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Biomedical subjects

K Ward

Publications and source records attributed to K Ward.

At least 163 records · Page 9Linked to original sources

Type 3 procollagen peptide in bronchoalveolar lavage fluid. Poor indicator of course and prognosis in sarcoidosis.

To investigate the role of bronchoalveolar lavage type 3 procollagen peptide as a prognostic indicator in sarcoidosis, we measured type 3 procollagen N-terminal peptide levels in lavage fluids from 84 sarcoidosis patients and monitored disease progress in these patients for a period of 12 months. Lavage procollagen peptide levels were significantly elevated in sarcoidosis patients compared to control subjects (p less than 0.001). No association was observed between lavage type 3 procollagen peptide and disease severity, as assessed by lung function tests. Follow-up monitoring of patients failed to demonstrate any relationship between subsequent functional deterioration and initial lavage type 3 procollagen peptide. These results suggest that elevated lavage type 3 procollagen peptide concentrations in sarcoidosis may reflect increased type 3 collagen synthesis associated with the inflammatory process rather than signal an early event in the development of chronic disease.

Adult↗

Intravenous immunoglobulin treatment of pregnant patients with recurrent pregnancy loss caused by antiphospholipid antibodies and Rh immunization.

A patient with antiphospholipid antibodies and nine consecutive fetal deaths and a severely Rh-immunized woman with one previous live birth and seven fetal/neonatal deaths achieved live births after antepartum administration of intravenous immunoglobulin. This agent shows promise as a new treatment for patients with previous repetitive fetal deaths from immunologic causes.

Adult↗

Localization and conditional redundancy of regulatory elements in rbcS-3A, a pea gene encoding the small subunit of ribulose-bisphosphate carboxylase.

Expression of the pea rbcS-3A gene, one of a family of genes encoding the small subunit of ribulose-bisphosphate carboxylase [EC 4.1.1.39], is regulated by light and is restricted to chloroplast-containing cells. We analyzed the effects of light and development on rbcS-3A expression in transgenic plants. Two highly conserved sequences ("boxes" II and III) around nucleotide position -150 (relative to the transcription initiation site, +1) are required for rbcS-3A expression. The so-defined positive elements overlap with previously identified negative light-regulatory elements. In the case of box II, which has sequence similarity to the core enhancer motif of simian virus 40, a GG----CC transversion is sufficient to abolish expression. The effect of mutations in boxes II and III can only be measured when sequences upstream of -170 are removed, and because sequences both 5' and 3' of -170 can direct light-regulated and organ-specific expression. This implies that there is a redundancy of cis-acting elements in the 5' noncoding region of rbcS-3A. However, we show that the sequences upstream of -170 are dispensable only in the mature leaves of a green plant. In contrast, in the young, expanding leaves at the top of a green plant, as well as in seedlings, the distal elements are required for high-level expression. Therefore, redundancy is not absolute, and the requirements for rbcS-3A expression change during plant development.

Base Sequence↗

Altered gastrointestinal immune response in sarcoidosis.

Because of the possible clinical association between coeliac disease and sarcoidosis, the incidence of humoral sensitivity to dietary proteins was examined in patients with sarcoidosis. Raised concentrations of circulating IgG antibodies to alpha gliadin were found in 41/99 sarcoid patients whereas antibody levels to casein, beta lactoglobulin and ovalbumin were similar to normal controls. Subsequently, a group of 26 sarcoid patients were selected for small intestinal biopsy; 11 had raised and 15 normal alpha gliadin antibody (AGA) levels. One AGA positive patient had villous atrophy consistent with coeliac disease. Intraepithelial lymphocyte (IEL) counts were raised in AGA positive (median 30; 95% confidence limits 22-46) and AGA negative (median 24; 95% confidence limits 19-32) sarcoid patients when compared with a control group (median 13.5; 95% confidence limits 10-18) p less than 0.01. Serum IgG concentrations were raised in 11/52 patients tested but there was no correlation between IgG levels and the presence of IgG antigliadin antibodies. HLA Dr typing was done in 21 of the 26 biopsied patients. The coeliac disease associated antigen Dr3 was present in eight of 21 (38%) which is very similar to the prevalence in unselected blood donors (34%). There was no significant difference in IEL counts between Dr3 positive and Dr3 negative sarcoid patients. These findings suggest that in patients with sarcoidosis, there is an altered gastrointestinal mucosal immune response, accompanied in about 40% of patients by specific sensitisation to wheat protein.

Adolescent↗

Real-time echocardiography: a new technique to facilitate Swan-Ganz catheter insertion.

Real-time echocardiography was used to position a pulmonary artery catheter in a septic child in whom the usual placement methods were not successful. This technique to facilitate pulmonary artery catheter placement avoids radiation, is portable and allows direct visualization of intracardiac catheter orientation. When smaller children and infants undergo pulmonary artery catheterization at the bedside, real-time echocardiography may allow catheter insertion when the usual techniques have failed.

Catheterization, Swan-Ganz↗

A paracentric inversion of 7q illustrating a possible interchromosomal effect.

A family is described in which the proband has a rearranged X chromosome involving monosomy Xp and trisomy Xq, while the mother has a paracentric inversion of chromosome 7. It is suggested that the phenomenon of interchromosomal effect may link these observations. A brief review of the published and computer catalogued data on paracentric inversion in man is included.

Chromosome Inversion↗

Sonography of the normal and abnormal stomach (excluding hypertrophic pyloric stenosis in children.

Prospective sonographic evaluation after water ingestion in 25 normal children aged 2 days to 15 years (mean 6.3 years) demonstrated that normal gastric wall thickness was less than 3 mm. Gastric walls of 5-15 mm thickness were seen in nine of about 6500 children undergoing abdominal sonographic examinations. These nine patients had a variety of unusual diseases, including varioliform gastritis, gastric ulcer, lymphoid hyperplasia, and gastric hamartoma. Previously unreported sonographic appearances were seen. The sonographic examination was instrumental in the detection of five clinically unsuspected gastric lesions and helpful in follow-up in four others.

Adolescent↗

Peripheral neuropathy and myopathy in chronic alcoholism.

Nineteen chronic alcoholics referred for investigation of their medical complications and for alcohol re-education were subjected to quadriceps muscle biopsy and detailed peripheral nerve electrophysiological studies. Thirteen patients showed type II muscle fibre atrophy by histomorphometric analysis. The presence of atrophy did not correlate with peripheral neuropathy as determined by clinical examination or with objective indices of nutritional status. There was no association of muscle atrophy with neurophysiological evidence for neuropathy and both occurred independently of each other. It was concluded that chronic alcoholic myopathy was due to a toxic effect of ethanol on the muscle fibres and was not merely secondary to a peripheral neuropathy.

Adult↗

Ischemic conduction failure and energy metabolism in experimental diabetic neuropathy.

We examined the effect of ischemia on nerve conduction in experimental diabetic neuropathy (EDN) and related electrophysiological changes to nerve adenosine triphosphate (ATP), creatine phosphate (CP), and lactate under anoxic conditions. Rats rendered diabetic with streptozotocin had a resistance to ischemic conduction block (RICB). Caudal nerve action potential (NAP) was well maintained for 10 min in controls and for 15 min in EDN, after which time NAP declined in both groups but more rapidly in normal rats. Time to 50% reduction in nerve ATP and CP was 10 and 3 min, respectively, in controls and delayed to 20 and 8 min in EDN. Rate of utilization of high-energy phosphate (approximately P) was linear for 5 min in controls to be followed by a progressive decline. In EDN rate of utilization of approximately P was linear to 15 min to be followed by a more gradual decline than in normal nerves. These findings suggest that the maintenance of nerve transmission in anoxic-ischemic states depends on anaerobic metabolism and that RICB in EDN is due in part to the ability of diabetic nerves to maintain a higher level of anaerobic glycolysis and for a longer time than normal nerves.

Action Potentials↗

Alcoholic skeletal myopathy, a clinical and pathological study.

One hundred and fifty-one inpatients with a history of chronic heavy alcohol intake were examined for evidence of muscle disease. Ninety-two patients (60 per cent) had histologically abnormal biopsies of the quadriceps muscle. The most common abnormality, which was often severe, was type II muscle fibre atrophy. Seven patients (5 per cent) had histological evidence of acute myopathy, one of whom presented with the full clinical picture of acute rhabdomyolysis. Twenty-three patients had cirrhosis, 36 were significantly malnourished and 98 had evidence of a peripheral neuropathy. None of these features, however, were sufficient to account for the muscle abnormalities. There was no clear relationship between musculo-skeletal symptoms and muscle biopsy histology. Serum creatine kinase activity was elevated in only 23 subjects and was an insensitive indicator of subclinical acute myopathy and of chronic alcoholic myopathy. Follow-up studies after abstinence from alcohol invariably showed both objective and subjective improvement of muscle function - often in the absence of any clinical recovery from the peripheral neuropathy. Continued alcohol consumption was accompanied by persistence and often deterioration of muscle fibre atrophy. It is concluded that chronic skeletal myopathy is a frequent consequence of alcohol abuse and may result from a direct toxic effect of ethanol on muscle fibres.

Acute Disease↗

Neonatal upper limb ischaemia. The case for conservative management.

General supportive measures, the ability to avoid infection, the natural tendency to improvement and the feasibility of major reconstructive procedures later suggest that neonatal limb ischaemia should be managed conservatively at first, despite an alarming appearance. The number of infants at risk, especially due to prematurity and effective resuscitation, is theoretically increasing.

Arm↗

Variations in circulating catecholamines fail to alter human platelet alpha-2-adrenergic receptor number or affinity for [3H]yohimbine or [3H]dihydroergocryptine.

A series of studies were performed to determine the relationship between physiologic levels of circulating plasma norepinephrine and epinephrine and human platelet alpha-2 binding site number and the affinity (KD) of these sites for antagonist radioligands. In one study, alpha-2-adrenergic binding site number and affinity were compared using both [3H]yohimbine and [3H]dihydroergocryptine as radioligands. There was good absolute and relative comparison for binding site number, but only a relative relationship for KD. In 46 normal subjects, there was no significant relationship between site number or KD and age, plasma epinephrine, or plasma norepinephrine concentration. Even after plasma epinephrine was raised nearly 20-fold by means of an intravenous infusion for 4 h in seven normal subjects, neither sites (608 +/- 68 vs. 567 +/- 120 sites/platelet) nor KD (2.01 +/- 0.94 vs. 2.14 +/- 1.15 nM) were significantly changed. Similarly, neither sites (445 +/- 55 vs. 421 +/- 53 sites/platelet) nor KD (1.44 +/- 0.29 vs. 2.10 +/- 0.75 nM) were significantly changed in six normal subjects when plasma norepinephrine levels increased during oral administration of prazosin for 1 wk. Thus, in a cross-sectional analysis and after a change in plasma catecholamine concentrations, there was no relationship in normal subjects between platelet alpha-2 binding site number or affinity of these sites for antagonist radioligands and the circulating catecholamine levels to which the platelets were exposed. In a group (n = 7) of patients who lack epinephrine-induced platelet aggregation due to abnormal thrombopoiesis, binding site number was decreased (304 +/- 36 vs. 572 +/- 29 sites/platelet, P less than 0.001) and KD tended to be greater (8.69 +/- 2.44 vs. 5.40 +/- 0.31 nM, P = NS) than in normal subjects (n = 46), despite having similar plasma catecholamine levels. There was no difference in binding site number (491 +/- 116 sites/platelet) and KD (5.61 +/- 0.84 nM) in patients (n = 5) with autonomic insufficiency and low levels of upright plasma norepinephrine when compared with the normal subjects. Two patients were examined before and after the removal of a pheochromocytoma. Their binding site number and KD were normal before the operation and essentially unchanged after the tumor removal and fall of plasma catecholamines. Thus, this study demonstrates that within the physiologic and pathophysiologic range of plasma catecholamines (in men), there is no relationship between the circulating catecholamine concentration and either platelet alpha-2 adrenergic binding site number or the affinity of these sites for antagonist radioligands.

Adult↗