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Biomedical subjects

M R Wallace

Publications and source records attributed to M R Wallace.

At least 73 records · Page 4Linked to original sources
PubMed1997

Identification of mutations in two major mRNA isoforms of the Chediak-Higashi syndrome gene in human and mouse.

Chediak-Higashi syndrome is an autosomal recessive, immune deficiency disorder of human (CHS) and mouse (beige, bg) that is characterized by abnormal intracellular protein transport to, and from, the lysosome. Recent reports have described the identification of homologous genes that are mutated in human CHS and bg mice. Here we report the sequences of two major mRNA isoforms of the CHS gene in human and mouse. These isoforms differ both in size and in sequence at the 3' end of their coding domains, with the smaller isoform (approximately 5.8 kb) arising from incomplete splicing and reading through an intron. These mRNAs also differ in tissue distribution of transcription and in predicted biological properties. Novel mutations were identified within the region of the coding domain common to both isoforms in three CHS patients: C-->T transitions that generated stop codons (R50X and Q1029X) were found in two patients, and a novel frameshift mutation (deletion of nucleotides 3073 and 3074 of the coding domain) was found in a third. Northern blots of lymphoblastoid mRNA from CHS patients revealed loss of the largest transcript (approximately 13.5 kb) in two of seven CHS patients, while the small mRNA was undiminished in abundance. These results suggest that the small isoform alone cannot complement Chediak-Higashi syndrome.

Alternative Splicing↗
PubMed1997

Neurocognitive impairment in human immunodeficiency virus infection is correlated with sexually transmitted disease history.

BACKGROUND AND OBJECTIVES: Neurocognitive impairment is common in human immunodeficiency virus (HIV)-infected subjects. The relationship of sexually transmitted diseases to neurocognitive changes is unknown. GOAL: To establish whether HIV-infected patients with a history of syphilis or gonorrhea have a higher rate of neurocognitive dysfunction. STUDY DESIGN: Neurocognitive function was measured by a battery of quantitative tests in a 453-person HIV-infected cohort and a 219-person HIV-seronegative control group. Neurocognitive function was then correlated with histories of either syphilis or gonorrhea to assess for possible relationships between these sexually transmitted diseases and neurologic impairment. RESULTS: Human immunodeficiency virus-infected subjects with a history of either syphilis or gonorrhea tended to perform worse on neurocognitive testing than their counterparts. This difference could not be explained by educational attainment, age, race or CD4 cell count, and was not noted in the HIV-uninfected control subjects. CONCLUSIONS: Sexually transmitted diseases in HIV-infected subjects are correlated with neurocognitive impairment through an unidentified mechanism.

Adult↗
PubMed1997

Four frameshift mutations in neurofibromatosis type 1 caused by small insertions.

We have been using heteroduplex analysis to assay individual exons within the NF1 gene in an effort to identify disease causing constitutional mutations in neurofibromatosis type 1 patients. Here we report the identification and characterisation of four insertional NF1 frameshift mutations in an analysis of exons 28-39 in a set of 78 patients. These include three 1 base pair insertions and one 2 base pair insertion. Three of these mutations can be attributed to replication slippage errors, while the mechanism behind the fourth may be related to formation of secondary structure during replication. It may be of significance that a majority of the previously reported small insertions in NF1 also lie within exons 28-39.

Adult↗
PubMed1997

Cutaneous aspergillosis.

The authors present a patient with advanced acquired immunodeficiency syndrome who developed a cutaneous lesion under the transparent dressing of a venous catheter. Histologic examination of the lesion revealed suppurative granulomatous inflammation in the dermis with numerous branching hyphae within the follicular infundibulum. A culture of the biopsy material grew Aspergillus fumigatus. Aspergillus must be considered in the differential diagnosis of cutaneous lesions in patients infected with the human immunodeficiency virus, especially when the lesion occurs under an occlusive dressing.

AIDS-Related Opportunistic Infections↗
PubMed1996

Early clinical markers and CD4 percentage in subjects with human immunodeficiency virus infection.

In a clinical trial involving asymptomatic, HIV-seropositive subjects treated with either the HIV-1 immunogen (an inactivated, gp120-depleted HIV-1 virus in incomplete Freund's adjuvant) or an adjuvant control, we examined the relationship between changes in the percentage of CD4 cells over time and early clinical markers of HIV disease progression. Subjects who had an early clinical event were more likely to have a greater decline in the percentage of CD4 cells than those subjects who did not have a clinical event (p = 0.054). The greatest decline in CD4 percentage occurred within 10 weeks prior to a clinical event (mean 11% decrease from baseline). Subjects from the quartile with the greatest decline in CD4 percentage had a fivefold greater risk of having a clinical event than subjects from the quartile with the second largest decline (p = 0.045). These results demonstrate a relationship between changes in the percentage of CD4 cells and early clinical events. Further validation of this association may be useful in clinical monitoring and in evaluating therapies to treat HIV infection.

AIDS Dementia Complex↗
PubMed1996

Malaria among United States troops in Somalia.

PURPOSE: United States military personnel deployed to Somalia were at risk for malaria, including chloroquine-resistant Plasmodium falciparum malaria. This report details laboratory, clinical, preventive, and therapeutic aspects of malaria in this cohort. PATIENTS AND METHODS: The study took place in US military field hospitals in Somalia, with US troops deployed to Somalia between December 1992 and May 1993. Centralized clinical care and country-wide disease surveillance facilitated standardized laboratory diagnosis, clinical records, epidemiologic studies, and assessment of chemoprophylactic efficacy. RESULTS: Forty-eight cases of malaria occurred among US troops while in Somalia; 41 of these cases were P falciparum. Risk factors associated with malaria included: noncompliance with recommended chemoprophylaxis (odds ratio [OR] 2.4); failure to use bed nets (OR 2.6); and failure to keep sleeves rolled down (OR 2.2). Some patients developed malaria in spite of mefloquine (n = 8) or doxycycline (n = 5) levels of compatible with chemoprophylactic compliance. Five mefloquine failures had both serum levels > or = 650 ng/mL and metabolite:mefloquine ratios over 2, indicating chemoprophylactic failure. All cases were successfully treated, including 1 patient who developed cerebral malaria. CONCLUSIONS: P falciparum malaria attack rates were substantial in the first several weeks of Operation Restore Hope. While most cases occurred because of noncompliance with personal protective measures or chemoprophylaxis, both mefloquine and doxycycline chemoprophylactic failures occurred. Military or civilian travelers to East Africa must be scrupulous in their attention to both chemoprophylaxis and personal protection measures.

Anti-Bacterial Agents↗
PubMed1996

Treatment of adult varicella with sorivudine: a randomized, placebo-controlled trial.

The antiviral and clinical efficacy of sorivudine in adults with varicella was evaluated in a double-blind, placebo-controlled randomized trial. A total of 186 patients were hospitalized for isolation and treatment within 96 h of rash onset. The diagnosis of varicella was confirmed in 184 patients with paired sera. Patients were randomly assigned to receive 10 or 40 mg of sorivudine or an identical placebo once a day for 5 days. Treatment with 40 mg of sorivudine (compared with placebo) shortened the mean time to 100% crusting from 6.6 to 5.8 days (P = .004) and reduced the mean days that new lesion formed from 3.9 to 3.1 (P = .014). Mean days of cutaneous viral shedding were reduced from 3.3 in the placebo group to 2.6 in the 40-mg sorivudine group (P = .002). The effectiveness of therapy was not affected by the duration of rash before initiation of therapy. Sorivudine is a promising new agent for the treatment of varicella-zoster virus infections.

Administration, Oral↗
PubMed1996

Nitric oxide and angiotensin II regulation of renal hemodynamics in the developing piglet.

UNLABELLED: We have previously shown that nitric oxide (NO) is a more important intrarenal vasodilator in the developing animal compared with the adult. The interaction between NO and the renin angiotensin system in the developing kidney is not known. The purpose of this study was to determine the role of NO and angiotensin II in the regulation of developing renal function. We examined the effects of the inhibition of intrarenal NO synthesis with N-nitro-L-arginine methyl ester (L-NAME), 3 micro g/kg/min, intrarenally, administered after intrarenal infusion of either saline or an angiotensin II AT1 receptor antagonist [ATX (A-81988), 0.4 micro g/kg/min] in piglets, age 3 wk, and adult pigs. The developing piglet demonstrated significantly greater renal responses to L-NAME alone. Intrarenal NO synthesis inhibition after saline preinfusion decreased renal blood flow (RBF) in the piglet 29% compared with the adult pig 9%, but only in the piglet decreased GFR 31%, and increased plasma renin activity 57%. Intrarenal infusion of ATX significantly increased RBF in the piglet, 23%, although not altering RBF in the adult. The renal responses to L-NAME were significantly attenuated by ATX preinfusion in both age groups. After ATX pretreatment, L-NAME in piglets decreased RBF 14%, and abolished the change in GFR, whereas in adult pigs decreased RBF only 5%. IN CONCLUSION: 1) angiotensin II may be a more important vasoconstrictor in the developing kidney and 2) NO is a more important regulator of renal function in the developing kidney through modulation of the renin angiotensin system.

Angiotensin II↗
PubMed1996

Neurological Symptoms, Not Signs, Are Common in Early HIV Infection.

UNLABELLED: Objective. To examine the cross-sectional prevalence of neurological symptoms and signs in a large cohort of human immunodeficiency virus (HIV)-seropositive men, and determine the relationship of the symptoms to disease stage, immunologic markers, and independent variables from neuropsychological (NP) testing and psychiatric interview. METHODS: One hundred-nine controls and 386 HIV-infected volunteers enrolled in the HIV Neurobehavioral Research Center (HNRC) longitudinal study. The majority, without acquired immune deficiency syndrome (AIDS), were screened for alcohol/substance abuse; previous diagnosis of HIV-associated dementia; and HIV-unrelated developmental, neurological, medical, and neurobehavioral conditions which potentially impair cognition; and underwent a structured neurological interview and examination, standardized NP testing, and psychiatric interview as part of a more extensive battery. A large subset (N = 377) underwent lumbar puncture for cerebrospinal fluid (CFS) examination. We examined the relationship of sixteen select but independent variables, using stepwise multiple regressions, from demographic/staging, immunological, NP, and psychiatric domains to neurological symptoms in an effort to identify possible predictors of subclinical nervous systems involvement. Results. All categories of neurological symptoms were significantly more prevalent among medically asymptomatic (CDC stage A) subjects than controls, with a further rise in prevalence in those with more advanced stages of infection. The most marked rise was seen in cognitive and sensorimotor complaints. In contrast, significant findings on neurological examination were evident in only the sicker (stage C) subjects. Stage of illness, serum β2-microglobulin, psychiatric indices of depressed mood or anxiety, and NP "motor" performance were the most significant independent variables associated with the presence of neurological symptoms. CSF pleocytosis was seen early (CDC stage A), and may reflect the presence of HIV in the central nervous system (CNS) at the least stages of infection. We also confirmed the value of CSF β2m and neopterin as important markers of advancing disease stage. Whether they predict subclinical CNS involvement is to be determined by longitudinal observations. Conclusion. Neurological complains are common in medically asymptomatic HIV subjects whereas signs are not. The symptoms correlate with commonly determined independent measures of depression, anxiety, NP tests of fine motor speed and strength, as well as indices of disease worsening (CDC stage, serum β2m).

AIDS Dementia Complex↗
PubMed1996

Somatic mosaicism in a patient with neurofibromatosis type 1.

Using loss of heterozygosity analysis, a method designed to detect moderate to large gene deletions, we have identified a new-mutation neurofibromatosis type 1 (NF1) patient who is somatically mosaic for a large maternally derived deletion in the NF1 gene region. The deletion extends at least from exon 4 near the 5' end of the gene to intron 39 near the 3' end. The gene-coding region is, therefore, mostly or entirely deleted, encompassing a loss of > or = 100 kb. We hypothesize that the deletion occurred at a relatively early developmental timepoint, since signs of NF1 in this patient are not confined to a specific body region, as seen in "segmental" NF, and since both mesodermally and ectodermally derived cells are affected. This report provides the first molecular evidence of somatic mosaicism in NF1 and, taken together with a recent report of germ-line mosaicism in NF1, adds credence to the concept that mosaicism plays an important role in phenotypic and genetic aspects of NF1 and may even be a relatively common phenomenon.

Adult↗
PubMed1995

Sequential emergence of multi-resistant Klebsiella pneumoniae in Bahrain.

During the mid-1980s, nosocomial infections due to aminoglycoside-resistant Klebsiella pneumonia were prevalent in the intensive care unit (ICU) of the Salamanya Medical Centre, Bahrain. In an attempt to control the spread of such organisms, the third-generation cephalosporins were introduced in early 1987. Subsequently there was a marked increase in the incidence of cephalosporin resistance among Klebsiella spp. isolated in the ICU. In 1990, over 60% of Klebsiella isolates were resistant to both cephalosporins and aminoglycosides. Cephalosporin resistance was due to production of extended-spectrum beta-lactamases encoded on the same plasmid as aminoglycoside resistance. The incidence of cephalosporin resistance declined during 1991-1992, which was coincident with severe restrictions on the use of third-generation cephalosporins and the preferential use of ciprofloxacin and imipenem for nosocomial klebsiella infections. Sequential overuse of aminoglycosides and cephalosporins for nosocomial klebsiella infection may select for organisms resistant to both classes of antibiotics.

Aminoglycosides↗
PubMed1995

Syphilis and neurosyphilis in a human immunodeficiency virus type-1 seropositive population: evidence for frequent serologic relapse after therapy.

OBJECTIVE: To describe clinical and treatment aspects of syphilis infection among patients seropositive for the human immunodeficiency virus (HIV). PATIENTS AND METHODS: Results of serologic tests for syphilis, CD4+ T-lymphocyte counts, and clinical response to therapy were retrospectively monitored in 100 HIV-infected adults with syphilis from a tertiary-care military HIV program. RESULTS: Of the 1,206 HIV-infected patients, 100 (8.3%) in the cohort had syphilis; 61 patients were treated for active syphilis. Serologic or clinical relapse eventually occurred in 10 of the 56 treated patients (17.9%) with follow-up available; 7 of the 10 who relapsed had previously received high-dose intravenous or procaine penicillin therapy. Relapse occurred more than 12 months after initial therapy in 6 of 10 patients (60%) who experienced relapse; 5 patients experienced multiple relapses. The mean CD4+ T-lymphocyte count was not predictive of relapse. Patients with reactive cerebrospinal fluid (CSF) Venereal Disease Research Laboratory (VDRL) test titers (4 of 7 patients [57%]) or the rash of secondary syphilis (4 of 14 patients [29%]) were at highest risk of subsequent relapse or treatment failure when monitored for an average of 2 years. CONCLUSION: Standard penicillin regimens, including high-dose intravenous penicillin, transiently lowered serum VDRL titers in nearly all cases, but were sometimes inadequate in preventing serologic and clinical relapse in patients infected with HIV type-1, especially among those with secondary syphilis and reactive CSF VDRL titers. Careful long-term follow-up is essential, and repeated courses of therapy may be needed for patients infected with HIV type-1 who have syphilis.

AIDS-Related Opportunistic Infections↗