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Biomedical subjects

A Palmer

Publications and source records attributed to A Palmer.

At least 91 records · Page 5Linked to original sources
PubMed1995

Recombinant aprotinin in coronary artery bypass graft operations.

OBJECTIVE: To evaluate the role of recombinant bovine aprotinin in reducing blood loss in coronary artery bypass graft surgery. DESIGN: An open-label, randomized, controlled study evaluating two dosage levels of recombinant aprotinin. SETTING: Two acute care hospitals (Northwestern Memorial Hospital, Chicago, Ill., and the Scott & White Memorial Hospital, Temple, Texas). PATIENTS: Patients undergoing primary and reoperation coronary artery bypass grafting were assigned to groups by means of a computer-generated table of random numbers. Treated (n = 48) and control (n = 36) patients did not differ significantly in age, sex, weight, number of grafts, or preoperative hemoglobin level. INTERVENTIONS: Recombinant aprotinin was given at two dosages. Dosage level 1 consisted of a bolus of 2 mg/kg intravenously immediately after the induction of anesthesia, 1 mg/kg added to each liter of the oxygenator prime, and 0.5 mg.kg-1.hr-1 infused continuously during operation. At dosage level 2, doses were doubled. Intraoperative monitoring of anti-factor Xa activity was performed, and additional doses of heparin were given on the basis of anti-factor Xa results. MAIN OUTCOME MEASURES: Preoperative and postoperative hemoglobin levels, amounts of autotransfusion device and chest tube drainage blood, and transfusions of allogeneic red blood cells. Adverse clinical events (alterations in renal function, graft thrombosis, myocardial infarction, and death) were recorded. RESULTS: Additional heparin was given to 48% patients in the aprotinin group and to 44% of control patients. Overall red blood cell loss (in milliliters, mean +/- standard deviation [SD]) was decreased with aprotinin at dosage level 1 for reoperations (1040 +/- 162 vs 1544 +/- 198, p < 0.01), and at dosage level 2 for all operations (primary operations, 886 +/- 362 vs 1333 +/- 618, p = 0.02; reoperations, 1191 +/- 560 vs 1815 +/- 1116, p = 0.2). Fewer patients in the aprotinin than in the control group had transfusions of donated blood (6/48 vs 12/36, p = 0.02) or reinfusion of chest tube drainage blood (12/48 vs 20/36, p < 0.01). Among patients receiving dosage level 1, there were no myocardial infarctions or deaths. At dosage level 2, one patient had profound bradycardia and died on day 12 and two patients had late graft closures. Two control patients had hypotension after bypass necessitating intraaortic balloon pumps, and one of these patients died. Postoperative increases in blood urea nitrogen and creatinine levels were small in both aprotinin and control groups. No hypersensitivity or other allergic reactions occurred. CONCLUSION: We conclude that, at the dosages given, recombinant bovine aprotinin decreases surgical blood loss and transfusion requirements in patients undergoing coronary artery bypass grafting, but its use requires appropriate monitoring of heparin use during bypass. Whether higher dosages of aprotinin increase the risk of graft thrombosis must be further assessed with a larger patient sample.

Aged↗
PubMed1995

The effects of low concentrations of antibiotics on epithelial damage caused by non-typable Haemophilus influenzae and bacterial morphology.

Sterile culture filtrates from non-typable Haemophilus influenzae (NTHi) grown in medium containing no antibiotics or 0.25 MIC of amoxycillin, ciprofloxacin or loracarbef were examined for their effect on the ciliary beat frequency (CBF) and structure of human respiratory epithelium. CBF slowing was significantly (P < 0.05) less with 0.25 MIC of all three antibiotics. The epithelium was significantly (P < 0.05) less disrupted with ciprofloxacin. The morphology of NTHi infecting human adenoid organ cultures after 24 h with or without 0.25 MIC of the same antibiotics was measured by scanning electron microscopy. Only ciprofloxacin caused a significant (P < 0.05) change in morphology.

Anti-Bacterial Agents↗
PubMed1995

Human tubal fluid: formation and composition during vascular perfusion of the fallopian tube.

A vascularly perfused preparation of the Fallopian tube has been developed as a model to study the formation and composition of human tubal fluid. An artery serving the tube was cannulated and perfused at a rate of 0.7 ml/min for 1 h with Medium 199 supplemented with bovine serum albumin, heparin and antibiotics. A cannula was also inserted into the lumen. Light and scanning electron micrographs of control and perfused tubes showed that the epithelial lining was intact after perfusion. Tubal fluid was collected in 13 out of 19 experiments. Fluid could always be collected from patients who were in the follicular phase of their ovarian cycle. The mean rate of appearance was 48 microliters/h. The glucose, lactate and pyruvate concentrations in the tubal fluid, as assessed by fluorescence microanalysis, were 0.53, 8.58 and 0.17 mM respectively. There were no correlations between metabolite concentration and the length of perfusion, cannulation time, patient's age or condition. This technique provides a controlled method with which to access and examine human tubal fluid and will allow the physiology of both healthy and diseased tubes to be studied.

Adult↗
PubMed1995

Differences in cultured cardiac fibroblast populations isolated from SHR and WKY rats.

1. The mechanisms whereby angiotensin converting enzyme inhibitors reverse cardiac remodelling appear to involve angiotensin and/or bradykinin receptors. Previously we reported that cultured rat cardiac fibroblasts express angiotensin II (AII) receptors. In the present study we compared AII receptor binding, gene expression of angiotensinogen and the AII, Subtype 1A (AT1A) receptor, as well as morphological changes induced by selected hormonal treatments in cultured fibroblasts derived from SHRLJ or WKYLJ rats. 2. Fibroblasts were isolated from adult rat left ventricle by either collagenase B or collagenase P digestion. Collagenase B yielded cell preparations from SHRLJ which grew slower than cells from WKYLJ rats and expressed nearly two-fold fewer AII receptors (compared to WKYLJ) while collagenase P yielded SHRLJ cells with similar binding and growth properties to WKYLJ. A good correlation was observed between receptor binding and AII receptor, type 1A (AT1A) mRNA concentrations. In the presence of steroids collagenase B cells showed a higher tendency to transform towards a preadipocyte cell type, estimated by the formation of lipid containing vacuoles/cell, while collagenase P cells, mainly the SHRLJ type, start to differentiate toward a myofibroblast-like cell type in the presence of AII, as calculated by the expression of alpha-smooth muscle actin. 3. From the results obtained in this study it is evident that a subset of fibroblasts can be isolated from the SHRLJ heart using collagenase B or P which differ in growth rates, AII receptor binding, AT1A and angiotensinogen mRNA levels, morphology and steroid responsiveness when compared to fibroblasts isolated from cardiac WKYLJ tissue.

Actins↗
PubMed1995

Risk factors for ischaemic heart disease and stroke mortality in young and old hypertensive patients.

We investigated the predictors of cardiovascular mortality at different ages in a longitudinal study of 10186 hypertensive patients attending clinics in the UK. There were 7374 patients (51% were men) < 60 years of age and 2799 patients (44% men) were > or = 60 years. For IHD death the age-adjusted relative risks (RRs) and 95% confidence intervals (CI) for a 1 mmol/l increase in cholesterol were RR = 1.17 (1.07, 1.27) (men) and RR = 1.22 (1.12, 1.33) (women). The RRs for stroke were 0.99 (men) and 1.07 (women). In men and younger women, urea and smoking were important predictors of IHD and stroke death. Age differences were present in women for both urea and smoking. For IHD in women, smoking: RR = 2.65 (1.80, 3.89) (< 60 years) and RR = 1.38 (1.01, 1.88) (> or = 60 years). For stroke in women, smoking: RR = 2.03 (1.23, 3.35) (< 60 years) and RR = 1.06 (0.70, 1.61) (> or = 60 years). We conclude that urea and smoking are important risk factors for stroke and IHD death in hypertensive women aged < 60 years, but are less important in those aged over 60 years. Cholesterol predicted IHD death in all men and women, but did not predict stroke death.

Adult↗
PubMed1994

The Hypertension in the Very Elderly Trial (HYVET). Rationale, methodology and comparison with previous trials.

The Hypertension in the Very Elderly Trial (HYVET) is a multicentre, open, randomised, controlled trial. The aim of this trial is to investigate the effect of active treatment on stroke incidence in hypertensive patients over the age of 80 years. Secondary end-points include total cardiovascular mortality and morbidity. Entry criteria include a sustained sitting systolic blood pressure of 160 to 219mm Hg plus a sustained sitting diastolic pressure of 95 to 109mm Hg. Also required is a standing systolic blood pressure of at least 140mm Hg. Patients must give their informed consent, and be free of congestive heart failure requiring treatment, gout, renal failure or a recent cerebral haemorrhage. Patients are to be randomised to 3 groups-(i) no treatment; (ii) treatment with a diuretic [bendroflumethiazide (bendrofluazide)]; or (iii) treatment with an angiotensin converting enzyme (ACE) inhibitor (lisinopril). Starting dosage for bendroflumethiazide and lisinopril is 2.5 mg/day. In order to achieve goal sitting systolic and diastolic blood pressures (< 150/80 mm Hg), a doubling of the dosage is allowed. Furthermore, slow release diltiazem (120 mg/day increasing to 240 mg/day if required) may be added to the medication of the actively treated groups. These drugs have been chosen as inexpensive and appropriate representatives of their therapeutic classes. 700 patients in each group (a total of 2100) will be sufficient to detect a 40% difference in cerebrovascular events between no treatment and active treatment (alpha = 0.01, 1-beta = 0.90). These numbers will also detect a difference in total mortality of 25% and in cardiovascular mortality of 35%. The pilot phase of the trial has been started with support from the British Heart Foundation. Centres which are interested in taking part should contact C.J. Bulpitt or any of the other authors.

Aged↗
PubMed1994

Proliferating cell nuclear antigen (PCNA) as a diagnostic marker of acute cellular rejection in routinely processed biopsies of renal allografts.

Seventy-eight renal allograft biopsies taken for the management of graft dysfunction were analysed retrospectively by labelling with antibodies to proliferating cell nuclear antigen (PCNA) to assess whether this marker could distinguish episodes of rejection. Routinely processed, paraffin-embedded biopsies with focal or diffuse cellular infiltrates were selected and the percentage of infiltrating cells in the cortical interstitium which stained with PCNA antibody were counted (PCNA index). The area of cellular infiltration was also estimated by a morphometric point-counting technique. The biopsies were divided into two groups based on standard clinical criteria; those with acute rejection (n = 31) and those with other causes of graft dysfunction (n = 47). The PCNA index was significantly higher in episodes of acute rejection (7.9%) compared to non-rejection (2.1%). This was independent of time after transplantation. The PCNA index was also greater in rejecting kidneys containing only focal cellular infiltrates (percentage area of cellular infiltration < 13.1%). Thus PCNA staining may be of use in the differential diagnosis of rejection in routinely processed biopsies of renal allografts where there are only focal inflammatory infiltrates, otherwise not diagnostic of cellular rejection.

Acute Disease↗
PubMed1994

Changes in proteasome localization during the cell cycle.

We have investigated proteasome localization in synchronized cells using polyclonal anti-proteasome antibodies. Proteasomes were localized in the nucleus and cytoplasm at all phases of the cycle, but changes in localization were observed which explain the different immunofluorescence patterns found in asynchronous cells. In the nucleus, the intensity of staining in early S phase was low and showed a punctate distribution which changed to a more diffuse and intense labeling during S to G1. In the cytoplasm, proteasomes were concentrated in the perinuclear region at G1 and at the start of S phase and gradually moved towards the periphery of the cell as the cell cycle progressed to G2. No cell cycle-dependent changes were detected in the rate of synthesis or level of proteasomes. An apparent colocalization of proteasomes with elements of the cytoskeleton mainly observed in G2 was investigated further in PtK2 cells. The overall distribution of proteasomes and cell cycle-dependent changes in PtK2 cells were similar to those in L-132 cells. Double-label immunofluorescence studies using anti-proteasome and anti-cytokeratin (TROMA-1) antibodies showed that proteasomes do colocalize with intermediate filaments of the cytokeratin type, mainly during G2. In mitosis, proteasomes were found by immunogold electron microscopy to be localized around the chromosomes in both PtK2 and L-132 cells. Cell cycle-dependent changes in the localization of proteasomes suggest that they may have a regulatory function related to the cell cycle, for example, in the degradation of proteins which control its progression.

Animals↗
PubMed1992

Magnetic resonance angiography of renal transplants.

Stenosis of the artery of transplanted kidneys is an important cause of graft dysfunction. Diagnosis and follow-up of this condition normally requires intra-arterial digital-subtraction angiography (IADSA), which is invasive and may cause complications. A possible alternative to IADSA is magnetic resonance angiography (MRA), and we have assessed this technique in 50 renal transplant patients who were referred for investigation of possible renal arterial stenosis. In every patient, MRA was compared prospectively with conventional IADSA. Compared with IADSA, MRA had a sensitivity of 83% and a specificity of 97%, and when all images were graded retrospectively for severity of stenosis, the two techniques showed a significant correlation (r = 0.74, p less than 0.001). MRA can provide an accurate image of the renal transplant artery in a non-invasive manner with a high sensitivity and specificity.

Angiography, Digital Subtraction↗
PubMed1992

Initiation and stability of reentry in two coupled excitable fibers.

Reentry in the heart is the repeated excitation of the same tissue by a single excitation wave; it is responsible for several types of cardiac arrhythmia. The simplest model which permits the phenomenon of reentry is two laterally coupled excitable fibers; in this paper we examine such a model in order to establish a basis for the understanding of the fundamental physical processes underlying the process of reentry. Two versions of the FitzHugh-Nagumo equations are used to develop complementary numerical and analytical results for the coupled fiber model. On the basis of numerical studies, regions of qualitatively different behaviour are mapped in the parameter space of excitation threshold and coupling strength between the fibers, and the effect of the rate of recovery is explored. Some of these regions are also obtained analytically, in good agreement with the numerical results. Finally, the results are discussed in the light of recent work on the role of the anisotropy of cardiac tissue in the initiation of reentrant activity in the heart.

Animals↗
PubMed1992

The role of the lymphatic system in coronary atherosclerosis.

Arguments are presented to support the hypothesis that the integrity of the coronary lymphatic system is an important factor in the development of coronary atherosclerosis. It is proposed that the lymphatic drainage of the epicardial coronary arteries is genetically inadequate, and that the flow of lymph from the heart is further impaired by gravitational factors due to man's upright position. Arguments are presented to support the concept that the intramural coronary arteries are protected from atherosclerosis because of a highly effective pericoronary lymphatic and venous capillary system and that the internal thoracic (internal mammary) artery is similarly protected from atherosclerosis because of its close relationship to an extensive lymphatic chain. It is proposed that the failure of the cardiac lymphatic system in the allogenic transplanted heart is a cause of the accelerated atherosclerosis in both epicardial and intramural coronary arteries.

Animals↗