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Biomedical subjects

C A Robinson

Publications and source records attributed to C A Robinson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Regulation of the synthesis and secretion of vasopressin.

We have developed a transgenic system that, for the first time, facilitates the monitoring of the regulatory dynamics of a central peptidergic system from transcription of a neuropeptide gene to the storage and release of the mature secretory product. Here we describe novel studies on the regulation of this system by physiological stimuli. The rat hypothalamic vasopressin (VP) mRNA responds in two ways to the functional demand imposed by an osmotic challenge. Firstly, the abundance of the VP RNA increases, and secondly, the size of the VP transcript increases as a consequence of a lengthening of the poly(A) tail. We have previously shown that chronic ingestion of 6-n-propyl-2-thiouracil (PTU), while not affecting plasma osmolality or VP mRNA size, results in a significant increase in the abundance of the hypothalamic VP mRNA. We now show that chronic PTU ingestion results in a dramatic increase in the abundance of the mRNA encoded by a modified rat vasopressin transgene that is expressed in rat vasopressinergic magnocellular neurons. This is accompanied by a significant depletion in neural lobe stores of a VP. However, this increase in transgene expression is accompanied by an increase in the proportion of transgene encoded products reaching the neural lobe--the pituitary content of a unique peptide encoded by the modified transgene does not change. These observations are further evidence in support of models of neurohypophyseal homeostasis that suggest that pituitary VP peptide levels passively reflect changes in hormone release and synthesis and that the availability of mRNA is the primary determinant of pituitary VP content in the basal state.

Animals↗
PubMed1998

Fatal multiple drug intoxication following acute sertraline use.

A 53-year-old Caucasian male victim of suicide was suspected of overdose with sertraline and alprazolam after death-scene investigation. The concentration of sertraline, a selective serotonin reuptake inhibitor, was determined by a gas chromatograph with mass selective detection. The concentration of alprazolam, a triazolobenzodiazepine, was determined by high-performance liquid chromatography. The sertraline concentration was reported at 1.0 mg/L in peripheral blood, which is greater than previously reported in other postmortem cases in which death was attributed to a multiple drug overdose. The N-desmethylsertraline concentration was reported at 0.2 mg/L in peripheral blood, which is far less than in other postmortem cases and suggests acute intoxication in this case. The alprazolam concentration was reported at 33 microg/L in heart blood, which is within the therapeutic range. The cause of death was multiple drug intoxication following acute use of sertraline, the manner of death was suicide, and the mechanism of death is an unexplained drug interaction and/or toxicity.

Alprazolam↗
PubMed1998

Low serum antimycobacterial drug levels in non-HIV-infected tuberculosis patients.

BACKGROUND: Despite the use of directly observed therapy (DOT) by tuberculosis control programs, patient treatment failure, relapse, and acquired drug resistance remain problematic in a small number. We investigated serum drug levels in non-HIV-infected tuberculosis patients who were receiving DOT by the health department and did not respond to treatment as expected. METHODS: The indications for checking levels were as follows: (1) slow clinical response or failure to convert the sputum culture within 12 weeks; (2) treatment failure, early disease relapse < 13 months since being declared cured; (3) relapse, late disease reactivation > or = 13 months since being declared cured; and (4) acquired drug resistance while receiving DOT. Baseline characteristics of control subjects who responded to therapy as expected were compared. Venous blood for analysis was obtained at 2 h after directly observed ingestion and measured by high-performance liquid chromatography. RESULTS: Twenty-four patients receiving daily or twice-weekly standard therapy with isoniazid (INH, 300 or 900 mg) and rifampin (RMP, 600 mg) were identified; 22 had drug levels evaluated at 2 h. For INH, 15 of 22 patients (68%) had levels less than the reported target range. For RMP, 14 of 22 patients (64%) had low levels. Among the 14 patients receiving INH, 900 mg, and RMP, 600 mg, 4 (29%) had very low levels of both. Use of a combination INH/RMP tablet was associated with lower INH levels (p=0.04); however, RMP levels were higher (p<0.02). Alcohol use was associated with significantly higher RMP (p<0.01) serum concentrations. CONCLUSIONS: Important questions remain concerning the utility and timing of serum drug measurements. However, if a patient is not responding to therapy as expected and one is assured that the Mycobacterium tuberculosis organism is susceptible to the drugs given and that the patient is taking the medication as prescribed, drug level monitoring should be considered.

Adult↗
PubMed1997

Randomised trial of efficacy and safety of oral ganciclovir in the prevention of cytomegalovirus disease in liver-transplant recipients. The Oral Ganciclovir International Transplantation Study Group [corrected].

BACKGROUND: Cytomegalovirus (CMV) disease is a frequent cause of serious morbidity after solid-organ transplantation. The prophylactic regimens used to prevent CMV infection and disease have shown limited benefit in seronegative recipients. We studied the safety and efficacy of oral ganciclovir in the prevention of CMV disease following orthotopic liver transplantation. METHODS: Between December, 1993, and April, 1995, 304 liver-transplant recipients were randomised to receive oral ganciclovir 1000 mg or matching placebo three times a day. Seronegative recipients of seronegative livers were excluded. Study drug was administered as soon as the patient was able to take medication by mouth (no later than day 10) until the 98th day after transplantation. Patients were assessed at specified times throughout the first 6 months after surgery for evidence of CMV infection, CMV disease, rejection, opportunistic infections, and possible drug toxicity. FINDINGS: The Kaplan-Meier estimate of the 6-month incidence of CMV disease was 29 (18.9%) of 154 in the placebo group, compared with seven (4.8%) of 150 in the ganciclovir group (p < 0.001). In the high-risk group of seronegative recipients (R-) of seropositive livers (D+), incidence of CMV disease was 11 (44.0%) of 25 in the placebo group, three (14.8%) of 21 in the ganciclovir group (p = 0.02). Significant benefit was also observed in those receiving antibodies to lymphocytes, where the incidence of CMV disease was 12 (32.9%) of 37 in the placebo group and two (4.6%) of 44 in the ganciclovir group (p = 0.002). Oral ganciclovir reduced the incidence of CMV infection (placebo 79 [51.5%] of 154; ganciclovir 37 [24.5%] of 150; p < 0.001) and also reduced symptomatic herpes-simplex infections (Kaplan-Meier estimates: placebo 36 [23.5%] of 154; ganciclovir five [3.5%] of 150; p < 0.001). INTERPRETATION: Oral ganciclovir is a safe and effective method for the prevention of CMV disease after orthotopic liver transplantation.

Administration, Oral↗
PubMed1997

Quantification of alternatively spliced RUSH mRNA isoforms by QRT-PCR and IP-RP-HPLC analysis: a new approach to measuring regulated splicing efficiency.

Quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) and the ion-pair reverse-phase (IP-RP)-HPLC product purification and detection system were developed to facilitate the isolation and proportional quantification of alternatively spliced RUSH mRNAs. RUSH isoforms result from alternative splicing of a 57-bp exon and encode SNF/SWI-related proteins that bind to the uteroglobin promoter. QRT-PCR was performed using total RNA, and a pair of primers designed to flank the 57-bp exon. When more than one splice variant was expressed, IP-RP-HPLC identified the specific homoduplex products, as well as the heteroduplexes formed as a consequence of partial sequence complementarity between the products. Data analysis included the correct re-allocation of heteroduplex components to achieve accurate quantitation of changes in the relative levels of RUSH message isoforms. The preferential expression of the RUSH-1alpha isoform by all the tissues except estrous uterine endometrium and lactating mammary gland indicates RUSH pre-mRNAs are alternatively spliced in a tissue-specific manner. A 61-fold difference in the relative rate of RUSH pre-mRNA splicing is indicated by the difference in the ratios of RUSH mRNA isoforms from uterine endometrium and testis. Clearly, QRT-PCR and IP-RP-HPLC are powerful and versatile tools for the detection and quantitation of mRNA splice variants.

Alternative Splicing↗
PubMed1997

Is there justification for using indomethacin in preterm labor? An analysis of neonatal risks and benefits.

OBJECTIVE: Recent reports have suggested that the use of indomethacin for tocolysis may independently increase the risk for major adverse neonatal events such as intraventricular hemorrhage and necrotizing enterocolitis. The objective of this study was to determine whether this potential risk of indomethacin is outweighed by the benefit of delivery delay at gestational ages < 32 weeks. STUDY DESIGN: We constructed separate decision trees to compare strategies of tocolysis with indomethacin versus no tocolysis for hypothetic cohorts of patients with idiopathic preterm labor at 24, 26, 28, 30, and 32 weeks' gestation. Probabilities for these decision models, including estimates of indomethacin efficacy and the potential for increase in adverse neonatal events with indomethacin, were obtained from the medical literature. The primary outcome was the number of expected adverse neonatal events per 1000 women for each strategy at each gestational age. RESULTS: In the base case analysis tocolysis with indomethacin was a more favorable strategy than no tocolysis across all gestational ages that we studied. As expected, the difference in the number of events between the two strategies declined with advancing gestational age because of a decreasing baseline risk for adverse neonatal events as gestational age increased. The models at 26, 28, 30, or 32 weeks were not sensitive to our estimates of indomethacin efficacy, nor to our estimates of baseline neonatal morbidity or steroid efficacy, or to the relative increase in some neonatal morbidities with indomethacin use. CONCLUSIONS: On the basis of current estimates, the benefits of indomethacin outweigh the potential risks to the neonate at gestational ages < or = 32 weeks. Thus the use of indomethacin for tocolysis at these ages is a reasonable strategy.

Cerebral Hemorrhage↗
PubMed1997

Detection of alprazolam in three cases of methadone/benzodiazepine overdose.

Benzodiazepine abuse is common among clients at methadone maintenance clinics. Diazepam and lorazepam are readily detected by immunological screening methods and confirmed by GC/MS. Alprazolam has been relatively difficult to confirm. We recently reported a modification of an existing serum HPLC procedure which allows us to analyze whole blood. We report here three cases of fatal drug overdose caused by co-ingestion of methadone and alprazolam. In all three cases, alprazolam was detected by HPLC and could not be identified by alkaline extraction GC/MS. Postmortem blood concentrations of methadone were at the lower range or below the concentrations previously identified in methadone overdose fatalities, suggesting an increased risk from co-ingestion of methadone and alprazolam.

Adult↗
PubMed1996

Prolonged administration of granulocyte colony-stimulating factor (filgrastim) to patients with Fanconi anemia: a pilot study.

This report examines the effect of filgrastim (granulocyte colony-stimulating factor, [G-CSF] in 12 patients with neutropenia [absolute neutrophil count [ANC] < 1,000/mm3]) caused by Fanconi anemia (FA). Two of 14 patients who were evaluated for study entry were ineligible because of unsuspected cytogenetic abnormalities in their bone marrow (BM). G-CSF was started at 5 micrograms/kg/d. All patients had an increase in their ANC at week 8 (mean increase = 15,664/mm3). The median ANC during therapy was 5,030/mm3. Eight of 10 patients who completed 40 weeks on study maintained an ANC > 1,500/mm3 on G-CSF given every-otherday. Four patients had an increase in their platelet count by week 8 without transfusion (maximum increase = 23,000 to 45,000/mm3); however, platelet counts fell toward baseline levels as the G-CSF dose was reduced. BM CFU-MK were increased at week 8 in three of four evaluable patients. Four patients who did not receive red blood cell transfusions had an increase in their hemoglobin level of at least 2.0 g/dL. A fifth patient had a red blood cell transfusion in week 2 and then had a similar increase in hemoglobin level without subsequent transfusion. Eight of 10 patients who completed 40 weeks of treatment showed increases in the percentage of BM CD34+ cells measured by flow cytometry. The same proportion showed increases in peripheral blood CD34+ cells. Increased BM cellularity and myeloid hyperplasia were constant findings and were associated with increased expression of the proliferating cell nuclear antigen. Adverse experiences were mild fever (1 patient) and a new BM cytogenetic abnormality at week 40 (1 patient). This study shows that prolonged administration of G-CSF exerts a stimulatory effect on the BM of FA patients and may be used to maintain a clinically adequate ANC in these patients. G-CSF has beneficial effects on multiple hematopoietic lineages in some patients and may be a good candidate for use in combination cytokine protocols for FA patients with progressive aplastic anemia. G-CSF use results in an increase in circulating CD34+ cells, a finding with important implications for future gene transfer protocols.

Adolescent↗
PubMed1996

Determination of a HIV protease inhibitor (DMP 450) in animal and human plasma by solid-phase extraction and high-performance liquid chromatography.

Extraction of DMP 450 from plasma was performed with C2 solid-phase extraction columns, using 0.1 M ammonium acetate in 90% methanol to elute DMP 450. The extraction recovery over the range of 10 to 10 000 ng/ml averaged 81.0, 96.2, 77.4, 95.2 and 68.0% from rat, dog, monkey, chimpanzee (25-10 000 ng/ml) and human plasma, respectively. HPLC analysis was carried out with a C18 column and a mobile phase of acetonitrile, methanol and 30 mM potassium phosphate (pH 3), the composition dependent on the type of plasma being analyzed, and monitored at a wavelength of 229 nm. Intra-day and inter-day coefficients of variation were less than 9.9 and 12.9%, respectively. Absolute differences were less than 11.5%.

Acetonitriles↗
PubMed1996

Lighten up.

Explore the source record for details and available documents.

Attitude of Health Personnel↗
PubMed1996

Pharmacokinetic interactions of moricizine and diltiazem in healthy volunteers.

Sixteen healthy male volunteers completed a nonrandomized, sequential, three-phase study. The three phases were 1) moricizine at 250 mg every 8 hours for 7 days with 12 days washout; 2) diltiazem at 60 mg every 8 hours for 7 days; and 3) concomitant administration of moricizine at 250 mg and diltiazem at 60 mg every 8 hours for 7 days. The plasma concentration-time profiles were obtained at the end of each phase for moricizine, diltiazem (with its metabolites desacetyl-diltiazem and N-desmethyl-diltiazem), and both when administered together. Under steady-state conditions, there was a two-way (opposing) pharmacokinetic drug interaction when moricizine and diltiazem were coadministered in healthy volunteers. Both maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve from time 0 to the end of administration (AUC tau) of moricizine increased significantly by 88.9% and 121.1%, respectively. Oral clearance (Clo) decreased by 54%. The terminal half-life (t1/2) of moricizine was not affected, however (2.1 +/- 0.5 hours versus 2.4 +/- 0.7 hours). It is believed that these changes were due to the inhibition of hepatic metabolism by diltiazem, which resulted in an increased systemic availability of moricizine. Moricizine had opposite effects on the pharmacokinetics of diltiazem. Moricizine decreased the Cmax of diltiazem significantly (by 36%) and increased Clo by 52%. A small but statistically significant decrease in the t1/2 from 4.6 +/- 1.3 hours to 3.6 +/- 0.7 hours was observed. Despite this result, no remarkable changes (e.g., in Cmax, AUC, or t1/2) were found for the two major diltiazem metabolites desacetyl-diltiazem and N-desmethyl-diltiazem. It appears that the pharmacokinetic interaction of moricizine and diltiazem was metabolic. With the increase in moricizine concentrations and the decrease in diltiazem concentrations, adjustments in dose may be required to achieve optimal therapeutic response when coadministering both agents.

Adolescent↗
PubMed1996

Does station of the fetal head at epidural placement affect the position of the fetal vertex at delivery?

OBJECTIVE: The objective study was to determine whether epidural placement before engagement of the fetal head is associated with an increase in the incidence of malposition at delivery. STUDY DESIGN: We performed a retrospective cohort study to ascertain the relation between station at epidural placement and malposition. Three hundred fifty-seven patient records were reviewed; 320 records of patients in spontaneous or induced labor who received epidural analgesia were included in the analysis. Patients with a contraindication to labor, antepartum fetal death, or twins were excluded. Maternal demographics, cervical examination at epidural placement, epidural medication characteristics, and labor and delivery data were abstracted from medical records. Station was characterized as high if the fetal vertex was above the level of the maternal ischial spines or low if the vertex was at or below the level of the ischial spines at the time of epidural placement. RESULTS: The relative risk of occiput malposition was significantly increased with epidural placement at high station. This risk remained after we controlled for age and birth weight. Cervical dilatation was not independently associated with occiput position at delivery. CONCLUSIONS: Epidural placement before engagement of the fetal head is associated with an increased incidence of malposition at delivery. This finding may provide an insight into the empiric observation that operative delivery is variably increased for patients laboring under epidural anesthesia.

Adult↗
PubMed1996

Tuberculosis: current implications and management in obstetrics.

After years of decline, tuberculosis has again emerged as a serious public health issue. Following the introduction of effective chemotherapy at mid-century, cases of tuberculosis decreased until 1986. Since that time, the number of cases of tuberculosis have dramatically increased, particularly among young persons. The reemergence of tuberculosis is localized to urban areas and is linked to the increase in the incidence of human immunodeficiency virus infection and drug resistance. Since pregnant women are at risk for tubercular infection, an effective method exists to identify women who are asymptomatically infected, provide them with treatment to prevent progression of disease, and investigate their contacts. This review will discuss the issues of diagnosis and treatment of asymptomatic infection and active tuberculosis in pregnant women. Additionally, the need for universal screening of all prenatal patients and the benefit and potential perinatal toxicity of chemotherapy in both immunocompetent patients and those infected with human immunodeficiency virus will be addressed.

Drug Resistance, Microbial↗
PubMed1996

Osteonecrosis of the femoral head in patients with inflammatory arthritis or asthma receiving corticosteroid therapy.

The utilization of corticosteroids in the management of acute and chronic inflammatory processes, such as asthma or inflammatory arthritis, has been implicated in the adverse effects of multiple organ systems. One potential area of these negative consequences in the use of corticosteroids is the development of osteonecrosis of the femoral head. A direct time/dosage relationship for treatment with corticosteroids of patients with an established diagnosis of asthma or inflammatory arthritis and femoral osteonecrosis is unknown. A prospective study was undertaken to evaluate the use of corticosteroids and the incidence of osteonecrosis of the femoral head and potentially establish a time/dosage relationship in this patient population. No direct relationship between corticosteroid dosage and the development of femoral head osteonecrosis in 1420 hip-years was demonstrated at 10-year follow up.

Adrenal Cortex Hormones↗
PubMed1995

Stomach cancer--is it a lost cause?

A retrospective study of 7 years of endoscopy at Trafford General Hospital from 1986-1993 identified 143 patients diagnosed as having gastric cancer, of whom 13 cases were identified as early gastric cancer. Epigastric pain was the main symptom (66%) of those presenting with resectable disease. Weight loss (70%) was the most common symptom of patients presenting with advanced disease. Forty-seven patients had no surgery and 25 had palliative non-resective surgery. These two groups account for 50% of cases. With such a small detection rate of early gastric cancer and consequent curative surgery rate one must debate whether treatment of stomach cancer in the Trust hospital of the future is a lost cause.

Adult↗
PubMed1995

High-performance liquid chromatography of alprazolam in postmortem blood using solid-phase extraction.

Screening and analysis of the numerous benzodiazepines presents a challenge for the forensic toxicologist. The newer benzodiazepines, which are prescribed in daily dose regimens of 0.5-3 mg, are particularly difficult to screen and analyze. Frequently, history or careful investigation by the medical examiner is the only clue that the laboratory has to follow. We describe four cases involving alprazolam and the modification of an existing serum high-performance liquid chromatographic (HPLC) procedure, which allowed us to analyze whole blood. This HPLC procedure for alprazolam uses a protein precipitation step followed by solid-phase extraction. The method is sensitive to 18 ng/mL and linear from 18 to 200 ng/mL. Reproducibility was determined by extracting and analyzing duplicate samples on five separate occasions. The recovery averaged 84% using postmortem blood spiked with 18 and 150 ng/mL alprazolam.

Adult↗
PubMed1995

Beyond dichotomies in the nursing of persons and families.

The dichotomy of individual and family nursing has served the discipline well. However, the time has come for a reconciliation of these perspectives and the redefinition of nursing as inclusive of both individuals and families. A conceptual framework that draws distinctions among four different nursing focuses of persons and families is described.

Education, Nursing↗