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Biomedical subjects

R W Jones

Publications and source records attributed to R W Jones.

At least 109 records · Page 6Linked to original sources

Efficacy and safety of cilazapril in elderly patients with essential hypertension. A multicenter study.

The efficacy and safety of cilazapril monotherapy was evaluated in a multicenter, open-label, ascending-dose titration study in 83 elderly essential hypertensive patients. After a four-week, single-blind, placebo run-in period, patients received 1 mg of cilazapril once daily for the first four weeks. This dose was then increased to 2.5 mg once daily for the next four weeks for patients whose pre-dose sitting diastolic blood pressure was above 90 mm Hg. Similarly, at Week 8 the dose was increased in such patients from 1 to 2.5 mg or from 2.5 to 5 mg once daily. A 12-hour blood pressure profile was performed on the first day of active treatment and of each dose increase. Mean decrease of sitting diastolic blood pressure from baseline (102.7 +/- 0.4 mm Hg) at Week 12 was 13.3 +/- 1.1 mm Hg (p less than 0.001). Seventy-five percent of patients had a decrease of 10 mm Hg or more from baseline sitting diastolic blood pressure, and in 60 percent sitting diastolic blood pressure normalized. Unexpectedly large decreases of blood pressure after the first dose were seen only in three patients and none had clinical symptoms. Fourteen patients (16.9 percent) reported adverse events, but most of these were judged unlikely to be related to therapy. Four patients with predisposing underlying diseases experienced potentially serious adverse events (angina pectoris, myocardial infarction, arrhythmia, and blood pressure elevation) whose relationship to therapy was judged remote or only possible. There was no particular pattern of changes in laboratory values. The results indicate that cilazapril is an effective, safe, and well-tolerated antihypertensive drug for the elderly.

Aged↗

Pharmacokinetics of a single dose of ofloxacin in healthy elderly subjects using noncompartmental and compartmental models.

The pharmacokinetics of ofloxacin following a single 200 mg oral dose were studied in twelve healthy elderly volunteers. Relevant pharmacokinetic parameters were analysed by both noncompartmental and compartmental models. In compartmental analysis, the data on plasma concentrations was best described by an open two-compartment model. A zero-order absorption behaviour was found in some volunteers. The terminal half-lives were slightly prolonged and ranged from 6.2-11.6 h. A linear relationship was found between the renal clearance of the drug and the estimated creatinine clearance. Computer predictions of a multiple 200 mg dose regimen showed no important accumulation of ofloxacin. The recommendation of some authors that, in general, ofloxacin dosage may be halved in the elderly could not be confirmed. This has to be determined through further clinical experience in elderly ill subjects.

Aged↗

Adenovirus infection retards ribosomal RNA processing.

Eight hours after infection of KB cells with adenovirus type 12, the rate of conversion from the 32S ribosomal RNA (rRNA) precursor to mature 28S and 5.8S rRNA decreased. An additional RNA species was detected, which appears to be novel, on the basis of its estimated size (about 6.5 kilobases) and its high level of radiolabeling early after infection at low multiplicity.

Adenoviridae Infections↗

RNA synthesis and stability in UV-irradiated and nonirradiated mouse L cells.

In mouse L cells, relatively low doses of UV light (e.g., about 35 J/m2) induced the rapid breakdown of the molecules of many RNA species transcribed shortly before irradiation. This included 28S, 18S, 5.8S, and 5S rRNA, U1, U2, U3, U4, and U5 small nuclear RNA, but not the main band of transfer RNAs or 7SL RNA. At higher UV doses, an RNA band that contains tRNAleu was also degraded rapidly after UV irradiation. RNA molecules synthesized long before irradiation (e.g., 22 h for small RNAs, 4 h for large rRNAs) were not affected. Our results suggest that the maturation and/or assembly into fully mature ribonucleoprotein particles of several small RNA species is not completed 4 h after transcription. The effect of UV radiation occurred in mouse L cells, but not in human HeLa or KB cells. In a previous report, L cells were transformed by DNA transfection with two mouse U1b RNA genes, named U1.1 and U1.2. We observed now that, in L cells transformed with the U1.2 gene, the ratio of radioactivity in the apparent U1b and U1a RNA precursors after 5 min of labeling was about 20 times higher than a) this ratio in briefly labeled L cells that had been transformed with the U1.1 gene, and b) the ratio of radioactive mature U1b and U1a RNA after 20 h of chase in L cells transformed with the U1.2 gene. These results suggest that very high levels of U1b RNA are transcribed from the exogenous U1.2 gene copies, followed by the rapid degradation of most of these transcripts.

Animals↗

Body surface potential mapping to monitor the effects of thrombolytic therapy following acute myocardial infarction.

The authors demonstrate the value of body surface potential mapping (BSPM) and a limited lead system in monitoring complete ECG evolution following myocardial infarction (MI) and the effects of thrombolytic therapy. They produced ST-segment isopotential maps, which indicate the site and extent of myocardial injury. Pathological Q wave maps were also produced, which intimate the extent of myocardial necrosis. Analysis of a sequence of maps recorded during the acute phase of MI revealed sudden changes attributed to reperfusion, reinfarction or "silent" events.

Adult↗

Cervical cytology in the Auckland region.

A two week prospective study of the characteristics of women having cervical smears in the Auckland region in 1985 is presented. European and Maori women have about the same rate of smears while Pacific Islanders have a slightly lesser rate. Many women are not having smears taken during pregnancy or at the postnatal examination. Doctors initiate twice as many smears as their patients. More than half of the women had smears taken in less than the three year interval recommended for screening. Five per cent of smears have some degree of cervical intraepithelial neoplasia (CIN) and nearly half of these showed evidence of human papilloma virus (HPV) infection. There is a spectrum extending from young women in their early twenties with HPV infection alone through their later twenties with HPV and CIN and finally women in their thirties and forties with carcinoma-in-situ (CIS) alone.

Adolescent↗

Metabolism of U6 RNA species in nonirradiated and UV-irradiated mammalian cells.

We observed a series of rapidly labeled U6 RNA bands, which were hybrid selected with U6 DNA, in nonirradiated human cells. The electrophoretic mobility of these bands in denaturing gels was lower than that of the known mature U6 RNA species, and was equivalent to transcripts up to approximately 7 nucleotides longer. These multiple U6 RNA species lost their label during a chase without a proportional increase in radioactivity in the known mature U6 RNA, which suggests that a substantial fraction is not processed into the major mature U6 RNA. During a label chase, the multiple U6 RNA bands appeared first in the cytoplasmic fraction and later in nuclei. One of the major rapidly labeled U6 RNA bands had the electrophoretic mobility of an RNA species one nucleotide shorter than the known mature U6 RNA. UV light induced a UV dose-dependent, preferential disappearance of recently synthesized molecules of the U6 RNA species of higher gel electrophoretic mobility, including the known mature U6 RNA. Since this effect was seen in cells pulse-labeled immediately before or after irradiation, it suggests that UV radiation induces the specific degradation of the electrophoretically faster moving species of U6 RNA, which are apparently shorter chains. The effect of UV light was RNA species-specific, was not seen in molecules synthesized long (e.g., 22 hr) before irradiation, and occurred in human and mouse cells.

Animals↗

Comparative sequence analysis of the genomic segment 6 of four rotaviruses each with a different subgroup specificity.

The nucleotide sequences of the genes that code for the major inner capsid protein, VP6, of the human rotavirus strain 1076 (subgroup I), porcine rotavirus Gottfried (subgroup II), equine rotavirus strain H-2 (non-I/II) and equine rotavirus strain FI-14 (both subgroups I and II) have been determined. The sixth segment positive-stranded RNA encodes a protein of 397 amino acids in all strains with the exception of strain H-2 in which it encodes a protein of 399 amino acids. Alignment of amino acid sequences of the VP6 protein of strain FI-14 and subgroup II rotaviruses (Wa and Gottfried) indicates a high degree of homology (94%), while homology between strain FI-14 and subgroup I rotaviruses (SA-11, RF and 1076) was somewhat less (90 to 92%). On the other hand a high degree of conservation of amino acid sequence (95 to 97%) was observed between the H-2 strain and subgroup I rotaviruses. Five regions that may contribute to subgroup epitopes were identified. Region A (amino acids 45, 56) and region C (amino acids 114, 120) may contribute to subgroup I epitopes and regions B (amino acids 83, 86, 89, 92), D (amino acids 312 or 314, 317 or 319) and E (amino acids 341 or 343, 350 or 352) may contribute to subgroup II epitopes. When analysed using the Western blot technique monoclonal antibodies specific for VP6 epitopes shared by all rotaviruses were observed to react with both monomeric and trimeric forms of VP6, while monoclonal antibodies specific for a subgroup I or II epitope reacted only with the trimeric form of VP6. This observation and the sequence analyses suggest that subgroup antigenic specificity is determined by conformational epitopes produced by the folding of VP6 or the interaction between VP6 monomers.

Amino Acid Sequence↗

The Corfu delta beta zero thalassemia: a small deletion acts at a distance to selectively abolish beta globin gene expression.

The Corfu delta beta zero thalassemia is characterized by the clinical picture of thalassemia intermedia. In the homozygous state there is a complete absence of hemoglobin (Hb) A and Hb A2 and a high level of Hb F. A DNA fragment containing the gamma and beta globin genes has been cosmid cloned, and the deletion breakpoint region, the beta globin gene and the promoter regions of the gamma globin genes sequenced. The deletion removes 7,201 base pairs (bp) containing part of the delta globin gene and sequences upstream. The beta globin gene contains a G----A mutation at IVS 1 position 5. The gamma globin gene promoters are normal. Analysis of the transcription of the mutated beta globin gene in transfected HeLa cells shows that normal message is produced at a level of approximately 20% compared with a normal gene, the remaining 80% being spliced at cryptic sites in exon 1 and intron 1. This indicates that the mutation in the beta globin gene is not the sole cause of the absence of Hb A in Corfu delta beta zero thalassemia. It is concluded that the 7.2 kilobase (kb) of deleted DNA contains sequences necessary for the normal activation of the beta globin gene. Possible mechanisms for the effect of the deletion on the expression of beta and gamma globin genes are discussed.

Base Sequence↗

Use of bar code labels on collection tubes for specimen management in the clinical laboratory.

A new generation in specimen handling has arrived with the introduction of bar code readers on medical laboratory equipment. The incorporation of this technology into laboratory information systems offers a streamlining of specimen workflow never before achievable in a laboratory environment. The use of evacuated collection tubes as the primary sampling container on a random-access chemistry analyzer interfaced to a laboratory information system creates a very simplified sampling/analysis system with tremendous advantages. There are significant labor savings, superior service to clinicians, and reduced chances for clerical error.

Computers↗

Acute effects on psychomotor performance of binedaline alone and with alcohol.

The effects of single oral doses of binedaline (100 mg), imipramine (50 mg) and placebo administered without and with alcohol (0.8 g/kg) were compared on performance tasks (posturographic recordings, i.e., body sway to study alertness, squares test to explore attention and concentration) and subjective assessments in 12 healthy volunteers. The tasks were completed 1.4 and 8 h after drug administration. Blood samples were collected at the same times. Binedaline had no significant effects on any of the task parameters and did not interact with alcohol. Imipramine alone impaired performance at 4 h as shown on posturographic parameters. These disturbances were potentiated by the intake of alcohol. No pharmacokinetic interaction was noted.

Adult↗

Antiradiation compounds. XXII. Methyl 3-amino-2-phenyldithiopropenoates and 1,1-bis(methylthio)-3-amino-2-phenyl-1-propenes.

The title compounds were prepared in the attempt to provide methylthio and bis(methylthio) analogues of the radioprotective pyridinium- and quinolinium-2-dithioacetic acid derivatives in which the methylthio function is attached to an amino group through an aliphatic chain. The methyl 3-amino-2-phenyldithiopropenoates were obtained by the reaction of amines with 4-phenyl-3-methylthio-1,2-dithiolium iodide, and the 1,1-bis(methylthio)-3-amino-2-phenyl-1-propenes were obtained by methylation and reduction of the dithiopropenoates. The methyl dithiopropenoates with aliphatic substituents on the nitrogen gave only fair or poor radiation protection in mice, and one example of the reduced bis(methylthio) derivatives tested was inactive. The precursor 1,2-dithiole-3-thione and its methiodide, predicted to be radiation protective, were found inactive in this test.

Alkenes↗

Antiradiation compounds. 20. 1-Methylquinolinium(and pyridinium)-2-dithioacetic acid derivatives.

A new class of radiation-protective compounds has been found in the bis(methylthio) and methylthio amino derivatives of 1-methylquinolinium- and 1-methylpyridinium-2-dithioacetic acids. The compounds gave good protection to mice vs. 1000-rad gamma-radiation in ip doses of 10 mg/kg or less, much lower than those required for the aminoalkyl thiols (approximately 150-600 mg/kg). The dithioacetic acid zwitterions were prepared from the base-catalyzed reaction of carbon disulfide with quinaldine and picoline methiodides, and the bis(methylthio) derivatives resulted from reaction with methyl iodide at room temperature. Replacement of one methylthio moiety took place readily on reaction of the bis(methylthio) derivatives with 1 molar equiv of an amine. The best protective activity was found with the methylthio piperidino derivative in both the quinolinium and pyridinium series.

Animals↗

Lisinopril in elderly patients with hypertension.

The antihypertensive efficacy and safety of lisinopril, a long-acting angiotensin-converting enzyme inhibitor, were assessed in 40 elderly patients (aged 65 years or over) with mild to moderate systolic/diastolic or isolated systolic hypertension, in an open study of 12 weeks' duration. Lisinopril was given orally in single daily doses. The starting dose was 5 mg in patients with glomerular filtration rate (GFR) of 30-60 ml/min and 10 mg in patients with GFR greater than 60 ml/min. The dose of lisinopril could be titrated upwards to a maximum of 40 mg daily according to blood pressure response. A thiazide diuretic was then added if blood pressure was not controlled. Thirty-six patients completed the study. Mean sitting blood pressure was significantly reduced by lisinopril treatment. There was no significant alteration in the heart rate, and postural hypotension did not occur. The median dose of lisinopril given was 20 mg daily (range 5-40 mg daily), and only two patients had a diuretic added to the lisinopril. One patient was withdrawn from the study because of unstable angina, and another was discontinued from lisinopril treatment because of anorexia and facial flushing. One patient was withdrawn after 8 weeks because of interruption of lisinopril therapy for a transurethral resection of the prostate, and one patient was lost to follow-up. No clinically significant haematological or biochemical changes were observed. The mean glomerular filtration rate was unchanged during the study. Proteinuria did not occur de novo, nor did established proteinuria increase. Thus lisinopril was well-tolerated and effective therapy in a group of elderly hypertensive patients.

Aged↗

The Aldridge sling procedure in the treatment of urinary stress incontinence.

The long-term results of the Aldridge sling procedure for the treatment of recurrent urinary stress incontinence was assessed in 50 women most of whom had had previous failed vaginal surgery; 78% of patients were cured of all symptoms and a further 20% were symptomatically improved--a 2% failure rate. Only one patient reverted from a cure to improved during the lengthy follow-up. The procedure is not difficult to perform and is a good surgical option in patients with failed vaginal surgery.

Evaluation Studies as Topic↗

Conversion of viridin to viridiol by viridin-producing fungi.

The fungistatic compound viridin, produced by the fungus Gliocladium virens, was found to be irreversibly reduced to the phytotoxin viridiol in liquid culture. Conversion occurred only in the presence of viridin-producing fungi and was subsequent to viridin production. Radiolabelled viridin was rapidly taken up by the mycelium of G. virens and reduced to radiolabelled viridiol, while labelled viridiol was not taken up to any significant extent by the mycelium. Reduction of viridin to viridiol was independent of culture pH, carbon source, and nitrogen source or quantity. A simple production system consisting of peat moss amended with dextrose and calcium nitrate and inoculated with G. virens supported production of 86 micrograms viridiol/g peat. This production system, when applied to soil, may have value as a herbicide.

Androstenediols↗