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Melaka Manipal Medical College (Manipal Campus; Manipal, Karnataka, India) conducts the Bachelor of Medicine and Bachelor of Surgery program, for which the admission intakes are during the months of March and September. The present study was undertaken to study the differences in learning approaches to physiology of undergraduate medical students in a partially problem-based learning (PBL)- and non-PBL-oriented curriculum. PBL was introduced as a curricular reform for the September 2006 batch of students (partially PBL group), whereas it was not incorporated for the March 2006 batch of students (non-PBL group). Learning approaches to physiology of both groups of students were compared using the short inventory of approaches to learning. Mean scores for deep and strategic approaches were found to be significantly higher for the partially PBL group compared with the non-PBL group. The results of the present study support the earlier observation that PBL promotes a deep approach to learning. (Contains 3 tables.)

Background: Participation in research during undergraduate studies may increase students' interest in research and inculcate research essentials in them. Aims: The purpose of this study was to evaluate the effectiveness of the mentored student project (MSP) program. Settings and Design: In the MSP program, students in groups (n = 3 to 5) undertook a research project, wrote a scholarly report, and presented the work as a poster presentation with the help of a faculty mentor. To begin with, the logic model of the program was developed to identify short-term outcomes of the program on students, mentors, and the institution. A quasi-experimental design was used to measure the outcomes. Materials and Methods: A mixed method evaluation was done using a newly-developed questionnaire to assess the impact of the MSP on students' attitude, a multiple-choice question (MCQs) test to find out the impact on students' knowledge and grading of students' project reports and posters along with a survey to check the impact on skills. Students' satisfaction regarding the program and mentors' perceptions were collected using questionnaires. Evidence for validity was collected for all the instruments used for the evaluation. Statistical Analysis: Non-parametric tests were used to analyze data. Based on the scores, project reports and posters were graded into A (> 70% marks), B (60-69% marks), and C (< 59% marks) categories. The number of MSPs that resulted in publications, conference presentation and departmental collaborations were taken as impact on the institution. Results: Students' response rate was 91.5%. The students' attitudes regarding research changed positively (P = 0.036) and score in the MCQ test improved (P < 0.001) after undertaking MSP. Majority of project reports and posters were of grade A category. The majority of the items related to skills gained and satisfaction had a median score of 4. The MSPs resulted in inter-departmental and inter-institutional collaborations, 14 publications and 15 conference presentations. An area for improvement noted was to have the MSP implemented in the curriculum without increasing students' overall workload and stress. Conclusion: The study identified strengths and weaknesses of the MSP program. Our model of undergraduate research project may be incorporated in undergraduate medical programs to foster positive attitude and knowledge base about scientific research and to instill research skills among students. [ABSTRACT FROM AUTHOR]

The relationship between dynamic pupillary function and peripheral nerve function was studied in 85 randomly-selected diabetic patients and 67 age-matched normals using a portable infrared pupillometer (Pupilscan Version 5). Seven measurements were chosen to represent different components of the pupillary constriction-redilatation curve after a standardized light stimulus. Constriction latency was significantly prolonged in diabetic patients (p = 0.05), as was time to 63% redilatation (p = 0.001). Thermal thresholds at the feet weakly correlated with relative reflex amplitude (warm: r = -0.22, p = 0.05; cool: r = -0.23, p = 0.05), but vibration perception thresholds were more strongly associated with constriction and redilatation velocity (r = -0.42, p = 0.001; r = -0.28, p = 0.03). Among the cardiovascular autonomic function tests, only respiratory R-R variation correlated with constriction velocity (r = 0.47, p < 0.001), and Valsalva ratio with redilatation velocity (r = 0.25, p = 0.04), but postural systolic blood pressure change was also correlated with reflex amplitude and latency time (r = -0.42, p < 0.001; r = 0.41, p = 0.001). There were no significant associations with three measures of sweating function in the feet. Pupil measurements were abnormal in 4-11% of diabetic patients, while other neurological tests were abnormal in 8-35%, consistent with the length-dependence of diabetic neuropathy. Median coefficients of variation were 2.0-7.2% in diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied ten obese patients on prolonged caloric restriction by metabolic balance techniques two weeks before and two weeks after the start of treatment with triiodothyronine (T3) (0.36-1.01 micrograms/kg/d). The rate of weight, nitrogen and fat loss calculated from metabolic balance increased during T3 therapy and these effects were maximal in the second week of treatment. In seven patients studied continuously for four weeks on T3 therapy, the rates of weight and fat loss during the fourth week of treatment were not significantly different from pretreatment values while nitrogen loss was still significantly greater. The increase in nitrogen loss, studied after the period of adaptation to caloric restriction, implies that prolonged treatment with T3 can result in significant losses of lean tissue in addition to that resulting from caloric restriction alone. Mean weight loss increased by 92 g/d during T3 therapy. T3 significantly increased the metabolic rate as measured by two other independent measures: the resting energy expenditure (REE), measured by indirect calorimetry (fourteen patients), and the sleeping heart rate (six patients).

The circulating levels of ACTH and alpha-melanocyte stimulating hormone (alpha-MSH) were measured in 9 patients with Nelson's syndrome after the administration of saline, ovine corticotrophin releasing factor (oCRF), bromocriptine or TRH. The concentrations of ACTH were grossly elevated and alpha-MSH levels ranged from undetectable to higher than the normal range. In seven of eight subjects there was a rapid corticotrophic response, but no change in the alpha-MSH level, following oCRF. This response was delayed in one subject. Following oCRF injection, the plasma oCRF profile was variable but circulating oCRF was detectable even at the end of the experiment in all cases. There was no significant change in circulating ACTH or alpha-MSH following either bromocriptine or TRH. Cultured tumour cells from one case of Cushing's disease showed a corticotrophic response but no change in alpha-MSH to oCRF and the response was enhanced by vasopressin. Bromocriptine added to the same tumour depressed ACTH secretion without affecting the output of alpha-MSH. The present data suggest that the tumours in these subjects are responsive to oCRF and arise from corticotrophs rather than melanotrophs.

Resting energy expenditure (REE) was measured by indirect calorimetry during dieting (2.74-3.30 MJ/day) for up to 200 days in overweight patients undergoing continuous metabolic balance studies. The initial rapid reduction in REE in the first 2 weeks of dieting was related to the extent of the immediate nitrogen deficit that follows caloric restriction and was larger (p less than 0.01) in men dieting de novo than either women (NS) or 4 patients of comparable lean body mass who had dieted prior to admission (NS). Because of their smaller metabolic energy deficit on our diets, the reduction in REE in women was small and not significant. In men, the slower long-term reduction in REE (p less than 0.05) was related to a continuing loss of lean tissue with no changes in the REE/m2, REE/kg body weight and REE/mmol creatinine excreted with time. We have previously shown that total energy expenditure (estimated from the rate of fat loss as measured by the difference between body weight changes and weight changes in fluid and protein) does not change significantly during prolonged dieting. The fall in REE in parallel with lean body mass suggests that some increase in the energy expended in daily activities must have occurred.

The effects of dietary carbohydrate (CHO) content and of tri-iodothyronine (T3) administration on calcium, zinc and phosphate balances and on urinary hydroxyproline output were examined in eight obese subjects undergoing therapy with low energy (2741-3301 kJ/day), high calcium (28.9-35.1 mmol/day) diets. Calcium balances were generally positive at the high levels of intake used, but significantly more calcium was retained when dietary CHO intake (as proportion of total energy intake) was increased. Zinc balances were more positive when the proportion of dietary CHO was high and correlated both with nitrogen balance and with daytime insulin concentration. Urinary hydroxyproline output generally increased with dieting irrespective of dietary CHO content. Administration of T3 (30-80 micrograms/day) markedly increased zinc loss without affecting calcium balance.

In a controlled trial of a double-blind cross-over design, it has been shown that "Marvie', a non-calorigenic sweetener containing 58 per cent maltitol by weight, is an effective sweetener which has no influence on routine haematological and biochemical parameters. The dose that could be tolerated without undesirable symptoms was between 20 and 30 g per day. Above this dose, flatus production with abdominal discomfort could limit tolerance to this sweetening agent.

The sensory action potential of the medial plantar nerve (MPSAP), using needle recording electrodes subcutaneously, was measured in 119 patients with diabetes ((75 insulin-dependent, mean age 43.7 +/- 1.2 SEM years (range 15-73) and in 75 age-matched normal subjects (mean age 44.0 +/- 1.5 years (range 19-75)). The MPSAP was not detectable in 56 out of 119 diabetics; there was only one absent MPSAP response in the normal group, in a patient aged 71 years. Diabetics with absent MPSAP responses were significantly older, heavier and taller and had diabetes of longer duration. The amplitudes and conduction velocities in the sural, common peroneal, and tibial nerves were also significantly smaller. The amplitudes of the MPSAP, when present, correlated with height (r = -0.47(43), p less than 0.001), weight (r = -0.44(43), p less than 0.001), the distal tibial compound motor action potential (r = 0.37(43), p less than 0.01), and the common peroneal nerve conduction velocity (r = 0.32(43), p less than 0.02). The MPSAP was always absent if the sural SAP was less than 5uV but also in 14/59 patients whose sural SAP amplitudes were within 1 sd of the normal mean (greater than 10.7 uV). The MPSAP was absent at a younger age and with diabetes of shorter duration than is seen with unrecordable sural SAPs. It may therefore represent an early manifestation of neuropathy in diabetes.

Thirty-five patients with symptoms or signs of diabetic neuropathy were tested for autonomic neuropathy by measuring heart rate and blood pressure changes during an orthostatic tilt test, a single deep breath and the Valsalva manoeuvre and these results were related to electrophysiological measurements made on the common peroneal and sural nerves. The sural sensory action potential (SAP) was more strongly correlated with these tests of autonomic function (particularly with the brake index of the orthostatic tilt test (P less than 0.001) and the fall in systolic blood pressure 1 min after tilt (P less than 0.001], than the common peroneal nerve compound motor action potential, its minimum F wave latency or nerve conduction velocities. Patients with a detectable sural SAP had significantly higher brake indices than those with absent sural SAPs. Significant correlations were also obtained with the common peroneal motor nerve conduction velocity (MNCV) and autonomic tests and patients with MNCV less than and greater than 38 m/sec showed significant differences in many autonomic tests. The sural SAP amplitude, being less susceptible to factors that influence nerve conduction velocity, may be useful in identifying patients with an autonomic neuropathy.

It has been demonstrated that the insulin secretagogue beta-cell-trophin, ACTH(22-39), is present in human plasma. The hormone, separated from plasma by affinity chromatography on a corticotrophin-like intermediate-lobe peptide antibody column, behaves similarly to synthetic beta-cell-trophin on a gel filtration column and on reverse-phase high-performance liquid chromatography. Sufficient amounts of the hormone were isolated from the plasma of two patients with Nelson's syndrome to demonstrate its biological activity on the perfused rat pancreas.

Rates of weight and fat loss in sixteen female and nine male obese patients during calorie restriction (655-789 kcal/day) for up to 120 days were studied by a method for estimating daily changes in body composition. Fat mass is calculated by subtracting daily fluid (calculated from sodium and potassium balances) and protein mass changes from daily weight changes. After the natriuresis of the first 4 days, there was a slower rate of weight loss between days 5 and 28 due largely to a decreasing contribution from fluid and protein losses. No significant change in the rate of weight loss could be shown after the first 28 days. The rate of fat loss did not change significantly from day 5 onwards suggesting no significant change in total energy expenditure during the study period. After 68 days, 93.4% of the weight loss was fat.

Thirty diabetic patients (mean age (+/- SD) 45.7 +/- 11.4 years, mean duration of diabetes 7.5 +/- 7.0 years, 17 insulin-dependent), were given 3 months of placebo injections followed by either 3-4 or 6 months injections of 100 mg mixed gangliosides (Cronassial) every weekday intramuscularly in a double-blind placebo-controlled study. There was an improvement of 0.77 +/- 1.25(10) degrees C and 0.65 +/- 1.05(10) degrees C in the thermal thresholds of the Cronassial treated group after 13-19 weeks and greater than 20 weeks respectively (p less than 0.22 from change of 0.04 +/- 0.59 degrees C in group treated with placebo. Compared to those with normal thresholds, patients with abnormal thermal thresholds (greater than 1.2 degrees C) improved significantly after Cronassial treatment for 13-19 weeks (-1.13 +/- 1.72(12) vs. 0.03 +/- 0.45(16) degrees C, p less than 0.006) and for greater than 20 weeks (-1.83 +/- 1.46(6) vs. 0.06 +/- 0.59(11), p less than 0.004) but this may have been related to the fact that the degree of improvement in thermal sensation was correlated with the initial thermal threshold (r = -0.80(28), p less than 0.001). There were no significant changes in electrophysiological measurements or vibration thresholds. Gangliosides are known to increase nerve sprouting and dendritogenesis and their effects in diabetic patients may be more easily seen using tests of small fibre function.

It has previously been reported that sodium valproate (Epilim) lowers plasma ACTH levels in Nelson's syndrome. This report describes further experience with its use. Ten patients with Nelson's syndrome were treated with sodium valproate (600-1200 mg/day) for 5-32 weeks. Plasma ACTH was measured by cytochemical methods and RIA. Initial treatment for 5-12 weeks significantly (P less than 0.005) lowered plasma ACTH from a pretreatment mean of 2460 +/- 1870 ng/liter to 480 +/- 330 ng/liter, and the ACTH circadian rhythm was restored in two patients. On discontinuing treatment, plasma ACTH levels remained suppressed for 3 weeks and rose to pretreatment values in 5-12 weeks. Two patients' plasma ACTH levels failed to show a second response to treatment, while a third patient had a favorable second response to treatment over 32 weeks. In six patients, skin pigmentation lightened with treatment, and in one patient, a reduction in size of a pituitary microadenoma, demonstrated radiographically, occurred with treatment. gamma-Aminobutyric acid and sodium valproate were shown to be ineffective in inhibiting ACTH secretion from cultured pituitary tumor cells from a patient with Nelson's syndrome. The results show that sodium valproate is effective in some cases of Nelson's syndrome. We suggest that it reduces the hypersecretion of ACTH by enhancing gamma-aminobutyric acid function in the hypothalamus, thereby inhibiting the release of corticotropin-releasing factor.

The method of constant infusion of U14C tyrosine tracer was used to measure whole body protein turnover in 24 patients with liver disease of varying severity. Whilst on a basic diet of glucose alone (5 g/hr), protein turnover and endogenous breakdown was significantly elevated in patients with cirrhosis and fulminant hepatic failure (F.H.F.), breakdown rising to 700 g/d greater than normal in F.H.F. In addition plasma aromatic aminoacids were significantly elevated and positively associated with the increases in endogenous protein breakdown (r = 0.78, p less than 0.05). Fourteen patients had a second infusion after dietary supplementation with either complete aminoacids (3 g/hr, n = 8) or branched chain aminoacids (BCAA, 4 g/hr, n = 6). The complete mixture did not worsen encephalopathy, improved the plasma aminoacid pattern, reduced protein breakdown and resulted in positive aminoacid balance. The BCAA supplements significantly reduced protein oxidation and endogenous breakdown. The results indicate that protein restriction in cirrhosis and fulminant hepatic failure will not significantly affect the load of aminoacids on the liver, nor their accumulation in plasma. Nutritional support of such patients should therefore include 40 - 60 g. protein per day to prevent protein depletion, and hypertonic glucose and insulin to suppress catabolism. BCAA supplementation may play a useful supportive role in increasing the utilisable nitrogen content of the diet and further suppressing catabolism.

Six patients with Nelson's syndrome were given sodium valproate with or without diazepam for 3 or 5 weeks. Initial high plasma adrenocorticotropic hormone (ACTH) concentrations were greatly reduced by treatment and returned to high levels when treatment was stopped. Diazepam did not add significantly to the effects of sodium valproate alone. Three patients reported a decrease in the severity and frequency of headaches while on sodium valproate. In five patients abnormal skin pigmentation was reduced. Sodium valproate is a gamma-aminobutyric acid (GABA) transaminase inhibitor and it is suggested that the drug raises GABA levels in the hypothalamus and that this is responsible for the reduction in ACTH secretion. The data are consistent with the hypothesis that Nelson's syndrome is a neuroendocrine disease caused by a deficiency in the hypothalamic GABA-ergic system.

Immunoreactive alpha-MSH was found in human plasma and in normal subjects ranged from less than 10-45 pg/ml. Plasma alpha-MSH concentrations were within the normal range in 13 out of 15 subjects during the last trimester of normal pregnancy and only just outside the normal range in the remaining two. Elevated plasma alpha-MSH concentrations were found in 6 of the 11 patients with Nelson's syndrome and in 10 of the 11 patients with pituitary dependent Cushing's disease. Separation on high pressure liquid chromatography (HPLC) revealed two major peaks of immunoreactivity. These peaks, which were identified as des-acetyl alpha-MSH and alpha-MSH were similar in size in normal subjects and Cushing's disease. In Nelson's syndrome, on the other hand, there was a greater proportion of des-acetyl alpha-MSH and it is possible that this peptide is secreted from tumour cells of anterior lobe origin. Although there was no correlation between the circulating alpha-MSH and the degree of pigmentation the high concentrations of plasma immunoreactive alpha-MSH in Cushing's disease and the HPLC profiles in Nelson's syndrome could provide useful information as to the localization of the defects in these particular disorders.