Activation of muscarinic and serotonergic receptors results in phosphoinositide hydrolysis but not in mobilization of calcium in sympathetic neurons.

The effects of various neurotransmitters on phosphoinositide hydrolysis, mobilization of Ca2+ and release of [3H]-norepinephrine ([3H]-NE) were studied in cultures of sympathetic neurons of chick embryos. [3H]-inositol-1,4,5-triphosphate ([3H]-IP3) was increased in sympathetic neurons by acetylcholine (ACh), muscarine and serotonin (5-HT). Dopamine and norepinephrine did not stimulate phosphoinositide hydrolysis. Intracellular concentration of free Ca2+ ([Ca2+]i) was measured in Indo-1-loaded sympathetic neurons at rest and after addition of test agents. Measurements were made in the cell body and growth cone regions since Ca2+ mobilization is known to be different in different regions of the sympathetic neurons. ACh (nicotinic component was blocked by hexamethonium) and 5-HT failed to increase the [Ca2+]i, in the cell body as well as in the growth cone. The spontaneous release of [3H]-NE was not affected by ACh and 5-HT. Caffeine increased the [Ca2+]i only in the cell body but not in the growth cone and had no effect on the release of [3H]-NE. These results suggest that an IP3-insensitive but caffeine-sensitive pool of Ca2+ is present only in the somatic region of sympathetic neurons and is not coupled to the transmitter release.     

RENAL TRANSPLANTATION – AN EARLY EXPERIENCE

Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection     

Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both?

We have studied 477 8-year-old Indian children to define the relationship between birth weight and cardiovascular risk factors, including insulin resistance syndrome (IRS) variables and plasma total and LDL cholesterol concentrations. All risk factors were strongly related to current weight. After adjustment for current weight, age, and sex, lower birth weight was associated with higher systolic blood pressure (P = 0.008), fasting plasma insulin and 32-33 split proinsulin concentrations (P = 0.08 and 0.02), glucose and insulin concentrations 30 min postglucose (P = 0.06 and 0.04), subscapular/triceps skinfold ratio (P = 0.003), and plasma total and LDL cholesterol concentrations (P = 0.002 and 0.001). Lower birth weight was associated with increased calculated insulin resistance (homeostasis model assessment [HOMA], P = 0.03), but was not related to the HOMA index of beta-cell function. The highest levels of IRS variables and total and LDL cholesterol were in children of low birth weight but high fat mass at 8 years. Taller height at 8 years predicted higher fasting plasma insulin concentrations, insulin resistance, and plasma total and LDL cholesterol concentrations. The most insulin-resistant children were those who had short parents but had themselves grown tall. Although the implications of our findings in relation to height are unclear, interventions to improve fetal growth and to control obesity in childhood are likely to be important factors in the prevention of cardiovascular disease and IRS in India.     

Improvement in gait parameters after lengthening for the treatment of limb-length discrepancy

BACKGROUND: Patients who have limb-length discrepancy demonstrate an altered gait pattern or a limp. The purpose of this prospective study was to compare the objective gait parameters for the shorter lower limb with those for the longer lower limb before and after lengthening and to compare these data with those for a group of twenty subjects who had no limb-length discrepancy. METHODS: Eighteen patients had equalization of limb length to within one centimeter. We analyzed the stance time, the second peak of the vertical ground-reaction-force vector, and the rate of loading with use of two force-plates arranged in a series. RESULTS: The difference in the mean stance times between the shorter and longer limbs before lengthening was 12 percent, whereas that after lengthening was 2.4 percent; the difference between the values before and after lengthening was significant (p<0.001). The difference in the stance times between the limbs of the patients who did not have limb-length discrepancy was 2 percent. Preoperatively, the mean second peak was 104 percent of body weight for the shorter limb compared with 116 percent for the longer limb; this difference was significant (p<0.001). After lengthening, the mean second peak for the shorter limb increased to 113 percent of body weight. The difference in the means for the second peak before and after lengthening was significant (p<0.001). With the numbers available, no significant difference was detected in the means for the second peak between the shorter and longer limbs after lengthening (p = 0.12). CONCLUSIONS: This study shows that lengthening of the shorter limb of patients who have limb-length discrepancy can normalize symmetry of quantifiable stance parameters and eliminate a limp.     

A molecularly integrated grade for meningioma

BackgroundMeningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management.MethodsWe evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms.ResultsWe developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score.ConclusionWe propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.     

Nodding syndrome in Mundri county,South Sudan: environmental,nutritional and infectious factors

Background

Nodding Syndrome is a seizure disorder of children in Mundri County, Western Equatoria, South Sudan. The disorder is reported to be spreading in South Sudan and northern Uganda.

Objective

To describe environmental, nutritional, infectious, and other factors that existed before and during the de novo 1991 appearance and subsequent increase in cases through 2001.

Methods

Household surveys, informant interviews, and case-control studies conducted in Lui town and Amadi village in 2001–2002 were supplemented in 2012 by informant interviews in Lui and Juba, South Sudan.

Results

Nodding Syndrome was associated with Onchocerca volvulus and Mansonella perstans infections, with food use of a variety of sorghum (serena) introduced as part of an emergency relief program, and was inversely associated with a history of measles infection. There was no evidence to suggest exposure to a manmade neurotoxic pollutant or chemical agent, other than chemically dressed seed intended for planting but used for food. Food use of cyanogenic plants was documented, and exposure to fungal contaminants could not be excluded.

Conclusion

Nodding Syndrome in South Sudan has an unknown etiology. Further research is recommended on the association of Nodding Syndrome with onchocerciasis/mansonelliasis and neurotoxins in plant materials used for food.