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Biomedical subjects

M W Brown

Publications and source records attributed to M W Brown.

At least 91 records · Page 5Linked to original sources

A quantitative study of the actions of excitatory amino acids and antagonists in rat hippocampal slices.

1. A quantitative pharmacological investigation of the actions of excitatory amino acids on hippocampal CA1 neurones has been made using a new slice preparation developed for grease gap recording; d.c. potential was measured across a grease barrier placed between alvear fibres and the bathing medium. 2. In Mg2+-free perfusate, N-methyl-D-aspartate (NMDA, 1-100 microM), quisqualate (1-500 microM), kainate (1-200 microM) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 1-100 microM) caused dose-dependent depolarizations. 3. The dose-response relationships were fitted to logistic expressions. The maximum responses to AMPA, NMDA and kainate were similar; their respective EC50 values were 5, 13 and 23 microM. Quisqualate had a smaller maximum; its EC50 value was 10 microM. The slopes of the dose-response relationships were different for the 4 agonists; the order of steepness of the slopes was NMDA greater than AMPA greater than kainate greater than quisqualate. 4. Similar amino acid-induced depolarizations were observed in slices of just the CA1 region or in whole slices bathed in tetrodotoxin. Isolated alvear fibres, however, were insensitive to the excitatory amino acids. 5. D-2-Amino-5-phosphonovalerate (APV, 50 microM) selectively and reversibly antagonized responses induced by NMDA (apparent pA2 = 5.21). 6. Kynurenic acid (1 mM) reversibly depressed responses to the three agonists tested. The dose-ratios for antagonism of AMPA, kainate and quisqualate were 6.9, 5.6 and 4.6 respectively. 7. This preparation has a different sensitivity profile to agonists from those of previously reported preparations of spinal cord, neocortex and cerebellum. The greater sensitivity to NMDA may be due to the higher density of NMDA receptors in the hippocampus. The effects of the antagonists, APV and kynurenate, are similar to those found in other brain areas.

Amino Acids↗

Magnetic resonance imaging of renal transplants: initial experience.

Magnetic resonance imaging (MRI) was used in 45 renal transplant investigations (38 patients) using a Picker 0.15 T resistive system and a localized surface coil. An attempt was made to define optimal sequences in the evaluation of both normal and pathological transplants. Three sequences were found to be of value; a T1 weighted sequence (IR2180/700/40) to assess corticomedullary differentiation and its loss in acute rejection and acute tubular necrosis, a T2 weighted sequence (SE2000/80) for assessment of renal vessels and disturbances in blood supply, and a STIR (short tau inversion recovery) sequence (IR800/100/40) to define further the distended collecting system in obstruction and the presence of any perirenal collection. Encouraging results have been obtained, particularly in cases of acute rejection. It is suggested that the MRI scan is a useful screening test in cases of clinical doubt and may even obviate biopsy in some cases.

Adult↗

Gastroesophageal varices. Management of hemorrhage in the cirrhotic patient.

The appropriate management of the cirrhotic patient with bleeding gastroesophageal varices presents a continuing challenge for the primary care physician. These patients demand rapid assessment and skillful resuscitation. Confirmation of the suspected diagnosis should be sought by endoscopy. Endoscopic sclerotherapy currently is the treatment of choice for acute variceal hemorrhage. Unfortunately, despite prevention of recurrent hemorrhage, neither sclerotherapy nor portosystemic shunting has effected any significant alteration in the poor long-term survival of these patients. Newer approaches such as the use of propranolol offer some hope but doubtless will be hampered by the failure to alter the underlying liver disease.

Esophageal and Gastric Varices↗

Neuronal evidence that inferomedial temporal cortex is more important than hippocampus in certain processes underlying recognition memory.

Amnesia has been reported to result from combined damage to the amygdala, hippocampus and inferomedial temporal cortex in man and monkey. Evidence is presented that neuronal activity in the monkey inferomedial temporal cortex reflects memory for the previous occurrence of visual stimuli: 26 (15%) of 173 single units responded more strongly to first than to subsequent presentations of unfamiliar stimuli. No such responses were found for neurones recorded in the hippocampus and subicular cortex. The findings suggest that the inferomedial temporal cortex plays a central role in processes necessary for recognition memory.

Animals↗

Metallothionein gene expression and cadmium toxicity in freshwater fish.

Certain species of fish e.g. rainbow trout, are particularly susceptible to poisoning by cadmium in their aquatic environment whereas others e.g. roach and stone loach, are much more resistant. It is postulated that the vulnerability of the salmonids arises because 1) existing metallothionein (MT) in the tissues of these fish is unable to bind cadmium and 2) the toxic metal (in contrast to zinc) cannot switch on the gene(s) for apo-thionein production de novo. Consequently, cadmium is sequestered in the liver, kidney and gills of these fish by two low mol.wt. non-metallothionein proteins for which no excretion mechanism appears to exist.

Animals↗

Sequestration of environmental cadmium by metallothionein in the roach (Rutilus rutilus) and the stone loach (Noemacheilus barbatulus).

Two species of coarse fish that are relatively resistant to cadmium poisoning were exposed to sub-lethal concentrations of the metal in their aquarium water. Thus, roach were exposed to cadmium concentrations between 30 and 500 micrograms/l for periods of 14-70 days whereas stone loach were exposed to 1250 micrograms Cd/l for 21-77 days. Under all conditions of exposure, it was found upon analysis of the major organs of accumulation of cadmium in the two species that the toxic metal was sequestered by a single isoform of metallothionein. The amino acid compositions of roach and stone loach metallothionein were determined and found to be similar to those reported for other piscine metallothioneins. The two proteins were found to contain Cd:Zn:Cu in approximate ratios of 4:1:2 per mole of protein. The sequestration of Cd by metallothionein in the two resistant species of fish is contrasted with the situation observed previously in a cadmium-sensitive species, the rainbow trout.

Amino Acids↗

Zinc and paired-pulse potentiation in the hippocampus.

Zinc was added to the perfusate of rat hippocampal slices to determine the effect on the potentiation of evoked responses in subfield CA3 following paired-pulse stimulation of mossy fibres. Paired-pulse potentiation across a range of interpulse intervals and currents was significantly depressed by 50 and 500 microM zinc chloride. Additionally but only at the higher concentration, the amplitude of the first evoked potential was significantly increased. These results provide further evidence of a role for zinc in hippocampal neurotransmission.

Animals↗

Development of intractable ascites following upper abdominal surgery in patients with cirrhosis.

Recently, two patients with cirrhosis in whom ascites intractable to medical therapy had developed were referred to Medical Center Hospital and Audie L. Murphy Memorial Veterans Administration Hospital. Ascites had developed in both following upper abdominal surgery. To better characterize postoperative ascites, the records of all patients with cirrhosis who had upper abdominal operations at these hospitals during a five-year period were reviewed. Patients with portacaval shunts or pre-existing ascites were excluded. Of the 31 patients meeting the study requirements, ascites developed in 12 in the immediate postoperative period. In 10, the ascites resolved with medical management. As a group, these 10 patients had more severe liver disease than the group in whom ascites did not develop. The remaining two patients had ascites intractable to medical therapy. The ascitic fluid protein level was high in these two patients as well as in the two referred patients with a mean value of 4.5 +/- 1.6 g/dl. One patient with intractable ascites died and the other three required operative management. No clinical or laboratory features distinguished the patients in whom intractable ascites developed from the patients in whom postoperative ascites did not develop. It is suggested that intraoperative injury to vessels draining hepatic lymph was the cause of the intractable ascites.

Abdomen↗

A comparison of the differential accumulation of cadmium in the tissues of three species of freshwater fish, Salmo gairdneri, Rutilus rutilus and Noemacheilus barbatulus.

Roach and stone loach were exposed to cadmium dissolved in their aquarium water at 500 and 1250 micrograms/l, respectively, and the distribution of the metal accumulated in the major body organs was determined. The pattern of distribution for each species was somewhat different and was distinct in each case from that observed previously with rainbow trout. The total body loads of cadmium accumulated by the three species were assessed during the period of exposure and found not to correlate directly with the concentration of cadmium to which the individual species had been exposed. An alternative comparator was devised which as the quotient of the total body cadmium accumulation (microgram/100 g body wt) and the notional cadmium dose (microgram/l) X weeks was described as a fractional retention coefficient for cadmium. The coefficient was constant for each species at different periods of exposure to cadmium alone. The values of the coefficient for roach and stone loach were however much lower than that for rainbow trout. When rainbow trout were preexposed to zinc (100 micrograms/l, 5 days) before being exposed to cadmium, the fractional retention coefficient for cadmium fell to a value similar to those seen with roach and stone loach exposed to cadmium alone. The significance of these observations in relation to the nature of the intracellular proteins to which cadmium is bound in the three species is discussed in the light of their differential susceptibility to the toxic effects of cadmium.

Animals↗

Comparison of the costs and morbidity of percutaneous and open flank procedures.

A series of 47 percutaneous procedures for renal calculi was matched by description of calculi and previous flank exploration to 47 open flank procedures for comparison of relative morbidity and cost-efficiency. A retrospective analysis of paired data demonstrated that patients undergoing percutaneous procedures experienced significantly decreased duration of anesthesia, number of transfusions, postoperative disability, and duration and cost of hospitalization. These findings support the cost-effectiveness of the percutaneous approach to removal of renal calculi.

Adult↗

A note on the recovery of micro-organisms from an oil-in-water cream.

The isolation of micro-organisms from the oil-in-water Aqueous Cream BP, has been examined using a variety of solvent systems to disperse the cream prior to membrane filtration or direct inoculation. Pour-plate methods which utilize combinations of either peptone-water (containing 5% w/v polysorbate 80) or nutrient broth (containing 4% w/v Lubrol W) provided the most efficient recovery of Pseudomonas aeruginosa but still allowed less than 20% recovery. White spirit and isopropyl myristate allowed no recovery when used as dispersants. Recoveries of P. aeruginosa varied according to the source of the cream. A combination of 1% w/v polysorbate 80 in 0.1% w/v peptone-water and membrane filtration allowed 63.2% w/v and 67.0% w/v recoveries respectively of Aspergillus niger and Candida albicans from unpreserved aqueous cream, but gave unreproducible results for Escherichia coli and P. aeruginosa. Chlorocresol 0.1% w/v) did not meet the British Pharmacopoeial requirements for efficacy of antimicrobial preservatives when tested against C. albicans using membrane filtration to isolate the micro-organism.

Aspergillus niger↗

Cadmium accumulation and protein binding patterns in tissues of the rainbow trout, Salmo gairdneri.

Rainbow trout were exposed to defined levels of cadmium in their aquarium water for differing periods at a variety of near-lethal concentrations that ensured the survival of the majority of the fish. The gills, liver and kidney together accounted for 99% of the accumulated load of body cadmium in the fish under these conditions. Although the proportion of total cadmium present in the liver remained relatively constant throughout, the distribution of the remainder between gill and kidney altered with the time of exposure. The cadmium in all three organs was bound by two low molecular weight proteins distinct in character from metallothionein. The isoforms of metallothionein were also present but were found to bind only zinc and copper. By contrast, when trout were injected with cadmium intraperitoneally, most of the metal accumulated in the liver where it was sequestered by the two isoforms of metallothionein. Pre-exposure of the trout to either a low concentration of cadmium (for several months) or to an elevated concentration of zinc (for 5 days) allowed the animals to survive a subsequent exposure to a high, otherwise lethal concentration of cadmium. The proteins responsible for sequestration of the two metals were identified, but two different mechanisms seemed to be involved in the protection of the animals. The significance of these observations in terms of the induction of proteins and the prevention of the toxic effects of cadmium is considered.

Animals↗