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Biomedical subjects

D Dunn

Publications and source records attributed to D Dunn.

At least 109 records · Page 6Linked to original sources

[Simultaneous removal of liver and pancreas does not have an effect on results of transplantation of these organs].

In a retrospective clinical study we compared the outcome after pancreas and liver transplantation when both organs were retrieved from the same donor to the outcome when only one or the other organ was retrieved. The results in this article demonstrate that simultaneous procurement of liver and pancreas grafts has no detrimental effect on the rate of technical failures, or allograft or patient survival after either pancreas or liver transplantation.

Adult↗

Tissue plasminogen activator: hospital experience.

Tissue plasminogen activator (t-PA) is administered safely and efficiently in the treatment of acute myocardial infarction (MI). A study of 74 patients administered t-PA for acute MI associated with a low complication rate showed an acceptable patency rate, and a good outcome.

Adult↗

HIV-2 infection among prostitutes working in The Gambia: association with serological evidence of genital ulcer diseases and with generalized lymphadenopathy.

Three hundred and fifty-five prostitutes working in The Gambia were enrolled in a study of retroviral infections. Eight-seven (24.6%) were infected with HIV-2 only, two (0.6%) with HIV-1 only, four (1.1%) had sera showing double HIV-1/HIV-2 reactivity, and 37 (10.4%) were seropositive for HTLV-I. After allowing for socioeconomic and serological variables in a multivariate analysis, HIV-2 infection was associated with serological evidence of a previous episode of syphilis [a rapid plasma reagin (RPR) positive/Treponema pallidum haemagglutination assay (TPHA) positive; odds ratio (OR) = 2.18, 95% confidence interval (CI) = 1.19-3.98], with having antibodies against Haemophilus ducreyi (OR = 2.05, 95% CI = 0.89-4.70) or against HTLV-I (OR = 2.17, 95% CI = 0.91-5.19). HIV-2-seropositive prostitutes were three times more likely [17 out of 78 (22%) versus 15 out of 219 (7%), P less than 0.001] to have generalized lymphadenopathy than those who were seronegative. These data suggest that genital ulcer diseases may facilitate the transmission of HIV-2, and that HIV-2 rapidly induces the appearance of generalized lymphadenopathy in a substantial proportion of infected individuals.

AIDS-Related Complex↗

The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae.

Sequencing of the neurofibromatosis gene (NF1) revealed a striking similarity among NF1, yeast IRA proteins, and mammalian GAP (GTPase-activating protein). Using both genetic and biochemical assays, we demonstrate that this homology domain of the NF1 protein interacts with ras proteins. First, expression of this NF1 domain suppressed the heat shock-sensitive phenotype of yeast ira1 and ira2 mutants. Second, this NF1 domain, after purification as a glutathione S-transferase (GST) fusion protein, strongly stimulated the GTPase activity of yeast RAS2 and human H-ras proteins. The GST-NF1 protein, however, did not stimulate the GTPase activity of oncogenic mutant ras proteins, H-rasVal-12 and yeast RAS2Val-19 mutants, or a yeast RAS2 effector mutant. These results establish that this NF1 domain has ras GAP activity similar to that found with IRA2 protein and mammalian GAP, and therefore may also regulate ras function in vivo.

Cloning, Molecular↗

The neurofibromatosis type 1 gene encodes a protein related to GAP.

cDNA walking and sequencing have extended the open reading frame for the neurofibromatosis type 1 gene (NF1). The new sequence now predicts 2485 amino acids of the NF1 peptide. A 360 residue region of the new peptide shows significant similarity to the known catalytic domains of both human and bovine GAP (GTPase activating protein). A much broader region, centered around this same 360 amino acid sequence, is strikingly similar to the yeast IRA1 product, which has a similar amino acid sequence and functional homology to mammalian GAP. This evidence suggests that NF1 encodes a cytoplasmic GAP-like protein that may be involved in the control of cell growth by interacting with proteins such as the RAS gene product. Mapping of the cDNA clones has confirmed that NF1 spans a t(1;17) translocation mutation and that three active genes lie within an intron of NF1, but in opposite orientation.

Amino Acid Sequence↗

A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations.

Overlapping cDNA clones from the translocation breakpoint region (TBR) gene, recently discovered at the neurofibromatosis type 1 locus and found to be interrupted by deletions and a t(17;22) translocation, have been sequenced. A 4 kb sequence of the transcript of the TBR gene has been compared with sequences of genomic DNA, identifying a number of small exons. Identification of splice junctions and a large open reading frame indicates that the gene is oriented with its 5' end toward the centromere, in opposition to the three known active genes in the region. PCR amplification of a subset of the exons, followed by electrophoresis of denatured product on native gels, identified six variant conformers specific to NF1 patients, indicating base pair changes in the gene. Sequencing revealed that one mutant allele contains a T----C transition changing a leucine to a proline; another NF1 allele harbors a C----T transition changing an arginine to a stop codon. These results establish the TBR gene as the NF1 gene and provide a description of a major segment of the gene.

Amino Acid Sequence↗

Treatment of experimental Salmonella typhimurium infection in mice with lomefloxacin.

To evaluate the difluorinated quinolone lomefloxacin in murine typhoid, mice were inoculated intraperitoneally with the LT-2 strain of Salmonella typhimurium and treated with graded doses of the drug given once daily by an orogastric needle. Treatment with lomefloxacin for seven days reduced mortality with a 50% effective dose of 2.5-7.8 mg/kg/day. When given once daily for three days, doses greater than or equal to 5 mg lomefloxacin/kg/day caused significant reductions in splenic counts of S. typhimurium and prevented the inflammatory response to infection in the spleen.

4-Quinolones↗

Refinement and expansion of the Harvard Resource-Based Relative Value Scale: the second phase.

The Harvard resource-based relative value scale (RBRVS) for physician services has assumed a critical role in physician payment reform. We have demonstrated that the relative resource costs of providing physician services can be defined and measured in a rational and systematic way and that the results are reliable and valid. Consequently, the RBRVS is a viable basis for national payment policy and could be used for establishing a national fee schedule for physician services or to identify "mispriced" physician procedures. Since the release of the final report of the first phase of the Harvard RBRVS study in September of 1988, there has been extensive review, discussion, and criticism of the RBRVS. Dr. Laurence F. McMahon, Jr., in the accompanying article, provides a further critique of our research. In this paper, we review the RBRVS study and results and respond to the major criticisms that have been raised by Dr. McMahon and others. We then describe the tasks we are currently undertaking to expand and validate our research and address the important criticisms and limitations.

Data Interpretation, Statistical↗

Evaluation of patient, physician, nurse, and family attitudes toward do not resuscitate orders.

We investigated attitudes toward resuscitation by interviewing 97 competent patients classified as do not resuscitate, 60 physicians, 80 family members, and 84 nurses. In addition, 58 family members of incompetent do not resuscitate patients were interviewed. Interview patients were generally elderly, female widows with a diagnosis of malignancy. The majority (66%) preferred that their medical decision making be shared with the physician and/or family. Only 38 patients (39%) could correctly define a "living will." After hearing the definition, 59 patients (61%) thought it was a good idea to ask noncritically ill patients at the time of hospital admission, if they had a living will. Fifty-six patients (58%) said they had discussed resuscitation with their physician, whereas 44 physicians (73%) said they had discussed it with the patient. Only 53 patients (55%) said that they thought their physician understood their wishes. Sixty-five patients (67%) wanted involvement in resuscitation decisions. Forty-eight patients (49%) offered "quality of life" reasons for not wanting to be resuscitated. Sixty-four patients (66%) did not think discussing resuscitation was cruel and insensitive. Eighteen physicians (30%) said they were uncomfortable discussing resuscitation with patients. We recommend introducing the topic of resuscitation early in the patient-physician relationship before diminished competency occurs.

Adult↗

Micropenis and congenital adrenal hypoplasia.

Micropenis is often an early sign of congenital hypopituitarism. It has also been associated with congenital adrenal hypoplasia in infants with anencephaly and pituitary agenesis. This report is on two infants with micropenis and congenital adrenal hypoplasia. One presented with a similar clinical course and postmortem findings to previously reported cases of adrenal hypoplasia and pituitary agenesis. The other patient represents the first reported case of an infant with micropenis and congenital adrenal hypoplasia in the absence of pituitary agenesis. The histologic patterns of adrenal hypoplasia, as well as the etiologic and clinical implications of its association with micropenis, are discussed.

Adrenal Glands↗

Causes of death and the histopathologic findings in fatal shigellosis.

Thirty-seven children (median age, 2 years) with shigellosis in Bangladesh were subjected to postmortem examination to determine causes of death and the spectrum of intestinal histopathology. Infecting species were: Shigella dysenteriae 1, 7 cases; S. dysenteriae 2, 2 cases; Shigella flexneri, 23 cases; Shigella boydii, 4 cases; and mixed infection with Shigella boydii and Shigella sonnei, 1 case. Complicating conditions detected before death included malnutrition in 25 cases, pneumonia in 11 cases and septicemia in 8 cases. In all 37 cases the colon showed gross colitis, consisting of mucosal erythema and edema; superficial ulcerations were visible in 15 cases. Microscopically in the colon the lamina propria showed inflammatory cellular infiltration in 27 cases and crypt abscesses were present in 22 cases. In 9 cases each there were colonic glands in the submucosa and branching of colonic crypts, indicating increased regenerative activity of crypt cells. Severe lesions were mucosal denudation and deep ulceration in 15 cases with a pseudomembrane in 7 and pseudopolyposis in 2 of these patients. The most common underlying cause of death was colitis, whereas the most common immediate and associated causes were, respectively, septicemia and pneumonia. These results indicated that fatal childhood shigellosis results from severe colitis, often complicated by septicemia and concomitant malnutrition and pneumonia.

Bangladesh↗

Hazard from weapons impulses: histological and electrophysiological evidence.

Current methods of rating the hazard of weapons impulses for the ear have recently been challenged by electrophysiological data from experiments with animal ears which indicate that the hazard from low-frequency impulses is much lower than the hazard from higher frequency impulses (Dancer et al., 1981; Price, 1986b). To supplement these data, histological data are reported here for 51 cats that were exposed on one occasion to either rifle or howitzer impulses at peak pressures from 145 to 155 dB or 153 to 166 dB, respectively. Histological procedures (scanning electron and light microscopy) were carried out over 2 months after the exposure and after electrophysiological measures had been made. For both types of impulse the losses tended to be in the middle of the cochlea in focused lesions, even though the spectral peaks of the acoustic stimuli had been at about 80 Hz (howitzer) and 1000 Hz (rifle). Outer hair cells were more susceptible than the inner hair cells and interindividual differences in effects were large. Furthermore, the two impulse sources were equally hazardous when the peak pressure of the rifle impulse was lower than the peak pressure of the howitzer impulse by about 9 dB. In terms of A-weighted energy, the exposures were equally hazardous when the rifle exposure contained about 35 times less energy than the howitzer exposure. The histological data are thus consistent with the electrophysiological data, which indicate that present standards for impulse noise exposure may overrate the hazard of low-frequency impulses relative to impulses in the midrange.

Animals↗

Results of pediatric kidney transplantation at the University of Minnesota.

In all, 473 renal transplants were performed at the University of Minnesota in 386 children 1-17 years old between August 14, 1963 and December 31, 1988. Standard immunosuppressive protocols, pretransplant blood transfusions, and discontinuation of routine splenectomy have led to improving graft and patient survival rates. Children receiving living-related donor kidneys had better graft and patient survival rates, compared to cadaver kidneys. Graft and patient survival rates were better in children who received primary grafts, compared to retransplants. Children who received DST plus conventional immunosuppression had poorer graft survival, compared to quadruple immunosuppression during the same era. Recently, 1-year graft survival rates with quadruple immunosuppression are equal for children receiving primary, living-related donor or cadaver kidneys. Graft and patient survival rates in children 1-4 years old are identical to those in children 5-17 years old. Age no longer appears to be a risk factor for children undergoing kidney transplantation. Good patient and graft survival rates can be achieved at centers specializing in kidney transplantation for small children. Currently, transplantation is the treatment of choice for all children who are candidates for renal replacement therapy.

Adolescent↗

Evaluation of the do not resuscitate orders at a community hospital.

Demographic, medical, and outcome characteristics for 821 do not resuscitate (DNR) patients were compared with 300 age- and sex-matched control patients, and with 230 patients for whom cardiopulmonary resuscitation had been performed. Do not resuscitate patients were more likely to be female and older than cardiopulmonary resuscitation patients and to have a child as next of kin. Although DNR patients in intensive care units had comparable illness levels before and at the time of the order, treatment levels were reduced when the order was written. In general, DNR patients received more nursing care than other patients. Hospital mortality was 59.8% for DNR, 83.9% for CPR, and 1.7% for control patients. We identified diagnosis, prior activity, hospital unit, and employment status as predictors of DNR. According to documentation, 20% of patients participated in the DNR decision. Introduction of a DNR progress note form significantly improved documentation of the DNR process, but further efforts to improve DNR practice and patient participation are recommended.

Adult↗