Iron and the sudden infant death syndrome.
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Biomedical subjects
Publications and source records attributed to M Murphy.
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The major function of the oligodendrocyte is to myelinate axons in the central nervous system (CNS). Two of the components of myelin, galactocerebroside (galc) and myelin basic protein (MBP), have been used as markers of oligodendrocyte maturation in the developing CNS, and it has been found that galc+ cells arise initially, which then mature into MBP+ oligodendrocytes several days later. We have been interested in the control of expression of MBP and have followed its appearance in cultures of brain cells isolated from 4 day-old mice. In low serum (0.5% foetal bovine serum), approximately 330 MBP+ cells arise per 2 x 10(5) brain cells after 3 days incubation. We have examined the ability of several growth factors to influence the expression of MBP in these cultures, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and the fibroblast growth factors (acidic and basic FGF). EGF was found to suppress strongly the developmental expression of MBP in these cultures, but the suppression was reversible, since the number of MBP+ cells approached control numbers 3 days after removal of EGF from the cultures. It was also found that MBP could be down-regulated in mature MBP+ oligodendrocytes. The action of EGF in these cultures could be mimicked by transforming growth factor-alpha (TGF alpha). The effects of EGF appear to be associated primarily with MBP production in oligodendrocytes since expression of galc is unaffected by EGF.
Anxiety, depression, self-esteem, behavioural deviance and prosocial behaviour were studied in children attending a normal school in a disadvantaged urban area, using self-rated and teacher-rated questionnaires. The prevalence of depression was rated as 5%. 15% described frequent suicidal thoughts. 40% scored as behaviourally deviant. Significant correlations were found between the variables studied. The rates of depression and behavioural deviance were higher than in comparable British populations.
Flecainide is a new drug that is effective for the treatment of ventricular arrhythmias. Optimal therapeutic response is obtained with serum levels maintained in the 200-1000 ng/ml range. To measure flecainide in this concentration range, a high-performance liquid chromatography procedure was devised using the rapid and convenient microscale protein precipitation procedure described previously by Lam et al. to prepare the specimen for chromatography. The drug in the supernatant was injected into a Nucleosil-5,C18 reversed phase column and eluted in 5 min with a mobile phase containing 300 ml of acetonitrile, 1 ml of phosphoric acid, and 0.5 ml of diethylamine in 1 L of distilled water at a flow rate of 2 ml/min. Flecainide was detected with a Perkin Elmer 650-10 LC fluorescence spectrophotometer at 370 nm upon excitation at 285 nm. It was resolved from the endogenous compounds found in serum and from the common cardiac drugs, which eluted close to the solvent front. Peak height was proportional to flecainide levels from 120 to 1200 ng/ml. A detection limit of 30 ng/ml with signal-to-noise level better than 5 is achieved. A coefficient of variance of less than 5.0% is obtained without an internal standard.
Previously we have described the isolation of seven monoclonal antibodies (MAbs) and two polyvalent rabbit sera directed against the product of herpes simplex virus type 1 (HSV-1) gene UL42, a 65K DNA-binding protein (65KDBP) which is essential for HSV DNA replication and virus growth. We now report the synthesis of all 483 overlapping hexapeptides of this 488 amino acid protein and describe their use for the identification of epitopes recognized by these MAbs and polyvalent sera. MAb 6898, derived from one fusion, recognizes the peptides EDLDGA and DLDGAA which correspond to amino acids 363 to 369 of 65KDBP. MAbs Z4D4, Z6F3, Z1A8, Z10Cl, Z3H12 and Z1F11, derived from a second fusion, all recognize the peptides GDPEDL and DPEDLD which correspond to amino acids 360 to 366. As expected both polyvalent sera recognize several different epitopes.
The problem of fasting hyperglycaemia remains unresolved on currently used twice-daily injection regimens. Human ultralente insulin is of longer duration than human lente and differs from it only in the nature of the zinc-insulin complex. In a 6-month double-blind crossover study these insulins were compared in 66 patients who were randomized to human ultralente or human lente insulin given together with human soluble insulin in a twice-daily injection regimen. Patients were seen monthly and crossed over after 3 months treatment. Fasting blood glucose concentrations on the ultralente regimen were considerably lower than on the lente regimen, the difference being statistically significant (6.6 +/- 0.5 vs 8.2 +/- 0.5 mmol l-1, p less than 0.05), but only present in those patients with fasting concentrations below the median. Glycosylated haemoglobin was identical on both regimens (9.3 +/- 0.2%). The evening ultralente dose was slightly but significantly lower than the evening lente dose (14.9 +/- 0.8 vs 15.5 +/- 0.8 U, p less than 0.05) thus endorsing the lowering effect of ultralente on the fasting blood glucose concentration. However, the incidence of serious hypoglycaemic events was higher on the ultralente regimen (0.38 +/- 0.10 vs 0.09 +/- 0.04 events per patient-month, p less than 0.02), the majority of nocturnal events occurring between 0500 h and breakfast. We conclude that ultralente insulin can give an improved fasting blood glucose concentration but that in those patients with more marked fasting hyperglycaemia or with a nocturnal hypoglycaemia problem it offers no clinical advantage over human lente insulin in a twice-daily injection regimen.
We examined like and unlike sex twinning rates in Great Britain by social class over the period 1974-85. Although twinning rates are believed to have changed over that period, we found no evidence of differential change by social class, suggesting that any factors affecting twinning are widespread in the population.
A large sample of stillbirth and infant death certificates for England and Wales from 1979-81 was analysed for the frequency of appearance of maternal and fetal conditions anywhere on the certificate, not just as the underlying cause. The results suggest there is presently no need to extend the use of the new stillbirth and neonatal death certificates, introduced in 1986, to the postneonatal period. Periodic multicause analysis of the old style death certificate should be sufficient to reveal the detail of conditions incriminated in postneonatal deaths.
Isophane (NPH) and lente insulin preparations have been the basis of insulin-injection regimens for many decades but were never formally compared. After a 2-mo run-in period, 82 patients were randomized to NPH (Protaphane) or lente (Monotard) insulin preparations given together with Actrapid as a twice-daily injection regimen in a double-blind study. Patients were seen monthly and crossed over after 5 mo of treatment. Control as assessed by glycosylated hemoglobin (NPH 9.2 +/- 0.1%, lente 9.3 +/- 0.1%, mean +/- SE) and fructosamine (1.55 +/- 0.02 and 1.57 +/- 0.02 mM) concentrations was identical for the two regimens as were home-collected laboratory-measured fasting blood glucose (BG) (NPH 8.8 +/- 0.5 mM, lente 9.0 +/- 0.5 mM) and mean BG (8.2 +/- 0.3 and 7.6 +/- 0.3 mM) concentrations. For both regimens, the major control problem was the BG concentration before and after breakfast. Total insulin dosage was similar (NPH 56.3 +/- 0.6 U/day, lente 57.2 +/- 0.6 U/day) with no tendency for a difference in the evening intermediate-acting dose (NPH 17.0 +/- 0.3 U/day, lente 17.0 +/- 0.3 U/day) to counter fasting hyperglycemia. Serum lipid concentrations and body weight confirmed the equivalence of control. Hypoglycemic events were recorded in personal diaries and graded by predetermined criteria. Self-treated, relative-assisted, and hospital/doctor-treated hypoglycemic events did not differ in frequency. We conclude that lente- and NPH-based twice-daily human insulin regimens give indistinguishable metabolic control.
These data indicate that chronic administration of CGS-12970 to renal allograft recipients maintains renal allograft function. These effects are probably due to selective inhibition of local tissue TXA2 production. These data also suggest that elevations in renal allograft tissue prostacyclin production may be secondary to ischemia since improving renal blood flow and GFR with selective thromboxane synthesis inhibitors leads to normalization of renal prostacyclin synthesis. The possible utility of using CGS-12970 as an adjunct therapy in human renal allotransplantation should be strongly considered.
Blood losses and transfusions have been analyzed prospectively for 63 lumbar fusion operations in 55 patients. The mean intraoperative loss was 550 ml, with a further 336 ml in postoperative drains. Factors increasing intraoperative loss included posterior vs. anterior approach, the use of instrumentation, multiple levels fused, male vs. female, and younger age. For anterior procedures (without instrumentation and using homograft bone) and single-level posterolateral fusions (PLF) without instrumentation, neither predeposit nor intraoperative salvage (cell saver) was required. Single-level PLF with instrumentation and two-level PLF without instrumentation required either cell saver or predeposit of one or two units. Multiple-level PLF with instrumentation and all 360 degrees procedures required cell saver and two units of predeposit. Two patients received homologous blood.
Postoperative analgesia using continuous epidural morphine or a single intrathecal injection of morphine has been compared with standard patient-controlled analgesia (PCA) in lumbar fusion patients. Pain relief with epidural morphine was dramatic in some cases (3/12) but was not predictable, and catheter displacement was a frequent occurrence. A single intrathecal bolus of morphine had no advantage over PCA alone. Complications of both intraspinal techniques included nausea and pruritus. No respiratory depression was observed.
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In a prospective randomized trial, moxalactam administered to 66 children was compared with ampicillin or chloramphenicol given to 68 children for the treatment of Haemophilus influenzae type b meningitis. Acute morbidity and mortality rates were equivalent between the two treatment groups. At 2 years after discharge, the results of psychologic tests (Bayley Scales of Infant Development or McCarthy Scales of Children's Abilities) were also equivalent between the two treatment groups for patients remaining in the study.
The purpose of this investigation was to evaluate carefully smoking-related knowledge and beliefs and their relationships to smoking status in a large, heterogeneous sample of smokers and nonsmokers in two settings: (a) a large, biracial southern city and (b) a small midwestern community. Participants were 611 (198 male, 413 female) adult respondents to a random-dialing telephone survey in Fargo, North Dakota (n = 200), and Memphis, Tennessee (n = 411). Each participant was given the Smoking Attitudes Survey, which assesses generalized health beliefs as well as health-related problems associated with smoking. Participants' knowledge of smoking-associated diseases (e.g., lung cancer) and of diseases not associated with smoking (e.g., kidney stones) was assessed. Stepwise regression analysis of composite knowledge scores revealed four independent predictors of the health consequences of smoking: education, race, smoking status, and income. Smokers, compared to nonsmokers, reported less knowledge related to the health consequences of smoking, were more likely to be male, were less concerned with the health consequences of smoking, and were more concerned about the health consequences of cholesterol. The best predictor of smokers who had never attempted cessation was their greater concern over weight control when compared to smokers with a history of smoking cessation attempts. The results are discussed in terms of smoking prevention and intervention efforts.