An objective way to predict remission and relapse in Cushing disease using Bayes' theorem of probability.

OBJECTIVE: In this study on patients with Cushing disease, post-transsphenoidal surgery (TSS), we attempt to predict the probability of remaining in remission, at least for a year and relapse after that, using Bayes' theorem and the equation of conditional probability. The number of parameters, as well as the weightage of each, is incorporated in this equation. DESIGN AND METHODS: The study design was a single-centre ambispective study. Ten clinical, biochemical, radiological and histopathological parameters capable of predicting Cushing disease remission were identified. The presence or absence of each parameter was entered as binary numbers. Bayes' theorem was applied, and each patient's probability of remission and relapse was calculated. RESULTS: A total of 145 patients were included in the study. ROC plot showed a cut-off value of the probability of 0.68, with a sensitivity of 82% (range 73-89%) and a specificity of 94% (range 83-99%) to predict the probability of remission. Eighty-one patients who were in remission at 1 year were followed up for relapse and 23 patients developed relapse of the disease. The Bayes' equation was able to predict relapse in only 3 out of 23 patients. CONCLUSIONS: Using various parameters, remission of Cushing disease can be predicted by applying Bayes' theorem of conditional probability with a sensitivity and a specificity of 82% and 94%, respectively. This study provided an objective way of predicting remission after TSS and relapse in patients with Cushing disease giving a weightage advantage to every parameter.

Unravelling a novel, promising and convenient tool for differential diagnosis of delayed puberty: GnRHa-stimulated inhibin B (GnRH-iB).

BACKGROUND: Etiological diagnosis of delayed puberty is difficult. Despite availability of various basal and stimulation tests differentiation between constitutional delay in puberty and hypogonadotropic hypogonadism is still challenging. OBJECTIVE: To elucidate the role of GnRH agonist-stimulated inhibin B (GnRH-iB) for the differential diagnosis of delayed puberty. STUDY DESIGN: Participants were recruited into "exploratory cohort" (n = 39) and "validation cohort" (n = 16). "Exploratory cohort" included children with spontaneous puberty and patients with hypogonadotropic hypogonadism. "Validation cohort" constituted children who presented with delayed puberty. INTERVENTION AND OUTCOME: GnRHa (Triptorelin) stimulation test along with measurement of inhibin B level at 24 h after GnRHa injection was performed in all the study participants. Cut-offs for GnRH-iB were derived from the "exploratory cohort". These cut-offs were applied to the "validation cohort". Basal LH, basal inhibin B(INH-B), GnRHa-stimulated LH at 4 h (GnRH-LH) and GnRH-iB were evaluated for the prediction of onset of puberty on prospective follow-up. RESULTS: GnRH-iB at a cut-off value of 113.5 pg/ml in boys and 72.6 pg/ml in girls had 100% sensitivity and specificity for the documentation of puberty. In the "validation cohort" basal LH, basal INH-B, GnRH-LH, and GnRH-iB had a diagnostic accuracy of 68.75%, 81.25%, 68.75% and 93.75% respectively, for the prediction of onset of puberty. Basal LH, basal INH-B and GnRH-LH used alone or in combination were inferior to GnRH-iB used alone. CONCLUSION: GnRHa-stimulated inhibin B (GnRH-iB) is a convenient and easily employable test for the differentiation of constitutional delay in puberty from hypogonadotropic hypogonadism. CTRI REGISTRATION NO: CTRI/2019/10/021570.

Remission in Cushing's disease is predicted by cortisol burden and its withdrawal following pituitary surgery.

AIM: To ascertain the predictors of remission and relapse in patients of Cushing's disease (CD) undergoing pituitary transsphenoidal surgery (TSS). METHODS: Patients with CD subjected to TSS over 35 years at a tertiary care center were included. Patients were grouped into remission and persistent disease at 1 year after surgery, and were further followed up for relapse. Demographic, clinical, biochemical, histological, radiological and post-operative follow-up parameters were analyzed. RESULTS: Of the 152 patients of CD, 145 underwent TSS. Remission was achieved in 95 (65.5%) patients at 1 year. Patients in remission had shorter duration of symptoms prior to presentation (p = 0.009), more frequent presence of proximal myopathy (p = 0.038) and a tumor size of < 2.05 cm (p = 0.016) in comparison to those with persistent disease. Post-TSS, immediate post-operative 0800-h cortisol (< 159.85 nmol/L; p = 0.001), histological confirmation of tumor (p = 0.045), duration of glucocorticoid replacement (median 90 days; p = 0.001), non-visualization of tumor on MRI (p = 0.003), new-onset hypogonadism (p = 0.001), 3-month 0800-h cortisol (< 384.9 nmol/L; p = 0.001), resolution of diabetes (p = 0.001) and hypertension (p = 0.001), and recovery of hypothalamic-pituitary-adrenal axis (p = 0.018) favored remission. In logistic regression model, requirement of glucocorticoid replacement (p = 0.033), and resolution of hypertension post-TSS (p = 0.003) predicted remission. None of the parameters could predict relapse. CONCLUSION: The study could ascertain the predictors of remission in CD. Apart from the tumor characteristics, surgical aspects and low post-operative 0800-h cortisol, the results suggest that baseline clinical parameters, longer glucocorticoid replacement, and resolution of metabolic complications post-TSS predict remission in CD. Long-term follow-up is essential to look for relapse.

Primary hyperparathyroidism in pregnancy: observations from the Indian PHPT registry.

PURPOSE: To present the data on primary hyperparathyroidism (PHPT) in pregnancy from India obtained from a large database maintained over 15 years. METHODS: We retrieved data of all women with gestational PHPT from the Indian PHPT registry between July 2005 and January 2020, and compared their clinical, biochemical, and other characteristics with age-matched non-pregnant women with PHPT. RESULTS: Out of 386 women, eight had gestational PHPT (2.1%). The common presenting manifestations were acute pancreatitis (50%) and renal stone disease (50%); two were asymptomatic. Five women (62.5%) had a history of prior miscarriages. Seven patients (88%) had preeclampsia during the present gestation. Serum calcium and intact parathyroid hormone (iPTH) were not statistically different from the age-matched non-pregnant PHPT group. Six patients with mild-to-moderate hypercalcemia were medically managed with hydration with/without cinacalcet while one patient underwent percutaneous ethanol ablation of the parathyroid adenoma; none underwent surgery during pregnancy. Mean serum calcium maintained from treatment initiation till delivery was 10.5 ± 0.4 mg/dl. One patient had spontaneous preterm delivery at 36 weeks; the remaining patients had normal vaginal delivery at term. None had severe preeclampsia/eclampsia. Fetal outcomes included low birth weight in three newborns (37.5%); two of them had hypocalcemic seizures. CONCLUSION: The prevalence of gestational PHPT was 2.1% in this largest Indian PHPT cohort, which is higher than that reported from the West (< 1%). Gestational PHPT can lead to preeclampsia and miscarriage. Pregnant PHPT patients with mild-to-moderate hypercalcemia can be managed with hydration/cinacalcet; however, long-term safety data and large-scale randomized controlled trials are required.

Non-donor specific anti-human leukocyte antigen (HLA) antibodies are not associated with poor outcome in hematopoietic stem cell transplant recipients.

Testing for anti-human leukocyte antigen (HLA) antibodies has now become standard practice in allogeneic hematopoietic stem cell transplantation (HSCT), and anti-HLA antibodies (both donor specific and non-donor specific) are being identified and have many potential consequences. Most studies suggest that donor-specific HLA antibodies lead to adverse outcomes, though little is reported on non-donor specific anti-HLA antibodies. We present the results of a retrospective cohort analysis of 157 patients who received HSCT at the University of Rochester over a period of four years. We identified 45 patients (28.7%) who had detectable anti-HLA antibodies, while only one patient (0.6%) had donor-specific anti-HLA antibodies. Patients with prior pregnancies and multiple transfusions were at increased risk to develop antibodies. In our cohort, the presence of non-donor specific anti-HLA antibodies did not significantly impact overall survival, progression free survival, graft failure, or transplant-related mortality.

Unmasking and aggravation of polycythemia vera by canagliflozin.

BACKGROUND: Sodium-glucose co-transporter-2 inhibitors are novel antidiabetes drugs that act via inhibition of renal glucose reabsorption. This action causes osmotic diuresis, reduces intravascular volume and is associated with various adverse effects. In the present paper, we describe the first report on the unmasking of underlying polycythemia vera by canagliflozin in a person with Type 2 diabetes mellitus, which was temporally related to the use of the drug. CASE REPORT: A 51-year-old obese man with Type 2 diabetes was prescribed canagliflozin 100 mg for control of his glycaemia. He presented 6 months later with asymptomatic elevation of his haemogram measurements (haemoglobin: 16.9 g/dl; haematocrit: 55%; red cell number: 8.1 million/mm3 ; total leukocytes: 23010/mm3 ; platelet count: 9.7 *106 /mm3 ). He had no history of smoking, exposure to high altitude or other drugs. Subsequent investigations revealed myeloproliferative neoplasm (polycythemia vera) on trephine biopsy of bone marrow, normal erythropoietin level and JAK2V617F positivity. Because of the possibility that the underlying condition had been unmasked by canagliflozin, the latter was stopped. This led to a remarkable improvement in the man's haematological profile, with no other significant intervention. The man subsequently restarted the drug of his own accord, causing his haematological profile to worsen again and thereby posing a challenge in monitoring of both polycythemia vera as well as diabetes mellitus. CONCLUSION: This report brings to light unmasking of a new adverse effect of sodium-glucose co-transporter-2 inhibitors in clinical practice caused by volume loss, apart from hypotension and falls.

Thoracoabdominal pressure gradient and gastroesophageal reflux: insights from lung transplant candidates.

Advanced lung disease is associated with gastroesophageal reflux disease (GERD). The thoracoabdominal pressure gradient (TAPG) facilitates gastroesophageal reflux, but the effects of TAPG on gastroesophageal reflux in patients with pulmonary disease have not been well defined. Patients diagnosed with end-stage lung disease are expected to have the most extreme derangement in respiratory mechanics. The aim of this study is to explore the relationship between TAPG and reflux in lung transplant (LTx) candidates. We reviewed LTx recipients who underwent pretransplant esophageal high-resolution manometry and a 24-hour pH study. Patients were excluded if they were undergoing redo LTx, had manometric hiatal hernia, or had previously undergone foregut surgery. TAPG was defined as the intra-abdominal pressure minus the intrathoracic pressure during inspiration. Adjusted TAPG was calculated by the TAPG minus the resting lower esophageal sphincter (LES) pressure (LESP). Twenty-two patients with normal esophageal function tests (i.e., normal esophageal motility with neither manometric hiatal hernia nor pathological reflux on 24-hour pH monitoring) were selected as the pulmonary disease-free control group. In total, 204 patients underwent LTx between January 2015 and December 2016. Of these, 77 patients met inclusion criteria. We compared patients with obstructive lung disease (OLD, n = 33; 42.9%) and those with restrictive lung disease (RLD, n = 42; 54.5%). 2/77 patients (2.6%) had pulmonary arterial hypertension. GERD was more common in the RLD group than in the OLD group (24.2% vs. 47.6%, P = 0.038). TAPG was similar between the OLD group and the controls (14.2 vs. 15.3 mmHg, P = 0.850); however, patients in the RLD group had significantly higher TAPG than the controls (24.4 vs. 15.3 mmHg, P = 0.002). Although TAPG was not correlated with GERD, the adjusted TAPG correlated with reflux in all 77 patients with end-stage lung disease (DeMeester score, rs = 0.256, P = 0.024; total reflux time, rs = 0.259, P = 0.023; total number of reflux episodes, rs = 0.268, P = 0.018). Additionally, pathological reflux was seen in 59.1% of lung transplant candidates with adjusted TAPG greater than 0 mmHg (i.e., TAPG exceeding LESP); GERD was seen in 30.9% of patients who had an adjusted TAPG ≤ 0 mmHg. In summary, TAPG varies based on the underlying cause of lung disease. Higher adjusted TAPG increases pathological reflux, even if patients have normal antireflux anatomy and physiology (i.e., no hiatal hernia and manometrically normal LES function). Adjusted TAPG may provide further insights into the pathophysiology of GERD.

p40 in metastatic pulmonary trophoblastic tumour: potential diagnostic pitfall on histopathology.

p40, one of the two isomers of p63, is nowadays widely used for diagnosis of squamous cell carcinoma, especially in subtyping non-small cell carcinoma on lung biopsies. We describe a case in which lung tumour was misdiagnosed as squamous cell carcinoma due to p40 immunopositivity. A 36-year-old lady presented with cough and left sided chest pain of 2 months duration. Chest imaging revealed a lesion in left lower lobe of the lung and biopsy was suggestive of squamous cell carcinoma. However, past history revealed amputation of great toe for non-healing discharging ulcer which on histopathology was diagnosed as choriocarcinoma. She also had a history of hysterectomy five years ago, details of which were not available. Post-amputation ß-hCG levels were high and she had been treated with multimodality chemotherapy for choriocarcinoma. She had good response to chemotherapy initially, however became resistant later on. Review of the lung biopsy in the light of the past history along with extensive literature review led to the final diagnosis of metastatic trophoblastic tumour to lung. Hence, awareness that p40 immunopositivity can be seen in trophoblastic tumours is essential to avoid misdiagnosis, especially in sites like the lung where squamous cell carcinoma is common.

Accuracy of glycated haemoglobin in screening for pre-diabetes in Asian Indians--a community survey: the Chandigarh Urban Diabetes Study (CUDS).

AIM: To compare American Diabetes Association and International Expert Committee recommended cut-off values of HbA(1c) for detecting the presence of pre-diabetes against plasma glucose values obtained from oral glucose tolerance tests in Asian Indians. METHODS: A cross-sectional randomly sampled population survey involving 2368 adults, aged ≥ 20 years. HbA(1c) was measured on a Bio-Rad 10 system in 1972 subjects. RESULTS: Of the 1972 subjects studied, 329 were detected to have pre-diabetes based on isolated impaired fasting glucose in 125 subjects (6.3%), isolated impaired glucose tolerance in 141 subjects (7.1%) and the presence of both in 63 subjects (3.2%). The HbA(1c) cut-off of 34 mmol/mol (5.7%), as recommended by the American Diabetes Association for detecting the presence of pre-diabetes, showed sensitivity of 62%, specificity 77%, with a positive predictive value of 34.7%, a negative predictive value of 89.5% and accuracy of 67.8%; whereas the HbA(1c) cut-off recommended by the International Expert Committee of 42 mmol/mol (6%) had a sensitivity of 36%, specificity of 90%, positive predictive value of 42.7%, negative predictive of 85.4% and an accuracy of 77%. However, both these HbA(1c) cut-offs underdiagnosed the presence of pre-diabetes in 38 and 64% of these subjects, respectively. CONCLUSIONS: The American Diabetes Association and the International Expert Committee recommended HbA(1c) cut-off values and oral glucose tolerance tests identify different pre-diabetes cohorts. Long-term prospective studies are required to define the usefulness of one over the other.

Prevalence and pattern of hand soft-tissue changes in type 2 diabetes mellitus.

AIMS AND OBJECTIVES: Hand soft-tissue changes are well described in patients with T1DM, but not in T2DM patients. For this reason, this study aimed at examining the prevalence and pattern of hand soft-tissue changes in patients with T2DM. METHODS: A total of 206 consecutive patients with T2DM and 203 age-, gender- and occupation-matched healthy controls were examined by two individual observers, and then underwent the appropriate investigations. RESULTS: The 132 (64%) patients with T2DM included 187 hands compared with 96 (23.6%) healthy controls including 133 hands (P=0.01 for both). Dupuytren's contracture (DC) (42 vs. 29.3%, respectively; P=0.01), limited joint mobility (LJM) (39 vs. 28.5%, respectively; P=0.01) and carpal tunnel syndrome (CTS) (5.3 vs. 1%, respectively; P=0.01) were significantly higher in T2DM patients than in the controls, but not stenosing flexor tenosynovitis (FTS, 'trigger finger'). Indeed, none of the patients or controls had FTS. In patients with T2DM, DC showed a radial shift, and was more horizontal and severe than in the controls. These hand soft-tissue changes correlated significantly with age (P=0.0001), duration of diabetes (P=0.001) and the presence of microangiopathy (P=0.001). CONCLUSION: Hand changes are more prevalent and severe in patients with T2DM, and are correlated with age, duration of diabetes and microvascular complications.

Predictors of pilosebaceous unit responsiveness to testosterone therapy in patients with hypogonadotrophic hypogonadism.

Testosterone replacement therapy is the mainstay of treatment in male patients with isolated hypogonadotrophic hypogonadism (HH) to achieve virilisation. However, responsiveness of pilosebaceous unit (PSU) to testosterone replacement therapy in these patients is quite variable. Androgen action is inversely proportional to the number of CAG repeats in exon 1 of androgen receptor gene; therefore, we hypothesised that CAG repeat length contributes to testosterone responsiveness in patients with HH. The CAG repeat length in 21 well-virilised men (hair score > 30, responders) and 25 poorly virilised men (hair score ≤ 30, non-responders) with HH on optimal testosterone replacement therapy at least for a period of 1 year was analysed. Serum LH, FSH, testosterone and 17 ß oestradiol were estimated. Polymerase chain reaction (PCR) amplification of exon 1 of androgen receptor gene was performed from genomic DNA, and these PCR-amplified products were sequenced for the number of CAG repeats. The difference between number of CAG repeats in responders and non-responders was statistically significant (19.19 ± 3.25 and 22.24 ± 2.65, P = 0.001) and showed a strong negative correlation with total body hair score (r = -0.538 and P = 0.0001). In conclusion, these results suggest that the number of CAG repeats influences the responsiveness of PSU to testosterone treatment in patients with HH.

Adolescent acromegaly: clinical parameters and treatment outcome.

BACKGROUND: Adolescent acromegaly is a rare disorder and these patients present with tall stature/gigantism, tumor mass effects and menstrual irregularities. PATIENTS AND METHODS: 34 consecutive (26 males) patients having onset of disease prior to 21 years of age were included in this retrospective analysis. Their clinical features and treatment outcome were studied. RESULTS: Mean age and lag time at presentation were 21.6 +/- 3.9 years and 5.1 +/- 3.5 years respectively. Common presenting manifestations included acral enlargement, tumor mass effects and menstrual irregularities. Mean height at presentation was 174.6 +/- 13.7 cms (range: 150-210 cm) and one third had gigantism (height > or =97th percentile, WHO growth charts). Hypertension and glucose intolerance were seen in 15% and 23.5% respectively. Mean nadir GH after glucose load was 58.2 +/- 13.7 ng/ml and IGF -1 was 534.8 +/- 132.8 ng/ml. Half of the patients had concomitant hyperprolactinemia. Almost all (97%) had macroadenoma and anterior pituitary hormone deficiencies were frequent (75%). Patients with gigantism were younger (19.6 +/- 4.9 vs. 22.6 +/- 2.9 years; p = 0.001), had higher GH values (66.68 +/- 27.22 vs. 53.98 +/- 15.99 ng/ml; p = 0.04) and hypogonadism was more common (90.9% vs. 56.5%, p = 0.03) than those with normal stature. 32 patients (94.1%) were treated primarily with surgery, 7 (21.9%) received post operative radiotherapy. Mean duration of follow up was 33.1 +/- 10.1 months. Only 30% had nadir GH values of <1 ng/ml. CONCLUSION: One third of adolescent patients had acrogigantism. These patients were younger, had higher GH levels and concurrent hypogonadism was more common. Cure could be achieved only in about one third of the patients.

Efficacy of cabergoline on rapid escalation of dose in men with macroprolactinomas.

BACKGROUND & OBJECTIVES: Since cabergoline has a long half-life and sustained occupancy of dopamine (D2) receptors in lactotrophs, its doses are slowly built up either monthly or two monthly. This possibly results in delayed normalization of serum prolactin and slow reduction in tumour size. This study was planned to assess the efficacy and safety of rapid escalation of cabergoline doses in men with macroprolactinomas. MATERIALS: Fifteen consecutive men with macroprolactinomas underwent evaluation for anterior pituitary functions, visual fields, quality of life (QOL) score and magnetic resonance imaging (MRI), at baseline and after 6 months of cabergoline therapy. Serum prolactin and testosterone levels were assessed at monthly intervals. Cabergoline was started at a dosage of 0.5 mg twice per week and increased to 1.5 mg twice per week (3 mg ) by the third week, as 3 mg is usually considered as effective dose. Subsequent increase in doses was done as per protocol. RESULTS: The mean age of patients at presentation was 31.7 +/- 3.3 yr and duration of symptoms was 25.0 +/- 3.6 months. Serum prolactin at baseline was 6249.3 +/- 3259.2 microg/l with a tumour volume of 28.9 +/- 8.3 cm(3). Eighty six per cent of the patients had visual field defects while 53 per cent had decreased visual acuity. The mean dose of cabergoline required was 3.2 mg/wk. Symptoms improved in majority (93%) of patients after four weeks of cabergoline therapy with a dramatic fall in serum prolactin by 99 per cent from 6249.3 +/- 3259.2 to 46.9 +/- 14.9 microg/l and it was normalized in 93 per cent of the patients by 8.2 wk. Improvement in visual field defects was noted in all but one, after one month and there was further improvement at 6 months. All patients had >25 per cent reduction in tumour size, and 73 per cent had > 50 per cent reduction after six months of cabergoline therapy. Basal circulating testosterone levels were low in 11 (73%) patients and started improving from first month of cabergoline therapy and became normal in around half of the patients after 6 months. No major side effects were observed requiring discontinuation of cabergoline therapy. INTERPRETATION & CONCLUSIONS: Our preliminary findings show that rapid build-up of cabergoline doses increases its efficacy as well as rapidity of response in terms clinical improvement, normalization of serum prolactin and gonadal functions and reduction in tumour size, without compromising its safety in men with macroprolactinomas. Further studies with a larger sample size and control group for comparison need to be done to confirm these findings.

A child with suprasellar mass and ascites.

A 7-year-old child having short stature presented with headache and vomiting of 6 months' duration. MRI of the brain showed a sellar and suprasellar mass suggestive of craniopharyngioma with hydrocephalus. He underwent a right ventriculo-peritoneal (V-P) shunting followed by a subtotal resection of the tumour. A year later, he presented with progressive ascites and umbilical hernia. Systemic examination was unremarkable except for massive ascites. Ultrasound abdomen confirmed free-fluid in the peritoneal cavity and the ascitic fluid was transudative. Ventriculo-cysternography revealed a functional and patent V-P shunt. A diagnosis of cerebrospinal fluid ascites (shunt ascites) was made and he underwent ventriculo-atrial shunting. After treatment the patient improved with the gradual disappearance of ascites.

A case of successful treatment of cutaneous Acanthamoeba infection in a lung transplant recipient.

Acanthamoeba species are known to cause 2 well-described entities: (1) granulomatous amoebic encephalitis (GAE), which usually affects immunocompromised hosts, and (2) keratitis, which typically follows trauma associated with contamination of water or contact lenses. Less common manifestations include pneumonitis and a subacute granulomatous dermatitis. We describe a case of granulomatous dermatitis secondary to Acanthamoeba infection in a lung transplant recipient and a successful outcome following treatment with lipid formulation of amphotericin B and voriconazole. We believe this is the second case report describing disseminated Acanthamoeba infection in a lung transplant recipient. We also describe successful outcome with a combination of lipid formulation of amphotericin B and voriconazole, drugs that have not been previously reported to treat Acanthamoeba.

Radioactive iodine therapy in Graves' hyperthyroidism: a prospective study from a tertiary referral centre in north India.

BACKGROUND: Radioactive iodine has gained widespread acceptance as the first-line therapy for Graves' hyperthyroidism and is the preferred treatment option in most situations. OBJECTIVE: A prospective study was conducted to look at the therapeutic practice of use of radioactive iodine in the treatment of Graves' hyperthyroidism, to determine whether the expected or desired therapeutic outcome is achieved. SETTINGS: A tertiary referral centre in north India, Delhi that caters to patients with thyroid disorders. METHODS: One hundred and seventy four consecutive subjects with Graves' hyperthyroidism, who were given radioactive iodine were followed up. RESULTS: There were 59 (33.9%) males and 115 (66.1%) females. The mean age was 41.8 +/- 9 years. The dose of radioactive iodine ranged from 2 mCi to 15 mCi and the mean dose administered was 5.2 +/- 1.9 mCi. After one year following radioactive iodine therapy, 29 (16.7%) subjects were euthyroid, 51 (29.3%) were hypothyroid and the remaining 94 (54%) had persisting hyperthyroidism. Those subjects with persisting hyperthyroidism at one year after radioactive iodine had received a significantly lower dose compared to the groups who had achieved cure (either euthyroidism or hypothyroidism). CONCLUSION: The study shows that the current practice of empirical low dose radioactive iodine therapy to avoid hypothyroidism results in majority of patients having persisting hyperthyroidism. There is a need to take a new look at the current practice to increase the cure rate.

Familial aggregation of autoimmune thyroiditis in first-degree relatives of patients with juvenile autoimmune thyroid disease.

Several studies have shown aggregation of autoimmune thyroiditis in families by estimation of thyroid antibodies. However, the prevalence by concurrent estimation with fine-needle aspiration cytology (FNAC) and thyroid antibodies has not been previously reported. We therefore studied 222 first-degree relatives (group 1) of 71 index cases diagnosed as lymphocytic thyroiditis on FNAC and 81 family members (group 2) of 23 goitrous children diagnosed as colloid goiter on FNAC for comparison. Successful FNAC conducted in 122 group 1 subjects revealed lymphocytic thyroiditis in 51 (42%), whereas lymphocytic thyroiditis was diagnosed in only 5 goitrous subjects (13%) in group 2. Among group 1 subjects with FNAC-proven lymphocytic thyroiditis, antithyroid peroxidase (TPO) antibodies were found in 35 (67%), while in anti-TPO antibody positive goitrous relatives of group 1, lymphocytic thyroiditis was found in 36 (78%). Eight new cases of overt hypothyroidism and 45 new cases of subclinical hypothyroidism were diagnosed among group 1 subjects. Our study suggests: (1). familial clustering of autoimmune thyroiditis; (2). if only FNAC or thyroid antibodies is used for diagnosis of autoimmune thyroiditis in children, 22%-33% of cases are likely to be missed; and (3). serum thyrotropin (TSH) should be offered to all first-degree relatives of patients with juvenile autoimmune thyroiditis.

Comparative immunological and histopathological study in fifty cases of mucosal/nonmucosal lichen planus.

Lichen planus is a common disorder and 40-50% of LP patients also reveal mucosal lesions. It is well known that mucosal LP lesions take very long to heal in comparison to cutaneous lesions. Rarely erosive mucosal LP can turn malignant. Both CMI and humoral immunity may play role in aetiopathogenesis of LP. Present study was conducted to study and compare CMI, Humoral Immunity, histopathology in mucosal and nonmucosal LP.

Enhancement of liposome-mediated gene transfer to human airway epithelial cells by replication-deficient adenovirus.

We hypothesized that replication-deficient adenovirus (Ad), when complexed with plasmid DNA (pl) and cationic liposomes (L), would enhance liposome-mediated gene transfer in cultured human airway epithelial cells. Pl/L/Ad complexes were formed using charge-charge interactions. A gel electrophoresis retardation assay showed plasmid DNA to be associated with the virus in a high-molecular-weight, low-mobility complex, the diameter of which was 300 to 350 nm. Compared to pl/L alone, pl/L/Ad enhanced luciferase expression on average by 1 log-fold in human airway epithelial cells which express either mutant or wild-type cystic fibrosis transmembrane conductance regulator (CFTR). Transgene expression was sustained at high levels for up to 7 days following transfection with pl/L/Ad. Using a heat-stable alkaline phosphatase reporter gene, we showed that a larger fraction of cells was transfected by pl/L/Ad compared to pl/L. Finally, cells were exposed to Ad for 0 to 24 hours prior to pl/L or exposed to pl/L prior to Ad. We found that enhancement was significantly greater using pl/L/Ad compared to the simultaneous addition of Ad with the pl/L complexes. In addition, when pl/L was added 4 to 24 hours prior to Ad, some enhancement was found, suggesting that plasmid DNA remained in a compartment in the cell for several hours and became available for transcription with the addition of Ad. When Ad was added prior to pl/L, enhancement was found suggesting that the effect of the virus on cell membranes may persist for up to 24 hours. We conclude that the tripartite pl/L/Ad complex significantly enhances liposome-mediated transgene expression for a prolonged period of time in human bronchial epithelial cells.