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J Reynolds

Publications and source records attributed to J Reynolds.

At least 73 records · Page 4Linked to original sources
PubMed1996

Reversal of stereoselectivity in the hepatic availability of verapamil in isolated perfused rat livers. Role of protein binding.

The effects of serum proteins on the stereoselective kinetics of the high clearance drug verapamil (VER) and its metabolite, norverapamil (NOR), were studied in isolated perfused rat livers (IPRLs). Livers were perfused, in a recirculating manner, with a solution containing human serum albumin (HSA), bovine serum albumin (BSA), or no serum albumin (N = 5 for each group). After presystemic administration of a single dose of racemic VER (2 mg), the concentrations of VER and NOR enantiomers in the perfusate were measured over 90 min. In addition, the fraction of the enantiomers bound to the plasma of perfusate was determined. Perfusate concentrations of both VER and NOR were stereoselective in all of the perfusates studied. However, the direction of stereoselectivity in the concentrations of VER enantiomers in the BSA perfusate (S-VER > R-VER) was opposite that in the HSA and albumin-free perfusates (R-VER > S-VER); this was associated with an opposite stereoselectivity in the concentrations of NOR in the BSA perfusate was higher than that in the HSA and albumin-free perfusates, an observation in agreement with the higher stereoselectivity in the binding of NOR to BSA. These data, along with other kinetic parameters such as apparent hepatic availability and intrinsic clearance, suggest that the apparent stereoselectivity in the presystemic elimination of VER by IPRLs is significantly influenced by the stereoselectivity in the protein binding of the drug.

Animals↗
PubMed1996

Mediators of adolescents' stress in a college preparatory environment.

This study examined four variables (sense of control, perceived social support, degree of achievement motivation, and experienced satisfaction) hypothesized to mediate or buffer adolescents from the negative impact of academic and social stressors. The subjects were 61 high school students enrolled in a college preparatory setting with high academic standards and 63 of their parents. Students and parents were asked to rate student responses to stress that is related to both academic and nonacademic activities. Student-reported Control, Support, and Achievement Motivation were found to be strongly related to reported stress levels, although only Control and Achievement were entered in the full model of a stepwise regression analysis. Differences in the sample in terms of boarding versus day-student status, as well as differences between male and female student reports were examined.

Achievement↗
PubMed1995

The therapeutic efficacy and prophylactic activity of doramectin against Dictyocaulus viviparus in cattle.

Three groups of 8, 4-month-old male Jersey or Jersey-cross calves were infected with 2400 Dictyocaulus viviparus L3 larvae and either left untreated or injected subcutaneously with 200 micrograms/kg doramectin 5 or 25 days after infection (DAI). Lungworms were found in all untreated cattle (geometric mean = 49) at necropsy 39 or 40 DAI. None was found in any of the treated cattle. In a second experiment, groups of 6, 8-month-old calves were untreated or injected with 200 micrograms/kg doramectin 28, 21 or 14 days before each calf was challenged with 2700 D viviparus larvae. Lungworms were recovered at necropsy 32 to 34 DAI. The geometric mean worm burden in the untreated cattle was 550. This was reduced by 100%, 99.5% and 94.1% in calves treated with doramectin 14, 21 or 28 days, respectively, before infection. It was concluded that doramectin is a highly effective anthelmintic against D viviparus adult or L4 infections of cattle, and that reinfection of treated cattle will be significantly reduced for at least 28 days after treatment.

Animals↗
PubMed1995

Input rate-dependent stereoselective pharmacokinetics. Experimental evidence in verapamil-infused isolated rat livers.

The input rate dependency of verapamil (VER) kinetics was studied in single-pass isolated rat livers perfused with a Krebs-bicarbonate buffer solution, containing albumin and red blood cells, at a flow rate of 15 ml/min. Racemic VER was infused at a constant rate of approximately 50 (low dose, N = 5) or approximately 100 (high dose, N = 5) micrograms/min through the inlet catheter (portal vein). Inlet and outlet samples were taken periodically over 90 min. Additionally, liver samples were obtained at the end of infusion. Perfusate and liver samples were analyzed using a chiral liquid chromatographic method for determination of the individual enantiomers of VER and its metabolites, norverapamil (NOR). After the low-dose infusion, the hepatic availability of S-VER (0.102 +/- 0.021) was greater than that of its antipode (0.071 +/- 0.020). A 2-fold increase in the input rate resulted in a significant increase in the hepatic availabilities of S-VER (0.195 +/- 0.040) and R-VER (0.182 +/- 0.048). However, the increase was more pronounced for R-VER, resulting in a significant decrease in the S:R availability ratio from 1.47 +/- 0.20 (low dose) to 1.09 +/- 0.14 (high dose) and loss of stereoselectivity at the high dose. The S:R ratio of NOR concentration was also input rate-dependent. However, the degree of stereoselectivity for the outlet concentrations of NOR (S:R ratios 2.42 +/- 0.42 and 1.88 +/- 0.20 for the low and high doses, respectively) was greater than that for the parent drug at both doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Recombinant retroviral vector interferes with the detection of amphotropic replication competent retrovirus in standard culture assays.

Many protocols for gene therapy employ recombinant retroviral vectors, which are replication-defective retroviruses engineered to serve as gene delivery vehicles. The use of retroviral vectors for human gene therapy requires careful screening of vector-producing cell lines and culture supernatants to ensure the absence of replication competent retrovirus (RCR) in clinical products. In this study we have examined several different culture assays routinely used to test for the presence of RCR. Results indicate that cocultivation of a vector-producing cell line with a permissive cell line can reproducibly detect a low level of contaminating RCR. RCR was detected less frequently in direct tests of cell-free culture supernatants from a contaminated vector-producing line. Further studies revealed that recombinant retroviral vector can interfere, to varying degrees, with the detection of low-level RCR in culture supernatants when a marker rescue assay, an extended mink S+L- assay or a PG-4 S+L- assay is used. Interference can be partially overcome by culturing the vector preparation with a permissive cell line for several days before testing on the indicator cell line. The interference phenomenon we have observed may also occur in other culture assays routinely used for the detection of RCR.

Animals↗
PubMed1995

Automated reconstruction of endoscopic images of the esophagus.

Endoscopic devices distort the image of a region under examination. Previous work has shown that there are computational methods which can precisely reconstruct planar structures in a model of the esophagus and that reconstruction in human subjects is operator independent. The purpose of this report is to show that much of the process can be automated and to provide additional evidence that the reconstruction is both accurate and reproducible.

Esophagoscopy↗
PubMed1995

Phase I study of intravenous Lu-labeled CC49 murine monoclonal antibody in patients with advanced adenocarcinoma.

CC49, a murine monoclonal antibody that recognizes the tumor-associated glycoprotein 72, was conjugated to the chemical chelate 1,4,7,10-tetraaza-1-(1-carboxy-3-(4-aminophenyl) propyl)-tris-4,7,10- ((carboxy)methyl)cyclododecane that had been labeled with a beta emitter, Lu. Preclinical studies had shown that Lu-labeled CC49 caused regression of human colon adenocarcinoma xenografts in nude mice. Patients with advanced adenocarcinoma who had failed standard treatment and whose tumors expressed the tumor-associated glycoprotein 72 antigen were eligible for treatment to determine the maximum tolerated dose of Lu-labeled CC49. The starting dose of Lu was 10 mCi/m2 given i.v. with the dose of CC49 held constant at 20 mg. Pharmacokinetic sampling and immunoscintigraphy were performed over the ensuing 3 weeks. The dose of radioactive Lu was escalated by 15 mCi/m2 for each successive dose level. Unexpected bone marrow toxicity developed in patients treated at the second dose level with 25 mCi/m2 Lu; two patients developed grade 4 thrombocytopenia, while the third patient developed grade 3 thrombocytopenia. Pharmacokinetic studies showed that the plasma half-life of the immunoconjugate was 67 h; whole-body retention, however, was prolonged with a biological half-life of 258 h. Serial gamma camera imaging localized known tumor in all patients, and also demonstrated prolonged Lu retention in the reticuloendothelial system (RES). Bone marrow dosimetry estimates ranged from 4 to 5 REMS/mCi Lu based on imaging and biopsy data. Analysis of bone marrow biopsies demonstrated that most of the Lu was localized in the cellular compartment and not in the bone. No antitumor responses were observed. Intravenous administration of 15 mCi/m2 Lu-labeled CC49 to previously treated advanced cancer patients was associated with acceptable hematological toxicity and was the maximum tolerated dose. However, prolonged retention of Lu in the RES, including the bone marrow, was observed and limited the dose of Lu that could be given. Additional studies are indicated to reduce RES uptake and retention of this immunoconjugate.

Adenocarcinoma↗
PubMed1994

Diabetes-induction reduction in the hepatic accumulation of 70-kDA dextran: role of hyperglycemia and hypoinsulinemia.

In vivo studies were conducted in rats to determine the role of hyperglycemia and hypoinsulinemia in the previously reported reduction in the hepatic accumulation and increase in the serum concentrations of 70-kDa fluorescein-dextran (FD-70) in diabetic (D) rats. The serum, urine, and hepatic concentrations of FD-70 were measured by size exclusion chromatography after i.v. administration of a single doses (5 mg/kg) of FD-70. Intravenous administration of a single 2 IU/kg dose of insulin to D rats at time zero or 4 h after the administration of FD-70 resulted in an increase in some and no change in other animals in their rate of elimination of FD-70 from serum. The presence or absence of a significant insulin effect on the disposition of FD-70 in these animals was, respectively, associated with the presence or absence of a significant insulin-induced hypoglycemic effect. Fasting D rats for 24 h caused normoglycemia, and subsequently, the disposition of FD-70 became similar to that in nondiabetic (ND) rats. Likewise, i.p. injections of glucose to ND rats rendered them hyperglycemic, and the disposition of FD-70 in these rats became similar to that in untreated D animals. However, i.v. injection of glucose, which did not result in sustained hyperglycemia, did not change the disposition of FD-70 in ND rats. Further, the disposition of FD-70 remained unaffected by an i.v. 2 IU/kg dose of insulin administered to ND rats at time zero. Considering all animals, there was a significant negative relationship between the 12-h hepatic recovery of FD-70 and the area under the serum concentration-time curves of glucose. It is concluded that the reduction in the hepatic accumulation of FD-70 in D rats is due to hyperglycemia and not

Animals↗
PubMed1994

Isolation of a GCC repeat showing expansion in FRAXF, a fragile site distal to FRAXA and FRAXE.

Three folate-sensitive fragile sites, termed FRAXA, FRAXE and FRAXF, have been identified on the distal end of chromosome Xq. The first two contain expanded, hypermethylated and unstable CGG (or GCC) repeats within CpG islands. We now report the isolation of similar sequences responsible for the third fragile site, FRAXF. A 5-kilobase EcoRI fragment derived from a cosmid coincident with the cytogenetic anomaly detects expanded, methylated and unstable sequences in five individuals who exhibit fragile sites in distal Xq; these individuals have normal repeat lengths at both FRAXA and FRAXE. By sequence analysis, the expanded region contains a GCC repeat. PCR and sequence analysis of chromosomes from the general population indicates that the repeat is polymorphic (6 to 29 triplets), and is stable upon transmission.

Alleles↗
PubMed1994

A sampling and analytical method for the simultaneous determination of multiple organophosphorus pesticides in air.

A sampling and analytical method for organophosphorus pesticides using a combined filter/XAD-2 sorbent sampler and gas chromatography (GC)-flame photometric detection (FPD) was developed. The method was evaluated for 19 organophosphorus pesticides based on the joint Occupational Safety and Health Administration/National Institute for Occupational Safety and Health Standards Completion Program methods evaluation protocol. The evaluation addressed analyte recovery, sampler capacity, sample stability, and precision and accuracy. Additional experiments addressed long-term sample stability (30-day storage), short-term exposure limits, limits of detection, and concentration levels down to 0.1 times an exposure limit value. Samples were stable for 30 days of storage under either ambient or refrigerated conditions. Based on this research, all 19 compounds studied can be successfully determined simultaneously using one method with an accuracy of +/- 25% of the true value 95 times out of 100.

Air Pollutants↗
PubMed1994

In vivo treatment with a monoclonal antibody to T helper cells in experimental autoimmune glomerulonephritis in the BN rat.

Experimental autoimmune glomerulonephritis (EAG) was induced in brown Norway (BN) rats by a single i.m. injection of homologous glomerular basement membrane (GBM) in Freund's complete adjuvant. This model of anti-GBM disease is characterized by the development, over several weeks, of circulating and deposited anti-GBM antibodies, accompanied by albuminuria. We examined the effects of treatment with MoAb W3/25 (anti-CD4) at different doses, starting at the time of immunization and continued for the duration of the study or for a limited period only. Continued treatment with W3/25, at a dose of 5 or 10 mg/kg intraperitoneally three times per week for 4 weeks, produced a marked reduction in circulating anti-GBM antibodies, absence of detectable deposited antibody and virtual absence of albuminuria. When W3/25 treatment, at 5 or 10 mg/kg, was stopped after 2 weeks, there was still a significant reduction in anti-GBM antibodies and albuminuria at 4 weeks. A similar effect on the disease was achieved when W3/25 was administered only three times during the first week at a dose of 30 mg/kg. Animals injected with W3/25 at a dose of 10 mg/kg through the course of disease showed < 10% W3/25+ cells by FACS analysis of splenic lymphocytes at week 4, while controls and animals treated for shorter periods showed > 30% W3/25+ cells. These results demonstrate that W3/25 can prevent the development of EAG, and that this effect is not dependent on persistent depletion of T cells. Further work is necessary to determine whether anti-T cell therapy is effective in established EAG, and may be worth investigating in human anti-GBM disease.

Albuminuria↗
PubMed1994

Written consent about sexual function in men undergoing transurethral prostatectomy.

OBJECTIVE: To review the written recording of consent about possible sexual dysfunction after transurethral resection of the prostate (TURP), and the incidence of sexual dysfunction in sexually active men after TURP, from a large scale audit of transurethral prostatectomy held in 12 hospital sites in the Northern Region. PATIENTS AND METHODS: Over an 8-month period data were collected from 12 separate hospital sites within the Northern Region by two independent nurse co-ordinators who travelled to each of the sites. Information was gathered from medical records, operation lists and theatre books using a standard proforma. The Nottingham Health Profile (NHP) was used as a quality of life instrument in a subgroup of patients who were asked about sexual function before and after operation. RESULTS: Advice about retrograde ejaculation was recorded infrequently, with only 30% of case notes including a statement about this (inter-site variations 0-78%). The mean age of patients in whom a written record was made was lower (70 [0.44 SEM] years) than those in whom there was no recording (72 [0.25] years; P < 0.001), but marital status did not appear to be a significant factor. No significant differences in NHP were found comparing men who did or who did not have written evidence about consent regarding retrograde ejaculation. In addition, in a subset of men who had been asked pre-operatively about sexual function, no significant differences were found in overall NHP measurements in those who did or who did not develop retrograde ejaculation. In men who were sexually active before operation, the incidence of major sexual problems, impotence and retrograde ejaculation were 12%, 11% and 24% respectively. CONCLUSION: The incidence of sexual dysfunction following TURP in this audit concurred with previously reported studies (4-40%), but despite this most urologists in our audit were not recording that they had advised their patients about this possible outcome.

Aged↗
PubMed1994

Deaths and complications following prostatectomy in 1400 men in the northern region of England. Northern Regional Prostate Audit Group.

OBJECTIVE: To determine the degree of variation in mortality and major morbidity following transurethral resection of the prostate (TURP), and to assess intersite variation for mortality and morbidity over 12 sites within the Northern Region. Further, to determine whether the previously observed effects on morbidity of unit size, patient through-put and emergency admission were borne out in contemporary urological practice in the Northern Region. PATIENTS AND METHODS: For an 8 month period, 1 April 1991-31 November 1991, an independent audit of TURP was performed on 12 different hospital sites throughout the Northern Region. A constant data set was designed which was collected on each patient before and 3 months after operation by two independent clinical co-ordinators who travelled to each of the sites. All case notes were reviewed at 3 months after operation by the co-ordinators using a standard proforma, rather than depending upon self reporting by medical staff. Data on factors potentially affecting mortality and morbidity were collected, including emergency admission, diagnosis of prostate cancer, American Society of Anesthesiologists' co-morbidity scores, and age and differences in throughput in the 12 sites. The effect of through-put or 'volume' on mortality and morbidity was assessed by comparing morbidity and the number of cases performed. RESULTS: The early mean death rate was 13 of 1396 patients (0.9%), with an inter-site variation ranging from 0% to 3.8%. A mean of 2.0% of men were returned to theatre after TURP, 2.4% of patients received a blood transfusion (> 2 units) after operation, and 8.0% of patients developed post-operative sepsis; these complications varied sixfold, sevenfold and 17-fold across the different sites respectively. Those units performing < or = 100 operations over the audit period (equivalent to < 150 operation per year) had a significantly increased rate of deaths and complications which was not related to population differences, though some low volume units had good results. Elderly men who were admitted as emergencies or with prostate cancer were particularly vulnerable to complications. CONCLUSIONS: The overall early mortality rate after TURP for benign prostatic hyperplasia across the Region compares well with other reported large series. The significant variation in morbidity rates found in this study suggests that careful attention needs to be paid by Urologists, Purchasers and Providers to morbidity rates after prostatectomy.

Age Factors↗
PubMed1994

Paralympics--Barcelona 1992.

The British Team at the 9th Paralympic Games in September 1992 in Barcelona comprised 151 men and 54 women athletes in a total of 15 sports. They were supported by a staff of 86 including a 12-strong medical team. The athletes were selected from the National Championships of the five disability organizations: British Wheelchair Sports Federation; British Blind Sport; Cerebral Palsy Sport; British Amputee Sports Association; and the British Les Autres Sports Association. This article outlines the organization and experience of the medical support team. The injury/illness profile was similar to those in able bodied sport. The team went on to achieve 40 gold, 47 silver and 41 bronze medals, maintaining third place on the medal table as achieved in Seoul in 1988.

Amputees↗
PubMed1994

Busulfan-containing pre-transplant regimens for the treatment of solid tumors.

This study investigated the toxicity and efficacy of busulfan-containing pre-transplant regimens in patients with solid tumors. The majority of these patients were also treated on protocols involving two transplant courses aiming at further reducing tumor burden. Between October 1984 and November 1993, we treated 44 patients with recurrent breast cancer (n = 28), sarcoma (n = 10) or ovarian cancer (n = 6) with one of two busulfan-containing regimens. All patients except two had measurable disease prior to transplantation. Twenty-one patients had not received chemotherapy for metastatic disease. Of the remaining 23 patients treated with standard-dose chemotherapy, 14 had progressive disease. Busulfan 16 mg/kg was paired with cyclophosphamide 200 mg/kg (BuCY) or with etoposide 60 mg/kg (Bu-Vp). The Bu-Vp combination (32 courses) was used as the second preparative regimen in patients who had received thiotepa, carboplatin and cyclophosphamide for their first transplant. The BuCY regimen was used in 16 courses, either for single or for tandem transplant. Bone marrow cells only were used in 17 transplants and peripheral blood progenitor cells, with or without bone marrow, in 31 courses. Treatments were usually well tolerated. Common toxicities included mucositis, skin rash and veno-occlusive disease of the liver (fatal in two). One patient developed generalized seizures during busulfan therapy. Hematologic recovery was significantly accelerated with peripheral progenitor cells and permitted the administration of closely spaced tandem transplants. Two patients receiving sequential transplants with BuCY experienced severe long-term neurologic and pulmonary toxicity. Objective responses were noted in 26 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Scintigraphy with iodine-131 metaiodobenzylguanidine in the study of paraganglioma. Comparison between benign and malignant tumors].

In order to evaluate 131I metaiodobenzylguanidine (MIBG) uptake in patients with benign or malignant paragangliomas, 28 patients (14 men and 14 women, mean age 37 +/- 10 years) with benign (no. = 15; group 1) or malignant (no. = 13; group 2) tumors underwent MIBG scintigraphy. A total of 110 lesions (20 benign and 90 malignant) were studied. In all patients histologic disease confirmation was obtained. MIBG uptake was quantified on 48 hours' images (Kodak NMC-1 films) using a photographic densitometer. The optical densities of tumor and adjacent or contralateral normal tissue were used to calculate the MIBG uptake intensity ratio for each lesion. In group 1, all patients exhibited 1 or 2 lesions with abnormal MIBG uptake. In group 2, all patients had 1 to 28 abnormal foci of MIBG uptake. In the patients with 2 or more lesions, the average MIBG uptake intensity ratio was calculated. MIBG uptake intensity ratio was significantly higher in malignant than in benign paragangliomas (5.2 +/- 2.4 vs 2.9 +/- 1.4, p < 0.01). Since MIBG uptake in paragangliomas reflects the intratumoral concentration of catecholamines, higher MIBG uptake in malignant lesions suggests a greater amount of stored catecholamines in these tumors. In conclusion, 131I MIBG scintigraphy may be useful to distinguish benign from malignant paragangliomas.

3-Iodobenzylguanidine↗