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Biomedical subjects

M J Green

Publications and source records attributed to M J Green.

At least 55 records · Page 3Linked to original sources

Dual antagonists of platelet activating factor and histamine. 3. Synthesis, biological activity and conformational implications of substituted N-acyl-bis-arylcycloheptapiperazines.

A series of N-acyl-4-(5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin- 11-ylidene)piperazines is described that are dual antagonists of PAF and histamine. The structural requirements for activity in this series parallel those of their previously reported piperidinylidene counterparts. Whereas their global minimum energy conformations are different for both series of compounds, computer assisted molecular modeling suggests that a common bioactive conformation is possible.

Histamine Antagonists↗

Case control study of risk factors for toxic mastitis in 26 dairy herds.

A retrospective case control study of farm level risk factors for toxic mastitis was carried out in November and December 1996. Twenty-six farms from mid-Somerset were visited: 13 case farms (had had a cow with toxic mastitis in the previous year) and 13 geographically matched controls (no case of toxic mastitis). The farmers were interviewed and the buildings were examined. Information was collected on the type and quality of housing, usual milking routines, milk quality and mastitis prevalence in the previous year. All the data were collected on to pretested recording sheets and loaded into a database. Simple and complex analysis was done. The following variable were significantly (P < 0.05) associated with an increased risk of toxic mastitis in the simple analysis: housing cows in October rather than November; a low number of calving boxes per cow; a high proportion of cows with intermediate body condition and low herd bulk milk somatic cell counts (HBMSCC). In the final model low HBMSCC and a high proportion of cows with intermediate body condition remained significant. The authors conclude that, despite the small size sample, the results of this study are consistent, plausible and support the information from previous experimental and observational studies about the role of somatic cell counts in toxic mastitis.

Animal Husbandry↗

4-[(1H-imidazol-4-yl) methyl] benzamidines and benzylamidines: novel antagonists of the histamine H3 receptor.

A series of amidine substituted phenyl-, benzyl-, and phenethylimidazoles based on the known H3 agonist SK&F 91606 (4) has been synthesized and tested as ligands for the histamine H3 receptor. Insertion of a phenyl ring between the imidazole ring and the amidine moiety produces antagonists. The benzyl series was found to be the most potent and was further investigated. Compounds 9c and 18 (entries 5 and 12, Table 1) are potent ligands for the H3 receptor with K(i) values of 16 nM and 7.2 nM respectively. In vivo, both compounds were shown to be equipotent to thioperamide (2), the standard H3 antagonist.

Animals↗

Prognostic indicators for toxic mastitis in dairy cows.

During a three-year study, 54 cows with toxic mastitis were examined and a number of clinical and laboratory measurements were taken. Twenty-five (46.3 per cent) of the cows died, and in comparison with those which survived, they had a significantly higher packed cell volume (PCV) (P < 0.01), longer eyelid skin tent time (P < 0.01) and lower rectal temperature (P < 0.01). In a model designed to predict the probability of survival, these variables correctly predicted survival in 84 per cent of cases and death in 73 per cent of cases. The cows with toxic mastitis had a significantly higher PCV than a normal cohort of cows sampled at the end of the study.

Animals↗

Trans-4-methyl-3-imidazoyl pyrrolidine as a potent, highly selective histamine H3 receptor agonist in vivo.

Extensive structural modification of immepyr (+)-2 led to the discovery of trans-4-methyl-3-imidazoyl pyrrolidine (+/-)-3a as a potent and highly selective H3 agonist. The pyrroline (+/-)-3a was resolved, and its (+) enantiomer, Sch 50971 [(+)-3a], showed a greater separation of H3 and H1 activities in vivo (H3/H1 ratio >> 330) than (R)-alpha-methylhistamine (+)-1 (H3/H1 ratio = 17), the standard H3 agonist.

Animals↗

Genetic testing for susceptibility to adult-onset cancer. The process and content of informed consent.

OBJECTIVE: To provide guidance on informed consent to clinicians offering cancer susceptibility testing. PARTICIPANTS: The Task Force on Informed Consent is part of the Cancer Genetics Studies Consortium (CGSC), whose members were recipients of National Institutes of Health grants to assess the implications of cancer susceptibility testing. The 10 task force members represent a range of relevant backgrounds, including various medical specialties, social science, genetic counseling, and consumer advocacy. EVIDENCE: The CGSC held 3 public meetings from 1994 to 1996. At its first meeting, the task force jointly established a list of topics. The cochairs (G.G. and J.R.B) then developed an outline and assigned each topic to an appropriate writer and reviewer. Writers summarized the literature on their topics and drafted recommendations, which were then revised by the reviewers. The cochairs compiled and edited the entire manuscript. All members were involved in writing this report. CONSENSUS PROCESS: The first draft was distributed to task force members, after which a meeting was held to discuss its content and organization. Consensus was reached by voting. A subsequent draft was presented to the entire CGSC at its third meeting, and comments were incorporated. CONCLUSIONS: The task force recommends that informed consent for cancer susceptibility testing be an ongoing process of education and counseling in which (1) providers elicit participant, family, and community values and disclose their own, (2) decision making is shared, (3) the style of information disclosure is individualized, and (4) specific content areas are discussed.

Adaptation, Psychological↗

Comparison of fluid and flunixin meglumine therapy in combination and individually in the treatment of toxic mastitis.

During a three-year study, 54 cows with toxic mastitis were allocated randomly to one of three treatment groups (A, B and C). Each cow was re-examined within 24 hours of the initial examination, and, during this time, group A received fluid therapy (45 liters of intravenous isotonic electrolyte solution) and flunixin meglumine (2000 mg), group B received fluid therapy only, and group C received flunixin meglumine only. In addition all the cases were treated with parenteral and intramammary tetracyclines, oxytocin and calcium boroglucoanate. There was no significant difference in the rate of survival between the treatment groups and 29 of the cows (53.7 per cent, 95 per cent confidence interval of 39 to 67 per cent) survived.

Animals↗

An interactive computer program for educating and counseling patients about genetic susceptibility to breast cancer.

Educating individuals who seek information about genetic testing for cancer susceptibility is a complex task. Because of the psychological and social risks to patients of being identified as susceptible to a genetic disorder, it is important that education take place before a patient undergoes gene testing. However, it is not known who will provide such education. Since primary care physicians have limited knowledge, time, and confidence with genetic counseling, they are not ideal educators. Genetic counselors are well trained to provide the service, but many patients lack access to them. Other specialists are scare. Interactive computers hold much promise as a supplemental or alternative modality for education. The authors describe their experience with developing an interactive CD-ROM on gene testing and breast cancer, and respond to anticipated criticisms of this technology.

Aged↗

Who should provide genetic education prior to gene testing? Computers and other methods for improving patient understanding.

As numerous new gene tests are introduced into clinical practice, patients have a growing need for accurate and comprehensive information about the risks and benefits of gene testing. However, in the changing healthcare environment, it is not clear who will provide such information because genetic counselors are scarce and their services are not widely utilized, and primary care providers lack time and expertise in genetics. Interactive computers may help fill the information gap. We review a variety of educational modalities for providing patient education and argue that interactive computers have potential advantages over other educational methods for providing information and promoting informed consent to genetic testing. Finally, some questions for further research are raised.

Computer-Assisted Instruction↗

Sigmoid caecal volvulus in a dairy cow treated by total typhlectomy.

A four-year-old pedigree Holstein, second lactation cow had been lethargic, with a reduced appetite, signs of colic and reduced milk yield for one day. There was a small swelling in the right paralumbar fossa and auscultation of this region revealed a tympanitic resonance (ping). An exploratory laparotomy revealed a sigmoid shaped caecal volvulus and extensive caecal necrosis. The condition was corrected surgically by a total typhlectomy. Recovery was slow for the first week after surgery but uneventful thereafter. One month later the cow was healthy, with normal faecal consistency, and in the milking herd. Over the following lactation the cow gave an excellent milk yield.

Animals↗

Do actions reported by physicians in training conflict with consensus guidelines on ethics?

OBJECTIVE: To assess the extent to which actions reported by internal medicine trainees conflict with published guidelines on ethics. METHODS: A confidential survey was sent to a random sample (N = 1000) of associate members of the American College of Physicians (ACP). Questions were asked about ethical decision making in areas addressed by the guidelines in the ACP Ethics Manual. Quoted manual guidelines were provided, followed by 55 yes or no questions, such that a yes answer represented an action that conflicted with a guideline. There were two follow-up mailings to nonresponders. RESULTS: Forty percent (n = 397) completed the questionnaire; 17% indicated they were aware of the guidelines on ethics. On average, associates responded yes to 16% of questions where a yes response indicated they have acted outside guidelines on ethics one or more times. The mean number of responses (n = 55) that conflicted with a guideline was 7.6 per person (SD, 4.7 responses; range, 0 to 33 responses). Ninety-eight percent of respondents reported actions falling outside a guideline one or more times and 80% did so four or more times. The most frequently reported reason (965/3219 [30%]) from a list of four choices for acting outside a guideline was "I was aware of the guideline, but this did not represent an ethical dilemma to me." CONCLUSIONS: Few responding ACP associates indicated awareness of the ACP guidelines on ethics. Physicians in training nevertheless reported acting according to the presented guidelines most of the time, although nearly all respondents acted outside a guideline at least once, and some did so many times. Reported behaviors were sometimes inconsistent with consensus ethical standards that apply to internists. Physicians in training need to know more about ethical standards that apply to their own practice and should be aware when their actions deviate from ethical norms. Before acting outside guidelines on ethics, trainees should discuss their conflicts with others, such as attending physicians, clinical ethicists, or hospital ethics committees.

Codes of Ethics↗

What (if anything) is wrong with residency overwork?

Long work hours during residency are a time-honored tradition. Efforts have recently been made to shorten work hours. This paper examines the main arguments supporting reform: that sleep deprivation is harmful to patients and residents and that it is exploitative. Because the data on the harms and benefits are mixed and because exploitation is difficult to prove, a stronger argument for reducing work hours is an ethical one: that overwork interferes with the development of professional values and attitudes that are an essential part of the moral curriculum of residency. Providing a climate that promotes moral growth during training is an important curricular objective that may be better achieved by shortening work hours, providing better resident supervision, and using substitute workers for some of the noneducational tasks of residency.

Attitude of Health Personnel↗

A novel pyrrolidine analog of histamine as a potent, highly selective histamine H3 receptor agonist.

Employing classical conformational analysis on a known H3 agonist, (R)-alpha-methylhistamine (1), a series of conformationally constrained H3 agonists were proposed and synthesized. Pyrrolidine (+/-)-4a, a compound proposed to mimic the anti-conformation of (R)-alpha-methylhistamine (1), was found to be a potent and selective H3 agonist. The pyrrolidine (+/-)-4a was resolved, and its (+) enantiomer, immepyr [(+)-4a], showed a greater separation of H3 and H1 activities in vivo (H3/H1 ratio >> 550) than (R)-alpha-methylhistamine (1) (H3/H1 ratio = 17), the standard H3 agonist. In fact, no evidence of H1 activity was detected at doses of immepyr [(+)-4a] as high as 100 mg/kg i.v. This pyrrolidine, immepyr [(2R,3S)-(+)-4a], represents, to our knowledge, the first reported cyclic, conformationally restricted analog of histamine to possess selective in vivo H3 agonist activity.

Histamine↗

Discovery and preliminary pharmacology of Sch 37370, a dual antagonist of PAF and histamine.

From a series of amide analogs of the histamine H1 antagonist, azatadine, a potent, orally active, dual platelet-activating factor (PAF) and histamine antagonist, Sch 37370, namely 1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo- [5,6]cyclohepta[1,2-b]pyridin-11-ylidine)piperidine, was discovered. Sch 37370 selectively inhibits PAF-induced aggregation of human platelets in vitro (IC50 = 0.6 microM), and in vivo inhibits PAF- and histamine-induced bronchospasm in guinea pigs with ED50 values of 6.0 and 2.4 mg/kg p.o., respectively. Sch 37370 is expected to be more efficacious than single mediator antagonists in allergic diseases, such as asthma.

Histamine Antagonists↗