Search PubMed⌕ Search

Biomedical subjects

C Simpson

Publications and source records attributed to C Simpson.

At least 37 records · Page 2Linked to original sources

Neuropeptide Y, the hypothalamus and the regulation of energy homeostasis.

Neuropeptide Y (NPY) neurones in the arcuate nucleus of the rodent hypothalamus may play a key role in responding to reductions in body energy stores with appropriate changes in energy homeostasis, namely an increase in food-seeking behaviour and hyperphagia, together with a reduction in heat production by brown adipose tissue. These adaptive responses are mimicked by the injection of NPY into the main sites of projection of the NPY neurones, and animals that are threatened by energy deficits (e.g. through starvation or insulin-deficient diabetes) show increased activity of these neurones. Genetically obese rodents also show hyperactivity of the NPY neurones, which is inappropriate to their energy needs and may contribute to their hyperphagia, reduced energy expenditure and excessive weight gain. The NPY neurones may be inhibited by insulin and leptin, which may both serve as signals of peripheral fat mass. Ultimately, characterization of the specific "feeding' receptors which mediate NPY's central effects on energy homeostasis may provide opportunities for designing drugs to manipulate and appetite and energy balance in man, notably obesity and the cachexia commonly associated with malignancy and chronic infection.

Animals↗

Complexity of the healthcare crisis in rural America.

Because osteopathic physicians comprise 15.3% of all physicians in small rural counties, while making up only 5.1% of the nation's physicians, the solutions to the healthcare crisis for rural America are of special interest to them. The authors explore the incredible diversity of rural communities and the difficulty with defining the term "rural." They give the background of efforts to address rural health problems and the reasons accessible healthcare--available, acceptable and affordable--has been so elusive in rural settings. The authors also explain the relative success of the osteopathic medical profession and address the role osteopathic physicians can play in the future. Finally, they explore the exciting new possibilities that telemedicine offers.

Health Care Reform↗

Hyperinsulinaemia in ischaemic heart disease: the importance of myocardial infarction and left ventricular function.

Elevated circulating insulin levels have been reported in ischaemic heart disease, and may be of aetiological importance. Previous studies have not considered the potential influence of heart failure or of previous myocardial infarction, as opposed to stable angina. We therefore measured the insulin response to a 75 g oral glucose tolerance test in five groups with normal glucose tolerance, comparing normal male controls to men with chronic stable angina, men with recent myocardial infarction (two groups, 3 weeks and 3 months post infarction), and men with chronic severe heart failure. Only patients with chronic heart failure had fasting hyperinsulinaemia, probably reflecting associated neuroendocrine abnormalities. Stimulated hyperinsulinaemia was present in all patient groups, but was less pronounced and of shorter duration in patients with angina. At 120 min, only patients with heart failure or previous myocardial infarction were hyperinsulinaemic. The degree of stimulated hyperinsulinaemia was not influenced by the presence of heart failure or by the length of time from infarction. Hyperinsulinaemia is associated with impaired peripheral muscle glucose uptake and metabolism, and might contribute to muscular fatigue on exertion in patients with previous myocardial infarction or heart failure.

Administration, Oral↗

Toxicity of bile acids to colon cancer cell lines.

Quantitative aspects of bile acid cytotoxicity to colon cancer cell lines were investigated because of the etiological role in colon carcinogenesis attributed to the toxic effects of bile acids on colon mucosal cells. The cytotoxicity of major colonic bile acids differed. Lithocholate was the most toxic, followed by chenodeoxycholate and deoxycholate, with cholate being non-toxic over the concentration range studied. Cytotoxicity increased with time of exposure. Values for IC50 for some of the acids were determined to be in the physiological range, as estimated from their concentrations in fecal water. The results suggest dietary factors that contribute to bile acid mucosal damage. They also identify factors of possible importance in the association of high concentrations of bile acids in fecal water with risk for colon cancer.

Bile Acids and Salts↗

Detection of antisense transcripts in transgenic plants by RT-PCR.

A reverse transcriptase-polymerase chain reaction (RT-PCR) where one oligonucleotide primer is end-labelled has been used to analyse expression in transgenic plants carrying antisense gene constructs. Specific detection of both sense and antisense RNA transcripts of the spliceosomal protein gene, U2B'', was achieved using the same pair of oligonucleotide primers. To maintain specificity, a reaction step in which reverse transcriptase was inactivated and RNA digested was found to be essential.

Base Sequence↗

Human olfactory marker protein maps close to tyrosinase and is a candidate gene for Usher syndrome type I.

Olfactory marker protein (OMP) shows olfactory neuron-specific expression in rodents. We recently reported tight linkage on mouse chromosome 7 of OMP to the shaker-1 deafness mutant, between the tyrosinase and globin loci. Here we isolate and map the human homologue. Our results show that OMP maps immediately centromeric to tyrosinase on the long arm of human chromosome 11. Genetic linkage to this region has recently been established for Usher Syndrome Type I, an autosomal recessive blindness and deafness disorder and a putative homologue of the shaker-1 mutant. OMP is thus a candidate gene for both congenital deafness defects.

Animals↗

A process of dying by default.

Les T is a man with a difficult personality and chronic heart disease, facing the end of his life. Alterations in his therapy at this stage are probably not going to greatly affect his final outcome. My aim in management has been to educate and motivate him about risk factors, to minimise dyspnoea and so improve his quality of life and to allow him a freedom to discuss his death so that he may develop a form of acceptance of his dying.

Attitude to Death↗

Medical management of ocular malakoplakia.

A 14-year-old girl had a granulomatous conjunctival lesion, proven histologically to be malakoplakia. This is the first reported case of malakoplakia arising from conjunctiva, although three others have involved the ocular adnexa. Malakoplakia is a rare disease often associated with immunodeficiency and is characterized by the presence of intracellular inclusions and organisms due to deficient intracellular bacteriolysis. Medical management is difficult because an effective antibacterial agent requires three properties: activity against the organism involved, good intracellular penetration, and the capacity to maintain its effectiveness in the intracellular milieu. Escherichia coli was isolated from a biopsy specimen and from conjunctival swabs. Treatment with systemic ciprofloxacin, which has good intracellular penetration and activity, led to rapid resolution of the lesion. This is the first report concerning the successful use of this drug to treat malakoplakia of any organ.

Adolescent↗

Comparison of immunodiffusion and enzyme linked immunosorbent assay in the detection of abnormal antibodies in pigeon breeder's disease.

AIMS: To compare the sensitivity of two methods for the detection of serum antibodies to pigeon faecal antigens in patients with pigeon breeder's disease. METHODS: Serum samples stored at -20 degrees C from 50 patients with pigeon breeder's disease, 50 control samples from patients with other respiratory diseases, and 50 healthy blood donors were examined for the precipitating antibodies and IgG antibodies to antigens present in extract of pigeon droppings by immunodiffusion and enzyme linked immunosorbent assay (ELISA), respectively. RESULTS: Both antigen preparations of pigeon dropping extract were equally effective. A positive immunodiffusion reaction gave one or more precipitin lines and these antibodies were detected only in undiluted sera from 80% of the patients with pigeon breeder's disease. In the ELISA the sera were tested at a starting dilution of 1 in 100 because positive reactions were observed with sera from healthy blood donors at lower dilutions. All sera which gave optical density readings above 3 SD of the control value were considered to have IgG antibodies. These antibodies were detected in sera from all the patients with pigeon breeder's disease. The antibody titres were much higher in those patients who had precipitating antibodies (range 800-51,200) than those without (range 100-800). The antibodies were not detected in the sera of patients with respiratory diseases or healthy blood donors by either method. CONCLUSIONS: Antibodies to pigeon dropping antigens were detected by immunodiffusion and ELISA in sera from patients with pigeon breeder's disease but not in control sera. ELISA was a more sensitive method for detecting antibodies and therefore seems to have considerable potential as a routine technique in the serological diagnosis of pigeon breeder's disease.

Adolescent↗

Unexplained infertility: evaluation of treatment with clomiphene citrate and human chorionic gonadotropin.

A double-blind, randomized, prospective therapeutic trial was conducted in 148 couples with unexplained infertility. Treatment consisted of 4 consecutive months of placebo or clomiphene citrate (CC) (100 mg) by mouth on cycle days 5 to 9, and placebo or human chorionic gonadotropin (hCG) (5,000 IU) intramuscularly on cycle days 19, 22, 25, and 28. There were 14 pregnancies during the trial and 39 pregnancies during observation before and after the trial. Placebo treatment resulted in no pregnancies over 4 months. Clomiphene citrate was significantly better than placebo (P less than 0.04), with a pregnancy rate of 19% over the course of 4 months. The pregnancy rate with hCG either alone (11%) or in combination with CC (7.6%), was not significantly better than placebo. Treatment-independent pregnancies, defined as those before treatment (but after enrollment), or more than 1 month after therapy, occurred in 16% of the couples, with a mean time to conception of 8.8 months. As part of their follow-up, 39 of the study couples subsequently underwent in vitro fertilization (IVF), and 43% were found to have a previously unrecognized male factor or fertilization defect. A pregnancy rate of 16% was achieved after a mean of 1.1 cycles in these 39 couples. The authors conclude that CC is useful in treating unexplained infertility and is a reasonable initial therapy. For couples who fail to conceive, IVF may be diagnostic as well as therapeutic.

Adult↗

Smooth muscle neoplasms of the uterus other than ordinary leiomyoma. A study of 46 cases, with emphasis on diagnostic criteria and prognostic factors.

Thirty-seven cases of uterine leiomyosarcoma are presented, along with nine cases of leiomyoma variants from which they were distinguished. All patients were followed for a minimum of 10 years. In cases with nuclear pleomorphism, leiomyosarcoma was diagnosed when there were five or more mitotic figures in ten consecutive high-power (X400) fields in the most active area of the tumor, and also when there were fewer mitotic figures but extensive tumor necrosis (there was only one leiomyosarcoma without nuclear pleomorphism, and it had more than 20 mitotic figures in ten high-power fields). Tumor size was the major prognostic factor in the leiomyosarcoma group; five of eight patients with neoplasms measuring less than 5 cm in maximum dimension survived, whereas no patient with a larger tumor did so. Other pathologic and clinical variables, including mitotic rate, tumor necrosis, degree of nuclear pleomorphism, vascular invasion, and patient age, had no significant relationship to survival or tumor behavior in leiomyosarcoma when tumor size was taken into account. The nine cases of leiomyoma variants consisted of three atypical leiomyomas (which had nuclear pleomorphism, one or no mitotic figures per ten high-power fields, and no necrosis), two plexiform leiomyomas, two cases of peritoneal leiomyomatosis, one palisaded leiomyoma, and one case of intravenous leiomyomatosis; all of these patients were tumor-free on follow-up.

Adult↗

Plasma and tissue concentrations of ceforanide and cefazolin in women undergoing hysterectomy.

Thirty-four women who underwent vaginal hysterectomy received either ceforanide or cefazolin as perioperative antimicrobial prophylaxis. Samples of plasma, myometrium, endometrium and fallopian tubes were obtained at various intervals after injection and were assayed for cephalosporin concentration. Following intramuscular injection approximately 1 h prior to surgery, both drugs provided adequate tissue levels at the time of the procedure. Although both antimicrobials achieved similar tissue concentrations, all tissue samples for ceforanide exceeded the MIC90 for Escherichia coli while in the cefazolin group 9/18 myometrial samples and 10/15 endometrial samples fell below the MIC90 for this organism.

Adult↗

Management of carotid artery trauma.

We have treated 45 patients with carotid artery injuries--33 caused by penetrating wounds and 12 secondary to blunt trauma. Preoperative angiography is useful in stable patients to rule out associated vascular injuries, and it is crucial for operative planning in cases of blunt trauma. Not unexpectedly, the results of carotid artery repair in neurologically stable patients have been excellent, as have been the results of revascularization in patients with equivocal or less-severe neurologic deficits. This has led us to be aggressive in repair of carotid artery injuries in patients with questionable neurologic deficits. In the eight patients with severe preoperative deficits, one death each followed both ligation and repair, but neurologic improvement was noted in several patients. Distal internal carotid injuries at the base of the skull that were not amenable to direct repair were observed with serial angiograms in four patients with either stabilization or improvement in the intimal injury.

Adolescent↗