Biomedical subjects
Publications and source records attributed to D Armstrong.
The occurrence of moyamoya disease in a child with Down's syndrome is reported. Ten previously published instances of this association are briefly reviewed, with comments on its possible significance.
The effects of 3'-azido-3'-deoxythymidine (AZT), phosphonoformate (PFA), and 2',3'-dideoxythymidine (ddT) and their combination on human immunodeficiency type 1 (HIV-1) replication were studied by measuring the HIV-1 p24 antigen expression and reverse transcriptase (RT) release in HIV-1-infected MT4 cells in vitro. RT activity was also measured in a cell-free system by using poly(rA)-oligo(dT) as the primer-template, and cell growth inhibition was measured in noninfected MT4 cells. The interactions of these two- and three-drug combinations were evaluated by the combination index (CI) method and isobologram techniques. The 50% effective concentrations (EC50s) of AZT, PFA, and ddT were 0.014 to 0.005, 9.4 to 8.8, and 8.4 to 2.5 microM, respectively, for p24 enzyme-linked immunosorbent assays (ELISAs) and 0.005 to 0.0034, 1.43 to 1.37, and 2.87 to 2.83 microM, respectively, for RT activity in vitro; for RT activity in the cell-free system, the EC50s were 0.00019 to 0.00024, 0.012 to 0.02, and 0.00074 to 0.0005 microM, for AZT-5'-triphosphate, PFA, and ddT-5'-triphosphate, respectively. AZT in combination with PFA (1:200) or ddT (1:5) as well as the combination of these three drugs (1:200:5) synergistically inhibited HIV-1 replication and RT activity in the cell-free system over a wide range of drug concentrations, with the CIs ranging from 0.5 to 0.09, in which CIs of less than 1, 1, and greater than 1 indicate synergism, additive effect, and antagonism, respectively. Three- and two-drug combinations of AZT, PFA, and ddT showed similar degrees of synergism against HIV-1 replication in p24 assays and RT release assays, whereas the combination of AZT and ddT was found to be the most selective in terms of its anti-HIV-1 effect versus cytotoxicity. Dose reduction indices calculated from both HIV-1 replication inhibition, as measured by p24 ELISA and by RT activity in the cell-free system, indicated that two- and three-drug combinations at high effect levels and the selected combination ratios allow 2- to 240-fold dose reduction over the single drug alone in terms of their anti-HIV-1 effects. The three-drug combination showed the highest dose reduction index. These finding suggest that increased efficacy and reduced toxicity may be achieved in AIDS therapy by using AZT, PFA, and ddT in two- or three-drug combinations.
Male Sprague-Dawley rats were treated with cortisone acetate and fed a low-protein diet for 3 weeks. At the end of week 2, animals were infected intratracheally with 10(5) conidia of Aspergillus fumigatus H11-20. Despite discontinuation of steroids and the low-protein diet 1 week after the infection, 94% of controls died of invasive pulmonary aspergillosis within 3 weeks postinfection. When rats were treated with a single dose of 1.6 mg of aerosolized amphotericin B per kg of body weight 48 h prior to the infection, mortality was reduced to 11% within 3 weeks postinfection. Despite apparent good health and rapid weight gain, all survivors showed multiple lesions in histopathological sections of the lungs, and 10(3) to 10(4) CFU of aspergilli was recovered from cultures of their lungs. With discontinuation of immunosuppression, the infection was slowly cleared; however, when cortisone acetate was restarted during week 5, reactivation of progressive invasive pulmonary aspergillosis was observed. On the basis of these results, we conclude that a single low dose of aerosolized amphotericin B prophylaxis is effective in preventing an exogenous aspergillus infection of the lung. Additional therapy is needed to prevent recurrent infection caused by endogenous aspergilli when immunosuppression is resumed.
Lipid peroxidation was induced with porcine retinal homogenates using ferric iron or UV light. A number of lipid and aqueous-soluble antioxidants were tested and their protective effects measured after 60 min of exposure. The iron system produced up to 5 times more lipid hydroperoxides as quantified by the fluorescence thiobarbituric acid (TBA) assay. Of the three substituted dialkyl phenols evaluated, the most efficient was compound S-17224 which was able to afford greater than 90% protection at 10(-4) M concentration in the iron-induced system. At 10(-5) M, inhibition was 78% and at 10(-6) M 33%. By comparison, 10(-4) M gamma-oryzanol inhibited the reaction by 61% and alpha-tocopherol by only 14%. The combination of 10(-6) M S-17224 and 10(-4) M gamma-oryzanol potentiated the effect by another 23%. In the light-catalyzed system. S-17224 and alpha-tocopherol were more efficient (71%). The model system described here is simple and can be employed to study additional antioxidants as well as in the retinotoxic evaluation of ophthalmic drugs.
We have established an assay to detect JC viral DNA in brain tissue and CSF of patients with progressive multifocal leukoencephalopathy (PML) and amplified a 106-base pair segment of the gene encoding JC viral large T antigen by polymerase chain reaction (PCR) from the brains of eight patients with PML and from one of six CSF samples. Brain and CSF of patients without PML did not yield JC virus-specific DNA amplification products. Southern analysis documented that the sequences of the 106-base pair PCR product and JC viral DNA are identical. This assay can be used in the diagnosis of PML and to investigate the biology of JC virus.
The design and early clinical results with uncemented porous-coated long-term stable fixation anatomic and midstem total hip systems (Implant Technology, Inc, Secaucus, NJ) are described. In an ongoing Food and Drug Administration-approved Investigational Device Exemption-Premarket Approval Program, a random selection method is used to determine patients receiving implants with a hydroxyapatite (HA) coating applied to the porous surface and those receiving uncoated implants. The early clinical results with the HA-coated systems show them to appear superior to the uncoated systems. A greater percentage of patients with HA-coated systems have clinical scores in the excellent to good range, which is primarily a reflection of less prostheses-related pain. Radiographically, all components appear well fixed, with evidence of bone ingrowth. The HA-coated systems have a decreased incidence of radiolucencies, particularly in proximal zones.
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Suicide attempters admitted to a general hospital psychiatric ward completed questionnaires to elicit information following their suicide attempt. Compared to normal controls who had never attempted suicide, suicide attempters were significantly more hopeless, depressed, and hostile. The suicide attempts seemed to occur in response to stress. A crisis intervention model was suggested as the most appropriate way of managing these patients.
AL 721, a lipid mixture with reported in vitro activity against human immunodeficiency virus (HIV) via cell membrane or virion cholesterol depletion, was evaluated in a multicenter, open-label, dose-ranging trial. Forty men with persistent generalized lymphadenopathy or AIDS-related complex were treated with doses of 20, 30, 40, or 50 g orally twice daily for 8 weeks, and monitored for toxicity, disease progression, and with immunologic, virologic, and serum lipid profiles. The compound was found to be well tolerated over the broad range of doses examined; adverse reactions were confined to the gastrointestinal tract, of mild to moderate severity, and self-limited in duration. Modest weight gains observed on treatment were reversed within 4 weeks following cessation of therapy. While disease progression was not observed in this short-term study, we could find no indication of an immunorestorative or antiviral effect of AL 721, as determined by T-lymphocyte subset quantitation or HIV culture. All three patients who were HIV p24 antigenemic at entry retained positive antigen levels throughout treatment. As a consequence of therapy, however, significant increases in serum lipids were observed, including elevations in both triglyceride and total cholesterol levels. In conclusion, our experience on the largest group of HIV-infected patients treated with the highest doses of AL 721 provides no support for the use of this compound as an antiretroviral agent.
Seven hundred and sixty patients from four general practices in an urban health centre were asked to evaluate the relative importance of 20 statements describing different aspects of general practice. Significant differences were observed between sub-groups of the patients, in particular those who would be likely to make greater use of the general practitioner--the elderly and the ill. Patients who reported not good or poor health status were more likely to value second opinions and, conversely, undervalue efficient prescribing, and an emphasis on vaccinations, cervical smears and check ups. Elderly patients placed greater emphasis on second opinions, protection in their relationship with the hospital, routine visits to the elderly and friendly staff, and similarly undervalued an emphasis on vaccinations, cervical smears and check ups. This means that practices which increase their list size to benefit from higher capacitation payments might, depending on their characteristics, attract predominantly healthy people and increase patient numbers without a commensurate increase in workload. Other facets of the payment system, in particular fees for health promotion work, further support this bias against ill patients.
OBJECTIVE: To compare the effect of directing and sharing styles of consultation by a general practitioner on patients' satisfaction with the consultation. DESIGN: Patients were randomised to receive a directing or sharing style in the part of the consultation concerned with giving treatment, advice, and prognosis. SETTING: An inner London general practice. PATIENTS: 359 Randomly selected patients consulting with one general practitioner. Four patients refused to participate and five were excluded. Thirty failed to complete the initial assessment and 110 failed to complete the assessment a week later, giving response rates of 89% and 58% respectively. MAIN OUTCOME MEASURES: Patients' satisfaction with the general practitioner's perceived understanding of their problem and the explanation they received and whether they felt that they had been helped immediately after the consultation and one week later. RESULTS: Patients who had the directing style of consultation reported significantly higher levels of satisfaction on almost all the outcome measures. This was particularly striking for patients with physical problems (excellent explanation 23/68 (34%) v 10/65 (15%), p less than 0.02; excellent understanding 25/68 (37%) v 9/66 (14%), p = 0.004), and for patients who received a prescription (excellent explanation 20/60 (33%) v 9/59 (15%), p less than 0.04; excellent understanding 27/60 (45%) v 10/59 (17%), p = 0.04). There was no significant difference in the responses to the directing and sharing styles in longer consultations (8/31 (26%) v 8/31 (26%)), in which the main treatment was advice (10/30 (33%) v 7/36 (19%)), and among patients with psychological (6/17 (35%) v 6/27 (22%)) or chronic problems (14/28 (50%) v 8/32 (25%)). CONCLUSIONS: Style of consultation does influence the satisfaction of the patient, but its effect is most noticeable in consultations with patients with physical problems and patients who receive a prescription.
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Female adult rats were as responsive as males to initiation by diethylnitrosamine (DEN) as measured by numbers of GST-P positive hepatocytes appearing early, and do develop hepatocellular cancers. However, when females and males were exposed to four promotion regimens including orotic acid (OA), choline deficiency, deoxycholic acid (DOC), or selection for resistance (to 2-acetylaminofluorene; 2-AAF) after DEN initiation, very significant sex differences were observed with respect to oval cell proliferation and growth rates of hepatocytic foci. These results suggest that responses to promotion such as growth of foci and oval cell proliferation can accompany carcinogenesis but may not be essential to the development of hepatocellular cancer.
High-flow cerebral arteriovenous fistulae are well known to present in the neonatal period with macrocephaly, cranial bruits and high-output cardiac failure. This report describes a newborn infant with such a clinical presentation, who had unilateral megalencephaly without macroscopic arteriovenous shunts. Ultrasound Doppler examination of the carotid and cerebral vessels showed diastolic flow, or a decreased pulsatility index, consistent with decreased intracranial vascular resistance. The ipsilateral cerebral arteries and veins were markedly enlarged at angiography and at post-mortem examination, but there was no arteriovenous malformation. The infant expired from high-output cardiac failure and hypoglycemia. It is postulated that the high-output cardiac failure was due to increased blood flow through the enlarged, dysplastic cerebral hemisphere.
Diurnal variations in the pattern of esophageal motility and acidity were studied in 14 healthy volunteers. Data from a two-channel manometry and one-channel pH-metry recording were stored in a portable 1-MByte, solid-state data logger for subsequent computerised analysis. Comparison of predefined nighttime, mealtime and nonmeal daytime periods showed that propagated contractions predominated during mealtimes (56% of all contractions) and nonmeal daytime periods (53.5% of contractions) and that their propagation velocity (2.98 cm/sec) was at its lowest and the AUC of all contractions (134.6 hectoPascal.sec) at its greatest during mealtime periods. During the night, propagated contractions (0.136/min) and simultaneous contractions (0.025/min) were significantly less frequent than during both meal (1.31/min and 0.172/min, respectively) and nonmeal daytimes (0.665/min and 0.133/min, respectively), whereas the nocturnal segmental contraction frequency (0.181/min) was not significantly lower than the nonmeal daytime contraction frequency (0.243/min). Median reflux time was in the normal range (1.2%), although two subjects had prolonged reflux times (9.5% and 14.5%). In conclusion, all subjects showed similar patterns of diurnal esophageal contractory activity determined partly by meal intake and partly by a characteristic clustering of nocturnal contractions that could not be explained by episodes of nocturnal gastroesophageal reflux. It may, therefore, be speculated that nocturnal contraction clusters are associated with rhythmic phenomena such as MMC or specific sleep stages.