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Biomedical subjects

B Porter

Publications and source records attributed to B Porter.

At least 55 records · Page 3Linked to original sources

[Infantile neuroaxonal dystrophy].

Infantile neuroaxonal dystrophy is a degenerative disease, mostly of nerve endings in the central and peripheral nervous system, with typical pathological findings. We describe a 3-year-old boy who had suffered from nystagmus, progressive muscle weakness and dementia since the age of 10 months. Biochemical work-up, MRI of the brain, and electrophysiological studies were within normal limits. Only skin biopsy, and sural nerve biopsy at a later stage, were diagnostic. We stress the importance of performing tissue biopsy even when intensive investigation is negative.

Biopsy↗

Conformationally constrained tachykinin analogues: potent and highly selective neurokinin NK-2 receptor agonists.

The design and synthesis of potent and selective neurokinin NK-2 receptor agonists 12 (GR64349) and 31 are described, together with structure-activity relationships for related analogues. Compound 12 (EC50 = 3.7 nM at NK-2 receptors in the rat colon; selectivity > 1000- and > 300-fold with respect to NK-1 and NK-3 receptors, respectively) was derived by incorporation of a Gly-Leu gamma-lactam conformational constraint into the C-terminal region of the neurokinin A octapeptide analogue [Lys3]-NKA(3-10). Compound 31 (EC50 = 15 nM in rat colon) contains a novel fused-bicyclic constraint at the corresponding site in the substance P hexapeptide analogue [Ava6]-SP(6-11).

Amino Acid Sequence↗

Highly potent and selective heptapeptide antagonists of the neurokinin NK-2 receptor.

Incorporation of D-Pro9 into substance P related peptides is known to enhance neurokinin NK-2 receptor agonist potency and selectivity with respect to other neurokinin receptors. We now report that replacement of D-Trp9 by D-Pro9 in the nonselective neurokinin antagonist [Arg5,D-Trp7,9, Nle11]-SP(5-11) gave a partial agonist with NK-2 receptor selectivity. Further incorporation of Pro10 provided the weak but selective NK-2 antagonist Arg-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (compound 4; NK-2 pKB = 5.9; NK-1 pKB = 4.7; NK-3 pKB less than 4.6). Addition of a suitable lipophilic N-terminal substituent (e.g. Boc, PhCO, cyclohexylcarbonyl) to this compound greatly enhanced NK-2 antagonist activity (compound 10, GR 83074; NK-2 pKB = 8.2), and combined with further optimization of the N-terminal amino acids, provided the extremely potent and selective NK-2 antagonist PhCO-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (compound 34, GR 94800; NK-2 pKB = 9.6; NK-1 pKB = 6.4; NK-3 pKB = 6.0). Compounds of this class produced a potent inhibition of NK-2 agonist-induced bronchoconstriction in the anaesthetized guinea-pig.

Amino Acid Sequence↗

A community pre-registration year: the continuation of a community-oriented medical school curriculum.

A voluntary community-based preregistration year (internship) was created for graduates of a community-oriented medical school in Beersheva, Israel. Graduates were placed in community clinics which had been upgraded to meet the needs of the programme through provision of on-site laboratory facilities and specialist consultation, and placement of social workers and health education personnel in the clinics. The graduates participated in a weekly postgraduate education programme directed to their specific needs. There was a high degree of satisfaction with the programme among the trainees, the clinic team members and the patients. Relatively few of the trainees indicated a desire to pursue careers entirely devoted to primary care, despite their positive evaluation of the pre-registration experience. Though this might have been explained by problems encountered in the programme, such as the lack of adequate on-site supervision and lack of support from the health service providers, external factors such as a general move of graduates towards more lucrative subspecialties and the relative lack of status of family practice were probably the more significant reasons. Increasing focus on the internship year, in addition to the undergraduate and residency periods, is needed to help direct medical education to ambulatory settings.

Attitude of Health Personnel↗

Weissenbacher-Zweymuller syndrome: long-term follow-up of growth and psychomotor development.

A child with the distinguishing characteristics of Weissenbacher-Zweymuller syndrome (WZS), a rare syndrome characterized by multiple skeletal and radiological abnormalities, dwarfism and developmental delays, was followed from birth to eight years. Follow-up showed that the radiographic anomalies eventually disappeared, and that height, motor, cognitive and language development returned to normal by eight years of age. The child's normal development at school age supports the theory that WZS is a dysmaturational, rather than dysplastic, syndrome. Diagnosis of the syndrome at birth is essential to ensure proper management of the child and counselling for the parents.

Abnormalities, Multiple↗

High dose radiolabeled antibody therapy of lymphoma.

A trial has been initiated testing the effects of high dose radiolabeled monoclonal antibody administered in conjunction with marrow transplantation for treatment of lymphoma. This study is based on observations in mice demonstrating that radiolabeled antibody against a normal lymphocyte-associate antigen can induce regression of lymphoma masses. These preclinical studies also showed that large amounts of antibody are needed to achieve adequate biodistribution in vivo and that potentially curative doses of radionuclide induce substantial hematopoietic toxicity. Consequently, in patients with recurrent lymphoma, we are first evaluating the influence of dose on the biodistribution of a pan B-cell antibody, MB-1 (anti-CD37). In four patients, the biodistribution studies indicated that at the highest amount of antibody tested 131I-labeled antibody MB-1 (10 mg/kg) could deliver more radiation to tumor than to normal organs. These patients were treated with antibody MB-1 labeled with 250 to 482 mCi 131I estimated to deliver 380 to 1570 cGy to normal organs and 850 to 4260 cGy to tumor. Myelosuppression occurred in all patients and required infusion of cryopreserved marrow in one patient. Complete tumor regressions were observed in each patient. In three other patients with splenomegaly and/or large tumor burden, biodistribution studies indicated that 131I-labeled antibody could not deliver more radiation to tumor than to normal organs and these patients were not treated. Thus, tumor burden and spleen size may determine the feasibility of treatment with radiolabeled antibody. Treatment with this antibody labeled with high doses of 131I was well tolerated and may prove therapeutically useful. These studies are being continued to determine the maximal doses of radiation that can be tolerated by nonhematopoietic tissues after infusion of 131I-labeled antibody.

Animals↗

"Abandoned" parents. Loss of traditional family support systems. A challenge for health professionals.

Maternal incompetence in childrearing is described in three widely different cultural settings in the southern Negev area of Israel. It is suggested that this incompetence stems from "abandonment" of the parents by traditional family support systems and is reinforced by the inability or lack of readiness of the health system to supply the missing support mechanisms. This picture of parental "abandonment" in widely different cultural settings in Israel may represent an end result of cultural and social upheaval common to other communities in the world. Techniques for prevention include improving awareness of health workers to this problem, teaching appropriate strategies for improving parental confidence and competence, and ensuring that maternal and infant care focuses appropriately on issues of infant behavior and parental concerns.

Cross-Cultural Comparison↗

Effects of a health activist course on knowledge and awareness of antibiotic use.

A cohort study investigated the specific outcomes of a health education coursed carried out by recently graduated physicians in an urban primary care setting in Israel. Questionnaires were used to study the effects of the programme on knowledge and awareness concerning antibiotic usage. The results showed a significant gain in knowledge about the causes of infectious disease, appropriate duration of antibiotic intake, side effects of antibiotics and the importance of compliance. In contrast with other studies, low income blue collar workers with less than high school education showed the most significant gains from the programme. Inexperienced physicians were able to implement a community health education programme with clearly defined goals.

Anti-Bacterial Agents↗

Comprehensive pediatric primary care vs traditional care in an Israeli population: their influence on pediatric emergency room use and hospitalization.

Emergency room (ER) utilization and hospitalization were studied as indicators of the impact of improvements in pediatric primary care services in an Israeli development town, Ofakim, population 12,000. One of the two pediatric services was upgraded in 1976 through the introduction of pediatric faculty, integration of preventive and curative services and conversion of the medical records to a problem-oriented format ("experimental" clinic "B"). The primary care system remained unchanged in the second clinic ("traditional" clinic "A"). During 1980, ER utilization by the "B" clinic population was 9.3/100 compared with 17.6/100 for the "A" clinic population. Fifty two percent of the "B" clinic population patients reaching the ER were hospitalized compared with 25% of "A" clinic patients. The lower ER utilization rate represents a significant saving for the health services, and educational interventions are suggested from the study. Analysis of ER utilization data seems to offer useful information for overall planning and monitoring of ambulatory services for a community.

Adolescent↗