Carbamazepine-induced Life-threatening Stevens-Johnson Syndrome and Agranulocytosis: The Maiden Case.

Stevens-Johnson syndrome is one of the few dermatological emergencies in clinical practice. The syndrome is often secondary to the usage of drugs, of which allopurinol, penicillins, sulfa drugs, ibuprofen, sodium valproate, phenytoin, lamotrigine and carbamazepine are commonly implicated. Agranulocytosis is the existence of a clinically significant reduction in neutrophil count. This condition is a serious threat to the patient, as he/she is at a greater risk of contracting bacterial or fungal infections, which may prove to be fatal. The co-existence of Stevens-Johnson syndrome and agranulocytosis in the same patient further increases the risk of morbidity and mortality. To the best of our knowledge, there are no reports available in the existing literature, of cases that were reported with both these life-threatening conditions in a single patient, at the same point of time. This is a case narrative of a patient who presented with both Stevens-Johnson syndrome and agranulocytosis, following the administration of carbamazepine The patient's differential leucocyte count revealed a neutrophil proportion of 2.33%. A causality assessment done using Naranjo's algorithm showed that carbamazepine "definitely" caused Agranulocytosis and "probably" caused Stevens-Johnson syndrome.

Role of leptin in delayed embryonic development in the Indian short-nosed fruit bat, Cynopterus sphinx.

An adiposity-associated rise in leptin occurs at the time of delayed embryonic development in Cynopterus sphinx. The aim of present study was to examine the mechanism by which leptin may inhibit progesterone, and therefore could be responsible for delayed development. The study showed a significant increase in circulating leptin level during the period of increased fat accumulation, which coincided with significant decrease in serum progesterone level and delayed embryonic development in C. sphinx. The study showed increased Ob-R expression in the corpus luteum and in the utero-embryonic unit during the period of delayed embryonic development. The in vitro study showed suppressive effect of leptin on progesterone synthesis. The effect of high dose of leptin on ovarian steroidogenesis was found to be mediated through decreased expression of StAR and LH-R proteins in the ovary. The treatment with leptin caused increased expression of STAT 3 and iNOS proteins in the ovary, which correlated with decreased expression of StAR protein in the ovary. The inhibitory effects of leptin on progesterone synthesis in the ovary are thus mediated through STAT 3 and iNOS-NO signaling pathways. This study further demonstrated low expression of PCNA coinciding with the increased concentration of the leptin receptor in the utero-embryonic unit and high circulating leptin level during November. In conclusion, adiposity associated increased leptin level during November-December might play role in suppressing progesterone synthesis in the corpus luteum as well as suppressing the rate of cell-proliferation in the utero-embryonic unit thereby causing delayed embryonic development in C. sphinx.

Melatonin regulates delayed embryonic development in the short-nosed fruit bat, Cynopterus sphinx.

The aim of the present study was to evaluate the seasonal variation in serum melatonin levels and their relationship to the changes in the serum progesterone level, ovarian steroidogenesis, and embryonic development during two successive pregnancies of Cynopterus sphinx. Circulating melatonin concentrations showed two peaks; one coincided with the period of low progesterone synthesis and delayed embryonic development, whereas the second peak coincided with regressing corpus luteum. This finding suggests that increased serum melatonin level during November-December may be responsible for delayed embryonic development by suppressing progesterone synthesis. The study showed increased melatonin receptors (MTNR1A and MTNR1B) in the corpus luteum and in the utero-embryonic unit during the period of delayed embryonic development. The in vitro study showed that a high dose of melatonin suppressed progesterone synthesis, whereas a lower dose of melatonin increased progesterone synthesis by the ovary. The effects of melatonin on ovarian steroidogenesis are mediated through changes in the expression of peripheral-type benzodiazepine receptor, P450 side chain cleavage enzyme, and LH receptor proteins. This study further showed a suppressive impact of melatonin on the progesterone receptor (PGR) in the utero-embryonic unit; this effect might contribute to delayed embryonic development in C. sphinx. The results of the present study thus suggest that a high circulating melatonin level has a dual contribution in retarding embryonic development in C. sphinx by impairing progesterone synthesis as well as by inhibiting progesterone action by reducing expression of PGR in the utero-embryonic unit.

Relationship between delayed embryonic development and metabolic factors and fat deposition in fruit bat Cynopterus sphinx.

The present study was undertaken in the fruit bat Cynopterus sphinx, which breeds twice in quick succession at Varanasi, India. Its gestation period varies significantly in the two successive pregnancies of the year owing to delayed embryonic development during the first (winter) pregnancy. The primary aim of the present study was to determine the role of metabolic factors in delayed embryonic development in the fruit bat C. sphinx. Variation in bodyweight, fat deposition, oxygen (O(2)) consumption rate, basal metabolic rate (BMR), body temperature (Tb) and hepatic succinate dehydrogenase (SDH) activity, along with circulating levels of thyroid hormones (tri-iodothyronine and thyroxine), were examined as metabolic factors during the two successive pregnancies in C. sphinx. The increase in bodyweight observed in November was due to accumulation of white adipose tissue in the posterior abdominal region. A significant decline in O(2) consumption rate, BMR, Tb and SDH activity was found in early winter in November-December, which coincides closely with the period of fat accumulation and with the period of delayed embryonic development in C. sphinx. A significantly higher O(2) consumption rate, BMR, Tb and SDH activity was noted during the second pregnancy in, when embryonic development was relatively faster. Thyroid hormone levels were high during the period of embryonic delay compared with levels during the remaining months. The results of the present study suggest that the delayed embryonic development in C. sphinx during early winter may be due to a low O(2) consumption rate, BMR, Tb and SDH activity in November-December. The energy saved by suppressing embryonic development in this species may be advantageous for fat accumulation. Increased thyroid hormone levels during the early winter period might facilitate fat accumulation in C. sphinx.

Characteristics of gestational diabetic mothers and their babies in an Indian diabetes clinic.

AIMS AND OBJECTIVES: To compare clinical and metabolic features of mothers with gestational diabetes (GDM) and their offspring with those in non-diabetic pregnancies at the King Edward Memorial Hospital, Pune, India. MATERIALS AND METHODS: Antenatal information was obtained from hospital records. GDM was diagnosed by 75 g OGTT (Oral Glucose Tolerance Test) in clinically high-risk women. Anthropometric measurements of mother and the babies were recorded within 24h of delivery and a maternal blood sample collected for hematological and biochemical measurements. RESULTS: Between the period Jan 1998 to December 2003,265 women with gestational diabetes were treated in our Unit. Forty nine percent had first-degree relatives with diabetes. Compared to non-diabetic mothers (n=215) GDM mothers were older (29.0 vs. 26.0y, p<0.001), more obese (body mass index- BMI 26.0 vs. 22.0 kg/m2, p<0.001), centrally obese (Waist hip ratio-WHR 0.89 vs 0.86, p<0.001), adipose (sum of 4 skinfolds 98.4 vs. 61.4 mm, p<0.001) and had higher blood pressure (127/80 vs. 122/70 mmHg, p<0.001). GDM mothers had higher concentrations of plasma triglycerides (195.0 vs. 153.0 mg/dl, p<0.01); blood hemoglobin (11.7 vs 10.9 g/dl, p<0.001) and higher platelet count but lower concentration of HDL cholesterol and albumin. Sixty percent GDM mothers and 34% of non-diabetic mothers were delivered by caesarean-section, 23% of GDM mothers delivered pre term (<37 wk). Despite the smaller gestation, babies of GDM mothers were heavier (BW 2950.0 vs. 2824.0g, p<0.001, adjusted for gender), longer (48.9 vs. 48.0 cm, p<0.01) and more adipose (sum of 2 skinfolds 10.5 vs. 8.5 mm). Only 5% of babies born to GDM mothers weighed > 4000 g but 30% were >90th centile of birth weight of babies born to non-diabetic mothers. Babies of GDM mothers suffered higher neonatal morbidity. CONCLUSIONS: GDM mothers in urban India are more obese and more adipose than non-diabetic mothers, frequently have a family history of diabetes and show metabolic features of insulin resistance syndrome, suggesting high cardiovascular risk. Neonates of GDM mothers are heavier, longer and more adipose than those born to non-diabetic mothers, and suffer higher neonatal morbidity.

Effects of metformin treatment on luteal phase progesterone concentration in polycystic ovary syndrome.

The causes of luteal phase progesterone deficiency in polycystic ovary syndrome (PCOS) are not known. To determine the possible involvement of hyperinsulinemia in luteal phase progesterone deficiency in women with PCOS, we examined the relationship between progesterone, luteinizing hormone (LH) and insulin during the luteal phase and studied the effect of metformin on luteal progesterone levels in PCOS. Patients with PCOS (19 women aged 18-35 years) were treated with metformin (500 mg three times daily) for 4 weeks prior to the test cycle and throughout the study period, and submitted to ovulation induction with clomiphene citrate. Blood samples were collected from control (N = 5, same age range as PCOS women) and PCOS women during the late follicular (one sample) and luteal (3 samples) phases and LH, insulin and progesterone concentrations were determined. Results were analyzed by one-way analysis of variance (ANOVA), Duncan's test and Karl Pearson's coefficient of correlation (r). The endocrine study showed low progesterone level (4.9 ng/ml) during luteal phase in the PCOS women as compared with control (21.6 ng/ml). A significant negative correlation was observed between insulin and progesterone (r = -0.60; P < 0.01) and between progesterone and LH (r = -0.56; P < 0.05) concentrations, and a positive correlation (r = 0.83; P < 0.001) was observed between LH and insulin. The study further demonstrated a significant enhancement in luteal progesterone concentration (16.97 ng/ml) in PCOS women treated with metformin. The results suggest that hyperinsulinemia/insulin resistance may be responsible for low progesterone levels during the luteal phase in PCOS. The luteal progesterone level may be enhanced in PCOS by decreasing insulin secretion with metformin.

Effects of metformin treatment on luteal phase progesterone concentration in polycystic ovary syndrome

The causes of luteal phase progesterone deficiency in polycystic ovary syndrome (PCOS) are not known. To determine the possible involvement of hyperinsulinemia in luteal phase progesterone deficiency in women with PCOS, we examined the relationship between progesterone, luteinizing hormone (LH) and insulin during the luteal phase and studied the effect of metformin on luteal progesterone levels in PCOS. Patients with PCOS (19 women aged 18-35 years) were treated with metformin (500 mg three times daily) for 4 weeks prior to the test cycle and throughout the study period, and submitted to ovulation induction with clomiphene citrate. Blood samples were collected from control (N = 5, same age range as PCOS women) and PCOS women during the late follicular (one sample) and luteal (3 samples) phases and LH, insulin and progesterone concentrations were determined. Results were analyzed by one-way analysis of variance (ANOVA), Duncan's test and Karl Pearson's coefficient of correlation (r). The endocrine study showed low progesterone level (4.9 ng/ml) during luteal phase in the PCOS women as compared with control (21.6 ng/ml). A significant negative correlation was observed between insulin and progesterone (r = -0.60; P < 0.01) and between progesterone and LH (r = -0.56; P < 0.05) concentrations, and a positive correlation (r = 0.83; P < 0.001) was observed between LH and insulin. The study further demonstrated a significant enhancement in luteal progesterone concentration (16.97 ng/ml) in PCOS women treated with metformin. The results suggest that hyperinsulinemia/insulin resistance may be responsible for low progesterone levels during the luteal phase in PCOS. The luteal progesterone level may be enhanced in PCOS by decreasing insulin secretion with metformin.