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Biomedical subjects

D P Moore

Publications and source records attributed to D P Moore.

At least 73 records · Page 4Linked to original sources

Adolescent idiopathic scoliosis as developmental instability.

Adolescent idiopathic scoliosis is the most common spinal deformity affecting children, with a prevalence from mass screening programmes of 1-3%. Despite centuries of study, it remains a problem with no generally accepted theory of aetiology, and disagreement on its natural history and management. Because the deformity consists ultimately of gross left-right asymmetry, a study was undertaken to test the hypothesis that it might be a manifestation of developmental instability. Palmar dermatoglyphics in 112 normal subjects, 62 with non-scoliosis trunk asymmetry and 85 with defined adolescent idiopathic scoliosis were examined and both the absolute right-left difference and the ratio of this to the total were considered. There was increased fluctuating asymmetry of atd difference in those with any asymmetry, scoliotic or not, and increased directional asymmetry of ab and cd ridge counts only in those with pure scoliosis. This suggests that, at adolescence, developmental instability may result in a loss of symmetry in growth, and that in the presence of an increased developmental left-right gradient, this may be of sufficient severity to be classified as deformity and come to the attention of orthopaedic surgeons. This interpretation changes the focus of many previous observations on scoliosis and raises the prospect that developmental stability in humans has relevance to problems hitherto restricted to clinical practice.

Adolescent↗

Double or nothing: a Drosophila mutation affecting meiotic chromosome segregation in both females and males.

We describe a Drosophila mutation, Double or nothing (Dub), that causes meiotic nondisjunction in a conditional, dominant manner. Previously isolated mutations in Drosophila specifically affect meiosis either in females or males, with the exception of the mei-S332 and ord genes which are required for proper sister-chromatid cohesion. Dub is unusual in that it causes aberrant chromosome segregation almost exclusively in meiosis I in both sexes. In Dub mutant females both nonexchange and exchange chromosomes undergo nondisjunction, but the effect of Dub on nonexchange chromosomes is more pronounced. Dub reduces recombination levels slightly. Multiple nondisjoined chromosomes frequently cosegregate to the same pole. Dub results in nondisjunction of all chromosomes in meiosis I of males, although the levels are lower than in females. When homozygous, Dub is a conditional lethal allele and exhibits phenotypes consistent with cell death.

Alleles↗

Hotspots for unselected Ty1 transposition events on yeast chromosome III are near tRNA genes and LTR sequences.

A collection of yeast strains bearing single marked Ty1 insertions on chromosome III was generated. Over 100 such insertions were physically mapped by pulsed-field gel electrophoresis. These insertions are very nonrandomly distributed. Thirty-two such insertions were cloned by the inverted PCR technique, and the flanking DNA sequences were determined. The sequenced insertions all fell within a few very limited regions of chromosome III. Most of these regions contained tRNA coding regions and/or LTRs of preexisting transposable elements. Open reading frames were disrupted at a far lower frequency than expected for random transposition. The results suggest that the Ty1 integration machinery can detect regions of the genome that may represent "safe havens" for insertion. These regions of the genome do not contain any special DNA sequences, nor do they behave as particularly good targets for Ty1 integration in vitro, suggesting that the targeted regions have special properties allowing specific recognition in vivo.

Base Sequence↗

A rare tRNA-Arg(CCU) that regulates Ty1 element ribosomal frameshifting is essential for Ty1 retrotransposition in Saccharomyces cerevisiae.

Translation of the yeast retrotransposon Ty1 TYA1(gag)-TYB1(pol) gene occurs by a +1 ribosomal frameshifting event at the sequence CUU AGG C. Because overexpression of a low abundance tRNA-Arg(CCU) encoded by the HSX1 gene resulted in a reduction in Ty1 frameshifting, it was suggested that a translational pause at the AGG-Arg codon is required for optimum frameshifting. The present work shows that the absence of tRNA-Arg(CCU) affects Ty1 transposition, translational frameshifting, and accumulation of mature TYB1 proteins. Transposition of genetically tagged Ty1 elements decreases at least 50-fold and translational frameshifting increases 3-17-fold in cells lacking tRNA-Arg(CCU). Accumulation of Ty1-integrase and Ty1-reverse transcriptase/ribonuclease H is defective in an hsx1 mutant. The defect in Ty1 transposition is complemented by the wild-type HSX1 gene or a mutant tRNA-Arg(UCU) gene containing a C for T substitution in the first position of the anticodon. Overexpression of TYA1 stimulates Ty1 transposition 50-fold above wild-type levels when the level of transposition is compared in isogenic hsx1 and HSX1 strains. Thus, the HSX1 gene determines the ratio of the TYA1 to TYA1-TYB1 precursors required for protein processing or stability, and keeps expression of TYB1 a rate-limiting step in the retrotransposition cycle.

Base Sequence↗

Cardiopulmonary response to exercise in patients with intrapulmonary vascular shunts.

The majority of patients with intrapulmonary right-to-left shunting due to pulmonary arteriovenous malformations-exhibit good maximum exercise capacity (> 70% predicted) despite profound arterial oxygen desaturation. We studied seven such patients to assess tissue oxygen delivery during steady-state exercise. From rest to exercise [50 +/- 7 (SE) W] arterial saturation fell from 80 +/- 3 to 74 +/- 3%, and mean right-to-left shunt increased slightly from 31 +/- 4 to 34 +/- 5% (P = NS). Minute ventilation was high for oxygen uptake, and the ventilatory equivalent was raised (174 +/- 19% predicted) and was correlated with shunt size (r = 0.93). The majority of the patients maintained pulmonary alveolar blood flow within the predicted range for their power output, but total cardiac output was increased to 142 +/- 11% predicted due to flow through the shunt. Consequently, on exercise, oxygen delivery per unit oxygen consumption [2.3-3.3 (normal range 1.6-2.4)] and calculated mixed venous oxygen tension (27.0 +/- 0.8 Torr) were preserved. Arterial PCO2 rose on exercise by 2.8 +/- 1.2 Torr, in proportion to the ratio of flow through the shunt to total cardiac output (r = 0.73), but remained low (33.1 +/- 1.4 Torr) in absolute terms. The high cardiac output on exercise may be facilitated by a low pulmonary vascular resistance (0.33 +/- 0.08 mmHg.1-1.min, measured at rest), which may explain why exercise performance is better in these patients than in patients with equivalent hypoxemia from other causes.

Adolescent↗

Effects of increased inspired oxygen concentrations on exercise performance in chronic heart failure.

Exercise capacity in patients with stable heart failure may be influenced by prolonged drug treatment or exercise training, but acute interventions are generally thought to have little effect. Cardiorespiratory responses to exercise were studied in 12 consecutive patients with chronic congestive heart failure who underwent serial submaximal and maximal exercise tests at inspired oxygen concentrations of 21% (room air), 30%, and 50%. Mean (SD) exercise duration during progressive testing to maximum exercise capacity was prolonged from 548 (276) s on room air to 632 (285) s on 50% oxygen (p = 0.012). During steady-state exercise at 45 W, oxygen enrichment to 50% was associated with significantly increased arterial oxygen saturation (94.6 [1.9]% to 97.5 [1.3]%), and significantly reduced minute ventilation (36.1 [8.6] l/min to 28.1 [5.9] l/min), cardiac output (7.5 [2.3] l/min to 6.5 [1.9] l/min), and subjective scores for fatigue and breathlessness (13.9 [3.1] to 11.5 [3.5]) compared with room air intermediate changes were observed with 30% inspired oxygen. Increased inspired oxygen concentrations can improve exercise performance acutely and modify the ventilatory response to exercise in patients with heart failure. Hyperoxia reduces ventilatory response and circulatory demand while maintaining oxygen delivery at a given workload. The potential benefits of increased inspired oxygen concentrations in the treatment of chronic heart failure merit further assessment.

Adult↗

Acute epidemic aluminium osteomalacia secondary to water supply contamination.

When the aluminium content of the water supply to our Haemodialysis Unit rose from less than 0.5 mumol/l to 6 mumol/l over a two month period, we carried out bone biopsies and desferrioxamine infusion tests on twelve (12) patients who had been on haemodialysis for less than one year (mean 8 months) and had normal serum aluminium levels. The patients had no bone symptoms. Eight patients had positive aluminium bone stains. The aluminium osteomalacia group (n = 8) had a mean PTH of 1.4 ng/ml s.e. 0.3 whereas the non-ALO group had a mean PTH of 2.9 ng/ml s.e. 0.7. The difference in mean PTH is significant (p less than 0.05). There was no evidence of encephalopathy, fractures or microcytic anaemia in the ALO positive group. The aluminium contamination of the water supply occurred because of a change in the reservoir purification system from sand-filtration to alum.

Adolescent↗

Aluminium osteomalacia in chronic renal failure patients neither on dialysis nor taking aluminium containing phosphate binders.

The incidence of aluminium osteomalacia (ALO) in patients with chronic renal failure neither on dialysis nor taking aluminium-containing phosphate binders (ACPB) is not well documented. Biochemical and histological bone investigations were performed in 35 patients fulfilling the above conditions, among whom we found an incidence of ALO of 17%. In the ALO group, salient findings were PTH level (mean +/- s.d.) of 3.1 +/- 1.4 ng/ml (normal less than 0.5 ng/ml); elevated home tap-water aluminium levels of 6.5 +/- 1.2 umol/l (normal less than 2 umol/l); and a GFR of 20.5 mls/min/1.73m, (range 2-50 mls/min/1.73m). We conclude that the aetiology of ALO in this group involves the absorption of toxic home water aluminium in the presence of an elevated PTH level and a GFR less than 50 mls/min/1.73m.

Adult↗

Mortality and morbidity associated with hip fractures.

In this study 147 patients with hip fractures were reviewed and reassessed to establish their mortality and morbidity. The early mortality was 10.8% and this rose to 27% at three months. The major factors which determined mortality and morbidity were the age of the patient, male sex, and the degree of social dependence of the patient both before and after the fracture. The site of the fracture or the type of anaesthetic used did not significantly affect the outcome. The shortage of Nursing Home and long-term care facilities resulted in prolonged hospital stay for many patients.

Aged↗

Pulmonary berylliosis on corticosteroid therapy, with cavitating lung lesions and aspergillomata--report on a fatal case.

A fatal case of pulmonary berylliosis in a 42 year old male is described. The patient was exposed to beryllium while working in a chemical plant over a 9 year period, and presented two years after ceasing such employment. The berylliosis was diagnosed on open lung biopsy in 1971. The patient was commenced on steriod therapy at that time. He suffered progressive dyspnoea from severe restrictive lung disease over the next 14 years. A chest X-ray of June 1985 revealed a lesion in the left upper lobe suggestive of a mycetoma. Before any therapy could be instituted he suffered a massive haemoptysis and died. Post-mortem examination revealed two large mycetomata in the right and left upper lobes. Parenchymal histology showed evidence of chronic inflammation with non-caseating granulomata and the cavity wall showed localized invasion by Aspergillus fumigatus. It is possible that the long term steroid therapy with multiple boosters of treatment may have contributed to the development of the mycetoma. This is the first case report known to the authors of a fatal aspergilloma in association with chronic berylliosis treated with steroids.

Adult↗