Baxter and MICRO Healthsystems form a strategic alliance to promote time-saving technology. Interview by Bill W. Childs.
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Biomedical subjects
Publications and source records attributed to G Young.
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The integrity of the pre-lens tear film (PLTF) is an important determinant of the clinical performance of contact lenses. The PLTF of eight hydrogel lenses, ranging from 36.5% to 85% water content, was assessed on six asymptomatic lens wearers in a randomized, double-masked experiment. Using a specular reflection technique, the thicknesses of the lipid and aqueous phases were found to be greater on lenses of higher water content. Water content was measured before and after 90 min wear using a hand-held refractometer. Non-invasive tear break-up time was also found to be greater for higher water content lenses. No association was found between lens dehydration and PLTF characteristics. The differences in PLTF noted in this study may help to explain the differences noted between some lenses in their rates of surface deposition.
Elevated levels of macromolecules, within the peripheral blood of head and neck cancer patients, capable of binding the first component of complement (C1qBM) in vitro have prognostic implication. Namely, elevated levels of C1qBM have been associated with nonresponse to induction chemotherapy. In this investigation, a series of in vitro studies regarding the biological properties of C1qBM were combined with a longitudinal analysis of 112 previously untreated head and neck cancer patients. Our purpose was to shed light on the biological significance of this circulating macromolecule, a substance composed, in part, of IgG and IgM. A potential confounding influence of C1qBM with induction chemotherapy, which could contribute to observed prognostic findings, was negated by two in vitro observations: the macromolecule failed both to bind the chemotherapeutic agents cisplatin, bleomycin, and 5-fluorouracil and to impede the cytotoxic effect of these same drugs on a cultured human head and neck cancer cell line. The clinical relevance of C1qBM was reinforced by the observation that elevated levels predicted a high probability of death with disease (P = 0.005 by Cox's proportional hazards model). The prognostic implication was independent of the use of induction chemotherapy, i.e., patients with high C1qBM levels treated with multimodality therapy not composed of anticancer drugs did equally poorly. Thus, the prognostic significance of C1qBM in patients undergoing induction chemotherapy appears independent of drug effect and appears reflective of tumors that are more rapidly progressive and potentially less responsive to therapeutic intervention, including combinations of surgery, radiation, and/or chemotherapy.
A flow cytometric assay was used to detect the lytic and binding capacities of both fresh peripheral blood lymphocytes and purified Leu-19+ natural killer cells against head and neck cancer cell lines. Results demonstrated that natural killer cell-mediated cytotoxicity and effector-target conjugate formation evaluated by flow cytometry was significantly correlated with the standard chromium 51 release assay and the single-cell microscopic assay, respectively. The sorted Leu-19+ natural killer cells demonstrated higher lytic capacity with a corresponding higher binding rate compared with the unsorted peripheral blood lymphocytes and sorted Leu-19- cells. Flow cytometric analysis of natural killer cell activity (a rapid, simple, and quantifiable procedure) is an alternative to the standard chromium 51 release assay.
Binding sites for native chum salmon growth hormone (sGH) in coho salmon (Oncorhynchus kisutch) hepatic membranes were analyzed by radioreceptor assay. Displaceable (specific) binding represented up to 25% of total radiolabeled sGH added. Binding was dependent on buffer pH and membrane protein concentration, and was complete by 24 hours at 15 degrees C. Specific binding was greatest in liver membranes, and was also detected in muscle, ovary, gill, kidney, and brain. Scatchard analyses indicated a single class of hepatic binding sites that were specific for sGH. In stunts, abnormal seawater salmon with elevated plasma GH levels and inhibited growth, specific binding of sGH to liver membranes was three times lower than in normal seawater smolts. The concentration of salmon GH binding sites was decreased in stunt livers by 60%, while their affinity for sGH was unchanged. Down-regulation of hepatic GH receptors by high plasma GH levels may explain in part the low sGH binding in stunts.
Specific binding of 125I-ovine prolactin (oPRL) to microsomal fractions from gill, kidney, and liver of adult tilapia was determined. Specific binding varied among tissues, the highest values being displayed by kidney membranes. In the liver, the binding of oPRL was not strongly displaced by tilapia prolactins (tPRL177 and tPRL188), although tPRL177 was six times more potent than tPRL188. On the other hand, in kidney and gill membranes, the two tPRLs were equipotent. Tilapia PRLs showed low potency in competing for oPRL-binding sites when pregnant rat liver membranes were utilized. Tilapia growth hormone (tGH) and human growth hormone (hGH) displaced 125I-oPRL from liver as well as did tPRL177 but were not recognized well by renal or branchial receptors. Two 125I-oPRL-binding sites were detected in every tissue tested. These binding sites are subject to physiological regulation since adaptation to seawater resulted in a significant decrease in specific binding.
The effects of hypophysectomy and subsequent replacement therapy with ovine prolactin (oPRL) on specific binding of 125I-oPRL to gill, kidney, and liver membranes of male tilapia were examined. The possible control of prolactin receptors by cortisol (F) and triiodothyronine (T3) was also studied using intact animals. In gill and kidney, hypophysectomy resulted in a significant decrease in specific binding that was partially restored (threefold increase) by three injections of oPRL, suggesting a role of the pituitary in the control of prolactin receptors. However, removal of the pituitary and replacement therapy with oPRL had no effect on binding by liver membranes. Cortisol and T3 treatment, alone or in combination, did not significantly affect prolactin binding by any of the tissues tested.
The records of 314 patients who suffered blunt chest trauma and underwent thoracic aortography between 1968 and 1986 were retrospectively reviewed. The patients ranged in age from 7 to 84 years (mean, 37.7 years). There were 255 male and 59 female patients. The majority of injuries were the result of motor vehicle accidents. The most common indication for aortography was a widened mediastinum on chest roentgenogram (83.4%). The aortogram was positive for cardiovascular injury in 19.7% of cases. There were 47 patients with aortic rupture, 15 with subclavian artery disruption, and 1 with traumatic aortic insufficiency. Complications occurred in 1.7% of patients. Two patients sustained groin hematomas and one patient suffered an intimal tear of the ascending aorta from the angiographic catheter. None of the complications required treatment. Aberrant origin of the arch vessels occurred in 0.96% of patients, and ductus diverticulum occurred in 0.64%. There were two false-positive and no false-negative aortograms. It was concluded that thoracic aortography after trauma is accurate and safe.
We measured the modulation transfer functions (MTF's) of five simultaneous vision bifocal contact lenses: center-near (Alges, University Optical Products), center-distance (BiSoft, CIBA Vision), diffractive rigid gas-permeable (Diffrax, Pilkington Barnes-Hind), diffractive hydrogel (Hydron Echelon, Allergan), and varifocal center-near (PS-45, G. Nissel). MTF's were measured at various aperture sizes (1 to 7 mm) and at a wavelength of 546 nm. The soft diffractive bifocal MTF's were measured at various wavelengths. The results tended to confirm previous theoretical calculations. The optical performance of the concentric designs was highly sensitive to variations in aperture size. The optical performance of both the rigid and soft diffractive lenses was largely (but not entirely) independent of aperture size. The varifocal lens was sensitive to changes in aperture size with respect to both optical quality and optimal focus.
Neonatal exposure to the synthetic estrogen, diethylstilbestrol, is known to affect the structure of the male reproductive system; thus, changes may also occur in the levels of hormone receptors. Prolactin receptor levels from the reproductive systems of male BALB/c mice exposed neonatally to diethylstilbestrol were analyzed. Neonatal exposure to diethylstilbestrol caused significant decreases (i) in prolactin receptor levels in the seminal vesicle, ductus deferens, and anterior and ventral prostates and (ii) in tissue weight and protein content in reproductive organs other than the ventral prostate.
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The relative efficacy of three commercial pancreatic enzyme supplements in improving fat absorption was studied using the [14C]triolein breath test in 12 patients with chronic pancreatitis. Two of the supplements were enteric coated. The one nonenteric coated product was studied twice: with and without ranitidine coadministration. Doses complied with the manufacturers recommendations. Baseline studies included pentagastrin-stimulated gastric acids, 72-hr fecal fat excretion, and [14C]triolein absorption while not on supplementation. Acid outputs were variable (BAO: 0.3-4.1 meq/hr; MAO: 3.5-34.6 meq/hr). Three patients had mild steatorrhea (i.e., less than 10 g/day) and the remaining severe fat malabsorption (56.9 +/- 41.5 g/day). Although fat absorption was significantly improved by all three supplements, the nonenteric coated preparation was most effective (P less than 0.001). However, laboratory analysis demonstrated that lipase content was four times greater, ie, 17,000 IU/4 tablets. Pretreatment with ranitidine failed to further improve the absorption in patients given nonenteric supplements but was effective in those found to have high or normal acid outputs (P less than 0.001). Our results suggest that the recommended dosage of enteric coated preparations is insufficient for adult patients with severe chronic pancreatitis. Secondly, the marked variability of acid secretion in such patients possibly accounts for the variability of results obtained by others on the usefulness of coadministration of antacids and H2 antagonists. Routine measurement of gastric acid secretion status may help optimize the choice and form of pancreatic enzyme supplementation.
The status of circulating growth hormone and prolactin during the parr-smolt transformation and during seawater adaptation of coho salmon (Oncorhynchus kisutch) was investigated in relation to changes in plasma levels of thyroxine, triiodothyronine, and cortisol, and in hypoosmoregulatory ability. Sampling (biweekly or monthly) occurred between early February and October. When peak hypoosmoregulatory ability was achieved (mid-April), one group of fish was acclimated to seawater over a period of 18 hr and was sampled 1, 3, and 7 days after the introduction of fish to seawater and biweekly thereafter. Plasma prolactin levels rose steadily from the first sampling date to a peak of 15 ng/ml in early April, declined rapidly, and remained low until June when a second increase occurred. Prolactin declined to 2 ng/ml within 1 day of the beginning of seawater adaptation. Growth hormone increased twofold from February to late March, and achieved plateau levels of 20 ng/ml in the period from mid-April to July and then gradually declined to 10 ng/ml in September and October. Plasma levels of growth hormone in seawater-acclimated fish were similar to those of freshwater coho, but with larger fluctuations; no increase was apparent during the first week of seawater acclimation. Plasma cortisol and plasma triiodothyronine increased at the same time as plasma growth hormone; increases in plasma thyroxine occurred later. In general, both growth hormone and cortisol levels were elevated when hypoosmoregulatory ability was high. Conversely, prolactin levels generally showed a negative relationship with hypoosmoregulatory ability.
In order to examine the dynamics of ion regulation, osmoregulation, and plasma calcitonin during the parr-smolt transformation (smoltification), blood and gill tissue were collected from yearling coho salmon, Oncorhynchus kisutch, from February to October. Fish were kept in fresh water (FW) throughout this period. In addition, fish were exposed to seawater (SW) at the peak of smoltification in mid-April, and samples from these fish were collected until July. Plasma osmolality, gill Na+,K+-ATPase activity, plasma levels of calcitonin, and free and total calcium and magnesium were measured. SW adaptability of FW fish was assessed throughout the study by measurements of plasma osmolality following a 24-hr exposure to seawater. The greatest hypoosmoregulatory ability occurred in April-May, although SW-adapted fish had higher plasma osmolality than FW-adapted fish at all times. Gill Na+,K+-ATPase activity in FW-adapted fish increased from April to June and increased rapidly following exposure of fish to SW, and remained elevated in SW-adapted fish. Free plasma calcium and magnesium levels increased following SW exposure, but returned to prior levels within 1 week. Netting and confinement stress during sampling caused an increase in plasma osmolality and free calcium and magnesium levels in both FW- and SW-adapted fish. Changes in hypoosmoregulatory ability during smoltification and SW adaptation were correlated with changes in gill Na+,K+-ATPase activity. A sharp transitory peak in plasma calcitonin levels occurred early in smoltification (March) and in SW-adapted fish in June. Plasma calcitonin levels gradually increased in FW-adapted fish during the period of desmoltification. However, no change in plasma calcitonin levels occurred during SW-induced hypercalcemia, suggesting that the hormone does not play a major role in short-term plasma calcium regulation in coho salmon.
To obtain more information on the role of prolactin and growth hormone during the parr-smolt transformation of Atlantic salmon, a population of fish in fresh water was sampled from January to June during two consecutive years. Gill Na+,K+-ATPase activity increased steadily during smoltification and a plasma thyroxine peak was observed 2-3 weeks before the gill Na+,K+-ATPase peak. On the basis of these two parameters, smoltification was considered complete in our populations in April 1985 and May 1986. Two peaks in plasma growth hormone levels occurred in 1986, one in mid-April and the second in mid-May. In both cases, these peaks coincided with a peak in plasma triiodothyronine and preceded the thyroxine peak by 1-2 weeks. Moreover, the second peak which lasted for 1 month coincided with maximal gill Na+,K+-ATPase activity. A decrease in plasma prolactin levels was observed during smoltification of Atlantic salmon in 2 consecutive years. During this period of decreasing and low plasma prolactin levels, gill Na+,K+-ATPase activity increased to its highest values. Atlantic salmon smolts were also directly transferred into seawater. After 2 days or more in seawater, plasma prolactin levels were not significantly different from those on Day 0, whereas in fresh water they showed large fluctuations. All these data indicate that growth hormone may play an important role in the development of hypoosmoregulatory activity. Increased hypoosmoregulatory ability also appears to be associated with low prolactin levels.
A 26 year old man with no previous history of convulsions presented in status epilepticus and severe lactic acidosis. He regained consciousness and the acidosis resolved after several hours of conservative management without intravenous bicarbonate, but he developed severe myalgia associated with marked elevation of creatine kinase and moderate raised plasma creatinine levels which resolved spontaneously after 3 days. Severe lactic acidosis and rhabdomyolysis may accompany status epilepticus, although they appear to be self-limiting without important sequelae.