FUNCTIONAL LIMITATIONS AND ADIPOKINES IN HIV-INFECTED OLDER ADULTS.

BACKGROUND: There is a significant increase in the number of HIV-infected older adults (HOA). This population may experience functional decline at a much younger age. Little is known about the relationship between functional limitations and systemic adipokines in HOA. OBJECTIVE: Our study aimed to evaluate the relationship between functional limitations and systemic adipokine levels in HOA population. DESIGN: Cross-sectional. SETTING: Academic hospital-based infectious disease clinic. PARTICIPANTS: The study investigated community-dwelling HIV-infected adults >50 years old and compared this group with age, gender and BMI comparable healthy controls. MEASUREMENTS: We measured functional status, body composition and plasma concentrations of adipokines. RESULTS: Fifty-four HOA were studied (mean: age 57 years, BMI 29 kg/m2, CD4 604, duration of HIV 17 years) and compared with thirty-two age, gender and BMI comparable healthy controls. The HOA group showed significantly higher functional limitations compared to the age, gender and BMI comparable controls (p<0.05). Levels of adipokines were significantly different between the two groups (p<0.05). Multiple regression analyses indicated that adiponectin and visfatin were significantly correlated with several physical function measures after controlling for age, sex, and metabolic comorbidities. Adiponectin was negatively correlated with functional limitations, and this relationship was stronger in the control group compared to the HOA group. Conversely, visfatin was positively correlated with functional limitations only in the HOA group. CONCLUSION: HOA have significant functional limitations and alteration in adipokine levels compared to controls. Adiponectin and visfatin were associated with functional limitations. Visfatin was a correlate of physical function only in the HOA group. Prospective longitudinal studies could provide further insight on the role of adipokines in HIV-related functional decline.

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.

Controversies in febrile seizures.

Febrile seizures are benign, self limiting, common neurological problems encountered in children between 3 months and 5 years. Controversies exist regarding its definition and it is important to distinguish between the terms febrile seizures and convulsions with fever. In the vast majority, febrile seizures occur within the first 24 hours of illness, and an encephalitic process should be considered if it occurs later, especially with exanthema. The temperature threshold varies in the same child and from one child to another. Febrile seizures are classified as simple and complex and debate continues regarding the usage of these terms and their prognostic value. Practice parameters are suggested regarding the performance of lumbar puncture in a child with first febrile seizure, but they should be used as guidelines and the decision depends on the experience and judgement of the physician. EEG is of limited value and not a guide to treatment or prognosis and neuroimaging not recommended. The predictors of recurrent febrile seizures include younger age, lower threshold of temperature, onset within one hour of fever and positive family history. Whether the syndrome of mesial temporal sclerosis beginning with prolonged febrile seizure has a causal relationship with pre existing brain disease is a matter of debate. There are effective therapies to prevent febrile seizures but the potential side effects of drugs outweigh their benefit. Intermittent prophylaxis during fever may be effective but long term prognosis is not influenced by the treatment applied in early childhood. A practical approach to a child with febrile seizure is suggested.

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.

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.

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.

Juvenile Huntington's disease.

A rare case of juvenile Huntington's disease manifesting since the age of seven years is reported. The inheritance was typically autosomal dominant as three other members on the paternal side died of similar disease. A definite family history can becrucial in the diagnosis of juvenile Huntington's disease.

Experience with the International League Against Epilepsy classifications of epileptic seizures (1981) and epilepsies and epileptic syndrome (1989) in epileptic children in a developing country.

Four hundred eighty-three epileptic children attending the Pediatric Epilepsy Clinic at Bai Jerbai Wadia Hospital for Children, Bombay, India were classified according to the International League Against Epilepsy (ILAE) classification of epileptic seizures (1981) and epilepsies and epileptic syndromes (1989). The predominant seizures were partial (53.6), generalized (40.3%), and unclassifiable (6%). In epilepsies and epileptic syndromes, 55.3% were partial, 27% were generalized, 13.5% were undetermined, and 4.1% were special syndromes. Although our results were similar in many respects to those of other reported series, some differences were observed in the incidence of partial and generalized seizures, and partial and generalized epileptic syndromes and their subgroups, such as idiopathic, symptomatic, and cryptogenic partial syndromes, idiopathic generalized syndromes, and symptomatic specific syndromes. These differences are probably due to different age limits, methods of case ascertainment and inclusion criteria, different genetic and environmental factors, variable interpretation of clinical and EEG features, and lack of facilities for investigation in developing countries. Despite various limitations, we were able to classify most cases; the ILAE classification can be used in developing countries so that comparison can be made with other studies.

A study of phenobarbital and dilantin in neonatal seizures.

A total of 40 cases of neonatal convulsions of different nonmetabolic aetiological factors were studied. Patients with kernicterus were included in the study. Peak plasma phenobarbital concentrations after incremental loading doses of phenobarbital i.e. 10 mg/kg, 15 mg/kg, and 20 mg/kg were determined. Diphenylhydantoin was added if phenobarbital alone was unable to control seizures. In three patients, a combination of phenobarbital and diphenylhydantoin was used as the initial loading therapy. Increase in the loading dose of phenobarbital was associated with an increase in its peak plasma concentration. Despite increase in the plasma phenobarbital concentration beyond the 'therapeutic' levels suggested by the Western studies, doses of 15 mg/kg and 20 mg/kg of phenobarbital were unable to score over the traditional regimen of 10 mg/kg. Convulsions were controlled in 50% of the patients with any of these three regimens, irrespective of the aetiology. Convulsions were controlled in 7 out of the 9 cases where diphenylhydantoin was added, because of the failure of phenobarbital in controlling the convulsions as a single drug. Convulsions of all the three patients, in whom a combination of phenobarbital and diphenylhydantoin was used by random selection as the initial bolus, were controlled. Seizure effects were difficult to distinguish from drug effects but major side effects were not encountered despite the fluctuating drug levels in the sick neonate.

Neonatal gastrointestinal perforations.

Fourteen neonates presented with clinical and radiological evidence of gastrointestinal perforation, of which 13 were treated by operative intervention. No infant was formula fed, had rectal bleeding or radiological evidence of pneumatosis intestinalis. Operative findings revealed localized perforation in ten of which three were gastric, two distal ileal, three cecal and two in sigmoid colon. Gangrene with extensive perforation of jejunum, ascending colon and transverse colon were seen in one each. Blood cultures were positive in four, one grew E. coli and three Klebsiella while peritoneal cultures were positive in six, one grew E. coli and five Klebsiella. Ten neonates survived and are being followed up. Three of the four cases who died had white blood cell count greater than 25 x 109/L and grew Klebsiella on peritoneal culture. Factors predisposing to gastrointestinal perforations in neonates are discussed, emphasis is made on the cautious use of umbilical, gastric and rectal catheters, and the need for early surgical intervention.

EEG recognition of holoprosencephaly and Aicardi syndrome.

Two cases of alobar holoprosencephaly and two of Aicardi syndrome are reported for their highly specific electroencephalographic (EEG) changes. The asynchronous sharp waves and spikes over the frontal regions with decreasing gradient of potential to the occipital leads were seen in alobar holoprosencephaly while burst suppression pattern with total asynchrony between the two hemispheres was seen in Aicardi syndrome. Even though EEG changes cannot be pathognomic of any abnormality, it is suggested that as in conditions like subacute sclerosing panencephalitis and petitmal epilepsy, so also in alobar holoprosencephaly and Aicardi syndrome, the characteristic features seen on EEG may provide the initial clue to the correct diagnosis.

Transvesical vesicovaginal fistula repair: a revival.

Vesicovaginal fistulae are usually traumatic in nature, following obstetric or gynecologic trauma. Here, our experience with vesicovaginal fistula repair in 68 cases, performed transvesically (58 cases) or transperitoneally-transvesically, with pedicled omental interposition in 10 cases over the last 8 years is described. The size of fistulae ranged from 1 to 5 cm, and most were situated near or above the trigone. Two cases required ureteric reimplantation. Recurrent fistulae were found in 4 cases. We attribute our success to the simple access, the construction of a vascularized flap, the tension-free grid-iron closure, and the utilization of Vicryl suture.

Medication compliance in children.

Children of various ages and both sexes (numbering 1,004) attending the out-patient department of Conwest Jain Clinic Group of Hospitals were studied for medication compliance (MC). MC was divided into total, partial, poor and excessive. Various parameters influencing MC like acute or chronic illness, age, sex, community, income, parental education and occupation, number of children, number of family members, form of medicine and number of medicines were studied in details. Only three factors e.g. community, occupation of the father and form of medicine were found to influence MC. No single factor consistently influenced MC. Negligence and poverty play a very important role in MC.