Ketamine decreases cerebral infarct volume and improves neurological outcome following experimental head trauma in rats

In brain injury, concentrations of extracellular excitatory amino acids are increased and stimulate glutamate receptors in general and the N-methyl-D-aspartate (NMDA)-preferring subtype in particular. That stimulation causes substantial calcium influx, which appears to initiate a cascade of events leading to neuronal death. Blockage of NMDA receptors with specific antagonists or noncompetitive ion channel blockers provides protection against excitatory amino acid-induced neurotoxicity. We previously reported that the NMDA receptor antagonist dizocilpine maleate improved the neurological severity score (NSS) after head trauma in rats. The present study was designed to determine whether ketamine, a NMDA receptor antagonist like dizocilpine maleate, improves neurological outcome following head trauma in rats. Thirty-two male Sprague-Dawley rats (235-250 g) were divided into four groups. Groups A and B were surgically prepared only. Groups C and D were surgically prepared and then a nonpenetrating impact was delivered to the cranium over the left hemisphere. Groups A and C received no treatment. Groups B and D were treated with ketamine, 180 mg/kg i.p., 1 h after head trauma. The NSS was determined at 1, 2, 4, 10, 24, and 48 h following head trauma. After killing at 48 h, cortical slices were taken adjacent to the lesion on the traumatized hemisphere and from comparable sites on the nontraumatized hemisphere to measure the tissue specific gravity and water content. Brains were then placed in 4% formaldehyde and the volume of hemorrhagic necrosis measured 4 days later. Head trauma increased the NSS and, in the traumatized hemisphere, decreased the specific gravity, increased the water content, and caused cerebral infarction. With ketamine, the NSS at 24 and 48 h following head trauma was 7.4 +/- 2.6 and 6.7 +/- 2.6 (mean +/- SEM), respectively, significantly improved compared to the NSS in the untreated group of 12.6 +/- 2.6 and 11.3 +/- 2.6, respectively (p <0.02, Mann-Whitney U test). With ketamine, the volume of hemorrhagic necrosis was 88.0 +/- 23.1 mm, significantly less than that in the untreated group (147.4 +/- 22.4 mm; p <0.05, unpaired t test). The brain tissue specific gravity and water content at 48 h and the rectal temperature at 4 and 48 h after head trauma were not significantly different between treated and untreated groups. It is concluded that in this model of closed cranial impact, ketamine improves neurological outcome and decreases the volume of hemorrhagic necrosis without altering brain edema.     

Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea

OBJECTIVE: To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea. DESIGN: Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks. SETTING: A diarrhoeal disease hospital in Dhaka, Bangladesh. PATIENTS: 111 children, 3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded. MAIN OUTCOME MEASURES: Total diarrhoeal stool output, duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation. RESULTS: Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239 v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v 329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v 6.2 days, p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v -0.3 mumol/l, p < 0.001) during two weeks of supplementation, and better mean weight gain (120 v 30 g, p < 0.03) at the time of discharge from hospital. CONCLUSIONS: Zinc supplementation is a simple, acceptable, and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished.     

Central motor conduction time in malnourished children

The functional status of the descending motor pathways was assessed in malnourished children using transcranial electromagnetic stimulation of the cortex. Twenty children with different severities of malnutrition and 20 control subjects were studied electrophysiologically. The circular coil of a Dentac MAG 2 magnetic stimulator was applied tangentially over the vertex to stimulate the cortex. The muscle evoked potential in the children's arms was recorded from the abductor pollicis brevis muscle and in their legs from the extensor digitorum brevis muscle on both sides of the body using surface electrodes. The muscle evoked potential of the abductor pollicis brevis and extensor digitorum brevis muscles was further obtained using root stimulation by applying the coil at the cervical and lumbar spine, respectively. The indices of cortical threshold, cortical latency, and central motor conduction time (ms) were evaluated in both arm and leg muscles on both sides. The results showed an increased cortical threshold (mean (SD) 1232.5 (134.06) in the study group v 1147.5 (99.31) in the control group) for the abductor pollicis brevis muscle and for the extensor digitorum brevis muscle (1325.00 (115.70) in the study group v 1190.0 (125.24) in the control group). Similarly, significant prolongation of the central motor conduction time (ms) (study group 6.67 (0.91) v control group 5.71 (0.74)) in the abductor pollicis brevis muscle was seen in malnourished children.     

Does a single plasma phenylalanine predict quality of control in phenylketonuria?

A 1993 MRC working group on phenylketonuria suggested standardising blood phenylalanine measurements by taking blood samples at the same time each day. Since it is not known how representative of a 24 hour period a single phenylalanine concentration is, the aim of this study was to investigate the 24 hour variability of plasma phenylalanine in well controlled children with phenylketonuria. Sixteen subjects, 12 girls and four boys aged 1 to 18 years, had hourly venous blood samples collected for 13 hours between 09.00 and 21.00 on one day. Serial skin puncture blood specimens were then collected at 24.00, 03.00, and 06.00 within the same 24 hour period. All food and drink was weighed. The median variation in plasma phenylalanine concentration was 155 mumol/l/day, with a minimum of 80 and a maximum of 280. The highest concentration occurred in the morning between 6.00 and 9.00 in 63% of subjects; the lowest occurred between midday and midnight in 94%. Concentrations < 100 mumol/l occurred in 46% of children below 11 years, three having concentrations < 30 mumol/l for two, six, and seven hours respectively. Three of five subjects had concentrations above the MRC guidelines for 24% of the period studied. Except in two subjects, the blood concentrations did not rise in response to phenylalanine consumption. However, the greater the quantity of protein substitute taken between waking and the 16.00 specimen, the larger the decrease in daytime phenylalanine concentration (r = -0.7030) (p < 0.005). There is therefore wide variability in phenylalanine concentrations in a 24 hour period in children with phenylketonuria which is not reflected in a single observation. Further study is needed to investigate the effects of timing of protein substitute on the stability of phenylalanine concentrations.     

VASCULAR EMBOLOTHERAPY-HOW MUCH HAS BEEN ACHIEVED?

Emergency and elective embolotherapy of various systemic arteries in 64 patients was carried out at a tertiary centre of Armed Forces. Specific indications were haemoptysis (n=43), preoperative (n=18), haematuria (n=1), epistaxis (n=1) and chemoembolization (n=1). The procedures were performed with gelfoam pellets (n=46), gelfoam pellets and absolute alcohol (n=1), polyvinyl alcohol particles (PVA) (n=14), steel coils (n=2) and Adriamycin-in-oil emulsion (n=1). Embolotherapy resulted in complete haemostasis in 37 (82.2%) out of 45 cases of haemorrhage. In eight cases (17.8%), it resulted in significant improvement. Complete haemostasis was achieved in both cases of haematuria and epistaxis. Pre-operative embolotherapy resulted in considerable reduction of peroperative blood loss in all the cases. Chemoembolization of Hepatocellular carcinoma resulted in partial regression of the tumour. The purpose of this study was to assess the efficacy, safety and reliability of vascular embolotherapy for control of life threatening haemorrhage and preoperative reduction of lesions.KEY WORDS: Embolization, Embolotherapy, Haemorrhage     

COSMETIC SCAR AND SCOPE OF REVERSAL AFTER PUERPERAL STERILISATION

Female sterilisation is an important component of National Family Welfare Programme. The target group is best motivated during the puerperium for such a procedure. However laparoscopic sterilisation which has got some distinct advantages, is not technically feasible at this time. The authors have used a technique where the advantages of cosmetic appearance, reduced post operative morbidity and reversibility can be conferred on the puerperal women.After trying out the method individually in some cases, a formal case control study design has been made and an evaluation study has been performed in 122 cases. The technique has been found to be cosmetically more acceptable, both at clientele and peer evaluation levels (p<0.001). Though all the four parameters of post operative morbidity have shown better results for the technique evaluated as against the conventional technique, statistical significance has been achieved in two of the parameters (p<0.05).KEY WORDS: Cosmetics, Female sterilisation, Post operative morbidity     

Bilateral skeletonized internal thoracic artery grafting in 303 patients seventy years and older

OBJECTIVES: Higher patency rates of the internal thoracic artery have led myocardial revascularization with bilateral internal thoracic arteries to be a procedure designated primarily for young patients. Fewer leg wound complications and sternal collateral flow preservation with the skeletonizing dissection technique can make bilateral internal thoracic artery grafting attractive also for elderly patients. METHODS: Between May 1996 and May 1998, 303 consecutive patients aged 70 years or older (mean age 75.5 years; range 70-92 years) underwent coronary artery bypass grafting with double skeletonized internal thoracic arteries. Forty-four (14.5%) patients were 80 years or older, and 89 (28%) had diabetes. The mean number of grafts was 3.1 per patient (2-6). RESULTS: Operative mortality was 2.6% (n = 8): it was higher for octogenarians (6.8%) than for younger patients (1.9%) (P =.06). The only significant preoperative predictors of early mortality were complicated percutaneous transluminal coronary angioplasty (P =.03) and preoperative use of intra-aortic balloon pumping (P =.03). Six patients (2%) had sternal wound infections for which chronic lung disease (P =.02) and emergency operation (P =.006) were the only significant predictors. Twenty-two (7.2%) late deaths occurred, and 1- and 3-year survivals were 93% and 90%, respectively. The 3-year survival of patients 80 years old or older was 92%. CONCLUSIONS: Bilateral grafting of the skeletonized internal thoracic artery carries relatively low morbidity and mortality in elderly patients and can be recommended for selected patients including octogenarians.     

Blunted temperature and cortisol responses to ipsapirone in major depression: lack of enhancement by electroconvulsive therapy

Depression has been shown in some studies to be associated with a reduction in hypothalamic 5-HT(1A) receptor function, as indicated by reduced hormone and/or hypothermic responses to 5-HT(1A) agonists such as ipsapirone. The hypothermic response to ipsapirone was reduced in depressed patients treated with amitriptyline. Hormone and hypothermic responses to 5-HT(1A) agonists were reduced in normal subjects administered specific serotonin reuptake inhibitors. Effects of electroconvulsive therapy (ECT) on 5-HT(1A) receptor-mediated responses in humans have not been reported. In the present work, ten depressed patients and 15 control subjects were challenged with placebo and with 0.3 mg/kg ipsapirone, administered 48 h apart in a randomised double blind design. Hypothermic, growth hormone (GH) and cortisol responses were measured. Seven of the depressed patients were treated with a course of ECT, and placebo and ipsapirone challenges were repeated 24 and 72 h after the last treatment. The cortisol response to ipsapirone was significantly reduced in the depressed patients compared with controls. The hypothermic response to ipsapirone was totally abolished in the depressed patients. When tested after a course of ECT, the seven depressed patients again showed reduced or blunted responses. We conclude that hypothalamic 5-HT(1A) receptor function is reduced in depression. In contrast to the effects of electroconvulsive shock (ECS) on post-synaptic 5-HT(1A) receptor function in animals, which have chiefly been measured in the hippocampus using electrophysiological techniques, ECT in humans does not induce an increase in sensitivity of post-synaptic 5-HT(1A) receptors in the hypothalamus.