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Biomedical subjects

J Porter

Publications and source records attributed to J Porter.

At least 19 recordsLinked to original sources
PubMed1992

Gonadotropin-releasing hormone antagonists with N omega-triazolylornithine, -lysine, or -p-aminophenylalanine residues at positions 5 and 6.

In order to be used as fertility regulators in humans, gonadotropin releasing hormone (GnRH) antagonists must be extremely potent and long acting and exhibit negligible side effects such as stimulating histamine release. To this aim, we have recently synthesized a series of analogues with the standard Ac-DNal1-DCpa2-DPal3 substitutions, where the N omega-amino function of ornithine, lysine, or p-aminophenylalanine (Aph) was converted to the aminotriazolyl (atz) derivatives at positions 5 and 6 with further modifications at positions 7 and 10. The analogues were tested for their ability to bind to pituitary cell membranes, to release histamine in a mast cell assay, to inhibit luteinizing hormone (LH) secretion by castrated male rats or cultured pituitary cells, and to interfere with the ovulation in intact female rats. While the subcutaneous (sc) injection of 50 micrograms of Azaline A (7, [Ac-DNal1,DCpa2,DPal3,Lys5(atz),DLys6++ +(atz),ILys8,DAla10]GnRH) dissolved in 0.2 mL of an aqueous media significantly inhibited LH release in the castrated male rat for 24 h, the same dose of Azaline B (11), [Ac-DNal1,DCpa2,DPal3,Aph5(atz),DAph6++ +(atz),ILys8,DAla10]GnRH, inhibited LH release for 72 h. A similar long duration of action was observed for Antide ([Ac-DNal1,DCpa2,DPal3,Lys5(Nic),DLys6(Nic ),ILys8,DAla10]GnRH) but not for Nal-Glu ([Ac-DNal1,DCpa2,DPal3,Arg5,4-(pmethoxybenzoy l)-D-2-Abu6,DAla10]GnRH). In the same paradigm, a 5-fold dilution of the peptide (50 micrograms in 1 mL) and the use of three injection sites rather than one resulted in significantly shorter duration of action for most of the peptides tested. This suggested that long duration of action might be the result of slow release from the injection site(s). In order to investigate this possibility, Nal-Glu and Azaline B were injected intravenously (i.v.) at three doses (10, 50, 250 micrograms) to castrated male rats. At all doses, both peptides significantly lowered LH levels for 8 h. By 24 h, Nal-Glu (250 micrograms) and Azaline B (50 and 250 micrograms) still measurably inhibited LH secretion. Finally, only Azaline B (250 micrograms) was still active at 48 h. These findings demonstrate that subtle structural modifications will yield peptides with different half-lives after iv administration. These findings led us to investigate the effects of other structural modifications on duration of action. We observed that systematic substitutions at positions 7 (NMeLeu) and 10 (Pro9-NHEt, and Gly-NH2) were found to be deleterious. Of interest was the observation that only the DAla10-NH2 substitution led to long duration of action and enzymatic stability under the conditions tested.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Granulocytic sarcomas of small intestine and brain are associated with acute myelomonocytic leukaemia with abnormal eosinophils and inversion of chromosome 16.

We report two cases of acute myelomonocytic leukaemia with abnormal eosinophils (M4Eo) in which the presenting feature was small bowel obstruction. We suggest there is a unique clinicopathological association between small intestine involvement with leukaemia and the M4Eo subtype. Central nervous system involvement by myeloblastoma occurred in one of the two cases which is a recognised feature of M4Eo and should necessitate prophylaxis with intrathecal therapy. Inversion of chromosome 16 which is a cytogenetic marker for M4Eo was demonstrable in one of the two cases.

Biomarkers, Tumor↗
PubMed1979

Drug-related superinfection in hospitalized patients.

In a series of 14,077 hospitalized medical patients receiving antibiotics, superinfection developed in 95 (0.7%) during drug therapy. The majority were yeast and fungal infections, and serious infections occurred with a frequency of less than one per 1,000 patients treated. Concurrent immunosuppression and impaired renal function increased the risk of new infections.

Adult↗
PubMed1979

Brain damage and global stereopsis.

When a single object lies in front of or beyond the plane of fixation its retinal image lies on disparate positions in the two eyes. This 'local' retinal disparity is an excellent cue to depth, and retinal disparties of a few seconds of arc are detectable by people and monkeys. However, most visual scenes produce a complex array of contours in each eye and we can detect the disparity in the arrays despite the ambiguous nature of the disparities, i.e. each contour in one eye could be related to any of several similar contours in the other eye. This ability, known as 'global' stereopsis, may be selectively impaired following brain damage in man. Global stereopsis was measured in rhesus monkeys before and after removing a different cortical visual area in different groups of animals. Only removal of the inferotemporal cortex impaired global stereopsis. The result is related to the findings with human patients and to receptive field properties of neurons in the inferotemporal cortex of monkeys.

Animals↗
PubMed1979

Psychological reaction to chronic skin disorders: a study of patients with vitiligo.

Diseases that cause physical handicaps can seriously interfere with the life of a patient. Some disorders such as vitiligo cosmetically disfigure patients without producing any physical disabilities. The effects of such diseases as vitiligo on the life of a patient have not been widely investigated. The investigation reported here utilized a questionnaire survey to focus on emotional disturbances caused by vitiligo and on the factors that differentiated patients who cope well from those who cope poorly with this stress. The results indicate that the cosmetic disfigurement of a seemingly inconsequential skin disease also can seriously disrupt the lives of a large number of patients. Those who cope well with their disfigurement have higher self-esteem than a matched control group without the disorder. Those who cope poorly have significantly lower self-esteem, which suggests that response to disfiguring diseases is affected by basic ego strength. Younger patients and those individuals in the lower socioeconomic groups show especially poor adjustment. A number of suggestions for better patient care are offered.

Adaptation, Psychological↗
PubMed1979

Clinical importance of the interaction of phenytoin and isoniazid: a report from the Boston Collaborative Drug Surveillance Program.

Six (27 percent) of 22 hospitalized medical patients who received phenytoin and isoniazid concurrently for at least five days experienced toxic effects on the central nervous system (CNS). In contrast, only 30 (3 percent) of 1,093 patients who received phenytoin without isoniazid had toxic effects on the CNS. Thus, the risk of toxic effects from therapy with phenytoin is greatly increased among patients concurrently receiving isoniazid, probably because of isoniazid-induced impairment of the clearance of phenytoin. Schedules of dosage for phenytoin whould be appropriately adjusted to compensate for this clinically important interaction of drugs.

Central Nervous System↗
PubMed1979

Lung cancer in young women.

A comparison was made between cigarette smoking histories of 31 women below age 50 years who had a diagnosis of lung cancer on hospital discharge and smoking histories of 124 women below age 50 years who had been hospitalized for other conditions. Of the women with lung cancer, 28 (90%) were current or former cigarette smokers; 72 (58%) of the comparison women were smokers. The relative risk estimate for lung cancer among smokers as compared with nonsmokers is 6.7, with 90% confidence limits of 4.0 and 11. Risk of lung cancer increased with the amount that the women smoked. The smokers with lung cancer had been smoking for longer periods than the smokers with other conditions. Assuming that the association is causal, cigarette smoking was responsible for about 77% of the lung cancer of young women in this survey.

Adult↗
PubMed1978

Drug-induced gastrointestinal bleeding. Report from the Boston Collaborative Drug Surveillance Program, Boston University Medical Center.

Rates of drug-induced gastrointestinal bleeding were estimated from data on 16 646 consecutively monitored medical inpatients who had no known predisposing illness. Heparin, warfarin, ethacrynic acid, steroids, and aspirin-containing drugs were associated with gastrointestinal bleeding and were estimated to account for about two-thirds of such bleeds. Major gastrointestinal bleeding, defined as bleeding severe enough to require transfusion, occurred in only 57 patients (0.3%).

Anticoagulants↗
PubMed1978

Oral contraceptives and nonfatal stroke in healthy young women.

The Boston Collaborative Drug Surveillance Program obtained medical histories on 29 premenopausal women with a discharge diagnosis of stroke. Of these women, 14 were otherwise healthy with no known predisposing illnesses. Eleven of the 14 patients were taking oral contraceptives just before admission compared with seven of 56 otherwise healthy control women (13%). The relative risk estimate for stroke among oral contraceptive users compared with nonusers is 26 (lower 90% one-sided confidence bound = 7.0). Cigarette smoking was only weakly associated with stroke in this group of women.

Adult↗
PubMed1978

Thrombophlebitis of the lower extremities and ABO blood type.

Of 86 medical patients with a hospital discharge diagnosis of thrombophlebitis of the lower extremity, 70 (81%) were of blood type A,B, or AB (non-O). Of the 344 reference patients matched for age, sex, and country, 187 (54%) were of non-O blood type. The estimate of risk ratio of non-O blood type patients to O blood type patients was 3.7 with 90% confidence limits 2.3 and 6.0. The association between non-O blood type and thrombophlebitis of the lower extremity was strongest among the younger patients and women.

ABO Blood-Group System↗