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Biomedical subjects

P Walker

Publications and source records attributed to P Walker.

At least 181 records · Page 10Linked to original sources

Colposcopic assessment of the accuracy of cervical cytology screening.

Two hundred asymptomatic women in a general practice were screened both cytologically and colposcopically for evidence of cervical intraepithelial neoplasia. The prevalence detected by cytology alone was 5%, but the prevalence detected by cytology and colposcopy together was 11%. None of the larger lesions of cervical intraepithelial neoplasia (affecting more than two quadrants of the cervix) was associated with negative cytology. The false negative cytology rate for smaller lesions was 58%. The clinical importance of the smaller lesions that were not accurately detected by cytology screening is unknown. As these lesions affected 6% of the screened population further studies of their clinical course are urgently required. Local destructive treatment in such cases may represent considerable overtreatment. If these lesions prove to be clinically important, however, the results of this study predict an increasing epidemic of preinvasive and invasive disease of the cervix.

Adolescent↗

Physician-accompanied transport of surgical intensive care patients.

During a one-year period, 107 critically ill adult patients were transferred by a physician-accompanied transport system (PATS). Most patients required both tracheal intubation (82 per cent) and mechanical ventilation (71 per cent), while continuous vasopressor support was required in 27 per cent of transfers. Patients were classified as either potential organ donors (n = 21) or nondonor patients (n = 86). Nondonor patients had a mean time of patient transfer documented from the initial telephone contact to final arrival of the patient in the ICU of 345 +/- 221 min (range 65-1350 min); the mean time the patients were out-of-hospital was 73 +/- 58 min (range 5-330 min); the average distance travelled by the patient and PATS was 342 +/- 692 km (range 1-4000 km). Ultimate nonsurvivors of ICU admission (36 per cent) had shorter out-of-hospital times, shorter travel distances, and increased interventional support, as assessed by the Therapeutic Intervention Scoring System applied over the telephone and prior to departure at the referring hospital. Significant interventions were undertaken by PATS in 23 per cent of the nondonor patients prior to departure. During the transport process, there was at least a seven per cent morbidity (arrhythmia, hypotension, and vehicular difficulties) and a 0.9 mortality rate. We conclude that PATS offered significant advantages to this patient population through its ability to maintain acceptable morbidity and mortality rates while transferring patients over long distances and for prolonged periods of time.

Adolescent↗

Life events stress and psychosocial factors in men with peptic ulcer disease. II. Relationships with serum pepsinogen concentrations and behavioral risk factors.

We examined in a controlled study whether psychologic disturbances in men with peptic ulcer disease were related to other potential ulcer "risk factors" (serum pepsinogen concentrations, cigarette smoking, and intake of alcohol, aspirin, or coffee). Psychopathology in general, personality features of hostility, irritability, and hypersensitivity, and impaired coping ability (low ego strength) each correlated significantly with serum pepsinogen concentration in ulcer patients (p less than or equal to 0.005). Cigarette smoking and intake of alcohol and aspirin were increased in ulcer patients but unrelated to psychopathology. Depression was the variable that best discriminated ulcer patients from nonulcer controls; a negative perception of life events, number of relatives with ulcer, and serum pepsinogen I concentration also had a major, unique discriminating value, whereas smoking played a relatively minor role independent of the other variables examined. Our study supports the concept that several interacting factors (psychologic, behavioral, and genetic/physiologic) are likely involved in peptic ulcer disease. Emotional stress may predispose to ulcers by producing gastric hypersecretion, as manifested by hyperpepsinogenemia.

Acetaminophen↗

Quantitation of postischemic skeletal muscle necrosis: histochemical and radioisotope techniques.

Skeletal muscle necrosis will result from prolonged periods of ischemia. The purpose of this study was to develop a method to estimate the extent of necrosis using nitroblue tetrazolium staining and technetium scanning. The bilateral canine gracilis muscle preparation with total vascular isolation was exposed to 4 hr of complete normothermic ischemia followed by reperfusion. After 45 hr of reperfusion 99mTc pyrophosphate (PYP) was injected and 3 hr later the muscles were harvested, cut into six slices, and stained with nitroblue tetrazolium. Biopsies were taken from tetrazolium-positive and -negative areas for electron microscopy to confirm the ability of the stain to distinguish viable from necrotic muscle. Computerized planimetry of the staining pattern was used to estimate the extent of necrosis as a percentage of the total muscle. Electron microscopy confirmed the validity of nitroblue tetrazolium to discriminate between viable and necrotic skeletal muscle in this experimental model. After 4 hr of ischemia the percentage necrosis was 30.2 +/- 6.1% (mean +/- SEM, n = 12), there was no difference in the extent of necrosis in left vs right paired muscles, using tetrazolium staining or technetium PYP uptake. There was a statistically significant correlation between the percentage necrosis and the density of 99mTc PYP uptake per muscle (r = 0.83, P less than 0.001) and per slice (r = 0.94, P less than 0.001). This study demonstrates the ability of tetrazolium staining to accurately differentiate between viable and necrotic skeletal muscle and provides a reproducible method for estimating the extent of necrosis in the gracilis muscle model.

Animals↗

Androgens modulate epidermal growth factor receptor levels in the rat ventral prostate.

In order to further understand the factors which influence the normal or pathologic growth of the prostate, we have characterized the receptor for epidermal growth factor (EGF) in the rat ventral prostate and have studied the hormonal regulation in this receptor. EGF binds to a single class of saturable, high affinity binding sites in total prostatic homogenate. Scatchard analysis of the binding data reveals an apparent dissociation constant (KD) of 0.93 +/- 0.08 nM and a number of sites of 4.01 +/- 0.24 fmol per mg protein. Among the peptides tested, only native EGF can displace bound [125I]EGF. Castration stimulates the concentration of prostatic EGF receptors from 25.5 +/- 3.0 to 43.4 +/- 5.4 fmol/100 mg tissue in intact and castrated animals, respectively (P less than 0.01). Treatment of castrated rats with dihydrotestosterone (DHT) inhibits the rise in prostatic EGF receptor concentration induced by orchiectomy, while estradiol, progesterone or the dopaminergic agonist CB-154, have no effect. Combined administration of DHT with the other above-mentioned steroids or CB-154 does not modify the inhibition of prostatic EGF receptor concentration induced by the androgen in castrated animals. When the data are expressed as changes in EGF receptor number in the total prostate, DHT treatment reverses the inhibitory effect induced by castration and yields an EGF binding capacity comparable to that measured in intact animals. Chronic treatment with a pure antiandrogen or a potent LHRH agonist (LHRH-A) alone has no significant effect on EGF receptor concentration in prostatic tissue, although, secondary to a reduction in prostatic weight, total prostatic EGF binding capacity is reduced following antiandrogen or LHRH-A treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

Comparison of amlodipine and verapamil in the treatment of mild to moderate hypertension.

One hundred sixty patients with mild to moderate essential hypertension entered this double-blind parallel group comparison of amlodipine, verapamil, and placebo. Sixteen centers from the United Kingdom and Norway participated in this multicenter study. Administration of amlodipine (2.5 mg with adjustment to 5.0 mg and to 10.0 mg o.d.) or verapamil (80 mg b.i.d. titrating to 160 mg b.i.d.) for 8 weeks to patients with mild to moderate hypertension was associated with clinically important and statistically significant decreases in both supine and standing blood pressures. After 8 weeks of double-blind therapy, the mean (amlodipine-placebo) difference in the falls from baseline in blood pressures measured 24 h postdose were -11.9/-7.0 mm Hg (supine) and -11.4/-6.3 mm Hg (standing). The corresponding figures were -7.7/-4.6 mm Hg and 8.3/-4.0 mm Hg for verapamil (12 h postdose). Mean reductions from baseline of the amlodipine group exceeded those of the verapamil group by 2-4 mm Hg for all pressure measurements, and this difference was statistically significant for diastolic blood pressures. Responder rates were 72, 48, and 33% for amlodipine, verapamil, and placebo, respectively. Mean doses at 8 weeks were 9.1 mg (amlodipine) and 296 mg (verapamil). There were no significant changes in pulse rate. Both active drugs maintained their antihypertensive effect through the day (0-12 h postdose) with amlodipine showing a sustained 24-h effect. Twenty-two patients in the amlodipine, 19 in the verapamil, and 14 in the placebo groups had side effects possibly related to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Amlodipine and captopril in moderate-severe essential hypertension.

The therapeutic usefulness of adding once-daily amlodipine (10 mg) for four weeks in moderate-severe hypertensive patients uncontrolled on low dose captopril (25 mg twice daily) alone was studied in 29 patients in a double-blind, placebo-controlled two-way crossover comparison. Once daily amlodipine was shown to be an effective antihypertensive drug when combined with captopril. The amlodipine minus placebo differences in mean changes from captopril baseline values were: -18/-12 mmHg and -20/-12 mmHg for supine and standing systolic/diastolic pressures (P less than 0.001 for all four pressure variables). The combination was well tolerated, and no patient discontinued therapy. Five patients experienced ankle oedema and four patients reported flushing while receiving amlodipine/captopril.

Adolescent↗

Strategies for improving fixation of femoral components in total hip arthroplasty.

As strategies are considered for improving fixation of femoral components in total hip arthroplasty (THA), one is challenged to exceed the standard set by contemporary cement procedures. However, despite the improved ten- to 15-year clinical results anticipated with current cementing techniques, the limited fatigue strength of polymethylmethacrylate warrants continued investigation of alternative systems, particularly for younger patients and in revision arthroplasty. Design considerations for femoral stems for cementless THA include (1) initial mechanical stability afforded by the stem shape, (2) strength and stiffness of the stem, and (3) surface features relating to biocompatibility and attachment to bone. In one approach a fit-and-fill algorithm has been implemented to design stems that maximize contact between prosthesis and cortex in priority areas to achieve stability. Titanium is recommended for the fabrication of such stems because of its corrosion resistance, its biocompatibility, and its modulus, which is lower than that of cobalt-chromium alloy. Long-term fixation of these implants will be dependent upon the maintenance of normal strain patterns in the host bone. Achievement of this goal will require additional strategies that combine optimal fit and optimal material properties of the prosthesis.

Biocompatible Materials↗

Linker scanner mutagenesis of the Xenopus laevis ribosomal gene promoter.

We have assayed a series of linker scanner mutants which cover the Xenopus laevis ribosomal gene promoter at approximately ten base pair intervals. All of these mutations adversely affect promoter activity with the exception of one mutation which stimulates activity. Thus, none are neutral. We show that most of the mutations can be partially rescued by ligating a block of enhancer elements upstream of the promoter. In addition, we have made extracts from liver nuclei which produce DNaseI protection footprints over the promoter. Analysis of both strands reveals a prominent footprinting domain from about -5 to -30. However, lesser changes in the digestion pattern are detected over most of the promoter. Previously published analyses have suggested that this promoter might be composed of three functional domains. The experiments presented here suggest that either 1) the three putative domains are so closely arranged that the boundaries are difficult to discern, or 2) the situation is more complex.

Animals↗

Thyroxine accelerates the differentiation of granular convoluted tubule cells and the appearance of epidermal growth factor in the submandibular gland of the neonatal mouse. A fine-structural immunocytochemical study.

The effects of the administration of thyroxine (T4) on the postnatal cytodifferentiation of granular convoluted tubule (GCT) cells of the submandibular gland (SMG) of Lewiss-Webster mice were studied by light and electron microscopy. From birth, mice of both sexes were injected daily with T4 (sc 0.4 micrograms/g BW) and were sacrificed 24 h after the last injection at 7, 9, 11, 14 and 21 days of age. Control mice received vehicle only. In control mice, granulated striated duct (SD) cells were first detected at 9 days and 7 days of age by light- and electron microscopy, respectively. Furthermore, a few scattered granulated SD cells were observed by light microscopy as early as day 7 in T4-treated mice of both sexes. At 21 days of age, in mice given T4, GCT cells were larger and more numerous and the Golgi apparatus, rough endoplasmic reticulum, and secretion granules were more abundant. In control mice, immunocytochemical staining for epidermal growth factor-(EGF) was first detectable at day 21 at the light- and electron-microscopic levels. However, positively stained cells were first observed in T4-treated mice by light- and electron-microscopic immunocytochemistry at 14 and 11 days of age, respectively. Moreover, in the 21-day-old T4-treated mice, the number of immunoreactive GCT cells, as well as the intensity of the staining per cell, was markedly increased as compared to controls. EGF immunostaining was restricted to GCT cells, and by immuno-electron-microscopy was only seen in apical secretory granules in granulated SD cells and GCT cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Noninvasive pulse oximetry in children with cyanotic congenital heart disease.

Arterial oxygen saturation, determined noninvasively by pulse oximetry in 32 pediatric patients with cyanotic congenital heart disease (CHD), was compared with oxygen saturation measured by a cooximeter in simultaneously obtained arterial blood samples. The patients were studied in the cardiac catheterization laboratory, operating room, and ICU. Excellent correlation by linear regression (n = 108, r = .95) was observed between the two methods at oxygen saturations ranging from 35% to 95%. These observations show that in infants and children with cyanotic CHD, arterial oxygen saturations can be determined accurately and reliably by pulse oximetry at rest and during changing circulatory states.

Blood Gas Monitoring, Transcutaneous↗

Demonstration of epidermal growth factor binding sites in the adult rat pancreas by light microscopic autoradiography.

The distribution of epidermal growth factor (EGF) receptors was studied in the pancreas using light microscopic autoradiography, which was performed at different time intervals (2-60 min) after injecting 125I-labeled EGF intravenously into the adult rat. In the exocrine pancreas, a labeling was found to occur over the pyramidal cells of the acini and cells lining the intercalated ducts. Moreover, substantial binding of EGF to cells of the islets of Langerhans was also revealed. At the 2-min time interval, most silver grains were found at the periphery of the target cells. The localization, as well as the diminution of silver grains over the cytoplasm of these cells, between 7 and 60 min, suggested the internalization and degradation of 125I-labeled EGF. Control experiments indicated that the autoradiography reaction was due to specific interaction of 125I-labeled EGF with its receptor. These results clearly indicate that EGF receptors are present in the acinar cells and the cells of intercalated ducts of the exocrine pancreas, as well as the cells of the endocrine pancreas. Finding that there are EGF binding sites in pancreatic acinar cells supports the physiological role of EGF in the regulation of pancreatic exocrine function. The presence of EGF receptors in cells of the islets of Langerhans suggests that EGF may play a role in the regulation of the endocrine pancreas.

Animals↗

A minority of patients with rheumatoid arthritis show a dominant rearrangement of T-cell receptor beta chain genes in synovial lymphocytes.

The clonality of T lymphocytes isolated from the synovial fluid and peripheral blood of patients with rheumatoid arthritis was investigated by restriction enzyme fragment mapping of the rearrangements of the beta chain gene of the T-cell antigen receptor. Three patients showed a dominant rearrangement amongst their synovial fluid T cells which was not seen in their peripheral blood T-cell population, suggesting the presence of a predominating T-cell clone. However, most of the patients examined (8 out of 11) demonstrated polyclonal T-cell populations in both their synovial fluid and peripheral blood. Of four synovial fluid T-cell lines investigated, one showed evidence of a dominant T-cell clone.

Arthritis, Rheumatoid↗

Validation of coronary heart disease hospital discharge data.

Data from a 1983 Auckland coronary heart disease register applying current World Health Organization criteria have been used to validate routine hospital discharge data. The register contained 905 patients under 65 years admitted to hospital and 858 of these patients were matched with hospital discharge records. Of the registered definite myocardial infarction cases 86% received the International Classification of Diseases code 410 (acute myocardial infarction); 9% of these cases received a code 411-414 (other forms of coronary heart disease or angina) and 5% received other codes. Only 405 of the 604 cases (67%) coded 410 in the hospital discharge data were true definite myocardial infarctions according to the World Health Organization criteria. The routine hospital International Classification of Diseases data do not provide diagnostic groups sufficiently close to World Health Organization categories for them to be used alone to monitor trends in coronary heart disease morbidity rates.

Adult↗