Possible role of dopamine in central effects of cocaine as measured by apomorphine gnawing test in mice

Apomorphine (10 mg/kg, s.c.) does not induce in mice a compulsion to gnaw, but pretreatment with cocaine (10–40 mg/kg, i.p.) caused gnawing activity. This effect of cocaine was inhibited by pretreatment with -methyl-p-tyrosine, haloperidol, and physostigmine, but not with FLA-63, phenoxybenzamine and tetrabenazine. These findings would suggest that dopaminergic mechanism plays a significant role in the potentiation of apomorphine gnawing activity by cocaine and also support the view that inhibition of dopamine uptake is responsible for the stimulatory action of cocaine.     

MRI of the intraorbital optic nerve in patients with autosomal dominant optic atrophy

Measurements of the intraorbital optic nerve were made using high-resolution coronal MRI in 10 adults with autosomal dominant optic atrophy. Comparisons were made with previous studies of 10 normal adult subjects. The cross-sectional diameters of the optic nerve and the perineural subarachnoid space were measured and a ratio of there diameters at anterior, mid and posterior positions along the optic nerve was determined. We found a statistically significant difference in the mean optic nerve: sheath ratio between the control group and patients with autosomal dominant optic atrophy. At anterior, mid and posterior locations along the optic nerve it is significantly smaller in patients with optic atrophy. We have demonstrated that the loss of ganglion cells, previously documented in dominant optic atrophy, is associated with a significant loss of optic nerve tissue and thinning of the nerve along its length. Received: 6 July 1999/Accepted: 22 July 1999     

Lack of microvessels in well-differentiated regions of human head and neck squamous cell carcinoma A253 associated with functional magnetic resonance imaging detectable hypoxia, limited drug delivery, and resistance to irinotecan therapy.

PURPOSE: Combination chemotherapy with irinotecan (CPT-11; 50 mg/kg/week x 4 intravenously), followed 24 hour later by 5-fluorouracil (50 mg/kg/week x 4 intravenously), results in 10 and 100% cure rates of animals bearing human head and neck squamous cell carcinoma xenografts A253 and FaDu, respectively. A253 consists of 30% well-differentiated and avascular and 70% poorly differentiated regions with low microvessel density (10/x400), whereas FaDu is uniformly poorly differentiated with higher microvessel density (19/x400). Studies were carried out for determining the role of well-differentiated and avascular regions in drug resistance in A253 and detection of such regions with noninvasive functional magnetic resonance (fMR) imaging. EXPERIMENTAL DESIGN: Tumors were harvested for histopathologic evaluation and immunohistochemistry (CD31, CD34; differentiation marker: involucrin; hypoxia markers: carbonic anhydrase IX, pimonidazole; vascular endothelial factor (VEGF) and Ki67) immediately after fMR imaging following the 3rd dose of chemotherapy. High-performance liquid chromatography determination of intratumoral drug concentration of 7-ethyl-10-hydroxyl-camptothecin and autoradiography with (14)C-labeled CPT-11 was done 2 hours after CPT-11 administration. RESULTS: Although A253 xenografts showed three times higher concentration of 7-ethyl-10-hydroxyl-camptothecin, FaDu was more responsive to therapy. After therapy, A253 tumor consisted mostly (approximately 80%) of well-differentiated regions (positive for involucrin) lacking microvessels with a hypoxic rim (positive for carbonic anhydrase IX and pimonidazole) containing few proliferating (Ki67 positive) poorly differentiated cells. Autoradiography revealed that well-differentiated A253 tumor regions showed 5-fold lower (14)C-labeled CPT-11 concentrations compared with poorly differentiated areas (P < 0.001). Blood oxygen level dependant fMR imaging was able to noninvasively distinguish the hypoxic and well-vascularized regions within the tumors. CONCLUSION: Avascular-differentiated regions in squamous cell carcinoma offer sanctuary to some hypoxic but viable tumor cells (carbonic anhydrase IX and Ki67 positive) that escape therapy because of limited drug delivery. This study provides direct evidence that because of a specific histologic structure, avascular, well-differentiated hypoxic regions in tumors exhibit low drug uptake and represent a unique form of drug resistance.     

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     

Evoked potential monitoring in anaesthesia and analgesia

Electrophysiological monitoring of selected neural pathways of the brain, brainstem, spinal cord and peripheral nervous system has become mandatory in some surgery of the nervous system where preventable neural injury can occur. Evoked potentials are relatively simple methods of testing the integrity of various aspects of the nervous system. This review covers the variety of evoked potentials that can be monitored and outlines the principles of their measurement. Their use in specific situations and how factors such as anaesthesia might affect them is presented.     

Impacts of Informal Caregiver Availability on Long-term Care Expenditures in OECD Countries

Objective. To quantify the effects of informal caregiver availability and public funding on formal long-term care (LTC) expenditures in developed countries.
Data Source/Study Setting. Secondary data were acquired for 15 Organization for Economic Cooperation and Development (OECD) countries from 1970 to 2000.
Study Design. Secondary data analysis, applying fixed- and random-effects models to time-series cross-sectional data. Outcome variables are inpatient or home heath LTC expenditures. Key explanatory variables are measures of the availability of informal caregivers, generosity in public funding for formal LTC, and the proportion of the elderly population in the total population.
Data Collection/Extraction Method. Aggregated macro data were obtained from OECD Health Data, United Nations Demographic Yearbooks, and U.S. Census Bureau International Data Base.
Principal Findings. Most of the 15 OECD countries experienced growth in LTC expenditures over the study period. The availability of a spouse caregiver, measured by male-to-female ratio among the elderly, is associated with a $28,840 (1995 U.S. dollars) annual reduction in formal LTC expenditure per additional elderly male. Availability of an adult child caregiver, measured by female labor force participation and full-time/part-time status shift, is associated with a reduction of $310 to $3,830 in LTC expenditures. These impacts on LTC expenditure vary across countries and across time within a country.
Conclusions. The availability of an informal caregiver, particularly a spouse caregiver, is among the most important factors explaining variation in LTC expenditure growth. Long-term care policies should take into account behavioral responses: decreased public funding in LTC may lead working women to leave the labor force to provide more informal care.