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Biomedical subjects

B Garrett

Publications and source records attributed to B Garrett.

At least 19 recordsLinked to original sources

A comparison of the calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients.

Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia and aluminum-based binders that result in total body aluminum accumulation over time. This investigation describes the use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis patients and compares it with a standard calcium-based phosphate binder. An open-label, randomized, crossover study was performed to evaluate the safety and effectiveness of sevelamer hydrochloride in controlling hyperphosphatemia in hemodialysis patients. After a 2-week phosphate binder washout period, stable hemodialysis patients were administered either sevelamer or calcium acetate, and the dosages were titrated upward to achieve improved phosphate control over an 8-week period. After a 2-week washout period, patients crossed over to the alternate agent for 8 weeks. Eighty-four patients from eight centers participated in the study. There was a similar decrease in serum phosphate values over the course of the study with both sevelamer (-2.0 +/- 2.3 mg/dL) and calcium acetate (-2.1 +/- 1.9 mg/dL). Twenty-two percent of patients developed a serum calcium greater than 11.0 mg/dL while receiving calcium acetate, versus 5% of patients receiving sevelamer (P < 0.01). The incidence of hypercalcemia for sevelamer was not different from the incidence of hypercalcemia during the washout period. Patients treated with sevelamer also sustained a 24% mean decrease in serum low-density lipoprotein cholesterol levels. Sevelamer was effective in controlling hyperphosphatemia without resulting in an increase in the incidence of hypercalcemia seen with calcium acetate. This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis patients, and its usage may be advantageous in the treatment of dialysis patients.

Acetic Acid↗

Effect of RenaGel, a non-absorbed, calcium- and aluminium-free phosphate binder, on serum phosphorus, calcium, and intact parathyroid hormone in end-stage renal disease patients.

BACKGROUND: Control of dietary phosphate absorption in end-stage renal disease patients is essential to prevent the deleterious sequelae of phosphorus retention. Efficacy of currently available calcium- and aluminium-containing phosphate binders is constrained by the side-effects associated with the absorption of calcium and aluminium. The current study examined the efficacy of RenaGel, a calcium- and aluminium-free, polymeric phosphate binder, in end-stage renal disease patients. METHODS: Administration of calcium- or aluminium-containing phosphate binders ceased during a 2-week washout period. RenaGel, at starting doses of one, two, or three 500-mg capsules three times per day with meals, was administered for 8 weeks. RenaGel dose was titrated up 1 capsule per meal at the end of each 2-week period if necessary to achieve phosphorus control. A second 2-week washout period followed the end of RenaGel treatment. RESULTS: Mean serum phosphorus rose from a pre-washout level of 6.9 mg/dl (2.23 mmol/l) to 8.1 mg/dl (2.62 mmol/l) at the end of the initial 2-week washout. With RenaGel treatment, serum phosphorus declined and returned to pre-washout levels after 4 weeks. Serum phosphorus reached a nadir of 6.5 mg/dl (2.10 mmol/l) after 7 weeks of RenaGel treatment. Serum phosphorus rose to 8.2 mg/dl (2.65 mmol/l) 2 weeks after cessation of RenaGel treatment. As anticipated, calcium declined during the initial washout period when calcium-based phosphate binders were stopped for the majority of patients. The rise in serum phosphorus and decline in serum calcium during washout resulted in an increase in median intact parathyroid hormone (iPTH) levels from 292 pg/ml to 395 pg/ml. iPTH fell to 283 pg/ml after 6 weeks of RenaGel treatment despite a persistently lower serum calcium. RenaGel treatment also reduced serum total and LDL cholesterol by 25 mg/dl (0.65 mmol/l) and 23 mg/dl (0.59 mmol/l) respectively. CONCLUSIONS: RenaGel appears to be an effective phosphate binder free of calcium and aluminium. Phosphorus control with two to four RenaGel capsules per meal appears to result in comparable phosphorus lowering seen with calcium- or aluminium-based phosphate binders. RenaGel may offer an alternative for the control of phosphorus retention in end-stage renal disease patients.

Adult↗

In situ hybridization for somatostatin mRNA in the adult rat: cingulate, insular, prepiriform, perirhinal, entorhinal, and retrosplenial cortical regions.

The expression of somatostatin mRNA within the allocortex of the rat was examined by in situ hybridization with an alkaline phosphatase labeled probe. We sought to determine whether parcellation of the allocortex could be based upon the number and laminar location of the hybridized cells and to contrast the allocortical features with those of the isocortical areas. The cingulate region was characterized by intense, moderate, and faint cells, small to medium in size throughout the laminae. The retrosplenial region demonstrated a somewhat stratified appearance with an abundance of cells expressing somatostatin mRNA in the upper portion of the composite layer II-IV and also in the upper portion of layer VI. The insular region displayed more heterogeneity. The distribution of the cells hybridized for somatostatin mRNA formed distinctive configurations within the insular region (dorsal and ventral agranular insular areas) with no obvious generality. The perirhinal area resembled the ventral agranular insular area, and the cell distribution of the entorhinal and prepiriform areas displayed a common characteristic in that the primary axis of the perikarya of somatostatin mRNA expressing cells within the lower layers were oriented at almost every possible angle. The conclusion of the investigation is that in situ hybridization for somatostatin mRNA provides a means by which the areal boundaries within the allocortex may be drawn.

Animals↗

Parcellation of cortical areas by in situ hybridization for somatostatin mRNA in the adult rat: frontal, parietal, occipital, and temporal regions.

The expression of somatostatin mRNA within the neocortex of the rat was examined by in situ hybridization with an alkaline phosphatase-labeled probe. We sought to determine whether parcellation of the neocortex could be based upon the number and laminar location of the hybridized cells. Our investigation demonstrated that the boundaries of the neocortical areas can be determined by the distribution pattern of neurons expressing somatostatin mRNA. Few hybridized cells were located within layer IV, and this sparsity of cells within their wide granular layer marked the primary sensory areas. The occipital region was stratified, with intensely labeled cells in layers II/III and VI and faintly labeled cells in layer V. The parietal region carried a similar stratification, but more space between intensely labeled cells in layers III and V and between layers V and VI gave the region a three-tiered appearance. The temporal region displayed intensely labeled cells dispersed throughout layers III and VI and many in layer V as well as those faintly labeled without any breaks between the laminae. The distribution of the cells hybridized for somatostatin mRNA formed two configurations within the frontal region. It was difficult to identify any lamination in the first area, whereas the second area demonstrated a stratification reminiscent of the parietal region, but with only two tiers. The conclusion of the investigation is that in situ hybridization fro somatostatin mRNA provides an exceptional means by which the area boundaries within the neocortex may be drawn.

Animals↗

Cytoarchitecture and staining for acetylcholinesterase and zinc in the visual cortex of the Parma wallaby (Macropus parma).

Cytoarchitecture and distributions of acetylcholinesterase-containing fibers and zinc-containing neuropil are described in the primary visual cortex of a metatherian, the Parma wallaby (Macropus parma). Although some cytoarchitectural features of layer III suggest that a subdivision and a corresponding layer IIIa-c terminology may be employed, neurochemistry is more concisely described using a simple layer I-VI terminology. Horizontal acetylcholinesterase-containing fibers in layer I take on a vertical course as they pass through layer II to form a reticulate pattern in upper layer III. Fibers gather into vertical groups in lower layer III and, markedly, in layer IV. No dominant orientation is seen in layer V, whereas an horizontal course is often seen in layer VI. Zinc-containing neuropil is very dense layers I, II and upper III, where particles are homogeneously distributed. Particles begin to form strands in lower layer III and form conspicuous vertical clusters in an otherwise almost unstained layer IV. There is a sharp transition to a densely and homogeneously stained layer V, a decrease in staining intensity in layer VI, and a further decrease within layer VI towards the white matter. The distribution of acetylcholinesterase-containing fibers in M. parma, a metatherian representative, adds to the number of species-specific patterns observed in eutherians. The distribution of zinc-containing neuropil in M. parma resembles the consistent pattern seen in eutherian species. Thus, pathways incorporating zinc, as a putative neuromodulator of excitatory amino acid receptor responses, may be organized similarly in the cortex of meta- and eutherians.

Acetylcholinesterase↗

Diversity of relative intensities of acetylcholinesterase staining within the laminae of the visual cortex of four mammals.

The histological staining patterns of acetylcholinesterase fibers in the visual cortex of the hamster, bank vole, yellow necked wood mouse, and rabbit are described. Between the species there are variations in staining intensities of the laminae in the visual cortex. In the hamster and bank vole layers IV, V, and VI are intensely stained. The yellow necked wood mouse demonstrates little difference in staining intensity between the layers of the visual cortex. The rabbit evidences a dense precipitate in the lower portion of layer IV and also in layer V. Staining intensity patterns suggest that the cholinergic afferents to the visual cortex may develop preferential innervation to laminae which receive low sensory stimulation during the formative period.

Acetylcholinesterase↗

Fluoro-Gold tracing of zinc-containing afferent connections in the mouse visual cortices.

To identify zinc-containing projections to the visual areas, we injected Fluoro-Gold into the occipital cortex of the mouse. Five days later, the mice underwent an intravital selenium-labeling procedure to demonstrate the somata of neurons that give rise to zinc-containing boutons. Numerous double-labeled cells were seen in the ipsi- and contralateral primary (layers II/III and VI), and secondary visual cortices (layers II/III and VI). A few double-labeled cells were apparent in other cortical areas concerned with visual processing: the orbital cortex (layers II and III), the posterior portion of the medial agranular frontal cortex (layer V/VI border), and the temporal cortex (layer VI). The cingulate, retrosplenial, perirhinal, and lateral entorhinal cortices had lamina projecting to the visual cortex and separate lamina harboring zinc-containing cells. A spatial segregation of fluorescent and zinc-containing neurons was also seen in the claustrum. This integration or segregation of projecting and zinc-containing neurons may reflect the function of the cortical areas. N-methyl-D-aspartate receptor function is antagonized by physiological concentrations of zinc in vitro. It is proposed that zinc-positive projections from areas that perform basic visual functions are less likely to be modified by N-methyl-D-aspartate receptor-mediated processes than the zinc-negative connections from associational areas.

Animals↗

Postnatal development of zinc-containing cells and neuropil in the visual cortex of the mouse.

The postnatal development of zinc-containing synaptic boutons and their cells of origin in the visual cortex of a pigmented mouse is described. Two phases can be distinguished. During the early phase zinc-containing neuropil is first apparent by postnatal day 3. By day 7 a light, but distinct neuropil staining sketches the primary and secondary visual cortices. The primary visual area contains light precipitate in layers V and VI as well as the monocular portion of layer II/III. The secondary visual areas contain slightly denser precipitate in layers II/III through VI. The transition to the second phase is marked by a large increase in precipitate density by day 11. Thereafter, the intensity of the neuropil staining increases to day 28, first in layer II/III and then in layer V, as the adult pattern of neuropil staining gradually develops. In the primary visual cortex precipitate is dense in layers II/III and V, moderate in layer VI, and sparse in layers I and IV. In the secondary visual areas the precipitate is dense in layers II/III and V and moderate in the lower portion of layer I and in layers IV and VI. Cells of origin of zinc-containing boutons are visible by the end of the second postnatal week in layer II/III of the secondary visual cortex. By 21 days of age the pattern of staining in the mature mouse is established, and cells in layers II/III and VI are labeled in both the primary and secondary visual cortices. The developmental sequence of zinc-containing cells and neuropil does not preclude an involvement of zinc in the postnatal regulation of NMDA receptor function.

Animals↗

Back injuries among nursing personnel: the relationship of personal characteristics, risk factors, and nursing practices.

Reducing the total number of work related back injuries among nurses is important, but reducing those injuries that are severe enough to result in lost time and/or disability is critical. Results of this study indicate that female nurses in the early phases of assignment on long term care units are at greatest risk for back injury, but risk factors that relate significantly to the severity of the injury are tour of duty (evening) and weight of the nurse (200 + pounds). Recommendations suggested by this study include: evaluation of lifting techniques and practices; orientation whenever assignments are changed; accurate assessment of nurse, client, and situation; and the regular use of an assessment tool which incorporates all of these factors.

Absenteeism↗

Distribution of acetylcholinesterase and zinc in the visual cortex of the mouse.

The distributions of acetylcholinesterase (AChE) and zinc-containing boutons and their cells of origin in the visual cortex of the house mouse (Mus musculus domesticus) are described. The primary visual area is defined by both acetylcholinesterase and zinc staining. The AChE staining pattern is dark in upper layer I and layers IV and VI. It is light in layers II/III and V. The lack of a densely stained layer IV in the secondary visual cortices defines the borders between primary and secondary areas. Large, multipolar AChE-positive neurons are located throughout the cortical layers, but preferentially in layer VI. Dense zinc-positive neuropil in the primary visual cortex is apparent in layer Ib, upper layer II/III, and layers V and VI. Neurons that give rise to zinc-containing boutons are situated in layers II/III and VI. The medial and lateral borders can be distinguished by a bold contrast of staining in lower layer II/III; the secondary areas have more zinc-positive neurons, and the neuropil stains darker. A surprising observation of this study is the disparity between the mouse and rat visual cortex of the AChE staining pattern. Layer V is very light in the mouse, whereas a dark stain has been described in layer V of the rat. Layer VI stains heavily in the mouse while less AChE activity has been observed in layer VI of the rat.

Acetylcholinesterase↗

Antihypertensive effectiveness of the nifedipine gastrointestinal therapeutic system.

The results of a multicenter trial conducted in order to determine the therapeutic efficacy of the gastrointestinal therapeutic system (GITS) formulation of nifedipine in comparison with hydrochlorothiazide and placebo in the management of mild to moderate essential hypertension are presented. During a one-week wash-out phase, antihypertensive therapy was discontinued in all patients. After a three-week single-blind placebo period, eligible patients were randomly assigned in a double-blind fashion to one of three treatment groups for a one-week titration period and a nine-week efficacy period. Patients received either nifedipine GITS, 30 or 60 mg daily; hydrochlorothiazide, 25 or 50 mg daily; or placebo. Sitting and standing blood pressures decreased by an average 11.6/10.4 and 10.8/10.8 mm Hg, respectively, with nifedipine GITS therapy, and 14.8/10.8 and 14.3/8.2 mm Hg, respectively, with hydrochlorothiazide therapy. Compared with placebo, these changes were highly significant for both sitting (p less than or equal to 0.005) and standing (p less than or equal to 0.02) measurements. Heart rate remained essentially unchanged in all three groups. It was therefore concluded that monotherapy with nifedipine GITS, at doses of 30 or 60 mg given once daily, effectively reduces blood pressure in patients with hypertension to a degree comparable with that seen in hydrochlorothiazide therapy.

Adult↗

Isolation of Mycoplasma pulmonis membranes and identification of surface antigens.

Labeling of Mycoplasma pulmonis cells by iodination with the Bolton-Hunter reagent was shown to efficiently label membrane-associated proteins without significant loss of viability. Labeled proteins proven to be surface exposed by differential proteolytic digestion were analyzed by autoradiography of two-dimensional polyacrylamide gel electrophoresis (PAGE), and seven labeled major polypeptides were identified. To identify all the membrane-associated antigens, pure membranes were isolated by using the surface-labeled proteins as markers. Analysis of the isolated membranes by autoradiography of both sodium dodecyl sulfate-PAGE and the two-dimensional PAGE indicated that the labeled surface proteins were retained in the pure membranes; by immunoblotting with sera from naturally infected animals, these surface proteins were shown to be the predominant antigens recognized by the host during natural infection.

Antigens, Bacterial↗