Phosphatidylinositide-3 kinase: a newer molecular target in metabolic and hormonal pathway of polycystic ovary syndrome.

Polycystic ovary syndrome is characterized by hyperandrogenemia, hyperinsulinemia and/or abnormal ovulation, which are the 3 main consequences of polycystic ovary syndrome. The occurrence of polycystic ovary syndrome is higher and 1 out of 45 women gets affected by this disorder. The pathophysiology of polycystic ovary syndrome is very unique, and many hormonal and metabolic changes occur at molecular level. Polycystic ovary syndrome is a hormonal disorder that affects multiple organ systems within the body, which is caused by insensitivity to the hormone insulin. The target organs of insulin action are skeletal muscles, adipose tissue, fibroblasts where metabolic actions of insulin take place. In polycystic ovary syndrome condition, due to insulin resistance, the actions like glucose uptake and glycogen synthesis gets declined along with exhibiting steroidogenic effect in ovaries. The action of phophatidylinositide-3 kinase varies in different tissues. It plays major role in several kinases. The inhibition and activation of phophatidylinositide-3 kinase in different tissues results in differential outcomes. The inhibition of phophatidylinositide-3 kinase in ovary leads to decreased androgen synthesis and the activation affects the positive actions of insulin like glucose uptake. Targeting the hyperandrogenemia of polycystic ovary syndrome, we can get more ameliorating action in polycystic ovary syndrome because glucose uptake, which is mediated by phophatidylinositide-3 kinase activation, is not much altered during polycystic ovary syndrome as much as the androgen levels in polycystic ovary syndrome. Therefore, it is beneficial to control the androgen level. Thus, phophatidylinositide-3 kinase inhibition can be a promising target in the treatment of polycystic ovary syndrome.

Kearns Sayre Syndrome--case report with review of literature.

Kearns-Sayre Syndrome is form of rare mitochondrial cytopathy, first described by Thomas P. Kearns and George Pomeroy Sayre in 1958 and is characterized by progressive external opthalmoplegia, cardiac conduction block, pigmentary retinal degeneration, variable number of red ragged fibers on muscle biopsy. It presents before the child reaches the age of twenty. Kearns-Sayre syndrome may affect many organ systems and additional features may include myopathy, dystonia, bulbar symptoms in the form of dysarthria and nasal regurgitation and bilateral facial weakness. Endocrine abnormalities (e.g., diabetes, growth retardation/short stature, and hypoparathyroidism), bilateral sensorineural deafness, dementia, cataracts, and proximal renal tubular acidosis, skeletal muscle weakness (proximal more than distal) and exercise intolerance are additional features. Kearns Sayre Syndrome occurs as a result of large-scale single deletions (or rearrangements) of mitochondrial DNA (mtDNA), which is usually not inherited but occurs spontaneously, probably at the germ-cell level or very early in embryonic development. No disease-modifying therapy is available for Kearns-Sayre syndrome (KSS). Management is supportive vigilance for detection of associated problems. In the future, potential treatment in patients with Kearns-Sayre syndrome may attempt to inhibit mutant mtDNA replication or encourage replication of wild-type mtDNA.

Cytoplasmic localization of BAG-1 in leukoplakia and carcinoma of the tongue: correlation with p53 and c-erbB2 in carcinoma.

BACKGROUND: The present study evaluated the clinical significance of BAG-1, an antiapoptotic protein, in leukoplakia and carcinoma of the tongue. METHODS: BAG-1 expression was evaluated by immunohistochemistry in paraffin-embedded tissues of leukoplakia (n=25) and carcinoma of the tongue (n=61). RESULTS: Cytoplasmic expression was predominantly seen in 80% and 70% of patients with leukoplakia and carcinoma, respectively. BAG-1 expression was found to be significantly lower in tobacco users than in non-tobacco users. BAG-1 expression in tobacco-using leukoplakia and carcinoma patients was compared by grouping the carcinoma patients according to lymph node status and disease stage. Carcinoma patients with tumor-positive lymph nodes had significantly lower BAG-1 expression than patients with negative lymph nodes and leukoplakia. Further, a trend towards an inverse correlation was observed with p53 and c-erbB2. In univariate and multivariate survival analysis, patient subgroups with 2+ or 3+ marker positivity (BAG-1 negativity, p53 and c-erbB2 positivity) had a reduced overall survival compared with patient subgroups with 1+ marker positivity or negativity. CONCLUSION: BAG-1 negativity in association with p53 and c-erbB2 positivity identified a subgroup of tongue cancer patients with an aggressive phenotype. Hence, an antiapoptotic protein, BAG-1, was found to be down-regulated in chewing-tobacco-mediated tongue carcinogenesis.

Hemifacial seizures and cerebellar tumor: a rare co-existence.

We report a 4-year-old boy with multiple daily episodes of abnormal eye movements, hemifacial spasms. Neuro-imaging revealed a cerebellar tumor. We believe that this association constitutes a rare but important syndrome of epilepsy characterized by seizures of cerebellar origin.

Does treatment change the outcome of seizures and computerized tomographic lesions in intracranial granulomas?

In children, intracranial granuloma diagnosed on computerized tomography (CT) scan and presenting with seizures as the sole manifestation has traditionally been treated with antitubercular (ATB) therapy or albendazole (Alb) in addition to antiepileptic drugs (AED). This study was conducted to determine whether AED therapy alone or specific treatment (ATB + Alb) influences the outcome of seizures and the CT lesion. Sixty-eight children presenting with seizures along with intracranial granuloma on CT scan were selected for the study. They were randomly divided into two groups. Group A (n = 34) was treated with AED alone and group B (n = 34) received antitubercular therapy and albendazole in addition to AED. Seizure type was noted and electroencephalogram (EEG) and CT scan were done in all. They were followed up for a period of 2 to 9 years, during which a record of seizure count and type was maintained. CT scans were repeated at 3 monthly intervals and EEGs were repeated whenever indicated. Four patients in each group were lost to follow-up. Seizures persisted in four out of 30 in group A and six out of 30 in group B. There was no statistically significant difference (p > 0.05) in the outcome of seizures in the two groups. Taking the whole group together (n = 60), of the 13 who had presented with multiple seizures at onset, epilepsy was a sequela in five (p < 0.05); and of the 17 in whom the lesion had calcified, seizures persisted in seven (p < 0.05), irrespective of treatment modality. In conclusion, though specific treatment did not alter the outcome of seizures, children with multiple seizures at presentation and calcification of CT lesion had epilepsy as a sequela.

Hypothalamic hamartomas and precocious puberty.

Ten children, five boys and five girls with true precocious puberty at an early age were found to have hypothalamic hamartomas on brain imaging. Very early onset of puberty, varying from a few weeks to three years of age, and rapid progression were characteristic. Accelerated growth velocity and markedly advanced bone age were evident in all. Gonadotropin and gonadal hormone levels were elevated above the prepubertal range. Six children had associated developmental delay or hyperactivity.

Proptosis: management of 22 patients.

The clinical features and management of 22 cases with proptosis is highlighted. Proptosis was unilateral in fifteen and bilateral in seven cases. The common etiologic factors were neoplasms, infections and bleeding diatheses. Of the ten cases with neoplasms as many as 7 expired, whereas of nine cases due to infections only one expired and one developed phthisis bulbi. All three patients with proptosis due to bleeds recovered completely without sequelae. Orbital CT scan was done in fourteen and ultrasound in eight cases, while in five cases both investigations were done. As neoplasms are a frequent cause of proptosis in children and there is a high mortality in this group, a thorough systemic examination and hematological profile is essential to arrive at a speedy diagnosis. CT and USG are useful imaging modalities of the orbit, the latter being particularly useful for follow up of the lesion.

Experience with penile venous surgery.

Venogenic impotence was detected in 37 out of 141 patients who attended our clinic with a complaint of erectile dysfunction. Eighteen patients presented with primary impotence and the rest had progressive secondary impotence. All 37 patients have shown partial or poor response to 60 mg of intracavernosal papaverine. The corporovenous leak (CVL) was diagnosed on the careful workup of dynamic pharmacocavernosometry and cavernosography. Concomitant arterial cause was noted in 10% cases on the basis of penile duplex Doppler ultrasound study. 24 patients in the age group of 23-60 years underwent the penile venous surgery. The CVL was noted in the deep dorsal vein (23 cases), cavernous vein (16) and in the crural vein (2). The operation consisted of deep dorsal vein (DDV) ligation and excision with all tributaries (8 cases) or DDV ligation and excision+cavernous vein ligation (13 cases), through an infrapubic curvilinear incision. One patient had crural vein ligation and corporoplasty through a perineal incision, one had direct corporeal revascularization for associated arteriogenic impotence with venous leak and another had distal spongiolysis and closure of a corporospongiosal shunt. The results were excellent in 11 cases, improved in 6 and 7 had failures. Surgical intervention is effective in CVL in selected cases but limiting factors in the form of increasing age, concomitant arteriogenic cause, significant crural leak, missing tributaries, recurrent venous leak and unknown factors may also be present to prevent total cure.