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Biomedical subjects

S Harris

Publications and source records attributed to S Harris.

At least 235 records · Page 13Linked to original sources
PubMed1990

Treatment of Paget's disease of bone with aminohydroxybutylidene bisphosphonate.

This study examined the effects of aminohydroxybutylidene bisphosphonate in 30 patients with Paget's disease of bone, administered as an intravenous infusion for 5 consecutive days. Treatment (5 mg IV daily) induced marked suppression of biochemical indices of disease activity. Urinary excretion of hydroxyproline fell to 50% of pretreatment values within 2 weeks and was followed by a similar, but later, decline in the serum activity of alkaline phosphatase. Disease activity remained suppressed throughout the 6 months of observation, and only 1 patients showed biochemical signs of an early relapse. Symptomatic improvement was noted in 27 of the 30 patients. Bone biopsies, undertaken in 10 patients, indicated no adverse effects on mineralization. Transient falls were noted in the total white cell count, particularly the lymphocyte and neutrophil fractions, and were associated with short-lived fever in 3 patients. We conclude that short courses of intravenous AHButBP provide a promising treatment for active Paget's disease of bone.

Aged↗
PubMed1990

Evaluation of long-term aggressive dietary management of chronic renal failure in children.

Ten children with chronic renal failure (CRF) were managed for 3 years using a strict low-protein and low-phosphorus diet supplemented by a mixture of the keto and amino forms of the essential amino acids and histidine (phase II). All of these children were previously managed for at least 2 years with a less rigorous diet of limited protein intake with no specific reduction of phosphorus (phase I). Energy, vitamin D, bicarbonate, phosphate binders and vitamin and mineral mixtures were added as required during both dietary phases. Data on dietary intake showed a significant fall in protein and phosphorus intake and a rise in calcium intake during phase II compared with phase I. Plasma calcium increased and phosphate fell, with an associated fall in intact parathyroid hormone levels. There was a marked improvement in urea creatinine ratios, which suggested an improved anabolic state. Cholesterol and triglyceride levels were improved. Height and weight velocity were increased, becoming significant after 3 years of phase II. Renal function deteriorated at a slower rate than predicted. The diet was well tolerated by the children, with fitness and school performance showing improvement. We conclude that long-term strict dietary management of children with CRF is feasible. Our data suggest an overall improvement in general health and an apparent reduction in the rate of deterioration of renal function.

Adolescent↗
PubMed1990

The real number of road traffic accident casualties in The Netherlands: a year-long survey.

Between August 1986 and July 1987 more than 24,000 households, containing nearly 67,000 persons, were surveyed by telephone about traffic injuries during the past three months. Expressed on an annual basis, approximately 430,000 people, or about 1 in 34 of the Dutch population, had suffered some sort of injury in a road accident. The road traffic morbidity was, therefore, 2,942 per 100,000 inhabitants. Of these, about 135,000 had to be treated in hospital (20,000 as inpatients). More than 100,000 did not need treatment. Cyclists formed by far the largest category of road user, but mopedists had the highest injury rate per kilometer travelled. 210,000 of these casualties fell within the definition for recording by the police. The police recorded only 49,748 traffic casualties, or about 25%, during the same period. The police data were not representative; the completeness declined according to severity of the injuries: inpatients, about 70%; outpatients 26%; extramural about 11%. Cyclists (11%), children (9%), and single vehicle accidents (5%) were very much underrepresented. The largest category of road user is cyclists, not car occupants as indicated by the police data. A number of recommendations are made for supplementing the police data and the existing hospital inpatient data. These include extending the Home Accident Recording System of outpatients and the General Practitioner Panel to include road accident victims. Together a representative sample of 95% of all those receiving medical treatment would thus be obtained.

Accidents, Traffic↗
PubMed1990

Spinal antinociceptive synergy between clonidine and morphine, U69593, and DPDPE: isobolographic analysis.

The spinal antinociceptive interaction between the opiate receptor subtype agonists morphine (mu), U69593 (kappa) and [D-Pen2,5]-enkephalin (DPDPE; delta) with clonidine (alpha 2 adrenergic) was examined. Male SD rats received fixed ratios of clonidine to morphine (10:1), U69593 (1:3), or DPDPE (10:1) through catheters terminating at the lumbar cord. Graded dose-response curves (DRC) were constructed from tail-flick latencies converted to % maximal possible effect (%MPE), and the ED50 calculated. The DRCs of morphine and U69593 but not of DPDPE were parallel to the DRC of the opiate plus clonidine. Synergy was determined by isobolographic analysis. The ED50 values for the mixtures were significantly less than the theoretical additive ED50 values, indicating synergy between clonidine and morphine, U69593, or DPDPE.

Analgesics↗
PubMed1990

Blood pressure and retinopathy in type I diabetes.

The relationship between blood pressure and diabetic retinopathy was evaluated in 249 young subjects with type I diabetes. Although hypertension is known to be associated with an increased risk for retinopathy, the effects of high-normal blood pressure are unknown. Retinopathy (158 of 249 subjects, 63%) is considerably more common in a young diabetic population than is hypertension (7 of 249 subjects, 2%). Thus, if blood pressure is important in the etiology or progression of diabetic retinopathy, levels below the hypertensive range (less than 141/90 mmHg) must be considered. The combined effect of hypertension and high-normal blood pressure (greater than 90th percentile but less than 141/90 mmHg) was studied. Elevation in diastolic blood pressure, alone, and in combination with elevated systolic blood pressure, correlated significantly (P less than 0.03) with retinopathy. The presence of high-normal blood pressure resulted in a prospectively higher occurrence of retinopathy and of progression of preexisting retinopathy. Glycohemoglobin (HbA1) and duration of diabetes also correlated with retinopathy. Both good glycemic control and maintenance of diastolic blood pressure below the 90th percentile for age may be important in relation to diabetic retinopathy.

Adolescent↗
PubMed1990

Antinociceptive interaction between opioids and medetomidine: systemic additivity and spinal synergy.

The antinociceptive interaction on the tail flick (TF) and hot plate (HP) tests between opioid analgesics and medetomidine after intravenous (iv) or intrathecal administration were examined by isobolographic analysis. Male Sprague-Dawley rats received fixed ratios of medetomidine to morphine, fentanyl, and meperidine of 1:10 and 1:30, 10:1, and 1:3, respectively, by iv administration or 10:1, 3:1 and 10:1, and 1:3 by intrathecal administration, respectively. Data were expressed as the percentage maximal possible effect (%MPE). The A50 (dose producing 50% MPE) for each drug or drug combination was determined from the dose-response curve. Isobolographic analysis revealed that the effect of medetomidine combined with fentanyl, morphine, or meperidine was additive after iv administration. The intrathecal administration of combinations of medetomidine with the opioids produced a synergistic antinociceptive effect in the TF but not HP test. These data confirmed that the interaction between medetomidine and opioids in producing antinociception may be additive or synergistic, depending on the route of administration, drug ratio administered, and level of processing of the nociceptive input (i.e., spinal vs. supraspinal). Moreover, these results were consistent with a spinal role for alpha-2 adrenoceptors in mediating antinociception. The authors suggest that the interaction between the opioid and alpha-2 adrenergic receptors occurs within the spinal cord.

Adrenergic alpha-Agonists↗
PubMed1990

Intra-abdominal palpation of a nasogastric tube in the stomach does not assure appropriate placement.

Improperly placed nasogastric (NG) tubes have been associated with considerable morbidity. The only reliable indicator of correct NG tube placement appears to be the aspiration of gastric contents. We have reported a case of major morbidity from an improperly placed NG tube that perforated the cervical esophagus, dissected the mediastinum, and terminated in the omental bursa. No gastric aspirate was obtained by suctioning of the tube, but correct placement was presumed based upon the surgeon's direct intraoperative palpation of the tip of the tube. Failure to aspirate gastric contents should alert the practitioner to the possibility of improper NG tube placement.

Abdomen↗
PubMed1990

Lymphocyte predominance Hodgkin's disease--an immunohistochemical study.

Lymph node biopsies from 57 local and referred cases, previously diagnosed at Southampton between 1978 and 1987 as lymphocyte predominance Hodgkin's disease were examined using the monoclonal antibodies MT1, UCHL1, L26, LN-1, E29/68 (EMA), Leu-M1 (CD15) and Ber-H2 (CD30). Of the 34 cases with a nodular architecture, 21 (19 male, two female) contained polylobated Reed-Sternberg cell variants with a B-cell phenotype, which lacked expression of CD15. In all cases, the polylobated cells showed positive staining with L26 and LN-1. Six cases expressed EMA and three showed positive staining with Ber-H2. Two cases lacking polylobated cells were reclassified as reactive follicular hyperplasia with progressive transformation of germinal centres. The remaining 11 cases had an atypical immunophenotype and were reclassified, mainly as mixed cellularity Hodgkin's disease. In six cases, the lymph node architecture showed a mixture of nodular and diffuse growth patterns. Five of these cases contained polylobated cells with the typical morphology and immunophenotype of those seen in nodular lymphocyte predominance Hodgkin's disease. The sixth case contained cells expressing CD15, and was reclassified as nodular sclerosing Hodgkin's disease. Of the fifteen biopsies with a diffuse architecture, four contained polylobated B-cells lacking expression of CD15. These were considered to be diffuse lymphocyte predominance Hodgkin's disease. The remaining 11 cases were reclassified as either Hodgkin's disease, mixed cellularity or as T-cell lymphomas.

Adult↗
PubMed1990

Auditory filter shapes at 8 and 10 kHz.

Auditory filter shapes were derived from notched-noise masking data at center frequencies of 8 kHz (for three spectrum levels, N0 = 20, 35, and 50 dB) and 10 kHz (N0 = 50 dB). In order to minimize variability due to earphone placement, insert earphones (Etymotic Research ER2) were used and individual earmolds were made for each subject. These earphones were designed to give a flat frequency response at the eardrum for frequencies up to 14 kHz. The filter shapes were derived under the assumption that a frequency-dependent attenuation was applied to all stimuli before reaching the filter; this attenuation function was estimated from the variation of absolute threshold with frequency for the three youngest normally hearing subjects in our experiments. At 8 kHz, the mean equivalent rectangular bandwidths (ERBs) of the filters derived from the individual data for three subjects were 677, 637, and 1011 Hz for N0 = 20, 35, and 50 dB, respectively. The filters at N0 = 50 dB were roughly symmetrical, while, at the lower spectrum levels, the low-frequency skirt was steeper than the high-frequency skirt. The mean ERB at 10 kHz was 957 Hz. At this frequency, the filters for two subjects were steeper on the high-frequency side than the low-frequency side, while the third subject showed a slight asymmetry in the opposite direction.

Adult↗
PubMed1990

Use of guardianship under the 1983 Mental Health Act.

The powers of guardianship under the 1983 Mental Health Act confer on the guardian powers to require the patient to reside in a specified place, to require attendance for treatment and to require access to the patient for appropriate health and social services personnel. This paper presents a descriptive study and analysis of the use of guardianship over a 5-year period in four geographical areas. Cases were collected retrospectively from a variety of sources and scrutinized systematically. Three cases of guardianship for mental impairment were excluded from the analysis leaving 23 patients with mental illness. All but two of the patients were female. Older patients, mostly with dementia, accounted for three-quarters of the sample and the majority of orders in this group were to require residence in an old people's home (usually with an apparently good outcome), though three were intended to facilitate home care. In most of the younger patients a functional psychiatric illness was diagnosed and powers were used to maintain the patient at home. The absence of a specific 'power to convey' needs to be resolved for elderly patients needing residential care. The use of guardianship orders to maintain older patients in the community needs further exploration.

Adult↗
PubMed1990

Gene expression in the mammary gland.

We have demonstrated that the ovine genomic clone SS1 can be used to generate transgenic mice that produce significant quantities of BLG protein in milk. The smallest BLG construct so far examined that retains the ability to direct BLG to mouse milk encompasses approximately 7.3 kb of genomic DNA, of which about 0.8 kb is derived from the promoter region. Gene expression is tissue-specific and regulated in a temporal and developmental fashion that is similar to that reported for sheep. We conclude, therefore, that the cis-acting sequences determining mammary expression of the ovine BLG gene are correctly interpreted in mice, despite the absence of an equivalent gene in this species, and that conclusions drawn from future work on BLG expression in the mammary gland of transgenic mice will be broadly applicable in sheep and other ruminant species. Work is currently in progress to define other sequences within the promoter of BLG that are required for regulated expression in transgenic mice. These and other studies into the DNA-protein interactions within the promoter which are required for efficient tissue-specific, regulated expression should lead to a greater understanding of milk protein gene expression in the mammary gland. Furthermore, in the current absence of a suitable in-vitro system, the mouse will be most useful for evaluating the expression of further constructs designed to express foreign proteins in milk of domestic ruminants.

Animals↗
PubMed1990

Distal coronary hemoperfusion and prolonged balloon inflation for acute occlusion: occurring during percutaneous transluminal coronary angioplasty.

We report 3 cases that demonstrate the use of distal coronary hemoperfusion with prolonged balloon inflation to treat acute coronary occlusion occurring during percutaneous transluminal coronary angioplasty. Despite acute occlusion, 2 of the patients had a good angioplasty result, and the 3rd underwent elective coronary bypass surgery. Thus, emergency coronary bypass was avoided in all 3 cases.

Journal Article↗
PubMed1990

Modification of milk composition.

Revolutionary new opportunities for the modification of milk composition have been created by the development of methods for gene transfer and targeted mutation of genes may extend the range of opportunities still further. Exploitation of these opportunities depends upon selection and cloning of milk protein genes and identification of the sequences that govern tissue-specific hormonally induced expression in the mammary gland. Fragments of the ovine beta-lactoglobulin gene fused to cDNA for the human therapeutic proteins clotting factor IX and alpha-1 antitrypsin have directed production of these proteins in the milk of transgenic mice and sheep. Factor IX was biologically active and co-migrated with authentic proteins, but was present at too low a concentration for commercial exploitation. Recent observations suggest that fusion genes containing genomic clones direct production of higher concentrations of protein. Mouse whey acidic protein genomic sequences also directed production of low concentrations of human tissue plasminogen activator in the milk of transgenic mice. Targeted expression of this kind may be used for the production of therapeutic and industrial proteins, to increase the concentration or modify the nature of milk proteins, reduce the concentration of lactose, change the composition of fat or direct production of bacteriocidal proteins in milk in order to combat mastitis.

Animals↗
PubMed1990

An isobolographic analysis of the antinociceptive effect of systemically and intrathecally administered combinations of clonidine and opiates.

The antinociceptive interaction of opiate analgesics with clonidine was examined with the tail-flick and 55 degrees C hot plate tests. Male Sprague-Dawley rats received fixed ratios of clonidine to fentanyl, meperidine or morphine by i.v. and intrathecal injection. Data are expressed as percentage of maximal possible effect and the dose producing 50 percentage of maximal possible effect for each drug or drug combination is used to index potency. The rank order of potency in both tests after i.v. administration is fentanyl much greater than clonidine greater than meperidine greater than or equal to morphine and after intrathecal administration it is morphine greater than fentanyl much greater than clonidine much greater than meperidine. Isobolographic analysis shows that the effect of clonidine combined with an opiate is additive after i.v. administration; the exception is that morphine and clonidine are synergistic in the hot plate test. The intrathecal combinations of clonidine with morphine or meperidine produces a supra-additive antinociceptive effect in the tail-flick test but not in the hot plate test. Fentanyl does so in both tests. These data confirm a positive interaction between clonidine and opiates in producing antinociception. This interaction may be additive or synergistic, depending on route of administration and the nociceptive test used. The timing of injections and pharmacokinetic factors may also influence the results. Moreover, these results suggest that the interaction between the opiate and alpha-2 adrenergic receptors occurs within the spinal cord.

Animals↗
PubMed1990

High-normal blood pressure and early diabetic nephropathy.

The relationship between high-normal blood pressure (BP) levels and early diabetic nephropathy is currently unknown. Blood pressure levels were checked longitudinally for a mean of 6.6 years in 230 subjects to determine their relationship to early diabetic nephropathy as monitored by microalbuminuria. High-normal BP level correlated with the presence of microalbuminuria. Microalbuminuria was 2.8 times as common in subjects with high-normal BP levels compared with those subjects with BP levels below the 90th percentile for their age. The elevated microalbumin excretion was primarily associated with high-normal diastolic BP levels. Our data suggest that either microalbuminuria or high-normal BP levels can precede the other. In a logistics model, diastolic BP and mean HbA1 (over 6.6 years) entered the model at similar levels, followed by duration of diabetes. When the influence of mean HbA1 was removed using logistic regression, the diastolic BP level remained a significant associated factor for the presence of microalbuminuria.

Adolescent↗
PubMed1990

Effects of storage time and temperature on measurement of small concentrations of albumin in urine.

Accurate measurement of albumin excretion rates is important in choosing treatment regimens that may reverse early diabetic renal damage. We report here determinations of slight albuminuria ("microalbuminuria") by radioimmunoassay of fresh specimens, frozen aliquots (stored at -20 degrees C for two, eight, and 24 weeks), and refrigerated specimens (stored at 4 degrees C for one, two, and eight weeks). Seven separate analyses were performed on 101 specimens of urine obtained from 37 subjects with insulin-dependent diabetes mellitus and from 10 nondiabetic healthy controls of a similar age. Storage of urine samples at -20 degrees C resulted in significantly lower measurements of microalbuminuria than in fresh urine (ANOVA, corrected for repeated measures: P = 0.01 to 0.0001). In contrast, storage of urine samples at 4 degrees C for as long as eight weeks did not significantly affect urinary albumin results. The pH values of the specimens were minimally altered and were not a likely cause of the decreased albumin values in the frozen specimens. We conclude that urine specimens for microalbuminuria measurements should either be analyzed as fresh specimens or stored at 4 degrees C and assayed as soon as possible.

Adult↗
PubMed1989

An analysis of the relationship between the cellular distribution and the rate of turnover for the separate classes of unoccupied, noncovalently occupied, and covalently occupied insulin receptor.

To further investigate insulin's role in regulating the turnover of insulin receptor during down-regulation in 3T3-L1 adipocytes, the relationship between the cellular distribution and turnover of unoccupied, noncovalently occupied, and covalently occupied receptor was examined. At steady-state 12% of the unoccupied receptors and 46% of covalently occupied receptors are intracellular. The apparent first-order rate constant (Kapp) for turnover of the total pool of covalently occupied receptors (0.16 h-1) is 3.8-fold higher than that for unoccupied receptors (0.042 h-1). When unlabeled insulin is added, identical values for both Kapp (0.10 h-1) and distribution (26% internal) are measured for noncovalently and covalently occupied receptors. The rate constant (Kdeg), describing the relative sensitivity of internalized receptor to degradation, is identical (0.36-0.41 h-1) for unoccupied, noncovalently occupied, and permanently occupied pools of internal receptor. Mechanisms for down-regulation postulating: (a) an occupancy-dependent alteration in the conformation of internal receptor increasing receptor sensitivity to internal proteases, (b) a preferential sorting of internal occupied receptor to degradative pathways, or (c) induction of intracellular proteases by insulin, would all reflect a substantial change in Kdeg for occupied receptor and thus are unlikely mechanisms by which insulin increases the rate of receptor turnover. The turnover of insulin receptor in 3T3-L1 adipocytes is regulated primarily by its intracellular concentration and not by the state of occupancy of internalized receptor.

Adipose Tissue↗