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Biomedical subjects

L McFarland

Publications and source records attributed to L McFarland.

At least 19 recordsLinked to original sources

Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus.

Alzheimer disease (AD) is a progressive neurodegenerative disorder of later life with a complex etiology and a strong genetic component. Several genomic screens have suggested that a region between chromosome 12p13 and 12q22 contains at least one additional locus underlying the susceptibility of AD. However, localization of this locus has been difficult. We performed a 5 cM microsatellite marker screen across 74 cM on chromosome 12 with 15 markers in 585 multiplex families consisting of 994 affected sibpairs and 213 other affected relative pairs. Analyses across the entire data set did not reveal significant evidence of linkage. However, suggestive linkage was observed in several subsets. In the 91 families where no affected individuals carry an ApoE varepsilon4 allele, an HLOD score of 1.55 was generated at D12S1042. We further examined the linkage data considering the proposed linkages to chromosome 9 (D9S741) and chromosome 10 (alpha-catenin gene). There was a modest (P=0.20) increase in the LOD score for D12S368 (MLOD=1.70) when using the D9S741 LOD scores as a covariate and a highly significant (P<0.001) increase in the MLOD score (4.19) for D12S1701 in autopsy-confirmed families (n=228) when using alpha-catenin LOD scores as a covariate. In both cases, families with no evidence of linkage to D9S741 or alpha-catenin demonstrated most of the evidence of linkage to chromosome 12, suggesting locus heterogeneity. Taken together, our data suggest that the 16 cM region between D12S1042 and D12S368 should be the subject of further detailed genomic efforts for the disease.

Age of Onset↗

Cerebrospinal fluid abeta42, tau, and f2-isoprostane concentrations in patients with Alzheimer disease, other dementias, and in age-matched controls.

OBJECTIVE: To test the hypothesis that quantification of cerebrospinal fluid (CSF) F(2)-isoprostanes (F(2)-IsoPs), in vivo biomarkers of free radical damage, along with CSF Abeta(42) and tau levels improves laboratory diagnostic accuracy for Alzheimer disease (AD). PARTICIPANTS: Patients with probable AD (n = 19), dementias other than AD (n = 8), and age-matched controls (n = 10). MAIN OUTCOME MEASURES: Cerebrospinal fluid concentrations of Abeta(42) and tau were determined by a commercially available test (Athena Diagnostics, Worcester, Mass). Cerebrospinal fluid F(2)-IsoP levels were quantified by gas chromatography/mass spectrometry. RESULTS: Individuals were classified as AD or non-AD by a published method using CSF Abeta(42) and tau levels (95% sensitivity, 50% specificity), by CSF F(2)-IsoP levels greater than 25 pg/mL and Abeta(42) concentrations less than 1125 pg/mL (90% sensitivity, 83% specificity), and by combined analysis using CSF F(2)-IsoP, Abeta(42), and tau levels (84% sensitivity, 89% specificity). CONCLUSION: Cerebrospinal fluid F(2)-IsoP quantification may enhance the accuracy of the laboratory diagnosis of AD.

Aged↗

Increased CSF F2-isoprostane concentration in probable AD.

OBJECTIVE: To quantify F2-isoprostane levels in CSF obtained from the lumbar cistern of patients with AD, ALS, and controls. BACKGROUND: Studies of human postmortem tissue and experimental models have suggested a role for oxidative damage in the pathogenesis of several neurodegenerative diseases, especially AD and ALS. F2-isoprostanes are exclusive products of free-radical-mediated peroxidation of arachidonic acid that have been widely used as quantitative biomarkers of lipid peroxidation in vivo in humans. Recently, we showed that F2-isoprostane concentrations are significantly elevated in CSF obtained postmortem from the lateral ventricles of patients with definite AD compared with controls. METHODS: F2-isoprostanes were quantified by gas chromatography/negative ion chemical ionization mass spectrometry. RESULTS: CSF F2-isoprostanes were increased significantly in patients with probable AD, but not in ALS patients, compared with controls. CONCLUSIONS: Increased CSF F2-isoprostanes are not an inevitable consequence of neurodegeneration and suggest that increased brain oxidative damage may occur early in the course of AD.

Aged↗

Fatal illness associated with a new hantavirus in Louisiana.

A fatal case of hantaviral illness occurred in Louisiana, outside of the range of P. maniculatus, the rodent reservoir for Sin Nombre virus. Hantavirus RNA and antigens were detected in patient autopsy tissues, and nucleotide sequence analysis of amplified polymerase chain reaction (PCR) products identified a newly recognized unique hantavirus, provisionally named Bayou virus. Prominent features of the clinical illness are compatible with hantavirus pulmonary syndrome (HPS), but several features such as renal insufficiency and intraalveolar hemorrhage are more compatible with hemorrhagic fever with renal syndrome (HFRS), a disease associated with Eurasian hantaviruses.

Antigens, Viral↗

Hurricane Andrew-related injuries and illnesses, Louisiana, 1992.

To determine the extent and types of injuries and illnesses in Louisiana associated with or related to Hurricane Andrew, we gathered data from hospital emergency departments and coroner's offices on demographic variables, institution, nature and cause of the injury or illness, body part affected, location, and date and time of the event. A hurricane-related injury or illness was defined as one that occurred from noon on August 24, 1992, through midnight on September 21, 1992, as a direct or indirect result of the preparation for (preimpact), the impact of, or the clean-up after the hurricane (postimpact). Nineteen parishes in south-central Louisiana that were most affected by Hurricane Andrew provided data from patients seen in emergency departments and reports from coroner's offices. Active, advance surveillance of this type promotes and facilitates the reporting of disaster-related health outcomes. Future planning for hurricanes should take into account the high rate of cuts, lacerations, and puncture wounds, particularly during the postimpact phase.

Adolescent↗

A mutation of Escherichia coli SecA protein that partially compensates for the absence of SecB.

The Escherichia coli SecB protein is a cytosolic chaperone protein that is required for rapid export of a subset of exported proteins. To aid in elucidation of the activities of SecB that contribute to rapid export kinetics, mutations that partially suppressed the export defect caused by the absence of SecB were selected. One of these mutations improves protein export in the absence of SecB and is the result of a duplication of SecA coding sequences, leading to the synthesis of a large, in-frame fusion protein. Unexpectedly, this mutation conferred a second phenotype. The secA mutation exacerbated the defective protein export caused by point mutations in the signal sequence of pre-maltose-binding protein. One explanation for these results is that the mutant SecA protein has sustained a duplication of its binding site(s) for exported protein precursors so that the mutant SecA is altered in its interaction with precursor molecules.

ATP-Binding Cassette Transporters↗

Clinical implications of HIV seroprevalence in childbearing women: the Louisiana experience.

An epidemiologic analysis of the HIV Seroprevalence Survey of Childbearing Women in Louisiana and the Louisiana AIDS Surveillance Report was conducted to inform health care practitioners of the trends in HIV infection and AIDS cases in women and children. HIV seropositivity in childbearing women has increased by 64% from 1988 to 1991 with an overall rate of 0.15% (202,178 tested). The rate in Orleans Parish is 0.53% (22,833 tested). Louisiana pediatric AIDS cases have increased yearly with 85% due to perinatal transmission. Assuming a 30% perinatal transmission rate, approximately 93 children are expected to develop AIDS in Louisiana within the next few years. Because of anticipated larger numbers of pediatric AIDS cases, health care providers for women and children need to identify their HIV infected patients so that early intervention can begin.

Acquired Immunodeficiency Syndrome↗

Survey of Louisiana physicians on communicable disease reporting.

We evaluated the participation of Louisiana physicians in the reporting of communicable diseases. In the spring of 1990 we surveyed a stratified random sample of Louisiana physicians from specialties likely to see patients with reportable diseases. Between 30% and 67% of physicians indicated that they reported all the cases of the queried diseases they had seen during the past year. The proportion reporting all cases differed by disease. AIDS and pertussis were always reported by more than half of the respondents. Mumps was least reported. Perceived barriers and suggestions to improve reporting are discussed.

Communicable Diseases↗

Clinical and laboratory features of an outbreak of Vibrio cholerae O1 infections in the United States.

A point source outbreak of Vibrio cholerae O1 El Tor Inaba infections occurred aboard an oil rig south of Port Arthur, Texas, in September 1981. Sixteen crew members had V. cholerae O1 infections as determined by serology or stool specimens; 15 were symptomatic. The high percentage of symptomatic infections was attributed in part to the ingestion of a large number of V. cholerae O1 organisms by susceptible individuals. Symptoms included diarrheal stools (100%), weakness (60%), abdominal cramps (53%), nausea (40%), and vomiting (27%). Only one of the three patients who sought medical attention was diagnosed by his physician as having cholera. Physicians who treat patients who live near or travel to the Gulf Coast should consider cholera in patients with watery stools. If cholera is suspected, laboratories should use thiosulfate-citrate-bile salts-sucrose (TCBS) agar in addition to routine enteric media for processing stool specimens.

Adult↗

Serological and virological evidence of a Hantaan virus-related enzootic in the United States.

The first isolation of a Hantaan-related virus from a feral rat in the United States was made from a Rattus norvegicus caught in New Orleans. The strain, designated Tchoupitoulas virus, is antigenically related to, but distinct from, the prototype strain 76-118 of Hantaan virus and is the first Hantaan-like virus isolated from the pancreas of a naturally infected animal. Serosurveys of wild rodents from urban and rural areas in the United States indicated that Hantaan-related viruses infected urban rats in coastal and inland cities and infected five species of New World rodents in the western United States (Peromyscus maniculatus, Peromyscus difficilis, Peromyscus californicus, Neotoma mexicana, and Neotoma cinerea). Serosurveys disclosed no evidence of Hantaan-virus infection in rats in large-scale breeding colonies.

Animals↗

Infections with Mycobacterium chelonei in patients receiving dialysis and using processed hemodialyzers.

Between April and November 1982, 27 of 140 patients in a hemodialysis center in Louisiana were infected with rapidly growing mycobacteria; 14 had bacteremia alone, 3 had soft-tissue infections, 1 had an access-graft infection, and 9 had widely disseminated disease. Of 26 identified isolates, 25 were Mycobacterium chelonei ssp. abscessus, and one was an M. chelonei-like organism. One factor common to all patients was exposure to processed hemodialyzers (artificial kidneys). Environmental sampling of the water-treatment system showed widespread contamination with nontuberculous mycobacteria, which were also recovered from the patient's side (blood compartment) of five of 31 hemodialyzers that had been processed and were ready for use. The formaldehyde concentration was less than 2% in two of three such contaminated dialyzers tested. We hypothesize that patients became infected when their blood circulated through processed dialyzers that contained viable rapidly growing mycobacteria. This outbreak demonstrates that hemodialysis patients may be at risk for developing infections with rapidly growing mycobacteria and that such infections may go unrecognized when routine culture methods are used. It also emphasizes the importance of using effective procedures to disinfect dialyzers in hemodialysis centers.

Adult↗

Gonococcal sensitivity to fecal lipids can be mediated by an Mtr-independent mechanism.

Various factors affect the sensitivity of Neisseria gonorrhoeae to physiological levels of hydrophobic molecules. A total of 98 N. gonorrhoeae strains from rectal, cervical, and urethral cultures of homosexual men and heterosexual men and women were examined for their sensitivities to fecal lipids. Isolates were characterized according to cell envelope phenotype, auxotype, and protein I serogroup. Although cell envelope phenotype was an important factor in the resistance of this organism to fecal lipids (Mtr phenotype greater than wild type greater than Env phenotype), other factors were also of importance. AHU- strains (strains having a requirement for arginine, hypoxanthine, and uracil) uniformly exhibited a wild-type envelope phenotype but were as sensitive to fecal lipids as were Env strains. The protein I serogroup was not a factor in determining the sensitivity of wild-type envelope phenotype non-AHU- strains to fecal lipids. However, sexual preference and site of isolation were important factors. Wild-type envelope phenotype (non-AHU-) strains from homosexual men and heterosexual women were more resistant to fecal lipids than were similar isolates from heterosexual men. When these strains were compared by isolation site, it was observed that rectal isolates from homosexual men and heterosexual women were more resistant than were cervical isolates from heterosexual women or urethral isolates from heterosexual men. Urethral isolates from homosexual men were also more resistant to fecal lipids than were urethral isolates from heterosexual men. These data suggest that the host environment can select for increased resistance to hydrophobic molecules by an Mtr-independent mechanism. The basis for this Mtr-independent resistance is presently unknown, but it is likely that it involves an alteration of the target site(s) for fecal lipid inhibition.

Arginine↗

Gonococcal strains from homosexual men have outer membranes with reduced permeability to hydrophobic molecules.

Loci designated penA, penB, and mtr contribute additively to penicillin G resistance in Neisseria gonorrhoeae; the mtr locus also confers resistance to hydrophobic dyes, detergents, and antibiotics, env mutations suppress the phenotypic expression of mtr and penB and are responsible for increased sensitivity to various hydrophobic molecules. We postulated that the host environment is important in the selection of gonococcal strains with these particular outer membrane phenotypes. Thus, mtr strains should predominate in environments that are high in hydrophobic molecules. To test this hypothesis we determined the outer membrane phenotype of 152 strains of N. gonorrhoeae. Rectal and urethral isolates from 58 homosexual men, urethral isolates from 55 heterosexual men, and cervical and rectal isolates from 39 heterosexual women were used in this study. Strains from 43 of the homosexual men were matched with those from heterosexual men with respect to auxotype and year and season of isolation. Cell envelope phenotype was determined for each strain on the basis of its resistance to various hydrophobic compounds. The identity of mtr strains was confirmed by genetic transformation. Among the matched pairs, mtr strains were significantly more prevalent among isolates from homosexual men than among those from heterosexual men (P = 0.03). Serogrouping by coagglutination demonstrated that 17 of 19 mtr strains versus 76 of 131 non-mtr strains belonged to coagglutination group WII (P = 0.01). Coagglutination group WII strains were also associated with homosexuality (P = 0.02). Gonococci were also tested for resistance to fecal lipids, mtr strains were more resistant to growth inhibition by fecal lipids than were non-mtr strains.

Bacterial Outer Membrane Proteins↗

Cholera--a possible endemic focus in the United States.

In September and October 1978, after a case of cholera had been discovered in southwestern Louisiana, 10 more Vibrio cholerae O-Group 1 infections were detected in four additional clusters. All 11 infected persons had recently eaten cooked crabs from five widely separated sites in the coastal marsh, and a matched-triplet case-control study showed a significant relation between cholera and eating such crabs (P = 0.007). V. cholerae O1 was isolated from estuarine water, from fresh shrimp, from a leftover cooked crab from a patient's refrigerator, and from sewage in six towns, including three without identified cases. All isolates in Louisiana and an isolate from a single unexplained case in Texas in 1973 were biotype El Tor and serotype inaba; they were hemolytic and of a phage type unique to the United States--suggesting that the organism persisted undetected along the Gulf Coast for at least five years.

Adolescent↗