization. Primary prevention of CHD: Euro report & studies. Copenhagen: Regional Office for Europe, World Health Organization, 1985:98.
20. Singh G, Kaur D, Khan H. A new stressful life events scale. Indian J Psychiatr 1984;27:179-82.
21. Paykel ES. Life events, social support and depression. Acta Psychiatr Scand 1994;377(Suppl):50-8.
22. Frasure-Smith N, Lesperance F, Talajic M. Depre-ssion and 18-month prognosis after myocardial infarction. Circulation 1995;91:999-1005.
23. Geyer S, Broer M, Haltenhof H, Buhler KE, Merschbacher U. The evaluation of life event data. J Psychosom Res 1994;38:823-35.
24. Cornelis CM, Ameling EH, de Jonghe F. Life events and social network in relation to the onset of depression: a control study. Acta Psychiatr Scand 1989;80:174-8.

Thyroid Disorders in Pregnancy

Introduction

Over the past several years it has been proved that maternal thyroid disorder influence the outcome of mother and fetus, during and also after pregnancy. The most frequent thyroid disorder in pregnancy is maternal hypothyroidism. It is associated with fetal loss, placental abruptions, pre-eclampsia, preterm delivery and reduced intellectual function in the offspring.1 In pregnancy, overt hypothyroidism is seen in 0.2% cases2 and sub clinical hypothyroidism in 2.3% cases3. Fetal loss, fetal growth restriction, pre-eclampsia and preterm delivery are the usual complications of overt hyperthyroidism (low TSH and high T3, T4) seen in 2 of 1000 pregnancies whereas mild or sub clinical hyperthyroidism (suppressed TSH alone) is seen in 1.7% of pregnancies and not associated with adverse outcomes4. Autoimmune positive euthyroid pregnancy shows doubling of incidence of miscarriage and preterm delivery. Worldwide more than 20 million people develop neurological sequel due to intra uterine, iodine deprivation5. Other problems of thyroid disorders in pregnancy are post partum thyroiditis, thyroid nodules and cancer, hyper emesis gravidarum etc. Debates and disputes persist regarding several protocol and management plan in this specific spectrum of diseases. An attempt is made hereby to formulate an acceptable and applicable guideline in the scenario of country, based on evidences and background knowledge.

Physiology of Thyroid in Pregnancy

Thyroid hormones consist of thyroxin (T4) and triiodothyronine (T3) of which active forms are the free portions (fT3, fT4) consisting of 1% of total hormones. The fT3 fraction is biologically more significant and derived from conversion of fT4 at liver, kidney and muscle. The fT3 hormone acts through specific nuclear receptors of fT3, situated in most of the tissues. TSH secreted from anterior pituitary act as negative feedback from fT3 levels. Dietary iodine is essential for this thyroid hormone synthesis.

Fetal aspects

In pregnancy, fetus receives iodine from maternal source in all the trimesters. Fetus receives thyroxin from mother up to 12 weeks through placental circulation but not TSH or fT3. Thyroxin is partially converted to fT3 and combines with receptors in fetal brain and responsible for fetal brain development. From 12th week, placental changes resist T4 passage to fetus and fetal pituitary thyroid axis start functioning like adult.

Maternal aspects

1. In pregnancy, half life of Thyroxin Binding Globulin (TBG) increases from 15min to 3days and concentration becomes 3 times by 20weeks due to the effect of oestrogen driven glycosylation, which increases the level of T3 and T4 making its estimation non reliable. But fT3 and fT4 remain unaffected, and are of choice for estimating the thyroid function during pregnancy.
2. HCG and TSH due to structural similarity produce hormone spillover syndrome in 1st trimester, manifested as stimulation of TSH receptors by HCG and biochemical hyperthyroidism. This is common in multiple pregnancy, hyper emesis gravidarum and trophoblastic diseases. Diagnosis of false hyperthyroidism should be avoided in these cases.
3. Depletion of iodine can occur due to increased glomerular filtration and greater thyroidal uptake due to higher T4 concentration. In several maternal iodine deficiency, compensation if fails can lead to cretinism in the offspring.
4. Concentration of the enzyme deiodinase III (which converts T4 to T3 and further breakdown) is increased in placenta and reduces thyroxin transfer.

About 2 to 5% of pregnant woman suffer from any variety of thyroid disorders and timely intervention can be done if detected early.6 Because of physiological changes values of thyroid hormones during pregnancy differ from non-pregnant values. Values in pregnancy also vary from trimester to trimester and no consensus about this value has been made yet. Coutez C et al., established the following value as shown in table 1.7

In 2008, Marwaha RK et al, first time presented the trimester specific thyroid function values in Indian Woman.8 These are shown in table 2.

Recommendations

Screening: Screening should be with minimum TSH only and if necessary fT3 and fT4 may be tested. Universal screening or screening of high risk woman is to be practiced is not yet settled. Majority is of the opinion, that evidence is insufficient in favor of routine screening. But the message from the study of Vaidya et al9 should also be given due consideration, who commented that most pregnant woman with thyroid disease would be diagnosed by case finding but at least 30% will remain undetected. But we will have to wait till the report of Controlled Antenatal Thyroid screening Study (CATS)10 by John Lazarus, is completed. This is a prospective randomized study directly testing the value of screening for thyroid disease and treating woman with TSH elevations. Probably at present moment we would only screen the high group woman who should be tested definitely are the following.

Screening of pregnant women

1. History of hypo / hyperthyroidism or thyroid lobectomy or post partum thyroiditis
2. Family history of thyroiditis
3. Goiter
4. Thyroid auto-antibodies
5. Symptoms, signs or biochemical markers suggestive of thyroid disease
6. Type 1 diabetes
7. Other autoimmune disorders
8. Infertility
9. Previous head or neck irradiation
10. History of miscarriage or preterm delivery

Routine screening in pregnancy and neonates

The problem of thyroid disease in pregnancy is receiving increasing attention from many scientific concerns. Thyroid function in pregnancy is characterized by a T4 surge at 12 weeks which declines subsequently. There is a fall in the serum thyroid hormone concentrations in the second half of pregnancy. However, data shows that some women may have thyroid hormone levels within reference ranges even in the second half of pregnancy. Development of the fetal brain is dependent on T4 transportation to the fetus, which eventually depends upon adequate maternal iodine supply. There is current concern that adequate iodisation is not present in large parts of India and other countries. A growing amount of evidence suggests that thyroid autoimmunity is associated with fetal loss, however, the mechanism remains unclear and carefully conducted studies are required to elucidate optimal therapy. The incidence of hyperthyroidism in pregnancy is uncommon, but effects on both mother and child are critical if untreated. Substantial evidence also exists which shows that low maternal T4 (or high TSH) during pregnancy have deleterious effects on child IQ. Many genetic causes of congenital hypothyroidism have been elucidated with the advancement of molecular biology. However, further research is required in order to elucidate the etiologies of majority of cases, which still remain unclear. About 10% of pregnant women have TPO antibodies early during gestation and are at increased risk of developing subclinical hypothyroidism during pregnancy and thyroid dysfunction post-partum. The latter condition occurs in 5-9% of women and 25-30% progress to permanent hypothyroidism. This review suggests that routine screening for thyroid function in early pregnancy to detect maternal overt or subclinical thyroid disorders should be considered but evidence is awaited. Screening for both thyroid dysfunction and thyroid antibodies ideally at a preconception clinic but certainly in early gestation is recommended. Neonates born of mothers with thyroid disorders must undergo routine thyroid screening.

Guideline for Treatment of Thyroid Disorders

Hypothyroidism and pregnancy

1. Both maternal and fetal hypothyroidism exert serious adverse effects on the fetus, so maternal hypothyroidism should be avoided by early diagnosis at the first prenatal visit or at diagnosis of pregnancy
2. In cases of hypothyroidism diagnosed before pregnancy, adjust the preconception T4 dose to reach a TSH level not higher than 2.5m/ml before pregnancy.
3. By 4-6 weeks of gestation, the T4 dosage needs to be increased by about 30-50%.
4. If overt hypothyroidism is diagnosed during pregnancy, thyroid function should be normalized as rapidly as possible. The target is to achieve and maintain TSH concentrations below 2.5mU/ml in the first trimester (or 3m U/ml in the second and third trimesters) or to trimester-specific normal TSH ranges. This can be achieved by rapidly titrating the T4 dosage to reach and maintain the target TSH levels. A reassessment of the thyroid function should be carried out within 30 to 40 days.
5. Women who have thyroid antibodies in the early stages of their pregnancy but are otherwise euthyroid, should be monitored for elevations of TSH above the normal range because they are risk of developing hypothyroidism.
6. Sub clinical hypothyroidism: Recommend T4 replacement as T4 treatment has been shown to improve obstetrical outcome, though do not modify long-term neurological development in the offspring.
7. After delivery, dose of T4 need to be decreased in most hypothyroid women.

Maternal hypothyroidism

1. If a below normal serum TSH level is detected, hyperthyroidism must be distinguished from both normal physiology during pregnancy and hyperemesis gravidarum. Presence of autoimmunity, a goiter, and TRAb can differentiate Graves’ disease from gestational thyrotoxicosis.
2. In cases of frank hyperthyroidism due to Graves’ disease or toxic nodules, Anti Thyroid Drug (ATD) therapy should be either initiated (for those with new diagnoses) or adjusted (for those with a prior history) to maintain the maternal thyroid hormone levels for free T4 in the upper nonpregnant reference range.
3. ATD Propylthiouracil is of choice than methimazole (may be associated with congenital anomalies), especially during first-trimester the time for organogenesis.
   In case of non-availability of or intolerance to or adverse events with propylthiouracil, methimazole can be prescribed.
4. Subtotal thyroidectomy is indicated in cases of
   • Severe adverse reaction to ATD therapy,
   • Persistently high doses of ATD requirement,
   • Patient noncompliance.
   The optimal timing of surgery is in the second trimester.
5. Pregnant patients with subclinical hyperthyroidism should not be treated without evidence to show that treatment improves pregnancy outcome, keeping in mind the potential of adverse effects on fetal outcome.
6. TRAb (either TSH receptor-stimulating or –binding antibodies) freely cross the placenta and can stimulate the fetal thyroid. Women with Grave’s disease or with a history of Grave’s disease or treatment with 131I or thyroidectomy, or with a previous newborn with Grave’s disease should undergo measurements of TRAb antibodies either prior to becoming pregnant or by the end of the second trimester. Women who have a negative TRAb and do not require ATD have a very low risk of fetal or neonatal thyroid dysfunction.
7. 131Iodine should be avoided in a woman who is or may be pregnant. 131I should not be used in a pregnant woman. However, on inadvertent use, the patient should be promptly informed about the danger of radiation to the fetus and about thyroid destruction if the patient has been treated after the 12th week of gestation. There are no data for or against recommending termination of pregnancy after 131Iodine exposure.
8. Pregnant women with TRAb or those treated with ATD should have a fetal ultrasound to detect fetal thyroid dysfunction. This may include growth restriction, hydrops, presence of goiter, and cardiac failure.
9. Evaluate newborns of mothers with Graves’ disease for thyroid dysfunction and treated if indicated.

Gestational hyperemesis and hyperthyroidism

1. Measure Thyroid function tests in all patients with hyperemesis gravidarum
2. ATD treatment to be given to overt hyperthyroidism due to coincident Graves’ disease and few women with hyperemesis gravidarum

Autoimmune and thyroid disease and miscarriage

Universal screening for anti thyroid antibodies and possible treatment cannot be recommended as there are very few reports regarding positive association between the presence of thyroid antibodies and pregnancy loss.

Thyroid nodules and cancer

1. Fine-needle aspiration (FNA) cytology, preferably Ultrasound-guided should be advised if thyroid nodules larger than 1 cm are detected in pregnancy.
2. Pregnancy should not be interrupted and surgery should be offered in the second trimester before fetal viability when nodules discovered in the first or early second trimester are malignant. Women found to have cytology indicative of papillary cancer or follicular neoplasm without evidence of advanced disease and who prefer to wait until the delivery, they that can be counseled that most well differentiated thyroid cancers are slow growing and surgical treatment soon after delivery is unlikely to adversely affect prognosis.
3. In pregnant women with a previously treated thyroid cancer, a positive FNA for cancer or suspicion of cancer, and those who elect to delay surgery until postpartum, treatment with thyroid hormone to achieve suppressed but detectable TSH is advisable.
4. 131Iodine should not be given to lactating women. Pregnancy should be avoided for 6 months to 1 yr in them.

Iodine nutrition during pregnancy

Increase daily iodine intake to 250 mg on average during pregnancy and breastfeeding by encouraging the use of iodized salt.

Postpartum thyroiditis (PPT)

1. TSH estimation at 3 and 6 months in women known to be thyroid peroxidase antibody positive, for women with type 1 diabetes mellitus (PPT 3-fold greater).
2. Women with a history of PPT have a markedly heightened risk of developing permanent primary hypothyroidism within 5 to 10 years, should undergo annual TSH assessments.
3. Asymptomatic women with PPT who have a TSH above the reference range but less than 10mU/ml and who are not planning a subsequent pregnancy do not necessarily require intervention but should, if untreated, be re-monitored in 4–8 weeks. Symptomatic women and women with a TSH above normal and who are attempting pregnancy should be treated with levothyroxine.
4. Women with postpartum depression should be screened for hypothyroidism and appropriately treated

Conclusions

• Uncontrolled or inadequate control of thyroid dysfunction in pregnancy is associated with adverse fetal and maternal outcomes
• Hyperthyroidism in pregnancy requires careful control of maternal disease whilst avoiding fetal hypothyroidism
• Propylthiouracil is the preferred antithyroid drug in pregnancy although methimazole can be used where propylthiouracil is unavailable
• Synthetic levothyroxine is the treatment of choice in hypothyroidism
• Patients with pre-existing hypothyroidism usually require an increase in thyroxine dose in pregnancy
• Most patients with postpartum thyroiditis will require treatment during the hypothyroid phase
• Long-term follow-up of patients with this syndrome is essential owing to the risk of permanent hypothyroidism
• Subclinical hypothyroidism in pregnancy requires replacement treatment
• Excellent maternal and fetal outcomes can be achieved with appropriate management of thyroid dysfunction in pregnancy.

References

1. Abalovich M, Gutierrex S, Alcaraz G, et al. Overt and subclinical hypothyroidism complicating pregnancy Thyroid 2002;12:63–8.
2. Casey BM, Leveno KJ Thyroid disease in pregnancy. Obstet Gynecol 2006;108:1283–92.
3. Biondi B, Cooper DS The clinical significance of subclinical thyroid dysfunction. Endocr Rev 2008;29:76–13 .
4. Casey BM, Dashe JS, Wells CE, Subclinical hyperthyroidism and pregnancy outcomes. Obstet Gynecol 2006;107:337–341.
5. Girling J, Thyroid disease in pregnancy. Obstet, Gynec and Reprod Medicine 2008;18:10.
6. Glinoer D, Soto MF, Bourdoux P, et al. Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions. J Clin Endocrinol Metab 1991;73:421–7.
7. Cotzias C, Wong SJ, Taylor E et al. A study to establish gestation-specific reference intervals for thyroid function tests in normal singleton. Eur J Obstet & Gynecol and Reprod Biol 2008;137:61–6.
8. Marwaha RK, Chopra S, Gopalakrishnan S et al. Establishment of reference range for thyroid hormones in normal pregnant Indian women, BJOG An Int J Obstet and Gynaec 2008;602-6.
9. Vaidya B, Anthony S, Bilous M et al. Detection of thyroid dysfunction in early pregnancy: universal screening or targeted high-risk case finding. J Clin Endocrinol Metab 2007;92:203–7.
10. Brent GA. Diagnosing Thyroid Disease in Pregnant Women J Clin Endocrinol Metab 2007;92:39–41.
11. Abalovich M, Amino N, Barbour LA et al. Green. Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab 2007;92:S1–47.

Retinal detachment associated with thalassemia major and Marfan's syndrome-A case report

Abstract

The thalassaemias, unlike a few other disorders of the haemopoietic system, are very rarely accompanied by ophthalmological changed. Marfan's Syndrome, on the other hand, exhibits a number of ocular manifestations. This article describes a case of uniocular retinal detachment associated with both these conditions.

Case report

The patient a ten-year-old girl with disproportion­ately long thin limbs and fingers, had attended the outpatients department at NRS Medical College and Hospital, Calcutta. She complained of blurring of vision in both her eyes (more in the right eye than in the left) over a period of one year. She also mentioned that she suffered from occasional episodes of bleeding from the gums and pain in her left upper abdomen, She gave no history of having received any treatment or blood trans­fusions before.

The patient was tall for her age and possessed extremeties that were dolichostenomelic, with arachnodactyly. The ratio of the upper to the lower segment of her body was0.82. The metacarpal and phalangeal indices were 8.65 and 6.20 respectively. Flatfeet deformity and lax ankle joints were pre­sent Osteoporotic changes with flattening and erosion of the vertebrae were demonstrated radiographically in the lower thoracic and lumbar regions Radiographs of the skull and chest were normal.

A moderate degree of pallor was noted. There was no evidence of jaundice. Frank bleeding from the gums, crowding of teeth and a high arched palate were present The spleen was enlarged 9 cm below the left costal margin in the left midclavi­cular line and felt firm on palpation. The liver was not palpable There was no lymphadenopathy Clinical, radiological and electrocardiographic tests showed a normallyfunctioning cardiovas­cular system.

Examination of the eyes revealed normally-react­ing pupils which, however, resisted dilatation with all available mydriatics The lenses were dislocated in a downward and inward direction resulting in iridodonesis and phacodonesis The vitreous could not be studied in detail owing to the small pupils Neverthless no marked changes were seen. There was a total retinal detachment in the right eye without any detectable hole or tear. The fundus of the left eye was normal. No mesoder­mal abnormality of the anterior chamber angle was observed on gonioscopy. The intraocular pressures were normal - 12.2 and 17.3 mm of Hg (Schiotz tonometry) in the right and left eyes respectively. While vision in her right eye was reduced to perception of hand movements, she counted fingers at 0.75 m with her left eye The visual acuity failed to improve with glasses or a pin hole aperture.

The haematological investigations proved most interesting. The haemoglobin level was estimated to be 9.57 g/100 ml (9.57 g/dl) of blood (66%). Foetal haemoglobin comprised 41.7% of the total. Study of the red blood cells (Figure 1) showed the presence of reticulocytosis (15%), microcytes, target cells, normoblasts, hypochromia, poikilo­cytosis and anisocytosis The total leucocyte count was 7,400 per cubic mm (7.4 x 10 ⁹/1) of blood of which 58% (4.29 x 10 ⁹/1) were, neutro­phils, 30% (2.22 x 10 ⁹/ 1) lymphocytes, 8% (0.59 x 10 ⁹/1) eosinophil granulocytes and 4% (0.29 x 10 ⁹/1) monocytes Platelets numbered 3,20,000 per cubic mm (320 x 10 ⁹/1) of blood The ESR was 47 mm/ at the end of first hour (Westergren). The sickling test was negative.

Other investigations such as Van den Bergh's test and the estimation of Serum bilirubin, GOT (AST), GPT (ALT) and post-prandial blood sugar gave normal results.

Serum protein electrophoresis showed a marginal reduction in albumin level and slightly raised acute phase proteins The a _l globulin fraction was normal in armount The /3 ₁gloublin fraction was almost normal but _I2 bloublin was decreased in proportion. Gamma globulins exhibited a pro­nounced increase in quantity.

Electrophoresis of haemoglobin showed a single band comprising Hb F. Traces of HB A ₂ were probably present but no quantitative estimates could be made. No other haemoglobin compon­ent could be identified

Biochemical examination of the urine (for evidence of homocystinuria) yielded negative results Rout­ine urine analysis provided no findings of any interest.

Results of the Mantoux test and the Wasserman reaction were negative. The patient had lost her father in her childhood. Her mother, who was living, had no significant ocular changes However, amongst her three brothers and a sister (Figure 2), all except one brother and the sister were found to have subluxation of lenses, glial tissue in the vitreous and over the retina, as well as retinal detachment without breaks Thalassaemia was detected in all siblings and their mother by haema­tological investigations.

Discussion

The paucity of information regarding ocular complications in the thalassemia syndromes is striking. Central retinal vein thrombosis and grade two hypertensive retinopathy are recorded to have been present in two separate cases of thalassae­mia . Only one case of retinal detachment without break/s in association with thalassaemia has been reported (Rudd et al). A case of thalassaemia with retinal haemorrhages leading to vitreo- retinal degeneration has also been described. On the other hand, retinal detachment is a well-known complication of Marfan's syndrome. However, the occurrence of retinal detachment accom­panied by both /3-thalassaemia and Marfan's syndrome in the same patient (which makes it impossible to ascertain the cause of the detach­ment) is perhaps unknown. At present it is difficult to correlate the two components of this intriguing association, but since both are inherited disorders of connective tissue, further work may someday unearth the possible missing link.

Summary

A ten-year-old female patient attending the ophthalmology section of the outpatients' depart­ment of Nil Ratan Sircar Medical College and Hospital, Calcutta, was found to have uniocular retinal detachment while at the same time having most of the clinical features of both J3-thalassaemia and Marfan's syndrome. Investigations revealed evidences of both conditions (as well as retinal changes) in some of her family members also. Efforts to find one common basis for explaining both the connective tissue disorders were, how ever, unrewarding. The peculiar association, nevertheless, has made reporting of the case worthwhile.

Acknowledgements

The help and co-operation of the following are gratefully acknowledged

1. Dr. M Rakshit 

Head of the Haematology Unit Department of Medicine, N R S Medical College and Hospital, Calcutta.

2. Superintendent

N R S Medical College and Hospital, Calcutta.

References

1.	Duke-Elder WS. System of Ophthalmology. London : Kimpton, 1967; 10: 399.
2.	Mckusick VA Heritable Disorders of Connective Tissue. St Louis : Mosby, 1972.
3.	Rudd C, Evans PJ, and Peeney ALP. Ocular complications in Thalassaemia minor. Br J Ophthalmol 1953; 37: 353.
4.	Kahan A, Kahan IL, Benko A Erythrocytic Anomalies in Hereditary Vitreo-Retinal degene­ration (Degeneratio Hyaloideoretinalis). Br. J. Ophthalmol 1963; 47: 620.
5.	Cross HE, Jensen AD. Ocular manifestations in the Marfan syndrome and Homocystinuria. Am. J. Ophthalmol 1973; 75: 405.
6.	Allen RA Straatsma MH, Apt L, Hall MO. Ocular manifestations of the Marfa syndrome. Trans Am Acad Ophthalmol Otolaryngol 1967; 71:18.
7.	Hudson JR. Marfan's syndrome with Retinal Detachment Br J Ophthalmol 1951; 35: 244.

Figures

Staphylococcal tricuspid valve endocarditis in a non-addicted patient with structurally normal heart

Abstract

Tricuspid valve endocarditis in non-addicted patients without underlying cardiac disease is extremely rare. Therefore, its diagnosis often presents a clinical challenge. We report a case of a 24-year-old female who presented with bilateral lower lobe cavitary pneumonia. She remained febrile in spite of 5 days of intravenous antibiotic therapy. On subsequent investigations, she was found to have isolated tricuspid valve endocarditis caused by Staphylococcus aereus. She was not an intravenous drug abuser and there was no underlying cardiac disease. She responded well to medical therapy. We report this case because of rarity of tricuspid valve endocarditis is a non-addicted person with structurally normal heart and its atypical presentation with paucity of cardiac symptoms at initial stage.

INTRODUCTION

Infective endocarditis designates microbial infection of the endothelial surface of the heart and great vessels. The hallmark of the infection is the formation of an adherent, bulky mass of thrombotic debris and organisms, called vegetation. Ninety-two percent involvement is in the left side and 8% is in the right side. Isolated tricuspid (TV) endocarditis accounts for 5%-10% of cases of infective endocarditis (IE). Predisposing factors are congenital heart disease, insertion of the central venous catheter, placement of a pace maker or implantable defibrillator, intravenous drug abuse, alcoholism, immunodeficiency, and genital sepsis. Staphylococcus aereus is the usual pathogen. TVIE is thought to be rare because the right-sided congenital heart diseases are rare and the tricuspid and pulmonary valves are not strained because of low pressure, and oxygen saturation is low. TV endocarditis is rarely considered in differential diagnosis of a febrile patient who is not an intravenous drug abuser or has no predisposing heart disease. Moreover, delay in diagnosis is common due to atypical presentations such as predominant respiratory symptoms or paucity of cardiac manifestation in the early stage of the disease. Here, we describe a case of TV endocarditis which occurred in a young female who was not addicted to intravenous drugs and had no underlying heart disease. She initially presented with cavitary pneumonia which failed to respond with antibiotics. She subsequently made a complete recovery with 6 weeks intravenous antibiotics.

CASE REPORT

A 24-year female patient attended the chest outdoor of NRS Medical College & Hospital with high fever with chill and rigor and cough with mucopurulent expectoration for two weeks. She was a nonsmoker, nonalcoholic and was not an intravenous drug abuser. She had no past history of any congenital or rheumatic heart disease. On examination, she appeared pale with pulse rate 120 beats/min, respiratory rate 24/min, blood pressure 120/84 mmHg and oral temperature 101 °F. Examination of respiratory system revealed bilateral course crepitations at both bases. There was no sign of infection in skin, oral cavity, bones, and joints. Examination of other systems was within normal limits. Blood examination revealed hemoglobin 8.8 g/dl, total leukocyte count of 8.2 × 10 ⁹ /l, neutrophils 62%, lymphocytes 26%, and ESR -102 mm in the first hour. Chest x-ray revealed bilateral lower zone infiltrates with multiple cavitations (Figure 1). Blood biochemistry and urinalysis were normal. Sputum for gram stain and acid-fast bacilli stain were negative. HIV serology was nonreactive. She was put on intravenous ceftriaxone and azithromycin. However, she remained febrile despite 5 days of antibiotic. She also developed a new pan-systolic murmur at the left sternal edge. There was no classical clinical sign of tricuspid regurgitation. Trans-thoracic echocardiography revealed mild right ventricular dilatation, moderate tricuspid regurgitation, pulmonary arterial hypertension (pulmonary arterial pressure 55 mmHg), and a vegetation of 1.4 × 0.4 cm size in the tricuspid valve (Figure 2). Blood cultures on two consecutive days grew S. aereus which was sensitive to cloxacillin, co-amoxiclav, gentamicin, cotrimoxazole, and clarithromycin.

Figure 1: Chest X-ray (PA View) showing bilateral lower zone infiltrations with cavities.

Figure 2: Echocardiography showing vegetation in the tricuspid valve.

A diagnosis of Staphylococcal endocarditis of TV was made on basis of Duke Criteria. She was treated with intravenous cloxacillin 2 g four times daily and gentamicin 80 mg IV thrice daily for six weeks. She made a complete recovery with normalization of chest radiograph, no residual vegetation in the TV, and sterile blood culture. 

DISCUSSION

Endocarditis of right heart valves is less common and almost always occurs in intravenous drug abusers, with more than 80% of TV endocarditis occurring in drug addicts. Isolated TV endocarditis in patients with structurally normal heart who do not abuse intravenous drugs is unusual. Generally, it occurs in younger patients, and the majorities have underlying medical conditions such as alcoholism, abortion, colonic disease, permanent catheter, and extra cardiac septic foci. Our case was a younger female but did not have any such abnormality.

The diagnosis is often delayed because the cardiac manifestation of the disease is subtle, and the murmur of tricuspid regurgitation is rarely present at initial presentation, as occurred in our case. Persistent fever associated with pulmonary events, anemia, and microscopic hematuria, the so-called ''tricuspid syndrome,'' are the signs of clinical alert for TV endocarditis. Symptoms related to pulmonary septic emboli usually dominate the clinical picture and force the patients to seek medical advice. Pulmonary events may be of various forms including minor atelectesis, pulmonary infiltrate mainly in lower lobe with or without cavitations, and pleural effusion. Sometimes chest radiograph may be normal requiring CT Thorax to reveal the abnormality. Absence of peripheral stigma of infective endocarditis is the rule, rather than the exception. Sometimes joint, muscle, or skin may dominate the clinical picture making diagnosis more difficult. Our case did not have hematuria or peripheral signs of infective endocarditis, but presented with persistent fever and cavitary pulmonary infiltrates.

As in any case is IE, Duke Criteria is the gold standard for diagnosis of native TVIE. Prognosis is excellent with intravenous bactericidal antibiotics which may need extension beyond six weeks. Only about 25% patient require surgery. Major indications of surgery are persistent sepsis despite appropriate antibiotic, recurrent pulmonary embolism and severe right heart failure. Surgical options include vegetectomy and valvulectomy, valve repair, and valve replacement. Mortality is about 14%-24% which is lower than described for IE in patients with predisposing conditions. 

REFERENCES

1.	Pachirat O, Chetchotisakd P, Klugboonkrong V, Tawelsangshuksakul P, Tantisivin C, Loapibon M. Infective endocarditis: Prevalence, characteristics and mortality in Khon Kaon, 1990-1999. J Med Assoc Thai 2002;85:1-10.
2.	Chan P, Ogilby JD, Segal B. Tricuspid valve endocarditis. Am Heart J 1989;117:1140-6.
3.	Morokuma H, Minato N, Kamohara K, Minematsu N. Three surgical cases of isolated tricuspid valve infective endocarditis. Ann Thorac Cardiovasc Surg 2010;16:134-8.
4.	Naidoo DP. Right sided endocarditis in the non- drug addict. Postgrad Med J 1993;69:615-20.
5.	Clifford CP, Eykyn SJ, Oakley CM. Staphylococcal Tricuspid valve endocarditis in patients structurally normal hearts and no evidence of narcotic abuse. Q J Med 1994;87:755-7.
6.	Robbins MJ, Frater RW, Soeiro R, Frishman WH, Strom JA. Influence of vegetation size on clinical outcome of right sided infective endocarditis. Am J Med 1986;80:165-71.
7.	Nandakumar R, Raju G. Isolated tricuspid valve endocarditis in non addicted patients: A diagnostic challenge. Am J Med Sci 1997;314:207-12.
8.	Varona JF, Guerra JM. Tricuspid valve endocarditis in a non-addicted patient without predisposing myocardiopathy. Rev Esp Cardiol 2004;57:993-6.
9.	Robins MJ, Soeiro R, Frishman WH, Strom JA. Right sided valvular endocarditis: Etiology, diagnosis and approach to therapy. Am Heart J 1989;111:128-35.
10.	Roberts WC, Buchbinder NA. Right sided valvular endocarditis: A clinicopathological study of twelve necropsy patients. Am J Med 1972;5:7-19.
11.	Rouviex E, Witchitz S, Bouvet E, Freidlander G, Wolff M, Regnier B, et al. Tricuspid infective endocarditis: 56 cases. Eur Heart J 1984;5:111-5.