Search PubMed⌕ Search

Biomedical subjects

B R Jones

Publications and source records attributed to B R Jones.

At least 163 records · Page 9Linked to original sources
PubMed1981

Kinetics of metoprine, a lipid-soluble antifolate.

1 Using a dihydrofolate reductase inhibition assay, we have conducted either pharmacokinetic studies in six patients receiving metoprine. 2 The serum level v time-curve for metoprine equivalents was irregular; first-order elimination was not observed during the study period of 0--120 h. A model-independent analysis was therefore performed, employing the area under the curve during the first 120 h (AUC). 3 At an oral dose of 65 mg/m2 without leucovorin, a peak level of 0.6 microgram/ml and an AUC of 52 micrograms ml-1 h produced significant leukopenia and thrombocytopenia. 4 At doses ranging from 100 mg/m2 to 175 mg/m2 orally, with leucovorin administration 40 mg/m2 intravenously at 24 and 96 h, haematologic toxicity was seen in only 1 patient who received 175 mg/m2. This patient also had the highest peak serum level (2.8 micrograms/ml) and AUC (228 micrograms ml-1 h). 5 One partial response and one minor regression were observed in the studied patients; these two patients had the 175 mg/m2 dose, highest peak levels (2.4 and 2.8 micrograms/ml) and highest AUCs (197 and 228 micrograms ml-1 h). The other patients had lower peak levels and AUCs and had neither therapeutic response nor hematologic toxicity. 6 The AUC and peak serum levels were linearly related to each other (P less than 0.001). 7 Total urinary excretion of dihydrofolate reductase inhibitors (as metoprine equivalents) in the first 120 h ranged from 5 to 17% of the administered dose.

Folic Acid Antagonists↗
PubMed1981

Bilateral herpetic keratitis.

Thirty patients with bilateral herpetic keratitis were evaluated, 40% of whom were atopic. Stromal keratitis occurred in 40% of the eyes and recurrent ulceration in 68%. Four patients (5 eyes) developed secondary microbial keratitis. Visual acuity decreased to 6/60 or less because of corneal opacification in 17% of the eyes.

Adolescent↗
PubMed1981

Immediate hypersensitivity in the guinea pig conjunctiva. III. long-term persistence of the hypersensitive state and characterization of antibodies.

The ocular immediate hypersensitivity reaction in guinea pigs to topically applied normal rabbit serum can be evoked as long as 4 years after sensitization. The reaction was as severe and tended to persist for longer than that evoked 6 months after sensitization. Passive cutaneous anaphylaxis tests showed that very high titres of homocytotropic antibodies were present and that both IgE- and IgG1-like antibodies were involved. Sensitization with one set of injections instead of two was not consistently successful and the response on challenge was mild to moderate. Pretreatment of eyes with Isoptocarpine before antigenic challenge had no effect on the response. The addition of bacterial lipopolysaccharide to the first set of sensitizing injections produced hypersensitivity in animals which were otherwise refractory to sensitization.

Animals↗
PubMed1981

Phase I and pharmacological studies of pentamethylmelamine administered by 24-hour intravenous infusion.

A Phase I study of pentamethylmelamine (PMM) was conducted, administering the drug as a 24-hr i.v. infusion once weekly for 3 weeks. Doses ranged from 80 to 3000 mg/sq m/week. Twenty-six evaluable patients received a total of 30 courses of PMM. The median performance status of the patients was 60% (range, 40 to 90%), and the median age was 58 years (range, 43 to 72 years). The highest tolerated dose was 2000 mb/sq m/week. Nausea and vomiting were the dose-limiting toxicities; myelosuppression was neither consistent nor severe. One objective response lasting 10 months was noted in a patient with renal cancer. Pharmacokinetic studies using [ring-14C]PMM demonstrated a postinfusion half-life of 14C of approximately 12 hr, with the majority of the radiolabel excreted in the urine. PMM was introduced as a parenteral form of hexamethylmelamine. The present schedule does not permit administration of PMM in a dose greater than the tolerated dose of hexamethylmelamine and does not appear to offer an advantage over the p.o. use of the parent compound.

Adult↗
PubMed1981

Cyclosporin A applied topically to the recipient eye inhibits corneal graft rejection.

Corneal graft survival in rabbits was significantly (P less than 0 . 001) prolonged by topical treatment to the recipient eye with cyclosporin A 1% in arachis oil applied five times daily for 4 weeks. No graft was rejected whilst treatment was maintained but all grafts subsequently underwent rejection by the 64th postoperative day. All animals in a simultaneous control group in this fully masked study developed allograft reactions by the 23rd day. No local or systemic side-effects attributable to cyclosporin A were observed. It is believed that this is the first report of inhibition of an allograft reaction by cyclosporin A applied topically.

Animals↗
PubMed1981

Electron microscope studies on the effects of dimethyl sulphoxide in mammary glands of Long Evan rats during foetalogeneis.

The effects of dimethyl sulphoxide (DMSO) in mammary glands of rats during foetalogeneis was studied by means of electron microscopy. Certain morphological alterations were observed in secretory tubules and epithelial cels of mammary glands. These alterations were not evident in control tissues. Secretory tubules of DMSO-treated mammary glands showed dissociation, thickening of granular fibrous-like material and profound darkening. Morphological alterations observed in epithelial cells involved decrease and dissociation of fibrillar complexes, numerous electron-dense droplets, mitochondria with disrupted cristae, hypertrophied granular endoplasmic reticuli, vacuoles and cellular debris. Thus, the results in this study suggest that DMSO at sublethal dosages induces morphological alterations in mammary gland tissue of rats during 16.5 days of gestation.

Animals↗
PubMed1980

Outcome of pregnancy in sickle cell anemia and sickle cell-hemoglobin C disease. An analysis of 181 pregnancies in 98 patients, and a review of the literature.

The outcome of pregnancy has been analyzed in 72 women with sickle cell anemia (SS) and 26 women with sickle cell-hemoglobin C disease (SC), part of an unselected population of 148 women over 18 years of age with these hemoglobinopathies, who have been followed at a sickle cell disease clinic for 8 years. In SS women, 22% of first pregnancies were aborted spontaneously, and the overall early fetal loss was 19.2%. A similar figure was calculated from the literature since 1956. In SC women, 12% of first pregnancies were lost, but the overall early fetal loss was only 8.9%. The perinatal mortality, under quite variable conditions of prenatal care and delivery, was 10.2% in SS women and 2% in SC women. There were no stillbirths or midterm deaths in utero among SC women, but these accounted for most of the perinatal mortality in SS women, particularly in first and second pregnancies. There was one neonatal death in each group, but eight third pregnancies in SS women were completed without perinatal mortality. A remarkable finding among the SC women was the number of successful pregnancies, ten in one woman, and many of the pregnancies were completed without the supervision of a physician. Our findings were compared with those in the literature, and the conclusion that we drew is that termination of pregnancy and sterilization of young women are not generally indicated solely on the basis of these hemoglobinopathies.

Abortion, Spontaneous↗
PubMed1980

Prognosis and management of corneal transplantation for herpetic keratitis.

One hundred thirty-two penetrating keratoplasties (91 patients) for herpetic keratoplasty were reviewed retrospectively. The overall survival rate of clear keratoplasties to two years was 64% and to five years was 62%. The significant prognostic factors were preoperative ocular inflammatory status and degree of corneal vascularization. The two-year survival rate of a clear keratoplasty was 69% where eyes were inflamed at the time of surgery, compared with 44% in actively inflamed eyes. Allograft rejection, the major cause of a clouded herpetic keratoplasty, increased in frequency with increasing corneal vascularization. Antiviral cover was not used with routine postoperative steroids or with steroid intensive therapy for rejection. Epithelial herpetic recurrences occurred in 32% of eyes undergoing allograft rejection within four months of initiation of treatment for rejection. This is compared with otherwise uncomplicated keratoplasties where the epithelial recurrence rate was 6% at four months, on high-dose postoperative corticosteroid therapy without antiviral cover.

Corneal Transplantation↗
PubMed1980

Renal injury in patients with rheumatoid arthritis treated with gold.

While severe nephrotoxicity is uncommon during gold therapy of rheumatoid arthritis (RA), the prevalence of mild nephrotoxicity has not been investigated. To study this, levels of leucine aminopeptidase (LAP) and N-acetyl-beta-glucosaminidase (NAG) (nmole/hr/mg urinary creatinine), and beta 2-microglobulin (beta 2M) (microgram/mg urinary creatinine) were measured in urine samples from 33 patients with RA receiving gold and 28 patients with various musculoskeletal diseases not receiving gold. Each patient had a normal urinalysis and blood urea nitrogen or serum creatinine. LAP was above 30 in 55% of RA patients and 7% of controls (p < 0.01). NAG was above 100 in 70% of RA patients and 14% of controls (p < 0.01). In 8 RA patients, NAG was over 200; LAP was over 100 in 4, but in none of the controls. Beta 2M was above 0.32 in 7 of 23 female RA patients and in none of 12 female controls (p = 0.012) and none of the male patients. Patients who excreted high levels of beta 2M also excreted high levels of NAG and LAP. These data show that gold in therapeutic doses affects renal tubular cells, cauing the release of NAG and LAP from lysosomes and brush borders of the cells. This may represent the mildest stage of nephrotoxicity. Elevated beta 2M in the urine of some patients indicate a degree of nephrotoxicity sufficient to cause renal tubular dysfunction.

Acetylglucosaminidase↗
PubMed1980

Comparison of methods of evaluating nephrotoxicity of cis-platinum.

The urinary excretion of leucine aminopeptidase (LAP), N-acetyl-beta-glucosaminidase (NAG), and beta 2-microglobulin was measured in 12 cancer patients receiving cis-platinum to evaluate the sensitivity of these indices for renal tubular damage. NAG and LAP excretion rose markedly in all patients, and beta 2-microglobulin rose in 11. Seven of the 9 patients who had received cis-platinum 6 wk before the study had prestudy dose elevations of one or more of these indices. We conclude that these urinary proteins are sensitive indicators of proximal renal tubular injury and may provide greater sensitivity for comparison of the nephrotoxic potential of future platinum analogs or for assessing the efficacy of regimens designed to protect the kidney from platinum nephrotoxicity than other measurements. The persistence of high excretion vales for these indices 6 wk after a dose demonstrates the persistent renal injury by cis-platinum.

Acetylglucosaminidase↗
PubMed1980

Evaluating patients' warfarin requirements.

Seventy consecutive patients receiving warfarin as an anticoagulant were evaluated for the relationship between the response to the loading dose of warfarin and the response to the maintenance dose. No patients were excluded because of complicating diseases or the concurrent use of other drugs. There was a moderate correlation (r = 0.54, p less than 0.01) between response to the loading dose and response to the maintenance dose. Thus, a relatively weak response to a loading dose of warfarin can be used to predict a need for a relatively large maintenance dose in unselected patients requiring anticoagulant therapy. Age seems to be a relatively weak determinant of warfarin sensitivity. Other factors such as the genetic control mechanism, concurrent drug therapy, and complicating diseases apparently are more important determinants.

Adult↗
PubMed1980

Effect of cyclosporin A on the survival of corneal grafts in rabbits.

Cyclosporin A given to rabbits intramuscularly in a dose of 25 mg/kg/day for up to 28 days after corneal transfer results in a marked prolongation in the survival of penetrating corneal grafts compared to that in an untreated control group. Cyclosporin A 1% drops did not prolong survival of the corneal graft, but this may be related to the need for skin transfer 14 days after corneal transfer to ensure rejection, and supports the idea that the drug plays an immunosuppressive role at the time and place of sensitisation.

Animals↗
PubMed1980

Comparative sensitivity of fluorescent antibody staining of conjunctival scrapings and irradiated McCoy cell culture for the diagnosis of hyperendemic trachoma.

The sensitivity of an indirect fluorescent antibody (FA) staining technique for detecting chlamydial inclusions in scrapings from the whole conjunctiva (upper tarsus, upper fornix, and lower lid) was compared with the sensitivity of culture in irradiated McCoy cells for the diagnosis of hyperendemic trachoma. In a group of 211 patients with various grades of active trachoma from the Bandar Abbas area of Southern Iran 42 patients were positive for chlamydiae by either method. There was little difference between the rates of positivity of FA staining of the scrapings from the whole conjunctiva (28 positives) and culture in irradiated McCoy cells (32 positives). In the patients included in this study chlamydial inclusions were detected in 15 eyes by examination of FA stained scrapings taken from the upper tarsal conjunctiva, whereas inclusions were detected in 40 eyes by the additional examination of scrapings taken from the upper fornix and lower lid (P less than 0.001). The examination of FA stained scrapings taken from the whole conjunctiva and spread as a single but larger smear may provide a satisfactory alternative to cell culture methods for the diagnosis of trachoma, particularly for field studies when cell culture facilities are not available.

Cells, Cultured↗