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Biomedical subjects

K Martin

Publications and source records attributed to K Martin.

At least 199 records · Page 11Linked to original sources

Clinical review 15: Management of ovulatory disorders with pulsatile gonadotropin-releasing hormone.

Pulsatile GnRH therapy has yet to achieve widespread acceptance as an alternative to exogenous gonadotropin therapy in women with hypothalamic amenorrhea and complete GnRH deficiency. However, when a physiologically based replacement regimen of pulsatile GnRH is used, a high rate of ovulation and conception can be anticipated in patients with complete GnRH deficiency and hypothalamic amenorrhea. Women with polycystic ovarian syndrome may also benefit from pulsatile GnRH, although rates of ovulation are lower. Pretreatment with a GnRH agonist may improve these rates considerably, but experience is limited. Whether an iv or sc route of administration is chosen, a simplified clinical monitoring protocol can be created which requires a minimum of patient monitoring while assuring maximum safety. Seventy five nanograms per kg appears to be a reasonable initiating dose, with subsequent increases in those who do not respond. The frequency of GnRH administration is best based on the GnRH pulse frequency in normal women. However, further information is needed to determine whether such a variable frequency is clearly superior to a fixed frequency regimen. When used appropriately, pulsatile GnRH is safe, effective, and offers an excellent alternative to conventional gonadotropin therapy for women with disordered endogenous GnRH secretion. Most importantly, and as opposed to exogenous gonadotropin therapy, pulsatile GnRH can be administered by most physicians in the office setting without the necessity of on-line E2 monitoring. This feature will enable more patients to receive treatment by their local physicians, whereas exogenous gonadotropin therapy should be administered by appropriately equipped referral centers. In the future, further studies will be required to determine which other categories of patients might benefit from pulsatile GnRH.

Adult↗

Basic extraction studies of benzylpenicillin and its determination by liquid chromatography with pre-column derivatisation.

In order to develop a sensitive and precise chemical bioanalysis of benzylpenicillin in biological fluids, basic studies on benzylpenicillin are presented. These studies include pH dependent stability, extraction in aqueous ethylacetate systems in different pH and buffer compositions. A pre-column derivatisation LC method for the detection of benzylpenicillin also is described. The derivatisation of the sample is performed by the beta-lactam ring specific formation of the mercuric(II)mercaptide of the penicillenic acid in the presence of imidazole. The UV spectral properties of the derivative are utilised for detection. The chromatographic conditions are optimised with reference to the pH, the methanol, the imidazole and the mercury(II)chloride content of the mobile phase as well as the column temperature.

Chromatography, Liquid↗

Determination of benzylpenicillin in milk at the pg ml-1 level by reversed-phase liquid chromatography in combination with digital subtraction chromatography technique.

A method for the determination of benzylpenicillin in milk at very low levels by a pre-column derivatisation LC-method is described. Nine millilitres of milk were precipitated and extracted. The sample was concentrated 40 times and the recovery of benzylpenicillin was about 90%. The derivatisation of benzylpenicillin was made by the beta-lactam ring specific formation of the mercuric mercaptide of the penicillenic acid in the presence of imidazole. A technique called digital subtraction chromatography (DSCh), which uses the built-in background compensation programme of the chromatographic data processor, was applied to the chromatographic step of the analysis. The blank sample required for this technique was obtained by the beta-lactam ring specific hydrolysis of benzylpenicillin by penicillinase. By this technique it was possible to reduce interfering background peaks on the chromatograms and to increase the specificity of the method. Standard curves were made in the range 0.2-1000 ng benzylpenicillin ml-1 milk. The relative standard deviation (RSD) at 1 ng ml-1 milk, corresponding to an injection of 3.9 ng benzylpenicillin-sodium converted to the mercuric mercaptide of the penicillenic acid, was +/- 7.8% and RSD at 10 ng ml-1 milk was +/- 1.6%.

Animals↗

Determination of benzylpenicillin in plasma and lymph at the ng ml-1 level by reversed-phase liquid chromatography in combination with digital subtraction chromatography technique.

A method for the determination of benzylpenicillin (Pc-G) at very low levels in plasma and lymph is described. Detection at 325 nm of the mercuric mercaptide of benzylpenicillinic acid was made by liquid chromatography via a pre-column derivatization method. By using a digital subtraction chromatography technique, the bioanalytical method could be applied to different kinds of samples whether interfering peaks were present or not. Two different clean-up steps were used for two concentration ranges 0.1-100 micrograms and 1-1000 ng Pc-G ml-1; namely, precipitation of a 100-microliters sample with acetonitrile, or precipitation of a 1- or 2-ml sample followed by concentration via liquid-liquid extraction. The pre-column derivative of Pc-G was achieved using mercury(II)chloride in the presence of imidazole. The blank samples required for the digital subtraction chromatography technique were obtained by penicillinase treatment. Standard curves were made in the two concentration ranges. The relative standard deviation (RSD) at 5 ng Pc-G ml-1 plasma was 4.9% and at 5 micrograms Pc-G ml-1 lymph it was 2.8%. The stability of Pc-G, including the problems with non-sterile samples, was studied.

Animals↗

Metabolic clearance rate and production rate of calcitriol in uremia.

We have previously demonstrated that while both normal humans and dogs tightly control serum calcitriol levels after 25(OH)D administration, anephric humans and 5/6 nephrectomized dogs significantly increase circulating 1,25(OH)2D when supraphysiological concentrations of 25(OH)D are reached in serum. Plasma 1,25(OH)2D level is determined not only by its rate of production but also by its rate of degradation. To further characterize the mechanisms involved in the responses to 25(OH)D therapy in normal circumstances and in chronic uremia, we measured metabolic clearance rate (MCR) and production rate (PR) of 1,25(OH)2D in normal dogs and in dogs with moderate and severe renal failure, at normal and supraphysiological serum concentrations of 25(OH)D. Basal MCR in uremic dogs, either with moderate or with severe renal failure, did not differ significantly from normals (6.7 +/- 0.7, 6.8 +/- 0.4 and 6.8 +/- 0.3 ml/min, respectively). Oral 25(OH)D administration for two weeks did not affect MCR either in normal animals or in both groups of uremic dogs. 25(OH)D treatment did not affect production rates in normal dogs and in animals with moderate renal failure (with normal basal values of 1,25(OH)2D), but significantly increased 1,25(OH)2D production from 0.13 +/- 0.01 to 0.25 +/- 0.04 micrograms/day (P less than 0.05) in dogs with severe renal insufficiency. These data suggest that it is the basal level of 1,25(OH)2D which regulates the synthesis of 1,25(OH)2D in response to 25(OH)D administration in normal and uremic animals.

Animals↗

Surgical glove perforation in dermatologic surgery.

Twenty-eight of 240 (11.7%) pairs of sterile surgical gloves collected from dermatologic surgery clinics had perforations. Only 17.1% of these perforations were known to the wearer at the time of surgery. Equal numbers of perforations were found in gloves of operators and assistants. Perforations were more numerous in dominant-handed gloves. Dermatologic surgeons should consider the incidence of unknown glove perforation when planning surgeries in patients with infectious diseases.

Dermatologic Surgical Procedures↗

Identification and function of brain stem neurons regulating rat ileal water absorption.

The central nervous system (CNS) regions regulating ileal water and ion absorption are unknown. We determined 1) the CNS origin of brain stem neurons that directly innervate the rat ileum, and 2) that these neurons influence intestinal water absorption. Horseradish peroxidase (HRP) was injected into the muscle layer of the rat ileum. The brains were examined for HRP reaction product (HRPRP) 3, 5, or 7 days later. Only cell bodies of the dorsal motor nucleus of the vagus (DMNV) were labeled. Unilateral cervical vagotomy prevented deposition in the ipsilateral DMNV. To determine whether the DMNV regulates ileal water absorption, electrical and chemical stimulation (30 microA, 4 Hz, 0.2 ms, and 300 pmol L-glutamate every 5 min, respectively) were used. Both the DMNV and the adjacent nucleus tractus solitarius (NTS) were stimulated, causing a reduction in water absorption. Bilateral vagotomy prevented the effect of bilateral electrical stimulation, but unilateral vagotomy did not prevent the decrease due to ipsilateral stimulation. These studies show that 1) the DMNV innervates the ileum, and 2) alteration of vagal efferent activity by stimulation of the DMNV and NTS reduces ileal water absorption.

Animals↗

The disposition of chloramphenicol in colostrum-fed and colostrum-deprived newborn pigs.

The pharmacokinetics of chloramphenicol (CAP) were studied in four colostrum-deprived and 4 colostrum-fed newborn piglets after an intravenous bolus dose of CAP, 77 mumol kg-1 (25 mg kg-1). The elimination half-lives in the colostrum deprived piglets had a tendency to be longer (17.2 +/- 3.9 hrs) than in the colostrum-fed piglets (12.7 +/- 1.1 hrs) and in both groups they were considerably longer than reported in older pigs. The long half-lives of CAP in the newborn pigs were a reflexion of very low clearance (Cl) values, 0.0391 +/- 0.007 and 0.0512 +/- 0.007 1 kg-1 hr-1, in the two groups, while the volume of distribution was of the same size in the two groups, 0.9549 +/- 0.247 and 0.9411 +/- 0.211 1 kg-1. The protein binding of CAP in pooled piglet plasma was concentration dependent, 53-45%, (P less than 0.001) in the concentration range 31-232 microM (10-75 micrograms ml-1) and the binding degree was significantly higher in plasma from colostrum deprived piglets, 53.0 +/- 0.8% compared to plasma from colostrum fed, 47.5 +/- 1.3% (P less than 0.01).

Animals↗

Dynamics of Soil Denitrifier Populations: Relationships between Enzyme Activity, Most-Probable-Number Counts, and Actual N Gas Loss.

To better understand temporal variability in soil denitrification, denitrifying enzyme activity (DEA) and denitrifier populations (as determined by most-probable-number [MPN] counts) were measured in field and laboratory experiments. Measurements of DEA and MPN provided highly contradictory indications of denitrifier dynamics. In laboratory incubations, under conditions favoring active denitrification, the synthesis of new denitrifying enzymes and the actual amount of denitrification were closely related. In other experiments, however, both DEA and MPN counts were poor indicators of actual denitrification. In some cases, we found significant increases in DEA but no significant production of N gas. Except with unnaturally high substrate amendments, changes in DEA were small relative both to the persistently high DEA background and to changes in MPN. As estimated by MPN counts, denitrifier populations increased significantly during denitrification events. It was apparent that only a small fraction of the denitrifiers were included in the MPN counts, but it appeared that this isolatable fraction increased during periods of active denitrifier growth. Use of DEA as an index of biomass of cells which have synthesized denitrifying enzymes suggested that denitrifier populations were persistent, stable, and much larger than indicated by MPN procedures.

Journal Article↗

Research in home care.

Past and present research in the home care setting predicts future trends. Home care research studies will continue to reflect social and economic issues of the future since research and researchers do not exist in a vacuum but are influenced by their era. Because of the generalized concern about economic stability and health care costs and the heightened interest in home care, investigations related to nursing interventions, client outcomes, and reimbursement will increase. As researchers search to identify long-term, positive client outcomes, the role of physical and psychosocial environmental factors will receive greater attention. Clients, too, do not exist in a vacuum but reflect the family and support systems which do, or do not, surround them. For home care research to serve as the scientific base for practice, continuing and increasing collaboration must occur between nursing service and education. More joint appointments or shared positions are likely as blending occurs in researchers' roles and nursing service staff assume more responsibility for research projects. The struggles involved with financial support of home care research will not cease. Home care researchers will continue to compete for funding with other nursing, health care, and research investigators. Specific strategies will enhance funding opportunities for home care nursing. These include: (1) increasing methodologic soundness, (2) increasing sophistication of studies and investigators, (3) publicizing findings and benefits of projects, and (4) developing a successful history of obtaining funding and conducting studies. Research in the home care setting will thrive if it attracts more and more nurses with scientific skills similar to those identified by Sir Medawar: "Among scientists are collectors, classifiers, and compulsive tidiers-up; many are detectives by temperament and many are explorers; some are artists and others artisans. There are poet-scientists and philosopher-scientists and even a few mystics."

Child↗

AIDS and antibodies to human immunodeficiency virus (HIV) in children and their families.

Infection with human immunodeficiency virus (HIV, previously known as HTLV-III/LAV) documented by a sensitive, specific immunoblotting (western blot) technique is described in 14 children with symptoms of AIDS or AIDS-related complex. For serodiagnosis of HIV infection, immunoblots blocked with milk were more sensitive than enzyme-linked immunosorbent assays or immunoblots blocked with gelatin. One or both parents of 13 of these children abused intravenous drugs. Sixteen of 17 parents of the affected children but only one of eight siblings living in the same household were positive for antibody to HIV. All siblings had experienced infection and acquired antibodies to Epstein-Barr virus, which is thought to spread by saliva. In contrast to their HIV-infected parents, children with AIDS or AIDS-related complex were less likely to have decreased numbers of circulating T4 cells, and their sera recognized fewer HIV polypeptides on western blots.

Acquired Immunodeficiency Syndrome↗

New findings in apparent mineralocorticoid excess.

We report two female siblings (ages 4 and 9 years) and one 8-year-old male with the syndrome of apparent mineralocorticoid excess (AME) presenting with low renin hypertension and hypoaldosteronism. The deficiency of 11 beta-hydroxysteroid dehydrogenase results in a defect of the peripheral metabolism of cortisol (F) to cortisone (E). As a result, the serum cortisol half-life (T1/2) is prolonged, ACTH is suppressed, and serum F is normal. The specific diagnosis of the disorder was made by the decreased ratio of the urinary metabolites of E (tetrahydrocortisone, THE) and F (tetrahydrocortisol, THF). Continuous i.v. hydrocortisone administration caused an increase in blood pressure and decrease in serum potassium demonstrating the abnormal mineralocorticoid activity of cortisol in these patients. Addition of spironolactone resulted in a decrease in blood pressure, rise in serum potassium and a gradual increase in plasma renin activity. These studies suggest that an abnormality in cortisol action or metabolism results in cortisol behaving as a potent mineralocorticoid and causing the syndrome of AME.

Adrenocorticotropic Hormone↗

Differences among human immunodeficiency virus strains in their capacities to induce cytolysis or persistent infection of a lymphoblastoid cell line immortalized by Epstein-Barr virus.

Four strains of human immunodeficiency virus (HIV) manifest consistent differences in biologic behavior after infection of the X50-7 line of human umbilical cord lymphocytes immortalized by Epstein-Barr virus (EBV). Some dilutions of the first strain examined, human T-cell lymphotropic virus type III B, which is derived from a pool of patient isolates propagated in H9 cells, caused transient cytopathic effects (CPE) followed by recovery of a subpopulation of X50-7 cells which became virus carrier cultures. Other dilutions of the same virus stock completely lysed X50-7 cells. Two other strains, RF2 and YW, both from individual patients with acquired immune deficiency syndrome, always induced complete cytolysis of X50-7 cells at all dilutions which infected the cells. However, RF2 did establish persistent infection of H9 cells. A fourth strain, PH1-MN, from a child with acquired immune deficiency syndrome-related complex, induced only transient CPE in X50-7 and H9 cells, which thereafter always recovered to form carrier cultures. For all four strains, the dilutions of HIV stocks which caused CPE corresponded to dilutions which resulted in the detection of HIV polypeptides by immunoblot. Cytolysis in HIV-infected X50-7 cells was accompanied by a decrease in the amount of EBV nuclear antigen; however, HIV infection did not induce EBV replication. Thus CPE in X50-7 cells is due to replication of HIV per se and not to activation of EBV. The observations indicate that there are differences in the cytolytic properties of HIVs and that these differences are influenced by the target cell.

Acquired Immunodeficiency Syndrome↗

Biological effects of aluminum on normal dogs: studies on the isolated perfused bone.

Although it is well known that aluminum (Al) plays a role in the development of osteomalacia in patients with chronic renal failure, the mechanisms are not fully understood. Since the osteoblasts are the cells responsible for the formation of osteoid tissue, which is greatly affected in patients with Al-induced osteomalacia, it is possible that Al could affect the number of osteoblasts or interfere with their function. To further characterize this potential mechanism, we performed studies in isolated perfused tibiae from normal and Al-treated dogs. In this system, when PTH is added to the perfusate, cAMP, a major marker of osteoblasts, is released. The dogs were divided into two groups: control, and Al-treated (0.75 mg/kg, iv, 5 days a week for 3 months). Thereafter, the dogs were killed, and the tibiae were perfused in vitro. PTH-(1-34) (3-4 ng/ml) and 3-isobutyl-1-methylxanthine (an inhibitor of phosphodiesterase) were added to the perfusate. Basal cAMP secretion was the same in both groups of dogs. After PTH was added to the perfusate, cAMP increased to a peak of 188.2 +/- 30.6 pmol/min in the normal dogs vs. 113 +/- 8.15 in Al-treated dogs (P less than 0.05). Cumulative cAMP secretion over a 30-min period was 766 +/- 127.9 pmol in the normal dogs vs. 455.6 +/- 38.2 pmol in the experimental animals (P less than 0.05). The histological appearance of bone biopsies taken before and after Al administration are consistent with a suppressive effect of the cation on osteoblast function. In particular, the number of osteoblasts had decreased 8-fold (P less than 0.01) under the influence of Al, and tetracycline-based measurements of mineralization kinetics show that osteoblast-mediated calcification was dysfunctional (P less than 0.01-0.025). On the other hand, the histological features of the post Al treatment biopsies suggest that at some time during its administration, the cation stimulates osteoblastic activity. For example, new (woven) bone formation was present in two dogs, and in another, lamellar bone, deposited under the influence of Al, covered the entire trabecular surface. Moreover, Al-associated osteoid was deposited independent of prior resorptive activity, indicating that the cation promotes bone formation in the absence of prior resorption. In keeping with its trophic effect on matrix deposition, Al also led to extensive marrow fibrosis in five dogs, indicating that Al also stimulates the activity of fibroblasts, cells closely related to osteoblasts.(ABSTRACT TRUNCATED AT 400 WORDS)

Aluminum↗