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Biomedical subjects

L Martin

Publications and source records attributed to L Martin.

At least 469 records · Page 26Linked to original sources

Mineral homeostasis in very premature infants: serial evaluation of serum 25-hydroxyvitamin D, serum minerals, and bone mineralization.

This study was designed to evaluate the role of vitamin D sufficiency, as reflected in serum 25-hydroxyvitamin D (25-OHD) concentrations, on serum minerals and bone mineralization in very premature infants. Seventy-two infants (mean +/- SD gestation 30.1 +/- 2.5 weeks, mean +/- SD birth weight 1178 +/- 278 gm) were observed serially for the first 3 months of life. Mean serum calcium and phosphorus values, but not magnesium, remained low prior to 12 weeks. The percentage of infants with moderate to severe hypomineralization was 75% at 3 weeks, 55% at 6 weeks, 54% at 9 weeks, and 15% at twelve weeks. Low serum calcium and phosphorus values, high alkaline phosphatase activity, and moderate-severe hypomineralization were more frequent in infants weighing less than 1000 gm and in those with lower mineral intake. With a 400 IU vitamin D supplement, 45% of infants could maintain an initially normal serum 25-OHD concentration or increase low concentrations, whereas 55% had falling or persistently low (less than or equal to 15 ng/ml) 25-OHD concentrations. Birth weight and mineral intakes were comparable in these two groups, yet the group with the lower serum 25-OHD concentration had lower serum calcium and higher alkaline phosphatase values, and a higher percentage of moderate to severe hypomineralization. Regardless of birth weight, mineral intake, or 25-OHD concentration, increases in serum calcium and phosphorus values and in mineralization were seen at postconception term (12 weeks in most infants, nine weeks in those weighing 1250 to 1600 gm). At 12 weeks of age, but not before, serum 25-OHD concentration was directly correlated with serum calcium (r = 0.47, P less than 0.01) and serum phosphorus (r = 0.47, P less than 0.01) and inversely correlated with alkaline phosphatase values (r = -0.71, P less than 0.01). Mineral availability and 25-OHD sufficiency both appear to be important and to act synergistically, with neither totally compensating for the other.

Alkaline Phosphatase↗

Absorption, dosage, and effect on mineral homeostasis of 25-hydroxycholecalciferol in premature infants: comparison with 400 and 800 IU vitamin D2 supplementation.

Because the efficiency of vitamin D absorption or hepatic uptake and 25-hydroxylation appears decreased in very premature infants, the routine use of 25-hydroxycholecalciferol (25-OHD3) supplementation has been suggested. Absorption studies of a 3 micrograms/kg orally administered dose of 25-OHD3 showed peak serum 25-hydroxyvitamin D2 and -vitamin D3 (25-OHD) concentrations at 4 to 8 hours similar in timing but of lesser magnitude to those seen in adults. Administration of 1 microgram/kg birth weight/day of 25-OHD3 corrected moderately low, but not very low serum (25-OHD) concentrations, and 2 micrograms/kg BW/day resulted in rapid and sustained increase in serum 25-OHD. Administration of 800 IU ergocalciferol (D2) also produced significantly higher serum 25-OHD concentrations than those in infants given 400 IU vitamin D2, but increases in serum 25-OHD were more gradual than in infants given 25-OHD3. In treatment trials with infants weighing less than 1500 gm, those given 800 IU D2, compared with those given 400 IU D2, had higher serum calcium concentrations and less frequent moderate or severe hypomineralization. Infants given 2 micrograms/kg BW 25-OHD3 had a significant increase in serum phosphorus values, but a decrease in serum calcium and magnesium concentrations, and parathyroid hormone also was suppressed to low normal values. The frequency of moderate to severe hypomineralization remained the same as in infants given 400 IU D2. In a subgroup of infants, serum 1,25-dihydroxyvitamin D was elevated over adult values, both in infants given 25-OHD3 (68.5 +/- 8.4 pg/ml) and in infants given vitamin D2 (60 +/- 6.7 pg/ml). Serum vitamin D concentrations were undetectable in four of six infants receiving 25-OHD3, but were elevated (5 to 31 ng/ml) in four infants receiving vitamin D2. Although 800 to 1000 IU D2 can be recommended as routine vitamin D supplementation in very premature infants fed standard formula, the use of 25-OHD3 requires further study.

Absorption↗

[Anesthesia with controlled hypotension for treatment of intracranial arterial aneurysm in an infant].

A case is reported of a ruptured intracranial aneurysm of the posterior cerebral artery in a 21/2 month old infant. The clinical picture of subarachnoid haemorrhage included coma, seizures and left hemiparesis. The aneurysm was detected by two dimensional ultrasonography and CT scan. The carotid and vertebral arteriogram showed an aneurysm located on the posterior cerebral artery. Surgery was performed after neurological improvement, 25 days after admission. The operation was conducted under controlled systemic hypotension using sodium nitroprusside. The mean blood pressure was decreased from 70 mmHg to 40 mmHg during 20 min. This technique established good haemostatic conditions during removal of the aneurysm. Postoperative recovery was uneventful with full neurological recovery. The interest of sodium nitroprusside as a hypotensive agent is discussed. The difficulties of monitoring haemodynamic variables in infants are stressed.

Anesthesia, General↗

A drug-resistant mutation in the ribosomal DNA of Tetrahymena.

A mutation that confers resistance to the drug paromomycin is shown to be in the structural gene that codes for the ribosomal RNA in Tetrahymena. This observation was made by exploiting a variant of the ribosomal DNA that distorts amplification of this locus when a new somatic nucleus develops during conjugation. Because the allelic forms of this locus have a restriction endonuclease site polymorphism, it was possible to correlate drug resistance with presence of a specific allele. The genetic results have been confirmed by sequence analysis (presented elsewhere). Thus, the crosses presented here provide a unique opportunity to identify mutations in the ribosomal DNA.

Alleles↗

Jaw wiring in the treatment of morbid obesity.

Fourteen patients originally presented with hyperphagia and intractable morbid obesity have had maxillomandibular fixation (MMF) applied in an effort to control their obesity. In 10 patients who were massively obese or considered poor risk candidates for surgical control of their obesity, MMF was applied with the aim of reducing the obesity to a level where a surgical gastric restrictive bariatric procedure could be safely carried out. Eight of these patients had been rejected for surgical control of obesity elsewhere and two were edentulous. Five of these patients after successful weight loss over periods from 16 to 40 weeks (mean percentage overweight lost 84.8, range 39-150) safely underwent a gastric restrictive procedure. All five patients have had continuous weight loss after bariatric surgery. Two patients requested removal of MMF 1 and 2 weeks after application. The remaining three patients, who were candidates for surgery, after successful weight loss over periods from 12 to 28 weeks (mean percentage of overweight lost 45, range 38-50) decided not to proceed with surgical control. All have subsequently regained the lost weight. Four originally morbidly obese patients, who had had a previously successful gastric restrictive procedure followed by weight loss, requested MMF in an effort to lose further weight. Over periods from 8 to 16 weeks three of the four had further weight loss (mean percentage of overweight lost 18.3, range 5-30). After removal of MMF all four patients regained some weight. In only one was there a significant maintenance of weight lost during MMF.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Weight↗

Sulfasalazine in severe rheumatoid arthritis: a study to assess potential correlates of efficacy and toxicity.

Thirty-one patients with chronic active rheumatoid arthritis (RA) resistant to gold and/or penicillamine therapy, were treated with sulfasalazine, 2-3 g daily, in a 12-week open study. Nineteen patients completed the study, and of these, 13 showed clinical improvement. Twelve patients were withdrawn from the study because of nausea (8), mouth ulcers (1), disease flare (1) and noncompliance (2). There was no significant difference in serum sulfasalazine concentrations among responders, nonresponders and patients who were withdrawn. Our data suggest that sulfasalazine may be of benefit in the treatment of RA. Further studies are necessary to determine if toxicity and/or efficacy might be related to serum concentrations of sulfasalazine metabolites.

Adult↗

A controlled comparison of tiaprofenic acid and ibuprofen in osteoarthritis.

A multicentre double-blind crossover study of tiaprofenic acid (600 mg daily) against ibuprofen (1.2 g daily) was undertaken in 77 patients with osteoarthritis to compare their efficacy and tolerance. No difference was found between the two agents, both giving pain relief and being safe and acceptable to the majority of patients. It is concluded that in this short-term study, both agents offer effective and safe treatment for osteoarthritis.

Adult↗

Measurements of maximum respiratory pressures in polymyositis and dermatomyositis.

Measurements of maximum respiratory pressures and routine pulmonary function tests were performed in 8 patients with polymyositis (PM) and 2 patients with dermatomyositis (DM). Serial measurements of routine pulmonary function tests in 8 patients remained unchanged. Maximum respiratory pressures were decreased initially in 7 patients with proximal muscle weakness and clinically active muscle disease and improved with corticosteroid therapy in the 5 patients who were followed serially. In 3 patients with clinically stable disease the maximum respiratory muscle power was normal. Serial measurements of maximum respiratory pressures have been of value in monitoring patients with PM and DM.

Adult↗

Stimulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in mouse uterine epithelial cells by oestradiol-17 beta.

The characteristics of 3-hydroxy-3-methylglutaryl-CoA reductase from mouse uterine epithelial cells were studied. Preliminary experiments showed that enzyme activity was stimulated approx. 10-fold 18h after administration of 100ng of oestradiol-17 beta. This activity was associated with all particulate fractions of the uterine luminal cell. The Km for D-3-hydroxy-3-methylglutaryl-CoA was 5.54 +/- 1.12 microM. The detailed time-course of oestrogen stimulation showed two peaks of activity, 9 and 15h after hormone treatment. The DNA content of the epithelial cells doubled between 6 and 12h after hormone treatment, whereas the protein content increased linearly over the 18h period. The peak of enzyme activity at 9h is associated with early S phase of the epithelial cells; the peak at 15h may be associated with a second S phase or with mitosis. Pretreatment with progesterone for 3 days before injection of oestradiol-17 beta (a treatment which inhibits uterine epithelial DNA synthesis) reduced the oestrogenic stimulation of enzyme activity by 63%; progesterone treatment alone did not stimulate enzyme activity. These data suggest that uterine epithelial 3-hydroxy-3-methylglutaryl-CoA reductase may play an important role in the cell cycle in this tissue.

Animals↗

The effects of ionizing radiation on cell cycle progression in ataxia telangiectasia.

Although ataxia telangiectasia (AT) cells are more sensitive than normal cells to killing by ionizing radiation, their DNA synthesis is more resistant to inhibition by radiation. It was thought that this anomaly in DNA synthesis was likely to perturb cell cycle progression. Flow cytometry and the fraction of labelled mitoses (FLM) were used to investigate effects of irradiation in normal and AT cell lines. The FLM indicated that radiation apparently induced a longer G2 delay in normal cells than in AT cells. However, flow cytometry showed that radiation induced much larger and more prolonged increases in the proportion of G2 cells in AT than in normals. AT populations also showed much larger postirradiation decreases in viable cell numbers. These data suggest that a large proportion of the radiosensitive AT cells are not reversibly blocked in G2 but die there, and never proceed through mitosis. The less radiosensitive normal cells are delayed in G2 and then proceed through mitosis. We suggest that the apparently shorter radiation-induced mitotic delay seen in AT cells by FLM is not real but is an artifact arising from perturbation of steady state conditions by selective elimination of a particular cohort of AT cells. Accumulation of AT cells in G2 is compatible with radiosensitivity of these cells and may arise from a defect in DNA repair or an anomaly in DNA replication.

Ataxia Telangiectasia↗

Albumin coating of a knitted polyester arterial prosthesis: an alternative to preclotting.

Coating a knitted polyester arterial prosthesis with cross-linked albumin fills the interstices of the graft and relieves the surgeon of the necessity to preclot . This is of particular value in patients whose blood clotting properties are hypercoagulable, or hypocoagulable . In addition, such prostheses require less handling, which can lower the risk of bacteremic colonization and shorten the operative time. The in vivo behavior of the implanted albuminated prosthesis in the thoracic aorta of dogs is similar to that of preclotted grafts, although the sequences of early healing are different. The preclotted graft develops a continuous, thick thrombotic matrix on its luminal surface during the first 4 hours of implantation. Following the initiation of the fibrinolytic mechanism 24 to 48 hours postoperatively, this thrombotic deposit quickly recedes , leaving blood cells and platelets adhering here and there to the prosthetic surface. In comparison, the albuminated coating is not associated with major early thrombotic deposits. The albumin remains visible between the filaments during the first 2 weeks of implantation. Both treated and control grafts contain numerous thrombi on their inner surface after 1 to 2 weeks. After 1, 3, and 6 months, both implants are well encapsulated and present a glistening and continuous luminal surface. This excellent healing, however, can be compromised should the graft adhere too closely to the animal's lungs.+2

Albumins↗

Blood pressure, electrocardiogram and echocardiogram measurements in the growing pony foal.

Twelve newborn pony foals underwent cardiovascular examinations (auscultation, arterial blood pressure measurements, electrocardiograms and M-mode echocardiograms) on their first day of life and then on Days 7, 14, 21, 30, 60 and 90. An age dependent, statistically significant, rapid increase of the arterial blood pressure in the first month was documented together with a slower decrease of the resting heart rate after two and three months of life. Innocent soft systolic murmurs were audible over the left heart base in a large number of the foals. The electrocardiograms showed age dependent increases of the PR-, QRS- and QT- intervals and a trend of the mean electrical axis in the frontal plane to rotate towards the left side. The ventricular dimensions, measured by M-mode echocardiography, increased with the growth of the pony foals. Linear regression equations were calculated for the right and left ventricular internal dimensions in relation to body weight (bwt). The other echocardiographic parameter had low correlations with bwt.

Animals↗

The 2-deoxyglucose uptake method as a first screen for neurotoxic compounds.

Our primary goal is to develop a screening procedure to detect and partially characterize neurotoxic compounds. There is a great need for a new approach to screening for neurotoxicants because our industrialized world abounds with untested and potentially neurotoxic compounds. A large number of new compounds are introduced each year. Although a number of testing approaches to the screening for neurotoxicants have been proposed in the recent years, a consensus on the most adequate approach is yet to emerge. The existing methods share a number of shortcomings. Thus, most methods only detect a fraction of the tested neurotoxicants. Other methods lack the necessary resolution to detect the neurotoxic damage reproducibly and reliably. Furthermore, many screening approaches are too time consuming and costly to be used for the large-scale screening of neurotoxicants. It is, therefore, imperative to develop reliable and efficient screening methods applicable in regulatory toxicology. In this report, we describe two versions of the same method that we feel may be very beneficial for the large-scale screening of neurotoxicants. The 2-deoxyglucose (2-DG) uptake method provides an indirect measure of neuronal activity in different areas of the brain. The ability of the method to detect most, if not all, neuroactive substances is reviewed in this report. In the context of this report, a neuroactive substance is defined as a substance acting directly on the central or peripheral nervous system neurons and (or) glia. The 2-DG method equals the sensitivity of the most sensitive alternative methods which were selectively designed to detect the effects of specific groups of compounds. The generality and sensitivity of the 2-DG method are of major importance. Thus, if a tested compound does not affect the uptake of 2-DG into the brain, it is not likely to be neuroactive. Since neurotoxic compounds are a subset of neuroactive compounds, a compound that is not neuroactive is also not neurotoxic. Thus, a single test may, in some instances, determine if a tested compound is nontoxic. In addition, it appears that each compound or, at least, each family of compounds produces a characteristic profile ("pattern") of the sites of altered 2-DG uptake. This pattern can be exploited to characterize the tested compound and help us decide whether it is neurotoxic or neuroactive. Preliminary results from our laboratory indicate classical neurotoxic agents such as acrylamide, triethyltin, and 2,5-hexanedione induce a generalized depression of the 2-DG uptake throughout the brain.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

On the source of uterine 'luminal fluid' proteins in the mouse.

Examination by light-, transmission electron- and scanning electron-microscopy showed that flushing the lumen of the mouse uterus with small volumes of fluid damaged the endometrium by rupturing and removing luminal epithelial cells, splitting the epithelial basement membrane and connective tissue stroma, and rupturing and leaching stromal cells and blood vessels. The damage increased with increasing progestation of the uterus and between Days 4 and 5 of pregnancy. I conclude that many so-called 'luminal fluid' proteins originate from luminal and stromal cells, intercellular fluid and blood and that apparent changes in luminal fluid protein content during early pregnancy may largely reflect alterations in the extent and type of damage produced by flushing, as a consequence of changes in the physical state of the uterus induced by hormones and the presence of blastocysts.

Animals↗