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Biomedical subjects

J A Johnson

Publications and source records attributed to J A Johnson.

At least 163 records · Page 9Linked to original sources

Managing hospitals in dynamic environments.

Hospital environments have changed dramatically over the past two decades. Hospitals now have to contend with the dynamics of regulation, market forces, and quality and cost-conscious environments. The strategies proposed here emulate the changes pursued by much of US industry. Provides a framework for analysing hospital environments. Applies Deming's total quality management concepts to hospitals. Also suggests strategies to deal effectively with different types of hospital environments.

Cost Control↗

Vibriocidal antibody responses in North American volunteers exposed to wild-type or vaccine Vibrio cholerae O139: specificity and relevance to immunity.

The emergence of a new agent of cholera, Vibrio cholerae O139, has prompted a reevaluation of the vibriocidal antibody assay. This assay, primarily directed to lipopolysaccharide, is an important correlate of O1 immunity. V. cholerae O139 strains are encapsulated, rendering them relatively resistant to killing by serum. Recent reports suggest that there is strain-to-strain variability in the sensitivity of the vibriocidal assay to fully encapsulated O139 strains. We have assessed a modified vibriocidal assay for fully encapsulated O139 strain AI-1837 and its unencapsulated mutant 2L in sera from 53 volunteers given wild-type AI-1837 or its attenuated derivative CVD 112 and from 48 controls challenged with V. cholerae O1 or strains of the family Enterobacteriaceae. Vibriocidal responses to the AI-1837 and 2L strains were seen in 67 and 89% of volunteers, respectively, following a single exposure to the wild-type strain. However, >50% of all controls had low-level vibriocidal responses to both strains. These nonspecific responses were transient and of the immunoglobulin G isotype. No binding activity against purified O139 lipopolysaccharide (LPS) by immunoblotting was seen in control sera. In contrast, vibriocidal assay and strain 2L LPS responses by immunoblotting were detectable in 91% of tested volunteers following a single exposure to O139. The presence of vibriocidal antibody to AI-1837 or 2L was not associated with protection in rechallenge studies with O139 strain AI-1837. The vibriocidal assay with unencapsulated strain 2L may be used to detect exposure to O139 strain AI-1837 in controlled research trials. However, its lack of specificity does not make it useful for determining exposure to V. cholerae O139 in the field.

Antibodies, Bacterial↗

C2 region-derived peptides of beta-protein kinase C regulate cardiac Ca2+ channels.

We have previously shown that alpha1-adrenergic activation inhibited beta-adrenergic-stimulated L-type Ca2+ current (I(Ca)). To determine the role of protein kinase C (PKC) in this regulation, the inositol trisphosphate pathway was bypassed by direct activation of PKC with 4beta-phorbol 12-myristate 13-acetate (PMA). To minimize Ca2+-induced Ca2+ inactivation, Ba2+ current (I(Ba)) was recorded through Ca2+ channels in adult rat ventricular myocytes. We found that PMA (0.1 micromol/L) consistently inhibited basal I(Ba) by 40.5+/-7.4% and isoproterenol (ISO, 0.1 micromol/L)-stimulated I(Ba) by 48.9+/-7.8%. These inhibitory effects were not observed with the inactive phorbol ester analogue alpha-phorbol 12,13-didecanoate (0.1 micromol/L). To identify the PKC isozymes that mediate these PMA effects, we intracellularly applied peptide inhibitors of a subclass of PKC isozymes, the C2-containing cPKCs. These peptides (betaC2-2 and betaC2-4) specifically inhibit the translocation and function of C2-containing isozymes (alpha-PKC, betaI-PKC, and betaII-PKC), but not the C2-less isozymes (delta-PKC and epsilon-PKC). We first used the pseudosubstrate peptide (0.1 micromol/L in the pipette), which inhibits the catalytic activity of all the PKC isozymes, and found that PMA-induced inhibition of ISO-stimulated I(Ba) was reduced to 16.8+/-7.4% but was not affected by the scrambled pseudosubstrate peptide. The effects of PMA on basal and ISO-stimulated I(Ba) were then determined in the presence of C2-derived peptides or control peptides. When the pipette contained 0.1 micromol/L of betaC2-2 or betaC2-4, PMA-induced inhibition of basal I(Ba) was 26.1+/-4.5% and 23.6+/-2.2%, respectively. Similarly, ISO-stimulated I(Ba) was inhibited by 29.9+/-6.6% and 29.3+/-7.8% in the presence of betaC2-2 and betaC2-4, respectively. In contrast, there was no significant change in the effect of PMA in the presence of control peptides, scrambled betaC2-4, or pentalysine. Finally, PMA-induced inhibition of basal and ISO-stimulated I(Ba) was almost completely abolished in cells dialyzed with both betaC2-2 and betaC2-4. Together, these data suggest a role for C2-containing isozymes in mediating PMA-induced inhibition of L-type Ca2+ channel activity.

Adrenergic beta-Agonists↗

Visceral fat and race-dependent health risks in obese nondiabetic premenopausal women.

Our previous finding that a waist-to-hip ratio (WHR) >0.85 was not associated with similar health risks in black, compared with white, obese premenopausal non-diabetic women of similar fatness is attributed to either 1) a different relationship between WHR and visceral adiposity or 2) differences in the relationship between visceral adiposity and the metabolic abnormalities of obesity. We measured visceral (VAT) and subcutaneous adipose tissue (SCAT) areas at midwaist in 25 black and 25 white obese nondiabetic pre-menopausal women with similar BMI, percentage body fat, and wide range of WHR (0.7-0.95 for black women and 0.7-0.9 for white women) and then compared insulin sensitivity index (SI), glucose and insulin areas under the 2-h curve (AUCs) during an oral glucose tolerance test (OGTT), and blood lipids in the two groups before and after adjustments for total body and visceral adiposity. After adjusting for total body fat mass (FM), obese black women had significantly less VAT (by 32 cm2) and lower VAT/SCAT for any given WHR. The regression equations predicting the SI the glucose and insulin AUCs, and the triglyceride and HDL cholesterol levels from regional adipose tissue measurements (VAT, SCAT, or VAT/SCAT) and from total body fat (FM or percentage body fat) had slopes that were not significantly different for black and white women. LDL cholesterol levels were independently related to VAT in black but not in white women. The black women had a similar SI insulin AUC, and triglyceride levels but significantly lower glucose AUC and higher HDL cholesterol levels (P < 0.001), after adjusting for VAT and FM. Regression analysis of the pooled data showed that high VAT and high VAT/SCAT, but not SCAT, predicted lower SI higher glucose and insulin AUCs during OGTT, and higher triglyceride levels, independent of total adiposity. We conclude that while increases in VAT and VAT/SCAT adversely affect metabolism in both black and white obese premenopausal women, similar levels of total body and visceral adiposity are associated with different metabolic risk factors in these groups.

Adipose Tissue↗

The McGurk effect in infants.

In the McGurk effect, perceptual identification of auditory speech syllables is influenced by simultaneous presentation of discrepant visible speech syllables. This effect has been found in subjects of different ages and with various native language backgrounds. But no McGurk tests have been conducted with prelinguistic infants. In the present series of experiments, 5-month-old English-exposed infants were tested for the McGurk effect. Infants were first gaze-habituated to an audiovisual /va/. Two different dishabituation stimuli were then presented: audio /ba/-visual /va/ (perceived by adults as /va/), and audio /da/-visual /va/ (perceived by adults as /da/). The infants showed generalization from the audiovisual /va/ to the audio /ba/-visual /va/ stimulus but not to the audio /da/-visual /va/ stimulus. Follow-up experiments revealed that these generalization differences were not due to a general preference for the audio /da/-visual /va/ stimulus or to the auditory similarity of /ba/ to /va/ relative to /da/. These results suggest that the infants were visually influenced in the same way as English-speaking adults are visually influenced.

Female↗

Advanced cement technique improves fixation in elbow arthroplasty.

An in vitro study was conducted to assess the efficacy of advanced cementing techniques in the fixation of the humeral stem in elbow arthroplasty. Sixteen fresh frozen cadaveric distal humeri were prepared to accept an acrylic sham humeral stem. Conventional cementing technique using doughy cement manually inserted and packed was performed in 8 specimens. The advanced cementing technique, consisting of canal irrigation, brushing and drying with gauze, canal plugging, and low viscosity cement pressurization with a delivery system was performed in the other specimens. All humeri subsequently were sectioned into 10 mm thick sections, photographed, and digitized to quantify the perimeter and area of the stem, cement mantle, corticocancellous junction, and cement voids. The degree of cement filling, determined from the area fraction of cement to the total available area within the corticocancellous junction, was significantly greater in the advanced group compared with the conventional group. Mechanical assessment of the specimens consisted of a push out load to failure test of the cement mantle from bone. For all locations in the distal humerus, the failure load and failure stress in the advanced group was significantly greater than the conventional group. It is concluded that development of an effective cement restrictor and application of advanced cement techniques in vivo should improve the initial fixation of the humeral component and may decrease the incidence of aseptic loosening associated with elbow arthroplasty.

Biomechanical Phenomena↗

Cloning and characterization of dnaE, encoding the catalytic subunit of replicative DNA polymerase III, from Vibrio cholerae strain C6706.

We report that Vibrio cholerae (Vc) contains a gene homologous to Escherichia coli dnaE, the structural gene for the alpha (catalytic) subunit of replicative DNA polymerase III (PolIII). Despite 24% amino acid (aa) differences in the encoded proteins, the Vc gene strongly complements an E. coli dnaE temperature sensitive (ts) mutant, indicating that all functional features essential for replication are conserved.

Amino Acid Sequence↗

A protein kinase C translocation inhibitor as an isozyme-selective antagonist of cardiac function.

Protein kinase C (PKC) isozymes translocate to unique subcellular sites following activation. We previously suggested that translocation of activated isozymes is required for their function and that in addition to binding to lipids, translocation involves binding of the activated isozymes to specific anchoring proteins (receptors for activated protein kinase C. Using cultured cardiomyocytes we identified inhibitors, the V1 fragment of epsilonPKC (epsilonV1), and an 8-amino acid peptide derived from it that selectively inhibited the translocation of epsilonPKC. Inhibition of epsilonPKC translocation but not inhibition of delta or betaPKC translocation specifically blocked phorbol ester- or norepinephrine-mediated regulation of contraction. These isozyme-selective translocation inhibitors provide novel tools to determine the function of individual PKC isozymes in intact cells.

Animals↗

1,25-Dihydroxyvitamin D(3) receptors in developing dorsal root ganglia of fetal rats.

We observed immunostaining for the 1,25-dihydroxyvitamin D(3) receptor (VDR) and calbindin-D(28k) in neurons, but not glial cells, of fetal rat dorsal root ganglia (DRG) from days 13 through 21 of gestation. Dispersed cultures of DRG collected from rat fetuses at gestational day 15 also contained epitopes for VDR and calbindin-D(28k) in neurons, but not in glial cells. 1,25-Dihydroxyvitamin D(3), through VDR, may perform significant functions in the development of neuronal cells.

Animals↗

Prenatal diagnosis of a fetal ventricular diverticulum associated with pericardial effusion: successful outcome following pericardiocentesis.

Congenital cardiac diverticula are rare abnormalities that may occur as isolated malformations. In this report, we describe a case of an isolated congenital cardiac diverticulum complicated by a large serous pericardial effusion diagnosed ultrasonographically at 19 weeks' gestation. Therapeutic pericardiocentesis at 20 weeks' gestation resulted in complete resolution of the effusion with a normal fetal outcome. There is only one previous report of a prenatal diagnosis of a cardiac diverticulum complicated by a pericardial effusion and that patient underwent termination of pregnancy (Carles et al., 1995). Given the otherwise favourable prognosis for this lesion, and the excellent response in this case, pericardiocentesis should be considered in similar cases.

Adult↗

Ontogeny of the 1,25-dihydroxyvitamin D3 receptor in fetal rat bone.

To gain insights into 1,25-dihydroxyvitamin D3 receptor (VDR) function during fetal bone development, we examined fetal rat tissues from gestational days 13-21 for the presence and distribution of VDR using immunohistochemistry. Prior to ossification, VDR epitopes were observed in the mesenchyme condensing to form skeletal tissues, on day 13 in the developing vertebral column and limbs, and on day 17 of gestation in developing calvaria. Immunostaining for VDR was seen in proliferating and hypertrophic chondrocytes and in osteoblasts of limb buds and the vertebral column by day 17 of gestation. In calvaria, VDR epitopes were observed in osteoblasts by gestational day 19. VDR immunostaining was also evident in the skin of fetal limbs at all gestational ages examined. We show for the first time that the VDR appears very early in the developing fetal rat skeleton, suggesting that the VDR, in concert with its ligand, 1,25-dihydroxyvitamin D3, may play a role in the differentiation of mesenchymal precursors into bone tissue.

Animals↗

Immunohistochemical detection and distribution of the 1,25-dihydroxyvitamin D3 receptor in rat reproductive tissues.

Vitamin D3, via its active metabolite 1,25-dihydroxyvitamin D3, plays a critical part in male and female reproduction in the rat. 1,25-Dihydroxyvitamin D3 activity is mediated by an intracellular receptor (VDR). VDR distribution in reproductive tissue has not been studied using antibodies against the receptor. We developed a polyclonal antibody against the VDR and used it to examine VDR distribution in male and female rat reproductive tissues. In rat testes, VDR epitopes were observed in seminiferous tubules, specifically in spermatogonia, Sertoli cells and spermatocytes. Spermatozoa stained faintly. Epithelial cells of the epididymis, seminal vesicles and prostate also expressed VDR epitopes. In the female rat reproductive tract, immunostaining for VDR was seen in ovarian follicles, specifically in granulosa cells. Weaker VDR immunostaining was observed in follicular thecal cells and in the ovarian stroma and germinal epithelium. Corpus luteal cells stained intensely for VDR. Epithelium of fallopian tubes and the uterus also contained VDR epitopes. Both nuclear and cytoplasmic VDR immunostaining was observed in male and female rat reproductive tissues. We conclude that the VDR is widely distributed in male and female reproductive tissues and that it is likely to mediate actions of 1,25-dihydroxyvitamin D3 in the tissues.

Animals↗

Accuracy of an electromagnetic tracking device: a study of the optimal range and metal interference.

The positional and rotational accuracy of a direct-current magnetic tracking device commonly used in biomechanical investigations was evaluated. The effect of different metals was also studied to determine the possibility of interference induced by experimental test fixtures or orthopaedic implants within the working field. Positional and rotational data were evaluated for accuracy and resolution by comparing the device output to known motions as derived from a calibrated grid board or materials testing machine. The effect of different metals was evaluated by placing cylindrical metal samples at set locations throughout the working field and comparing the device readings before and after introducing each metal sample. Positional testing revealed an optimal operational range with the transmitter and receiver separation between 22.5 and 64.0 cm. Within this range the mean positional error was found to be 1.8 percent of the step size, and resolution was determined to be 0.25 mm. The mean rotational error over a 1-20 degree range was found to be 1.6% of the rotational increment with a rotational resolution of 0.1 degrees. Of the metal alloys tested only mild steel produced significant interference, which was maximum when the sample was placed adjacent to the receiver. At this location the mild steel induced a positional difference of 5.26 cm and an angular difference of 9.75 degrees. The device was found to be insensitive to commonly used orthopaedic alloys. In this study, the electromagnetic tracking device was found to have positional and rotational errors of less than 2 percent, when utilized within its optimal operating range. This accuracy combined with its insensitivity to orthopaedic alloys should make it suitable for a variety of musculoskeletal research investigations.

Alloys↗

Angiographically silent atherosclerosis detected by intravascular ultrasound in patients with familial hypercholesterolemia and familial combined hyperlipidemia: correlation with high density lipoproteins.

OBJECTIVES: This study sought to evaluate the extent of atherosclerosis in coronary and iliac arteries in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia, using intravascular ultrasound imaging. BACKGROUND: Intravascular ultrasound imaging provides cross-sectional tomographic views of the vessel wall and allows quantitative assessment of atherosclerosis. METHODS: Forty-eight nonsmoking, asymptomatic patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia underwent intravascular ultrasound imaging of the left anterior descending coronary, left main coronary and common iliac arteries. Angiography showed only minimal or no narrowing in these vessels. Intravascular ultrasound images obtained during catheter pullback underwent morphometric analysis. Plaque burden was expressed as the mean and maximal intimal index (ratio of plaque area and area within the internal elastic lamina) and as the percent of vessel surface covered by plaque. RESULTS: Intravascular ultrasound detected plaque more frequently than angiography in the left anterior descending (80% vs. 29%, respectively), left main (44% vs. 16%) and iliac arteries (33% vs. 27%). Plaque burden was higher in the left anterior descending (mean intimal index [+/- SD] 0.25 +/- 0.16) than in the left main (0.11 +/- 0.16, p < 0.001) and iliac arteries (0.02 +/- 0.04, p < 0.001). Angiography detected lumen narrowing only in coronary arteries with a maximal intimal index > or = 0.42 (left anterior descending artery) and > or = 0.43 (left main artery). The area within the internal elastic lamina increased with plaque area in the left anterior descending (r = 0.82, p < 0.001) and left main arteries (r = 0.53, p < 0.001). By stepwise multiple regression analysis, the strongest predictor for plaque burden in the left anterior descending artery was the level of high density lipoprotein (HDL) cholesterol and total/HDL cholesterol ratio for the left main artery. CONCLUSIONS: In patients with heterozygous familial hypercholesterolemia and familial combined hyperlipidemia, extensive coronary plaque is present despite minimal or no angiographic changes. Compensatory vessel enlargement and diffuse involvement with eccentric plaque may account for the lack of angiographic changes. Levels of HDL cholesterol and total/HDL cholesterol ratio are far more powerful predictors of coronary plaque burden than are low density lipoprotein cholesterol levels in these patients with early, asymptomatic disease.

Adult↗

Laparoscopic skills enhancement.

BACKGROUND: Laparoscopy requires a unique subset of surgical skills that, for the inexperienced, can significantly delay the development of basic operative skills. We hypothesized that learning laparoscopic suturing and knot tying would improve laparoscopic skills. METHODS: A laparoscopic training seminar for junior surgical residents was established to test this hypothesis. Emphasis was placed on laparoscopic knot tying and suturing. Skills were assessed at the beginning and the end of the course. RESULTS: All residents showed significant improvement. Dominant and nondominant hand skills improved by 30.2% and 26.9%, respectively. Two-handed skills improved by 58.6% and 30.1%. Overall scores improved by 28.9%. CONCLUSIONS: A structured laparoscopic skills course stressing knot tying and suturing is an effective way to develop dexterity and significantly improve the performance of laparoscopic tasks. These improvements can be accomplished in a cost-effective curriculum that should enhance the surgical education of residents and speed the acquisition of competent operative skills.

Curriculum↗

A randomized blinded comparison of omeprazole and ranitidine in the treatment of chronic esophageal stricture secondary to acid peptic esophagitis.

BACKGROUND: Esophageal strictures due to gastroesophageal reflux disease are often resistant to medical therapy and require repeated dilation procedures. Our aim was to compare the efficacy of therapy with omeprazole (20 mg/day) to ranitidine (150 mg twice daily) in the treatment of chronic esophageal strictures. METHODS: Thirty-three patients with chronic esophageal stricture disease (mean length of prior treatment, 50.9 months) were entered into a randomized blinded trial. The majority (88%) of the patients had received multiple prior esophageal dilations (mean, 7.9 per patient). Endoscopy and barium esophagograms were performed initially and at the end of 10 months. Symptoms were considered every 2 months and dilations performed as needed. The patient groups were equivalent. RESULTS: One patient in each group was subsequently lost to follow-up. No significant differences were seen in symptom improvement or need of dilation. At the final endoscopy, 8 of 17 (47%) patients receiving ranitidine had residual erosions or ulceration, compared with 1 of 14 (7%) patients receiving omeprazole (p >0.2). All patients receiving ranitidine had persistent strictures, whereas 8 of 14 (57.1%) patients receiving omeprazole had radiographic and endoscopic resolution of their strictures (p <0.004). CONCLUSION: These data further emphasize the need for vigorously treating esophagitis in patients with acid peptic strictures.

Aged↗