In vitro methods and selection of HLA-matched unrelated donors for bone marrow transplantation.
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Biomedical subjects
Publications and source records attributed to J Bridge.
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HLA 'matched' unrelated donor bone marrow transplantation (BMT) is associated with an increased incidence and severity of acute graft-versus-host disease (GVHD) in comparison with HLA-identical sibling transplants. Using a limiting dilution analysis system for quantitating frequencies of alloreactive cytotoxic T lymphocyte precursors (CTL-p), we previously demonstrated a correlation between CTL-p frequency and HLA disparity between responder and stimulator, and between CTL-p frequency and the incidence of acute GVHD following HLA A, B, DR matched unrelated donor BMT. In this study we assayed CTL-p frequencies in two HLA 'matched' unrelated donor/patient pairs, with single HLA antigenic mismatches detected by allogenotyping or isoelectric focusing but not by HLA serology, and demonstrated that the CTL-ps were specifically directed at the mismatched antigen. Both class I and class II antigens were detected. These data, and our previous work, suggest that high CTL-p frequencies in HLA 'matched' unrelated pairs are indicative of HLA antigenic variants undetected by serology but recognized by molecular typing, and that these are responsible for the value of the assay in predicting acute GVHD after BMT. We propose that this assay system be used in aiding final donor selection before unrelated or mismatched related donor BMT.
We performed a retrospective review of an outbreak of Salmonella gastroenteritis that occurred in a community nursing home in 1987. Forty-four of 199 residents had a diarrheal illness; Salmonella heidelberg was isolated from the stool in 19 cases. Although the distribution of cases suggested a common source for the outbreak, no common source of infection could be demonstrated, despite extensive investigation. The clinical presentation of symptomatic individuals ranged from mild diarrhea to a severe gastrointestinal illness, and 26% of symptomatic, culture-positive patients required hospitalization. The median duration of pathogen excretion during convalescence in untreated residents was six weeks, but six patients who were treated with antibiotics shed S. heidelberg for a median duration of 14.5 weeks. We conclude that (1) the clinical spectrum of Salmonella gastroenteritis in nursing-home patients is variable, ranging from mild to severe illness; and (2) nursing-home Salmonella outbreaks impose a high economic burden because of expense of epidemiologic investigation, prolonged isolation measures, hospitalization for severely ill residents, and potential institutional closure.
Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly frequent in both acute care facilities (ACFs) and skilled nursing facilities (SNFs). Admissions to SNFs from ACFs with endemic MRSA are one likely source of infection in SNFs. The occurrence of MRSA in SNFs and the relative roles of ACFs and SNFs in MRSA transmission have not been well characterized. We conducted an epidemiologic investigation in an SNF reporting a high incidence of MRSA cases and found that the prevalence of MRSA exceeded that reported in acute care settings. Fifteen (9.1%) of the 164 residents were colonized or infected with MRSA. Risk factors for MRSA identified through a prevalence case-control study were nasogastric intubation (odds ratio = 5.5; 95% confidence interval = 1.2, 26.4), antibiotic therapy (OR = 3.9; CI = 1.2, 13.0), and hospitalization in an acute care facility within the previous six months (OR = 2.9; CI = 0.9, 9.7). During a three-month period, 6 of 100 new admissions were MRSA-positive; all positive patients were from ACFs. Five new cases also emerged from previously MRSA-negative residents. SNF residents are often discharged to ACFs. Transmission of MRSA within the SNF and the transfer of patients to ACFs increases the reservoir of potentially infective patients and the potential for MRSA infections in ACFs. Modest control measures, including targeted surveillance culturing and cohorting of colonized residents, may minimize MRSA transmission in the SNF and decrease the reservoir of MRSA in the community.
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Two or more cytogenetic studies of lymph node biopsy specimens from 12 patients with non-Hodgkin's malignant lymphoma were performed. Each of the 12 patients had at least one clonal structural chromosome abnormality in their initial biopsy specimen. A comparison of the chromosome abnormalities in the initial lymph node biopsy specimens with those in subsequent biopsy specimens was made. Structural and numerical chromosome changes were not always accompanied by a change in the histologic type of the lymphoma. Similarly, a change in histologic type was not always associated with the appearance of new structural or numerical abnormalities. Serial cytogenetic studies from additional patients will further our understanding relevant to which chromosome changes are associated with lymphomagenesis and which are secondary or more of an evolutionary nature.
A newborn female was found to have a deletion of the terminal portion of 17q. Prominent manifestations included microcephaly, apparent hypertelorism, epicanthic folds, a broad nasal bridge with anteverted nostrils, posteriorly angulated ears, micrognathia, widely spaced nipples, arachnodactyly with proximal thumbs, and a coxa vara deformity. The unbalanced translocation was inherited from the mother, who had a reciprocal translocation involving the terminal portions of 2p and 17q. To the best of our knowledge, this is the first report of a liveborn infant with deletion of the distal portion of 17q with the exception of reports of patients with ring chromosome 17.
A male propositus and an older sister had a similar pattern of congenital anomalies, including facial asymmetry with hypertelorism, frontal bossing and temporal narrowness, a broad nasal bridge, epicanthal folds, a wide mouth with a thin upper lip, micrognathia, webbed neck, low-set posteriorly angulated ears, and an abnormal hairline. There was also postaxial polydactyly, flexion contractures of the digits, hypotonia, and a congenital heart anomaly. The propositus also had renal anomalies whereas the sister did not, and the sister had a cleft lip and palate not present in her brother. The propositus and a subsequent fetus identified through genetic amniocentesis were determined to have a 46, XY, -18, +der(18),t(17;18)(q25.1;q23)mat chromosome constitution. Clinical findings are compared to those of other reported cases of dup(17q).
Since the therapeutic management of an empyema is significantly different from that for a subphrenic abscess it is important to define the location of the diaphragm in relation to an abscess cavity. A patient is presented who underwent unnecessary laparotomy due to misinterpretation of the clinical and radiographic findings.
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The existence of a tilted binocular disparity space was experimentally established. The results of the experiment showed that a texture surface which under binocular viewing appears to be oriented vertically and perpendicular to the line of sight in fact is tilted such that the portions of the texture surface above and below fixation incline toward and away from the observer, respectively. Under monocular viewing such a discrepancy between apparent and objective vertical tilt is not observed. This suggests that under binocular viewing the cortical representations of the upper and lower visual hemifields are biased toward uncrossed and crossed disparities, respectively. The tilted binocular disparity space is explained in terms of an experientially induced disparity gradient effected during development of the binocular system.
Multiple metastatic melanoma lesions from three patients were cytogenetically characterized in order to assess the degree of intra-patient karyotypic heterogeneity. A total of 20 specimens were analysed: 12 samples from patient No. 1, five samples from patient No. 2, and three samples from patient No. 3. Sufficient mitoses were obtained to perform detailed analysis in 19/20 specimens following short-term culture. The modal chromosome number of all three cases was near-diploid, with all samples demonstrating multiple structural abnormalities. Abnormalities shared by all three patients were alterations of chromosomes 1 and 8. Other structural abnormalities common to two of the three patients involved chromosomes 6, 7, 9 and 10. Minor intra-tumour karyotypic variation was detected in all three cases. However, the majority of clonal alterations were retained in all metastatic lesions, clearly indicating the karyotypically stable and clonal nature of this neoplasm.
This article characterizes the academic, administrative, clinical service, and fiscal characteristics of departments of psychiatry in traditional children's hospitals to determine the characteristics of fiscally successful programs. A survey of chairs of psychiatry from short-term general children's hospitals was conducted based on 38 questions addressing the descriptive characteristics of their respective departments. The characteristics of psychiatry programs identified as fiscally successful were compared to those of programs that required subsidy. Nine of 45 eligible children's hospitals (20%) did not have a department or section of psychiatry, and surveys were returned by 35 of 36 department chairs (97% response). Considerable variation exists in the academic, administrative, clinical services, and fiscal characteristics of programs, although over half are operating at a deficit. Fiscal success was associated with availability of inpatient and intermediate levels of psychiatric care, better integration of the psychiatry program within the children's hospital, and adequate fiscal information being provided to the psychiatry chair. Additional research regarding the potential of psychiatric services to generate clinical success and cost savings is warranted. Pediatric health care professionals and third-party payers should be educated regarding the relevance of psychiatric services within children's hospitals and in physically ill children.