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Biomedical subjects

B Simon

Publications and source records attributed to B Simon.

At least 91 records · Page 5Linked to original sources

The history of psychiatry: an opportunity for self-reflection and interdisciplinary dialogue. Essay review.

"Can you recommend a good one volume history of psychiatry?" I am often asked this question, being a psychiatric and psychoanalytic clinician who has also been deeply involved in the history of psychiatry, as a writer and as a teacher. "Single authored or multiple authored?" I ask in return and explain that if single authored the answer is no; if multiple authored I respond, "You have to await the publication of the huge encyclopedic volume(s), edited by John Gach and Edwin Wallace, sometime in the next few years. That 'definitive' work will not be definitive for very long; neither will it be inexpensive nor light reading, either in heft or in style." "What about Zilboorg's History of Medical Psychology?-I remember it as readable, portable, and quotable," my student or colleague continues. To that I reply, "Definitely worth reading, but you will have to do a lot of other reading to fill in the important omissions, to correct the errors of fact and interpretation, and to understand the author's unquestioned assumptions and biases." "Erwin Ackernecht's Short History of Psychiatry?" "Good book, amazing what's packed into it, but it really is short. If you read German very well, there is Der Wahnsinn by Leibbrand and Wettley, which would serve you better, but that is a huge book with small print, and for that too you would have to do a lot of extra reading to fill in gaps and to understand their biases."

Adult↗

Evaluation of the VA's Pilot Program in Institutional Reorganization toward Primary and Ambulatory Care: Part I, Changes in process and outcomes of care.

PURPOSE: To evaluate the impact of the reorganization of an academic Veterans Affairs medical center toward primary and ambulatory care--including the implementation of a medical-center-wide interdisciplinary firm system and ambulatory care training program--on the quality of primary ambulatory care. METHOD: Randomly selected male veterans visiting the Veterans Affairs Medical Center in Sepulveda, California, were surveyed in 1992, early in the implementation of the program, and in 1993, after the program had been fully implemented. Two surveys were used: one before the veterans saw their primary care providers (practice-based survey) and the other immediately after patient visits (visit-based survey). Survey-participant data were then linked to computerized utilization and mortality data. Survey topics were mapped to the medical center's strategic plan and goals for ambulatory care, and focused on patients' reports about the care they had received in terms of continuity, access, preventive care, and other aspects of the biopsychosocial model of care. Administrative computer data were then used to evaluate effects on medical center workload. Statistical analyses included analysis of variance, analysis of covariance, chi-square, and logistic regression. RESULTS: For practice-based comparisons, complete data were available for 1,262 veterans in 1992 and 1,373 in 1993. For visit-based comparisons, complete data were available for 1,407 veterans in 1992 and 643 in 1993. Results included statistically significant improvements in continuity of care and detection of depression as well as increased rates of preventive care counseling (smoking and exercise). The proportion of veterans reporting being seen by physicians increased, as did the proportion of patients seen for check-ups rather than for acute problems. Fewer patients were seen in subspecialty clinics than in general medicine clinics. Patient satisfaction increased, hospitalizations decreased, and death rates decreased. Alcohol counseling and access to care for acute symptoms declined. Workload shifted from subspecialists to generalists and from inpatient care to outpatient care. CONCLUSION: The institutional reorganization toward primary and ambulatory care succeeded in substantially improving the quality of ambulatory care, reflecting improvements in the system of care and of health care provider training in ambulatory care.

Ambulatory Care↗

Long-term functional status and mortality of elderly patients with severe closed head injuries.

OBJECTIVE: To evaluate long-term clinical outcome of elderly patients with severe closed head injuries. DESIGN: Retrospective study. PATIENTS AND METHODS: All patients older than 65 years of age admitted to a regional trauma center with a diagnosis of closed head injury and an admission Glasgow Coma Scale (GCS) score of 8 or less. Using chi 2 analysis, Student's t test, and multiple logistic regression, we correlated age, sex, mechanism of injury, pupillary reactivity, alcohol and drug use, admission GCS score, Injury Severity Score, Revised Trauma Score, heart rate, and blood pressure to the main outcome measures, i.e. long-term functional outcome and mortality. RESULTS: Among 40 elderly patients who met the criteria, 27% were still alive at the end of 38 +/- 3 month follow-up. Eighty-five percent of patients who were discharged from the hospital were still alive long-term, but did not show significant neurologic improvement. In a univariate analysis, GCS and pupillary reactivity were predictive for long-term functional outcome and mortality. In a multivariate analysis, GCS and heart rate were predictive. All patients with an admission GCS score of 3 died in-hospital. All patients with an admission GCS score of 3 to 7 were either deceased or lived in persistent vegetative or dependent functional states. CONCLUSIONS: Elderly patients with severe closed head injuries have high in-hospital mortality. Those who survived the hospital stay had high long-term survival, but did not show significant functional improvement. Prediction of long-term functional status is vital to the trauma care of elderly patients with severe closed head injuries.

Age Distribution↗

Sucralfate gel versus placebo in patients with non-erosive gastro-oesophageal reflux disease.

BACKGROUND: Gastro-oesophageal reflux disease, a term used to refer to chest symptoms that result from reflux of gastric acid into the oesophagus, occur at least daily in 7% and every 3 days in 33% of the population. METHODS: One hundred and forty-one patients with moderate to severe gastro-oesophageal reflux symptoms occurring at least three times per week (but no oesophageal erosions or ulcers at endoscopy) were treated in this randomized, double-blind, placebo-controlled study at six trial centres. Treatment was given for 6 weeks and consisted of daily doses of either 1 g sucralfate gel b.d. or placebo. The evaluation of efficacy was based on data of 139 patients. RESULTS: The responder rate at Day 42 was statistically significantly higher for the patients treated with sucralfate (71%) than for the placebo patients (29%) (P < 0.0001, Fisher's exact test). The overall response of the non-ulcer dyspepsia and gastro-oesophageal reflux disease symptoms was better for sucralfate gel than for placebo with 45% of patients treated with sucralfate gel being considered as having a 'good' or 'excellent' overall response compared with 22% of the patients who received placebo (P < 0.0001, Wilcoxon test). Only a few adverse experiences were reported by 10% of sucralfate patients and 7% of placebo patients. CONCLUSION: In this trial, we demonstrated a statistically significant superiority of sucralfate gel at a dosage of 1 g b.d. compared to placebo in the treatment of patients with gastro-oesophageal reflux disease. Sucralfate gel was well tolerated.

Adolescent↗

gamma-Aminobutyric acid concentrations in the cerebrospinal fluid of newborn infants determined by high performance liquid chromatography.

gamma-Aminobutyric acid (GABA), a major inhibitory amino acid, has a central role in cardiorespiratory regulation. Its measurement in the cerebrospinal fluid (CSF) complements the study of neurotransmission systems. Forty-one children were studied (postnatal age < 1 year). For each child, date of birth, date of sampling and current treatments were collated and their postnatal (days) and postconception (weeks) ages were calculated. CSF samples were studied using reverse phase high performance liquid chromatography (HPLC) with o-phthaldialdehyde derivation and spectro-fluorimetric measurement. A clear increase in levels of GABA was observed around 41 weeks postconception, followed by a progressive decrease, with levels stabilizing after 57 weeks postconception. GABA-regulated neuromodulation therefore appears to be mature at 41 weeks postconception and not at birth. The data could be used in further studies investigating amino acid metabolism in relation to brain function in various neurological disorders.

Age Factors↗

Bacteriostatic and bactericidal activities of benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis and Mycobacterium avium in human macrophages.

Inhibitory and bactericidal activities of KRM-1648 were determined against Mycobacterium tuberculosis and M. avium residing in human monocyte-derived macrophages and extracellular M. tuberculosis and M. avium. MICs and MBCs of KRM-1648 against intracellular and extracellular bacteria were substantially lower than those of rifampin. The MICs and MBCs of either drug against the intracellular bacteria were only twofold lower than or equal to the values found for extracellular bacteria. The prolonged effect of KRM-1648 found in this study is probably associated with high ratios of intracellular accumulation, which were 50- to 100-fold higher than that found for rifampin. Further studies on intracellular distribution of KRM-1648 and on the sites of actual interaction between the drug and bacteria residing in macrophages are necessary, as well as evaluation of combined effects of KRM-1648 with other drugs in long-term macrophage culture experiments.

Antibiotics, Antitubercular↗

[Status of ranitidine in eradication of Helicobacter pylori].

Permanent removal of Helicobacter pylori leads to a dramatic drop in the recurrence rate of peptic ulcers. The NIH Consensus Conference recommends that Hp-positive patients with duodenal or gastric ulcer should undergo eradication treatment. To date, however, there is no consensus on what constitutes optimal eradication treatment. Presently available therapy may be triple (bismuth plus two antibiotics), dual (acid inhibition and one antibiotic) or modified triple therapy (acid inhibition and two antibiotics). Among numerous treatment proposals, results gained with the H2 blocker ranitidine stand out, on account of the double-blind nature of the studies and the adequate number of cases involved. With modified triple therapy (300 mg ranitidine nocte and 3 times 750 mg amoxicillin daily) eradication rates ranging from 85 to 90%, and with dual therapy (600 mg ranitidine and 2 g amoxicillin daily) 60 to 65%, are obtained.

Amoxicillin↗

Effect of membrane potential on surface Ca2+ receptor activation in rat osteoclasts.

Osteoclasts are known to possess a divalent cation-sensitive receptor, the Ca2+ receptor (CaR). The latter monitors changes in the local Ca2+ concentration generated as a result of hydroxyapatite dissolution. CaR activation elevates cytosolic [Ca2+] and thereby inhibits osteoclastic bone resorption. Recent studies have used Ni2+ as a surrogate CaR agonist to elicit changes in cytosolic [Ca2+]. This article examines the effects of membrane potential changes on the kinetics of the cytosolic [Ca2+] signal resulting from such Ni(2+)-induced CaR activation. Membrane potential was altered through variations in the extracellular [K] in combination with applications of the K+ ionophore, valinomycin. Membrane potential changes were confirmed by independent electrophysiological patch clamp studies of whole osteoclasts. The application of valinomycin produced a distinct, sustained elevation of cytosolic [Ca2+] in single fura 2-loaded cells, a "primary" response. This response was independent of valinomycin concentration (between 5 nM to 5 microM) and persisted in Ca(2+)-free, EGTA-containing solutions. It also persisted both in high (105 mM) and low (5 mM) extracellular [K+]. A gradual "secondary" elevation of cytosolic [Ca2+] then followed with the continued application of valinomycin, but this was eliminated by sequestering the extracellular [Ca2+] or by increasing extracellular [K+] from 5 to 105 mM. In a separate set of experiments, the presence of 5 microM [valinomycin]-([K+] = 5 mM) prolonged the cytosolic [Ca2+] signal elicited by 50 microM-[Ni2+] application. These prolonged kinetics persisted in low extracellular [Ca2+] (zero-added Ca2+), but reverted to a rapid time-course in the presence of 105 mM-[K+] or at higher [Ni2+] (500 microM and 5 mM). The experiments thus indicate that membrane voltage modifies the kinetics of CaR activation by Ni2+ and therefore suggests that the CaR is an integral protein in the osteoclast surface membrane.

Animals↗

The alpha 6-integrin receptor in pancreatic carcinoma.

BACKGROUND/AIMS: The alpha 6-containing integrin was suggested to be involved in the process of tumor invasion and metastasis. Therefore, the aim of the study was to investigate the expression and function of this adhesion receptor in pancreatic carcinoma. METHODS: Integrin expression was investigated in pancreatic tissue and tumor cell lines using immunohistochemistry. Radioimmunoprecipitation was used to determine the complex composition of alpha 6. To analyze the function of the alpha 6-containing integrin in pancreatic cancer, in vitro adhesion, migration, and invasion experiments were performed. RESULTS: The alpha 6-containing integrin was differentially expressed in normal pancreas and pancreatic carcinoma. Immunoprecipitation of different pancreatic carcinoma cell lines showed that alpha 6 was expressed together with the beta 4 subunit as alpha 6 beta 4 complex. However, adhesion of pancreatic cancer cells to laminin could be inhibited with anti-alpha 6 and anti-beta 1 integrin antibodies but not by anti-beta 4 integrin antibody. Migration of the cells through laminin was almost completely inhibited by anti-beta 1 antibody but not by other anti-integrin antibodies. Tumor cell invasion through a reconstituted basement membrane was only slightly inhibited by anti-alpha 6 antibody. In contrast, a marked inhibition was observed using anti-beta 1 antibodies, anti-alpha 2-anti-alpha 5 antibodies, and RGDS. CONCLUSIONS: The alpha 6-containing integrin is a laminin adhesion receptor in pancreatic carcinoma cells, possibly involved in tumor invasion through the basement membrane.

Antigens, Surface↗

Molecular cloning of major and minor allergens of Alternaria alternata and Cladosporium herbarum.

The two moulds, Alternaria alternata and Cladosporium herbarum, are recognized as major causes of fungal allergies. Cloning, sequencing and heterologous expression of the allergens of the two moulds is a necessary step in understanding fungal allergy and in the development of new and improved methods of diagnosis and therapy. The seven new mould allergens presented here represent four new allergen proteins: aldehyde dehydrogenase (ALDH), enolase, YCP4 (previously found as a Saccharomyces cerevisiae protein of unknown function), and the acidic ribosomal protein, P2. Three of them (ALDH, YCP4 and P2) were found to be allergens in both fungi, Alternaria and Cladosporium. All allergens found so far are cytoplasmic proteins and are rather well conserved in evolution even when comparing distant species. Most of the allergens have "household" functions (ALDH, enolase). One allergen (P2) is a homolog of a very highly conserved human lupus erythematodes (LE) antigen. None of the fungal allergens is clearly related to other known non-fungal allergens.

Allergens↗

Increasing the impact of quality improvement on health: an expert panel method for setting institutional priorities.

BACKGROUND: Successful implementation of modern ongoing quality improvement (QI) methods requires investment of institutional resources, but can produce significant improvements in medical care. A health care organization's goals and objectives for improving care are expressed in strategic plan documents, which could provide a framework for planning quality improvement initiatives. However, institutional strategic planning processes are often not well linked to QI staff and resources. We developed the Quality Action Program (QAP) to connect QI to strategic planning. HISTORY: In 1991, Sepulveda VHAMC implemented a major primary care initiative, documented in a comprehensive strategic plan. The QAP was developed to enable the initiative to be evaluated within a QI context. THREE-ROUND EXPERT PANEL PROCESS: To carry out the QAP, members of an institution's quality council engage in a structured consensus process. The first round involves reading educational materials and filling out a quality action survey the second round includes participation in an expert panel meeting, and the third round involves making final priority rankings. EIGHT-STEP QAP IMPLEMENTATION PLAN: QI staff carry out activities to prepare for and carry out the three-round expert panel process. RESULTS: QAP induced significant institutional QI activity directed toward achieving the top-ranked QI criterion--ensuring continuity of care. Continuity of care improved significantly over time between the pre- and post-QAP periods. CONCLUSIONS: Expert panel methods can be used to link strategic plan goals and objectives to QI efforts.

California↗

Effects of a temperature increase on oxygen consumption of yellow freshwater eels exposed to high hydrostatic pressure.

Oxygen consumption was measured in yellow freshwater eels, Anguilla anguilla, during exposure to a hydrostatic pressure (HP) of 101 atmosphere absolute (ATA) for 3 h, either with or without a 5 degrees C increase in water temperature. It was found that concomitant increases in temperature and pressure resulted in an increase in oxygen consumption that was lower than when pressure alone was increased. When eels were acclimated to HP for 21 days and then submitted to a temperature increase of 5 degrees C, this induced a significant increase in oxygen consumption but only during the first hour. It is therefore concluded that raising the water temperature during the first hours under pressure could counterbalance the pressure effects on membrane fluidity in a thermodynamic manner and thus help shallow-water fish acclimate to high pressure. In contrast, when acclimation processes are ended, the temperature effect disappears within 1 h.

Acclimatization↗

Comparison of activities of rifapentine and rifampin against Mycobacterium tuberculosis residing in human macrophages.

The activities of rifapentine and rifampin against Mycobacterium tuberculosis residing in human monocyte-derived macrophages were determined. The MICs and MBCs of rifapentine for intracellular bacteria were two- to fourfold lower than those of rifampin. For extracellular bacteria, this difference was less noticeable. Nevertheless, the more favorable pharmacokinetics of rifapentine over rifampin was addressed in other experimental models. These models showed substantial differences after short pulsed exposures of the infected macrophages to the drugs and when the infected macrophages were exposed to changing drug concentrations that imitated the pharmacokinetic curves observed in blood. Once-a-week exposures to rifapentine concentrations equivalent to those attained in blood after one 600-mg dose resulted during the first week in a dramatic decline in the number of bacteria, and this decline was maintained at a minimal level for a period of four weeks. The results of this study have shown the suitability of rifapentine for intermittent-treatment regimens. The prolonged effect of rifapentine found in this study may be associated with high ratios of intracellular accumulation, which were four- to fivefold higher than those found for rifampin. Further studies on the intracellular distribution of rifamycins and on the sites of actual interaction between the drugs and bacteria residing in macrophages are necessary.

Antitubercular Agents↗

Strategy to detect and identify Bartonella species in routine clinical laboratory yields Bartonella henselae from human immunodeficiency virus-positive patient and unique Bartonella strain from his cat.

We wished to develop a cost-effective, rapid strategy to detect and identify Bartonella species in the clinical laboratory and to determine the prevalence of Bartonella infection in the Houston veteran population. Bartonella colonies were identified by colony morphology, Gram stain, RapID ANA, repetitive extragenic palindromic-PCR (REP-PCR) and whole-cell fatty acid (CFA) analysis, and these methods were compared for their usefulness. A new test order for "Rochalimaea culture" (the genus Bartonella was previously known as the genus Rochalimaea) was instituted, and in addition, all blood specimens submitted for fungal culture (obtained in an isolator tube) were processed for Bartonella culture. Over a 16-month period we isolated Bartonella henselae from only 0.4% (2 of 533) of total cultures but from 1% (2 of 204) of human immunodeficiency virus-positive patients. After sufficient growth, identification of the Bartonella isolates to the species level could be obtained in 2 days. The REP-PCR allowed discrimination of all known species, whereas CFA analysis distinguished all except B. henselae and Bartonella quintana. The RapID ANA results failed to differentiate between B. henselae and B. quintana, and results for other species differed by only one or two tests. Blood obtained from a kitten which had been introduced into the household of one patient 2 months before the onset of fever yielded a Bartonella strain which was shown to be different from the strain from the patient and distinct from other Bartonella species by a combination of REP-PCR, CFA, and growth characteristics. Subsequent analysis of the citrate synthase gene sequence showed only an 86% similarity with any of the other known Bartonella species, suggesting that this isolate represents a distinct, previously uncharacterized species of Bartonella.

AIDS-Related Opportunistic Infections↗

Caffeine modulates Ca2+ receptor activation in isolated rat osteoclasts and induces intracellular Ca2+ release.

A ryanodine-sensitive pathway is involved in intracellular Ca2+ release in response to activation of the osteoclast cell surface Ca2+ receptor. We now report that the ryanodine-receptor modulator, caffeine itself released intracellularly stored Ca2+ and, strongly inhibited Ca2+ release triggered in response to Ca(2+)-receptor activation by Ni2+, a surrogate cation agonist. Caffeine yielded a bell-shaped concentration-response curve (0.005-2 mM) and displayed use-dependent inactivation. Furthermore, responses to caffeine were abolished on prior application of Ni2+ (5 mM). Subthreshold (0.005 mM) caffeine concentrations abolished Ni(2+)-induced elevations in the cytosolic Ca2+ concentration ([Ca2+]). However, in a Ca(2+)-free, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-containing solution (extracellular [Ca2+] < 10 nM), caffeine (0.5 mM) neither elevated [Ca2+] nor inhibited the response to Ni2+. Finally, when caffeine was applied to intercept the plateau phase of the cytosolic Ca2+ signal triggered by extracellular Ca2+ elevation (10 mM), a rapid but reversible inactivation followed. These studies strongly indicate the existence of a caffeine-sensitive mechanism for the release of intracellularly stored Ca2+ in the osteoclast.

Animals↗

Methods for determining concentrations of antimicrobial agents in human monocytes.

Human monocytes can be derived from the leukocyte-rich by-product of donors' blood available after platelet separation. Large volumes of the monocyte samples obtained from this product provided an opportunity to conduct experiments with relatively high concentrations of the antimicrobial agents sufficient for their detection in bioassays, thus avoiding the necessity of working with the radiolabelled drugs. Washing of the cells after their exposure to the drug may lead to an extraction of the tested agent from the cell, especially if it is a substance of low molecular weight. In our experiments we excluded the washing step, and separated the monocytes from the extracellular medium by velocity gradient centrifugation. In experiments with two rifamycins, the cell pellet as well as the extracellular fluid were subjected to a bioassay using Micrococcus luteus as a target organism. The method showed good reproducibility and consistency in results obtained.

Anti-Bacterial Agents↗