Development of a composite indicator to prioritize districts for implementation of human immunodeficiency virus programmes in Maharashtra,India

A key recommendation of the National AIDS Control Programme‐IV of India was to develop new strategies for geo‐prioritization of the human immunodeficiency virus (HIV) epidemic. We conducted this study to categorize the districts in Maharashtra (India) based on a multidimensional framework for geo‐prioritization of services. Programmatic data on trends of HIV prevalence, coverage of marginalized populations and vulnerability factors were included. A composite indicator based on these was developed, and the cumulative score was calculated for each district. HIV prevalence among general population has declined steadily from 0.60% in 2007 to 0.33% in 2017. The programme coverage was stable but inadequate for men who have sex with men (MSM). The coverage for female sex workers (FSWs) was inadequate and reduced over time. Nine districts were categorized as high priority, 13 as moderate priority and 11 were classified as low‐priority districts based on burden and vulnerability for HIV. The high‐priority districts were Pune, Solapur and Yavatmal for FSW interventions and Pune, Thane and Latur for MSM interventions. This multidimensional indicator is based on existing programmatic data, dynamic and can be made state‐specific. It is useful to categorize and prioritize districts for allocation of resources and geo‐prioritization of services in resource limited settings.     

Evaluation of inhibitory effect of diphenhydramine on benzodiazepine dependence in rats

Effect of diphenhydramine was investigated on withdrawal signs in lorazepam dependent rats. Physical dependence was produced by giving lorazepam admixed with the food in the following dose schedule: 10 x 4, 20 x 4, 40 x 4, 80 x 4 and 120 x 7 (mg/kg, daily x days). The parameters observed during the periods of administration of lorazepam and after its withdrawal were spontaneous locomotor activity (SLA), body temperature, reaction time to pain, foot shock aggression (FSA) and audiogenic seizures. Diphenhydramine was administered orally in the dose schedules of once daily (10, 20 and 40 mg/kg) and twice daily (5, 10 and 20 mg/kg) in separate groups during the withdrawal period. The withdrawal signs observed in control group (without diphenhydramine) were hyperkinesia, hyperthermia, hyperaggression and audiogenic seizures. Hyperkinesia and hyperthermia were blocked in all the groups of diphenhydramine-treated rats. FSA was inhibited only by diphenhydramine (10 and 20 mg/kg) given twice daily. Audiogenic seizures were completely blocked by once daily (20 and 40 mg/kg) as well as twice daily (20 mg/kg) doses of diphenhydramine. It may be concluded that diphenhydramine exerts a protective effects on benzodiazepine withdrawal syndrome.     

Neuro-otological profile of Episodic Vertigo

Episodic Vertigo Comprises a large group of patients seen in any neurootology unit. A total of 118 subjects were reviewed who attended the neurootology unit. Vertigo of shorter duration was noted in 78 and of longer duration in 40 cases. 51 cases showed bilateral neurosensory deafness, 15 cases had bilateral and another one case had unilateral conductive loss. Spinovestibular tests were abnormal in all cases of vertigo of short duration but only 29 cases showed abnormal reflex in patients with a long duration of illness. Thermal vestibulometry revealed hyporeflexia in 33 cases, directional preponderance in 30 cases and 4 cases showed hyperreflexia 28 cases had peripheral lesions while 81 cases had central lesions. The acute cases showed significant improvement on follow up except cases with abnormality in thermal vestibulometry . The cases with positional nystagmus showed improvement with head and body balance exercises expect in those who received treatment with vestibulosedative and vestibular suppersive drugs. Hearing loss remained the same except in patients with middle ear disorders.     

Value of antenatal echocardiography in high risk patients to diagnose congenital cardiac defects in fetus

Results of fetal echocardiography in 1062 high risk pregnant patients are described. It was performed before 28 weeks of gestation in 770 cases. These were 38 abnormal scans (3.6%). A fetal arrhythmia was diagnosed in 14 cases and structural abnormality of the heart in 24. Complete atrioventricular block was commonest (n=12), structural heart disease associated in two of these cases. Other lesions identified were atrioventricular septal defect (n=5), hypoplastic left heart syndrome (n=4), ventricular septal defect (n=4), Ebstein’s anomaly (n=3), coarctation of aorta (n=2) and others (n=9). Postnatal confirmatory echocardiography is available in a total of 993 babies including 36 of 38 abnormal cases. There were eleven neonatal deaths amongst babies with abnormal scans. Errors in interpretation were observed in six instances. An anomaly was missed in five cases; in two of these, the main cardiac malformation was picked up but secondary lesions were missed. In one case, a false positive diagnosis of atrial septal defect was made. These errors did not influence the management of the pregnancy. Fetal echocardiography is a very sensitive (91.6%) and specific (99.9%) tool for antenatal diagnosis of congenital heart disease in high risk pregnancies. The information so obtained helps in guiding the optimal obstetric and neonatal management of these cases.     

Surgical repair of pectus carinatum

Pectus carinatum represents a variety of protrusion deformities of the anterior chest wall. Although various non-operative methods of treatment have been employed, surgery has been widely accepted as the only effective method for the correction of pectus carinatum. We evaluate our 14 year single center experience of pectus carinatum correction on 111 patients using a uniform technique of internal stabilization employing stainless steel struts. Operative correction required double bilateral chondrotomy parasternally and at points of transition to normal ribs, followed by detorsion of the sternum, retrosternal mobilization and correction of the everted sternum as well as of the everted and inverted ribs. The mobilized sternum after incomplete wedge osteotomy was finally stabilized by one transternal and two bilateral parasternal metal struts. The corrections were completed with successful repair in 109 patients (98.2%). Major recurrences in 2 patients (1.8%) were corrected while mild recurrence were observed in 3 patients (2.7%).     

Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine

Functional brain imaging studies of subjects with Major Depressive Disorder (MDD) have suggested that decreased dorsolateral (DLPFC) and increased ventrolateral (VLPFC) prefrontal cortical activity mediate the depressed state. Pre- to post-treatment studies indicate that these abnormalities normalize with successful treatment. We performed [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans on 16 outpatients with MDD before and after treatment with paroxetine (target dose = 40 mg/day). Regions of interest (ROIs) for this analysis were drawn by a rater blind to subject identity on the magnetic resonance image of each subject and transferred onto their coregistered PET scans. We hypothesized that DLPFC metabolism would increase, while ventral frontal metabolism [in the VLPFC, the orbitofrontal cortex (OFC), and the inferior frontal gyrus (IFG)] would decrease with successful treatment. Treatment response was defined as a decrease in the Hamilton Depression Rating Scale of > 50% and a Clinical Global Improvement Scale rating of 'much' or 'very much' improved. By these criteria, nine of the subjects were classified as treatment responders. These responders had significantly greater decreases in normalized VLPFC and OFC metabolism than did non-responders. There were no significant effects of treatment response on change in the DLPFC or IFG in this sample. However, there was a positive correlation between change in HAM-D scores and change in normalized IFG and VLPFC metabolism. There were no significant interactions with laterality. On pre-treatment scans, lower metabolism in the left ventral anterior cingulate gyrus was associated with better treatment response. These findings implicate ventral prefrontal-subcortical brain circuitry in the mediation of response to serotonin reuptake inhibitors in MDD.     

Pharmacological aspects of experimental headache models in relation to acute antimigraine therapy.

The last decade has witnessed a tremendous progress in the acute therapy of migraine, with sumatriptan, belonging to a new class of drugs, now known as 5-HT(1B/1D/1F) receptor agonists, leading the way. The undoubted success of sumatriptan stimulated the development of new triptans as well as other suitable pharmacological tools and experimental models to probe into complex migraine mechanisms. In this review, we discuss the main experimental models for migraine, against the background of the disease pathophysiology and 5-HT receptors considered most important for migraine therapy. We believe that the use of these migraine models will provide even better treatment for migraine patients in the next millennium.     

5-Hydroxytryptamine-induced increase in left ventricular dP/dtmax does not suggest the presence of ventricular 5-HT4 receptors in the pig

Summary Although 5-hydroxytryptamine (5-HT) increases porcine atrial force and rate via 5-HT₄ receptors, its effect on left ventricular contractility is not known. Therefore, using the maximum rate of rise of left ventricular pressure (LVdP/dt_max) as an index of cardiac contractility, we have attempted to analyze the possible role of ventricular 5-HT₄ receptors in the anaesthetized pig. The full agonists at 5-HT₄ receptors, 5-HT and 5-methoxytryptamine (each 3, 10 and 30 g · kg^–1), and the -adrenoceptor agonist, isoprenaline (0.01, 0.03 and 0.1 g · kg^–1), increased heart rate, LVdP/dt_max and cardiac output. For a given degree of tachycardia, the increase in LVdP/dt_max by isoprenaline was substantially more than that observed with either 5-HT or 5-methoxytryptamine. The 5-HT₄ receptor partial agonist, renzapride (3, 10, 30, 100 and 300 g · kg^–1), also increased heart rate and LVdP/dt_max dose-dependently. When the heart was paced at 150 beats · min^–1, increases in LVdP/dt_max as well as cardiac output (except with the highest doses) by 5-HT, 5-methoxytryptamine and isoprenaline were clearly attenuated. However, the magnitude of attenuation of LVdP/dt_max responses by cardiac pacing was more marked in the case of 5-HT and 5-methoxytryptamine than with isoprenaline.The effects of renzapride (300 g · kg^–1) and tropisetron (0.3 and 3 mg · kg^–1) on increases in heart rate and LVdP/dt_max by 5-HT, 5-methoxytryptamine and isoprenaline were also studied. In the absence of atrial pacing, both renzapride and tropisetron (3 mg · kg^–1) effectively antagonized the responses to 5-HT and 5-methoxytryptamine; except for some decrease in the LVdP/dt_max response by tropisetron, the effect of isoprenaline remained essentially unchanged after the antagonists. During atrial pacing, renzapride significantly antagonized the responses to the first two doses of 5-HT, but the responses to the highest 5-HT dose and to 5-methoxytryptamine remained unaffected. Though, particularly after its higher dose, tropisetron reduced the responses to 5-HT and 5-methoxytryptamine, isoprenaline responses were also affected.The above results show that a significant part of the increase in LVdP/dt_max by 5-HT receptor agonists in the anaesthetized pig is a consequence of tachycardia elicited by these compounds via 5-HT₄ receptors. Since the increase in LVdP/dt_max, compared to tachycardia, was much less with 5-HT and 5-methoxytryptamine than with isoprenaline, and since the antagonism by renzapride and tropisetron against 5-HT and 5-methoxytryptamine during atrial pacing was relatively weaker and/or unspecific, it appears unlikely that the increase in LVdP/dt_max, during atria] pacing is mediated by ventricular 5-HT₄ receptors. This view is substantiated by our recent in vitro experiments where 5-HT (0.01 to 100 mol/l) failed to significantly increase contractions of porcine left ventricular trabeculae.Correspondence to P. R. Saxena at the above address