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Biomedical subjects

R Allen

Publications and source records attributed to R Allen.

At least 19 recordsLinked to original sources

Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease.

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional growth factor that has profound regulatory effects on many developmental and physiological processes. Disruption of the TGF-beta 1 gene by homologous recombination in murine embryonic stem cells enables mice to be generated that carry the disrupted allele. Animals homozygous for the mutated TGF-beta 1 allele show no gross developmental abnormalities, but about 20 days after birth they succumb to a wasting syndrome accompanied by a multifocal, mixed inflammatory cell response and tissue necrosis, leading to organ failure and death. TGF-beta 1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions.

Animals

Phase II study of Edatrexate in stage III and IV non-small-cell lung cancer.

A total of 49 patients with advanced, previously untreated non-small-cell lung cancer (NSCLC) were treated with a new antifolate, Edatrexate (10-ethyl-10-deaza-aminopterin; 10-EdAM). Patients received 80 mg/m2 weekly for 12 weeks, and responders received a further 6 cycles at 2-week intervals. Dose reductions were carried out for haematological toxicity and mucositis. Response was assessed prior to each treatment according to WHO criteria. Among the 45 evaluable patients, 6 [13.3%; 95% confidence interval (CI), 6%-26%] achieved a partial response (PR) and 9 (20%; 95% CI, 11%-34%) showed a minor response (MR; 25%-50% reduction in the sum of 2 perpendicular tumour diameters). In those receiving four or more cycles of treatment, the PR and MR rates were 17.6% and 26.4%, respectively. The resultant toxicity mainly constituted skin rash, mucositis and myelosuppression. Edatrexate is active against NSCLC and produces toxicity profile similar to that of methotrexate.

Aged

Sequence of a small subunit rRNA gene of Schistosoma mansoni and its use in phylogenetic analysis.

The complete sequence of a small ribosomal RNA gene of Schistosoma mansoni contained within plasmids pSM389 and pSM889 is presented. It was found to be 1992 bp in length, larger than that of most eukaryotes. Extra nucleotides occur in regions known to be variable (V4 and V7). The predicted secondary structure of the nucleotides 660-853 revealed additional helices which have been designated E21-1A and E21-1B. The other region to differ from higher eukaryotes lies between nucleotides 1457 and 1569. Secondary structure prediction demonstrated that a single extended helix may be formed from this part of the schistosome small subunit rRNA sequence. Nucleotides that could be unambiguously aligned with those of 12 other eukaryotes were used to estimate phylogenetic relationships. The consensus tree obtained by Maximum Parsimony analysis showed the schistosome as a sister taxon to the flatworm Dugesia tigrina.

Amino Acid Sequence

Structure of Sm25, an antigenic integral membrane glycoprotein of adult Schistosoma mansoni.

Sm25 is the principal antigen recognised by antibodies from mice protectively vaccinated with isolated tegumental membranes of adult Schistosoma mansoni. The full-length amino acid sequence of this protein has been deduced from the sequence of two cDNAs, one isolated by screening a cDNA library and the other, including the 5' end of the gene, amplified directly from adult worm RNA using the polymerase chain reaction. The predicted sequence represents a nascent polypeptide of Mr 21,500. Following cleavage of a predicted signal sequence, the Mr of the resulting polypeptide is 17,600. The polypeptide contains 2 potential sites for N-linked glycosylation and a hydrophobic domain at the C-terminus that could facilitate membrane association. Analysis of the mature gene product confirmed that Sm25 is an N-glycosylated integral membrane protein and that the Mr of the deglycosylated polypeptide is between 15,000 and 20,000.

Amino Acid Sequence

Molecular cloning and characterisation of the 22-kilodalton adult Schistosoma mansoni antigen recognised by antibodies from mice protectively vaccinated with isolated tegumental surface membranes.

A cDNA clone from an adult Schistosoma mansoni lambda gt11 expression library (A12) encoding an antigenic polypeptide of 22 kDa is described. A12 is 797 bp long and has one open reading frame encoding a protein of 190 amino acids which does not contain a signal sequence or membrane anchor motif and has no homologies with any sequences on the currently available data bases. Its product (sm22.6) is recognised by antibodies from mice protectively vaccinated with purified adult S. mansoni tegumental membranes and by serum from S. mansoni-infected Brazilians. It is present in all post-snail life cycle stages except the egg, is not sex-specific, and is found in 9 species of Schistosoma, but not in a range of other helminths. Data are presented which suggest that sm22.6 is a soluble, peripheral membrane protein.

Amidohydrolases

Shoulder dystocia recognition: differences in neonatal risks for injury.

Shoulder dystocia (SD) is an event whose current diagnostic approach is based on subjective criteria alone. Since the risk for immediate neonatal morbidity is critically linked to recognition and appropriate management of this obstetric emergency, we hypothesized that infants having injuries consistent with SD are frequently delivered without the intrapartum identification of this condition. A retrospective analysis of 26,033 vaginal births from January 1979 to April 1987 identified 162 maternal cases in which SD was diagnosed during delivery (incidence, 0.62%). Within this subset of patients, 24 neonates (15%) were identified as having either brachial plexus or fractured clavicle injuries associated with delivery. An additional 60 neonates were identified as having similar injuries immediately following delivery but without obstetric recognition of SD. Therefore 71% of all the injured infants were the product of deliveries without SD recognition. A comparison was made of maternal and neonatal variables for three groups (SD, uninjured; SD, injured; unrecognized SD, injured). The SD, injured group distinguishes itself from the other two groups by significant differences in the degree to which variables previously associated with SD are present. Conversely, both other groups are similar in all parameters except for accepted SD maneuvers utilized. These results support our hypothesis that SD is underreported in the obstetric literature and that unrecognized SD is associated with an increased risk of neonatal injury. Efforts to define objectively the threshold forces associated with neonatal injury and to develop SD teaching models should improve this clinical dilemma.

Adult

Neuropeptide Y radio-immunoassay: characterization and application.

1. A sensitive and specific neuropeptide Y (NPY) radio-immunoassay has been developed. This radio-immunoassay does not detect the NPY-related peptides pancreatic polypeptide or peptide YY. NPY extracted from rat plasma using sequential C18 sorbent and affinity chromatography co-eluted with synthetic rat NPY when applied to high pressure liquid chromatography. 2. The procedure of stabilization of platelets followed by high speed centrifugation reduced basal values of NPY by 60%, and this may be consistent with removal of platelets that release NPY. Administration of the cholinesterase inhibitor physostigmine (0.3 mg/kg), intravenously, produced a small but significant increase (39%) from basal concentrations of NPY. 3. NPY concentrations in young (2-3-month-old) Sprague-Dawley and Fisher 944 rats were similar; however, NPY concentrations were significantly increased (55%) in 2-year-old Fisher 944 rats. Similar to plasma concentrations of noradrenaline, NPY levels increase with age.

Aging

Addressing racism in psychiatry: is the therapeutic community model applicable?

Several reports have documented the failure of statutory psychiatric services in Britain to provide for the needs of clients from minority ethnic groups. Black clients are particularly underrepresented in Psychotherapy for reasons which are complex and varied, but include the institutionalised racism which pervades British society. We argue that the Therapeutic Community (TC) model of treatment (or aspects of it deployed in other mental health situations) provides a potential for a less racist service. Using the Henderson Hospital TC as a case in point, we argue that the TC is an approach which can meet the needs of black peoples. However, it is acknowledged that despite the ideological suitability of the TC model for black clients, in practice the Henderson Hospital is not fulfilling its role in providing therapy to this group. We discuss possible explanations and suggest the practical changes necessary, so that Henderson Hospital can meet the needs of clients in a multi-cultural Britain.

Black or African American

Infant care and wives' depressive symptoms.

Although some investigators show that division of child care between spouses is related to the psychological well-being of wives, little attention has been given to the relevance of specific dimensions of child care or to nonemployed as well as employed wives. In this study we differentiate basic child care tasks, i.e., those that are essential for the family's physical well-being from other, more supplemental, or auxiliary tasks. We hypothesize that husbands' failure to perform auxiliary child care will be distressing for wives, regardless of employment status because it contributes to perceptions of marital inequity. On the other hand, husbands' lack of participation in the more time-consuming, basic, tasks will be most distressing for employed wives because it results in an increased overall work load. We also hypothesize that when employed mothers are responsible for arranging child care, and when such care entails financial strains, they are more likely to experience psychological distress. To evaluate these hypotheses we use data drawn from a mail survey of a sample of mothers of infants. Using multiple regression analysis, we find that husbands' involvement in child care and housework, especially in the time-consuming tasks, is relatively low and that the most consistent predictor of husbands' involvement is wives' relative income. In terms of the impact of husbands' involvement on wives' well-being, lower levels of husbands' participation in auxiliary, but not basic, child care are associated with increases in reported symptoms, regardless of wives' employment status. When child care is relatively more costly, employed wives report increased symptoms of depression. We discuss these results in terms of the role played by expectations of husbands and wives about parental responsibility for child care.

Age Factors

Closure of a bronchopleural fistula with bronchoscopic instillation of tetracycline.

Persistent bronchopleural fistulas (BPF) due to infection, trauma, or thoracic surgical procedures are often difficult to manage. We report a patient with fulminant Staphylococcus aureus pneumonia complicated by chronic BPF formation which prevented weaning from mechanical ventilation due to severe air leak. Fistula closure was obtained by instillation of tetracycline into the fistula via a fiberoptic bronchoscope using a balloon catheter and blood clot occlusion technique. This closed the BPF and allowed successful weaning from mechanical ventilation.

Adolescent

A comparison of the cardiovascular effects of phenylpropanolamine and phenylephrine containing proprietary cold remedies.

1. The cardiovascular effects of the proprietary cold remedies, Mu-cron and Boots Cold Relief tablets were compared with 'placebo' Boots Pain Relief tablets in a double-blind study involving 16 healthy volunteers. Measurements (impedance cardiography, forearm plethysmography) were made over 4 h after oral drug administration. 2. Two Mu-cron tablets (containing phenylpropanolamine [(1R,2S)- plus (1S,2R)-norephedrine] 50 mg) increased blood pressure (maximal effect 18 +/- 1/8 +/- 1 mm Hg (mean +/- s.e. mean), P less than 0.001), stroke volume (4.9 +/- 0.8 ml m-2, P less than 0.05), total peripheral resistance (243 +/- 27 dyn s cm-5 m2, P less than 0.001) and forearm vascular resistance (1.3 +/- 0.3 mm Hg ml-1 min, P less than 0.01) and reduced the ratio of pre-ejection period to ventricular ejection time (-0.031 +/- 0.003, P less than 0.05) and forearm blood flow (-2.6 +/- 0.5 ml min-1, P less than 0.05) but did not affect heart rate or cardiac index. 3. Two Boots Cold Relief tablets (containing phenylephrine 10 mg and caffeine 60 mg) caused a small and short-lived increase in total peripheral resistance but did not have consistent effects on other measurements. Two Boots Pain Relief tablets (containing caffeine 60 mg) did not have important cardiovascular effects. 4. The cardiovascular effects of phenylpropanolamine, including vasoconstriction and an increase in cardiac performance, are consistent with its alpha- and beta 1-adrenoceptor agonist action. While it may help the symptoms of rhinitis, its use in patients with heart disease or hypertension is hazardous.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Randomized, double-blind trial of deflazacort versus prednisone in juvenile chronic (or rheumatoid) arthritis: a relatively bone-sparing effect of deflazacort.

Thirty-four children with juvenile chronic (rheumatoid) arthritis were recruited to a randomized, double-blind study of deflazacort (an oxazolone derivative of prednisone) vs prednisone. All had been receiving glucocorticoid therapy for at least 1 year and required at least 5 mg/d of prednisolone (usually as 10 mg every 2 days). Thirty-one children completed the study. Bone density trends were measured in the spine by dual photon absorptiometry and in the forearm by single photon quantitative computed tomography at 3-monthly intervals. Trends (velocities) in bone and soft tissue growth were calculated. In the spine, bone growth correlated well with indices of soft tissue growth, but covariance analysis showed a significant advantage (P less than .007) of deflazacort when spinal bone mineral growth was compared to body surface area and weight. In part this was due to a temporary interruption in weight by children receiving deflazacort, whose gain in height was comparable with that of the prednisone group. Some children in both groups improved clinically and showed catch-up growth; in these children relative spinal bone mineral growth velocities were about twice those observed for height and weight. It is concluded that during the first year of deflazacort, their spinal bone mineral content at a level that was appropriate for their height and weight. Further observations are required to establish whether this advantage can be maintained subsequently. The anti-inflammatory effects of the two glucocorticoids appeared similar.

Adolescent

Naproxen induced pseudoporphyria in juvenile chronic arthritis.

We report 6 cases of porphyria-like skin reactions in children taking naproxen for juvenile chronic arthritis. The lesions mimicked either erythropoietic protoporphyria or porphyria cutanea tarda, with both forms occurring in 2 patients. Biochemical studies excluded abnormal porphyrin metabolism.

Adolescent

Preoperative screening for perioperative cardiac risk.

Preoperative screening for potential cardiac complications is crucial in making rational decisions about surgery. A number of classification schemes are available to aid the primary care physician in assessing a patient's perioperative cardiac risk. In general, these schemes enable the physician to place patients in low-risk, moderate-risk and high-risk categories. Patients at low risk can often be safely referred for surgery with minimal preoperative evaluation, while those at potentially high risk frequently need further assessment and medical or surgical treatment of cardiac disease prior to surgery. The classification schemes are most accurate in identifying patients at high risk for perioperative cardiac complications. However, patients with silent underlying cardiac disease are often underclassified with respect to potential risk. For those patients, accurate prediction of perioperative cardiac complications can be challenging.

Health Status

Referral patterns and the results of antireflux operations in patients more than sixty years of age.

The role of antireflux operations in the elderly is ill-defined. Often, these patients are managed medically despite refractory symptoms for fear of surgical morbidity and mortality by referring physicians. This investigation was done to review the referral patterns and results of antireflux operations for patients more than 60 years old. The charts of all patients undergoing operation for reflux were reviewed during an eight year period from 1981 to 1989. One hundred and three patients underwent Nissen fundoplication. All patients had been treated with H2 blockers or antacids, or both, prior to referral for operation. Group 1 (N = 43) consisted of all patients who were 60 years of age and group 2 (N = 60), all patients less than 60 years of age. The mean age of those in group 1 was 70.6 years versus 43.7 years for those in group 2. The mean duration of symptoms was far greater in the elderly group versus the younger group (14.4 versus 4.1 years) (p less than 0.001). Twenty-eight patients in group 1 were referred for surgical treatment because of complications of reflux versus only four in group 2 (p less than 0.01) in whom intractability was the main indication for surgical treatment. The specific complications of gastroesophageal reflux disease that led to the referral of elderly patients for operation were stricture, bleeding, aspiration and Barrett's esophagus. There was one death and this occurred in a 46 year old woman who had a massive pulmonary embolism postoperatively. The mean duration of follow-up study was 5.1 years. Improvement in symptoms was noted by 37 patients in group 1 versus 56 in group 2. We conclude that elderly patients are most often referred for antireflux operations for complications of reflux versus younger patients in whom intractability is the most common indication. Earlier referral is warranted if reflux symptoms persist despite adequate medical therapy. Despite advanced esophageal disease, the results of antireflux operations are good, and surgical morbidity and mortality rates are low enough to warrant intervention in this group of patients, provided no medical contraindications exist.

Adult

Risk factors for shoulder dystocia: an engineering study of clinician-applied forces.

We report on engineering risk factors associated with clinician-applied forces during vaginal delivery of newborns. Specifically, we present and interpret data from a series of experiments using force-sensing devices on 29 randomly selected vaginal births, including two shoulder dystocia deliveries and one birth injury. The results indicate that clinician-applied peak forces are typically about 47 N for routine deliveries, 69 N for difficult deliveries, and 100 N for a shoulder dystocia delivery (P less than .01). The time required to deliver fetal shoulders doubles for nonroutine deliveries (P less than .01). In addition, impulse and rate of application of force distinguish between routine and nonroutine deliveries (P less than .03). We conclude that, if properly perceived, force, force rate, and the duration of force are objective parameters that can be used in recognizing and managing shoulder dystocia and in predicting thresholds for birth injury.

Biophysical Phenomena