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Biomedical subjects

J Cook

Publications and source records attributed to J Cook.

At least 145 records · Page 8Linked to original sources

Disparate effects of phosphoramidon on blood pressure in SHR and DOCA-salt hypertensive rats.

Phosphoramidon inhibits both endothelin converting enzyme (ECE) and neutral metalloendopeptidase (NEP). The contribution of ECE and NEP inhibition to the antihypertensive effects of phosphoramidon was investigated in SHR and DOCA-salt hypertensive rats. SCH 32615, an active acid of the potent and selective NEP inhibitor prodrug SCH 34826 was used as a reference compound. Intravenous infusion of SCH 32615 (1.0 mg/kg/min x 2 hr) or phosphoramidon (0.3 and 1.0 mg/kg/min x 2 hr) did not reduce blood pressure (BP) in conscious SHR. The combination of SCH 32615 (100 mg/kg + 1.0 mg/kg/min) and phosphoramidon (0.3 mg/kg/min) also did not alter BP in SHR. In comparison, the BP of conscious DOCA-salt rats was significantly reduced by phosphoramidon (0.01, 0.1 and 1.0 mg/kg/min x 2 hr) (-28 +/- 6, -51 +/- 5 and -85 +/- 6 mmHg, respectively). SCH 32615 (100 mg/kg, i.v.) over 5 min followed by a sustained infusion of 1.0 mg/kg/min for 2 hr also reduced BP by 49 +/- 7 mmHg (P < .05) in DOCA-salt rats. However, phosphoramidon (0.1 mg/kg/min x 2 hr) failed to cause a further reduction in BP in DOCA-salt rats concurrently receiving SCH 32615. In contrast, a higher dose of phosphoramidon (0.3 mg/kg/min) in combination with SCH 32615 caused a greater reduction in BP in DOCA-salt rats than SCH 32615 alone. In anesthetized normotensive rats, phosphoramidon (0.01-1.0 mg/kg/min x 30 min) dose-dependently inhibited the BP responses to big endothelin-1 (BET-1) without blocking the pressor responses to ET-1. SCH 32615 failed to attenuate the pressor responses to either BET-1 or ET-1. The results indicate that SCH 32615 lacks in vivo ECE inhibitory activity. It is concluded that the antihypertensive action of SCH 32615 and low doses of phosphoramidon can be attributed to the inhibition of NEP which may presumably cause an accumulation of ANF. In comparison, at higher doses phosphoramidon causes a further reduction of BP in DOCA-salt hypertensive rats by inhibition of endothelin bioconversion.

Animals↗

The effect of surgical floor mats in prolonged standing: an EMG study of the lumbar paraspinal and anterior tibialis muscles.

The purpose of this study was to determine whether or not surgical floor mats affect low back and leg muscle activity during prolonged standing. The EMG activity was measured continuously using surface electrodes on the paraspinal muscles of the low back and on the anterior tibialis muscles; the subjects were normal and stood on two different surfaces. Six male subjects were each instructed to stand for two hours on a specially designed surgical floor mat and then, on a separate day, to stand for two hours on a linoleum-covered concrete surface. Six other subjects carried out the same procedure, but stood on the linoleum first. There was no difference in EMG activity obtained from the anterior tibialis muscles and paraspinal muscles of the low back when the subjects stood on the surgical mat, as compared with the linoleum-covered concrete.

Adult↗

Cloning and functional characterisation of the human TRH receptor.

Thyrotrophin-releasing hormone (TRH) is a hypothalamic tripeptide known to act via its receptor in the anterior pituitary gland to stimulate the release of thyrotrophin (TSH) from thyrotrophs and prolactin (PRL) from lactotrophs. It is also thought to act as a neurotransmitter/neuromodulator in the central and peripheral nervous systems. We have isolated a cDNA encoding the human pituitary TRH receptor (TRH-R) protein with a predicted amino acid sequence of 398 amino acids. Comparison of the amino acid sequences of the human TRH-R with the previously published rodent TRH-Rs showed that it is similar to both the rat and mouse TRH-Rs, except that each species has variant amino acids at the carboxy (COOH) terminus. The human TRH-R belongs to the family of seven transmembrane domain, G-protein-coupled receptors, and it is believed that the COOH terminal region of this family of receptors may play an important role in receptor downregulation/internalisation, and possibly G-protein coupling. COS-1 cells expressing the human TRH-R showed high affinity receptor binding. Stimulation of these cells with TRH produced a typical phosphoinositide response and mobilisation of intracellular calcium [Ca2+]i.

Amino Acid Sequence↗

Coordinated strategies for controlling micronutrient malnutrition: a technical workshop.

Participants in a November 1991 workshop concluded that coordinated strategies for controlling malnutrition due to iodine, iron, vitamin A and other micronutrients deficiencies are technically feasible and should be given consideration in planning control efforts. Coordinated surveys involving clinical, biochemical and dietary assessment of multiple micronutrients are feasible. Multiple fortification is also possible using such vehicles as salt, processed rice or sugar. Supplementation efforts can be integrated with existing health care programs. Food-based strategies are also effective. The best examples have been community-based and have included a strong nutrition and health education component designed to change food consumption patterns, improve food preservation and preparation practices, and link income-generating activities with food production activities. Successful coordinated efforts will require a strong political commitment and a supportive infrastructure. Specific recommendations include the formation of national coordinating bodies for micronutrient deficiency control, establishment of a micronutrient information network and expansion of technical exchange and training.

Developing Countries↗

The ventricular-synchronous, skeletal-muscle ventricle: preliminary feasibility studies.

The two requirements for the optimal use of skeletal muscle wrapped around a pouch used to pump blood are:(1) a low pouch diastolic pressure (to assure a high muscle capillary blood flow; and (2) a high pouch precontraction pressure (PCP) (to assure a forceful muscle contraction). Both requirements are satisfied with the pumping method described herein. This new type of skeletal-muscle ventricle (SMV) consists of a rectus abdominis muscle wrapped around a pouch connected to the left ventricular apex (with no valve) and to the aorta via a one-way valve. Consequently, the pressure in the SMV pouch is always equal to left ventricular pressure. The high PCP is obtained by stimulating the rectus muscle to contract at the desired left ventricular pressure. The R (or P) wave of the cardiac electrogram initiates a delayed train of stimuli to cause the rectus muscle to contract tetanically and expel blood from the pouch. We have designated this pumping configuration the ventricular-synchronous SMV (VS-SMV). In this study, eight acute anesthetized dogs were used. The muscles were unconditioned and among the items investigated were the importance of the delay (d) between the R (or P) wave and the onset of the stimulus train, the optimal stimulus frequency and train duration, the VS-SMV output with different ratios of VS-SMV to left ventricular contractions, unloading of the left ventricle, Frank-Starling curves for the VS-SMV, pressure-volume loops for the VS-SMV with and without contraction of the rectus muscle, and washout characteristics of the VS-SMV. It was found that a stimulus frequency of 40/sec, and a train duration of 250 msec is optimal. It was also found that choice of the proper delay from the R or P wave provided maximal augmentation in stroke volume, typically 20 to 40 mL. Pumping with a ratio of 1:2 provided VS-SMV outputs ranging from 20 to 140 mL/min per kg of body weight. With this same pumping ratio, cardiac output increased by 28% and the post-VS-SMV contraction, left ventricular stroke volume was reduced. The Frank-Starling curves showed that PCPs on the order of aortic pressure are needed for the most forceful muscle contraction. With this new pumping configuration, the left ventricle resembles an atrium which delivers blood to the VS-SMV that is stimulated to contract when the desired PCP is reached. Studies were also conducted in which the VS-SMV outlet (valve end) was closed and filling and emptying occurred through the left ventricle.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdominal Muscles↗

The importance of timing muscle contraction in dynamic cardiomyoplasty.

This acute dynamic cardiomyoplasty (CMP) study used ten dogs (weight range 21-32 kg) and was designed to determine the importance of the train of stimuli initiation time when applied to the thoracodorsal nerve, which innervates the latissimus dorsi (LD) muscle that is wrapped around the ventricles. Using the P wave of the cardiac electrogram to trigger a special delay circuit, the stimulus train could be initiated from the apex of the R wave to any time throughout and at the end of the isovolumic period, signaled by opening of the aortic valve. The cardiac electrogram (which contained the R wave), left ventricular pressure (LVP), aortic flow velocity (AFV), beat-by-beat stroke volume (SV), femoral artery pressure, and the envelope of the stimulus train were recorded as the onset of the stimulus train was varied from the R wave to the end of the isovolumic period with a pumping ratio of one LD contraction for every seven ventricular contractions. In four dogs there was a pronounced increase in the augmentation in LVP, AFV, and SV when the stimulus train was initiated later than 40 msec after the first peak of the R wave. In five dogs the augmentation in LVP, AFV, and SV was not as clearly apparent, although all of these dogs exhibited an optimal train delay. Data were not obtained on one dog due to an anomalous LD muscle blood supply. For all of the dogs, the optimum train delay from the R wave averaged 58 msec (range 40-80 msec). The average augmentation in SV was 26% (range 13%-45%). The same muscle-wrap tightness was used in all dogs. In one dog, the muscle-wrap tightness was varied, and by tightening the wrap the SV augmentation increased from 17% to 27%. For all dogs the range of augmentation in SV (13%-45%) perhaps represents variations in muscle-wrap tightness, which may be a major uncontrolled factor in dynamic CMP.

Animals↗

Impact of assertive community treatment on the use of state hospital inpatient bed-days.

OBJECTIVE: The purpose of the study was to determine whether use of inpatient services at a state hospital was reduced by implementation of an assertive community treatment program among persons in one of the hospital's catchment areas who were at high risk for rehospitalization. METHODS: Bed-day utilization by program participants during the fiscal year before the program was implemented (1986) and three subsequent fiscal years was compared with utilization by persons in catchment areas not served by the program. For the 66 program participants, hospital use during the year before program intake was compared with use in the year after intake using t tests. RESULTS: Utilization of bed-days by persons in the program's catchment area was reduced by 28 percent in the third fiscal year after program implementation, compared with an increase of 15 percent among persons in the hospital's other catchment areas. In the year after the program was implemented, participants were hospitalized a mean of 27.7 days, compared with a mean of 80 days in the year before the program. CONCLUSIONS: The assertive community treatment program significantly reduced use of inpatient days and improved continuity of care.

Adult↗

Single photon emission computerised tomography in elderly patients with Alzheimer's disease and multi-infarct dementia. Regional uptake of technetium-labelled HMPAO related to clinical measurements.

Single photon emission computerised tomography (SPECT) was used to measure regional brain uptake of technetium-99m hexamethylpropyleneamine oxine (Tc99m-HMPAO) in elderly patients with Alzheimer's disease (AD), multi-infarct dementia (MID) and normals (n = 20 in each group). Different patterns of uptake were found between groups when cortical uptake was normalised to cerebellar uptake. Reductions occurred in all regions in AD, being most marked in temporal and posterior parietal areas. Significant correlations were found in AD between memory impairment and decreased temporal uptake bilaterally, and between duration of illness and reduced uptake in most brain regions. MID patients showed higher uptake in the anterior parietal region than did the other groups. A variable comparing anterior to posterior uptake significantly discriminated the two patient groups.

Aged↗

Selection and integration of a radiology information system.

A comprehensive and reliable computer-based RIS can significantly improve patient care. The authors present case studies that illustrate different approaches to selection and implementation of an RIS. Detailed coverage is given to criteria for the RIS, the selection process, integration with hospital information systems and planning for the future.

Arizona↗

Vitamin B12 and folate. Pediatric reference ranges.

Pediatric reference ranges were obtained for vitamin B12 and folate (Quantaphase radioimmunoassay, BioRad, Hercules, Calif) using a large hospital population. Data were analyzed employing the Hoffman approach, which was computer adapted. For folic acid, the range for subjects aged 1 to 12 years averaged 5.7 to 31.3 nmol/L for female subjects and 4.5 to 27.0 nmol/L for male subjects. There was a significant decrease in folic acid concentrations after 13 years, the upper limit being 16.5 nmol/L in female subjects and 19.9 nmol/L in male subjects. For vitamin B12, the values in the 0- to 1-year age group were nearly double those in the 13- to 18-year age group. For female subjects, the values in the 0- to 1-year age group were 168 to 1116 pmol/L and in male subjects were 216 to 891 pmol/L. At 13 to 18 years, for female subjects the values were 158 to 637 pmol/L and for male subjects, 134 to 605 pmol/L.

Adolescent↗

Characterization of ursolic acid as a lipoxygenase and cyclooxygenase inhibitor using macrophages, platelets and differentiated HL60 leukemic cells.

A new property of ursolic acid, lipoxygenase and cyclooxygenase inhibition, has been described in an acetone-extract of heather flowers (Calluna vulgaris) which could help explain the anti-inflammatory characteristics of this plant. In mouse peritoneal macrophages, human platelets and differentiated HL60 leukemic cells, ursolic acid, at 1 microM, blocks arachidonate metabolism.

Animals↗

Prevention of the spread of HIV-1 infection with nonnucleoside reverse transcriptase inhibitors.

Certain bisheteroarylpiperazines (BHAPs) directly inhibit the replication of human immunodeficiency virus type 1 (HIV-1) and block the spread of infection to susceptible populations of cells. At a 1 microM concentration three analogs, U-87201, U-88204, and U-89674, inhibited the replication of HIV-1 in MT-2 cells by 83, 100, and 93%, respectively. At the same concentration, U-88204 completely inhibited replication of primary HIV-1 isolates in peripheral blood mononuclear cells. Replication of 3'-azido-2',3'-dideoxythymidine (AZT)-resistant strains of HIV-1 was also inhibited by U-88204. When MT-2 cells that were lytically infected with HIV-1 were mixed with uninfected MT-2 cells, U-88204 provided complete protection to the uninfected cells. Integrated proviral DNA sequences were not detected by the polymerase chain reaction technique in this culture after 15 days in the presence of drug. The resultant healthy cell culture was subsequently maintained without drug with no evidence of latent proviral DNA. Serial passage of a laboratory strain and a primary isolate of HIV-1 in cell culture in the presence of increasing concentrations of U-88204 yielded virus populations which were at least 100-fold resistant to the drug. These resistant viruses also showed cross-resistance to the pyridinone class of nonnucleoside inhibitors but were sensitive to AZT. Analysis of the nucleotide sequence of resistant viruses revealed mutations at conserved regions of the reverse transcriptase (RT) gene. The results presented here suggest the therapeutic potential of U-88204 in the combination therapy for HIV-1 infection.

Cell Line↗

NZB/NZW F1 mouse nephritis and immune response are not changed by treatment with a 15-lipoxygenase derivative.

15-HETE is an arachidonic acid derivative issued from the 15 lipoxygenase pathway. This fatty acid possesses immunomodulatory capabilities since it was reported that it generates CD8 + suppressor T-cells either in vitro or ex vivo. The aim of the present report was to study if the suppressive capabilities of 15-HETE were able to influence the onset of the NZB/NZW Fl auto-immune disease. For that purpose we produced 15-HETE and injected the eicosanoid twice a week to NZB/WFI mice for 40 weeks. During the 15-HETE treatment of the animals it was observed an augmentation of the proliferative response of lectin-stimulated splenocytes (at weeks 20 and 30) then the thymidine uptake decreased (at week 40). In fact we observed that among 15-HETE treated mice the evolution of the nephropathy was not changed, the 'glomerular activity score' remained the same for the treated animals compared to controls. On the contrary antinuclear antibodies occurred earlier even if in some experiments the generation of CD8 + cells was demonstrated.

Animals↗

A comparison of laser cautery and sub-mucosal diathermy for rhinitis.

A randomized prospective trial was conducted to compare the efficacy of laser cautery against sub-mucosal diathermy to the inferior turbinates in 29 patients with rhinitis. Laser diathermy was performed using an arthroscopic fitment to a CO2 laser. Subjective and objective measurement of airway obstruction were performed, using a linear analogue scale and a nasal peak inspiratory flow meter, before operation and at 3 days and 6 weeks afterwards. In both groups there was a similar and significant improvement in subjective scores at 6 weeks (SMD from 3.6 to 1.8, P less than 0.01; laser from 3.9 to 2.1, P less than 0.001), but only the laser group was significantly better at Day 3 (SMD from 3.6 to 3.5, n.s.; laser from 3.9 to 3.0, P less than 0.05). In addition, there was significantly more general subjective morbidity at Day 3 in the SMD group (P less than 0.01). The objective scores improved equally in both groups but were not significant. We conclude that laser cautery of the inferior turbinate is a superior alternative to SMD for the treatment of rhinitis.

Adult↗

Reversible late potentials due to ischemia.

The role of ischemia in the development of reversible late potentials was assessed in 19 patients undergoing percutaneous transluminal coronary angioplasty. Signal-averaged electrocardiograms were performed before angioplasty, during ischemia caused by balloon inflation and after angioplasty. Five of 19 patients developed late potentials that reverted to normal after angioplasty. Age, sex, ejection fraction, left ventricular end diastolic pressure, vessels involved, and extent of myocardium in jeopardy did not predict the development of late potentials. Patients with a prior history of myocardial infarction were more likely to develop late potentials. Therefore, patients with prior myocardial infarction appear more likely to develop the substrate for reentrant ventricular tachycardia during periods of ischemia.

Angioplasty, Balloon, Coronary↗