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Biomedical subjects

L Horn

Publications and source records attributed to L Horn.

At least 19 recordsLinked to original sources
PubMed2006

Administrative monitoring of tuberculosis treatment in Switzerland.

SETTING: Treatment of tuberculosis (TB) is critically dependent on adherence. Directly observed treatment (DOT) has been shown to be effective. OBJECTIVE: To determine operational treatment outcome using administrative treatment monitoring (ATM) to assess the need for more vigorous promotion of DOT. DESIGN: Cohort study in eastern Switzerland, where ATM was started in 2002. Bi-monthly progress forms and a treatment outcome form (after 6 months) were sent to the treating doctors. Forms not returned within 6 weeks were followed up with phone calls. RESULTS: Between 2002 and 2004, 98 (87.5%) of 112 new TB patients completed a 6-month treatment course. Eight elderly patients died of causes other than TB while on treatment, four travelled out of the region and two were lost to follow-up. Treating doctors opted for DOT in only seven cases. CONCLUSION: Given the high success rate of 87.5% in our cohort, more vigorous promotion of DOT is not a priority for TB case management in eastern Switzerland. In our setting, ATM in collaboration with the family doctors offers a valuable alternative to the more time-consuming universal DOT.

Adult↗
PubMed2001

Cost-effectiveness of tuberculosis screening and observed preventive therapy for active drug injectors at a syringe-exchange program.

This study examined whether costs associated with tuberculosis (TB) screening and directly observed preventive therapy (DOPT) among drug injectors attending a syringe exchange are justified by cases and costs of active TB cases prevented and examined the impact of monetary incentives to promote adherence on cost-effectiveness. We examined program costs and projected savings using observed adherence and prevalence rates and literature estimates of isoniazid (INH) preventive therapy efficacy, expected INH hepatoxicity rates, and TB treatment costs; we conducted sensitivity analyses for a range of INH effectiveness, chest X-ray (CXR) referral adherence, and different strategies regarding anergy among persons affected with human immunodeficiency virus (HIV). For 1,000 patients offered screening, incorporating real observed program adherence rates, the program would avert $179,934 in TB treatment costs, for a net savings of $123,081. Assuming a modest risk of TB among HIV-infected anergic persons, all strategies with regard to anergy were cost saving, and the strategy of not screening for anergy and not providing DOPT to HIV-infected anergic persons resulted in the greatest cost savings. If an incentive of $25 per person increased CXR adherence from the observed 31% to 50% or 100%, over a 5-year follow-up the net cost savings would increase to $170,054 and $414,856, respectively. In this model, TB screening and DOPT at a syringe exchange is a cost-effective intervention and is cost-saving compared to costs of treating active TB cases that would have occurred in the absence of the intervention. This model is useful in evaluating the cost impact of planned program refinements, which can then be tested. Monetary incentives for those referred for screening CXRs would be justified on a cost basis if they had even a modest beneficial impact on adherence.

AIDS-Related Opportunistic Infections↗
PubMed2001

Pharmacological determinants of 9-aminocamptothecin cytotoxicity.

The camptothecins are a group of anticancer agents with a unique mechanism of action: poisoning of eukaryotic DNA topoisomerase I. 9-aminocamptothecin (9-AC), a potent water-insoluble derivative of camptothecin, is currently undergoing clinical testing. The kinetics of the active derivative 9-AC lactone in cell culture media was defined, and then 9-AC cytotoxicity against human breast (MCF-7), bladder (MGH-U1), and colon (HT-29) cancer cell lines was studied. The relationship between cytotoxic effects, drug concentration, and exposure time was then explored. For all of the three cell lines, 9-AC cytotoxicity increased with both higher drug concentrations and longer exposure times. However, when the duration of exposure was less than 24 h, cytotoxicity was limited and less than 1 log of cell killing occurred, even with very high drug concentrations. Minimal cell killing was also observed unless 9-AC concentrations exceeded a threshold of 2.7 nM. No fixed relationship between the survival fraction and the area under the drug concentration-time curve could be modeled that would fit all of the three cell lines. However, data for the three cell lines from the multiple exposure time experiments were fitted very well to the pharmacodynamic model C(n)t = k (r2, 0.90-0.99), where C is the drug concentration, n is the drug concentration coefficient, and t is the exposure time. For the three cell lines, to kill 1 log of cells, 0.30 < n < 0.85, which indicated that duration of exposure was more important than concentration. Our data support the use of 9-AC by infusion for 24 h or longer in clinical studies providing target plasma concentrations can be achieved.

Antineoplastic Agents↗
PubMed1998

Oxidative stress and 1-methyl-2-nitroimidazole cytotoxicity.

The 2-nitroimidazoles have been used clinically to radiosensitize resistant hypoxic cells, but a dose-limiting peripheral neuropathy has restricted their therapeutic effectiveness. A model compound, 1-methyl-2-nitroimidazole (INO2), was used to investigate the possible role of oxidative stress in this normal tissue toxicity. Chinese hamster ovary (CHO) cells were 10-15 times more resistant to 20 mM INO2 under aerobic than hypoxic conditions. In comparison, a pair of transformed rat embryo fibroblasts (ER17-1wtp53 and ER12L5mtpP53), differing in their p53 genotype, were approximately 3- to 4-fold more sensitive than Chinese hamster ovary cells to INO2 under aerobic conditions, but had the same sensitivity as Chinese hamster ovary cells under hypoxic conditions. These results are consistent with an earlier hypothesis that the mechanism of aerobic toxicity is different from that of hypoxic toxicity (nitroreduction) and show that neither toxicity is dependent on cellular p53 status. There was an increase in the production of reactive oxygen intermediates and a decrease in the antioxidant glutathione following aerobic exposure to INO2, which correlated with cell survival in all three cell lines. No evidence of reductive adducts of the 2-nitroimidazole 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetam ide (EF5) was found by immunofluorescent techniques in aerobic cells. Differing activities of the antioxidant enzymes superoxide dismutase and catalase could be correlated with INO2 aerobic cytotoxicity. DNA strand breaks, as measured by the comet assay, paralleled the appearance of INO2 aerobic cytotoxicity in all three cell lines. Taken together, these results strongly support the conclusion that the aerobic toxicity of IN02 is due to active oxygen species created by futile redox cycling of the parent compound.

Aerobiosis↗
PubMed1997

Vasoactive intestinal polypeptide (VIP) innervation of rat spleen, thymus, and lymph nodes.

In the thymus, VIP-positive (+) fibers were found in the capsular/septal system, cortex, and medulla. In the spleen, VIP+ nerves coursed along large arteries and central arterioles, and in the white pulp, venous/trabecular system, and red pulp. Splenic VIP innervation was more robust in Long-Evans hooded rats than in Fischer 344 rats. VIP+ nerves in mesenteric lymph nodes were found in the cortex, and along the cortical vasculature and medullary cords. No VIP innervation was observed in popliteal lymph nodes. Immunocytes also were VIP+, suggesting that both neural and cellular synthesis of VIP contributes to VIP concentration in lymphoid organs. Surgical sympathectomy did not alter splenic or thymic VIP content, respectively, and VIP innervation of these organs was not altered, suggesting an origin for VIP+ nerves other than the sympathetic nervous system.

Animals↗
PubMed1991

Biochemical and physiological characterization of the efrotomycin fermentation.

An efrotomycin fermentation was characterized through physical, chemical and biochemical studies. Growth of the actinomycete, Nocardia lactamdurans occurred during the first 50 h of the fermentation cycle at the expense of glucose, protein, and triglycerides. The initiation of efrotomycin biosynthesis was observed when glucose dropped to a low concentration. Upon glucose depletion, cell growth ceased and a switch in the respiratory quotient occurred. Efrotomycin biosynthesis was supported by the utilization of soybean oil and starch. Analysis of triglyceride metabolism showed that no diglycerides or monoglycerides accumulated during the fermentation. The activity of extracellular enzymes (lipase, protease, and amylase) increased during the cell growth phase and decreased significantly after 150 h. The concentrations of DNA, tetrahydro-vitamin K2 (a membrane component), and free amino acids in the supernatant increased dramatically late in the fermentation cycle (225 h), indicating massive cell lysis. During this same time period, a reduction in cellular respiratory activity and efrotomycin biosynthesis were observed.

Amino Acids↗
PubMed1989

Advances in the use of computerized gas chromatography-mass spectrometry and high-performance liquid chromatography with rapid scanning detection for clinical diagnosis.

A multi-component analytical system designed for the diagnosis of metabolic disorders is described. The urinary components are separated by a variety of chromatographic techniques, including automated amino acid analysis, high-performance liquid chromatography with diode-array detection and gas chromatography-mass spectrometry with a computerized mass spectral library search for identification of organic acids. The complete system can be used to diagnose over 100 different metabolic diseases. The usefulness of the chromatographic system is exemplified by the pre- and postnatal diagnosis of glutaric aciduria type I, the diagnosis of lysinuric protein intolerance and of alkaptonuria. Drugs and diet may cause interfering metabolites, as exemplified by glycofurol, used as a solvent for intravenous drugs, and saccharin. It is predicted that chromatography and mass spectrometry will continue to be important diagnostic tools for many years ahead.

Acids↗
PubMed1989

The EASI: a self-administered screening test for cognitive impairment in the elderly.

The Early Assessment Self Inventory (EASI), a rapid self-administered screening test for cognitive impairment in the elderly, was constructed to permit individuals to be assessed in a group or singly without examiner intervention. This paper-and-pencil device requires a fourth-grade reading level and makes minimal demands on literacy while assessing orientation, recent and remote memory, language, visual-construction, calculation, and attention. In the present study, the EASI was group-administered to 146 elderly persons attending senior centers and completed individually without examiner intervention by 19 outpatients at a memory disorders clinic. Participants were 60 to 95 years old with 5 to 18 years of education. The EASI demonstrated good internal consistency and test-retest reliability and was significantly correlated with the Mini-Mental State Exam and the Mattis Dementia Rating Scale, both widely used screening instruments. Neuropsychological measures of memory, attention, and verbal fluency correlated as well with the EASI as with the examiner-administered screening instruments, suggesting that the EASI may provide an efficient method of screening for cognitive impairment.

Aged↗
PubMed1988

Computerized 3-D reconstruction of small blood vessels from high voltage electron-micrographs of thick serial cross sections.

Morphological analysis of compartments in terms of volumes and the orientation of the cells and their nuclei within very small mesenteric arteries and arterioles is being carried out. Samples were from simultaneously sham operated and instrumented control and one-clip two kidney Goldblatt sustained (30 days) hypertensive dogs. Collection of specimens was standardized, i.e. sampling location, perfusion fixation, embedding, staining, and sectioning by methods proven to preserve in vivo dimensions. Serial thick cross sections (0.5 mu) were subjected to high voltage electromicrography (1.0 MeV) at 2500x and then linearly enlarged 3x photographically. The glossy micrographs (7500x) were made into montages and the contours of the smooth muscle layer (vascular smooth muscle), the endothelium (E), nuclei (N), and the internal lamina (IL) were digitized on a large GTCO digi-pad with input to a microcomputer (PC-Limited, Turbo) equipped with a 20 MB hard disk and coprocessor. Solid and transparent image reconstructions and computerized dissection of cell compartments were performed. Compartment volumes of vascular smooth muscle, IL, E and N, and individual cell and nuclear volumes, as well as nuclear/cytoplasmic ratios were calculated. Image reconstructions are presented. The emphasis is on methods and these are discussed in terms of useability for determining accurate microvessel morphology in health and disease, with particular emphasis on assessment of hypertrophy and hyperplasia in experimental hypertension, and architectural angiogenesis in general.

Animals↗
PubMed1986

Systematic laboratory diagnosis of human metabolic disorders.

A multicomponent analytical system for diagnosis of human metabolic disorders is overviewed. After preliminary analysis of the urine with simple chemical tests and standard clinical chemistry methods, the samples undergo a variety of chromatographic separations. Paper chromatography and thin-layer chromatography determine carbohydrates and mucopolysaccharides. Amino acids are analysed by automatic ionexchange chromatography. Gas chromatography - mass spectrometry with computerized library search is used to separate and identify organic acids, and high performance liquid chromatography with computerized diodearray detector is used to analyse metabolites of nucleic acids and other non-volatile or labile constituents. The system, gradually developed during the past two decades, is routinely used to diagnose, via its detection of pathological metabolites, around 100 different metabolic disorders. The methods may also be used to monitor the efficacy of therapeutic treatment in some of the cases where this is possible.

Chromatography, High Pressure Liquid↗
PubMed1986

Urinary excretion of N-acetyl amino acids in patients with some inborn errors of amino acid metabolism.

Urinary organic acid profiles of patients with Maple Syrup Urine Disease (MSUD), hereditary tyrosinemia and phenylketonuria (PKU) have been studied by means of capillary GC-MS-computer technique. In addition to the characteristic metabolites of these disorders, increased amounts of N-acetylleucine, N-acetylisoleucine and N-acetylvaline were found in MSUD-urine. Increased excretion of N-acetylphenylalanine occurred in PKU, and in tyrosinemia both the latter compound and increased N-acetyltyrosine excretion were observed. These results together with literature reports of similar studies on patients with other aminoacidopathies may indicate that most disorders which result in accumulation of one or more specific amino acids, will convert a small fraction of them into their corresponding N-acetyl derivative.

Acetylation↗
PubMed1984

An evaluation of Salmonella (Ames) test data in the published literature: application of statistical procedures and analysis of mutagenic potency.

We searched the published literature for Salmonella test data on some 450 chemicals. Only 137 of more than 400 articles containing original data satisfied minimum criteria for a quantitative analysis [1751 experiments, comprising data on 152 chemicals (Table 1)]. Many of these papers did not report basic information about the test protocol (Table 2). We used previously described statistical procedures (Bernstein et al., 1982) to estimate the initial slopes of the dose-response curves and corresponding standard errors. We also applied tests for significance and linear goodness-of-fit. We then used the results of these analyses to examine several issues: (1) Linearity of the low dose region of the dose-response curve. We found that the overwhelming majority of curves were linear, though ability to detect non-linearity of dose-response curves in the standard plate test is only limited. 7% of all experiments to which the goodness-of-fit test was applied were curves of increasing slope, and with a few possible exceptions, these were not obviously associated with any particular mutagens, even those generally considered to produce non-linear effects such as MNNG and EMS (Table 3). (2) Performance of the statistical test for significance. Results of the statistical test for significance of the dose-response were compared with author's opinions as to positivity. In almost all cases (94%) results of the statistical test and authors opinions were the same. In the examples of conflicting opinions, the reasons were: (a) the statistical test places more weight than do most authors on the presence of a linear dose-response; (b) most authors tend to require at least a 2-fold increase over the spontaneous background for 'significance', and (c) when the number of spontaneous revertants is small (e.g., TA1537), authors tend to require a larger increase in induced revertants than when the spontaneous background is large, whereas the statistical procedure makes no such distinction. These factors result in the statistical test tending to identify more experiments as positive than do authors, provided there is a linear dose-response, and authors tending to judge more experiments as positive when the dose-response is not linear. (3) Reproducibility. Among the 1751 experiments there were 122 data-sets (a total of 333 experiments) in which the same chemical was tested by two or more different laboratories under the same protocol. 21 of the 122 data-sets had some disagreement between experiments as to whether results were positive or negative (Table 4).(ABSTRACT TRUNCATED AT 400 WORDS)

Dose-Response Relationship, Drug↗