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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 307 records · Page 17Linked to original sources

The Eph receptor family: axonal guidance by contact repulsion.

Eph receptors and their ligands have been implicated in axonal pathfinding during the formation of neuronal networks. Whereas other guiding molecules, such as netrins and most semaphorins, are diffusible factors that can guide axons over considerable distances, Eph receptors and their ligands are cell-surface bound and are, therefore, involved in short-range contact-mediated guidance. Those molecules that have been analyzed appear to guide axons by repelling the growth cone, rather than attracting it. Here, we summarize the known biological functions of Eph receptors and ligands focusing on the developing nervous system, and we review the data on possible mechanisms of action.

Animals↗

Excimer laser photorefractive keratectomy for hyperopia.

PURPOSE: To achieve less variation in the refractive outcome of hyperopic photorefractive keratectomy (PRK) by enlarging the treatment zone to 9.0 mm. SETTING: Marienhospital, Amberg, Germany, and Klinika Ocni A Esteticke Chirurgie, Zlin, Czech Republic. METHODS: This prospective clinical study was based on the results of PRK in 68 hyperopic eyes (62 patients) using an MEL 60 excimer laser. Mean attempted correction was +4.85 diopters (D) +/- 1.45 (SD) (range +2.00 to +8.25 D). Maximum follow-up was 12 months (68 eyes). RESULTS: One year after PRK, 55 eyes (81%) were within 1.00 D and 40 eyes (59%) were within 0.50 D of the intended correction (predictability). Best corrected visual acuity was unchanged or improved in 62 eyes (92%) (safety). Four eyes (6%) lost one line, 1 eye (1%), two lines, and 1 eye (1%), three lines. Sixty-six eyes (97%) had an uncorrected visual acuity of 20/40 or better (efficacy) and 27 (40%), 20/20 or better. CONCLUSION: Photorefractive keratectomy with a 9.0 mm treatment zone was an efficient and relatively safe procedure for correcting hyperopia of up to 8.25 D. The predictability was good. Great care must be taken to improve the centration of the optical zone.

Adult↗

Epidemiological evidence for the disruption of ionized calcium homeostasis in the elderly.

Ionized calcium (Ca2+), phosphate, albumin, total calcium, and pH measurements taken from participants in a large population-based epidemiological study were examined to determine the change in physiological variation with age for persons over 43 years old. Only Ca2+ showed a statistically significant increase in SD with age (p < 0.0001). The Ca2+ coefficients of variation (CV) increased from 2.92% in the youngest age group (43-54 years) to 3.69% in the oldest age group (75-86 years of age). In females, the increase in Ca2+ variability was nearly complete by age 55. Males also showed a significant (p = 0.006) increase in SD between the 43-54 age group and the 55-64 age group, however, Ca2+ variability did not plateau after age 55 in men as it did in women. In the 43-54 (p = 0.04) and 55-64 (p = 0.03) age group men showed significantly better physiological control of Ca2+ than women. Phosphate showed a slight decrease in CV with age. These data suggest that Ca2+ homeostasis is disrupted in the same age groups that are most vulnerable to osteoporosis.

Adult↗

Survival of inner ear sensory neurons in trk mutant mice.

Analysis of trkB-/-; trkC-/- double mutant mice revealed that peripheral and central inner ear sensory neurons are affected in these mice. However, a substantial amount of cochlear and vestibular neurons survive, possibly due to maintenance or upregulation of TrkA expression. To clarify the function of the TrkA receptor during development of the cochlear and vestibular ganglion we analysed trkA-/- mice and the expression of this receptor in inner ear sensory neurons of trkB-/-; trkC-/- animals. TrkA homozygous mutant mice showed normal numbers of neurons and no TrkA expression was detected in neurons of trkB-/-; trkC-/- double mutant mice. We conclude that TrkA is not essential for inner ear development and that in the absence of any of the known catalytic Trk receptors peripheral inner ear sensory neurons are prone to undergo cell death or must use a different signaling mechanism to survive.

Animals↗

Normal saline versus heparin flush for maintaining central venous catheter patency during apheresis collection of peripheral blood stem cells (PBSC).

Thrombotic occlusion is frequently a complication of central venous catheters (CVCs). The original designers and producers of CVCs recommended heparin flush regimens to prevent thrombosis and maintain patency. This has become standard practice although no studies have demonstrated a relationship between heparin flushing and reduction of catheter thrombosis. Many consider the routine use of heparin flushing innocuous. However, serious complications including drug interactions and heparin induced thrombocytopenia and thrombosis syndrome (HITS) have been reported in association with heparin flushing. Numerous studies comparing heparin to saline flushing in peripheral devices suggest equal rates of thrombotic occlusions. The purpose of this study was to examine the incidence of thrombotic occlusions in CVCs using heparin compared to saline flushing. The study involved 78 cancer patients undergoing apheresis collection for peripheral blood stem cells; 29 received saline flushes and 49 received heparin (100 U/ml of saline) flushes. Study endpoints included slow apheresis flow rate (< 50 ml/min), urokinase use for thrombolysis, and radiographic evidence of catheter thrombosis. No significant differences were found for any endpoint between the two groups. These findings suggest saline may be as effective as heparin for maintaining patency of CVCs.

Adult↗

Characterization of Natronobacterium magadii phage phi Ch1, a unique archaeal phage containing DNA and RNA.

A novel archaeal bacteriophage, phi Ch1, was isolated from a haloalkalophilic archaeon Natronobacterium magadii upon spontaneous lysis. The phage-cured strain N. magadii(L13) was used to demonstrate infectivity of phage phi Ch1. The turbid-plaque morphology and the fact that N. magadii cells isolated from plaques were able to produce phage indicated that phi Ch1 is a temperate phage. The phage morphology resembles other members of Myoviridae-infecting Halobacterium species. In solution below 2M NaCl, the phage lost its morphological stability and infectivity. One- and two-dimensional SDS-PAGE of phage particles revealed at least four major and five minor proteins with molecular masses ranging from 15 to 80 kDa and acidic isoelectric points. Southern blot analysis of chromosomal DNA of a lysogenic N. magadii strain showed that phi Ch1 exists as a chromosomally integrated prophage. The phage particles contain both double-stranded, linear DNA (approx. 55 kbp) as well as several RNA species (80-700 nucleotides). Hybridization of labelled RNA fragments to total DNA from N. magadii and phi Ch1 showed that the virion-associated RNA is host encoded. Part of the phage DNA population is modified and restriction analysis revealed evidence for adenine methylation. Phage phi Ch1 is the first virus described for the genus natronobacterium, and the first phage containing DNA and RNA in mature phage particles.

Archaea↗

Cytokines in primary biliary cirrhosis.

Immunoreactivity to intra- and extracellular antigens is regulated mainly by two different types of T-helper cells, namely TH1 (producing mainly IFN-gamma and Il-2) and TH2 (producing IL-4, -5, -10). Both types cross-regulate each other. TH1 mechanisms seem to be involved principally in organ-specific autoaggressive disorders, while TH2 response is an expression of allergic conditions characterized by eosinophilic reactions and increased IgE levels. There are only a few reports dealing with cytokine profiles in patients with primary biliary cirrhosis (PBC). From studies analyzing the cytokine gene expression and cytokines in supernatants of nonstimulated and antigen-specific lymphocytes derived from the affected liver or peripheral blood of PBC patients, there is evidence that, in the course of the disease, predominantly TH1 cells are activated. However, in view of the eosinophilic reaction observed especially in patients with early PBC, it may well be that a switch from TH2 to TH1 occurs. Concerning the regulatory function of TH1/TH2 cells, a more refined evaluation of these T-cell subsets could help to provide a new insight into the natural course of PBC.

Animals↗

Changes in the optic disc over a five-year interval: the Beaver Dam Eye Study.

PURPOSE: To determine the relationship of change in vertical optic disc cupping to change in intraocular pressure over a five-year interval. METHODS: Non-simultaneous stereoscopic photographs were taken of optic discs of participants in the baseline and follow-up examinations of The Beaver Dam Eye Study cohort. Optic discs and cups were measured and other disc features were graded according to a standard protocol by trained graders. Intraocular pressures were measured by Goldmann applanation tonometry. RESULTS: Change in pressure was significantly associated with change in vertical cup-to-disc ratio. Incident disc hemorrhage, flattened temporal rim, notching, cup reaching disc margin, and undercutting were not significantly associated with change in intraocular pressure. CONCLUSION: Change in intraocular pressure in this adult population was associated with increased optic disc cupping. This finding, if confirmed, would lend support to the practice of periodic follow-up of older adults who have shown changes in their intraocular pressure.

Adult↗

Determination of average glandular dose with modern mammography units for two large groups of patients.

Until recently, for mammography Mo anode-Mo filter x-ray tube assemblies were almost exclusively used. Modern mammography units provide the possibility to employ a variety of anode-filter combinations with the aim of adapting the x-ray spectrum to compressed breast thickness and composition. The present contribution provides information on the radiation exposure of two large groups of patients (one of 1678 and one of 945 women) who were mammographed with modern x-ray equipment, and on the dosimetry necessary for the evaluation. For dosimetric purposes spectral information is essential. X-ray spectra have been determined for various anode-filter combinations from measurements with a Ge detector. Based on these spectra, conversion factors from air kerma free in air to average glandular dose (g factors) have been calculated for different anode-filter combinations, compressed breast thickness ranging from 2 to 9 cm and breast compositions varying from 0 to 100% glandular tissue. Determinations of various quantities, including entrance surface air kerma (ESAK), tube output, tube loading (TL), fraction of glandular tissue (FGL) and compressed breast thickness, were made during actual mammography. Average glandular dose (AGD) was determined using g factors corrected for tissue composition as well as g values for standard breast composition, i.e. 50% adipose tissue and 50% glandular tissue by mass. It is shown that, on average, the influence of the actual breast composition causes variations of the order of about 15%. For group 1 and group 2, the mean values of average glandular dose (using g factors corrected for tissue composition) were 1.59 and 2.07 mGy respectively. The number of exposures per woman was on average 3.4 and 3.6 respectively. The mean value of compressed breast thickness was 55.9 and 50.8 mm respectively. The mean age of group 1 was 53.6 years (for group 2 the age was not recorded). The fraction by mass of glandular tissue FGL decrease with increasing compressed breast thickness and age of patient (from 75% at 25 mm to 20% at 80 mm, and from 65% at 20 years to 30% at 75 years). For a medium-sized breast, i.e. a compressed breast thickness of 55 mm, FGL is about 35%, indicating that the standard mix (FGL = 50%) might need some modification, particularly because of additional evidence from another investigation with similar results on FGL.

Adipose Tissue↗

Antimitochondrial antibody profiles in primary biliary cirrhosis distinguish at early stages between a benign and a progressive course: a prospective study on 200 patients followed for 10 years.

In recent retrospective studies, it was shown that subtypes of antimitochondrial antibodies (AMA) can help to discriminate between a benign [only anti-M9 and/or anti-M2 positive by enzyme-linked immunosorbent assay (ELISA)] and a rather progressive course (anti-M2, -M4 and/or -M8 positive). According to different constellations of these AMA subspecificities in ELISA and complement fixation test (CFT), four AMA profiles (A-D) were defined. In 1984 we started a prospective study based on 200 PBC patients with known AMA profiles in order to correlate the antibody pattern with the clinical outcome. Progression was defined primarily as the necessity of liver transplantation and death due to hepatic failure or variceal bleeding. At entry, 18 (9%) of the 200 patients had AMA profile A (only anti-M9), 57 (29%) profile B (only anti-M2 with or without anti-M9), 74 (37%) profile C (anti-M2 in association with anti-M4/-M8 by ELISA), and 51 (26%) profile D (anti-M2/-M4/-M8 by ELISA and CFT). At the beginning of the study, 177 patients had PBC stage I/II. During the observation period of ten years, ten patients died and in 18 orthotopic liver transplantation (OLT) was performed; all these patients belonged to profile C/D. Furthermore, 44% of the patients with profile C and 31% of the patients with profile D progressed to late stages, as defined by histology and clinical manifestations such as portal hypertension and increase of bilirubin, while only one of the patients with profile B and none of the profile A-patients developed late stage PBC. A significant increase of bilirubin was observed only in C/D-patients. AMA profiles did not change during the follow-up. In conclusion, AMA profiles discriminate between a benign and a progressive course of PBC already at early stages.

Adult↗

Incidence of self reported glaucoma in people with diabetes mellitus.

AIM: To determine the incidence of self reported glaucoma in a group of people with diabetes mellitus. METHODS: In an 11 county area in southern Wisconsin, a cohort of people with diabetes mellitus was identified and characterised by history, physical examination, fundus photographs, and laboratory evaluation in 1980-2 (n = 2366). The cohort was followed for 10 years with 891 younger onset and 987 older onset people participating in at least one follow up examination. RESULTS: The 10 year incidence of glaucoma was 3.7% in younger onset people, 6.9% in older onset people not using insulin, and 11.8% in older onset people using insulin. Univariate analyses revealed that in younger onset people greater body mass index, older age, longer duration of diabetes, history of cataract surgery, and increased severity of diabetic retinopathy at baseline conferred increased risk. In older onset people using insulin, older age and longer duration of diabetes, higher intraocular pressure, and history of cataract surgery at baseline were associated with increased risk of glaucoma. In multivariate analyses, only age was significantly related to increased incidence in younger onset people and age, intraocular pressure, and insulin use were significantly associated with increased risk in the older onset group. CONCLUSION: Most risk factors associated with self reported glaucoma in people with diabetes cannot currently be modified to decrease incidence. Older onset people who are at increased risk of many ocular complications of diabetes may be particularly in need of specialised ophthalmic observation.

Adult↗

Limb ischemia preconditions the heart against reperfusion tachyarrhythmia.

We investigated the hypothesis that a cardioprotective, antiarrhythmic effect might be obtained by brief ischemia of a remote part of the body before ischemia of the heart. Regional ischemia (RI) was induced in isolated Langendorff-perfused rat hearts: group I, 30-min RI and reperfusion (control hearts; n = 18); group II, 5-min RI before 30-min RI (a reference group of "classic" ischemic preconditioning; n = 12); and group III, ischemic preconditioning with in vivo 10-min limb ischemia (LI) before 30-min RI in the perfused heart (n = 20). A significant decrease in reperfusion arrhythmia was found in groups II and III compared with group I (P < 0.02). Release of norepinephrine (NE) and prostacyclin was higher in hearts from animals pretreated with LI (P < 0.05). Prostacyclin increased in all groups at minute 1 of reperfusion, but there was no correlation to the antiarrhythmic effect. NE increased at the beginning of reperfusion after 30 min of ischemia; this release was significantly diminished after preconditioning with LI (P < 0.05). We further investigated the role of NE in preconditioning with LI using drug interventions. Pretreatment with exogenous NE protected against tachyarrhythmia. Reserpine given 24 h before LI partially abolished the antiarrhythmic effect of LI preconditioning. However, the alpha1-adrenoreceptor blocker prazosin did not prevent the effect of LI preconditioning on either ischemic or reperfusion tachyarrhythmia. Therefore, brief ischemia of an extremity protects against reperfusion tachyarrhythmia. One of the humoral mediators involved in this response appears to be NE; others remain to be identified.

Animals↗

Learning from others: shall the last be the first?

The cross-national exchange of ideas and experience in health care reform has, in recent years, reached epidemic proportions. Taking stock of this suggests the need for critical caution. The various participants in the process have different motives; models may be exported before they have been fully tested; information may be sought chiefly as political ammunition; and selective perception often distorts the evidence. A more helpful approach might be to concentrate on evaluating the experience of countries over time, rather than concentrating on the latest fashionable panacea, and to focus more on the process of introducing change.

Canada↗

Managing TMD.

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American Dental Association↗

Risk of hypoglycemia in users of human insulin. The Wisconsin Epidemiologic study of Diabetic Retinopathy.

OBJECTIVE: To evaluate whether there has been a change in frequency of hypoglycemic reactions associated with use of insulin of animal or human type. RESEARCH DESIGN AND METHODS: Data are from a longitudinal population-based study of people with diabetes onset before 30 years of age who were receiving primary care in an 11-county area of south central Wisconsin in 1980. Interviews of study participants were conducted regarding occurrence of hypoglycemic reactions and the frequency, dose, and type of insulin used. At the 4-year follow-up, 727 of the 765 subjects were using only animal insulin and 33 were using human insulin; by the 10-year follow-up, 352 were using animal insulin and 388 were using human insulin. RESULTS: Those using animal insulin reported fewer hypoglycemic reactions than did users of human insulin (chi (1)2 = 4.66, P = 0.03). Those who changed insulin type between visits were no more likely to report more hypoglycemic reactions during the year before the visit than those who remained on the same type at the two examinations (chi (4)2 = 3.37, P = 0.50). At the 10-year exam, users of human insulin were more likely to be taking multiple doses of insulin (86.6%) than were users of animal insulin (73.9%; P < 0.0001). In multiple logistic regression, the following variables were significantly related to the frequency of hypoglycemic reactions at the 10-year visit: body mass index (lower), glycosylated hemoglobin (lower), and being female. CONCLUSIONS: In this population, level of glycemia is related to the frequency of hypoglycemic reactions. While type of insulin (human vs. animal) may be related to glycemia, it appears to have little independent effect on the frequency of reactions.

Adult↗

Moderate-to-severe diabetic retinopathy is more prevalent in Mexico City than in San Antonio, Texas.

OBJECTIVE: To compare the prevalence of diabetic retinopathy (DR) between low-income Mexicans from Mexico City and Mexican-Americans from San Antonio, Texas. RESEARCH DESIGN AND METHODS: We designed a cross-sectional population-based study in low-income neighborhoods of Mexico City and San Antonio. The men and non-pregnant women included in the study had NIDDM and were between 35 and 64 years of age. Ophthalmologic evaluation was performed in 414 patients, 204 in San Antonio and 210 in Mexico City. Seven field standard stereophotographs of each eye were obtained, adapting the Early Treatment Diabetic Retinopathy Study protocol, and graded at the Fundus Photograph Reading Center of the University of Wisconsin. RESULTS: Early nonproliferative DR occurred in 37 (17.6%) and 39 (19.1%) patients in Mexico City and San Antonio, respectively. Moderate-to-severe nonproliferative DR occurred in 55 (26.2%) and 37 (18.1%) patients in Mexico City and San Antonio, respectively, and proliferative DR occurred in 12 (5.7%) and 7 (3.4%) patients in Mexico City and San Antonio, respectively. Using univariate and multivariate logistic regression analysis with DR as the dependent variable, age, duration of disease, and fasting glucose concentration were positively and significantly associated with retinopathy, whereas city, systolic blood pressure, and other selected metabolic variables were not. We defined moderate-to-severe DR to include the categories of moderate-to-severe nonproliferative and proliferative DR. For this combined category, Mexico City patients with diabetes had a significantly higher prevalence (P < 0.01) than those from San Antonio when analyzed by multiple logistic regression analysis (odds ratio for Mexico City/San Antonio, 1.72; 95% CI 1.10-2.70). CONCLUSIONS: Overall prevalence of DR is similar in both cities. However, moderate-to-severe DR is significantly higher in Mexico City.

Adult↗

[Value of polymerase chain reaction (PCR) in diagnosis of tuberculosis and mycobacterium infections caused by ubiquitous mycobacteria].

The rise in both incidence and the number of multi-drug-resistant strains has made tuberculosis an alarming health problem even in some developed countries. Moreover, due to the HIV pandemic an increase in mycobacterial diseases caused by ubiquitous mycobacteria has been observed. The microbiological standard procedures are critical diagnostic tools, and a more rapid detection of mycobacteria by new laboratory techniques would be helpful. We investigated the role of the polymerase chain reaction (PCR) in the detection of M. tuberculosis complex and of ubiquitous mycobacteria. 580 clinical specimens obtained from 525 patients were examined. The majority of sampled material was bronchoalveolar lavage fluid. Based on cultural identification of mycobacteria, the incidence of tuberculosis in our patients was 3.4%. For detection of M. tuberculosis complex the insertion sequence IS 6110 was used. Relative to cultural identification, diagnostic specificity of PCR was 99.5%, and sensitivity was 66.7%, respectively. In 3.0% of the total patient group and in 8.8% of HIV-infected patients an infection by ubiquitous mycobacteria was found. Ubiquitous mycobacteria were detected using the hypervariable region of the 16S-rRNA-gene, and species-identification was done by sequence analysis. For ubiquitous mycobacteria, sensitivity of PCR was 60.0% relative to cultural identification and 62.5% relative to a proven disease. PCR is a useful method in the rapid diagnosis of pulmonary tuberculosis with excellent specificity but lack of sensitivity.

AIDS-Related Opportunistic Infections↗

Clinically occult avascular necrosis of the hip in systemic lupus erythematosus.

OBJECTIVE: To study the natural history of clinically occult avascular necrosis (AVN) of the hip in patients with systemic lupus erythematosus (SLE). METHODS: Sixty-six patients with SLE (without symptoms referable to the hip) receiving at least 5 mg/day prednisone for > or = 6 months were screened by magnetic resonance imaging (MRI) for AVN of the hip. A complete MRI evaluating class and percentage of femoral head involvement, AP and lateral radiographs of the hips, bone scan, and physical examination were performed for patients with positive MRI. Medical records were reviewed for serologic and clinical variables that might predict AVN. Repeat MRI were obtained at 3, 6, and 12 months to assess possible progression or resolution of the lesion. Patients with negative screening MRI underwent repeat screening after one year to assess the one year incidence rate. RESULTS: Eleven asymptomatic hips (8%) in 8 patients (12%) had MRI documented AVN. The percentage of femoral head involvement ranged from 1 to 46%. One lesion was MRI class B, the remaining lesions were class A. The radiographic stage of 10 hips was stage 1, the MRI class B hip was stage 2. Risk factors for clinically occult AVN included Afro-American origin, Raynaud's phenomenon, migraine headaches, and a maximal corticosteroid dose of at least 30 mg/day. After 12 months, 43 of 58 patients with an initially negative MRI underwent repeat screening examinations; no new lesions were observed. CONCLUSION: Clinically occult AVN of the hip is common in patients with SLE. The short term natural history of these lesions appears stable without spontaneous healing or clinical or radiographic progression. Risk factors for these asymptomatic lesions are similar to the risks for symptomatic AVN and surgical intervention appears not to be indicated in these patients.

Adolescent↗