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Biomedical subjects

H Jones

Publications and source records attributed to H Jones.

At least 199 records · Page 11Linked to original sources

T cell subpopulation dynamics following insulin-induced hypoglycaemia in normal subjects.

Using monoclonal antibodies OKT3, OKT4 and OKT8, T lymphocyte subpopulations were determined in eight normal male volunteers. One month later, the T cell populations were again measured before and during an insulin stress test. Compared to the month before, there was a statistically significant reduction in the numbers of OKT4 cells (P less than 0.01) in the basal sample. Administration of insulin produced a statistically significant rise in the numbers of total lymphocytes and in each of the T cell subpopulations at 30 and/or 60 min (P less than 0.01) when compared with the basal values. It was also noted that in some of the subjects, the sum of OKT4 and OKT8 cells was greater than the number of OKT3 cells after insulin administration. This suggests that under certain circumstances T cells in circulation may express both the helper and suppressor cell antigen. Insulin stress test is associated with increased production of stress hormones in response to the hypoglycaemia, and the observed lymphocyte changes may be mediated via these hormonal alterations.

Adult↗

Diclofenac sodium, diflunisal and naproxen: patient preferences for anti-inflammatory drugs in rheumatoid arthritis.

Ninety patients with active rheumatoid arthritis took part in a cross-over trial comparing diclofenac sodium, diflunisal and naproxen. The efficacy of the three drugs was similar though there were trends in favour of diclofenac sodium in some measurements. The incidence of side-effects was similar with the three drugs and each was chosen by a significant group of patients as continuation therapy at the end of the study.

Adult↗

Further characterization of putative alpha--adrenergic receptors in brain that affect blood pressure and the secretion of ACTH, GH and renin in dogs.

To determine if alpha 1-or alpha 2-adrenergic receptors mediate the inhibition of ACTH stimulation of growth hormone secretion, decrease in blood pressure and inhibition of renin secretion produced by release of catecholamines in the brain, drugs with varying amounts of alpha 1- and alpha 2-adrenergic activity were injected directly into the third ventricle in pentobarbital anesthetized dogs. To determine whether the receptors mediating the responses to clonidine were pre- or postsynaptic, the effect of intravenous clonidine was determined 2 weeks after intraventricular 6-hydroxydopamine, and 24 h after intravenous alpha-metyl-p-tyrosine. Norepinephrine, epinephrine and clonidine, but not methoxamine and phenylephrine inhibited ACTH secretion. None of these alpha-agonists affected growth hormone secretion. Epinephrine and clonidine lowered blood pressure. Clonidine decreased plasma renin activity, but the other agonists increased it. In dogs treated with 6-hydroxydopamine, the decrease in blood pressure and ACTH and renin secretion produced by clonidine was not altered but the growth hormone response was reduced. alpha-methyl-p-tyrosine had no effect on the ACTH and growth hormone responses to clonidine. The data suggest that postsynaptic alpha-adrenergic receptors mediate inhibition of ACTH secretion and stimulation of growth hormone secretion, although in the case of growth hormone secretion, a presynaptic receptor is also involved. In addition, postsynaptic alpha 2-adrenergic receptors mediate a decrease in blood pressure, and they may mediate decreased renin secretion.

Adrenergic alpha-Agonists↗

Selective inhibition of human leukocyte elastase and bovine alpha-chymotrypsin by novel heterocycles.

A number of N-arylbenzisothiazolinone 1,1-dioxides have been synthesized and examined for inhibitory activity against human leukocyte and porcine pancreatic elastase (EC 3.4.21.11), bovine alpha-chymotrypsin (EC 2.4.21.1), human leukocyte cathepsin G (EC 3.4.21.20), and bovine trypsin (EC 3.4.21.4). They are potent, selective, competitive inhibitors of human leukocyte elastase and chymotrypsin. The inhibitory capacity of these compounds is directly related to the electron-withdrawing capability of the aryl substituents. When sufficiently activated, the amide bond in the heterocyclic ring can be cleaved by the enzyme, resulting in inhibition which is highly specific. The most potent inhibitor of hummotrypsin. The inhibitory capacity of these compounds is directly related to the electron-withdrawing capability of the aryl substituents. When sufficiently activated, the amide bond in the heterocyclic ring can be cleaved by the enzyme, resulting in inhibition which is highly specific. The most potent inhibitor of human leukocyte elastase, the 2,4-dinitrophenyl derivative, has a Ki of 2.16 microM with elastase and 0.77 microM with chymotrypsin. This study demonstrates that it is possible to design specificity into non-peptide, low molecular weight serine protease inhibitors, which may have considerable pharmacologic potential.

Animals↗

Acute pelvic inflammatory disease in outpatients: association with Chlamydia trachomatis and Neisseria gonorrhoeae.

Among 830 women attending a clinic for sexually transmitted disease, Chlamydia trachomatis was isolated from 180 (22%) and Neisseria gonorrhoeae from 84 (10%). Retrospective analysis showed that 43 of the women were given outpatient treatment for acute pelvic inflammatory disease because they had low abdominal pain, deep dyspareunia, or unusual vaginal bleeding, or all of these, for less than 2 months in association with cervical motion or adnexal tenderness, or both. None had adnexal masses. C. trachomatis was isolated from 22 and N. gonorrhoeae from 15 of this subgroup of 43 women. This presentation of pelvic inflammatory disease occurred in 10 of the 37 women in the whole study with both C. trachomatis and N. gonorrhoeae, 12 of 143 women with C. trachomatis alone, five of 47 women with N. gonorrhoeae alone, and 16 of 603 women with neither organism. Thus, in North America, C. trachomatis is associated with a syndrome usually diagnosed as mild pelvic inflammatory disease and managed on an outpatient basis.

Acute Disease↗

13-cis retinoic acid and acne.

Patients with very severe acne which had not responded to conventional treatment were given 13-cis retinoic acid (0.1 mg-1.0 mg/kg body-weight) in a double-blind dose response study. Sebum excretion rate was reduced by 75% at 4 weeks, and all patients had an 80% improvement in their acne severity after 4 months treatment. There were dose-related side-effects, particularly dryness of the skin and mucous membranes. No patient wished to stop treatment.

Acne Vulgaris↗

Inhibition of elastase and other serine proteases by heterocyclic acylating agents.

The N-acylsaccharins and N-acylbenzoisothiazolinones form a new class of acylating inhibitors of the serine proteases with a broad spectrum of activity. However, they are unique in that they are able to differentiate between various serine proteases because of the differential stability of the presumptive acyl-enzyme formed. Furoyl saccharin was the best studied among this class of inhibitors. We report evidence that the amide bond in the heterocyclic ring of this compound is cleaved by porcine pancreatic and human leukocyte elastases and chymotrypsin, forming acyl-enzymes. Radioisotope studies indicate that the saccharin portion of furoyl saccharin is attached to these enzymes in approximately a 1:1 molar ratio with enzyme, blocking the active site serine. The acylelastases thus prepared are unusually stable to hydrolysis, with kdeacyl values at neutral pH of 2.3 x 10(-6) s-1 for porcine pancreatic elastase and 1.4 x 10(-6) s-1 for human leukocyte elastase. Trypsin appears to be inhibited by a different mechanism. These data suggest a new approach to the design of specific synthetic protease inhibitors.

Animals↗

Diazepam and lorazepam compared as sedatives for outpatient third molar surgery.

A clinical trial was designed to compare diazepam and lorazepam when administered intravenously immediately prior to third molar surgery. The two drugs were compared on three scores, patient behaviour during surgery, presence of amnesia and extent of psychomotor impairment. Within the confines of the investigation the principle difference between diazepam and lorazepam was the greater degree of psychomotor impairment induced by the latter drug two hours post-injection.

Adolescent↗

The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy.

In a group of 5 women on long-term anticonvulsant and oral contraceptive therapy, the plasma ethynylestradiol (EE) concentration on 50 microgram EE daily was 11.1 +/- 4.5 pg/ml. These values were at the lower end of the range found in normal women in this laboratory taking 30 microgram EE daily (6-190 pg/ml). Four women have been studied prospectively for 3 months, over 1 cycle before and 2 cycles during phenobarbital 30 mg b.i.d. therapy. Significant falls in the plasma EE concentration were seen in two women (from 104.8 +/- 13.4 to 37.7 +/- 2.0 pg/ml and from 125.6 +/- 23.8 to 34.8 +/- 6.7 pg/ml p less than 0.01) and breakthrough bleeding was seen in both women. No changes in plasma concentrations of follicle stimulating hormone, progesterone, norethindrone or norgestrel were seen. There was a significant increase in the sex hormone binding globulin capacity from 100.7 +/- 5.8 to 133.3 +/- 1.2 nmoles/1 (p less than 0.05). These changes are consistent with the known microsomal enzyme inducing effect of phenobarbital.

Adolescent↗

Utilization of diagnostic radiologic examinations in the emergency department of a teaching hospital.

A study to document the utilization by house officers of the Diagnostic Radiologic Examination (DRE) in trauma patients was carried out over 2 years at Stanford University Medical Center. Physicians recorded the likelihood of a fracture being present for patients requiring DRE's to evaluate traumatic injuries. The physician's opinion and the radiologist's final interpretation of the DRE were compared for 24 anatomic regions. Preliminary findings reveal: for almost half the DRE's the officer indicated that the reason for the DRE was medicolegal; 7% of the medicolegal cases had fractures present; less than 4% of these fractures was important enough to change the medical treatment. The levels of house officer experience are suggested as possible causes of excessive DRE utilization, as well as the influence of defensive medicine. Using Green and Swets' Theory of Signal Detection, it is possible to mathematically describe an accuracy index, and a "fear" index for each physician. We plan to use this model in analysis of the study data.

California↗

Are basic assumptions we hold about health education defensible?

Underlying numerous programs designed to promote healthfulness are several implicit and/or overlooked assumptions. These suppositions are considered to be "understood." However, more often they lack validation in an empirical sense. The article is intended to prompt a systematic appraisal of certain presumptions about health, health education and health educators.

Health↗

Correlation of bioavailability in man with simulated absorption data for three doxantrazole preparations.

The in vitro and in vivo availability of doxantrazole, a potential antiallergic compound has been evaluated. A solution was significantly less bioavailable than either tablet or suspension formulations and it is suggested that this is associated with the large volume of the solution vehicle altering the hydrophilicity of the gastrointestinal fluids. In vitro availability was determined from absorption rate constants and absorption profiles obtained using the Sartorius absorption and solubility simulators. A statistically significant correlation was found between the percentage absorbed in vitro at 1 h and both total urinary recovery and area under plasma curve values in vivo. It is considered that in vitro determination of diffusion through artificial lipid membranes may be a useful predictive method of in vivo availability.

Biological Availability↗

Synthesis and analgesic activity of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones and 3-(substituted phenyl)-1,2,3-triazolo[4,5-b]pyridines.

In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the pain thresholds of both the inflamed and normal foot were elevated. This is not commonly observed with nonsteroidal antiinflammatory agents. The most active compounds were 1,3-dihydro-3[3,4-(methylenedioxy)phenyl]imidazo[4,5-b]pyridin-2-one (I-15) and its N-allyl (I-21) and N-isopropyl (I-121) derivatives. In the triazole series the 3-(2-fluoro- and 2,4-difluorophenyl)triazolo[4,5-b]pyridines (T-1 and T-8) were the best. The imidazole compounds were somewhat superior in analgesic activity to codeine and d-propoxyphene without showing any narcotic characteristics. Some of the compounds also possessed activity against carrageenan-induced foot edema in the rat, so these compounds represent a new class of nonnarcotic analgesic antiinflammatories, capable of producing a greater degree of analgesia than that obtainable with other nonsteroidal antiinflammatory agents.

Animals↗