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V A Morrison

Publications and source records attributed to V A Morrison.

7 recordsLinked to original sources

Seven regions of the genome show evidence of linkage to type 1 diabetes in a consensus analysis of 767 multiplex families.

Type 1 diabetes (T1D) is a genetically complex disorder of glucose homeostasis that results from the autoimmune destruction of the insulin-secreting cells of the pancreas. Two previous whole-genome scans for linkage to T1D in 187 and 356 families containing affected sib pairs (ASPs) yielded apparently conflicting results, despite partial overlap in the families analyzed. However, each of these studies individually lacked power to detect loci with locus-specific disease prevalence/sib-risk ratios (lambda(s)) <1.4. In the present study, a third genome scan was performed using a new collection of 225 multiplex families with T1D, and the data from all three of these genome scans were merged and analyzed jointly. The combined sample of 831 ASPs, all with both parents genotyped, provided 90% power to detect linkage for loci with lambda(s) = 1.3 at P=7.4x10(-4). Three chromosome regions were identified that showed significant evidence of linkage (P<2.2x10(-5); LOD scores >4), 6p21 (IDDM1), 11p15 (IDDM2), 16q22-q24, and four more that showed suggestive evidence (P<7.4x10(-4), LOD scores > or =2.2), 10p11 (IDDM10), 2q31 (IDDM7, IDDM12, and IDDM13), 6q21 (IDDM15), and 1q42. Exploratory analyses, taking into account the presence of specific high-risk HLA genotypes or affected sibs' ages at disease onset, provided evidence of linkage at several additional sites, including the putative IDDM8 locus on chromosome 6q27. Our results indicate that much of the difficulty in mapping T1D susceptibility genes results from inadequate sample sizes, and the results point to the value of future international collaborations to assemble and analyze much larger data sets for linkage in complex diseases.

Adolescent

B-cell lymphoproliferative disorders in solid-organ transplant patients: detection of Epstein-Barr virus by in situ hybridization.

B-cell lymphoproliferative disorders (BLPDs) occur in approximately 2% of transplant recipients and are frequently fatal. Indirect serologic evidence has implicated Epstein-Barr virus (EBV) as an etiologic factor in these lesions. Direct evidence of the presence of EBV in these lesions has been obtained in relatively few cases. We used in situ hybridization (ISH) with a probe for the BamHI-W region of the EBV genome to study 52 tissue specimens from 28 solid-organ transplant patients who had BLPD. Epstein-Barr virus-infected lymphoid cells were identified in 26 of these 28 patients. The two patients without ISH evidence of EBV infection showed no distinctive clinical, morphologic, or serologic features. Previous filter-hybridization studies of these two patients had demonstrated evidence of EBV infection. Seven additional transplant patients without evidence of BLPD were studied as controls and showed no evidence of EBV in their lymphoid cells by ISH. These data provide further support for the etiologic role of EBV in the pathogenesis of posttransplantation lymphoproliferative disorders.

Adolescent

Corynebacterium JK: a new pathogen in ventriculostomy infections.

In the past decade, Corynebacterium JK has emerged as a pathogen in several distinct clinical settings, including sepsis in immunocompromised patients and prosthetic valve endocarditis. It is also recognized as a nosocomial pathogen in infections of prosthetic devices. We present a case of a patient with carcinomatous meningitis who developed a Corynebacterium JK infection of an internal ventriculostomy which was used for intraventricular chemotherapy. Treatment with systemic and intraventriculostomy vancomycin for three weeks resulted in bacteriologic resolution of the infection. Removal of the prosthetic device was not essential for cure in this patient. The clinical spectrum of infection with this organism and aspects of therapy are reviewed. As a greater awareness of the pathogenic nature of this organism develops, it is likely to be implicated as a causative agent in a variety of infections.

Corynebacterium Infections

Nosocomial septicemia in the cancer patient: the influence of central venous access devices, neutropenia, and type of malignancy.

Nosocomial septicemias that occurred over a 32-month period on an inpatient medical oncology service were reviewed. One hundred four episodes of septicemia occurred in 84 patients, 33% with solid tumors and 67% with leukemia or lymphoma. Sixty were primary septicemias, with the remainder being secondary. Of the 118 isolates recovered, 42% were Gram-positive organisms, 45% Gram-negative organisms, and 13% were fungi. Coagulase-negative staphylococci and Escherichia coli were the most common Gram-positive and Gram-negative isolates, respectively. The effect of the type of malignancy, neutropenic status, and presence of a central venous access device (CVAD) on the isolate(s) recovered was studied. Coagulase-negative staphylococci were more commonly isolated from leukemia-lymphoma patients (26% vs. 3%, P less than .01), while Gram-negative isolates (63% vs. 36%, P = .01), specifically Klebsiella species (21% vs. 5%, P = .02), were more common in solid tumor patients. Staphylococcus aureus was isolated more frequently from non-neutropenic patients than from those with neutropenia (19% vs. 4%, P = .02). Gram-positive isolates were more commonly found in patients with a CVAD (51% vs. 29%, P = .03), in particular coagulase-negative staphylococci (29% vs. 2%, P less than .001). In contrast, Gram-negative isolates (62% vs. 34%, especially Klebsiella species (22% vs. 3%, P less than .01) and S. aureus (18% vs. 5%, P = .07) were more commonly isolated from patients with no CVAD. Neither neutropenia nor the presence of a CVAD predisposed to early mortality. Our data suggest that empiric antimicrobial coverage for presumed nosocomial septicemia in the febrile cancer patient should include vancomycin for patients with a CVAD to cover coagulase-negative staphylococci and a cephalosporin for patients with solid tumors, especially those without a CVAD, to cover Klebsiella species.

Adolescent

Clinical manifestations of Kingella kingae infections: case report and review.

A patient with antecedent coccidioidal pulmonary cavitary disease who developed an empyema due to Kingella kingae prompted our analysis of the literature regarding this unusual bacterial pathogen. Formerly classified among other genera and considered a nonpathogen, K. kingae has been increasingly recognized as a cause of human infection. While the most commonly diagnosed infections due to this organism are endocarditis and septic arthritis, there have also been isolated reports of bacteremia, diskitis, abscesses, meningitis, and oropharyngeal infections. The treatment of choice is penicillin, to which K. kingae strains are uniformly susceptible. Recognition of the potential pathogenicity of this microorganism in appropriate clinical settings will probably result in more prompt and specific therapy.

Bacterial Infections

Cardiovascular and bacteremic manifestations of Campylobacter fetus infection: case report and review.

A case of bacteremia due to Campylobacter fetus subspecies fetus with concomitant pleuropericarditis in a previously healthy patient is presented. The organism is ubiquitous, but most commonly causes infection in patients with chronic underlying illnesses. The pathogenesis of human infection has not been definitively elucidated. Bacteremia is the most common clinical manifestation of this infection, although cases of thrombophlebitis, mycotic aneurysm, endocarditis, and pericarditis have also been reported. The treatment of choice for most infections is gentamicin, with chloramphenicol recommended for infection involving the central nervous system. Tetracyclines and erythromycin are alternative agents. Prolonged therapy is essential to the prevention of relapse. A high index of suspicion is necessary for the recognition of this organism in the appropriate clinical settings.

Campylobacter Infections