Biomedical subjects
Publications and source records attributed to D Morris.
Selective feticide was performed at 15 weeks' gestation in a twin pregnancy where one fetus was found to have beta-thalassaemia major after diagnosis by chorionic villus sampling at 10 weeks' gestation. The technical, medical, legal and psychological problems are discussed in relation to this case.
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Of 141 women with twin pregnancies, 72 were randomly assigned to outpatient care and 69 to hospital admission between 26 and 30 weeks' gestation. There were no differences between the groups in the frequencies of major maternal complications in pregnancy and labour but more of those admitted to hospital than of the outpatient group had to be admitted after 30 weeks. There were no differences between the groups in the mean birthweights of the twins by birth order, or in their mean gestation at birth whether analysed by intention to treat or by the treatment given. 22 infants were delivered before 32 weeks' gestation in the inpatient group compared with 10 in the outpatient group. With the exception of small-for-dates infants, any trend towards greater morbidity or mortality was seen in the inpatient group. The policy of routine hospital admission of women with twin pregnancies from 26 weeks' gestation is not beneficial to mother or babies and should be abandoned.
Changes in the use of coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) over the last several years have resulted in a new and different environment for the interventional treatment of coronary artery disease. This study explores these changes as applied to the treatment of chronic coronary artery disease. The study population comprised 14,078 patients undergoing diagnostic cardiac catheterization between 1981 and 1988. In 1981, 1,704 patients underwent a first known cardiac catheterization at Emory University Hospital or Crawford W. Long Hospital and were found to have significant coronary artery disease. Of these patients, 51.7% were treated medically, 44.0% by CABG and 4.3% with PTCA. A similar group comprised 1,719 patients in 1988. Of this group 41.2% were treated medically, 28.5% with CABG and 30.3% with PTCA. The data reveal a much more complex phenomenon than a simple increase in PTCA for the treatment of coronary disease at the expense of CABG. The CABG group aged such that the percent of the CABG population more than 65 years old increased from 26.0% of the total in 1981 to 44.9% of the total in 1988. The percent of patients with ejection fractions less than 50% in the CABG population increased from 24.5% in 1981 to 29.7% in 1988. The PTCA population had less severe disease, was younger and had better left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)
Strain gauges were used to determine the setting expansion of phosphate-bonded casting investments. The gauges were placed at the approximate site of the wax pattern. The isotropy of the expansion was evaluated with multidirectional strain gauges that measured the difference in expansion in two orthogonal directions. A large difference was found between the setting expansion measured externally (1% to 1.5%) and the method described here (0.01%). For casting rings lined with a nonasbestos layer, no statistically significant differences were found in the setting expansion parallel to the long axis of the ring and the expansion in the direction perpendicular to the long axis.
To determine whether a weight-adjusted high dose (2 mg/kg body weight over 3 h) rapid infusion of recombinant tissue-type plasminogen activator (rt-PA) was more efficacious than a weight-adjusted standard dose (1.25 mg/kg over 3 h) in achieving reperfusion in the setting of acute myocardial infarction, 175 patients were entered into a randomized multicenter trial. Eighty-four patients were entered into the high dose group, receiving 1.2 mg/kg (10% given as a bolus injection) over 1 h, followed by 0.8 mg/kg over the next 2 h. Ninety-one patients were given 0.75 mg/kg (10% given as a bolus injection) in 1 h, followed by 0.5 mg/kg administered over the next 2 h. The median dose in the group that received 2 mg/kg dose was 145 mg, compared with 100 mg in the group that received 1.25 mg/kg. The 90 min patency rate in the group that received 2 mg/kg was 84% compared with 70% in the group that received 1.25 mg/kg (p = 0.003). Sixty-four percent of the patients in each group underwent coronary angioplasty at the time of cardiac catheterization. The infarct-related artery patency rate at the end of catheterization was 91% in the group that received 2 mg/kg compared with 83% in the group that received 1.25 mg/kg (p = 0.08). Among patients with a patent infarct-related coronary artery after catheterization, the 6 month mortality rate in the group that received 2 mg/kg was 2.9% compared with 9.8% in the group that received 1.25 mg/kg (p = 0.15). The bleeding complication rate in the two groups was similar.(ABSTRACT TRUNCATED AT 250 WORDS)
The authors present three men with both acrocyanosis and Asperger's syndrome. Though the general incidence of acrocyanosis is unknown, they suggest that it is probably more common in autistic disorders and may be caused by hyperserotonaemia.
This study presents the clinical and management problems in 81 epileptic patients attending the Queen Victoria Hospital for 98 pregnancies between 1985 and 1988. Epileptic women were found to have a 26.1% risk of seizure deterioration during pregnancy and the single most important factor for predicting seizure prognosis was the severity of epilepsy prepregnancy. There was a significant increase in the complications of vaginal bleeding, preeclampsia, and preterm delivery, compared with a control group of women. Infants of epileptic mothers had an increased incidence of low birth-weight and lower Apgar scores at 5 minutes. The congenital abnormality rate was 14.3% (9 major and 5 minor abnormalities). These results confirm that pregnant epileptic women are a high risk group.
Women with ovarian hyperandrogenism frequently have insulin resistance, whose underlying mechanism remains to be determined. In the present study we have investigated the relationship between insulin sensitivity and the acute effect of endogenous insulin secretion on circulating androgen levels. Insulin sensitivity, glucose-mediated insulin release, and glucose/insulin-stimulated androgen responses were determined during a frequently sampled iv glucose tolerance test in a group of 19 women with clinical evidence of polycystic ovary syndrome (PCOS) and 9 age- and weight-matched controls. Insulin (I), glucose, androstenedione, testosterone (T), free T, and dehydroepiandrosterone (DHEA) levels were measured before and during the 3 h following iv administration of glucose (300 mg/kg). Intravenous tolbutamide (300-500 mg) was injected 20 min after the glucose injection. Insulin sensitivity (SI) was calculated by application of the minimal model of glucose kinetics. Fasting androstenedione, T, free T, and I concentrations were significantly higher in the women with PCOS than in controls (P less than 0.02). In PCOS subjects, fasting I was correlated with both T (r = 0.51; P less than 0.05) and DHEA (r = 0.706; P less than 0.01). SI was significantly lower in PCOS subjects [SI, 68.35 +/- 8.34 min-1/(nmol/mL] than in control subjects (SI, 133.36 +/- 21.7 min-1/(nmol/mL)]. A significant decline in DHEA levels was observed in control subjects 3 h after glucose administration (from 28.4 +/- 3.0; final, 16.2 +/- 2.4; P less than 0.02). PCOS women with normal insulin sensitivity [SI, greater than 75.0 min-1/(nmol/mL)] showed a similar fall in DHEA (from 20.3 +/- 2.5 to 12.8 +/- 1.8 nmol/L; P less than 0.02). No significant change occurred in insulin-resistant PCOS subjects [SI, less than 75.0 min-1/(nmol/mL)]. Other androgen levels showed a modest nonsignificant decline during the study in PCOS and control groups. These findings confirm the weight-independent insulin resistance of some hyperandrogenic women. The failure of glucose-stimulated endogenous insulin secretion to significantly depress DHEA levels in insulin-resistant women with PCOS may account in part for their androgen excess.
The estimation of incidence (or risk) of disease depends on accurate and complete reporting of new cases and precise estimation of the population at risk. Therefore, incidence studies are often based on population-based incidence registries. A critical problem in diabetes research, however, has been the lack of adequate population-based data. For diseases that have a distinct and rapid onset, the best method of obtaining population-based data is to develop registries of community health information. These disease registries form an important tool for assessing the clinical course of diseases and can lead to an understanding of their etiology and pathogenesis. Moreover, by facilitating identification of cases, disease registries can serve as a population source for genetic and immunological testing, the results of which can be directly related to absolute risk. Evaluation of factors associated with a disease can suggest methods for reducing its incidence and even lead to its eradication. Such registries also permit the evaluation of existing or proposed health care measures. Registry information can rapidly be communicated to the local area health authorities to assist in altering patterns of care. Registries are therefore important for understanding the etiology and complications of chronic diseases as well as for evaluation of medical care in populations. For diabetes, and in particular, insulin-dependent diabetes, the development and comparison of registries in diverse populations worldwide may be more important than for other diseases. A major reason for developing them is that the disease is very costly both for patients and society.(ABSTRACT TRUNCATED AT 250 WORDS)
The 7-bromoacetyl-7-desacetyl (BrAcFsk) and 7-chloroacetyl-7-desacetyl (CIAcFsk) analogs of forskolin were synthesized as alkylating agents to study the high affinity binding sites for forskolin. BrAcFsk and CIAcFsk activated adenylate cyclase in human platelet membranes with EC50 values of about 20 and 12 microM, respectively. Both analogs increased cyclic AMP in human platelets; however, they were less potent that forskolin. Forskolin inhibited [3H]forskolin binding to human platelet membranes with an IC50 of 20 nM, whereas BrAcFsk and CIAcFsk inhibited [3H] forskolin binding with IC50 values of 0.1 microM. Pretreatment of intact platelets with 10 microM BrAcFsk caused a 90% irreversible loss in [3H]forskolin binding sites, whereas pretreatment with 10 microM CIAcFsk led to a loss of 55% of the binding sites. The loss of binding sites occurred within 5 min for BrAcFsk and within 30 min for CIAcFsk. The time required for the loss of binding sites produced by either alkylating agent was increased by the inclusion of 200 microM forskolin in the pretreatment buffer. The inactive bromoacetyl analog of forskolin 7-bromoacetyl-7-desacetyl-1.9-dideoxyforskolin (1,9-dideoxy-BrAcFsk) did not activate adenylate cyclase, inhibit [3H]forskolin binding, or cause an irreversible loss of [3H]forskolin binding sites. Adenylate cyclase was assayed in membranes from platelets treated with either 10 microM BrAcFsk or 10 microM 1,9-dideoxy-BrAcFsk. The stimulation of adenylate cyclase by prostaglandin E1, guanosine-5'-O-(3-thio)triphosphate, and AIF4 was inhibited by about 50% in membranes from platelets treated with BrAcFsk. However, the stimulation of adenylate cyclase by forskolin was unaffected by preincubation with BrAcFsk. Pretreatment of human platelets with 1,9-dideoxy-BrAcFsk had no effect on the stimulation of adenylate cyclase by prostaglandin E1, AIF4, or forskolin.
Two information systems in the English National Health Service (NHS) are described and discussed. The performance indicator scheme enables service inputs and activity to be readily compared between district health authorities (DHAs) or hospitals. Quality of care is not measured directly by performance indicators but in certain circumstances a limited assessment may be inferred from the health service input and activity data. Experiments in management budgeting and resource management are reported in which the NHS accounting system is being changed to one which is more patient-based and from which costs can be identified for clinically meaningful groups of patients. Variation in service activity, derived from the performance indicator system, has been used by the government with other evidence to make the case for NHS reform. Realistic implementation of the proposed NHS reforms will depend on the success of the budgeting experiments.
The surgical management of each of the four stages of pressure ulcers is described. Preoperative management includes vigorous wound care, optimal nutritional status, spasticity control, patient education, and optimal patient physiology. Twelve basic principles of pressure ulcer surgery are presented and illustrated by location of ulcer. Examples include ischial, sacral, greater trochanteric, and lower extremity ulcers.
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Chorionic villus sampling (CVS) is a first trimester alternative to amniocentesis for the prenatal detection of genetic disorders. Initial experience in 48 patients, in whom transcervical CVS was utilised for the diagnosis of chromosomal, biochemical or molecular disorders, is reported. An adequate villus sample was obtained in all cases and a diagnostic result was achieved in 90% of cases. In this series, the miscarriage rate was 4.2%. It is concluded that CVS appears to be a relatively safe and reliable procedure, but the risk of miscarriage can only be accurately assessed after further investigation.
Two women, ages 53 and 46, presented with multiple spontaneous vertebral fractures. Serum calcium, 25OHD, 1,25-(OH)2D, PTH, and 24-h urinary calcium were all normal. Bone mineral analysis (BMA) was performed at the junction of the distal third of the radius by single photon absorptiometry. BMA on Patient 1 was 0.68 g/cm2 and on Patient 2 was 0.58 g/cm2, with the normal being 0.70 g/cm2 and 0.77 g/cm2, respectively. In addition to vertebral fractures, x rays of Patient 2 revealed lytic lesions of the tibia and ulna. Bone biopsies revealed osteopenia associated with generalized eosinophilic fibromastocytosis and increased resorption without evidence of increased numbers of osteoclasts. There was no evidence of extraskeletal mast cell involvement. Our observations contribute to the increasing evidence that mast cells play a direct role in the etiology of osteoporosis in certain patients. Possible pathophysiologic mechanisms include mast cell release of heparin, histamine, prostaglandin D2 or other osteolytic substances.
Two colorectal (HT29, LoVo) and one gastric (MKN45) human tumour cell lines were examined for their in vitro trophic response to human gastrin-17. MKN45 and HT29 responded by increased 75Se selenomethionine uptake to exogenous gastrin (139 +/- 5.5% and 123 +/- 3% of control values respectively) whereas LoVo showed no significant response to this hormone. When these same cell lines were grown as xenografts in nude mice, similar responses were seen to exogenously administered human gastrin-17 (10 micrograms mouse-1 day-1, subcutaneous injection). MKN45 xenografts showed a greater response to continuously administered gastrin (osmotic mini-pumps, (10 micrograms mouse-1 day-1) when compared to the same dose given via a subcutaneous bolus injection. The hormone-treated xenografts had a two-fold increase in tumour cross-sectional area and growth rate when compared to saline-treated controls. Dose-response studies revealed that 0.4 micrograms gastrin mouse-1 day-1 appeared to be the minimally effective dose. As gastric and colorectal tumour cells show a trophic response to gastrin, antagonists of the gastrin receptor may prevent this effect causing tumour stasis. The gastric tumour cell line, MKN45, is gastrin-responsive and would be an ideal model for screening potent receptor antagonists.
Evaluation of the use of diagnosis-related groups (DRGs) has revealed a number of technical problems in coding of diagnoses and operative procedures, as well as unresolved issues in the clinical acceptability of existing groupings. An investigation of the statistical homogeneity of DRGs, in terms of duration of patient stay, is described. Consideration of data relating to some 990,000 episodes of in-patient care in three English Regions discloses wide variations in statistical homogeneity, both between DRGs and in relation to individual clinical specialties. The greatest homogeneity is found in ENT surgery and gynaecology; and the least in general medicine and orthopaedic surgery. The need for improved data collection and coding procedures is discussed, together with the advisability of sensitivity in the interpretation of DRGs, as well as the need for a co-ordinated approach to their refinement for application in any wider introduction in the NHS.