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Biomedical subjects

J A John

Publications and source records attributed to J A John.

At least 19 recordsLinked to original sources
PubMed2006

Recent developments in clinimetric instruments.

Assessment of impairment and function is essential in order to monitor joint status and evaluate therapeutic interventions in patients with haemophilia. The improvements in the treatment of haemophilia have required the development of more sensitive tools to detect the more minor dysfunctions that may now be apparent. This paper outlines some of the recent developments in this field. The Haemophilia Joint Health Score (HJHS) provides a systematic and robust measure of joint impairment. The MRI Scoring System has been designed to provide a comprehensive scoring system combining both progressive and additive scales. The Functional Independence Score for Haemophilia (FISH) has been developed to assess performance of functional activities and can be used in conjunction with the Haemophilia Activities List (HAL) which provides a self report measure of function. It is recommended that both measures are evaluated as these tools measure different constructs. Further refinement and testing of the psychometric properties of all of these tools is in progress. More widespread use of these tools will enable the sharing of data across the world so promoting best practice and ultimately enhancing patient care.

Activities of Daily Living↗
PubMed2006

Construction of resolvable spatial row-column designs.

Resolvable row-column designs are widely used in field trials to control variation and improve the precision of treatment comparisons. Further gains can often be made by using a spatial model or a combination of spatial and incomplete blocking components. Martin, Eccleston, and Gleeson presented some general principles for the construction of robust spatial block designs which were addressed by spatial designs based on the linear variance (LV) model. In this article we define the two-dimensional form of the LV model and investigate extensions of the Martin et al. principles for the construction of resolvable spatial row-column designs. The computer construction of efficient spatial designs is discussed and some comparisons made with designs constructed assuming an autoregressive variance structure.

Analysis of Variance↗
PubMed2004

CrossOver: an algorithm for the construction of efficient cross-over designs.

A cross-over experiment involves the application of sequences of treatments to several subjects over a number of time periods. It is thought that the observation made on each subject at the end of a time period may depend on the direct effect of the treatment applied in the current period, and the carry-over effects of the treatments applied in one or more previous periods. Various models have been proposed to explain the nature of the carry-over effects. An experimental design that is optimal under one model may not be optimal if a different model is the appropriate one. In this paper an algorithm is described to construct efficient cross-over designs for a range of models that involve the direct effects of the treatments and various functions of their carry-over effects. The effectiveness and flexibility of the algorithm are demonstrated by assessing its performance against numerous designs and models given in the literature.

Algorithms↗
PubMed1999

Hansen's disease--an enigma.

Hansen's disease is an ancient condition that continues to remain endemic in several countries and also in parts of the United States. It has a varied clinical presentation that requires a high index of suspicion for diagnosis. The immune response of the patient is closely related to the presentation of the disease and is being used for immunotherapy and the development of a vaccine. The therapy regimen usually used is as recommended by the World Health Organization but several different regimens are undergoing trials to aid in decreasing the duration of therapy.

Adult↗
PubMed1985

Teratogenic potential of inhaled dichlorobenzenes in rats and rabbits.

Orthodichlorobenzene (ODCB) and paradichlorobenzene (PDCB) were evaluated for teratogenic potential in rats (ODCB only) and rabbits. Groups of bred rats and inseminated rabbits were exposed to 0, 100, 200, or 400 ppm of ODCB; groups of inseminated rabbits were exposed to 0, 100, 300, or 800 ppm of PDCB. Animals were exposed for 6 hr/day on Days 6 through 15 (rats) or 6 through 18 (rabbits) of gestation. Maternal toxicity, as evidenced by a significant decrease in body weight gain, was observed in all groups of ODCB-exposed rats and liver weight was significantly increased in the 400-ppm ODCB-exposed group. Slight maternal toxicity was observed in groups of rabbits exposed to 400 ppm ODCB or 800 ppm PDCB as indicated by significantly decreased body weight gain during the first 3 days of exposure. Inhalation of up to 400 ppm of ODCB was not teratogenic or fetotoxic in rats, and neither ODCB nor PDCB was teratogenic or fetotoxic in rabbits at exposure levels up to 400 or 800 ppm, respectively.

Abnormalities, Drug-Induced↗
PubMed1984

Comparison of the teratogenic potential of inhaled ethylene glycol monomethyl ether in rats, mice, and rabbits.

Studies to assess the effects of inhaled ethylene glycol monomethyl ether (EGME) on embryonal and fetal development were conducted on groups of Fischer 344 rats, CF-1 mice, and New Zealand White rabbits. Rabbits and rats were exposed to vapor concentrations of 0, 3, 10, or 50 ppm for 6 hr/day on Days 6 through 18, or Days 6 through 15 of gestation, respectively; mice were exposed to 0, 10, or 50 ppm on Days 6 through 15 of gestation. Exposure of pregnant rabbits to 50 ppm produced significant increases in the incidence of malformations, minor variations, and resorptions, as well as a decrease in fetal body weight. Rats and mice exposed to 50 ppm showed no evidence of a teratogenic effect, although indications of slight fetotoxicity were observed in both species. Transient decreases in maternal body weight gain among rats, mice, and rabbits exposed to 50 ppm were the only consistent signs of maternal effects. No significant treatment-related effects on fetal development were observed in any of the species tested at 10 ppm of EGME or below.

Abnormalities, Drug-Induced↗
PubMed1984

Inhalation teratology study on monochlorobenzene in rats and rabbits.

The embryotoxic and teratogenic potential of inhaled monochlorobenzene (MCB) was evaluated in rats and rabbits. Bred Fischer 344 rats and inseminated New Zealand White rabbits were exposed to 0, 75, 210, or 590 ppm of MCB via inhalation for 6 hr/day during the period of major organogenesis. Exposure to 590 ppm caused elevated liver weights in both species and decreased body weight gain and feed consumption in rats. Inhalation of MCB vapors during gestation was not embryotoxic or teratogenic in rats. In rabbits, a few MCB-exposed fetuses exhibited visceral malformations which were not observed among concurrent controls, though no dose-related increase in malformations occurred. To further evaluate the effects of MCB in rabbits, additional groups were exposed to 0, 10, 30, 75, or 590 ppm. This subsequent study did not result in any increase in malformations in the MCB-exposed groups. Fetal effects were limited to a slight delay in skeletal development which occurred only in rats exposed to 590 ppm, a maternally toxic concentration.

Abnormalities, Drug-Induced↗
PubMed1984

Teratologic evaluation of 3,6-Dichloropicolinic acid in rats and rabbits.

3,6-Dichloropicolinic acid (clopyralid), a new herbicide, was evaluated for teratogenic potential in Fischer 344 rats and New Zealand White rabbits. Rats were given 0, 15, 75, or 250 mg clopyralid/kg/day by gavage on Days 6-15 of gestation while rabbits were given 0, 110, or 250 mg clopyralid/kg/day on Days 6-18 of gestation. Maternal toxicity, as evidenced by decreased body weight gain, was observed among pregnant rats in the 250-mg/kg/day group. No evidence of maternal toxicity was observed among treated rabbits. A teratogenic effect was not detected in either species.

Abnormalities, Drug-Induced↗
PubMed1984

Ethylene glycol monomethyl ether (EGME) and propylene glycol monomethyl ether (PGME): inhalation fertility and teratogenicity studies in rats, mice and rabbits.

A combined dominant lethal-fertility study was conducted in which male and female Sprague-Dawley (CD) rats were exposed to 0, 30, 100 or 300 ppm of ethylene glycol monomethyl ether (EGME) vapor for 6 hr/day, 5 days/week for 13 weeks and then mated to untreated counterparts. Among males, fertility was completely suppressed after exposure to 300 ppm. A partial restoration of reproductive function was evident following 13 weeks of recovery. No treatment-related reproductive effects were observed among males exposed subchronically to 100 ppm, or among females exposed to 300 ppm or below of EGME. Studies to assess the effects of inhaled EGME on embryonal and fetal development were also conducted in Fischer 344 rats, CF-1 mice, and New Zealand White rabbits. Rats and rabbits were exposed to concentrations of 0, 3, 10 or 50 ppm for 6 hr/day on days 6-15 or 6-18 of gestation, respectively. Exposure of rabbits to 50 ppm resulted in significant teratologic effects, an increased resorption rate, and decreased fetal body weight. Slight fetotoxicity in the form of skeletal variations were observed among rats exposed to 50 ppm. Exposure of pregnant mice to 0, 10, or 50 ppm for 6 hr/day on days 6-15 of gestation resulted in slight fetotoxicity at 50 ppm. No significant treatment-related effects were observed at 10 ppm of EGME or below in any of the species tested. Separate groups of pregnant rats and rabbits were exposed to 0, 500, 1500 or 3000 ppm of propylene glycol monomethyl ether (PGME) during organogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Inhalation toxicity of epichlorohydrin: effects on fertility in rats and rabbits.

The effects of inhaled epichlorohydrin (ECH) on the fertility of Sprague-Dawley rats and New Zealand white rabbits were studied. Groups of 10 male rabbits, 30 male rats, and 30 female rats were exposed to 0, 5, 25, or 50 ppm of ECH vapor for 6 hr/day, 5 days/week for 10 weeks, and were held for a 10-week postexposure females. Exposed male rats were mated with unexposed females at several intervals during and after the exposure period. In addition, female rats which had been exposed for the 10-week period were mated with unexposed males and allowed to deliver their young. Exposure to 50 ppm of ECH vapor for 10 weeks resulted in transient infertility in the male Sprague-Dawley rats; recovery of fertility in rats occurred during the second week after termination of exposure. Male rats exposed to 25 ppm of ECH were able to impregnate unexposed females; however, fewer implantations were observed in these females than in the females mated to control males suggesting that fertility was adversely affected in this group as well. This effect also was reversed by the second week following termination of exposure. The incidence of resorptions in the unexposed female rats which were bred to the exposed males was not adversely affected. Among female rats exposed to ECH, no adverse effects were observed on estrus cycle, pregnancy rate, parturition, or the number and viability of the offspring. No discernible effects were noted on the volume of the ejaculate or on the motility, viability, concentration, or fertility of spermatozoa from male rabbits exposed to up to 50 ppm of ECH. Histologic examination of tissues from an interim and final termination of the exposed animals indicated that the most severely affected organ following inhalation exposure to 25 or 50 ppm of epichlorohydrin in both rats and rabbits was the nasal turbinates. These lesions, interpreted to be a result of irritation from the test material, were no longer present in animals which were held for the 10-week postexposure period. No adverse effects were observed among rats or rabbits exposed to 5 ppm of ECH for 10 weeks.

Animals↗
PubMed1982

Platelets in the prediction of thrombotic risk.

A study is reported which tries to identify those members of the general population who may be at increased risk of vascular disease. It is probable that patients who have had previous thrombotic episodes are inherently more at risk of further episodes and that a thrombus many months ago will not affect current tests. Accordingly we carried out a number of tests involving platelets on 'controls', and on patients with a past history of either myocardial infarction or deep vein thrombosis (DVT) and patients suffering from intermittent claudication who also are assumed to be at higher risk than the controls. Differences were demonstrated between controls and patient groups and these differences were utilized to develop statistical functions with the ability to discriminate between the groups. The functions were then tested using a second set of data from similar groups. Those designed to discriminate between myocardial infarction patients and controls and between patients with claudication and controls were validated. The heparin thrombin clotting time was found to be the prime predictor variable; the platelet count, platelet volume, platelet factor 3 clotting time and the bleeding time have some predictive value. The antithrombin clotting time, platelet aggregation and platelet adhesiveness tests as measured were not found to have discriminating potential. It is suggested that these appropriate risk functions could be of practical value in identifying members of the general population who may be at greater risk than average. The discriminate functions for DVT patients and controls could not be validated, suggesting differences in platelet involvement in arterial and venous thrombosis.

Analysis of Variance↗
PubMed1981

Vinyl chloride: inhalation teratology study in mice, rats and rabbits.

These studies evaluated the effects of inhaled vinyl chloride monomer (VCM) on mouse, rat and rabbit embryonal and fetal development. Groups of pregnant CF-1 mice, Sprague-Dawley rats and New Zealand white rabbits were exposed to 500 ppm VCM for 7 hr daily during the period of major organogenesis. Subsequently, other groups of mice were similarly exposed to 50 ppm VCM, and rats and rabbits were exposed to 2500 ppm. While maternal toxicity was observed, exposure to VCM did not cause significant embryonal or fetal toxicity and was not teratogenic in any of the three species at the concentrations tested. Simultaneous exposure of some of the pregnant animals to VCM by inhalation plus 15% ethanol in the drinking water resulted in toxic effects greater than those associated with exposure to VCM alone in the three species. The fetal effects observed were similar to those reported for these three species following administration of ethanol without VCM exposure.

Abnormalities, Drug-Induced↗
PubMed1981

Teratogenic effects of vitamin A palmitate in Fischer 344 rats.

Prior to employing the Fischer 344 rat in teratology studies, it was considered necessary to establish the responsiveness of this strain to teratogenic agents. Bred Fischer 344 rats were administered 0, 3.2, 32, or 128 mg/kg/day (approximately 1,000, 10,000, or 40,000 USP units per animal) of vitamin A palmitate by gavage on days 6 through 15 of gestation. Maternal toxicity, as evidenced by decreased body weight gain, and decreased food and water consumption, was observed at the 128 mg/kg/day dose level. This dosage level was embryolethal and teratogenic in the Fischer 344 rat. The incidence of fetal resorptions was statistically significantly increased as compared to controls. Among the surviving fetuses, malformations observed included cleft palate, exencephaly, microphthalmia, anophthalmia, hydronephrosis, brachygnathia, pinna anomalies, and great vessel and heart anomalies. Based on these findings, it is concluded that the Fischer 344 rat responded to a known teratogenic agent and hence is appropriate for use in studies designed to evaluate the teratogenic potential of test agents.

Animals↗
PubMed1981

Triethylenemelamine (TEM): dominant lethal effects in Fischer 344 rats.

Male Fischer 344 rats were administered triethylenemelamine orally at dose levels of 0, 0.5 or 1.0 mg TEM/kg/day, five days per week for four weeks. A separate group of males was administered TEM as a single intraperitoneal injection of 0.3 mg/kg. Following treatment, males were mated with two groups of untreated females for a period of one week each. The uterine contents of untreated females were examined for evidence of a dominant lethal effect as manifested in an increase in the average resorption rate. Significant increases in the resorption rate were seen at 0.5 mg/kg/day for the second breeding period, and at 1.0 mg/kg/day for both breeding periods following oral administration. Significant decreases in the number of implantations, and increases in the average pre-implantation loss and resorption rate were observed following intraperitoneal administration. These effects seen in Fischer 344 rats were comparable to results obtained with other strains following a similar treatment regimen.

Animals↗