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Biomedical subjects

K Newton

Publications and source records attributed to K Newton.

At least 37 records · Page 2Linked to original sources

Incidence, outcomes, and cost of foot ulcers in patients with diabetes.

OBJECTIVE: To determine the incidence of foot ulcers in a large cohort of patients with diabetes, the risk of developing serious complications after diagnosis, and the attributable cost of care compared with that in patients without foot ulcers. RESEARCH DESIGN AND METHODS: Retrospective cohort study of patients with diabetes in a large staff-model health maintenance organization from 1993 to 1995. Patients with diabetes were identified by algorithm using administrative, laboratory, and pharmacy records. The data were used to calculate incidence of foot ulcers, risk of osteomyelitis, amputation, and death after diagnosis of foot ulcer, and attributable costs in foot ulcer patients compared with patients without foot ulcers. RESULTS: Among 8,905 patients identified with type 1 or type 2 diabetes, 514 developed a foot ulcer over 3 years of observation (cumulative incidence 5.8%). On or after the time of diagnosis, 77 (15%) patients developed osteomyelitis and 80 (15.6%) required amputation. Survival at 3 years was 72% for the foot ulcer patients versus 87% for a group of age- and sex-matched diabetic patients without foot ulcers (P < 0.001). The attributable cost for a 40- to 65-year-old male with a new foot ulcer was $27,987 for the 2 years after diagnosis. CONCLUSIONS: The incidence of foot ulcers in this cohort of patients with diabetes was nearly 2.0% per year. For those who developed ulcers, morbidity, mortality, and excess care costs were substantial compared with those for patients without foot ulcers. The results appear to support the value of foot-ulcer prevention programs for patients with diabetes.

Aged↗

A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes.

Members of the tumour necrosis factor receptor family that contain a death domain have pleiotropic activities. They induce apoptosis via interaction with intracellular FADD/MORT1 and trigger cell growth or differentiation via TRADD and TRAF molecules. The impact of FADD/MORT1-transduced signals on T lymphocyte development was investigated in transgenic mice expressing a dominant negative mutant protein, FADD-DN. Unexpectedly, FADD-DN enhanced negative selection of self-reactive thymic lymphocytes and inhibited T cell activation by increasing apoptosis. Thus signalling through FADD/MORT1 does not lead exclusively to cell death, but under certain circumstances can promote cell survival and proliferation.

Adaptor Proteins, Signal Transducing↗

Gene trap integrations expressed in the developing heart: insertion site affects splicing of the PT1-ATG vector.

We describe the characterisation of three gene trap integrations in embryonic stem cells in which the lacZ reporter gene is repressed by retinoic acid (RA) in vitro and is expressed in the developing heart in vivo. In one of these, the gene trap vector has integrated into a gene that is located on chromosome 17 and is homologous to the human transcription factor gene, TFEB. Embryonic and adult cardiac expression of both the fusion transcript and the endogenous gene was confirmed. However, we show that the integration has not resulted in a null allele, because wild type transcripts, possibly resulting from splicing around the vector, are observed in homozygous tissue. The other two cardiac-expressing gene trap integrations have occurred into exons on chromosomes 1 and 5 and have used cryptic donor sites within the vector to generate functional fusion transcripts. One of these exon integrations results in a lethal neonatal phenotype.

Animals↗

Geriatric trauma.

This article reviews the salient aspects of geriatric trauma, including common injury mechanisms, physiologic differences in elderly patients, and their prehospital and emergency department evaluation. Specific organ injuries and associated mortality are also discussed.

Aged↗

The Bcl-2 family and cell death regulation.

Members of the Bcl-2 protein family fall into two categories on the basis of their ability to either promote or suppress apoptosis. Recent findings have linked these proteins to caspases, the cysteine proteases that effect the collapse of the cell via binding to CED-4. It seems that Bcl-2 proteins influence cell survival by regulating the activation of key caspases.

Animals↗

Rotavirus nonstructural glycoprotein NSP4 alters plasma membrane permeability in mammalian cells.

The endoplasmic reticulum-localized transmembrane glycoprotein NSP4 of rotavirus is a key protein involved in rotavirus cytopathology. We have used a dual-recombinant vaccinia virus system to express NSP4 in monkey kidney epithelial cells at a level comparable to that observed during rotavirus infection. Expression of NSP4 results in loss of plasma membrane integrity, which can be demonstrated by release of both 51Cr and lactate dehydrogenase into the medium. The cytotoxic behavior of NSP4 is dose dependent, and morphological analysis reveals gross changes to cell ultrastructure, indicative of cell death. Thus, intracellular expression of a single rotavirus protein which localizes to the endoplasmic reticulum membrane has profound effects on the stability of the plasma membrane and cell viability. Analysis of NSP4 deletion mutants indicates that a membrane-proximal region located within the cytoplasmic domain may mediate cytotoxicity.

Animals↗

Magnesium flux during and after open heart operations in children.

Hypomagnesemia and depletion of the body's magnesium stores is known to be associated with an increased incidence of both cardiac arrhythmias and neurological irritability. In a two-part prospective study we have evaluated whether magnesium deficiency is a significant occurrence in children treated in the intensive care unit after open heart operations, and subsequently have sought to identify how intraoperative metabolic changes were related to the resultant findings. In 41 children studied after operation the plasma magnesium concentration showed a significant decrease from 0.92 mmol/L (10th to 90th centile, 0.71 to 1.15 mmol/L) immediately after operation to 0.77 mmol/L (0.65 to 0.91 mmol/L) on the following morning. The subsequent change in grouped values was not significant but 14 (34.2%) and 7 (17.1%) possessed values of less than 0.7 mmol/L and 0.6 mmol/L, respectively. The occurrence of cardiac arrhythmias was not statistically related to the occurrence of hypomagnesemia. In 21 children perioperative changes in extracellular and tissue magnesium, potassium, and calcium content were measured. It was found that hemodilution with a prime low in magnesium caused a reduction from a median of 0.81 mmol/L to 0.61 mmol/L (p < 0.01). Plasma potassium level, however, was elevated from 3.7 mmol/L to 4.15 mmol/L (p < 0.05) and the ionized calcium content from 1.17 mmol/L (1.07 to 1.25 mmol/L) to 1.49 mmol/L (1.25 to 2.56 mmol/L) (p = 0.0009). The myocardial content of magnesium did not change significantly but skeletal muscle content was depleted from 6.75 mumol/g (2.85 to 8.35 mumol/g) to 5.65 mumol/g (2.45 to 7.2 mumol/g) (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗

Magnesium flux caused by coronary artery bypass operation: three patterns of deficiency.

We undertook a study to evaluate the patterns of magnesium deficiency that may develop during and following coronary artery bypass operation without cardioplegia. In 18 patients intraoperative measurements of plasma magnesium and potassium concentrations and measurements of cardiac and skeletal muscle content of these ions were taken. The changes in plasma concentrations and excretion were evaluated postoperatively. Hemodilution at initiation of cardiopulmonary bypass caused a 17.3% decrease in plasma magnesium concentration (p < 0.01), which persisted until the first postoperative day. By the fifth postoperative day the level was 19.5% greater than the preoperative value. Urinary excretion of magnesium reflected changes in plasma magnesium concentration. Cardiac muscle content of magnesium decreased by 13.3%. Plasma potassium concentration was elevated by hemodilution (p < 0.01), and muscle potassium was not depleted. We conclude that three patterns of magnesium depletion occur: hemodilution, intraoperative cellular depletion, and postoperative cellular depletion. The findings support the need for magnesium supplementation during and after cardiac operation.

Coronary Artery Bypass↗

Silicon and aluminium and their inter-relationship in serum and urine after renal transplantation.

The present study was undertaken to establish the relationship between serum and urine silicon and improve renal function and examine whether the increased urinary excretion of aluminium observed after successful renal transplantation was associated with silicon. The changes in silicon and aluminium concentrations in serum and urine were measured in 15 patients for a period of up to 17 days following a first renal transplant. Serum silicon, unlike aluminium, progressively decreased with improving renal function and was significantly positively correlated with serum aluminium but not with the silicon excretion. The urine excretion of aluminium peaked between 4-8 days post-transplantation and was highly significantly positively correlated with urine silicon. The individual patient fractional excretion profiles of aluminium and silicon were variable but in general gave significant positive correlations suggesting that the elements may be cleared by the kidney through a common mechanism or as a chemical species, possibly an hydroxyaluminosilicate. If soluble silicon can chemically interact with aluminium in vivo it may, as in the biosphere, be important in the control of aluminium toxicity and eventual detoxification. Thus, elevated serum silicon concentrations may help to alleviate aluminium toxicity in end-stage renal disease and assist in the rapid clearance of aluminium seen after kidney transplantation.

Adult↗

Inhibitory effects of enrichment media on the Accuprobe test for Listeria monocytogenes.

During an evaluation of the Accuprobe kit for the detection of Listeria monocytogenes, some of the enrichment media used were found to interfere with the test. Microscopic examination during the lysis step of the test revealed that media containing high salt greatly reduced or prevented cell lysis. This prevented the probe from binding to the cellular RNA, resulting in false-negative results.

Bacteriological Techniques↗

A study of adjunctive copper sulphate treatment in patients with rheumatoid arthritis who have relapsed while taking D-penicillamine.

Formation of a D-penicillamine-copper complex may be necessary for the anti-rheumatic effect of D-penicillamine. Thus, depletion of copper stores by D-penicillamine may eventually lead to relapse in D-penicillamine treated patients. Twenty-one patients who relapsed on D-penicillamine were randomised to copper sulphate 20 mg daily (n = 13) or matched placebo (n = 8) in addition to penicillamine daily for 16 weeks. Urinary copper was increased in the copper treated patients but no statistically significant or clinically important improvement occurred in either group.

Adult↗

A comparison of sucralfate dosage schedule in duodenal ulcer healing. Two grams twice a day versus one gram four times a day.

The conventional dosage schedule for sucralfate is 1 g 4 i.d., but a dose of 2 g 2 i.d. may be equally effective in duodenal ulcer healing. We compared the efficacy of these two regimens in duodenal ulcer healing. Seventy-seven patients with endoscopically proven duodenal ulceration were entered into a double-blind, controlled study and randomized to treatment with sucralfate 2 g 2 i.d. (on waking and at bedtime) or 1 g 4 i.d. (1/2 h before meals and at bedtime). The patients were endoscoped before entry into the study, after 4 weeks, and after 8 weeks if unhealed at 4 weeks. Of the patients considered suitable for analysis at 4 weeks, 79% (26/33) of those taking 2 g 2 i.d. had healed ulcers in comparison to 72% (23/32) of those taking 1 g 4 i.d. After 8 weeks, cumulative healing rates were 85% (28/33) and 80% (24/30), respectively. The results suggest that the more convenient dosage schedule of 2 g 2 i.d. is as effective as the 1 g 4 i.d. regimen in the short-term treatment of duodenal ulcer.

Adult↗

Orthostatic heart rates and blood pressures in healthy young women and men.

Orthostatic heart rate, systolic and diastolic blood pressure responses to standing were measured in 50 young healthy men and women. The responses of the men and women were the same. Heart rate stabilized after 45 seconds of standing, systolic blood pressure after 2 minutes, and diastolic blood pressure immediately on standing. There was considerable variability in the responses of these normal subjects, raising concerns about the validity of commonly accepted normal values.

Adult↗