The Treaty of Maastricht and public health.
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Biomedical subjects
Publications and source records attributed to P Allen.
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Between 1984-1989, 44 patients with stage I-II low grade lymphoma were treated prospectively with sequential chemotherapy and involved-field radiotherapy. The chemotherapy was cyclophosphamide, vincristine, prednisone, and bleomycin (COP-Bleo); doxorubicin was included (CHOP-Bleo) for patients with adverse prognostic features (high LDH; extranodal sites; bulky nodes). Of the 44 patients, 37 had measurable disease and all have responded. With a median follow-up of 32 months, the 5-year survival and failure-free survival were 89% and 74%, respectively. Compared to past experience with involved-field radiotherapy alone, the failure-free survival is significantly better with COP-Bleo plus radiotherapy. The potentially cured fraction has risen from 40% to 74%.
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This report describes a detailed mutational analysis of a major histocompatibility complex class II molecule--the alpha chain of the Ak complex. Each residue from 50-79 was replaced by an alanine, and the effects on recognition of Ak by panels of antibodies and T cells determined. The results provide the strongest existing experimental evidence that the antigen binding site on a class II molecule can be modelled on the crystal structure of a class I molecule. The data have also permitted the delineation of residues that actually contact antigenic peptides.
Acidic and basic fibroblast growth factors (aFGF and bFGF) are angiogenic polypeptide mitogens for cells of mesodermal and neuroectodermal origin. In this report we describe the purification from several normal human hearts (including a very fresh, nonischemic sample) of heparin-binding, acid-, heat- and trypsin-sensitive 14-18-kD peptides that crossreact with antisera against aFGF and bFGF. Further evidence includes (a) prevention of mitogenicity by protamine and by anti-bFGF, (b) displacement of 125I-bFGF from cell membranes, and (c) stimulation of capillary endothelial cell migration. Specific immunohistochemistry localized bFGF to endothelial cells and, surprisingly, to cardiac myocytes, with almost no immunoreactivity in smooth muscle cells. These peptides may function in cardiac embryogenesis, hypertrophy, atherogenesis, angiogenesis, and wound healing, and may also have endocrine, neurotropic, or vasomotor functions.
The beta-adrenergic agonist L-644,969 was evaluated to determine its effects on growth performance and carcass composition of Friesian steers. L-644,969 is the R,R isomer of 6-amino [[(1-methyl-3-phenylpropyl) amino] methyl]-3-pyridine methanol dihydrochloride. Four groups of 18 steers, averaging 380 kg body weight, were individually given ad libitum access to a pelleted concentrate diet that contained either 0, .25, 1.0 or 4.0 ppm L-644,969 for the final 12 wk of the finishing period. Live weight gain was not affected by L-644,969, but feed consumption was linearly reduced (5.5, 6.3 and 15.7%; P less than .01) and feed conversion efficiency was linearly increased (16, 25 and 31%; P less than .01) relative to unmedicated controls, respectively. In addition, L-644,969 quadratically increased carcass weight (3.7, 9.3 and 8.5%; P less than .01) and dressing percentage (2.7, 7.9 and 7.9%; P less than .001). The proportion of trimmed fat in the carcass was quadratically reduced (14.5, 29 and 36%; P less than .001) and yield of lean meat quadratically increased (6.7, 13 and 15.6%; P less than .001). beta-adrenergic agonist treatment altered the distribution of lean meat such that a greater (P less than .001) proportion of the total lean was in the hind portion of carcasses from treated animals. Based on these findings, we suggest that L-644,969 may have utility as an agent to improve efficiency of production of lean beef.
Sixty-three Friesian steers (9 mo old, 257 kg; n = 15 or 16/treatment) were employed in a 2 x 2 factorial to test bovine growth hormone (bGH) and estradiol (Compudose implant). Steers received daily subcutaneous injections of vehicle or bGH (40 micrograms/kg body weight) for 22 wk. Steers were slaughtered 8 wk after the end of bGH treatment (wk 30). Steers had ad libitum access to silage plus a fixed amount (4 to 5.5 kg/d) of concentrate. Average daily gain (ADG) and feed conversion efficiency (FCE) improved (P less than .05) in response both to bGH and to estradiol during wk 0 to 22. Although bGH did not affect ADG or FCE during wk 23 to 30, estradiol improved (P less than .05) them; bGH and estradiol appeared additive (nonsignificant interactions) during wk 0 to 22. At slaughter, estradiol increased (P less than .05) carcass weight and carcass and leg length while decreasing (P less than .05) conformation score and percentage of kidney, knob and channel fat (KHP); bGH decreased (P less than .05) KHP. Although both bGH and estradiol increased (P less than .01) plasma GH, their effects were not additive. Both bGH and estradiol increased (P less than .01) plasma somatomedin-C and decreased (P less than .01) plasma urea nitrogen concentrations; effects were additive. Estradiol, but not bGH, increased (P less than .05) plasma glucose, whereas neither bGH nor estradiol altered plasma creatinine and nonesterified fatty acids. In summary, both bGH and estradiol improved growth and FCE, and their effects appeared to be additive. It is likely that some of their effects were mediated by somatomedin-C.
The gradual closure of a long-stay hospital is stressful for staff. Some may have doubts about the case for community care, and almost all are affected by uncertainty and by the provisional step-by-step changes as patients gradually move out. The maintenance of staff morale during the transition is therefore important and difficult. This article examines some of the stresses and misunderstandings, and suggests how they could be managed.
An elderly woman who had been taking a fixed-dose combination of a thiazide and potassium-sparing diuretic for eight days, became severely hyponatraemic following total hip replacement. Her hyponatraemia resolved with fluid restriction, intravenous normal saline, and withdrawal of the drug. Hyponatraemia is a well-described side-effect of diuretic therapy; however, we are not aware of any previous reports of this condition developing acutely in the postoperative state. We attribute this to the natriuretic nature of the drug, compounded by the postoperative, anti-diuretic surge which itself may have been exacerbated by the drug. We thus advise caution in the use of this preparation in the elderly patient about to undergo major surgery.
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In vivo nuclear magnetic resonance (NMR) spectroscopy was used to define several intracellular high energy phosphate variables of the gastrocnemius muscle of normal subjects during rest, graded plantar flexion exercise to exhaustion, and recovery. There were nine males and eight females with an average age of 34 +/- 8 years. At rest, pH averaged 7.09 +/- 0.03 and the energy cost index (ECI)--the ratio of inorganic phosphate to phosphocreatine--averaged 0.13 +/- 0.03. At peak exercise, the ECI increased markedly to 2.71 +/- 2.0 (P less than 0.001) and pH fell precipitately to 6.76 +/- 0.17 (P less than 0.001), indicating the high intensity of the exercise. Exercise endurance averaged 12 +/- 5 mins; it was not highly correlated with sex, age (r = 0.35), rest pH (r = 0.26), rest ECI (r = 0.38), peak exercise pH (r = 0.23) or peak exercise ECI (r = 0.38), nor exercise changes in pH (r = 0.17) and ECI (r = 0.28). At 23 mins post exercise all variables were similar to rest. Rest pH was the only variable different between males (7.10 +/- 0.03) and females (7.07 +/- 0.03) (P less than 0.05). Thus, dynamic exercise of large skeletal muscles in normal subjects was characterized by marked temporal changes in high energy phosphate profiles and very low pH at exhaustion. No single metabolic variable correlated highly with exercise endurance, suggesting that the intracellular pathophysiology of exhaustive muscle exercise and clinical fatigue may be multifactorial.
Cyclic nucleotide phosphodiesterase (PDE) isozymes isolated by DEAE-Sephacel or Mono-Q High Performance Liquid Chromatography from cardiac left ventricular tissue of normal subjects and patients with end-stage heart failure have been compared. With both separation techniques, four major peaks of PDE activity were evident in the soluble fractions; only one peak of activity was present in particulate fractions. The specific activity of the particulate PDE from myopathics was approximately 30-50% of that of normals while the specific activity of a soluble form of this PDE (peak IIIa) was reduced by 30% in myopathics. No differences in comparison of the other peaks of PDE activity were evident. The particulate PDE isozyme has a low Km for cAMP (0.27-0.29 microM), is inhibited by cGMP (60-80% at 1 microM), is sensitive to inhibition by submicromolar concentrations of CI-930 but not rolipram, and is competitively inhibited by milrinone (Kj = 0.3 microM). The first soluble peak of PDE activity hydrolyzes both cAMP and cGMP and is stimulated by calmodulin while cyclic AMP hydrolysis by peak II PDE is stimulated by cGMP. The other soluble peak III fractions (IIIa and IIIb) hydrolyze cAMP; peak IIIa is inhibited by cGMP or by CI-930 and milrinone, whereas peak IIIb is also inhibited by rolipram when the cardiotonic sensitive PDE is inhibited by CI-930. Thus, cardiotonic-sensitive, cGMP-inhibitable, low Km cAMP PDE is present in both the soluble and particulate fractions of human cardiac left ventricular muscle of hearts from normal and cardiomyopathic subjects while the rolipram-sensitive PDE is present in the soluble fraction. The major differences in PDE activity of myopathic relative to normal left ventricular tissue are a reduced specific activity and Vmax of particulate PDE and one of the soluble peak III PDEs.
The Carpentier-Edwards standard porcine bioprosthesis was implanted in 1190 patients (1201 operations, 1303 valves) between January 1975 and June 1986; most implants were before 1982. The mean age of the patients was 57.2 years (range 8 to 85 years). The early mortality was 7.6% (aortic valve replacement 5.1%, mitral valve replacement 8.8%, and multiple valve replacement 15.3%). Late mortality was 3.9% per patient-year (aortic valve replacement 3.6%, mitral valve replacement 4.2%, and multiple valve replacement 3.8%). The total cumulative follow-up period was 6737 years. Thromboembolism was 1.5% per patient-year (fatal 0.4% per patient-year) (minor 0.6%, major 0.9%); antithromboembolic therapy-related hemorrhage was 0.5% (fatal 0.1%); prosthetic valve endocarditis was 0.6% (fatal 0.2%); nonstructural dysfunction was 0.5% (fatal 0.2%); and structural valve deterioration and/or primary tissue failure was 1.5% per patient-year (fatal, 0.2% per patient-year). Thromboembolism and structural valve deterioration were the significant complications, structural valve deterioration occurring primarily between the sixth and 10th year of evaluation. The overall patient survival was 65.0% for aortic valve replacement and 54.8% for mitral valve replacement (p less than 0.05) at 10 years. The patients were classified as 92.9% New York Heart Association functional classes III and IV preoperatively and 92.3% classes I and II postoperatively. Freedom at 10 years from thromboembolism was 84.3% for aortic valve replacement and 76.5% for mitral valve replacement (p = 0.05); structural valve deterioration was 78.6% for aortic valve replacement and 71.6% for mitral valve replacement (p less than 0.05); reoperation was 74.4% for aortic valve replacement and 67.1% for mitral valve replacement (p less than 0.05). Freedom from all valve-related complications at 10 years was 58.9% for aortic valve replacement and 46.8% for mitral valve replacement (p less than 0.05); valve-related mortality was 89.5% for aortic valve replacement and 82.6% for mitral valve replacement (p = not significant); mortality and reoperation was 58.9% for aortic valve replacement and 46.8% for mitral valve replacement (p less than 0.05); mortality and residual morbidity (treatment failure) was 87.2% for aortic valve replacement and 75.1% for mitral valve replacement (p = not significant); mortality, residual morbidity, and reoperation were 66.3% for aortic valve replacement and 54.9% for mitral valve replacement (p less than 0.05). The standard Carpentier-Edwards porcine bioprosthesis has provided satisfactory clinical performance and has afforded patients excellent quality of life.
A young man with leptospirosis developed massive pulmonary haemorrhage. This was remarkable both in its severity and in its occurrence early in the clinical course - before the onset or presence of jaundice, renal failure or of a serological diagnosis. It occurred in the absence of a coagulopathy or thrombocytopenia and presumably was a consequence of the capillary fragility characteristic of the disease - perhaps precipitated in this instance by mechanical ventilation.
The auditory frequency resolving ability of preschool children, school-aged children, and adults was assessed in a standard forced-choice masking experiment. Thresholds for pure-tone signals at 500 Hz, 2000 Hz, and 4000 Hz were obtained in two masking conditions. In one condition, the masker was a 4000-Hz-wide band of noise centered at the signal frequency; in the other, there was a notch in the noise spectrum, approximately one-half octave wide and 50 dB deep, centered at the signal frequency. Frequency resolving ability was inferred from the difference in signal threshold between the two masking conditions. The adaptive forced-choice psychophysical procedure was embedded in a video game in order to obtain rigorous psychophysical data within the attentional limits of young children. This procedure produced data from children as young as 3 years old that were qualitatively indistinguishable from adult data. However, the threshold estimates from the children were more variable from run to run than were the estimates obtained from adults. The mean data from this experiment suggest that frequency resolving ability improves at all frequencies with increasing age.