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Biomedical subjects

M McCarthy

Publications and source records attributed to M McCarthy.

At least 271 records · Page 15Linked to original sources

Diagnostic value for culture of cerebrospinal fluid from HIV-1-infected individuals for opportunistic viruses: a prospective study.

OBJECTIVE: To investigate the diagnostic value of cerebrospinal fluid (CSF) culture for opportunistic viruses from HIV-1-infected individuals. METHODS: A 4-year prospective study was conducted using a participant population consisting of 186 HIV-1-infected individuals without neurologic disease, 73 HIV-1-infected individuals with encephalopathy, myelopathy, and/or peripheral neuropathy, and 10 controls. CSF samples recovered at 1-year intervals were subjected to virus culture using technique commonly used in the clinical laboratory setting. RESULTS: CSF samples obtained from only 15 of the 269 (5.6%) participants yielded an opportunistic virus upon culture. Cytomegalovirus, herpes simplex virus types 1 and 2, adenovirus, and presumptive enteroviruses were identified. No consistent correlation was observed between the detection of an opportunistic virus within a CSF sample and the presence or future development of neurologic disease. However, a significant correlation was observed between culture of virus from CSF and the future development of abnormal CD4+ (chi 2, P = 0.0286) and CD8+ (chi 2, P = 0.0018) lymphocyte counts in HIV-1-infected participants without neurologic disease. CONCLUSION: These results show that culture of CSF to screen for opportunistic viruses is neither diagnostic nor predictive of neurologic disease in HIV-1-infected individuals. Nevertheless, the presence of virus within CSF may be an indicator of HIV-1-mediated immune dysfunction and a predictor for future development of abnormal CD4+ and/or CD8+ lymphocyte counts.

AIDS-Related Opportunistic Infections↗

A comparison of two measures of quality of life: their sensitivity and validity for patients with advanced cancer.

We compared two measures that have been used by professionals to assess the quality of life and care of patients with advanced cancer. The Support Team Assessment Schedule (STAS) is an instrument for palliative cancer support teams to record and evaluate their care; the Hebrew Rehabilitation Centre for the Aged Quality of Life (HRCA-QL) index was used in the National Hospice Study (USA) to assess patients with advanced cancer. STAS has 17 items, each scaled 0 (best) to 4 (worst), and HRCA-QL has five items scaled 0 (worst) to 2 (best). The STAS and the HRCA-QL were assessed contemporaneously by the members of one support team on 128 consecutive patients referred over 17 months. Seventy-four patients spent more than four weeks in care. Ratings for four out of five HRCA-QL items deteriorated significantly in the four to six weeks before death. HRCA-QL index items correlated with similar STAS items. Correlations were highest at referral, especially in patients seen more than four weeks before death (e.g. symptom control (STAS) with health (HRCA-QL) Spearman's rho = -0.64) and the HRCA-QL total was correlated with STAS subtotal of six items (rho = -0.45). There were few correlations at death. The findings support the validity of both measures for the aspects compared, but indicated that STAS was more sensitive to changes in patients in the last six weeks of life.

Humans↗

Chromosome 4q locus associated with insulin resistance in Pima Indians. Studies in three European NIDDM populations.

Markers on chromosome 4q have recently been shown to be associated with insulin resistance in Pima Indians, a population in which insulin resistance precedes and predicts the development of non-insulin-dependent diabetes mellitus (NIDDM). To examine whether genes in this region could play a major role in susceptibility to NIDDM in other populations, we have examined the allele frequencies of a trinucleotide repeat near the fatty acid-binding protein 2 (FABP2) gene on 4q28-31 in three European populations: Finnish, U.K. Caucasian, and Welsh. The U.K. NIDDM population was selected for insulin resistance by studying patients whose obesity-corrected fasting plasma insulin before treatment was above the 98th percentile. Seven alleles were detected. On cross-tabulation analysis, there were no significant associations between allele frequencies and glucose intolerance in any of the populations. Log-linear analysis of the results from all three populations suggested a moderately significant interaction of glucose tolerance status (normal versus diabetic) and the FABP2 allele (partial chi 2 = 24, df 6, P = 0.027). The parameter describing the interaction of allele A3 and glucose tolerance status was the only such parameter differing significantly from zero (z-score +2.003, P = 0.046). In both the Finnish and U.K. population, the A3 allele was found approximately twice as frequently in NIDDM than in control subjects (Finnish control subjects, impaired glucose tolerance, and NIDDM: 12.2, 22.4, and 26.6%, respectively; U.K. control subjects and NIDDM: 7.8 and 14.6%, respectively). In the Finnish populations, no associations were found between FABP2 alleles and plasma insulin levels or with homeostatic model assessment (HOMA) estimates of beta-cell function and insulin sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Stuttering induced by theophylline.

We retrospectively evaluated three fluent asthmatic children who developed speech dysfluency following administration of theophylline. The dysfluency ceased in all three, following discontinuation of the medication. The medication was re-instituted in two patients, prompting return of dysfluency. It is unknown whether the patients had characteristics of "acquired stuttering" or "developmental stuttering." We urge appropriate testing should this complication again occur. This might then provide pharmacologic information regarding stuttering.

Asthma↗

Arthropod-borne viral infections associated with a fever outbreak in the northern province of Sudan.

An outbreak of acute febrile illness occurred during August and September 1989 in the Northern Province of Sudan coinciding with a high population density of phlebotomine sandflies. An investigation was conducted to determine whether arboviruses were associated with human illness during this outbreak. Sera were obtained from 185 febrile individuals and tested for IgG and IgM antibody to selected arboviruses by enzyme immunoassay (EIA). The prevalence of IgG antibody was 59% for West Nile (WN), 53% for Sandfly Fever Sicilian (SFS), 32% for Sandfly Fever Naples (SFN), 39% for Yellow Fever (YF), 24% for dengue-2 (DEN-2), 23% for Rift Valley Fever (RVF), 12% for Chikungunya (CHIK) and 5% for Crimean-Congo haemorrhagic Fever (CCHF) viruses. Antibody prevalences tended to increase with age for WN and YF viruses. Antibody rates were about the same for males and females for most of the viruses tested. The prevalence of IgM antibody to SFN was 24% and reciprocal IgM titre exceeded 12,800 for some individuals suggesting that this virus was the cause of recent infection. The prevalence of IgM antibody for the other viruses did not exceed 5%. The study indicated that several arboviruses were endemic and some of them may have caused human disease in the Northern Province of Sudan.

Acute Disease↗

Panstromal Schnyder corneal dystrophy. A clinical pathologic report with quantitative analysis of corneal lipid composition.

BACKGROUND: The pathogenesis of Schnyder dystrophy is thought to be a primary abnormality of corneal lipid metabolism resulting in opacification secondary to lipid accumulation. Histochemical investigations have suggested the accumulated lipid includes unesterified cholesterol; however, quantitative analysis has not been done. METHODS: Quantitative biochemical analysis was performed on a corneal button obtained from a patient with clinically and pathologically proven Schnyder dystrophy. Results were compared with four age-, sex-, and size-matched corneal buttons obtained from cadaveric eyes. RESULTS: Corneal lipid accumulated in Schnyder dystrophy predominantly is composed of phospholipid, free cholesterol, and cholesterol ester. These constituents were markedly elevated in the Schnyder cornea when compared with cadaveric control corneas as follows: (1) phospholipid, 23.6 versus 4.05 mg/g; (2) unesterified cholesterol, 6.99 versus 0.52 mg/g; and (3) cholesterol ester, 3.16 versus 0.26 mg/g. CONCLUSION: Phospholipid, unesterified cholesterol and cholesterol ester are the predominant lipids in Schnyder dystrophy. The pathogenesis may be a primary disorder of corneal lipid metabolism.

Chromatography, Gas↗

A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy.

Twenty-six patients, whose B-cell lymphoma had relapsed after conventional therapies, were treated in a phase I dose escalation study with an immunotoxin consisting of a mouse CD22 monoclonal antibody (RFB4:IgG1K) coupled to chemically deglycosylated ricin A chain (dgA). Two to 12 doses of the immunotoxin were infused intravenously at 48-hour intervals. The peak serum concentration and half-life (T1/2) did not correlate directly with the dose and averaged 3.8 micrograms/mL and 7.8 hours, respectively. The main dose-limiting toxicity was caused by the vascular leak syndrome (VLS) consisting of weight gain, edema, serum albumin decrease, and critically by pulmonary edema. Myalgia occurred frequently and was only dose limiting in one patient who developed rhabdomyolysis. The presence of lymphoma cells in the blood (> or = 10(10)/L) and clinically detectable splenomegaly were associated with reduced toxicity and a shorter T1/2. Nine of 24 evaluable patients (37.5%) made antibody to either mouse Ig or dgA. There were five partial responses (PR) and one complete response (CR) lasting 30 to 78 days. High peak concentrations of immunotoxin in the serum, a long T1/2, and large areas under the curve (AUC) correlated with both clinical response and toxicity. None of three patients with CD5+ lymphomas (including two CLL patients) had more than mild toxicity or responded to the immunotoxin.

Adult↗

Funding policies for HIV and AIDS: time for change.

Funding for HIV and AIDS in England has been allocated to regions by a formula based on the number of cases of AIDS and HIV infection and on population size. Regions have distributed the resources directly to hospitals and community services. A survey of staff and managers in North East Thames region showed that funding arrangements have led to unsatisfactory development of services for HIV and AIDS. Firstly, because hospitals are funded according to current numbers of patients services are highly developed at the central London hospitals and underdeveloped in outer districts. Secondly, specialised community care teams have been established rather than integrating care for HIV and AIDS into generic primary care. Thirdly, the information on district of residence of infected patients is inaccurate, limiting allocation of funds according to population needs. Fourthly, prevention of infection has been given far less attention than treatment and care despite the lack of effective treatment. In future allocations for HIV and AIDS should be made to purchasers rather than directly to providers.

Acquired Immunodeficiency Syndrome↗

Derivatives of 4-amino-3,6-disulfonato-1,8-naphthalimide inhibit reverse transcriptase and suppress human and feline immunodeficiency virus expression in cultured cells.

We have developed a series of 4-amino-3,6-disulfonato-1,8-naphthalimide (ADSN) derivatives in an attempt to create nontoxic compounds effective against lentivirus infections. The ADSN derivative Lucifer Yellow CH ([N-(hydra zinocarbonyl)amino]-4-amino-3,6-disulfonato-1,8-naphthalimid e) (LYCH) was chosen as a parent compound because of its low toxicity in vivo and in vitro and its tendency to accumulate in monocyte/macrophages, a major reservoir for lentiviruses in vivo. Several ADSN derivatives inhibited reverse transcriptases (RTs) from human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV). Viral expression in HIV-infected human peripheral blood mononuclear cells was inhibited by noncytotoxic concentrations of two ADSN derivatives, designated A4 (biphenyl-4,4'-dicarboxaldehyde, Lucifer Yellow CH monohydrazone; EC50 = 29 microM after 6 days) and H4 (biphenyl-4,4'-dicarboxaldehyde, Lucifer Yellow CH dihydrazone; EC50 = 5.61 microM). A4 effectively suppressed the expression of FIV in infected Crandall feline kidney fibroblasts (CRFK) at 46.2 microM, reducing the RT levels by 97% after 19 days under conditions allowing direct cell-to-cell transmission of the virus. The viability of drug-treated FIV-infected CRFK cells increased significantly in the presence of A4 relative to the viability of untreated virus-infected cells. In contrast to A4 and H4, LYCH (which lacks the appended aromatic rings characteristic of A4 and H4) had no inhibitory effects on either virus and did not inhibit RT ex vivo. However, flow cytometry studies showed that both A4 and LYCH accumulate in two cell types that can support lentiviral infections: U937 human monocytic leukemic cells that have been induced to differentiate by using tetradecanoyl phorbol acetate, and CRFK cells.

1-Naphthylamine↗

"Auditory neglect after right frontal lobe and right pulvinar thalamic lesions": comments on Hugdahl, Wester, and Asbjørnsen (1991) and some preliminary findings.

We take issue with the claim recently made in this journal that extinction of left ear input during dichotic, but not monaural, stimulus presentation demonstrates "auditory attentional neglect" (Hugdahl, Wester, & Asbjørnsen, 1991). We also report on a patient suffering from unilateral visual neglect, who shows extinction under dichotic, but not monaural, conditions of stimulus presentation but this is not confined to one ear. Although this patient denies hearing both of two dichotically presented words, he recognizes the extinguished stimulus when given a forced-choice recognition task.

Aged↗