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Biomedical subjects

G Brown

Publications and source records attributed to G Brown.

At least 181 records · Page 10Linked to original sources
PubMed1997

Diode laser photocoagulation for retinopathy of prematurity.

OBJECTIVE: The purpose of this study was to determine the effectiveness of laser photocoagulation in eyes with threshold retinopathy of prematurity (ROP), defined as stage 3+, zone 2, with 5 or more contiguous or 8 cumulative clock hours of extraretinal fibrovascular proliferation. METHODS: Indirect ophthalmoscopic retinal examinations were performed on 18 premature infants born between 1991 and 1993 to identify those eyes with threshold ROP. Diode laser was used to treat 31 eyes within 48 hours of diagnosis. Each patient was followed post treatment at weekly intervals until regression was starting to occur. Subsequent follow-up visits were tailored to each patient. RESULTS: During the 41 to 60 month follow-up (average 49 months, median 46 months), 27 of 31 lasered eyes (87%) demonstrated regression of the extraretinal neovascularization, and 26 (84%) had functional vision. This includes two Stage 4B eyes that were reattached with scleral buckles. Twenty-two eyes (71%) were myopic and four (13%) progressed to stage 5 retinal detachment that could not be repaired. No cataracts occurred in this group of patients. CONCLUSIONS: Although a potentially blinding disorder, threshold ROP is, in many cases, treatable with laser photocoagulation, which may be easier to administer than cryotherapy. Follow-up of patients treated with diode laser demonstrates that functional vision is attainable.

Follow-Up Studies↗
PubMed1996

External radiotherapy in macular degeneration: technique and preliminary subjective response.

PURPOSE: This study attempted to assess the toxicity and possible preliminary benefits from the administration of low-dose external beam irradiation for age-related macular degeneration (ARMD). The premise of the treatment is that radiation induces regression and/or promotes inactivation of the subretinal neovasculature which would result in reabsorption of fluid and blood. This would reduce the risk for further leakage or bleeding, as well as subretinal fibrosis. Consequently, the beneficial effect could be translated into stabilization of visual acuity and prevention of progression of the wet ARMD with the possibility for slight improvement. METHODS AND MATERIALS: Allegheny University Department of Radiation Oncology treated 41 patients prospectively from January through October 1995 with low-dose irradiation for wet-type macular degeneration. A total of 39 patients were treated with a total dose of 14.4 Gy in eight fractions of 1.8 Gy/fraction over 10-13 elapsed days. The first two patients were treated with a total dose of 10 Gy in five fractions of 2 Gy. Patients were evaluated at 2-3 weeks and 2-3 months. Some of the patients (36.7%) had laser treatments in the study eye: 21.9% (9) once, 5% (2) twice, 9.7% (4) thrice or more. Subjective visual acuity and toxicity data were collected on all patients. RESULTS: At 2-3 weeks after treatment 29 patients (70%) retained their visual acuity without change, 10 (24.5%) stated they had improved vision, and 2 (4.8%) stated their vision continued to decrease. At 2-3 months after treatment, 27 patients (65.8%) had no change in their vision, 11 (27%) had an improvement in their vision, and 3 (7.2%) had a decrease in visual acuity. Six patients of 41 in the treated group had acute transient side effects. CONCLUSION: Our observations in this group of 41 patients support the conclusion that many patients will have improved or stable vision after treatment with low-dose irradiation for age-related wet-type macular degeneration.

Adult↗
PubMed1996

Low birth weight and neurocognitive status at six years of age.

We examined the relationship between low birth weight (LBW) (< or = 2500 g) and specific neurocognitive abilities at 6 years of age in a large-scale nonconcurrent prospective study. In 1990-1992, we randomly selected and evaluated LBW and normal birth weight (NBW) children from the 1983-1985 newborn lists of two major hospitals in southeast Michigan, one serving an urban and the other a suburban population. LBW children (n = 473) scored significantly lower than NBW children (n = 350) on tests measuring language, spatial, fine motor, tactile, and attention abilities, controlling for population site, race, maternal IQ, and education. Gradient relationships were observed across levels of LBW with language, spatial, tactile, and attention tests. Exploratory analysis, using general additive models, revealed that test performance varied within birth weight levels and that performance continued to improve with increased birth weight well above 3000 g. Follow-up assessments as the children mature will shed light on the persistence of these associations and their implications for learning disorders.

Attention↗
PubMed1996

Insulin exocytosis and glucose-mediated increase in cytoplasmic free Ca2+ concentration in the pancreatic beta-cell are independent of cyclic ADP-ribose.

Stimulation of pancreatic beta-cells by glucose gives rise to an increase in the cytoplasmic free calcium concentration ([Ca2+]i) and exocytosis of insulin. Cyclic adenosine 5'-diphosphate ribose (cADPR), a metabolite of beta-NAD+, has been reported to increase [Ca2+]i in pancreatic beta-cells by releasing Ca2+ from inositol 1,4,5-trisphosphate-insensitive intracellular stores. In the present study, we have examined the role of cADPR in glucose-mediated increases in [Ca2+]i and insulin exocytosis. Dispersed ob/ob mouse beta-cell aggregates were either pressure microinjected with fura-2 salt or loaded with fura-2 acetoxymethyl ester, and [Ca2+]i was monitored by microfluorimetry. Microinjection of beta-NAD+ into fura-2-loaded beta-cells did not increase [Ca2+]i nor did it alter the cells' subsequent [Ca2+]i response to glucose. Cells microinjected with the cADPR antagonist 8NH2-cADPR increased [Ca2+]i in response to glucose equally well as those injected with cADPR. Finally, the ability of cADPR to promote exocytosis of insulin in electropermeabilized beta-cells was investigated. cADPR on its own did not increase insulin secretion nor did it potentiate Ca2+-induced insulin secretion. We conclude that cADPR neither plays a significant role in glucose-mediated increases in [Ca2+]i nor interacts directly with the molecular mechanisms regulating exocytosis of insulin in normal pancreatic beta-cells.

Adenosine Diphosphate Ribose↗
PubMed1996

Potentiation of myeloid differentiation by anti-inflammatory agents, by steroids and by retinoic acid involves a single intracellular target, probably an enzyme of the aldoketoreductase family.

HL60 cells are human promyeloid cells that can be induced to differentiate by physiological stimuli (e.g. all-trans retinoic acid (ATRA), 1 alpha,25-dihydroxyvitamin D3 (D3), granulocyte colony-stimulating factor (G-CSF)) and by non-physiological agents such as dimethysulphoxide (DMSO) and protein kinase C-activating phorbol esters. The sensitivity of HL60 cells to physiological differentiating agents, but not to DMSO, is enhanced when cells are exposed to 'anti-inflammatory agents' (e.g. indomethacin) or are 'primed' (pretreated) with a small amount of ATRA: alone, neither treatment induces differentiation. We earlier suggested that indomethacin might act by inhibiting the endogenous formation of a differentiation-suppressing prostanoid (Bunce, C.M., et al. (1994) Leukemia 8, 595-604). Studies of the formation of prostanoids by HL60 cells and of the effects of prostanoids on these cells failed to identify any prostanoid that could be implicated in sensitization by indomethacin. 3 alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) is another target of such 'anti-inflammatory agents'. Steroid inhibitors of 3 alpha-HSD sensitized HL60 cells to inducers of differentiation in a manner similar to indomethacin. 3 alpha-HSD is a member of the aldoketoreductase enzyme family, which comprises many enzymes of similar size and primary sequence. A protein that was recognised by an antiserum to 3 alpha-HSD was found in HL60 cells, but the cells showed no detectable 3 alpha-HSD activity. The 3 alpha-HSD-like protein was strikingly down-regulated by 'priming' doses of ATRA. When treatment with a differentiation-sensitizing 'anti-inflammatory agent' or steroid was combined with ATRA "priming', the effects of the different treatments were not additive: the resulting increase in sensitivity equalled that achievable by either treatment alone. We conclude that interference with a single intracellular regulatory mechanism underlies the increases in sensitivity of cells to differentiating agents that are caused by anti-inflammatory agents, by certain steroids and by 'priming' with ATRA. Decreased activity of a yet-to-be-identified member of the aldoketoreductase family of dehydrogenases is likely to be a central feature of a previously unrecognised mechanism that controls the responsiveness of cells to environmental stimuli such as retinoids and D3.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4- isoxazoleproprionate (AMPA) glutamate-receptor antagonists have different interactions with the discriminative stimuli of abused drugs.

The effects of the AMPA-receptor antagonists NBQX and GYKI 52466 were compared with those of the NMDA-receptor channel blocker dizocilpine in two drug discrimination tests. In the first, rats were trained to discriminate morphine (2 mg/kg) from saline and in the second, to discriminate ketamine (7 mg/kg) from saline, using a two-lever food reinforced method. NBQX (1-6 mg/kg) did not substitute for either morphine or ketamine, even at a dose which reduced response rates (6 mg/kg). Likewise, the noncompetitive antagonist GYKI 52466 (5 and 10 mg/kg) produced only saline lever responding in the ketamine trained rats. When tested in combination with the training drug, NBQX (4.5 mg/kg) did not alter the morphine generalisation gradient, and similarly, neither NBQX (3 mg/kg) nor GYKI 52466 (5 and 10 mg/kg) interacted with the ketamine cue. In contrast, dizocilpine (0.05 mg/kg) significantly disrupted discrimination of morphine and produced clear drug lever responding (0.0125-0.1 mg/kg) in ketamine trained rats. These results suggest that AMPA-receptor antagonists and non-competitive NMDA-antagonists have different stimulus properties.

Analysis of Variance↗
PubMed1996

Electrophysiological, biochemical, neurohormonal and behavioural studies with WAY-100635, a potent, selective and silent 5-HT1A receptor antagonist.

Although considerable progress has been made in characterising the 5-HT1A receptor using agonists, partial agonists or non-selective antagonists, further studies of 5-HT1A receptor function have been hindered by the lack of highly selective antagonists. The term 'silent' antagonist has been used for such compounds in order to distinguish them unequivocally from several 5-HT1A receptor partial agonists which were initially designated 'antagonists'. In this report we provide a comprehensive review of the biochemical, pharmacological and behavioural properties of the first potent, selective and silent 5-HT1A receptor antagonist, WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2- pyridinyl)cyclohexanecarboxamide trihydrochloride). WAY-100635 had an IC50 (displacement of specific [3H]8-OH-DPAT binding to 5-HT1A receptors in the rat hippocampus) of 1.35 nM and was > 100-fold selective for the 5-HT1A site relative to a range of other CNS receptors. [3H]WAY-100635 was also characterised as the first 5-HT1A antagonist radioligand, displaying the same regional distribution of binding sites as [3H]8-OH-DPAT in rat brain. As would be expected for the binding of an antagonist to a G-protein-coupled receptor, the Bmax of [3H]WAY-100635 specific binding was consistently 50-60% greater than that of the agonist radioligand, [3H]8-OH-DPAT. Mn2+, but not guanine nucleotides, inhibited [3H]WAY-100635-specific binding. [3H]WAY-100635 was also shown to bind selectively to brain 5-HT1A receptors in vivo, following intravenous administration to mice. In vitro electrophysiological studies demonstrated that WAY-100635 had no 5-HT1A receptor agonist actions, but dose-dependently blocked the effects of agonists at both the postsynaptic 5-HT1A receptor in the CA1 region of the hippocampus, and the somatodendritic 5-HT1A receptor located on dorsal raphe 5-HT neurones. In vivo, WAY-100635 also dose-dependently blocked the ability of 8-OH-DPAT to inhibit the firing of dorsal raphe 5-HT neurones, and to induce the '5-HT syndrome', hypothermia, hyperphagia and to elevate plasma ACTH levels. In the mouse light/dark box anxiety model, WAY-100635 induced anxiolytic-like effects. WAY-100635 had no intrinsic effect on cognition in the delayed-matching-to-position model of short-term memory in the rat, but reversed the disruptive effects of 8-OH-DPAT on motor motivational performance. These data clearly demonstrate that WAY-100635 is the first potent, selective and silent 5-HT1A receptor antagonist. Furthermore, [3H]WAY-100635 is the first antagonist radioligand to become available for 5-HT1A receptor binding studies both in vitro and in vivo. The positive effects of WAY-100635 in an anxiety model also indicate that a postsynaptic 5-HT1A receptor antagonist action may contribute to the anxiolytic properties of 5-HT1A receptor partial agonists.

Adrenocorticotropic Hormone↗
PubMed1996

Growth of single HL60 cells in liquid culture: analysis of the influences of differentiative agents.

Treatment of serum-free grown HL60 cells with certain combined amounts of retinoic acid (9-cis or all-trans RA) and 1 alpha 25 dihydroxyvitamin D3 (D3) results in differentiation of 71-77% of cells towards either neutrophils or monocytes. Studies of the differentiation of HL60 cells in flask cultures does not reveal: (i) the extent to which selective growth of cells might have occurred; and (ii) the overall level of cell survival. This information can be obtained by monitoring the effects of differentiative agents on individual cells. Serum-free grown HL60 cells were cultured as single cells in microtitre wells in conditioned medium obtained from exponentially growing and serum-free cultures of HL60. This resulted in a cloning efficiency of 85% and HL60 cells doubled every 24 h. During a period of exponential growth < 0.5 to 2% of the cells generated died. Single HL60 cells were treated with 9-cis and all-trans RA (5 x 10(-7) M) together with a small amount of D3 (3.9 x 10(-14) M) to promote neutrophil differentiation. D3 alone (10(-7) M) and D3 (5 x 10(-9) M) in combination with 9-cis RA (10(-8) M) were used to promote monocyte differentiation. The growth kinetics of HL60 cell cultures that were differentiating to neutrophils and to monocytes were similar. Single-cell experiments have revealed that: (i) differentiating HL60 cells undergo a variable number of divisions (two to five) prior to arresting their growth; and (ii) up to 33% of the cells that are generated (by day 5) die. Seventy to eighty per cent of the cells in each of the wells had matured. These findings have important implications in regard to whether retinoids and D3 provide signals that determine the choice of maturation pathway or that merely facilitate selective survival and/or expansion of cells that have independently determined their differentiation fates.

Cell Differentiation↗
PubMed1996

Does once-daily dosing of aminoglycosides affect neuromuscular function?

OBJECTIVE: Aminoglycosides have been reported to produce a curare-like neuromuscular blockade in animals at serum concentrations higher than those obtained with traditional dosing (1-2 mg/kg every 8 h) in humans. Aminoglycoside-induced neuromuscular blockade is rarely, if ever, seen in humans with traditional dosing. The recent adoption of once-daily dosing of aminoglycosides has raised concerns about increased potential for this adverse effect because higher serum concentrations are produced. The objective of this study was to determine if once-daily dosing of aminoglycosides inhibits respiratory muscle function. METHOD: Nine mechanically ventilated ICU patients on once-daily dosing of gentamicin 6 mg/kg/day were assessed for respiratory muscle strength by measuring maximum inspiratory pressure (MIP). MIP is a measurement of the maximal negative pressure generated by repeated inhalations against an occluded airway over 20 s. This was measured within 1 hour before (MIPpre) and within 1 hour after each aminoglycoside dose (MIPpost). RESULTS: Mean values for MIPpre and MIPpost were -26.7 cm H2O and -26.5 cm H2O, respectively. The mean difference between MIPpre and MIPpost was -0.2 cm H2O, which was not statistically significant (P > 0.05). CONCLUSION: The effect of gentamicin (6 mg/kg/day) on respiratory muscle function was not statistically, nor clinically significant, and weaning from mechanical ventilation does not seem to be inhibited by once-daily dosing of aminoglycosides as detectable by measurement of MIP.

Anti-Bacterial Agents↗
PubMed1996

Continuous infusion of methylene blue for septic shock.

Nitric oxide has been determined to be a potential mediator of the haemodynamic changes associated with sepsis. The haemodynamic eects of nitric oxide can be partially antagonised by methylene blue, through inhibition of the enzyme, guanylate cyclase. The case report presented here demonstrates a beneficial haemodynamic eect of continuous infusion of methylene blue during sepsis. These findings could be extrapolated to other patients or prompt additional research.

Antidotes↗
PubMed1996

The economic impact of once-daily versus conventional administration of gentamicin and tobramycin.

This retrospective, observational study was designed to compare once-daily with conventional aminoglycoside administration for costs while determining equivalency in efficacy and toxicity. 100 consecutive patients who had been treated with once-daily aminoglycosides after 1st August 1993, were evaluated via retrospective chart review. For comparison, 100 consecutive patients who were treated with conventional regimens of aminoglycosides, over the same calender period 1 year earlier (beginning on 1st August 1992), were evaluated in a similar manner. Aminoglycoside antibacterials, excluding amikacin, were administered as a single daily dose of 6 mg/kg. 89 patients were cured or improved with once-daily administration versus 90 patients with conventional administration. One patient in each group developed definite aminoglycoside-induced renal toxicity. The total cost [in 1993 Canadian dollars ($Can)] per patient for once-daily and conventionally administered aminoglycosides was $Can97.62 and $ Can199.43, respectively. Thus, once-daily administration of aminoglycosides is as effective and well tolerated, while considerably less expensive than, aminoglycoside treatment utilising conventional regimens.

Cost-Benefit Analysis↗
PubMed1996

Harmonization of animal clinical pathology testing in toxicity and safety studies. The Joint Scientific Committee for International Harmonization of Clinical Pathology Testing.

Ten scientific organizations formed a joint international committee to provide expert recommendations for clinical pathology testing of laboratory animal species used in regulated toxicity and safety studies. For repeated-dose studies in rodent species, clinical pathology testing is necessary at study termination. Interim study testing may not be necessary in long-duration studies provided that it has been done in short-duration studies using dose levels not substantially lower than those used in the long-duration studies. For repeated-dose studies in nonrodent species, clinical pathology testing is recommended at study termination and at least once at an earlier interval. For studies of 2 to 6 weeks in duration in nonrodent species, testing is also recommended within 7 days of initiation of dosing, unless it compromises the health of the animals. If a study contains recovery groups, clinical pathology testing at study termination is recommended. The core hematology tests recommended are total leukocyte (white blood cell) count, absolute differential leukocyte count, erythrocyte (red blood cell) count, evaluation of red blood cell morphology, platelet (thrombocyte) count, hemoglobin concentration, hematocrit (or packed cell volume), mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. In the absence of automated reticulocyte counting capabilities, blood smears from each animal should be prepared for reticulocyte counts. Bone marrow cytology slides should be prepared from each animal at termination. Prothrombin time and activated partial thromboplastin time (or appropriate alternatives) and platelet count are the minimum recommended laboratory tests of hemostasis. The core clinical chemistry tests recommended are glucose, urea nitrogen, creatinine, total protein, albumin, calculated globulin, calcium, sodium, potassium, total cholesterol, and appropriate hepatocellular and hepatobiliary tests. For hepatocellular evaluation, measurement of a minimum of two scientifically appropriate blood tests is recommended, e.g., alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, glutamate dehydrogenase, or total bile acids. For hepatobiliary evaluation, measurement of a minimum of two scientifically appropriate blood tests is recommended, e.g., alkaline phosphatase, gamma glutamyltransferase, 5' -nucleotidase, total bilirubin, or total bile acids. Urinalysis should be conducted at least once during a study. For routine urinalysis, an overnight collection (approximately 16 hr) is recommended. It is recommended that the core tests should include an assessment of urine appearance (color and turbidity), volume, specific gravity or osmolality, pH, and either the quantitative or semiquantitative determination of total protein and glucose. For carcinogenicity studies, only blood smears should be made from unscheduled sacrifices (decedents) and at study termination to aid in the identification and differentiation of hematopoietic neoplasia.

Animal Welfare↗
PubMed1996

Chemical treatment of cavity walls following manual excavation of carious dentin.

PURPOSE: To improve the conditioning of cavity walls resulting from minimal mechanical preparation of carious lesions, such as is done in modified Class II tunnel preparations. MATERIALS AND METHODS: Proximal carious lesions in premolars and molars were excavated manually and the cavity walls studied using a stereomicroscope and by scanning electron microscopy (SEM) following treatment with either polyacrylic acid, sodium hypochlorite, the enzyme preparation Pronase, or sequential combinations of the agents. Polyacrylic acid (10%) was used according to the manufacturer's instructions, while concentrated sodium hypochlorite (5.25%) was applied with either intermittent scrubbing or with ultrasonic energy for 5-10 minutes, or the cavity wall was incubated with the agent at +/- 37 degrees C for periods up to 24 hours. Incubation with the proteolytic enzyme preparation Pronase was carried out at 37 degrees C for a period up to 48 hours. RESULTS: Manual excavation did not remove all carious dentin, neither did treatment with polyacrylic acid. Scrubbing or sonication with ample amounts of sodium hypochlorite, followed by treatment with polyacrylic acid, or prolonged incubation with sodium hypochlorite, removed most of the remaining carious dentin. However, the "cleanest" surfaces were obtained after 48 hours of incubation with Pronase. Spots of thicker, soft layers of decayed dentin that were left intentionally at some locations could be disintegrated only by the Pronase treatment. It was concluded that treatment with sodium hypochlorite and polyacrylic acid in tandem, or with Pronase may represent potential supplements to conventional cavity cleaning that deserve further investigation. In the clinic more efficient cavity cleaning may improve the bonding ability and thus reduce the risk of marginal ridge fracture in teeth with Class II tunnel restorations.

Acrylic Resins↗
PubMed1995

Exercise capacity and skeletal muscle structure and function before and after balloon mitral valvuloplasty.

This study evaluated the effects of balloon mitral valvuloplasty (BMV) on exercise capacity and skeletal muscle structure and function in 10 subjects with mitral stenosis (mean age +/- SD 33 +/- 5.5). Measurements were obtained before, and 2 weeks and 4 months after BMV to provide baseline data, to examine the effects of improved hemodynamics, and to examine the effects of resumption of normal physical activity, respectively. Valvuloplasty caused an increase in mitral valve area (0.89 +/- 0.04 to 1.75 +/- 0.07 cm2; mean +/- SE), and an increase in resting cardiac output (3.8 +/- 0.18 to 4.6 +/- 0.19 L/min, p < 0.05). At early follow-up after 2 weeks, subjects did more work (31% increase, p < 0.01) and had greater maximal oxygen consumption (11% increase, p < 0.01). However, measurements reflecting skeletal muscle histology, biochemistry, and function were unaltered at this stage. Four months after BMV, subjects had a further increase in exercise capacity compared with both baseline (58% increase, p < 0.01) and early follow-up (20% increase, p < 0.05). There were associated late increases compared with baseline in quadriceps cross-sectional area (66 +/- 5.8 vs 61 +/- 5.5 cm2, p < 0.05) and torque production (125 +/- 14 vs 118 +/- 16 Nm, p < 0.05). The percentage of slow twitch type I fibers increased compared with baseline (41 +/- 2.0% vs 33 +/- 3.1%, p < 0.05), as did the size of type II fibers (5.9 +/- 0.49 vs 4.9 +/- 0.57 microns2 x 10(3), p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗