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Biomedical subjects

M Grubb

Publications and source records attributed to M Grubb.

13 recordsLinked to original sources
PubMed2003

Ventral hippocampal lesions affect anxiety but not spatial learning.

Rats with cytotoxic ventral hippocampal lesions which removed approximately 50% of the hippocampus (including dentate gyrus) starting from the temporal pole, displayed a reduction in freezing behaviour following the delivery of an unsignalled footshock in an operant chamber. This was more plausibly a result of reduced susceptibility to fear than a result of a lesion-induced increase in general motor activity. There was no consistent difference between sham and lesioned animals in spontaneous locomotor activity, or locomotion following acute or chronic treatment with amphetamine. In contrast, ventral hippocampal lesioned animals were quicker to pass from the black to the white box during a modified version of the light/dark exploration test, and were quicker to begin eating during tests of hyponeophagia. Furthermore, rats with ventral hippocampal lesions defecated less than their sham counterparts both during open field testing and in extinction sessions following contextual conditioning. In contrast to these clear lesion effects, there were no signs of any spatial learning impairment either in the watermaze or on the elevated T-maze. Taken together these results suggest that the ventral hippocampus may play a role in a brain system (or systems) associated with fear and/or anxiety, and provide further evidence for a distinct specialisation of function along the septotemporal axis of the hippocampus.

Amphetamine↗
PubMed2002

Double dissociation of function within the hippocampus: spatial memory and hyponeophagia.

Complete and dorsal hippocampal lesions impaired spatial performance on 2 working memory tasks: rewarded alternation on the T maze and matching to position in the water maze. In contrast, ventral hippocampal lesions had no effect on these tasks, even when task difficulty was increased by the introduction of delays. Ventral lesions did resemble complete lesions in reducing anxiety in 3 commonly used tests of anxiety (social interaction, plus-maze, and hyponeophagia). Dorsal lesions also appeared to be anxiolytic in the social interaction and plus-maze tests, but they did not affect hyponeophagia. Complete- and dorsal-lesioned rats displayed hyperactivity, whereas ventral-lesioned rats did not. These results show a double dissociation between dorsal and ventral hippocampal lesions (hyponeophagia vs. spatial memory), suggesting differentiation of function along the septotemporal axis of this structure.

Amphetamine↗
PubMed2001

Capping the cost of compliance with the Kyoto Protocol and recycling revenues into land-use projects.

There is the concern among some countries that compliance costs with commitments under the Kyoto Protocol may be unacceptably high. There is also the concern that technical difficulties with the inclusion of land use, land-use change, and forestry activities in non-Annex I countries might lead to an effective exclusion of such activities from consideration under the Protocol. This paper is proposing a mechanism that addresses both these concerns. In essence, it is suggested that parties should be able to purchase fixed-price offset certificates if they feel they cannot achieve compliance through other means alone, such as by improved energy efficiency, increased use of renewable energy, or use of the flexible mechanisms in the Kyoto Protocol. These offset certificates would act as a price cap for the cost of compliance for any party to the Protocol. Revenues from purchase of the offset certificates would be directed to forest-based activities in non-Annex I countries such as forest protection that may carry multiple benefits including enhancing net carbon sequestration.

Energy-Generating Resources↗
PubMed1996

Ultrasound-guided compression closure of postcatheterization pseudoaneurysms during concurrent anticoagulation: a review of seventy-seven patients.

PURPOSE: Data from our institution and elsewhere have demonstrated that ultrasound-guided compression closure (UGCC) is an effective method of treating postcatheterization pseudoaneurysms. Whereas patients receiving anticoagulation do not have as high a success rate as those not receiving anticoagulants, there have been no large series evaluating the factors associated with success or failure in patients receiving anticoagulation. The purpose of this study is to determine whether uninterrupted anticoagulation interferes with successful UGCC of pseudoaneurysms and to identify factors associated with success or failure. METHODS: From May 1991 to September 1994, 238 cases of attempted UGCC of pseudoaneurysms were performed in our vascular laboratory. Only patients who received uninterrupted heparin, warfarin, or both at the time of pseudoaneurysm compression were eligible for inclusion into the study. Seventy-seven patients were identified who met the study criteria. RESULTS: Successful pseudoaneurysm compression was obtained in 56 (73%) patients, whereas 21 (27%) patients had a failed UGCC. In the successfully treated group, seven (12.5%) required between two to three compression attempts to induce sustained thrombosis. There was no statistical difference in age, sex, sheath size, days after procedure, location of pseudoaneurysm, or number of chambers in the pseudoaneurysm between those patients who had a successful repair and those who did not. If the pseudoaneurysm was less than 4 cm in diameter, 51 of 65 patients (78%) had a successful repair compared with 5 of 12 patients (42%) with a pseudoaneurysm of 4 cm or greater (p = 0.013). There was no statistical difference between success and failure in patients receiving warfarin alone (3.73 mean international normalized ratio, 72% success rate), heparin alone (mean activated partial thromboplastin time of 63 seconds, 92% success rate), or heparin and warfarin (mean activated partial thromboplastin time of 70 seconds, mean international normalized ratio of 4, success rate of 67%). No arterial or venous thrombosis occurred during pseudoaneurysm compression. CONCLUSION: Successful UGCC of pseudoaneurysms occurred in a large percentage of patients receiving full-dose, uninterrupted anticoagulation. The only factor influencing success was the size of the pseudoaneurysm.

Adult↗
PubMed1996

Improved cyclic urea inhibitors of the HIV-1 protease: synthesis, potency, resistance profile, human pharmacokinetics and X-ray crystal structure of DMP 450.

BACKGROUND: Effective HIV protease inhibitors must combine potency towards wild-type and mutant variants of HIV with oral bioavailability such that drug levels in relevant tissues continuously exceed that required for inhibition of virus replication. Computer-aided design led to the discovery of cyclic urea inhibitors of the HIV protease. We set out to improve the physical properties and oral bioavailability of these compounds. RESULTS: We have synthesized DMP 450 (bis-methanesulfonic acid salt), a water-soluble cyclic urea compound and a potent inhibitor of HIV replication in cell culture that also inhibits variants of HIV with single amino acid substitutions in the protease. DMP 450 is highly selective for HIV protease, consistent with displacement of the retrovirus-specific structural water molecule. Single doses of 10 mg kg-1 DMP 450 result in plasma levels in man in excess of that required to inhibit wild-type and several mutant HIVs. A plasmid-based, in vivo assay model suggests that maintenance of plasma levels of DMP 450 near the antiviral IC90 suppresses HIV protease activity in the animal. We did identify mutants that are resistant to DMP 450, however; multiple mutations within the protease gene caused a significant reduction in the antiviral response. CONCLUSIONS: DMP 450 is a significant advance within the cyclic urea class of HIV protease inhibitors due to its exceptional oral bioavailability. The data presented here suggest that an optimal cyclic urea will provide clinical benefit in treating AIDS if it combines favorable pharmacokinetics with potent activity against not only single mutants of HIV, but also multiply-mutant variants.

Administration, Oral↗
PubMed1995

The utility of duplex ultrasound scanning of the renal arteries for diagnosing significant renal artery stenosis.

OBJECTIVE: To determine the utility of duplex ultrasound scanning of the renal arteries in identifying patients with renal artery stenosis of 60% or more and in excluding patients with either normal renal arteries or renal artery stenosis of less than 60%. DESIGN: A prospective, blinded study. SETTING: Large tertiary referral center. PATIENTS: 102 consecutive patients (44 men and 58 women with a mean age [+@- SD] of 63.3 +/- 13.4 years) who had both duplex ultrasound scanning of the renal arteries and renal arteriography. All patients who were studied had hypertension that was difficult to control, unexplained azotemia, or associated peripheral vascular disease (alone or in combination), giving them a high pretest likelihood of renovascular disease. MAIN OUTCOME MEASUREMENTS: Peak systolic and end diastolic velocities, renal-aortic ratios, resistive index, and kidney sizes. RESULTS: Sixty-two of 63 arteries with stenosis of less than 60% using arteriography were correctly identified by duplex ultrasound scanning. Thirty-one of 32 arteries with 60% to 79% stenosis using arteriography were correctly identified as having 60% to 99% stenosis on duplex ultrasound, whereas 67 of 69 arteries with 80% to 99% stenosis on arteriography were correctly identified as having 60% to 99% stenosis on ultrasound. Twenty-two of 23 arteries with total occlusion on arteriography were correctly identified by duplex ultrasound. The overall sensitivity of duplex ultrasound compared with arteriography was 0.98, the specificity was 0.98, the positive predictive value was 0.99, and the negative predictive value was 0.97. CONCLUSION: Duplex ultrasound scanning of the renal arteries is an ideal screening test because it is noninvasive and can predict the presence or absence of renal artery stenosis with a high degree of accuracy.

Aged↗
PubMed1994

Antiinflammatory 4,5-diarylpyrroles: synthesis and QSAR.

A series of 2-substituted- and 2,3-disubstituted-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-1H- pyrroles was synthesized and found to be active in the rat adjuvant arthritis model of inflammation. The most active compounds were the 2-halo derivatives in the order of chloro > bromo > iodo. The same pattern of activity was observed for the 2,3-dihalopyrroles. Quantitative structure-activity relationship studies suggested that the activity could be correlated with the molar refractivity and the inductive field effect of the 2-substituent and the lipophilicity of the 3-substituent.

Animals↗
PubMed1992

Understanding vascular ultrasonography.

The technology of imaging has progressed rapidly; thus, physicians must stay abreast of the principles of utilization and the interpretation of these new tests. Most of the information about this technology is presented in subspecialty literature that is not readily accessible or easily interpretable by nonspecialists. Herein we review the current literature on vascular ultrasonography and present the information in a simple, practical manner. The safety, utility, and accuracy of the ultrasound devices are delineated for the study of various vascular conditions.

Blood Vessels↗
PubMed1985

Effects of reestablishing blood flow on extent of myocardial infarction in conscious dogs.

The effects of permanent circumflex coronary artery occlusion (PO) compared with reestablishing blood flow (OR) at 2 and 6 h after occlusion on the final extent of histological infarction (HI) was assessed in chronically instrumented awake dogs. The relationships between the extent of left ventricular ischemia measured by microsphere techniques and HI in the PO group were used as models to predict the expected infarction in the 2- and 6-h OR groups. Mean HI (+/-SD) in the PO and 6- and 2-h OR groups was 21 +/- 13, 19 +/- 10, and 13 +/- 12% of left ventricular weight, respectively; values were not significantly different. The extent of HI in samples grouped according to epicardial and endocardial layers and ischemic blood flow ranges (0-15, 16-30, 31-50, 51-75% of control region blood flow) was reduced in the 2-h but not 6-h OR group. Analysis of individual animals using total ischemic region blood flow to epicardial and endocardial layers demonstrated that OR at 2 h but not 6 h reduced infarction in most animals but not in certain animals with the largest ischemic regions.

Animals↗