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Biomedical subjects

C Johnson

Publications and source records attributed to C Johnson.

At least 199 records · Page 11Linked to original sources

Comparison of preoperative selective spinal angiography and somatosensory-evoked potential monitoring with temporary occlusion of segmental vessels during anterior spinal surgery.

STUDY DESIGN: The results of preoperative selective spinal angiography were compared with intraoperative occlusion of segmental arteries and somatosensory-evoked potential monitoring during anterior spinal surgery. OBJECTIVES: To determine if temporary occlusion of major radicular vessels supplying the spinal cord would result in intraoperative somatosensory-evoked potential changes. SUMMARY OF BACKGROUND DATA: Temporary occlusion of segmental spinal arteries with concomitant somato-sensory-evoked potential monitoring has been used during anterior spinal surgery to avoid intraoperative vascular paraplegias caused by permanent ligations of vessels critical to the blood supply of the spinal cord. METHODS: Preoperative selective spinal angiography was performed in 16 patients to identify important radicular arteries supplying the spinal cord. At the time of anterior spinal surgery, temporary occlusion of segmental vessels was accomplished with somatosensory-evoked potential monitoring. RESULTS: Thirty-two radicular arteries were identified by arteriography in 16 patients. Temporary occlusion of nine segmental arteries in the surgical field supplying these radicular vessels resulted in no somatosensory-evoked potential changes. CONCLUSIONS: The lack of somatosensory-evoked potential changes after temporary occlusion of segmental arteries from which radicular arteries supply the spinal cord demonstrates sufficient perimedullary collateral circulation in that area of the spinal cord.

Adolescent↗

Alternative splicing and differential expression of DT-diaphorase transcripts in human colon tumors and in peripheral mononuclear cells in response to mitomycin C treatment.

The two-electron bioreductive enzyme DT-diaphorase catalyzes the metabolism of quinones. The existence of several distinct sizes of DT-diaphorase mRNA transcripts has been observed in human tissues. One of these, an alternatively spliced mRNA that lacks exon 4, has been recently found to be expressed at levels comparable to those of the full-length mRNA. The protein encoded by the mRNA lacking exon 4 has minimal catalytic activity, consistent with the elimination of the quinone-binding site coded for by this exon. We have pursued a number of approaches to examine the significance of this splice variant. We identified a similar truncated transcript in a human HepG2 cDNA library. To determine the frequency of expression of this form of DT-diaphorase in the general population, we examined mRNA obtained from the peripheral mononuclear cells of 16 patients and found substantial interindividual variability in the patterns of transcript expression. Following treatment of these 16 patients with 20 mg/m2 mitomycin C (MMC), the induction of DT-diaphorase transcripts was demonstrated. In most patients, expression of the variant transcript (lacking exon 4) remained constant, while that of the full-length mRNA was elevated. The extent of induction also showed interindividual variability. In one patient, while both transcripts were present at baseline, expression of the variant transcript disappeared almost completely after MMC treatment. To analyze these events under more controlled conditions, we examined the effects of MMC treatment on two human colon tumor cell lines. MMC treatment induced expression of the full-length mRNA but did not influence the abundance of the variant transcript. We then performed single-strand conformational polymorphism analysis of genomic DNA from the 16 patients to investigate the potential role of cis-acting factors in the variable splicing responses. Two patients demonstrated sequence differences in the region spanning exon 4, but in neither was the change in a region critical to splicing regulation. These data demonstrate that the expression of DT-diaphorase in hyman cells is polymorphic, and that the levels of individual transcripts can be regulated by exogenous factors. The findings support a role for alternative splicing in the control of DT-diaphorase gene expression.

Alternative Splicing↗

Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia.

The monoclonal antibody LRP56 recognizes a 110-kD major vault protein (lung-resistance protein [LRP]) overexpressed in several P-glycoprotein-negative (Pgp-), multidrug resistant tumor cell lines. To determine the frequency of LRP overexpression, its prognostic significance, and its relation to Pgp, we analyzed bone marrow specimens from 87 consecutive patients with acute leukemia. Diagnoses included de novo acute myeloid leukemia (AML; 21 patients), leukemia arising from an antecedent hematologic disorder or prior cytotoxic therapy (secondary AML; 27 patients), AML in relapse (29 patients), and blast phase of chronic myeloid leukemia (CML-BP; 10 patients). A granular cytoplasmic staining pattern was detected by immunocytochemistry in 32 (37%) cases, including 7 (33%) de novo AML, 13 (48%) secondary AML, 11 (38%) relapsed AML, and 1 of 10 CML-BP. Among 66 evaluable patients with AML, LRP overexpression was associated with an inferior response to induction chemotherapy (P = .0017). Remissions were achieved in 35% of LRP+ patients as compared with 68% of LRP- patients. Although Pgp adversely affected response in univariate analysis (P = .0414), only LRP had independent prognostic significance when compared in a logistic regression model (P = .0046). Differences in remission duration (P = .075) and overall survival (P = .058) approached significance only for LRP. Sequential specimens from remitting patients receiving treatment with the Pgp modulator cyclosporin-A showed emergence of the LRP phenotype despite a decrease or loss of Pgp at the time of treatment failure (P =.0304). Significant associations were observed between LRP and age greater than 55 years (P = .017), Pgp (P = .040), and prior treatment with mitoxantrone (P = .020) but not with CD34. These findings indicate that overexpression of the novel transporter protein LRP is an important predictor of treatment outcome in AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Two pairs of male monozygotic twins discordant for Wiedemann-Beckwith syndrome.

Wiedemann-Beckwith syndrome (WBS) is a congenital anomaly syndrome which classically consists of exomphalos, macroglossia, and gigantism. The syndrome is also associated with a variety of minor anomalies and affected individuals have an increased risk of developing rare embryonal cell tumors. To date, 15 monozygotic (MZ) twin pairs have been reported of which 13 are discordant for WBS. All except one pair of the discordant WBS twin pairs have been female. We report two pairs of male MZ twins, each discordant for WBS.

Adult↗

3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents.

A series of substituted phenethyl derivatives of 3-benzisothiazolylpiperazine incorporating potent D2 and 5-HT2A antagonist activity was investigated as an approach to a novel atypical antipsychotic agent. The in vitro profile of 8e from this series is a combination of D2 receptor affinity comparable to the typical antipsychotic agent haloperidol and a 5-HT2A/D2 ratio comparable to the atypical agent clozapine. In vivo 8e possesses activity consistent with an efficacious antipsychotic agent with less tendency to induce extrapyramidal side effects in man.

Amphetamine↗

Traditional risk factors and ischemic stroke in young adults: the Baltimore-Washington Cooperative Young Stroke Study.

OBJECTIVE: To determine the association of hypertension, diabetes, and cigarette smoking with incidence of ischemic stroke in young adults. DESIGN: Case-control study. SETTING: Population-based sample of cases and controls. SUBJECTS: The study included 296 cases of incident ischemic stroke among black and white adults aged 18 to 44 years in central Maryland counties from the Baltimore-Washington Cooperative Young Stroke Study and 1220 black and white adults aged 18 to 44 years from the Maryland Behavioral Risk Factor Survey, a telephone survey of a random sample of the same region, to serve as controls. MAIN OUTCOME MEASURES: Logistic regression models were developed to determine the age-adjusted odds ratios for each risk factor. Population-attributable risk percent were computed based on the odds ratios and prevalence of each risk factor. RESULTS: The age-adjusted odds ratios (95% confidence intervals) for white men (WM), white women (WW), black men (BM), and black women (BW) were as follows: current cigarette smoking: WM, 2.0 (1.1-3.8), WW, 2.1 (1.1-4.3), BM, 3.3 (1.6-6.6), and BW, 2.2 (1.3-3.9); history of diabetes mellitus: WM, 22.9 (5.8-89.6), WW, 6.2 (1.9-20.2), BM, 4.2 (0.8-21.9), and BW, 3.3 (1.4-7.7); and history of hypertension: WM, 1.6 (0.7-3.2), WW, 2.5 (1.1-5.9), BM, 3.8 (1.8-7.9), and BW, 4.2 (2.4-7.5). The population-attributable risk percent (95% confidence intervals) were as follows: current cigarette smoking: WM, 22.6 (3.1-38.2), WW, 17.2 (4.0-34.0), BM, 40.5 (23.1-54.0), and BW, 29.1 (13.5-41.9); history of diabetes mellitus: WM, 19.0 (8.2-28.5), WW, 15.8 (3.8-26.3), BM, 13.2 (5.3-20.4), and BW, 22.1 (12.5-30.7); and history of hypertension: WM, 21.7 (6.2-34.6), WW, 21.3 (5.4-34.5), BM, 53.5 (39.0-64.4), and BW, 50.5 (37.1-61.1). CONCLUSIONS: Hypertension, diabetes mellitus, and current cigarette smoking are important risk factors in a biracial young adult population. Cigarette smoking and hypertension, the 2 most modifiable risk factors, were particularly important risk factors in young blacks.

Adolescent↗

Parents and peer group as mediators of the effect of community structure on adolescent problem behavior.

Used a sample of 207 single-parent families residing in 104 small, Midwestern communities to test hypotheses regarding the link between community context and adolescent conduct problems and psychological distress. For boys, community disadvantage had a direct affect on psychological distress, while it indirectly boosted the probability of conduct problems by disrupting parenting and increasing affiliation with deviant peers. Community disadvantage was unrelated to the deviant behavior or emotional well-being of girls. Proportion of single-parent households in the community had a direct effect on girls' conduct problems. It also contributed indirectly to girls' conduct problems by increasing the probability of involvement with deviant peers. Possible explanations for these gender differences are provided.

Adolescent↗

Telling patients about the diagnosis of HIV infection.

This study used a questionnaire to examine how patients in the HIV/AIDS Clinic at a Department of Veterans Affairs hospital were told of their diagnosis, by whom, and to what degree they were given emotional and educational support. Nearly 17% of patients were informed by someone not in the health professions (often military personnel), and 27% of patients were notified in a nonprivate setting. Forty-seven percent indicated they received little or no educational support at the time of diagnosis, while 39% received little or no emotional support. Educational and emotional support for patients at the time of HIV diagnosis may be lacking.

Adult↗

Are residents' work schedules related to their in-training examination scores?

OBJECTIVE: To study the relationship between residents' pre-test available study time and subsequent examination performance. METHODS: We compiled rotation schedules and in-training examination performances for all residents enrolled in the two University of Texas Medical School-Houston obstetrics and gynecology residencies between 1993 and 1995. Services on which the residents had rotated were ranked by surveying all enrolled residents as to their perceived available study time while on those services. A mean available study time rating was computed for each service, which was used to describe each resident's schedule. Pearson correlations between available preparation-time preceding the in-training examination and examination performance were calculated. "Tough" and "easy" rotation subgroups were defined; two-tailed t tests were performed to compare the in-training examination performance of these subgroups. RESULTS: No significant correlation was found between available study time and subsequent examination scores beyond that which could be accounted for by year of training. Scores of residents in the "tough" subgroup were not significantly different from those in the "easy" subgroup on any examination performance measure. For correlations at the one-tailed .05 level, statistical power to detect relationships predicting 16% of variance ranges from approximately 85% for samples of 42 to 68% for samples of 27. CONCLUSION: Residents' in-training examination performance was not significantly affected by their service obligations. Altering resident monthly schedules is not likely to improve in-training examination performance.

Educational Measurement↗

Lumpectomy and radiation treatment for invasive lobular carcinoma of the breast.

BACKGROUND: Large studies have shown a similar outcome when comparing mastectomy with lumpectomy and external beam radiation therapy in the treatment of infiltrating ductal carcinoma. However, this has not been studied extensively for invasive lobular carcinoma. We studied the pattern of recurrence and overall survival of patients treated with lumpectomy and radiation for either invasive lobular carcinoma (ILC) or combined invasive lobular carcinoma/invasive ductal carcinoma (ILC/IDC) of the breast. DESIGN: A retrospective chart review was performed for 111 patients with ILC or ILC/IDC who were diagnosed and/or treated at the university hospital between 1984 and 1994. RESULTS: Of the 111 patients, 93 had stage I or II tumors. Thirty-four patients (37%) were treated with lumpectomy and adjuvant postoperative radiotherapy with one (3%) local recurrence and a mean overall survival of 83.6 months. Fifty-nine patients (63%) were treated by modified radical mastectomy with two local recurrences (3%) and a mean overall survival of 71.7 months. CONCLUSIONS: Patients with ILC or ILC/IDC can be effectively treated with lumpectomy and radiation for stage I and II tumors while maintaining a low risk of local recurrence and equivalent overall survival.

Adult↗

An immunocytochemical study of H+ ATPase in kidney transplant rejection.

Kidney transplant rejection may be accompanied by defective urinary acidification. Its pathogenesis is unknown. There are shared histologic features between kidney transplant rejection and the distal renal tubular acidosis (RTA) of Sjogren syndrome, which led us to hypothesize that deficient collecting duct H+ adenosine triphosphatase (ATPase) expression--which is lacking in the RTA of Sjogren syndrome - may cause the RTA of kidney transplant rejection. Six kidney transplant recipients with biopsy evidence for rejection and two control subjects were studied physiologically and by immunohistochemistry. We found defective urinary acidification in all 6 kidney transplant patients. Ammonium excretion was diminished in relation to the degree of azotemia. There was an abnormal response to furosemide in all 6, suggesting distal tubular dysfunction. Distal H+ ATPase staining was reduced in relation to the degree of azotemia, although it was not totally absent even in the worst case. This was paralleled by the urinary PCO2 response. Both control subjects had good urine PCO2 and H+ ATPase staining and adequate urine pH response to furosemide. They had reduced urinary ammonium (NH4) concentrations in relation to modest azotemia. We conclude that kidney transplant rejection may be accompanied by defective urinary acidification, which is not primarily due to a lack of H+ ATPase. The RTA of kidney transplant rejection appears to result from defective ammonium excretion, generalized distal tubular malfunction, and--in severe cases--from a reduction in distal nephron H+ ATPase expression.

Acidosis, Renal Tubular↗

Trends in cigarette smoking among children in a southern community, 1976-1994: the Bogalusa Heart Study.

Cigarette smoking among adolescents continues to be a major public health problem in the United States. Smoking trends from 1976-1977 to 1992-1994 were examined in the Bogalusa Heart Study, an investigation of cardiovascular disease risk factors among black and white, male and female adolescents in a semirural town in the southern United States. Age-race-sex specific chi 2 tests for trends over five survey periods were conducted. In almost every age group, black boys and girls were less likely to be current smokers or to have ever smoked or tried cigarettes, as compared with white boys and girls, respectively (P < 0.01). Within age groups, few significant trends in smoking status from 1976-1977 through 1992-1994 were observed among white boys and girls. Among black males and females, however, sharp decreases were observed among all age groups in the prevalence of having ever smoked or tried cigarettes (P = 0.0001) and among the older age groups in the prevalence of being a current smoker (P = 0.0001). Thus, substantial declines in the prevalence of smoking were observed among black children but not among white children. Further research is required to understand why these ethnic differences in smoking occurred so that public health programs may target further the smoking behaviors in children.

Adolescent↗

Oral immunization of mice against candidiasis.

Oral immunization with live Candida albicans evoked antibody- and cell-mediated immune responses in gnotobiotic C.B-17 and BALB/c mice. No deaths or systemic candidiasis of endogenous origin were evident in these C. albicans-colonized (pure culture) mice. Histologic examination showed minimal to no infection of the stomach, esophagus, or tongue by C. albicans. Not only were orally immunized mice more resistant to systemic candidiasis (intravenous challenge) than were germfree (nonimmunized) controls, but immunity could be transferred to susceptible mice with immune spleen cells. Oral immunization elicited a Th1-type response in spleen cells and a Th2 response in Peyer's patch lymphocytes. The alimentary tracts of these orally immunized mice remained chronically colonized with C. albicans in spite of the presence of both antibody- and cell-mediated immune responses to C. albicans.

Administration, Oral↗

Immunoprophylaxis against klebsiella and pseudomonas aeruginosa infections. The Federal Hyperimmune Immunoglobulin Trial Study Group.

To determine if passive immunization could decrease the incidence or severity of Klebsiella and Pseudomonas aeruginosa infections, patients admitted to intensive care units of 16 Department of Veterans Affairs and Department of Defense hospitals were randomized to receive either 100 mg/kg intravenous hyperimmune globulin (IVIG), derived from donors immunized with a 24-valent Klebsiella capsular polysaccharide plus an 8-valent P. aeruginosa O-polysaccharide-toxin A conjugate vaccine, or an albumin placebo. The overall incidence and severity of vaccine-specific Klebsiella plus Pseudomonas infections were not significantly different between the groups receiving albumin and IVIG. There was some evidence that IVIG may decrease the incidence (2.7% albumin vs. 1.2% IVIG) and severity (1.0% vs. 0.3%) of vaccine-specific Klebsiella infections, but these reductions were not statistically significant. The trial was stopped because it was statistically unlikely that IVIG would be protective against Pseudomonas infections at the dosage being used. Patients receiving IVIG had more adverse reactions (14.4% vs. 9.2%).

Antibodies, Bacterial↗

Case study: risperidone treatment of children and adolescents with developmental disorders.

In a clinical trial, 20 children and adolescents with developmental disorders (age range 8 through 17 years) refractory to previous psychotropic treatments were administered the atypical neuroleptic risperidone (dose range 1.5 to 10 mg/day). In a follow-up period ranging from 8 to 15 months, risperidone demonstrated clinical efficacy in 13 children. Twelve patients were free of side effects and two had minor ones. Three patients had marked weight increase, and galactorrhea developed in two adolescent girls. In this open study, risperidone was associated with clinical improvement. However, controlled studies are needed to determine its relative efficacy and safety in this special population.

Adolescent↗

UCLA liver transplantation: analysis of immunological factors affecting outcome.

From 1988 to 1993, UCLA completed 938 first and 1,146 total orthotopic liver transplants (OLT). Race analysis demonstrated a 1-year patient survival of 89% in Blacks (n = 45) versus 80% in Whites (n = 492, p < 0.02), with no significant difference shown between Hispanics (n = 278) and Whites. The 1-year patient survival in Asians was 50% (n = 58, p < 0.02 vs. Whites) even when hepatitis B was excluded (59%, n = 43). The 1-year patient survival of hepatitis B surface antigen positive Asians (n = 15) was only 21% (p < 0.02 vs. all others). OLT patients whose panel reactive antibody (PRA) was < 10% (n = 339) demonstrated no graft or patient survival advantage versus recipients whose PRA was > 10% (n = 71). A positive antidonor flow cytometry crossmatch (> 30 mean channel shifts, n = 76) was associated with a decreased 1-year graft survival (56% vs. 73%, p < 0.05) when compared to flow negative recipients (n = 185). Graft survival for 0 DR mismatches was 74% at 1 year compared with 57% for 1 DR mismatches (p < 0.02) and 59% for 2 DR mismatches (p < 0.02).

Adult↗

Aerosolized recombinant human DNase in hospitalized cystic fibrosis patients with acute pulmonary exacerbations.

The goal of this study was to evaluate the safety and efficacy of recombinant human DNase (rhDNase) in hospitalized patients with cystic fibrosis (CF) experiencing acute pulmonary exacerbations. Eighty patients with documented CF were enrolled at 11 CF centers when admitted for antibiotic therapy. Patients were at least 5 yr old with a forced vital capacity (FVC) > or = 35% of predicted and an oxygen saturation > or = 90% on a fraction of inspired oxygen (FIO2) < 0.5. Patients were randomized to receive rhDNase 2.5 mg in 2.5 ml excipient twice a day (n = 43) or 2.5 ml excipient alone twice daily (n = 37) along with conventional treatment for exacerbations. Administration of rhDNase was not associated with acute adverse events or deaths, and no patients experienced allergic or anaphylactic reactions. Although forced expiratory volume in one second (FEV1) and FVC improved in both treatment groups during the double-blind period, there were no statistically significant differences in the mean change from baseline in FEV1 or FVC between the two groups. rhDNase therapy is safe and well tolerated in CF patients with acute exacerbations requiring hospitalization, but the study did not demonstrate a statistically significant therapeutic effect of rhDNase when added to a regimen of antibiotics and chest physical therapy.

Acute Disease↗

Can a lecture influence attitudes to suicide prevention?

Attitudes held by various groups of healthcare professionals with regard to suicide prevention were assessed using an attitude inventory before and after they attended a formal lecture. The lecture presented basic facts and statistics, discussed clinical techniques and challenged negative attitudes. Evidence is presented to suggest that a reduction in the proportion of expressed attitudes which were equivocal or negative towards the feasibility of suicide prevention in clinical practice, can be achieved by a lecture of this kind.

Attitude of Health Personnel↗