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Biomedical subjects

R W Morris

Publications and source records attributed to R W Morris.

At least 127 records · Page 7Linked to original sources

Azathioprine treatment in chronic actinic dermatitis: a double-blind controlled trial with monitoring of exposure to ultraviolet radiation.

Oral azathioprine was compared with placebo in a double-blind controlled trial of therapy in chronic actinic dermatitis (CAD), a rare eczematous photodermatosis. Eighteen severely affected patients were randomly allocated to azathioprine 50 mg t.d.s. or placebo over a 2-year period. Severity of itch and rash were assessed weekly by each patient on a visual analogue scale and overall clinical status monthly by a medical observer. Monitoring of patient ultraviolet radiation (UVR) exposure was undertaken throughout treatment by polysulphone film lapel-badge dosimetry. Five of 8 patients treated with azathioprine but none of 10 placebo patients achieved remission within 6 months. One patient could not tolerate treatment because of gastrointestinal effects. No haematological or hepatic abnormality was noted. The marked improvement in clinical status of actively treated patients (P less than 0.02, Fisher's exact test), led to early termination of the trial. Oral azathioprine therapy is an effective and usually well tolerated treatment in chronic actinic dermatitis.

Aged↗

DNA flow cytometry of thymomas.

Forty-seven thymomas have been examined by DNA flow cytometry and results correlated with histology, stage, associated clinical features and survival. Twenty-five cases were DNA diploid, 14 were aneuploid and no results could be obtained for eight cases. The presence of aneuploidy correlated with more advanced (stage II and III) disease and the presence of myasthenia gravis and was more frequent in epithelial predominant thymomas. Tumour recurrence was more frequent in DNA aneuploid tumours, stage II/III disease and epithelial predominant neoplasms. Multifactorial analysis showed that DNA aneuploidy was predictive of tumour recurrence independent of the effects of stage and histology.

Adult↗

An acceptable exercise test to study microalbuminuria in type 1 diabetes.

A modified test for studying the response of urinary albumin excretion (UAV) to exercise in diabetic patients is described. It is designed to produce a standardized increase in pulse rate (by 90-110%) rather than a standardized workload. Thirty-three normotensive Type 1 diabetic patients with normal pre-exercise UAV (less than 10 micrograms min-1) on the day of the test were compared with 25 non-diabetic subjects matched for age and sex. The patients developed a significantly greater increase in the median UAV (p less than 0.05) and systolic blood pressure (p less than 0.01) during exercise, despite the use of lower workloads (p less than 0.05). During exercise, the albumin excretion in the patients was not related to their heart rate, blood pressure, workload or fall in blood glucose; nor was it related to duration of diabetes, glycosylated haemoglobin or insulin dose. An exercise UAV greater than 15 micrograms min-1 was found in 10 of the 33 patients; it was significantly correlated (p less than 0.01) with the frequency of previous overnight microalbuminuria (greater than 10 micrograms min-1), and was associated with a greater progression of microalbuminuria (p less than 0.05) over a mean period of 24 months. Retinol-binding protein excretion rate was also measured as an indicator of proximal tubular function and did not increase in either group.

Adult↗

Testing statistical hypotheses about rat liver foci.

Tests of statistical hypotheses concerning treatment effect on the development of hepatocellular foci can be carried out directly on two-dimensional observations made on histologic sections or on estimates of the density and volume of foci in three dimensions. Inferences about differences in the density or size of foci from tests based on two-dimensional observations, however, can be misleading. This is because both the number of focus cross-sections observed in a tissue section and the percent area occupied by foci can be expressed in terms of the number of foci per unit volume of liver tissue and the mean focus size. As a consequence, a treatment difference may be caused by a difference in the density of foci, their average size, or both. Of more serious concern is the possibility that failure to detect a treatment effect may occur not only when there is no treatment effect but also when the density and size of foci differ between treatments in such a way that their product is unchanged. This can happen if the effect of treatment is to increase the number of foci and decrease their average size, or vice versa. A similar difficulty of interpretation is associated with hypothesis tests based on average focus cross-section area. Tests based on estimates of the number of foci per unit volume and mean focus volume allow direct inference about the quantities of interest, but these estimates are unstable because they have large variances. Empirical estimates of statistical power for the Wilcoxon rank sum test and the t-test from data on control rats suggest power may be limited in experiments with group sizes of ten and low observed numbers of focus cross-sections. If hypothesis tests based on estimates of the density and size of foci are to form the basis for a bioassay, then the power of statistical tests used to identify treatment effects should be investigated.

Animals↗

Morphological and stereological characterization of hepatic foci of cellular alteration in control Fischer 344 rats.

Quantitative evaluation of altered hepatocellular foci (AHF), followed by stereological analysis was performed on standard hematoxylin and eosin-stained liver sections from control Fischer 344 (F344) rats of both sexes from seven 2-yr carcinogenicity studies conducted by the National Toxicology Program (NTP). Liver samples were collected at 6, 9, 12, 15, 18, and/or 24 months on study. Although AHF had a broad spectrum of morphological features, they could be classified into the following 5 types using previously published criteria: basophilic, eosinophilic, clear, vacuolated, mixed cell foci. Approximately 50% of the animals had foci at 6 months, and the incidence reached nearly 100% at 15 months in both sexes. The number, size and volume fraction of AHF increased with age in both sexes; these changes were most evident for basophilic and clear cell foci. The number of basophilic foci was significantly greater in females than in males while clear cell foci were more numerous in males. This sex difference was observed at each time point. Mean number of all types of AHF in males and females at 24 months was 547 and 460 per cubic centimeter of liver, respectively. Despite the high incidence of AHF in control rats, the incidence of hepatocellular neoplasms is low. The implication is that most foci do not progress to neoplasia in control F344 rats used in 2-yr studies.

Animals↗

Observations on altered hepatocellular foci in National Toxicology Program two-year carcinogenicity studies in rats.

Retrospective characterization of morphological and stereological features of altered hepatocellular foci (AHF) in hematoxylin & eosin (H&E)-stained sections was performed on 6 conventional 2-yr carcinogenicity studies conducted in Fischer 344 (F344) rats by the National Toxicology Program (NTP). In 3 of these studies where there was clear evidence of hepatocarcinogenicity [1-amino-2,4-dibromoanthraquinone (ADBAQ), C.I. Acid Red 114, methyl carbamate], there was greater morphological variability in AHF than in the studies of chemicals that were not hepatocarcinogenic [4-hydroxyacetanilide, epinephrine, dimethoxane]. In addition to having the expected types of AHF, rats treated with ADBAQ, C.I. Acid Red 114, and methyl carbamate had atypical basophilic AHF. In addition, atypical eosinophilic AHF were present in rats treated with ADBAQ. Both types of atypical AHF showed a morphological spectrum and sequential changes suggesting they could develop into hepatocellular neoplasms. For the 3 liver tumor positive studies, there were dose and time-dependent increases in stereological parameters for the atypical as well as commonly occurring clear, vacuolated, and mixed cell AHF. Consistent stereological changes were not found for commonly occurring basophilic and eosinophilic AHF. Aside from some decreases in stereological measurements in some rats treated with 4-hydroxyacetanilide and epinephrine, there were no significant quantitative changes in AHF in the three liver tumor negative studies. These results show that hepatocarcinogens may induce unique types of AHF in conventional 2-yr carcinogenicity/toxicity studies in rats and may cause quantitative increases in commonly occurring clear, vacuolated, and mixed cell AHF. Such qualitative and quantitative changes are potentially useful predictors of hepatic neoplasia.

Animals↗

A comparison of fifteen pulse oximeters. Part I: A clinical comparison; Part II: A test of performance under conditions of poor perfusion.

Fifteen pulse oximeters were compared. Their physical characteristics, price, warranty, information handling and displays were catalogued. Times for changes in data display and susceptibility to interference were assessed. A model for comparison of oximeters under conditions of poor perfusion was developed using a tourniquet to progressively diminish limb perfusion pressure (systolic minus tourniquet pressure). The oximeters evidenced a wide variety of features and performance in poor perfusion states. Instruments lacking a beep varying in pitch with saturation or a waveform/pulse bar display of plethysmograph signal were considered less satisfactory. The majority of instruments, with some notable exceptions, performed remarkably well in a state of diminished perfusion. The study demonstrates that purchasers of pulse oximeters need to exercise care in assessing the suitability of particular instruments to their specific requirements.

Adult↗

Predicting reproductive outcome from sperm measurements in Swiss (CD-1) mice.

UNLABELLED: Recent advances in the quantification of sperm characteristics, particularly by techniques of videomicrography, raise the problem of identifying a subset of sperm measurements that can accurately predict reduced reproductive performance in the presence of a reproductive toxicant. This paper discusses and illustrates, with sperm data from Swiss (CD-1) mice, three properties of sperm measurements in addition to the association with reproductive outcome that can be used as objective criteria to distinguish among potentially useful sperm characteristics. Identification of these properties was motivated by the need to single out sperm characteristics that would yield hypothesis tests with good power to distinguish groups with altered sperm characteristics from those with normal sperm characteristics. The list of desirable properties of sperm characteristics includes: a) MEASUREMENT: The most useful sperm characteristics will exhibit low measurement bias and high measurement precision. b) Distribution: Sperm characteristics that follow the class of normal distributions allow easy identification of the most powerful hypothesis testing procedures. c) Variation: Sperm characteristics that exhibit limited variation from individual to individual will make altered values easier to detect. d) Correlation: Sperm characteristics that exhibit a high correlation with reproductive outcome will be most useful. MEASUREMENTs of sperm concentration, sperm motility, and abnormal sperm were examined for each of these properties in Swiss (CD-1) mice. For control animals, evidence of measurement bias between labs and significant variation among studies within labs was found for each sperm characteristic, with measurements of abnormal sperm exhibiting the least bias. Sperm concentration and the natural logarithm of abnormal sperm appeared normally distributed. Individual to individual variation was substantial for sperm motility and sperm concentration, both of which required an approximately 30% decrease in mean to achieve good statistical power. In contrast, abnormal sperm required only a 4% increase in mean to achieve the same power. In spite of the measurement noise associated with these sperm characteristics, data from 25 experiments indicated good agreement between the results of hypothesis tests based on sperm characteristics and reproductive outcome as judged by fertility and the number of pups. The same conclusions reached for reproductive outcome were reached in 19 of 24 experiments for sperm motility, in 19 of 25 experiments for sperm concentration, and in 17 of 24 experiments for abnormal sperm.

Animals↗

Urinary albumin excretion in healthy adult subjects: reference values and some factors affecting their interpretation.

A conventional radioimmunoassay has been used to measure urinary albumin concentration in overnight, recumbent and daytime, ambulant samples from 127 healthy, normotensive volunteers (mean age 33.3 yr SD 12.4; 59 males, 68 females). Reference values were obtained for urine albumin concentration (mg/l), albumin/creatinine ratio (mg/mmol), and albumin excretion rate (microgram/min). The frequency distributions of these variables were positively skewed, but became Gaussian on logarithmic transformation of the data. Albumin excretion was significantly higher in daytime, ambulant samples than in overnight, recumbent samples (p less than 0.001). Surface area was not correlated with urine albumin concentration but it was negatively correlated with urine albumin/creatinine ratio (p less than 0.05) due to the association between surface area and creatinine excretion. Urine albumin concentration was negatively correlated with age, but this was due to a higher urine flow rate in older subjects. There was no significant association with sex or with mean arterial blood pressure in the normal range. Two repeated measurements showed that variability was high and comparable for urine albumin concentration, albumin/creatinine ratio and albumin excretion rate: it was not significantly less in overnight, recumbent than in day-time, ambulant samples.

Adolescent↗

The prevalence of hypoxemia detected by pulse oximetry during recovery from anesthesia.

Pulse oximetry was used to assess the prevalence of hypoxemia (arterial oxygen saturation of 90% or less) at various times in the immediate postoperative period: five minutes after arrival, 30 minutes later, and just before discharge. Among 149 inpatients studied, one or more hypoxemic measurements were made in 21 (14%) during their postoperative course. Of 92 outpatients, 1 (1%) was found to be hypoxemic. For inpatients, the prevalence of hypoxemia preoperatively, 5 minutes after arrival in recovery, 30 minutes later, and at discharge was 2%, 4%, 6%, and 9%, respectively. Patient factors associated with a significantly higher prevalence of hypoxemia were obesity (22%), body cavity surgical procedures (24%), age over 40 years (18%), American Society of Anesthesiologists physical status (I, 7%; II, 17%; III, 18%; IV, 100%), duration of anesthesia longer than 90 minutes (18%), and intraoperative administration of greater than 1,500 ml of fluid (20%). Unrecognized hypoxemia in postsurgical inpatients with or without these risk factors is common. Therefore routine monitoring of these patients with a pulse oximeter is suggested.

Adult↗

Evaluation of rodent sperm, vaginal cytology, and reproductive organ weight data from National Toxicology Program 13-week studies.

Sperm morphology and vaginal cytology examinations (SMVCEs), which include evaluations of motility, concentration and head morphology of sperm from the cauda epididymis, and male reproductive organ weight data, were developed by the National Toxicology Program as a screening system for reproductive toxicants. An analysis was conducted of SMVCE studies carried out at the end of fifty 13-week studies (25 for rats, 25 for mice) over a 3-year period. Statistically significant changes in these studies were summarized, as were control data for each male endpoint (mean, SD, 95% confidence limits around the mean, median, and statistical power). Reproductive organ weights (testis, epididymis, cauda epididymis) and sperm motility were the most statistically powerful endpoints evaluated; sperm head morphology may also be a sensitive endpoint for detecting reproductive toxicants. For 24 chemicals tested in both rats and mice, the concordance of results [i.e., no adverse effect in either species, or at least one SMVCE endpoint (not necessarily the same one) adversely affected in both species] was 58%. These data suggest that detection of potential reproductive toxicants might be best when both species are used. Types of sperm head abnormalities and their relative proportion of the total did not differ among control and treatment groups. Estrous cycle data were obtained in the final week of forty-six 13-week studies (23 for mice, 23 for rats). Only 3 chemicals caused an increase in mean cycle length compared with the control group. More data from breeding studies in which female estrous cycle length is measured are needed to assess fully the association of cycle length with reproductive outcome; stages of the estrous cycle are so variable that they may not be useful in assessing potential toxicity. Interlaboratory variability in SMVCE values for many endpoints was documented. Very few of the chemicals that form the basis of this report have been evaluated in definitive reproductive toxicology protocols; a companion paper compares changes in SMVCE endpoints with the outcome of continuous breeding reproduction studies.

Animals↗

Association of sperm, vaginal cytology, and reproductive organ weight data with results of continuous breeding reproduction studies in Swiss (CD-1) mice.

In continuous breeding reproduction studies in which an adverse effect on fertility was detected over an 18-week treatment period, a crossover mating trial was then conducted to determine the affected sex. Results of 25 crossover breeding studies conducted using Swiss (CD-1) mice were compared with results of sperm morphology and vaginal cytology examinations (SMVCEs) conducted at the conclusion of the mating trial. SMVCE endpoints include sperm concentration, motility, and morphology, vaginal cytology, and male reproductive organ weights. In most SMVCE studies multiple endpoints were adversely affected. For male reproductive toxicants, sperm motility was decreased in 89% of the studies, and absolute right epididymis and right testis weights were affected less frequently (80% each). Among studies with no detectable reduction in male breeding performance, 87% exhibited no detectable decrease in epididymis weight. Eighty-two percent had no change in cauda epididymis weight and 80% had no significant change in sperm concentration. An increase in female cycle length was associated (100%) with an effect on breeding due to female dysfunction. Overall accuracy, defined as correct identification of toxicants and nontoxicants, was highest for epididymis weight (84%), followed by cauda epididymis weight and sperm motility (79% each), and sperm concentration (76%). Female cycle length was so variable that the overall accuracy of the parameter in 13 studies was 69%. With the variety of chemicals used in this analysis, the association of abnormal sperm morphology with reproductive outcome was 71%. Control data (mean, 95% confidence interval around the mean, median, and statistical sensitivity) for each male endpoint (parent, and offspring at 10 weeks of age following a single breeding) were summarized from each of the two laboratories that conducted the studies. For several endpoints, statistical power was dependent on the laboratory conducting the studies. In general, the statistical sensitivity was relatively high for reproductive organ weights, although it was less for smaller organs such as the prostate. On the basis of both the biological and statistical analyses, it is recommended that multiple SMVCE endpoints, including sperm measures, be included in screens for reproductive toxicants.

Animals↗

Side-room tests to screen for microalbuminuria in diabetes mellitus.

Three side-room tests (latex bead immunoagglutination test, LBT; 25% sulphosalicylic acid test, SST; microalbutest, MAT) for the detection of microalbuminuria in diabetics are described and their screening potential and practicability assessed. One hundred insulin-dependent diabetics attending a diabetic clinic provided an early morning urine sample (Albustix-negative) which was subjected to each of the three tests, and urinary albumin concentration (UA) was assayed by RIA. Tests were assessed in random order by two trained operators using a semiquantitative grading scale with 100% concordance between 10 observers. All test results greater than or equal to trace +ve were sufficiently sensitive (sensitivity greater than or equal to 90%) in detecting UA greater than 15 mg/l, but MAT exhibited a significantly reduced specificity (69%) and positive predictive value (58%). For a reference UA greater than 30 mg/l, LBT and SST results greater than or equal to trace +ve and MAT results greater than or equal to +ve showed a sensitivity of 100%, a specificity greater than 85% and a positive predictive value greater than 60%. Reagent shelf-life was shortest with LBT. SST involved centrifugation or filtration. Technical skill required was highest with LBT and lowest with MAT. Costs were slightly higher with LBT than SST and were not available for MAT.

Albuminuria↗

A statistical study of papers in the Journal of Bone and Joint Surgery [BR] 1984.

The statistical quality of 103 original articles published in The Journal of Bone and Joint Surgery (British Volume) in 1984 was assessed. Some papers were found to be deficient: thus, it was not always clear how series were selected and sometimes neither the data nor the results were clearly presented. Sample sizes were frequently inadequate for the conclusions reached and statistical techniques should have been used more frequently. A majority of papers were descriptions of case series for which no comparative data were made available. It is suggested that collaborative research would best advance knowledge about the relative benefits of various managements, and that statistical advice could make a substantial contribution.

Orthopedics↗

Supplemental oxygen after ambulatory surgical procedures.

The aim of this study was to determine the need for supplemental oxygen during recovery from general anesthesia for ambulatory surgery in healthy women without obesity or respiratory disease. Arterial oxygen saturation by pulse oximetry (SpO2) was monitored throughout the first postoperative hour in 164 patients. The patients breathed room air during recovery. Supplemental oxygen was given only to those who became hypoxemic (SpO2 less than or equal to 92%). It was discontinued at the end of 15 minutes and reinstituted for another 15 minutes if hypoxemia recurred. Twelve patients (7%) became hypoxemic and required supplemental oxygen for various periods of time up to 105 minutes. The need for supplemental oxygen increased with increasing age (P less than 0.05) but was not associated with a history of cigarette smoking, tracheal intubation, amount of opioids or sedatives given intraoperatively, anesthetic duration, or level of consciousness during recovery. Hypoxemia was neither predictable nor clinically apparent. We recommend that, unless arterial oxygenation is monitored, ambulatory patients should routinely receive supplemental oxygen during recovery from general anesthesia.

Adult↗

Prophylactic PUVA and UVB therapy in polymorphic light eruption--a controlled trial.

A double-blind controlled trial of low-dose prophylactic oral psoralen photochemotherapy (PUVA) and ultraviolet-B (UVB) irradiation therapy was undertaken from April to September 1983 in 42 patients with polymorphic light eruption (PLE). Patients were randomly allocated to three groups, PUVA with oral 8-methoxypsoralen (8-MOP), UVB with oral placebo, and control low-dose UVA with oral placebo. The initial dose given to each active treatment group was a third of the predetermined minimal phototoxic or erythema dose, followed three times weekly for 6 weeks by doses incremented by an eighth on each occasion in the PUVA group and by a seventh in the UVB group. Ultraviolet radiation exposure was monitored throughout with polysulphone film lapel badges. Patients recorded their symptoms on a visual analogue scale. Symptoms of rash and itch in patients treated with PUVA and UVB were significantly less affected by increasing exposure to ultraviolet radiation than were these symptoms in control patients.

Clinical Trials as Topic↗