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Biomedical subjects

R Davis

Publications and source records attributed to R Davis.

At least 163 records · Page 9Linked to original sources
PubMed1996

The significance of non-visualization of the fetal bladder during an ultrasound examination to evaluate second-trimester oligohydramnios.

Our objective was to determine the pregnancy outcome after targeted sonography performed for the evaluation of second-trimester oligohydramnios fails to visualize the fetal bladder. A retrospective review identified patients in 1990-94 who were referred for targeted sonography from 16 to 24 weeks to evaluate oligohydramnios. The ultrasound records and photographs from the initial examination were reviewed and compared to later pregnancy outcome data obtained by reviewing delivery and neonatal records, neonatal renal ultrasound reports or autopsy information. Complete outcome data were available in 98 patients. The fetal bladder was not visualized in 29 patients (30%). Post-delivery analysis of the fetal urinary tract was performed in 25 patients either by autopsy or by neonatal renal ultrasound scanning. A severe anatomic malformation of the urinary system was present and had been detected by targeted sonography in 23 of 25 cases (92%). The remaining two fetuses were found to have anatomically normal urinary tracts at autopsy, but other pathological findings suggested that a functional derangement of the urinary system had led to non-visualization of the bladder at ultrasound examination. Non-visualization of the fetal bladder during targeted sonography to evaluate oligohydramnios indicates a severe anatomic or functional problem of the fetal urinary tract. In our study, this ultrasound finding was associated with universal fetal or neonatal death.

Female↗
PubMed1996

Dose rate and mode of exposure are key factors in JNK activation by UV irradiation.

Single exposure of cells to UVC (254 nm for 30 s) or to UVB (300 nm for 10 min) was shown to activate jun-NH2 kinases which, in turn, phosphorylate their substrates ELK-1, c-jun and ATF-2. While UVC (40-80 J/m2) activates JNK up to 4 h, with maximal induction after 30 min, UVB (150-300 J/m2) activates JNK over a prolonged period, up to 24 h, with maximal induction after 6 h. UV-mediated activation of src-related tyrosine kinases and MAPK revealed different kinetics, with maximal induction after 24 h. As recent studies had indicated a role of a UVC component in mediating the ability of UVB to activate JNK, we have examined the effect of dose rate as well as of multiplicity of exposures on the activation of these kinases. The UVC portion found in 300 J/m2 UVB (5%, corresponding to 15 J/m2, administered within 10 s) did not activate JNK. However, when the same dose was administered at a lower rate (i.e. over 10 min, as needed for UVB irradiation) it was found capable of activating JNK, MAPK and src kinases, but to a lower degree and with different kinetics than found for UVB. Such differences point to cellular changes which are elicited by UVB, but not UVC. Although a single UVB exposure using a filter that blocks wavelengths below 300 nm prevented activation of JNK, multiple exposures of filtered UVB wavelengths (mimicking chronic exposure) were able to activate JNK. We conclude that the mode of UVB exposure (dose rate and multiplicity) is a crucial determinant for physiologically relevant activation of JNK.

3T3 Cells↗
PubMed1996

Occupational exposure leading to hantavirus pulmonary syndrome in a utility company employee.

Hantavirus pulmonary syndrome is a newly recognized rodent-borne zoonosis. We report a case of hantavirus pulmonary syndrome in an employee of a California utility company who was probably occupationally exposed to Sin Nombre virus. Environmental assessment and genetic comparison of the patient's hantavirus isolates to hantavirus isolates from rodents trapped at possible sites of exposure suggested that the patient contracted his infection at the work site. The study revealed a close correspondence between the patient's viral genotype and that from a rodent trapped at the work site. This report alerts the public health and medical community to the fact that employees of utility companies and similar industries may be an important risk group in areas where hantavirus is endemic and emphasizes the need to incorporate strategies for preventing exposure to hantavirus and other emerging infections into occupational safety protocols.

Animals↗
PubMed1996

Trauma recidivism in the elderly.

BACKGROUND: The incidence of recurrent trauma in the elderly is unknown. This study evaluated the risk of readmission for injury among elderly trauma patients compared with an uninjured geriatric cohort. The effects of age, sex, race, preexisting illness, and ISS on trauma recidivism were determined. METHODS: Population based retrospective cohort analysis of the elderly using administrative data from the Health Care Financing Administration was performed. The measured outcome was trauma admission within 5 years. The injured were identified using hospital discharge data and the Injury Severity Score generated by ICD-Map. The uninjured were identified from Medicare eligibility files. Comorbid illness was assessed using ICD-9CM codes from outpatient and inpatient data files. RESULTS: The injured members of the cohort had increased risk of subsequent new trauma admission (p < 0.001). Increasing Injury Severity Score, age, and comorbid illness are associated with trauma recidivism. CONCLUSION: Trauma in the elderly is recurrent. Further study is required to develop age and injury specific interventions to prevent recurrent injury.

Age Distribution↗
PubMed1996

Purification and characterization of the alternative nitrogenase from the photosynthetic bacterium Rhodospirillum rubrum.

The alternative nitrogenase from a nifH mutant of the photosynthetic bacterium Rhodospirillum rubrum has been purified and characterized. The dinitrogenase protein (ANF1) contains three subunits in an apparent alpha2beta2gamma2 structure and contains Fe but no Mo or V. A factor capable of activating apo-dinitrogenase (lacking the FeMo cofactor) from Azotobacter vinelandii was extracted from the alternative dinitrogenase protein with N-methylformamide. The electron paramagnetic resonance (EPR) signal of the dinitrogenase protein is not characteristic of the EPR signals of molybdenum- or vanadium-containing dinitrogenases. The alternative dinitrogenase reductase (ANF2) was purified as an alpha2 dimer containing an Fe4S4 cluster and exhibited an EPR spectrum characteristic of dinitrogenase reductases. The enzyme complex reduces protons to H2 very well but reduces N2 to ammonium poorly. Acetylene is reduced to a mixture of ethylene and ethane.

Acetylene↗
PubMed1996

Effect of ATP-induced permeabilization on loading of the Na+ probe SBFI into endothelial cells.

The fluoroprobe sodiumbinding benzofuran isophthalate (SBFI) is used to measure intracellular cytosolic sodium concentration ([Na]i). A problem with the use of this probe is the difficulty in loading it into cells. ATP reversibly increases membrane permeability of some cells via activation of receptors of the tetrabasic form of ATP (ATP4-). We investigated the effect of ATP-induced membrane permeabilization on loading of the acetoxymethyl ester (AM) form of SBFI (SBFI-AM) into bovine pulmonary arterial endothelial cells. Monolayers were incubated in a series of solutions that reversibly opened pores, loaded the fluoroprobe, and finally sealed the proes. ATP (1-5 mM) or 3'-O-(4-benzoyl)benzoyl-ATP (0.1-1 mM), an analogue 30-100x more specific for ATP4- receptors, was utilized to permeabilize the cell membrane. The signal-to-background ratio of the intracellular SBFI fluorescent signal was used as an indicator of the effectiveness of dye loading. ATP and 3'-O-(4-benzoyl)benzoyl-ATP significantly increased the signal-to-background ratio compared with the values obtained with the standard dye-loading procedure without ATP, indicating that permeabilization increased SBFI-AM entry into the cells. The permeabilization procedure produced a small decrease in cell viability, as determined with a fluorescent viability assay (ethidium dimer uptake), compared with the standard method of loading SBFI-AM. We used the procedure to measure baseline [Na]i and changes in [Na]i after the administration of ouabain (10(-4) M) and monensin (10(-5) M). Baseline [Na]i with this procedure (19.7 +/- 2.7 mM; n = 15 monolayers) was similar to measurements made in other cell types with the standard method of loading the probe. We conclude that 1) the ATP-induced permeabilization technique is an improved dye-loading method for SBFI-AM in endothelial cell monolayers that facilitates measurement of [Na]i and 2) these data suggest the presence of an ATP4 pore-forming mechanism in this cell type.

Adenosine Triphosphate↗
PubMed1996

Treatment of high-risk medulloblastoma and other primitive neuroectodermal tumors with reduced dose craniospinal radiation therapy and multi-agent nitrosourea-based chemotherapy.

PURPOSE: To investigate toxicity, and progression-free survival (PFS) of children and adults with newly diagnosed medulloblastoma, pineoblastoma, and other primitive neuroectodermal tumors (PNET) with a combined modality regimen of radiation therapy and adjuvant nitrosourea-based chemotherapy. PATIENTS AND METHODS: Between 1984 and 1992, 34 evaluable patients with newly diagnosed tumors were treated with chemotherapy and radiotherapy according to a single-arm phase II study. One cycle of chemotherapy was given prior to and for 6 cycles following craniospinal radiotherapy (CSA). Procarbazine, 6-thioguanine, and dibromodulcitol were given before lomustine (CCNU) to enhance CCNU-induced tumor cell kill and to reduce alkyltransferase repair of ethylated DNA. Vincristine was given 1 and 3 weeks after CCNU to kill cells that began to cycle after the challenge of the first four drugs. Chemotherapy was given in the outpatient setting. CSA radiation was planned to deliver a dose of 54 Gy to the primary tumor site and 24 Gy to the rest of the neuroaxis. Additional radiation was given to bulky disease outside the primary site if present. Hydroxyurea was used during radiotherapy as a radiosensitizer. RESULTS: Patients treated included 27 with medulloblastoma, 5 with pineoblastoma, and 2 with supratentorial PNET. All but 3 medulloblastoma cases were considered high risk either because of bulky residual disease remaining after surgery and/or metastatic disease detected during staging. For the 34 patients, 24 have progressed, 20 have died. Overall estimated PFS was 55% at 3 years and 35% at 5 years. The 5-year survival estimate is 56%. One patient had inadequate staging to determine M stage. Of the remaining 33 patients, there were 19 patients who had metastatic disease at diagnosis (M1 or higher stage) who had a 3- and 5-year PFS of 42 and 21% respectively and 5-year survival of 42%. There were 14 patients who had negative staging (M0 stage) who had a 3- and 5-year PFS of 69 and 52% respectively and 5-year survival of 71%. Of the 27 patients with medulloblastoma, 15 had M1 or higher stage. These 15 patients had a 5-year PFS and overall survival of only 20 and 40% respectively. Medulloblastoma patients with M0 staging had a 5-year PFS and overall survival of 52 and 73% respectively. Overall toxicity was primarily due to mild hematological toxicity and related to the use of the chemotherapy. CONCLUSIONS: The results using this therapy in high-risk groups of patients does not offer any improvement over results reported in other recent studies. The reason for these results may be due to the lowered craniospinal radiation dose.

Adolescent↗
PubMed1996

Fosinopril: a reappraisal of its pharmacology and therapeutic efficacy in essential hypertension.

Fosinopril is a phosphinic acid derivative which undergoes rapid hydrolysis after oral administration to the active diacid ACE inhibitor fosinoprilat. Cardiotropic effects have been associated with the drug, and the compensatory dual elimination route of fosinopril via renal and hepatic systems offers an opportunity for ACE inhibitor treatment of hypertension in patients with renal or hepatic impairment. Comparative trials of monotherapy with fosinopril 10 to 40 mg/day have demonstrated antihypertensive efficacy equivalent to that of sustained release nifedipine 40 mg/day, hydrochlorothiazide 25 to 50 mg/day, enalapril 5 to 10 mg/day amlodipine 5 to 10 mg/day and sustained release verapamil 240 to 480 mg/day, and superior to that of isradipine 5 mg/day. The efficacy of combination therapy with fosinopril 10 to 20 mg/day and hydrochlorothiazide 12.5 mg/day was significantly superior to that of hydrochlorothiazide alone, tended to be superior to that of fosinopril 20 mg/day alone and was similar to that of sustained release nifedipine 40 mg/day alone. The combination of fosinopril/chlorthalidone 20 to 40/25 mg/day was as effective as propranolol/chlorthalidone 80 to 160/25 mg/day. The incidence of adverse effects associated with fosinopril is low, and cough may possibly occur less often with this drug than with other ACE inhibitors. Fosinopril thus offers an effective and well tolerated option for the treatment of hypertension in adult and elderly patients, including those with renal or hepatic impairment.

Adult↗
PubMed1996

Ciprofloxacin. An updated review of its pharmacology, therapeutic efficacy and tolerability.

Ciprofloxacin is a broad spectrum fluoroquinolone antibacterial agent. Since its introduction in the 1980s, most Gram-negative bacteria have remained highly susceptible to this agent in vitro; Gram-positive bacteria are generally susceptible or moderately susceptible. Ciprofloxacin attains therapeutic concentrations in most tissues and body fluids. The results of clinical trials with ciprofloxacin have confirmed its clinical efficacy and low potential for adverse effects. Ciprofloxacin is effective in the treatment of a wide variety of infections, particularly those caused by Gram-negative pathogens. These include complicated urinary tract infections, sexually transmitted diseases (gonorrhoea and chancroid), skin and bone infections, gastrointestinal infections caused by multiresistant organisms, lower respiratory tract infections (including those in patients with cystic fibrosis), febrile neutropenia (combined with an agent which possesses good activity against Gram-positive bacteria), intra-abdominal infections (combined with an antianaerobic agent) and malignant external otitis. Ciprofloxacin should not be considered a first-line empirical therapy for respiratory tract infections if penicillin-susceptible Streptococcus pneumoniae is the primary pathogen; however, it is an appropriate treatment option in patients with mixed infections (where S. pneumoniae may or may not be present) or in patients with predisposing factors for Gram-negative infections. Clinically important drug interactions involving ciprofloxacin are well documented and avoidable with conscientious prescribing. Recommended dosage adjustments in patients with impaired renal function vary between countries; major adjustments are not required until the estimated creatinine clearance is < 30 ml/min/1.73m2 (or when the serum creatinine level is > or = 2 mg/dl). Ciprofloxacin is one of the few broad spectrum antibacterials available in both intravenous and oral formulations. In this respect, it offers the potential for cost savings with sequential intravenous and oral therapy in appropriately selected patients and may allow early discharge from hospital in some instances. In conclusion, ciprofloxacin has retained its excellent activity against most Gram-negative bacteria, and fulfilled its potential as an important antibacterial drug in the treatment of a wide range of infections. Rational prescribing will help to ensure the continued clinical usefulness of this valuable antimicrobial drug.

Anti-Infective Agents↗
PubMed1996

Dexfenfluramine. An updated review of its therapeutic use in the management of obesity.

Dexfenfluramine increases serotonergic activity by stimulating serotonin (5-hydroxytryptamine; 5-HT) release into brain synapses, inhibiting its reuptake into presynaptic neurons and by directly stimulating postsynaptic serotonin receptors. On the basis of the serotonin hypothesis of appetite control, these actions would be expected to reduce appetite and, consequently, bodyweight. Studies conducted in animals and in overweight patients with and without associated disorders have confirmed the weight-reducing efficacy and good tolerability of dexfenfluramine. In 3-month clinical studies in obese patients, weight reductions with dexfenfluramine 15mg twice daily combined with dietary support were significantly higher than those achieved with placebo and similar to those with ephedrine/caffeine 20/20mg 3 times daily, sibutramine 10mg once daily and fluoxetine 60 mg/day. Furthermore, dexfenfluramine recipients with non-insulin-dependent diabetes mellitus, hyperlipidaemia or hypertension consistently show improvements in glycaemic control, blood lipid profiles and blood pressure. 12-month trial results indicate that most weight loss occurs in the initial 6 months and appears to be maintained for a further 6 months. Weight regain after withdrawal of treatment in 12-month studies demonstrates that dexfenfluramine is effective in maintaining a stable bodyweight at a lower level than placebo and in limiting food intake over this time period. Commonly reported adverse events with dexfenfluramine include diarrhoea, tiredness, dry mouth and somnolence; these symptoms are generally mild and transient. Approximately 7 and 10% of dexfenfluramine recipients in short and long term studies withdrew because of adverse events. Dexfenfluramine was better tolerated than ephedrine/caffeine and fluoxetine in short term studies. Obesity is a chronic condition that is accompanied by a number of metabolic complications. It is a significant health problem in developed countries, and as a major risk factor for many chronic diseases, including diabetes and cardiovascular disease, the economic burden of this condition is considerable. As with other chronic conditions, there is a role for pharmacological intervention in patients with severe obesity. However, drugs should be considered as only one component of a weight-control programme, since additional lifestyle modification is required to maintain weight loss. The promising data on the long term efficacy and tolerability of dexfenfluramine as well as its favourable effects on risk factors associated with obesity requires confirmation in long term studies. In the meantime, dexfenfluramine should be considered a valuable adjunct to a reduced-calorie diet in the management of severe obesity, particularly in patients with associated disorders and those unsuccessful with conventional weight loss measures. Available data support the use of the drug for up to 1 year to maintain weight loss and thus dexfenfluramine should be considered for long term administration.

Animals↗
PubMed1996

Sertraline. A pharmacoeconomic evaluation of its use in depression.

Depression is a common condition that is often unrecognised, misdiagnosed and/or undertreated. It is associated with substantial direct, indirect and intangible costs. The indirect costs of lost earnings/productivity and premature death account for the majority of these costs; drug costs account for only about 1 to 2% of total costs and about 10 to 12% of direct costs. Thus, better recognition and appropriate treatment of depression would increase the direct costs associated with this illness, but would also have the potential to greatly reduce indirect costs and consequently the overall cost of depression. Because of their higher acquisition costs relative to tricyclic antidepressants (TCAs), there has been much debate about whether the use of sertraline or other selective serotonin reuptake inhibitors (SSRIs) for first-line treatment of depression can be justified. While these agents have similar efficacy to TCAs, they are better tolerated and have a lower risk of death on overdosage. Despite the large economic burden of depression on society, pharmacoeconomic data on sertraline and antidepressant drugs in general are scarce. Most of the available studies on sertraline are limited to considerations of direct costs and do not assess costs from a societal perspective. In addition, a number of studies have significant methodological problems which limit determination of meaningful conclusions. Nonetheless, data from 2 more recent studies with fewer methodological problems than earlier studies indicated that sertraline was more cost-effective than TCAs because of fewer psychiatrist consultations, and less costly than fluoxetine because of fewer absences from work and fewer medical consultations. The cost-utility ratio of maintenance therapy of depression with sertraline appears to fall within the range of accepted cost-utility ratios of common healthcare interventions. Thus, studies to date have generally shown that overall treatment costs with sertraline and other SSRIs are no greater than those for TCAs; this is despite the lower acquisition costs of the latter agents. Therefore, it is clear from these data that it is misleading to classify antidepressant agents as expensive or inexpensive based solely on their acquisition costs. Sertraline, therefore, can be considered as a first-line alternative to TCAs and other SSRIs for the treatment of depression on both clinical and pharmacoeconomic grounds.

1-Naphthylamine↗
PubMed1996

Ictal and interictal technetium-99m-bicisate brain SPECT in children with refractory epilepsy.

UNLABELLED: Identification of epileptogenic foci in patients with refractory epilepsy remains a significant diagnostic challenge. Magnetic resonance imaging studies frequently fail to reveal an anatomic origin for the seizures, and scalp electroencephalography is often limited to identification of the involved hemisphere. Functional imaging modalities such as PET and SPECT are more promising tools for this application because they reflect the functional pathology associated with the seizure. These changes are more pronounced ictally, but until recently, no radiopharmaceutical was available that could be used routinely for ictal SPECT. The present study was therefore undertaken to determine whether 99mTc-bicisate could be used in ictal SPECT in pediatric patients with refractory epilepsy, to compare the patterns of ictal and interictal blood flow in these patients and to compare the localization information provided by ictal SPECT with that available from other techniques. METHODS: Technetium-99m-bicisate/SPECT was compared prospectively with scalp EEG for its ability to identify a possible seizure focus in pediatric patients with refractory epilepsy. Ictal and interictal SPECT studies were performed in 10 patients (3-19 yr old, mean age 10.9 +/- 4.3 yr; 7 female, 3 male) in whom MRI scans revealed no lesions that might be responsible for the seizures. RESULTS: Ictal SPECT was performed in all patients, and all ictal studies revealed focal perfusion abnormalities. By comparison, four of the interictal SPECT studies showed regional hypoperfusion that corresponded to the regions of hyperperfusion in the ictal studies, and three showed regional hyperperfusion corresponding to the hyperperfused regions in the ictal studies. Three interictal studies revealed no abnormal perfusion. Scalp EEG provided localization information in five patients. CONCLUSION: These initial results suggest that ictal SPECT with 99mTc-bicisate is a more promising tool for the identification of epileptogenic foci than interictal SPECT or scalp EEG in patients without focal abnormalities on MRI.

Brain↗
PubMed1996

Summary of track A: basic science.

AIM: To review Track A, which is organized into five broad areas of emphasis. TOOLS: A variety of new virologic tools are allowing researchers to more effectively evaluate many aspects of HIV, from various therapies and vaccine candidates to the recombination and international spread of genotypes. PATHOGENESIS: The recent understandings of HIV-1 pathogenesis have led to potential new treatment strategies of early aggressive treatment with combination drugs and the potential for biologic or immunologic therapy directed to blocking viral entry through second receptors. TREATMENT: HIV treatment focused on chemical/drug advances and treatment, and immunologic/genetic advances. Some areas of development include optimizing combination therapies using the oncology model; continued work on new preclinical compounds (e.g. integrase and tat/rev inhibitors); evaluation of viral reduction in all compartments; and resistance surveillance and prevention. Biologics, including fusin/CC-CKR5 inhibitors and CD8 HIV-1 suppressor factors, ex vivo expansion of T cells and in vivo expansion of effector CD8 cells continue to be developed as possible future treatments. VACCINES: In order to obtain worldwide control over HIV, we must have a universally effective vaccine. The question remains as to what specifically is required for a protective response. Mechanisms of CD8 suppression, and cellular and antibody correlates of protection were discussed as areas of research that may shed light on the critical protective immune response. GENOTYPES: Discussion of HIV genotypes focused on international subtypes, correlates of diversity, and HIV-1 recombination. Numerous groups have shown an international intermixing of HIV-1 strains. Recombination during transcription was found to lead to extensive genomic shift and increased diversity, which may also increase HIV-1 fitness and enhance transmission. CONCLUSIONS: The spread and adaptation of HIV-1 is occurring independently of borders. Therefore, HIV-1 research must be global; vaccine development must be international in concept and application; collaboration in all areas is essential for success in combating HIV; and finally, the challenge for the future will be to actively involve all basic scientists in the science of the international epidemics.

AIDS Vaccines↗