Shifting the paradigm for health care leadership.
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Biomedical subjects
Publications and source records attributed to K Johnson.
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The location decision for a magnetic resonance imaging (MRI) services facility is evaluated through marginal analysis. Both population-based and referral-based data are applied. The results provide input for a series of practical recommendations for MRI service providers.
Nutritional screening, an important aspect of prevention, includes measurement of height and weight, laboratory values as indicated, and a dietary assessment. For primary prevention, nutrition information should be broad enough to maintain health and prevent disease in healthy persons. Recommendations need to address problems of dietary excess as well as the possibility of nutrient inadequacy. Although controversial, the routine recommendation of a basic multivitamin and mineral supplement for healthy older adults is favored by these authors.
Disease prevention through dietary management is a cost-effective approach to promoting healthy aging. Fats, cholesterol, soluble fiber, and the trace elements copper and chromium affect the morbidity and mortality of CHD. Decreasing sodium and increasing potassium intake improves control of hypertension. Calcium and magnesium may also have a role in controlling hypertension. The antioxidant vitamins A and beta-carotene, vitamin C, vitamin E, and the trace mineral selenium may protect against types of cancer. A decrease in simple carbohydrates and an increase in soluble dietary fiber may normalize moderately elevated blood glucose levels. Deficiencies of zinc or iron diminish immune function. Adequate levels of calcium and vitamin D can help prevent senile osteoporosis in both older men and women.
Q-MED is an automated history-taking system that uses speaker-independent continuous speech as its main interface modality. Q-MED is designed to allow a patient to enter her basic symptoms by engaging in a dialog with the program. Error-recovery mechanisms help to eliminate findings resulting from misrecognitions or incorrect parses. An evaluation of the natural language parser that Q-MED uses to map user utterances to findings showed an overall semantic accuracy of 87 percent; Q-MED asks more specific questions to capture findings that were not volunteered, or that were unable to be parsed in their initial, open-ended form.
This analysis compared retrospectively the morbidity and mortality of patients with endometrial cancer who had total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH/BSO) alone or with pelvic and para-aortic lymphadenectomy performed by the same surgeon at one private institution. Between August 1987 and March 1991, 77 women with endometrial cancer were staged surgically by a standard protocol without preoperative radiotherapy. Thirty-five patients (45%) had TAH/BSO alone and 42 (55%) had TAH/BSO with pelvic and para-aortic lymphadenectomy. The median number of lymph nodes removed was 18. Patients having lymphadenectomy had an increased mean (+/- standard deviation) operative time (129 +/- 29 versus 87 +/- 26 minutes; P less than .0001), increased mean estimated blood loss (391 +/- 192 versus 272 +/- 219 mL; P = .013), and a longer postoperative hospital stay (P = .017) compared with patients having TAH/BSO alone. However, there was no difference in transfusion rate, febrile morbidity, postoperative complications, or mortality. We conclude that pelvic and para-aortic lymphadenectomy can be added to TAH/BSO in patients with endometrial cancer without a clinically significant increase in morbidity or mortality.
OBJECTIVE: To define the region on human chromosome 19 carrying the gene for malignant hyperthermia susceptibility and to evaluate the use of flanking DNA markers in diagnosing susceptibility. DESIGN: Prospective molecular genetic linkage studies in a large malignant hyperthermia pedigree. SETTING: Irish malignant hyperthermia testing centre. SUBJECTS: A large Irish malignant hyperthermia pedigree. MAIN OUTCOME MEASURES: Routine diagnosis of susceptibility to malignant hyperthermia with in vitro contracture test on muscle biopsy specimens and genetic linkage between susceptibility and polymorphic DNA markers in a malignant hyperthermia family. RESULTS: Genetic typing of polymorphic DNA markers in a large Irish malignant hyperthermia pedigree generated a lod score of greater than 3 for the marker D19S9 and showed that the gene for susceptibility is flanked by the markers D19S9 and D19S16. These tightly linked flanking markers allowed non-invasive presymptomatic diagnosis of susceptibility in five untested subjects in the large pedigree with an accuracy of greater than 99.7%. CONCLUSIONS: DNA markers flanking the gene for susceptibility to malignant hyperthermia can be used with high accuracy to diagnose susceptibility in subjects in large known malignant hyperthermia pedigrees and may replace the previous in vitro contracture test for diagnosing this inherited disorder in large families with malignant hyperthermia.
Interleukin 10 (IL-10) and viral IL-10 (v-IL-10) strongly reduced antigen-specific proliferation of human T cells and CD4+ T cell clones when monocytes were used as antigen-presenting cells. In contrast, IL-10 and v-IL-10 did not affect the proliferative responses to antigens presented by autologous Epstein-Barr virus-lymphoblastoid cell line (EBV-LCL). Inhibition of antigen-specific T cell responses was associated with downregulation of constitutive, as well as interferon gamma- or IL-4-induced, class II MHC expression on monocytes by IL-10 and v-IL-10, resulting in the reduction in antigen-presenting capacity of these cells. In contrast, IL-10 and v-IL-10 had no effect on class II major histocompatibility complex (MHC) expression on EBV-LCL. The reduced antigen-presenting capacity of monocytes correlated with a decreased capacity to mobilize intracellular Ca2+ in the responder T cell clones. The diminished antigen-presenting capacities of monocytes were not due to inhibitory effects of IL-10 and v-IL-10 on antigen processing, since the proliferative T cell responses to antigenic peptides, which did not require processing, were equally well inhibited. Furthermore, the inhibitory effects of IL-10 and v-IL-10 on antigen-specific proliferative T cell responses could not be neutralized by exogenous IL-2 or IL-4. Although IL-10 and v-IL-10 suppressed IL-1 alpha, IL-1 beta, tumor necrosis factor alpha (TNF-alpha), and IL-6 production by monocytes, it was excluded that these cytokines played a role in antigen-specific T cell proliferation, since normal antigen-specific responses were observed in the presence of neutralizing anti-IL-1, -IL-6, and -TNF-alpha mAbs. Furthermore, addition of saturating concentrations of IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha to the cultures had no effect on the reduced proliferative T cell responses in the presence of IL-10, or v-IL-10. Collectively, our data indicate that IL-10 and v-IL-10 can completely prevent antigen-specific T cell proliferation by inhibition of the antigen-presenting capacity of monocytes through downregulation of class II MHC antigens on monocytes.
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In this, the first of two articles examining the epidemiology of non-fatal trauma in Johannesburg-Soweto, we define case inclusion criteria, and discuss the methodology and materials used in this low-cost, hospital-based survey. The survey was conducted between 8 June 1989 and 24 August 1990. Sampling of both inpatient trauma cases and those seen in casualty departments took place in 6 state and 5 private hospitals located within or nearby the Johannesburg magisterial district. Demographic details about each patient, as well as information concerning spatial and temporal details of the incident, involvement of alcohol or drugs, diagnosis, severity of injury, and placement after casualty treatment, were collected by interviewing each patient. Data concerning the age, sex and racial composition of the background population were assembled from a number of sources. After discussing the internal limitations of this methodology, it is concluded that its findings may be of limited use for improving secondary interventions, but are of definite value for trauma prevention programmes.
A total of 3,535 trauma cases were enumerated in Johannesburg-Soweto between 1989 and 1990 in the course of 271 hospital ward rounds and 43 casualty watches. The overall trauma incidence was 2,886 new cases per annum per 100,000 population, rising to 19,872 for coloured males aged 20 - 24 years and to 8,761 for black males aged 20 - 24 years. Overall the male/female ratio was 2.9 rising to 6 or more in adolescence (15 - 19) for blacks and coloureds. There were some 156 new resident cases of trauma daily; half these were victims of interpersonal violence, and coloureds constituted 22% of this group, although forming only 8% of the denominator population. With regards to cause, most trauma among blacks and coloureds arose from interpersonal violence and significantly less from transport accidents. Among blacks injured in transport accidents (the majority of which involved motor vehicles) most were pedestrians, whereas most whites injured in such accidents were occupants of vehicles. For all groups trauma was most likely to be incurred 'in the street' although for white and coloured women the home was most dangerous. The implications of these and related findings for treatment and prevention and briefly reviewed.
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We recently described the use of selective transposon mutagenesis to generate a series of avirulent mutants of a pathogenic strain of Salmonella typhimurium. Cloning and sequencing of the insertion sites from two of these mutants reveals that both have identical locations within an open reading frame that is highly homologous to a gene, htrA, encoding a heat-shock protein in Escherichia coli. DNA sequence analysis of S. typhimurium htrA reveals the presence of a gene capable of encoding a protein with a calculated Mr of 49316 that has 88.7% protein:protein homology with its E. coli counterpart. In E. coli, lesions in this gene, also known as degP, reduce proteolytic degradation of aberrant periplasmic proteins. Characteristics of the S. typhimurium htrA mutants, 046 and 014, in vivo and in vitro suggested that they are avirulent because of impaired ability to survive and/or replicate in host tissues. In vitro, the S. typhimurium htrA mutants 046 and 014 are not temperature-sensitive but were found to be more susceptible to oxidative stress than the parent, suggesting that they may be less able to withstand oxidative killing within macrophages.
Leucocin A-UAL 187 is a bacteriocin produced by Leuconostoc gelidum UAL 187, a lactic acid bacterium isolated from vacuum-packaged meat. The bacteriocin was purified by ammonium sulfate or acid (pH 2.5) precipitation, hydrophobic interaction chromatography, gel filtration, and reversed-phase high-performance liquid chromatography with a yield of 58% of the original activity. Leucocin A is stable at low pH and heat resistant, and the activity of the pure form is enhanced by the addition of bovine serum albumin. It is inactivated by a range of proteolytic enzymes. The molecular weight was determined by mass spectrometry to be 3,930.3 +/- 0.4. Leucocin A-UAL 187 contains 37 amino acids with a calculated molecular weight of 3,932.3. A mixed oligonucleotide (24-mer) homologous to the sequence of the already known N terminus of the bacteriocin hybridized to a 2.9-kb HpaII fragment of a 7.6-MDa plasmid from the producer strain. The fragment was cloned into pUC118 and then subcloned into a lactococcal shuttle vector, pNZ19. DNA sequencing revealed an operon consisting of a putative upstream promoter, a downstream terminator, and two open reading frames flanked by a putative upstream promoter and a downstream terminator. The first open reading frame downstream of the promoter contains 61 amino acids and is identified as the leucocin structural gene, consisting of a 37-amino-acid bacteriocin and a 24-residue N-terminal extension. No phenotypic expression of the bacteriocin was evident in several lactic acid bacteria that were electrotransformed with pNZ19 containing the 2.9-kb cloned fragment of the leucocin A plasmid.
We report on two cases of prenatal diagnosis of myotonic dystrophy (DM), using flanking markers APOC2 or CKMM on the proximal side and D19S51 on the distal side. By double digestion (TaqI and NcoI) of PCR amplified CKMM, the informativeness was increased from a PIC value of 0.57 to 0.69. Altogether, with a PIC value of 0.64 for APOC2, 0.69 for CKMM, and 0.27 for D19S51 (BglI), presymptomatic and prenatal diagnosis can thus be offered to approximately 24% of persons with a risk between 0.0004 and 0.0008 using these flanking markers.