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Biomedical subjects

M Hamilton

Publications and source records attributed to M Hamilton.

At least 109 records · Page 6Linked to original sources

Sensitive method for the quantitation of nortriptyline and 10-hydroxynortriptyline in human plasma by capillary gas chromatography with electron-capture detection.

A method for the determination of nortriptyline and 10-hydroxynortriptyline concentrations in human plasma by capillary gas chromatography with electron-capture detection is described. The procedure requires 1.0 ml of plasma and uses maprotiline as an internal standard. The compounds are extracted from alkalinized plasma with hexane-2-butanol (98:2) and back-extracted into hydrochloric acid. The acid solution is then made basic and the compounds are re-extracted into n-butyl chloride. The extract is evaporated to dryness, derivatized with heptafluorobutyric anhydride, and analyzed by gas chromatography on a fused-silica capillary column coated with phenylmethyl silicone. The calibration curves for nortriptyline and 10-hydroxynortriptyline are linear in the ranges 3-40 and 7-90 micrograms/l, respectively, with coefficients of variation for within-day and between-day precision of less than 12%. The quantitation limits for nortriptyline and 10-hydroxynortriptyline are 1 and 3 micrograms/l, respectively. This procedure was used to analyze more than 1400 samples following sub-therapeutic doses of nortriptyline in human subjects. The assay was sufficiently sensitive for use in pharmacokinetic analysis.

Chromatography, Gas↗

Prospective study of short and long regimens of gonadotropin-releasing hormone agonist in in vitro fertilization program.

OBJECTIVE: To assess the usefulness of a short regimen in ovulation induction in an in vitro fertilization (IVF) program. DESIGN: A prospective randomized trial was set up to compare long and short regimens of gonadotropin-releasing hormone agonist administration for ovulation induction in IVF. SETTING: Aberdeen Assisted Reproduction Unit. PATIENTS: Eighty-seven patients undergoing IVF were randomized between the two protocols. Stimulation regimen was the only variable being tested. MAIN OUTCOME MEASURES: Stimulation response and occurrence of luteinizing hormone (LH) surges. RESULTS: There was no difference in the stimulation requirements, response to stimulation, number of follicles aspirated, or the number of oocytes obtained. The fertilization rates, number of embryos transferred, and pregnancy rates were also similar in both groups. Like the long regimen, it prevents the occurrence of a premature LH surge. CONCLUSION: The short regimen is a useful and cheaper alternative in ovarian stimulation of patients undergoing IVF.

Adult↗

Prospective study of short and ultrashort regimens of gonadotropin-releasing hormone agonist in an in vitro fertilization program.

OBJECTIVE: To assess the usefulness of the ultrashort regimen of gonadotropin-releasing hormone agonist (GnRH-a) in ovulation induction in an in vitro fertilization (IVF) program. DESIGN: A prospective randomized trial comparing short and ultrashort regimens of GnRH-a. SETTING: Aberdeen Assisted Reproduction Unit. PATIENTS: Forty-eight patients having IVF for the first time were randomized between the two protocols. MAIN OUTCOME MEASURES: Response to ovarian stimulation and occurrence of spontaneous luteinizing hormone (LH) surges. RESULTS: In ovulation induction, fertilization, and pregnancy rates the ultrashort regimen produces results that were no different to the short regimen but it did not always prevent an LH surge. CONCLUSION: The ultrashort regimen can be a useful alternative for ovarian stimulation of patients undergoing IVF.

Adult↗

Physical examination of swine.

Swine may be examined to evaluate a disease state or a lowered economic performance or as a herd health consultation. As much of the examination as possible should be performed without handling the animal. A thorough history, evaluation of herd records, environmental examination, and herd examination should be performed prior to the evaluation of an individual animal. All necessary equipment should be available when starting the individual examination. The animals is then restrained and examined, and necessary samples are taken. Post-mortem examinations or slaughter house evaluations are a very frequent part of a health examination on swine. All samples taken should be in accordance with the standards of the laboratory that you use. You should work closely with the laboratory to obtain the best results. Physical examination of swine can be rewarding for the veterinarian as well as the producer. The most important aspect to remember is to have enough information and the proper equipment available to handle the animals for the minimal amount of time to gain the maximum benefits. Vietnamese pot-bellied pigs are similar to domestic swine in terms of their diseases and health but are dissimilar in management; pot-bellied pigs are frequently brought to the veterinarian for individual examinations. History is the most valuable part of the examination, followed by observation. Pot-bellied pigs prefer to be held securely with a hand under the chin and rump. The examination is conducted similarly to the examination of any companion animal. Chemical restraint often is necessary for sampling or minor surgical procedures. Owners should be consulted prior to the use of any restraint. This will help win their approval and confidence when working on their pets. While performing the physical examination, look at the pig's overall health as well as specific breed characteristics. Try to stay abreast of swine vaccination recommendations; you may be consulted in this regard. Most importantly, never forget even though they are pigs, pot-bellied pigs are companion animals and should be handled as such.

Animals↗

The consequences of a change in formulation of methadone prescribed in a drug clinic.

Methadone mixture DTF (1mg in 1ml) is a safe non-injectable alternative to methadone tablets (5mg). It also allows for a more gradual detoxification from opiate dependence. For these reasons it was decided to 'rationalise' our prescribing so that methadone in mixture form only would be dispensed. At the beginning of 1989, 66 opiate-dependent patients were receiving methadone tablets, 61 the methadone mixture. We report the consequences of instituting a policy change which was clearly very unpopular with patients. Of the 66 patients receiving methadone tablets prior to the change to mixture, 53 were represcribed tablets by the end of the 3-month follow-up period. In many cases this was because of an intense resistance to the change over, physical complications of methadone mixture occurred in very few. We were able to observe a decline in social stability and an increased use of non-prescribed drugs in some patients who changed to methadone mixture. More far-reaching consequences of the change included an increase in chemist break-ins, an increase in the street value of methadone tablets and greater hostility and threatening behaviour towards staff. These changes reflect psychological rather than pharmacological or pharmacokinetic effects.

Adult↗

Reduction of atherogenic risk factors by short-term weight reduction. Evidence of the efficacy of National Cholesterol Education Program guidelines for the obese.

Five hundred and ninety-nine overweight patients participated for at least 4 weeks in the weight reducing and physical activity promoting Diet and Fitness Center program at Duke University. Twenty-three percent were diabetic and 49% hypertensive. With only modest weight loss (11.8 kg in males and 8.2 kg in females) abnormal levels of blood pressure, fasting blood sugar, total cholesterol, LDL-cholesterol and triglycerides normalized. It was very rewarding to see these results achieved in a very limited period of time. Improvements in the lipid profile were consistent with the predicted outcome of obesity treatment stated by the National Cholesterol Education Program guidelines.

Adult↗

Utilization of dental services by older adults in four Ontario communities.

The elderly tend to use dental services less than most younger age groups. While the elderly's utilization rates may be rising, very low utilization by edentulous people depresses the overall rate for the group. We use data from the Ontario Study of the Oral Health of Older Adults to identify the variations in the use of dental services in the four study sites of Toronto, North York, Simcoe County and Sudbury and District. We reached 3,033 subjects by telephone and conducted dental examinations and a multi-item personal interview with 907 of them. The 907 subjects ranged in age from 50 to 87 years, 57 percent were female and two-thirds were born in Canada. Overall, 60.5 percent had seen a dentist or denturist in the previous year, but this was much lower among the edentulous (17 percent) when compared to the dentate (72 percent) (Chi-square test; p less than .0001). Of the 357 who did not visit a dentist or denturist in the previous year, nearly half (48 percent) felt they had nothing wrong and 20 percent reported they could not afford care. A high proportion (94 percent) of the edentulous reported visiting only for pain or trouble compared to 26 percent of the dentate (Chi-square test; p less than .0001). Using logistic regression, we found dental status (edentulous), community of residence (Sudbury), income (up to $20,000) and dental insurance coverage (none) were important factors in not making a dental visit in the last year. These same factors, plus education (elementary) were important where subjects reported visiting a dentist or denturist only when there was pain or trouble.

Aged↗

Excision of squamous cell carcinoma of forehead.

By the time 77-year-old Mr Mack was admitted to the plastic surgery ward, the 10-week-old recurrent swelling on the right side of his forehead was about 6 cm in diameter and cystic in appearance. Histologically confirmed as a squamous cell carcinoma, the growth did not appear to be fixed to the underlying bone, but nor was it fully mobile which suggested that the malignancy may have spread to the deep fascia. Red and shiny on top, two or three discharging puncti were evident.

Aged↗

Comparison of thermodilution and transthoracic electrical bioimpedance cardiac outputs.

Current methods of measuring cardiac output require the invasive insertion of a thermodilution catheter with its concomitant risks and complications. We examined the noninvasive method of transthoracic electrical bioimpedance (TEB) in comparison with thermodilution cardiac outputs in a sample of 44 critically ill patients with poor left ventricular function (left ventricular ejection fraction less than 30%) and with either ischemic or idiopathic dilated cardiomyopathy. Dyspnea, mitral regurgitation, tricuspid regurgitation, and difference between real and ideal weight had the most marked effects on the correlation between the two methods, with lesser influence by left ventricular ejection fraction, height, weight, hemoglobin, hematocrit, and aortic regurgitation. TEB and thermodilution cardiac outputs were correlated, at r = 0.51 (p less than 0.00009), but the low reliability and low percentage of TEB readings within 0.5 L/min of thermodilution cardiac outputs (31%) renders TEB inadequate for clinical measurement of cardiac outputs in this patient population.

Body Height↗

Importance of hemodynamic response to therapy in predicting survival with ejection fraction less than or equal to 20% secondary to ischemic or nonischemic dilated cardiomyopathy.

To identify patients with left ventricular ejection fractions less than 20% who are likely to survive on tailored medical therapy after referral to transplantation, this study of 152 patients addressed the hypotheses that (1) severely elevated filling pressures initially measured at referral would not necessarily predict poor outcome, (2) survival would be best when low pulmonary wedge pressures could be achieved with therapy tailored for hemodynamic goals, and (3) coronary artery disease would be an independent risk factor for early mortality. Despite an average initial ejection fraction of 0.15, cardiac index of 2.0 liters/min/m2 and pulmonary artery wedge pressure of 28 mm Hg, the actuarial survival with tailored therapy was 63% at 1 year, with 34 of 41 (83%) deaths occurring suddenly. Survival was not related to initial filling pressure elevation, but was best predicted by the pulmonary artery wedge pressures during therapy; patients achieving pressure of less than or equal to 16 mm Hg had 1-year survival of 83 vs 38% (p = 0.0001). The other independent predictors were serum sodium and coronary artery disease. Patients with high filling pressures during therapy and coronary artery disease had 21% survival at 1 year. Survival after referral to transplantation with an ejection fraction less than or equal to 20% is better than previously described. Patients in whom left ventricular filling pressures cannot be adequately reduced by tailored therapy, particularly if coronary artery disease is present, should be considered for early transplantation.

Adult↗

Kinetics of N-[(4-chlorophenyl)amino]carbonyl-2,3-dihydro-1H-indene-5-sulfonamide (LY186641) in humans.

The metabolism and disposition of LY186641, a diarylsulfonylurea with antineoplastic activity identified in preclinical tests, was determined in 21 patients who received 23 courses of orally administered drug. A linear correlation was found between the dose of drug administered and LY186641 peak plasma concentrations and LY186641 area under the curve measurements. Clearance (135 +/- 36 ml/h/m2), terminal half-life (31 +/- 11 h), and volume of distribution (10.2 +/- 2.8 liters) were independent of drug dose. No LY186641 was excreted in urine. Hydroxy and keto metabolites of LY186641 were identified in plasma and urine samples. Urinary excretion of these metabolites during the initial 48 h following drug administration accounted for 20% of LY186641 disposition. Plasma half-life of the hydroxy and keto metabolites was longer than that of parent drug (3.3 and 3.1 days, respectively). Plasma concentrations of parent drug correlated with the presence of methemoglobinemia, the dose-limiting toxicity found with LY186641.

Administration, Oral↗

Rejection of bone-marrow graft by recipient-derived cytotoxic T lymphocytes against minor histocompatibility antigens.

A female patient showed rejection of a T-lymphocyte-depleted bone-marrow graft from her phenotypically HLA-identical father. Before bone-marrow transplantation, there was strong recipient anti-donor cellular cytotoxic reactivity directed against several minor histocompatibility (mH) antigens, including the male-specific H-Y antigen. After conditioning treatment, no recipient anti-donor cytotoxic activity could be detected, and good graft function was shown a month after transplantation. Thereafter, however, graft function deteriorated rapidly, while recipient-derived anti-donor cellular cytotoxic reactivity, against similar mH antigens, reappeared. The recipient-derived cytotoxic T lymphocytes could completely inhibit growth of donor haemopoietic progenitor cells both before and after bone-marrow transplantation. Thus, cytotoxic T lymphocytes can survive very intensive conditioning regimens, and residual recipient cytotoxic T lymphocytes directed against mH antigens expressed on donor haemopoietic progenitor cells may cause graft rejection after HLA-identical T-lymphocyte-depleted bone-marrow transplantation.

Adult↗

An analysis of and intervention in the sexual transmission of disease.

Sexually transmitted diseases are a serious threat to the public health. Indeed, when an individual seeks medical treatment for a sexually transmitted disease, health authorities frequently attempt to identify, procure, and treat that individual's sexual contact(s). We conducted a comparative analysis of three alternative approaches to tracing the sexual partners of individuals diagnosed as having a sexually transmitted disease. The first approach involved counseling individuals (n = 27) infected with either gonorrhea or nongonococcal urethritis and exhorting them to procure their sexual partners for treatment. In addition to counseling, the second and third approaches involved distributing "occasion cards" for patients to use when informing sexual contacts of the need for treatment. Moreover, in the second approach, the counselor (a nurse or physician) informed infected patients (n = 19) that they and their partners could waive the $3 clinic fee contingent upon the partners seeking treatment within 1 week. In the third approach, the counselor asked infected persons (n = 19) to accept a follow-up telephone contact if their sexual partners failed to seek treatment within 1 week. The third approach was most effective. Ninety percent of the partners identified through this approach sought treatment, versus only about 60% of the partners in the other two conditions. The third approach was also the least expensive, costing about $2.95 to procure each partner for treatment.

Adolescent↗

Normal hematopoietic progenitor cells and malignant lymphohematopoietic cells show different susceptibility to direct cell-mediated MHC-non-restricted lysis by T cell receptor-/CD3-, T cell receptor gamma delta+/CD3+ and T cell receptor-alpha beta+/CD3+ lymphocytes.

To evaluate the capability of NK cells and cytotoxic T lymphocytes to interact with normal hematopoietic progenitor cells (HPC), as compared to neoplastic lymphohematopoietic cells, we investigated inhibition of colony growth of these cell populations in semi-solid culture systems, after incubation with cloned cytotoxic effector cells. Three different types of cloned effector cells were investigated: TCR-/CD3- NK cells, TCR-gamma delta+/CD3+ cells, and TCR-alpha beta+/CD3+ cytotoxic T lymphocytes. Effector cells showed differential levels of tumor cell colony inhibition, but no MHC-non-restricted lysis of normal HPC was observed. Pre-stimulation of normal HPC by culturing on established stromal layers had no effect. Cell-mediated lysis of HPC only occurred by Ag-specific MHC-restricted lysis by CTL, or by antibody-dependent cellular cytotoxicity. In cell mixing experiments, irradiated tumor cells, but not normal bone marrow cells inhibited tumor cell lysis. Furthermore, cloned effector lymphocytes were able to specifically eliminate malignant cells from tumor contaminated bone marrow without damaging normal HPC. When fresh leukemic cells were used as targets, growth of acute myeloblastic leukemia colonies was inhibited after incubation with several cytotoxic effector clones, whereas chronic myeloid leukemia precursor cells showed limited sensitivity to MHC-non-restricted cytolysis. These results indicate that MHC-non-restricted cytolysis by NK cells is selectively directed against neoplastic cells and not against normal HPC.

Antibody-Dependent Cell Cytotoxicity↗