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Biomedical subjects

H J Klein

Publications and source records attributed to H J Klein.

At least 19 recordsLinked to original sources
PubMed2000

A novel approach for assessing the quality and effectiveness of IACUC oversight in investigator compliance.

In research facilities that are registered with the U.S. Department of Agriculture (USDA), funded by the Public Health Service, or accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC) International, the Institutional Animal Care and Use Committee (IACUC) is charged with oversight and evaluation of animal care and use under the terms of the Animal Welfare Act and the Guide for the Care and Use of Laboratory Animals. Although the committee's oversight of investigator compliance may be evaluated annually during USDA inspections and triennially during AAALAC International site visits, routinely assessing the quality and effectiveness of the IACUC's performance is difficult. To measure the successfulness of IACUC oversight, our committee retained a management consultant to objectively design and conduct a confidential survey that could be used to determine how the IACUC could improve the process of facilitating researcher compliance with federal regulations and accreditation standards. The consultant based the content of the survey on confidential interviews with all IACUC members, the IACUC administrator, and a cross sectional representation of the key animal-user population at the facility. The survey was then distributed to the entire animal-user population. Vice-presidents, directors, principal investigators, and technicians were included in the distribution. With a response rate of 34%, the survey results indicated that the facilitation process warranted refinements. The consultant provided the IACUC with its recommendations, which were based on the discernible trending information indicated in the survey responses. The IACUC developed a specific plan of action to address the consultant's recommendations and intends to re-survey the animal-user population once the action plan has been fully implemented. In summary, the survey is an excellent way to assess the quality and effectiveness of IACUC oversight in investigator compliance by determining the level of researcher satisfaction. The evaluation, review, and follow-up process using a confidential interview and questionnaire technique can enhance the performance and effectiveness of IACUC oversight.

Accreditation↗
PubMed1999

Goal commitment and the goal-setting process: conceptual clarification and empirical synthesis.

Goals are central to current treatments of work motivation, and goal commitment is a critical construct in understanding the relationship between goals and task performance. Despite this importance, there is confusion about the role of goal commitment and only recently has this key construct received the empirical attention it warrants. This meta-analysis, based on 83 independent samples, updates the goal commitment literature by summarizing the accumulated evidence on the antecedents and consequences of goal commitment. Using this aggregate empirical evidence, the role of goal commitment in the goal-setting process is clarified and key areas for future research are identified.

Achievement↗
PubMed1998

Leptin gene therapy and daily protein administration: a comparative study in the ob/ob mouse.

We have compared the efficacy of daily injection of recombinant leptin protein (rh-leptin) with adenovirus-mediated delivery of the murine or human leptin gene (Ad-leptin) for treatment of obesity in the obese (ob/ob) mouse model. We demonstrate an improved correction profile for obesity and associated surrogate markers using the adenovirus delivery method. Rate of weight loss and percentage satiety were significantly greater in the mice treated with Adleptin. These findings were associated with lower peak serum leptin levels with Ad-leptin (22.9 +/- 2.6 ng/ml for the human gene, and 48.9 +/- 11.5 ng/ml for the murine gene) compared to rh-leptin (385.2 +/- 36.0 ng/ml). (Values are given as mean +/- standard error of the mean.) Importantly rh-leptin and ex vivo-expressed Ad-leptin were equivalently active in a functional cell-based assay. The primary difference in the two therapeutic approaches is the continuous chronic secretion of leptin mediated by gene delivery, versus the intermittent bolus delivery and rapid clearance of the daily injection of rh-leptin protein. Thus, in vivo findings suggest that leptin effects are better achieved at lower steady-state levels, a pharmacological feature attained here by gene therapy. These findings may have implications for the potential use of leptin in the treatment of obesity.

Adenoviridae↗
PubMed1997

Protease activity in a hapten-induced model of ulcerative colitis in rats.

Inflammatory bowel disease (IBD) is a painful and debilitating condition affecting the mucosal lining of the colon and other areas of the gastrointestinal tract. IBD generally falls into two major categories: ulcerative colitis (UC) and Crohn's disease. We have utilized dinitrobenzenesulfonic acid (DNBS) to induce experimental UC in rats. Histopathologic analysis indicates that DNBS induces a condition in animals similar to human UC. Biochemical results revealed 6- to 10-fold elevated levels of serine protease activity in colon tissue from animals with UC as compared with matched controls. We also observed elevated levels of protease activity in tissue samples obtained from human patients with UC. Hence, our results demonstrate that protease activity is increased in rodent and human UC. These proteases may play a significant role in destruction of colonic tissue in IBD. Protease inhibitors that target serine proteases may be useful pharmacological agents to limit tissue destruction in IBD.

Animals↗
PubMed1997

Diagnosis of Helicobacter pylori infection in a colony of rhesus monkeys (Macaca mulatta).

Twenty-three young adult rhesus monkeys from China were evaluated for the presence of Helicobacter pylori. Gastric body and antral biopsy samples were tested for H. pylori by PCR analysis, culture, rapid urease testing, and histologic evaluation. Serologic testing to detect H. pylori immunoglobulin G (IgG) antibodies was performed by using a commercially available human-based enzyme-linked immunosorbent assay (ELISA) test and an ELISA test which utilized homologous H. pylori antigens and an anti-rhesus IgG conjugate. PCR analysis with H. pylori-specific 26-kDa protein primers detected H. pylori in 21 of the 23 rhesus monkeys (91%). Culture testing identified the organism in 12 of the 23 animals (52%). Rapid urease tests were positive for all animals. H. pylori was diagnosed by histological examination in 11 of 23 monkeys (48%). Of the 21 monkeys positive for H. pylori by PCR, only 3 (14%) had positive results by the commercial ELISA test, yielding a sensitivity of 14%, a specificity of 100%, and an accuracy of 22%. However, 19 of the 21 PCR-positive animals (90%) had positive results by the ELISA test with homologous rhesus H. pylori antigen and anti-monkey conjugate, with predicted index values greater than or equal to 0.7 considered positive and values between 0.5 and 0.7 considered equivocal. This test had a sensitivity of 90%, a specificity of 100%, and an accuracy of 91%. Therefore, the ELISA test with rhesus monkey origin components was more accurate for detecting infected animals than the human-based ELISA.

Animals↗
PubMed1997

Effects of anesthesia and open-thorax surgery on coronary vascular reserve in swine.

The coronary reactive hyperemic response was examined in seven pigs under anesthetized and conscious conditions, (i.e., 5 days and 3 and 5 weeks after surgery). Tygon catheters were inserted in the descending aorta of five pigs; transonic flow probes and hydraulic occluders were placed on the left cranial descending and/or left circumflex coronary arteries. Two pigs underwent long-term implantation of similar instruments. The coronary reactive hyperemic response, expressed as repayment of flow deficit, was induced by brief complete coronary artery occlusion for 15 sec. Baseline mean arterial pressure, heart rate, and coronary blood flow were similar in the anesthetized and conscious pigs. There was also no significant difference in repayment of flow deficit between the anesthetized and conscious pigs 5 days after surgery. The repayment of flow deficit (709 +/- 144%) in conscious pigs 5 days after surgery tended to be greater, but was not statistically significant from that observed in the anesthetized pigs (510 +/- 79%). However, at 3 and 5 weeks after surgery, the reactive hyperemic flow and the repayment of flow deficit were numerically greater than those values observed in anesthetized pigs. The difference in reactive hyperemic flow between conscious and anesthetized pigs was statistically significant at week 3. The difference in repayment of flow deficit between conscious and anesthetized pigs was statistically significant at week 5. These results suggest that anesthesia, as well as recent surgery, attenuates coronary vascular reserve. The major factor in the attenuation of coronary reserve appears to be recent surgical manipulation, because repayment of flow deficit was still depressed in conscious pigs during the early phase of recovery from surgery.

Anesthesia, Inhalation↗
PubMed1996

Species specificity of 2-aryl carbapenem-induced immune-mediated hemolytic anemia in primates.

L-695,256 is a novel 2-fluorenonyl carbapenem antibiotic with significant antimicrobial activity against strains of methicillin-resistant Staphylococci. This prototype compound was administered intravenously to rhesus monkeys (Macaca mulatta) at does of 50 or 200 mg/kg/day for 2 weeks to assess toxicity and found to induce a hemolytic anemia characterized by extravascular hemolysis and splenomegaly. A subsequent study in this species in which 100 mg/kg/day was administered i.v. for 4 weeks showed that all animals were direct antiglobulin test (Coombs' test) positive for IgG with 20-25% reductions in the erythron. Following 3 weeks of recovery, the erythron had returned to normal, although it took an additional 2 months for the Coombs' test to become negative. Challenge of these same animals with 0.5 million U/kg (300 mg/kg/day) of penicillin intravenously indicated no apparent cross-reactivity. Since attempts to establish a model for this immune-mediated hemolytic anemia with this drug in rats or mice were unsuccessful, a 2-week i.v. study in squirrel monkeys (Saimiri sciureus) was conducted at a dose of 200 mg/kg/day. All animals in this study remained Coombs' test negative with no changes in the erythron, suggesting an increased sensitivity to beta-lactam-induced anemia in rhesus monkeys compared to other species. Further support for this hypothesis was obtained using the cephalosporin antibiotic, cefotetan. This compound induced a high incidence of Coombs' test positive hemolytic anemia at clinically relevant doses in rhesus monkeys, despite a very low incidence of this adverse effect in patients with many years of clinical use. These data suggest that although rhesus monkeys respond in a qualitatively similar manner to humans with regard to high doses of beta-lactam antibiotics, their sensitivity may overestimate the risk of immune-mediated hemolytic anemia for clinical use.

Anemia, Hemolytic, Autoimmune↗
PubMed1996

Findings and long-term results of subsequent operations after failed microvascular decompression for trigeminal neuralgia.

OBJECTIVE: To evaluate the indication of subsequent operations after failed microvascular decompression (MVD) for the treatment of trigeminal neuralgia, the intraoperative findings and long-term results of 16 subsequent operations are reported. METHODS: Subsequent exploration of the posterior fossa was performed for lack of pain relief (3 patients) and recurrent neuralgia (13 patients) after an average of 17 months (range, 4-62 mo). In all patients, typical arterial compression patterns at the root entry zone of the trigeminal nerve were found in the first procedure. The mean follow-up period after subsequent operation was 90 months (range, 78-104 mo). RESULTS: New arterial neurovascular conflicts were found in nine patients. After subsequent MVD procedures, seven patients were pain-free (with one recurrence after 6 mo), one had constant marked relief, and one was unchanged. Second exploration revealed no abnormalities in the other seven patients who experienced continued or recurrent pain; only careful neurolysis of the trigeminal nerve was performed in those patients. Initially, all seven patients obtained complete pain relief, but two experienced late recurrences after 64 and 68 months, respectively. Thus, subsequent operations failed in all 4 patients who had undergone prior destructive procedures but were successful in those 12 patients who had undergone only previous MVD. Two patients developed severe sequelae, and the other nine had minor complications, especially permanent (four patients) or transitory (three patients) ipsilateral trigeminal hypoesthesia. CONCLUSION: Subsequent MVD seems to have good long-term results. However, because of the significantly high incidence of complications, the indication for subsequent operations should be restricted to younger patients to avoid destructive procedures. In general, glycerol rhizolysis or radiofrequency rhizotomy may be the treatment of choice after failed MVD.

Adult↗
PubMed1995

A vaccine-elicited, single viral epitope-specific cytotoxic T lymphocyte response does not protect against intravenous, cell-free simian immunodeficiency virus challenge.

Protection against simian immunodeficiency virus (SIV) challenge was assessed in rhesus monkeys with a vaccine-elicited, single SIV epitope-specific cytotoxic T-lymphocyte (CTL) response in the absence of SIV-specific antibody. Strategies were first explored for eliciting an optimal SIV Gag epitope-specific CTL response. These studies were performed in rhesus monkeys expressing the major histocompatibility complex (MHC) class I gene Mamu-A*01, a haplotype associated with a predominant SIV CTL epitope mapped to residues 182 to 190 of the Gag protein (p11C). We demonstrated that a combined modality immunization strategy using a recombinant Mycobacterium bovis BCG-SIV Gag construct for priming, and peptide formulated in liposome for boosting, elicited a greater p11C-specific CTL response than did a single immunization with peptide-liposome alone. Vaccinated and control monkeys were then challenged with cell-free SIVmne by an intravenous route of inoculation. Despite a vigorous p11C-specific CTL response at the time of virus inoculation, all monkeys became infected with SIV. gag gene sequencing of the virus isolated from these monkeys demonstrated that the established viruses had no mutations in the p11C-coding region. Thus, the preexisting CTL response did not select for a viral variant that might escape T-cell immune recognition. These studies demonstrate that a potent SIV-specific CTL response can be elicited by combining live vector and peptide vaccine modalities. However, a single SIV Gag epitope-specific CTL response in the absence of SIV-specific antibody did not provide protection against a cell-free, intravenous SIV challenge.

Animals↗
PubMed1991

Method for transilial bone biopsy in baboons.

A surgical method for obtaining transilial bone biopsy specimens in baboons that provides adequate amounts of trabecular and cortical bone for histomorphometric analysis was developed. Biopsy specimens were removed from a site on the craniodorsal portion of the ilium by use of an 8-mm trephine.

Animals↗
PubMed1990

[Radiographic diagnosis of abdominal diseases in foals and ponys. II. Pathologic findings in 60 cases].

A diagnostic approach based on clinical and radiographic examinations for evaluation of young foals and small ponies with acute abdominal discomfort is presented. Standing right to left lateral abdominal radiographs were taken of 54 foals and 6 ponies using a previously described technique. Interpretation of the radiographs was in conjunction with all clinical and laboratory findings and patient management. Using this approach, the site and cause of acute abdominal discomfort could be diagnosed accurately in 55 of 60 (91%) patients as confirmed by clinical, surgical or necropsy findings. Typical radiographs and photographs taken at surgery or at necropsy are presented. Typical radiographic findings, their interpretation and possible underlying gastrointestinal diseases are listed. The incorporation of standing lateral abdominal radiography in the clinical evaluation of foals and ponies with acute abdominal diseases gives findings of high diagnostic significance and should contribute to clinical decision-making. Abdominal radiography can replace data from rectal palpation in foals and ponies.

Abdomen↗
PubMed1990

[X-ray diagnosis of abdominal diseases in foals and ponies. I. Technics and normal findings].

Clinical examination of foals and small ponies with abdominal disorders is limited by the inability to perform rectal palpation. In these patients, radiographic evaluation of the abdomen may contribute to the clinical diagnosis and may help to localize the site of abdominal diseases. The technique for lateral standing survey and contrast radiography of the abdomen in foals and the normal radiographic anatomy are described.

Animals↗
PubMed1989

[Total cholesterol findings in Austria--an overview of epidemiologic studies].

Hyperlipoproteinaemia is the most important public health risk factor for ischaemic heart disease. This publication gives a review of six Austrian epidemiological studies covering more than 87,000 people in all. The results are not representative for Austria, but give a picture of the epidemiology in Austria. Mean values were calculated age-standardized (age-adjusted when ten-year age groups are registered) to the Austrian population of 1985, for the age group 20 to 79 years. This age range covers 99.77% of the adult male population aged 20 or more, and 95.70% of the women. Mean total cholesterol level for the six studies is 224.2 mg/dl in men and 227.3 mg/dl in women. These results are similar to those of a representative study in the province of Vorarlberg in western Austria (220.0 mg/dl, and 227.4 mg/dl respectively). Variation range is 20.4 mg/dl in men, and 22.5 mg/dl in women; the coefficient of variation is 3.9% in both, men and women.

Adult↗
PubMed1989

Removal of tumors in the III ventricle using the lamina terminalis approach. Three cases of isolated growth of craniopharyngiomas in the III ventricle.

Tumors in the III ventricle were totally removed in three children using a route through the lamina terminalis. The cases are discussed on the basis of computed tomography and intraoperative findings. It seems that tumors 4 x 2 cm in size can be successfully removed via this relatively small opening if the neuroradiological findings and the probable histology (craniopharyngioma) provide secure evidence that the tumor site and growth matrix are located in the frontal and lower portion of the III ventricle. Besides the advantage of requiring no transparenchymal access, this quick axial (orthograde) approach exerts no pressure on the hypothalamus, a complication which cannot always be avoided with the transcallosal route or the route through the foramen of Monro. Furthermore, the immediate location of the tumor behind the usually protruding lamina terminalis permits a rapid operation without exploratory characteristics. The distance between the brain surface and the tumor with this procedure is 0 cm; however, it can be up to 9 cm, depending on the age of the patient, with other approaches.

Adolescent↗
PubMed1989

Arteriovenous malformation of the posterior ethmoidal artery as an unusual cause of amaurosis fugax. The ophthalmic steal syndrome.

We report the case of a patient with arteriovenous malformation fed by a posterior ethmoidal artery. The pre-operative amaurotic attacks on the diseased eye subsided after removal of the malformation. Doppler sonographic examination of the peripheral ophthalmic artery showed an inversion of the blood flow direction postoperatively. We describe a concept of an ophthalmic steal syndrome treated in this patient by removal of an arteriovenous malformation.

Arteries↗