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Biomedical subjects

A J Wright

Publications and source records attributed to A J Wright.

At least 19 recordsLinked to original sources

Clinical utility of bronchoalveolar lavage in immunocompromised hosts.

Bronchoalveolar lavage (BAL) has been used extensively for assessment of immunocompromised hosts with pulmonary infiltrates. Reported estimates of the diagnostic utility of BAL have varied because of differences in patient populations, diagnostic criteria, and study methods. Herein we report on the use of BAL to determine at least one of the final diagnoses in 150 immunocompromised patients. Although the frequency with which BAL provided at least one of the final diagnoses (overall diagnostic yield) was seemingly low (39%), the yield increased substantially when only patients with pathologically proven diagnoses were considered. The sensitivity of BAL was 82%, and the specificity was 53%. The use of rigid diagnostic criteria enabled us to distinguish pathogens from colonizers. Pneumocystis was considered a pathogen whenever it was identified. It was the most common infectious pathogen identified (50%) despite the fact that our study population had relatively few patients (only 4%) with acquired immunodeficiency syndrome (AIDS). Organisms such as cytomegalovirus, Aspergillus, and Candida were frequently identified in BAL specimens but were eventually proved to be pathogens in only 24%, 25%, and 0% of cases, respectively. BAL detected pulmonary malignant lesions on the basis of positive cytologic results in four of six patients eventually found to have primary or metastatic lung cancer. Our results should enhance the understanding of the strengths and weaknesses of BAL and assist in the interpretation of associated microbiologic findings.

Acquired Immunodeficiency Syndrome

Dietary fat intake and plasma lipid levels in adolescents.

The relationship between dietary fat intake and fasting plasma lipid levels was assessed in 35 female and 19 male adolescents recruited from two local education authority schools in Norwich, UK. Dietary intakes were assessed using a 7-day weighed dietary record method, coupled with the collection of duplicate diets. Fat and energy intakes calculated using food composition tables were compared with values obtained by direct analysis of duplicate diets. Fasting plasma lipid levels (total, HDL and LDL cholesterol and triglycerides) were measured and compared with total dietary lipids and fatty acid intakes. The average proportion of energy consumed as fat was higher than is currently considered desirable but lower than previous studies have reported for adults. Mean serum total cholesterol values were 4.2 (SEM 0.1) mmol for females and 4.5 (SEM 0.2) mmol for males; this difference was not statistically significant. In male subjects the dietary fatty acid profiles were significantly correlated with several parameters of plasma lipid status which are thought to be risk factors for coronary heart disease, and in particular with the ratio of total:HDL cholesterol.

Adolescent

The penicillins.

The penicillin family of antibiotics remains an important part of our antimicrobial armamentarium. In general, these agents have bactericidal activity, excellent distribution throughout the body, low toxicity, and efficacy against infections caused by susceptible bacteria. The initial introduction of aqueous penicillin G for treatment of streptococcal and staphylococcal infections was an important pharmacologic landmark. The emergence of penicillinase-producing Staphylococcus aureus prompted the development of the penicillinase-resistant penicillins (for example, methicillin, oxacillin, and nafcillin), in which an acyl side chain prevented disruption of the beta-lactam [corrected] ring. Subsequently, the aminopenicillins (such as ampicillin and amoxicillin) were developed because of the need for gram-negative antimicrobial activity. Their spectrum included Escherichia coli, Proteus mirabilis, Shigella Salmonella, Listeria, Haemophilus, and Neisseria. The search for a penicillin with additional antimicrobial activity against the Enterobacteriaceae and Pseudomonas aeruginosa led to the development of the carboxypenicillins (carbenicillin, ticarcillin, and temocillin) and the ureidopenicillins (mezlocillin, azlocillin, piperacillin, and apalcillin). Finally, the combination of a beta-lactamase inhibitor (clavulanic acid or sulbactam) and an aminopenicillin or ticarcillin has further extended their antibacterial spectra. The development of an ideal penicillin that is rapidly bactericidal, nonsensitizing, nontoxic, bioavailable, resistant to beta-lactamase, and without inoculum effect and that has a high affinity for penicillin-binding proteins remains the goal.

Humans

The fluoroquinolones.

The fluoroquinolone class of antibiotics promises to become as diverse and as important as beta-lactam agents. The fluoroquinolones inhibit bacterial DNA gyrase and are bactericidal. All fluoroquinolones have potent activity against most gram-negative bacteria; ciprofloxacin is the most active against Pseudomonas aeruginosa. Activity against gram-positive organisms is variable; methicillin-resistant Staphylococcus aureus has acquired resistance to the fluoroquinolones at an alarming rate. Currently available quinolones do not have, but new quinolone agents likely will have, substantial activity against anaerobic bacteria. Some quinolones are also active against Mycobacterium, Chlamydia, and Mycoplasma organisms. All fluoroquinolones have excellent absorption after oral administration; however, this process can be impaired by the presence of aluminum- or magnesium-containing antacids and by zinc, iron, or calcium supplements. Ciprofloxacin is also available for intravenous use. Although most fluoroquinolones do not achieve adequate cerebrospinal fluid levels, penetration into other tissues is excellent. Dosage adjustments for renal and hepatic dysfunction vary among the quinolones. Although side effects are rare, concomitant use of caffeine or theophylline with some quinolones may cause toxicity to the central nervous system. Because they may affect the development of cartilage, all fluoroquinolones are contraindicated in children, adolescents, and pregnant or breast-feeding women.

4-Quinolones

Riboflavin deficiency in the rat: effects on iron utilization and loss.

Iron absorption and daily loss of Fe were measured in riboflavin-deficient (B2-) Norwegian hooded rats and controls (B2+). Animals were fed on a test meal extrinsically labelled with 59Fe and whole-body radioactivity measured for 15 d. Riboflavin deficiency led to a reduction in the percentage of the 59Fe dose absorbed and an increased rate of 59Fe loss. All post-absorption 59Fe loss could be accounted for by faecal 59Fe, confirming that the loss was gastrointestinal. Fe concentrations and 59Fe as a percentage of retained whole-body 59Fe were higher in the small intestine of riboflavin-deficient animals than their controls, 14 d after the test meal. A separate experiment demonstrated that riboflavin deficiency was associated with a significant proliferative response of the duodenal crypts of the small intestine. These observations may explain the enhanced Fe loss in riboflavin deficiency.

Absorption

The effects of sugar-beet fibre and wheat bran on iron and zinc absorption in rats.

The addition of 1 g sugar-beet fibre (Beta Fibre) to 3 g semi-synthetic diet resulted in a 54% increase in iron and a 39% increase in zinc absorption in rats. The same amount of non-starch polysaccharides fed as wheat bran (1.9 g) had no effect on Fe absorption but reduced Zn absorption by 9%. The inhibitory effect of wheat brain is probably due to its high phytate content, but there is, as yet, no explanation for the enhancement of Fe and Zn absorption caused by Beta Fibre. If the effect also occurs in man, it will have important implications for high-fibre diets and mineral nutrition.

Animals

The effectiveness of various iron-supplementation regimens in improving the Fe status of anaemic rats.

Less frequent iron supplementation may be equally as beneficial to Fe-deficient subjects as routine daily supplementation because of the short-term suppressive effect of oral dosing with large amounts of Fe on subsequent Fe absorption. In the present study, the possibility that the administration of an Fe supplement every 2nd or 3rd day may be as effective in improving Fe status as a daily supplement was investigated in anaemic rats. Anaemic rats were given a 4 mg Fe supplement every day, on alternate days or every 3rd day, as a single dose with a midday meal or as a multiple dose with a morning, midday and evening meal. A low-Fe diet (13 mg/kg) was given at all other times. After 7 d, erythrocyte count, packed cell volume, mean cell volume, haemoglobin concentration and total liver Fe were measured and compared with those of meal-fed rats which had not been given any supplemental Fe. Rats which received a supplement every 3rd day, a total supplement of 12 mg, had a similar Fe status to those receiving a daily supplement, a total supplement of 28 mg. Administration of the supplement as a multiple, rather than as a single dose did not improve recovery from the Fe deficiency. It is suggested that less frequent supplementation with a smaller total amount of Fe, should be considered in human subjects. Such a regimen would minimize unpleasant side-effects of oral Fe therapy, decrease the risk of adverse effects of Fe on the absorption of other essential minerals and substantially cut the cost of supplementation programmes.

Anemia, Hypochromic

Crouzon's disease. Part I. One-stage correction by combined face and forehead advancement.

Crouzon's disease results in maxillary hypoplasia and a receding forehead, which produce characteristic exorbitism. Total correction of the deformity by Le Fort III osteotomy and face advancement with a simultaneous forehead advancement corrects all the deformities. The advantages and disadvantages of this major craniofacial procedure are discussed after 2 case descriptions.

Child

The effect of combined dietary iron, calcium and folic acid supplementation on apparent 65Zn absorption and zinc status in pregnant rats.

In the present study the effect of combined iron, calcium and folic acid supplementation of the diet on 65Zn retention and zinc status was studied in the pregnant rat. Female Wistar rats were fed on a low- (8 micrograms/g) or high- (60 micrograms/g) Zn diet for 14 d and then mated overnight. After mating, half the rats were fed on the low- or high-Zn diet as before, whilst the other half were fed on similar diets supplemented with Fe, Ca and folic acid. The level of supplementation was chosen to reflect proportionately the possible increase in daily intakes of these nutrients by pregnant women. Rats which did not mate successfully were used as non-pregnant controls. On day 18 of pregnancy, each animal was given a meal of the appropriate diet labelled extrinsically with 65Zn, and on day 20 rats were killed. Carcass 65Zn retention was lower in pregnant and non-pregnant rats fed on the supplemented diets compared with those fed on the unsupplemented diets. Rats which consumed the supplemented diets throughout pregnancy had reduced plasma Zn concentrations but femur and fetal Zn concentrations were unaffected. Maternal femur Ca and fetal Fe concentrations were lower in the high-Zn groups compared with rats fed on low-Zn diets. It was concluded that the risk of inducing fetal Zn depletion as a consequence of Fe, Ca and folic acid supplementation during pregnancy appeared to be slight.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption

The effect of differences in dietary iron intake on 59Fe absorption and duodenal morphology in pregnant rats.

The effect of iron intake on 59Fe absorption throughout pregnancy, and on maternal and fetal Fe status towards the end of pregnancy, was investigated in rats. The influence of pregnancy and dietary Fe on duodenal morphology was also studied. Female rats were fed on a diet containing 17 or 100 mg Fe/kg for 2 weeks before and throughout pregnancy. 59Fe absorption was measured on days 1 or 2, 8 or 9 and 17 or 18 of pregnancy, and maternal and fetal Fe status was determined on days 18 or 19. Pregnancy resulted in a fall in haemoglobin (Hb) concentration. Compared with non-pregnant counterparts, total liver Fe was reduced in the low-Fe group, but not in the high-Fe group, indicating that the fall in Hb in the high-Fe rats was not associated with an Fe-deficient state. 59Fe absorption in rats fed on both diets increased throughout pregnancy, demonstrating that Fe supplementation of the diet, to a level that prevented the development of Fe-deficiency, failed to suppress an increase in absorption. Fetal weight appeared to be an important determinant of the efficiency of Fe absorption in late pregnancy. Poor maternal Fe status was accompanied by a reduction in fetal Fe concentration but results also suggested that fetuses were partly protected from maternal Fe-deficiency. Pregnancy resulted in increased duodenal circumference and villus dimensions, whilst high dietary Fe reduced duodenal growth in both pregnant and non-pregnant animals. The relevance of this finding is discussed. It was concluded that, in rats, pregnancy per se causes an enhancement in Fe absorption and that the degree of enhancement is in part related to fetal mass.

Animals

Measurement of non-haem iron absorption in non-anaemic rats using 59Fe: can the Fe content of duodenal mucosal cells cause lumen or mucosal radioisotope dilution, or both, thus resulting in the underestimation of Fe absorption?

Male Wistar rats (188 g) were fed on a semi-synthetic (SS) diet (38 mg iron/kg) ad lib. for 7 d and then meal-fed for 1 d. After a 21 h fast each rat was given one meal (10 g) of high-Fe SS (500 mg Fe/kg; high-Fe group) or control (38 mg Fe/kg; control group) diet. After 16 h 2 ml of an 59Fe-labelled ferrous sulphate solution (18 kBq 59Fe; 120 micrograms Fe) was administrated by gavage and equal numbers of rats from each group were killed 6 or 24 h after dosing. Mucosal uptake of 59Fe from the gut lumen and transfer of 59Fe from mucosa into the carcass were measured. Total Fe content of the duodenum was also determined. Mucosal 59Fe uptake and transfer were markedly lower in the high-Fe group compared with the control group. The Fe content of the duodenum, the major region of Fe absorption, was significantly greater in the high-Fe group than in the controls. A larger amount of Fe may thus have been released into the lumen of the high-Fe rats, via mucosal cell turnover, resulting in a greater lumen dilution of the 59Fe dose in this group compared with the controls. Calculations are presented which demonstrate that such an effect could not possibly account for the observed difference in mucosal 59Fe uptake between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Beneficial effect of chronic bradycardial pacing on capillary growth and heart performance in volume overload heart hypertrophy.

We have previously reported that chronic bradycardial pacing increases both capillary density/mm2 (CD) and maximal work output in normal rabbit hearts. This technique has now been applied to rabbits with volume-overload hypertrophy due to lesion of the aortic valve. Four groups of animals were studied: controls (C), paced (P), valve-lesioned (VL), and paced valve-lesioned (PVL). The aortic valve was lesioned 8 weeks before the acute experiments; pacing was started 4 weeks before the acute experiments, and thus, the PVL group had developed hypertrophy before pacing was started. The degree of hypertrophy was similar in VL hearts whether paced or not: heart wt/body wt ratio increased by 33.5 +/- 8.9% (mean +/- SEM) in VL and 25.2 +/- 8.2% in PVL versus control animals of similar body weight (p less than 0.001). The hearts of the PVL animals showed a higher CD (2,277 +/- 107) than VL hearts (1,383 +/- 43), CD in C hearts of similar weights being 1,595 +/- 103, and in P hearts 2,350 +/- 194. Thus, CD was lower by 14% in VL and higher by 43% in PVL than in C hearts. Valve-lesioning had a significant effect in reducing maximal cardiac minute work (p less than 0.001), whereas pacing significantly improved maximal cardiac minute work (p less than 0.001) to 2.467 +/- 0.206 J/g x 10(-4) in the P group versus 1.609 +/- 0.105 in the C group.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance