Growing with the student unit. Interview by Teresa O'Connor.
Explore the source record for details and available documents.
Education, Nursing↗
Biomedical subjects
R Davis
Publications and source records attributed to R Davis.
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↗
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↗
Differential effects of UV-B and UV-C components of solar radiation on MAP kinase signal transduction pathways in epidermal keratinocytes.
Exposure to solar ultraviolet (UV) light is a major cause of skin cancer, the most common human neoplasm. The earth's upper atmosphere absorbs the high energy UV-C wavelengths (100-280 nm), while allowing transmission of UV-B (280-320 nm) and UV-A (320-400 nm). It is therefore UV-B and to some extent UV-A, that contributes to most human skin malignancies. We report that the exposure of cultured keratinocytes or skin to UV-C radiation causes activation of MAP kinases (ERK and JNK). In contrast, the solar radiation associated with skin cancer (UV-B) was an ineffective activator of the ERK and JNK signal transduction pathways. Therefore, while exposure of epidermal cells to UV-C radiation under laboratory conditions causes marked activation of MAP kinase signal transduction pathways, only a low level of MAP kinase signaling is involved in the response of skin to biologically relevant solar radiation.
Animals↗
Studies of Schizosaccharomyces pombe DNA polymerase alpha at different stages of the cell cycle.
The status of Schizosaccharomyces pombe (fission yeast) DNA polymerase alpha was investigated at different stages of the cell cycle. S.pombe DNA polymerase alpha is a phosphoprotein, with serine being the exclusive phosphoamino acid. By in vivo pulse labeling experiments DNA polymerase alpha was found to be phosphorylated to a 3-fold higher level in late S phase cells compared with cells in the G2 and M phases, but the steady-state level of phosphorylation did not vary significantly during the cell cycle. Tryptic phosphopeptide mapping demonstrated that the phosphorylation sites of DNA polymerase alpha from late S phase cells were not the same as that from G2/M phase cells. DNA polymerase alpha partially purified from G1/S cells had a different mobility in native gels from that from G2/M phase cells. The partially purified polymerase alpha from G1/S phase cells had a higher affinity for single-stranded DNA than that from G2/M phase cells. Despite the apparent differences in cell cycle-dependent phosphorylation, mobility in native gels and affinity for DNA, the in vitro enzymatic activity of the partially purified DNA polymerase alpha did not appear to vary during the cell cycle. The possible biological significance of these cell cycle-dependent characteristics of DNA polymerase alpha is discussed.
Cell Cycle↗
Comparative anterograde amnestic and anticonvulsant effects of two types of NMDA receptor antagonists: MK-801 and HA-966.
The anterograde amnestic effects of non-competitive NMDA antagonists MK-801 and HA-966 on classic fear conditioning in goldfish (Carassius auratus) were examined in a series of experiments. Experiments 1 and 2 contrasted the anterograde amnestic effects of MK-801, (+)HA-966, and (-)HA-966. Experiment 3 examined the effects of MK-801 and (+)HA-966 on the expression of conditioned responses. Experiments 4 and 5 investigated whether the potency of MK-801, (+)HA-966 or (-)HA-966 in blocking NMDA-induced convulsions paralleled their potency in producing amnesia. The results showed that MK-801 was more potent than (+)HA-966 in producing anterograde amnesia and impairing expression, while (-)HA-966 did not produce anterograde amnesia. The anticonvulsant potency of MK-801, (+)HA-966, and (-)HA-966 paralleled their amnestic potency. These findings suggested that MK-801 and (+)HA-966 produced anterograde amnesia by their specific antagonism of the NMDA receptor complex.
Amnesia↗
A cell type-specific silencer in the human choline acetyltransferase gene requiring two distinct and interactive E boxes.
We have previously reported that cholinergic neuron-specific expression of the human choline acetyltransferase gene is mediated by two co-operative silencers. We have now localized the proximal silencer to the region from nucleotide -2195 to -2409, which contains two distinct E boxes (CACCTG and CATGTG). Deletion or mutation of either of these E boxes results in a loss of silencer activity. There are specific nuclear proteins in adrenergic cells which bind to each of the two E boxes. However, nuclear proteins from cholinergic cells only bind the 5' E box not the 3' E box. It is this interaction which appears to be the cause of the inactivity of this silencer in these cells.
Base Sequence↗
The role of previous birthweight on risk for macrosomia in a subsequent birth.
Macrosomia (birthweight > or = 4,500 gm) is associated with increased perinatal morbidity and mortality. Although past studies have evaluated risk factors for macrosomia, little is known about the effect of a prior macrosomic birth on the risk for a macrosomic infant in a subsequent birth. To assess the risk for delivery of a macrosomic infant subsequent to a previous macrosomic infant, we performed a population-based cohort study utilizing the Washington State linked infant birth file for 1984-1990. We identified 1,793 infants with birthweight > or = 4,500 gm who were linked to a subsequent birth and 3,596 randomly selected infants with birthweight of < 4,500 gm also linked to a subsequent livebirth. We then compared the risks for subsequent macrosomic births between the two groups. Infants with birthweights > or = 4,500 gm were 7.0 times more likely (95% confidence interval = 5.4-9.1) to have a subsequent macrosomic sibling than were infants with smaller birthweights, after controlling for pregnancy smoking status, parity, and gestational age. Race, maternal age or marital status, and diabetes mellitus did not materially affect this relation. The overall prevalence of macrosomic infants subsequent to a previous macrosomic birth was 22%, a proportion that did not vary notably with parity, or when paternity changed between successive births. Mothers with one macrosomic infant are at markedly increased risk for repeat macrosomic births.
Adult↗
Fatal outcome of jugular vein cannulation.
We describe the case of a woman who had cannulation of the internal jugular vein for the placement of a hemodialysis catheter. The procedure was unsuccessful and resulted in a retropharyngeal hematoma, which in turn caused severe compression on a carotid artery that was already severely narrowed by atherosclerosis. This resulted in massive cerebral hemispheric infarction and death. During the course of hospitalization, ultrasonography, computed tomography, and angiographic studies were done. Cannulation of neck vessels in patients with bleeding diatheses must be done with caution, especially in the presence of severe stenotic disease of the carotid arteries.
Aged↗
Isla Vista virus: a genetically novel hantavirus of the California vole Microtus californicus.
Prospect Hill virus (PH) was isolated from a meadow vole (Microtus pennsylvanicus) in 1982, and much of its genome has been sequenced. Hantaviruses of other New World microtine rodents have not been genetically characterized. We show that another Microtus species (the California vole M. californicus) from the United States is host to a genetically distinct PH-like hantavirus, Isla Vista virus (ILV). The nucleocapsid protein of ILV differs from that of PH by 11.1% and a portion of the G2 glycoprotein differs from that of PH by 19.6%. ILV antibodies were identified in five of 33 specimens of M. californicus collected in 1975 and 1994-1995. Enzymatic amplification studies showed that 1975 and 1994-1995 ILV genomes were highly similar. Secondary infection of Peromyscus californicus was identified in Santa Barbara County, California. A long-standing enzootic of a genetically distinct hantavirus lineage is present in California voles.
Animals↗
The role of autologous blood transfusion in joint replacement surgery.
The efficacy of predeposited autologous blood transfusion (PABT) with and without intra/postoperative blood salvage to reduce or eliminate the need for homologous blood transfusion (HBT) in primary total hip or knee replacement surgery was investigated by retrospective and prospective studies. Depending on the type of surgery, one to three units of PABT eliminated the need for HBT in 50 to 78% of patients, but, intra/postoperative blood salvage alone reduced the need only in 11 to 29%. In contrast, blood salvage, when combined with three units of PABT, eliminated the need for HBT in all patients undergoing primary joint replacement surgery. A cost comparison analysis showed that blood salvage was more expensive than PABT, and therefore it should be limited to patients who had predeposited fewer than three units of autologous blood.
Adult↗
Diclofenac/misoprostol. A review of its pharmacology and therapeutic efficacy in painful inflammatory conditions.
Diclofenac is a well established nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of a variety of painful inflammatory conditions. Although generally well tolerated, diclofenac, like other NSAIDs, is associated with gastrointestinal adverse effects which infrequently can be serious and/or life-threatening. Misoprostol, a prostaglandin E1 analogue, reduces the incidence of NSAID related ulcers, both gastric and duodenal. The lack of conclusive pharmacoeconomic data for misoprostol and the widespread use of NSAIDs makes routine administration of misoprostol difficult to justify for all NSAID users. However, it appears to be an economically warranted approach in the elderly, who are at particularly high risk for NSAID-related gastrointestinal complications. The fixed combination of diclofenac 50mg and misoprostol 200 micrograms administered 2 to 3 times daily for 4 to 12 weeks has shown equivalent therapeutic efficacy to diclofenac (alone or combined with placebo), piroxicam and naproxen, and was slightly more effective than ibuprofen in clinical studies in patients with a variety of painful inflammatory conditions. No significant differences in therapeutic efficacy were noted between elderly (aged > or = 65 years) and younger patients in these studies. Gastrointestinal adverse events are common with diclofenac and misoprostol, administered alone or in combination. Diarrhoea (presumably attributable to the misoprostol component) appears to be more frequent in diclofenac/misoprostol recipients than in those receiving diclofenac alone or combined with placebo. However, diclofenac/misoprostol recipients had significantly fewer gastroduodenal ulcers at the end of treatment relative to patients receiving comparators in clinical trials. In addition, the types and incidences of adverse events are similar in elderly and younger patients. Routine ulcer prophylaxis with misoprostol in all NSAID users is not warranted from a pharmacoeconomic viewpoint. In common with other fixed combination products, dosage flexibility is somewhat compromised with diclofenac/misoprostol. However, once drug dosages are determined in the individual patient, the fixed combination of diclofenac and misoprostol offers the potential for increased patient convenience and possibly patient compliance, and lower drug acquisition costs than those of the individual drugs used together. Thus, it should be considered a useful treatment option in appropriately selected patients with a high risk for serious NSAID-related gastrointestinal complications who require NSAID therapy.
Aged↗
Aprotinin. A review of its pharmacology and therapeutic efficacy in reducing blood loss associated with cardiac surgery.
Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) experience transient haemostatic defects as a result of adverse changes to their blood components, blood cells and specific coagulation proteins. Aprotinin is a naturally occurring serine protease inhibitor isolated from bovine lung tissue which inhibits kallikrein and plasmin. A high dose aprotinin regimen (aprotinin 280mg loading dose over 20 to 30 minutes after anaesthesia induction followed by 70 mg/h for the duration of the operation and 280mg added to the priming fluid of the CPB circuit) has been used during CPB in order to reduce perioperative bleeding. Recent clinical trials confirm the efficacy of high dose aprotinin in reducing blood loss and transfusion requirements associated with primary cardiac procedures such as coronary artery bypass graft (CABG) or heart valve replacement surgery. High dose aprotinin is also effective in procedures known to possess a high risk for excessive blood loss, such as repeat CABG or heart valve replacement surgery, cardiac surgery in patients with infective endocarditis, or in patients receiving aspirin (acetylsalicylic acid) before surgery. Studies indicate that low dose aprotinin (280mg added to CPB pump prime fluid) is effective in reducing blood loss and transfusion requirements in patients undergoing primary CABG surgery. Additionally, low dose aprotinin regimens (both 280mg added to CPB pump prime fluid and 50% of the high dose regimen) have shown some benefit in repeat CABG surgery; however, more studies are needed to confirm these results. Data from clinical trials indicate that aprotinin is well tolerated. The types and incidences of adverse events reported with aprotinin therapy are generally consistent with those associated with major cardiac surgery, and are not significantly different from those observed in control groups. A trend towards lower graft patency rates, detected by ultrafast computerised tomography (CT), has been observed in aprotinin recipients in 2 US trials. These differences did not reach statistical significance and should be interpreted with caution since the ability of ultrafast CT to determine graft patency has not been validated. Mildly elevated plasma creatinine levels are more commonly observed in aprotinin-treated patients; these changes are transient in the majority of patients. Both high dose and low dose aprotinin regimens (280mg added to CPB pump prime fluid or 50% of the high dose regimen) have reduced blood loss and transfusion requirements in patients undergoing primary and repeat cardiac surgery. The role of aprotinin in paediatric cardiac surgery needs further clarification, while well-designed studies comparing aprotinin with other agents which inhibit fibrinolysis are also awaited with interest.(ABSTRACT TRUNCATED AT 400 WORDS)
Aprotinin↗
Life-threatening hemolysis following a brown recluse spider bite.
Explore the source record for details and available documents.
Adult↗
Oral sumatriptan is effective and well tolerated for the acute treatment of migraine: results of a multicenter study.
The efficacy and tolerability of oral sumatriptan (Imitrex tablets) were assessed in 187 migraineurs enrolled in a randomized, double-blind, parallel-group, placebo-controlled study. In the clinic, patients received oral sumatriptan 25 mg, 50 mg, or 100 mg, or placebo, for the treatment of a migraine attack. The results demonstrate that by 2 hours postdose, 52 to 57% of patients treated with sumatriptan 25 mg, 50 mg, 100 mg compared with 17% of patients treated with placebo achieved relief of headache (p < 0.05 for each sumatriptan group vs placebo). By 4 hours postdose, 65 to 78% of sumatriptan-treated patients compared with 19% of placebo-treated patients achieved relief of headache (p < 0.05 for each sumatriptan group vs placebo). Oral sumatriptan also effectively relieved nausea and photophobia and improved clinical disability. No serious or unusual adverse events were reported, and the pattern and incidence of adverse events did not vary among the sumatriptan doses. Each dose--25 mg, 50 mg, or 100 mg--of sumatriptan was effective and generally well tolerated.
Administration, Oral↗
Oral sumatriptan for the acute treatment of migraine: evaluation of three dosage strengths.
This randomized, double-blind, parallel-group, placebo-controlled study evaluated the efficacy and tolerability of oral sumatriptan (Imitrex tablets) in 259 migraineurs. In the clinic, patients received oral sumatriptan 25 mg, 50 mg, or 100 mg, or placebo for the treatment of a migraine attack. The results indicate that by 2 hours post-dose, 50 to 56% of patients treated with any of the three doses, compared with 26% of patients treated with placebo, achieved relief of headache (p < 0.05 for each sumatriptan group vs placebo). By 4 hours postdose, 68 to 71% of sumatriptan-treated patients, compared with 38% of placebo-treated patients, achieved relief of headache (p < 0.05 for each sumatriptan group vs placebo). Oral sumatriptan was similarly effective at relieving nausea and photophobia and at reducing clinical disability. The pattern and incidence of adverse events did not differ between treatment groups. All doses--25 mg, 50 mg, and 100 mg--of sumatriptan were effective and generally well tolerated. Dosing should be individualized according to the needs of the patient.
Administration, Oral↗
Right ventricular dysfunction in the brain-dead heart-beating organ donor.
Explore the source record for details and available documents.
Animals↗