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Biomedical subjects

M Singer

Publications and source records attributed to M Singer.

At least 127 records · Page 7Linked to original sources
PubMed1995

Recent evolution of genes encoding the prohormone-like protein SMR1 in the rat submandibular gland.

The Variable Coding Sequence (VCS) multigene family of Rattus norvegicus, is composed of at least 10 members, and shows extensive evolutionary divergence in the protein-coding region. Three members of the VCSA subclass, have been characterized: one of them, the VCSA1 gene mainly expressed in the submandibular gland (SMG) encodes the prohormone-like protein, SMR1-VA1. As VCSA-related genes have not been detected in Mus musculus, the VCSA genes subclass is presumed to have recently emerged. To study the evolution of this subclass, we have looked for VCSA genes in a closely related species, Rattus rattus. By Northern analysis, we demonstrate that VCS-related mRNAs are present in the SMG, and that the level of VCSA mRNA accumulation is approximately equal in both sexes. By contrast, in R. norvegicus, males accumulate about 3,000 times more VCSA1 mRNA than females. Using total SMG mRNA, an almost full-length cDNA, homologous to the cDNA of the R. norvegicus VCSA1 gene, was cloned by reverse transcriptase polymerase chain reaction (RT-PCR). The putative corresponding SMR1-VA1 protein is 146 amino acids long and presents the features characteristic of a secreted protein, with a potential signal peptide of 22 amino acids in the amino-terminal portion. The presence of potential processing multibasic sites suggests that small peptides could be generated (particularly a hexapeptide: Arg-Gln-His-Asn-Leu-Arg), as in the case of the SMR1-VA1 protein of R. norvegicus. From Southern blot analysis there appears that species-species modifications of VCSA gene copy number have occurred; R. rattus contains a greater VCSA1 copy number than R. norvegicus (two or three and one, respectively).

Amino Acid Sequence↗
PubMed1995

Continuous measurement of cardiac output during aortic cross-clamping by the oesophageal Doppler monitor ODM 1.

We have compared the Doppler against the thermodilution technique for measurement of cardiac output in six patients during aortic surgery. The correlation coefficient between the two methods was between 0.76 and 0.84 during the different periods of the operation. Using the integral nomogram instead of direct calibration, the Doppler system underestimated cardiac output in atherosclerotic patients. However, the Doppler method did register accurately significant changes in cardiac output.

Aged↗
PubMed1995

Immunotherapy in the management of sepsis.

The pathophysiological effects of severe sepsis, septic shock and related syndromes result from tissues damaged by the uncontrolled production of the mediators of inflammation. Early deaths are related primarily to the acute effects of the systemic inflammatory response. Later deaths are related more closely to the consequences of multiple organ dysfunction. Monoclonal antibodies and other immunotherapies have been developed against bacterial products, cytokines and other mediators involved in this systemic inflammatory response. Immunotherapies may improve outcome in the critically ill with sepsis if used early and as part of the therapeutic regimen of antimicrobial agents and intensive care support.

Animals↗
PubMed1995

High dependency units in the UK: variable size, variable character, few in number.

An exploratory descriptive survey was conducted to determine the size and character of high dependency units (HDUs) in the UK. A telephone survey and subsequent postal questionnaire was sent to the 39 general HDUs in the UK determined by a recent survey from the Royal College of Anaesthetists; replies were received from 28. Most HDUs (82%, n = 23) were geographically distinct from the intensive care unit and varied in size from three to 13 beds, although only 64% (n = 18) reported that all beds were currently open. Nurse: patient ratios were at least 1:3. Fifty per cent of units had one or more designated consultants in charge, although only 11% (n = 3) had specifically designated consultant sessions. Junior medical cover was provided mainly by the on-call speciality term. Twenty units acted as a step-down facility for discharged intensive care unit patients and 21 offered a step-up facility for patients from general wards. Provision of facilities and levels of monitoring varied between these units. Few HDUs exist in the UK and they are variable in size and in the facilities and monitoring procedures which they provide. Future studies are urgently required to determine cost-effectiveness and outcome benefit of this intermediate care facility.

Health Facility Size↗
PubMed1995

Oxygen tension in the bladder epithelium rises in both high and low cardiac output endotoxemic sepsis.

The effect of endotoxin on tissue oxygen tension measured at the bladder epithelium was assessed in spontaneously breathing Sprague-Dawley rats anesthetized with halothane. Hyperdynamic (high cardiac output, group A, n = 6) and hypodynamic (low cardiac output, group B, n = 6) circulatory responses were achieved by intravenous administration of Escherichia coli lipopolysaccharide, 10 mg/kg over 30 min or 20 mg/kg over 1 min, respectively. Comparison was made against sham-operated control rats (group C, n = 6). Aortic and renal blood flows increased in group A and fell in group B (P < 0.001). However, in both groups, bladder epithelial oxygen tension rose significantly compared with control (P < 0.01), despite an increasing metabolic acidosis. This is in contradistinction to previous studies of nonseptic insults where bladder epithelial oxygen tension fell in line with an increasing arterial base deficit. If a raised tissue oxygen tension could be demonstrated in other organ beds, this would suggest that decreased utilization of oxygen rather than reduced tissue oxygen availability is responsible for the apparent anaerobic respiration seen in sepsis.

Animals↗
PubMed1995

The effect of norepinephrine and dobutamine on bladder epithelial oxygen tension.

STUDY OBJECTIVES: To assess the effects of two contrasting vasoactive agents (dobutamine [DOB] and norepinephrine [NE]) on (1) global and regional cardiorespiratory variables, (2) acid base status, and (3) bladder epithelial oxygen tension (BEOT), a putative marker of organ perfusion. DESIGN: Measurement of aortic blood flow (ABF) and renal blood flow (RBF), mean arterial blood pressure, arterial blood gases, and BEOT were made during infusion of placebo and varying doses of DOB and NE. SETTING: Medical school laboratory. SUBJECTS: Eighteen anesthetized, spontaneously breathing, male Sprague-Dawley rats divided into three groups. INTERVENTIONS: Two groups were allocated to receive escalating doses of DOB (to 40 micrograms/kg/min) or NE (to achieve a 50% change in any hemodynamic variable). The drug therapy was then discontinued for 15 min and restarted at the previous maximum dose. A third group received 0.9% saline solution at the same infusion rate (16 mL/kg/h). MEASUREMENTS AND RESULTS: There was a dose-related increase in mean blood pressure with NE and fall with DOB. Compared with control values, NE had no effect on ABF but decreased RBF significantly whereas DOB significantly increased ABF but had no effect on RBF. Base excess and BEOT decreased significantly and in parallel with both agents, more so with NE. CONCLUSIONS: Despite their different macrocirculatory effects, DOB and NE both produced a significant but reversible fall in BEOT and a metabolic acidosis. BEOT shows potential as a monitor of the effectiveness of organ perfusion.

Animals↗
PubMed1995

Beyond the Ivory Tower: critical praxis in medical anthropology.

Recent discussion in critical medical anthropology has turned to the issue of application beyond the academy. Building on Gorz's notion of "non-reformist reform," that is, applied work that unmasks rather than mystifies the sources of social inequality and ill health, this article argues for the possibility of an applied critical medical anthropology, suggests concrete opportunities for such work in health settings, and identifies problems and social conditions that affect the development of a critical health praxis. These points are illustrated by reviewing case studies of anthropological work with the Farm Labor Organizing Committee in Indiana, the United Farm Workers Union in California, and the Hispanic Health Council in Connecticut. The article concludes with an examination of the skills and resources critical medical anthropology has to offer system-challenging movements in health care.

Anthropology↗
PubMed1995

AIDS prevention for African-American and Latina women: building culturally and gender-appropriate intervention.

African-American and Latino women are at high risk of HIV infection through heterosexual transmission, reflected in the significant increases in reported AIDS cases of women thus infected. Few AIDS-prevention programs have addressed this risk for women by directly, separately and, in appropriate ways, focusing on specific women's issues of gender roles, sexuality, and differential power relationships with men, in the context of racial and class relations, as these affect HIV transmission. This article discusses the contributions of a community-based AIDS-prevention program to the development of culturally and gender-appropriate intervention for African-American and Latina women at high risk. Further such programs are needed which build on the use of ethnic cultural concepts, racial and other social relations, and acknowledge issues specific to minority women in order to prevent their infection with HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Current nursing practices in fever management.

Data regarding fever management were obtained through a retrospective or concurrent review of the medical records of 150 patients. For 41% of the patients studied, nurses notified physicians of the fever episode. The decision to treat fever was significantly influenced by fever intensity and the drawing of blood cultures, but not by age, length of hospital stay, or the duration of the fever episode. Despite recent evidence of the protective value of fever, the majority of fever episodes were treated. Acetaminophen alone, and acetaminophen in combination with physical cooling methods, were effective in lowering fever.

Adult↗
PubMed1995

Evaluation of cannabinoid receptor binding and in vivo activities for anandamide analogs.

Recent evidence implicates anandamide as the endogenous ligand for the cannabinoid receptor. One purpose of this study was to determine the structural requirements for anandamide's receptor interaction and the influence of phenylmethylsulfonyl fluoride (PMSF), an enzyme inhibitor, on receptor affinity. A second objective was evaluation of the correlation between affinities of the analogs and in vivo pharmacological activities. The ability of anandamide and analogs to displace [3H]CP-55,940 ([3](-)-3-[2-hydroxyl-4-(1,1-dimethylheptyl)phenyl]-4-[3- hydroxylpropyl]cyclohexan-1-ol) was determined by a filtration assay. Displacement curves for anandamide in the presence of PMSF produced a Ki of 89 +/- 10 nM; without PMSF the Ki increased to 5400 +/- 1600 nM. Anandamide analogs were evaluated for their ability to produce antinociception and hypomotility. The levels of saturation of the anandamide structure were critical to receptor affinity and in vivo potency, with complete saturation and hydroxyl substitution with a fluorine moiety resulting in a compound with increased potency in the spontaneous activity and antinociception assays. Substitution of the hydroxyl with a fluorine atom increased affinity only in the presence of PMSF and reduced potency in the antinociception assay. Ethanolamide substitution with bromobenzenesulfonamide produced an inactive compound in all assays. Increasing the length of the N-substituent by one or two carbons decreased receptor binding affinity and potency in the tail-flick assay only. Certain structural modifications, such as methylations, allowed the analogs to retain affinity without the addition of PMSF. Linear correlation between the behavioral and binding assays were performed, and the greatest correlation was obtained with compounds that were either very potent or inactive.

Animals↗
PubMed1994

Synthesis and 5-lipoxygenase inhibitory activities of some novel 2-substituted 5-benzofuran hydroxamic acids.

A series of 2-substituted benzofuran hydroxyamic acids were synthesized as rigid analogs of simple (benzyloxy)phenyl hydroxamates, evaluated for their in vitro and in vivo 5-lipoxygenase activity and found to be potent inhibitors of the enzyme. Substituents which enhanced lipophilicity near the 2-position of the benzofuran nucleus increased inhibitor potency but reduced oral activity. Incorporation of small polar substituents such as methoxymethylene, hydroxymethylene, and amino (urea) on the acyl group led to more consistent oral activity. The most potent inhibitors of this series in vitro were N-hydroxy-N-[1-(2-phenyl-5-benzofuranyl)-ethyl]furancarboxamide (12) and methyl 5-[N-hydroxy-N-[1-(2-(3,4,5-trimethoxyphenyl)-5-benzofuranyl]ethyl]-5- oxopentanoate (17), both with IC50 values of 40 nM, and in vivo the most potent compound was N-hydroxy-N-[1-(2-phenyl-5-benzofuranyl)ethyl]urea, 20, with an ED50 = 10.3 mg/kg.

Animals↗
PubMed1994

Heparin clearance during continuous veno-venous haemofiltration.

OBJECTIVE: To determine whether premature clotting of haemofiltration circuits could be related to heparin removal across the filter membrane into the ultrafiltrate. DESIGN: Randomised study using either unfractionated (n = 8) or low molecular weight (n = 7) heparin for anticoagulation of the haemofiltration circuit at 1000 and 600 U/h respectively. Samples were drawn at 1 and 2 h from arterial and venous limbs of the haemofilter circuit for measurement of plasma heparin (as anti-Factor Xa activity), antithrombin III and haematocrit. Ultrafiltrate samples were collected at the same time for measurement of anti-Xa activity. SETTING: Intensive care unit. PATIENTS: Patients in acute renal failure requiring haemofiltration. RESULTS: Both unfractionated and low molecular weight heparin plasma levels were within the range required for therapeutic anticoagulation in all but one patient at 2 h. Ultrafiltrate anti-Xa levels were insignificant. Antithrombin III levels in these critically ill patients were subnormal in 11 of the 15 studies. CONCLUSIONS: Despite their small sizes, neither unfractionated nor low molecular weight heparins cross the haemofilter membrane into the ultrafiltrate in any measurable quantity. Both heparins were present in plasma at a level suitable for therapeutic anticoagulation. Subnormal levels of antithrombin III may be an important factor in determining filter longevity.

Acute Kidney Injury↗
PubMed1994

The cost of intensive care: a comparison on one unit between 1988 and 1991.

OBJECTIVE: To assess the changes in cost of intensive care in one unit after a 3 year period and to evaluate the relative costs of an integrated high dependency unit. DESIGN: Combined retrospective and prospective audit of all expenditure incurred in an intensive care/high dependency unit over two periods: April 1988-February 1989 and January-July 1991. SETTING: Combined 13-bedded intensive care/high dependency unit of a central London teaching hospital. RESULTS: The overall cost rose by 50%. Hidden costs such as infrastructure maintenance, capital assets, pathology and radiology services accounted for nearly a quarter of total expenditure. Pharmacy and supplies each accounted for some 10% of total expenditure whereas staff costs exceeded 50%. The cost of the intensive care section rose by 14% of 1149 pounds per patient day as increased bed occupancy offset increases in nurse: patient ratios and expenditure on consumables. However, the cost of the high dependency unit section rose by 87% to 437.83 pounds. This was due to a lower bed occupancy (through increased patient turnover), improved staffing ratios, and increased utilisation of equipment and supplies. CONCLUSIONS: Intensive care is an increasingly expensive speciality, the costs for which are rising over and above the rate of general inflation. Staff costs are by far the largest single item of expenditure. Large reductions in spending on drugs and consumables are unlikely to provide considerable savings on the total budget. Hidden costs account for a high proportion of the budget and should be taken into account when evaluating cost. The significantly lower cost of high dependency care should encourage studies into its cost-effectiveness.

Health Services Research↗
PubMed1994

AIDS and the health crisis of the U.S. urban poor; the perspective of critical medical anthropology.

The social identity of HIV/AIDS in the U.S. has been shaped, for the most part, by two factors, the prevailing configuration of social relations across class, racial, gender, and sexual orientation, on the one hand, and the prevailing array of public health, especially epidemiological, categories of disease transmission, on the other. Focusing on the AIDS epidemic among inner city people of color, this paper challenges the distortions wrought in our understanding from both of these factors and instead develops an alternative perspective for AIDS research among medical anthropologists and health social scientists generally.

Acquired Immunodeficiency Syndrome↗
PubMed1994

The politics of AIDS. Introduction.

From its first designation as a gay plague, HIV/AIDS has been a heavily politicized disease, a disease that has fractured official standard operating procedures in science, medicine, public health and governance. In many ways, AIDS helped to expose a battleground of contested interests while emerging as an arena for both the re-assertion of 'traditional' (i.e. dominant) values as well as rebellion against the traditional politics of exclusion and privilege. Yet the politics of AIDS has remained an understudied domain. This set of papers seeks to overcome this neglect by exploring underlying political dimensions of the AIDS pandemic, especially in the way the pandemic has been constructed by epidemiology, biomedicine, and medical anthropology. Authored by a group of medical anthropologists and an anthropologically oriented political scientist, the papers provide a jarring glimpse at the profound influence of society on health and disease.

Acquired Immunodeficiency Syndrome↗