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Biomedical subjects

D J Fletcher

Publications and source records attributed to D J Fletcher.

At least 19 recordsLinked to original sources
PubMed1995

Incidence of acute care complications in vertebral column fracture patients with and without spinal cord injury.

STUDY DESIGN: This study retrospectively analyzed vertebral column fractures in trauma patients during a 2-year period. Data from a multicenter trauma registry were used. OBJECTIVES: The purpose of this study was to ascertain and describe the initial in-hospital morbidity and mortality rates for patients with vertebral column fractures with and without spinal cord injury. SUMMARY OF BACKGROUND DATA: Patients with vertebral fractures and associated spinal cord injuries experience more medical complications than those without spinal cord injuries. However, the precise incidence and relative risk of complications during acute care hospitalization for these two groups are not well documented. METHODS: Vertebral column fractures in 419 adolescent and adult trauma patients hospitalized during a 2-year period were retrospectively analyzed using data from a multicenter trauma registry. RESULTS: Of the 419 patients, 104 (24.8%) had an associated spinal cord injury. More than half of the spinal cord injury patients (52.9%) and 20.6% of those without spinal cord injury had one or more complications during their hospitalization. Complications resulted in an average of 33.1 extra hospital days, which extrapolates nationally into 1.5 million additional days annually. The four complications differing most significantly in incidence between the spinal cord injury group and the non-spinal cord injury group were: urinary tract infections (24.0% vs. 8.6%), respiratory (23.1% vs. 8.6%), cardiac (11.5% vs. 3.2%), and decubitus ulcer (7.7% vs. 1.0%). Pneumonia, although not statistically different, was high in both groups (13.5% vs. 7.3%). CONCLUSIONS: The incidence of the 25 types of medical complications reported here provides specific and relevant information to assist health professionals in treating patients during their acute care. We estimate that complications during initial hospitalization add $1.5 billion annually to the cost of caring for patients with vertebral fractures in the United States.

Adolescent↗
PubMed1995

Improved method for computation of potentials in a realistic head shape model.

The Lead Field Analysis (LFA) algorithm, a new computational technique for the calculation of potentials on the surface of a realistic head shaped volume conductor model based on the Boundary Element Method and the Reciprocity Theorem, is presented. The new algorithm, in comparison to the Standard Boundary Element Method, offers improved computational efficiency and lower storage requirements. It also yields more accurate surface potential results in the face of varying dipole source locations for a head shape Boundary Element model with a given number of nodes. Additionally, the algorithm results in quasi-analytic expressions of the derivatives of the surface potential with respect to the location of the sources, allowing the use of optimization techniques with better convergence properties. A set of simulations demonstrating the increased robustness of the LFA Algorithm in the face of varying dipole source parameters is also described.

Algorithms↗
PubMed1995

MCF-7 breast cancer cells transfected with protein kinase C-alpha exhibit altered expression of other protein kinase C isoforms and display a more aggressive neoplastic phenotype.

Increased protein kinase C (PKC) activity in malignant breast tissue and positive correlations between PKC activity and expression of a more aggressive phenotype in breast cancer cell lines suggest a role for this signal transduction pathway in the pathogenesis and/or progression of breast cancer. To examine the role of PKC in the progression of breast cancer, human MCF-7 breast cancer cells were transfected with PKC-alpha, and a group of heterogenous cells stably overexpressing PKC-alpha were isolated (MCF-7-PKC-alpha). MCF-7-PKC-alpha cells expressed fivefold higher levels of PKC-alpha as compared to parental or vector-transfected MCF-7 cells. MCF-7-PKC-alpha cells also displayed a substantial increase in endogenous expression of PKC-beta and decreases in expression of the novel delta- and eta-PKC isoforms. MCF-7-PKC-alpha cells displayed an enhanced proliferative rate, anchorage-independent growth, dramatic morphologic alterations including loss of an epithelioid appearance, and increased tumorigenicity in nude mice. MCF-7-PKC-alpha cells exhibited a significant reduction in estrogen receptor expression and decreases in estrogen-dependent gene expression. These findings suggest that the PKC pathway may modulate progression of breast cancer to a more aggressive neoplastic process.

Animals↗
PubMed1995

Phorbol esters induce death in MCF-7 breast cancer cells with altered expression of protein kinase C isoforms. Role for p53-independent induction of gadd-45 in initiating death.

Protein kinase C (PKC) modulates growth, differentiation and apoptosis in a cell-specific fashion. Overexpression of PKC-alpha in MCF-7 breast cancer cells (MCF-7-PKC-alpha cell) leads to expression of a more transformed phenotype. The response of MCF-7 and MCF-7-PKC-alpha cells to phorbol esters (TPA) was examined. TPA-treated MCF-7 cells demonstrated a modest cytostatic response associated with a G1 arrest that was accompanied by Cip1 expression and retinoblastoma hypophosphorylation. While p53 was detected in MCF-7 cells, evidence for TPA-induced stimulation of p53 transcriptional activity was not evident. In contrast, TPA treatment induced death of MCF-7-PKC-alpha cells. Bryostatin 1, another PKC activator, exerted modest cytostatic effects on MCF-7 cells while producing a cytotoxic response at low doses in MCF-7-PKC-alpha cells that waned at higher concentrations. TPA-treated MCF-7-PKC-alpha cells accumulated in G2/M, did not express p53, displayed decreased Cip1 expression, and demonstrated a reduction in retinoblastoma hypophosphorylation. TPA-treated MCF-7-PKC-alpha cells expressed gadd-45 which occurred before the onset of apoptosis. Thus, alterations in the PKC pathway can modulate the decision of a breast cancer cell to undergo death or differentiation. In addition, these data show that PKC activation can induce expression of gadd45 in a p53-independent fashion.

Apoptosis↗
PubMed1994

Management of multisite occupational health services. A hospital/private clinic perspective: changing trends for the 1990s.

A strong regional program can be successful in either a single location or at multiple locations, but it cannot function properly if it is not well organized and staffed properly to deliver services. Extremely important elements to the success of an occupational health clinic that serves a wide geographical region are client retention, a strong information system to manage programs for multiple employers, and cutting-edge leadership that stays in the forefront and educates the business community on emerging issues in occupational health and safety.

Accidents, Occupational↗
PubMed1991

Age-dependent expression of protein kinase C isoforms in rat islets.

The appearance of the biphasic insulin secretory response several days after birth suggests that maturation of a critical step in stimulus-secretion coupling occurs during the early neonatal period. To clarify the role of protein kinase C (PKC) during this time, we examined the pancreatic islets of adult, 3-day neonatal, and 19-day fetal rats for the presence of different PKC isoenzymes. Western-blot analysis of islet extracts showed the presence of PKC isoforms in both adult and neonatal tissues. Immunocytochemistry of adult islets revealed a differential expression in islet cell types. PKC-alpha was found only in beta-cells, PKC-gamma in alpha-cells, and PKC-epsilon in delta-cells and vascular walls. Immunoreactivity for PKC-beta was not detected in any cell type. All three isoenzymes were also present in neonatal islets; however, in contrast to adult tissue, immunoreactivity for either PKC-alpha or PKC-gamma was present in relatively few cells. There was no apparent immunoreactivity for PKC-alpha or PKC-gamma in fetal islets, although these tissues contained strong staining for insulin and glucagon. These data show that three of the PKC isoforms are restricted to a particular islet cell type, where they may play a unique role in the secretion of a specific hormone. Moreover, our results demonstrate that these enzymes, especially PKC-alpha, appear during the early neonatal period. This age-dependent expression may be linked to the development of the biphasic insulin release response.

Aging↗
PubMed1990

Effects of combined secretagogues and extracellular calcium on neonatal insulin release.

The insulin response of 3-day old neonatal rat islets was evaluated following a 1 h incubation with glucose alone and in the presence of 30 nM sulfated cholecystokinin octapeptide (CCK) and/or 20 microM carbachol (CCh). Insulin secretion was found to be incrementally increased from the lowest glucose concentration and enhanced several fold in the presence of CCK and/or CCh. In combination, CCK and CCh increased glucose-stimulated insulin secretion by an amount equivalent to the sum of their individual increases. The presence of either CCK alone or CCK plus CCh increased phosphoinositide hydrolysis by the same relative amount that they increased insulin secretion when compared to 8.3 mM glucose. Glucose-stimulated insulin secretion was totally inhibited when calcium was omitted from the incubation buffer; this effect was partially negated by CCK alone and more so by CCK combined with CCh. Insulin secretion in response to 8.3 mM glucose alone was unchanged when calcium in the incubation buffer was increased from 1 to 5 mM; however, the insulin response to 16.7 mM glucose alone and 8.3 mM glucose in the presence of CCK and/or CCh was increased under this condition. Thus, we have shown that, even at 3 days postpartum, insulin secretion from isolated islets is a complex response capable of being molded by several secretagogues at once and ultimately determined by interplay of different signaling systems activated.

Animals↗
PubMed1990

Factorial designs for crossover clinical trials.

When measuring the joint effect of two factors it is advantageous to use a factorial design. If the application is suitable, efficiency may be further improved by using a crossover design. This paper presents a flexible method for amalgamating these two devices. Designs are constructed from smaller designs, known as bricks, generated cyclically from tabulated initial sequences. The bricks have known efficiencies for estimation of direct treatment main effects and interactions; the efficiencies can be simply combined to approximate the efficiencies of the whole design. This allows the user to build a design that is tailored to the particular objectives of the experiment. Three and four periods, and two factors with up to four levels are considered.

Antihypertensive Agents↗
PubMed1989

Age-dependent stimulation of neonatal insulin release and inositol phosphate accumulation by CCK-8 and carbachol.

Development of a robust insulin secretory response to glucose occurs during the early neonatal period. To determine if neuroendocrine agents play a role during this time, we studied the effects of selected peptides and neurotransmitters on insulin release and polyphosphoinositide metabolism in islets isolated from 1- and 3-day neonatal rats. Vasoactive intestinal peptide had no effect on glucose-stimulated release in either islet population. In contrast, sulfated cholecystokinin octapeptide (CCK-8) significantly enhanced glucose-induced insulin release in both islet groups. One-day islets were stimulated only by a concentration of 300 nM, whereas 3-day islets were responsive at 3 nM. Similar to CCK-8, there were clear differences in responses to carbachol between 1- and 3-day islets. One-day islets required a concentration of 200 microM for insulin release to be significantly greater than with glucose alone; 3-day islet insulin release was significant at 2 microM carbachol. Both agonists stimulated inositol phosphate accumulation in 3-day islets, but only CCK-8 caused a significant increase over glucose-induced levels in 1-day islets. These results indicate that islet responsiveness to CCK-8 and carbachol develops in parallel during the early neonatal period. This development may be linked to the maturation of a critical step of stimulus-secretion coupling through which these agents act.

Age Factors↗
PubMed1989

Regulation of insulin and interleukin-1 release after Propionibacterium acnes-induced macrophage activation in mice.

The administration of a potent activator of macrophages (M phi), Propionibacterium acnes, in nondiabetic mice was associated with the release of significant amounts of interleukin-1 (IL-1) in the peritoneal cavity and plasma within 4 hours after treatment. Shortly before IL-1 peaks were observed, the levels of pancreatic insulin, [3H]leucine-proinsulin, and insulin/total protein ratio were elevated, and followed by a transient but marked hyperinsulinemia at 4 hours after treatment. A single dose of recombinant murine IL-1 in mice was also associated with a 2- to 9-fold increase in the levels of insulin in the pancreas and plasma at 4 hours after treatment. During the period of observation after the administration of P. acnes, plasma glucose levels in treated mice were significantly less than in parallel controls. Mild hypoglycemia was observed at 7 to 10 days posttreatment. Although circulating IL-1-like activity could not be detected in plasma 1 to 10 days after P. acnes treatment, this activity was measured in activated peritoneal and liver M phi. IL-1-like activity (specific activity: 276 units/mg protein) was detected in plasma, after it was chromatographed on a Sephadex G-150 column to remove proteins with higher molecular weight. Peritoneal and liver M phi from P. acnes mice were also able to elaborate significant amounts of IL-1-like activity in their supernatants with or without Escherichia coli lipopolysaccharide. At the same time, total protein synthesis and insulin content in the pancreas in P. acnes mice were significantly lower than the parallel control (p less than 0.01). These results suggest that P. acnes-induced M phi activation in mice was associated with the modulation of insulin release and glucose homeostasis which may be attributed to the accumulation and release of IL-1 by activated M phi.

Animals↗
PubMed1988

Stimulation of breathing movements by L-5-hydroxytryptophan in fetal sheep during normoxia and hypoxia.

1. In fetal lambs in late gestation, systemic infusion of L-5-hydroxytryptophan (L-5-HTP) during normoxia greatly increases the incidence of fetal breathing movements (FBM) and high-voltage electrocortical activity (HV ECoG). It also induces FBM during HV ECoG and increases blood pressure. To investigate its mechanism of action, L-5-HTP was administered in conjunction with the 5-hydroxy-tryptamine (5-HT) antagonists ketanserin or cyproheptadine. L-5-HTP was also infused with or without the antagonists during hypoxia, to test whether it would overcome the inhibition of FBM by hypoxia. 2. When L-5-HTP was given in normoxia, cyproheptadine blocked and ketanserin reduced the increase in blood pressure, both drugs blocked the stimulation of FBM, but neither drug prevented the induction of prolonged episodes of HV ECoG. 3. In hypoxia, L-5-HTP similarly stimulated FBM. This effect was also blocked by cyproheptadine and was delayed by ketanserin. 4. The antagonism of the effects of L-5-HTP on blood pressure and the incidence of FBM in normoxia and hypoxia is consistent with the action of L-5-HTP via 5-HT receptors. At present there is no clear explanation of the mechanism by which L-5-HTP induces HV ECoG.

5-Hydroxytryptophan↗
PubMed1987

Down-regulation of insulin receptors in Propionibacterium acnes-activated macrophages in the mouse.

Intraperitoneal administration of Propionibacterium acnes in CD-1 mice was associated with the reduction in number of insulin receptors in peritoneal macrophages (M phi), and with elevated levels of insulin in plasma and the peritoneal cavity. When insulin levels returned to normal, insulin receptors in P. acnes-M phi were still reduced. Insulin appears to contribute significantly to the down-regulation of the M phi-insulin receptors during the early stage of activation. Other biologically active substances released during M phi activation might assume greater influence on insulin resistance in activated M phi at a later stage. The induction of transient hyperinsulinemia in P. acnes-treated mice might be attributed to the effect of concurrently elevated interleukin-1 (IL-1) released in the early course of M phi activation.

Animals↗
PubMed1987

Health promotion for children. Key to a lifetime of health.

Evidence indicates that preventive healthcare in childhood reduces healthcare costs and enhances health. Physicians can assume a leadership role in promoting children's health by incorporating health promotion measures into their everyday practice, serving as resource persons or leaders in community and school efforts in health promotion, and lobbying for legislation aimed at preventive care. The goals of these efforts are to achieve a healthy childhood, provide a foundation for a healthy adulthood, and develop in children positive values about personal health responsibility and use of healthcare services.

Adolescent↗
PubMed1987

Vasoactive intestinal polypeptide enhances hormone content and insulin release in cultured fetal rat islets.

The effect of porcine vasoactive intestinal polypeptide (VIP) on development of the biphasic insulin release response in cultured fetal rat islets was investigated. Fetal islets, 21.5 days gestational age, were cultured for 7 days in RPMI 1640 culture medium containing either 2.8 or 11.1 mM glucose adn subsequently challenged with 16.7 mM glucose in a perfusion system. Islets were exposed to VIP at a final concentration of 13.2 nM by adding the peptide to the perifusion buffer (acute exposure) or by adding it to the culture medium throughout the culture period (chronic exposure). Islet hormone and DNA contents were also quantitated at the end of the culture period. Acute exposure to VIP resulted in no alterations of the insulin release pattern after culture in the presence of either glucose concentration. However, chronic treatment of islets with 13.2 nM VIP in the presence of 2.8 mM glucose resulted in significant increases in the maximum rate of insulin release during the first phase and the total amount of insulin release during both phases. Similarly, islets cultured in the presence of 11.1 mM glucose and 13.2 nM VIP demonstrated enhanced biphasic insulin release patterns with increased maximum rate and total amount of release during both phases. The presence of VIP and 2.8 mM glucose increased islet glucagon and somatostatin contents, but islet DNA and insulin contents remained unchanged. These findings indicate that VIP plays a significant role in the in vitro development of the biphasic insulin release pattern and may be a factor controlling the maturation of the fetal islet in vivo.

Animals↗
PubMed1986

Coping with insomnia. Helping patients manage sleeplessness without drugs.

Sleep, a vital ingredient in life, is often taken for granted until something goes awry and sleep no longer comes easily. Occasional bouts of sleeplessness are normal, but for some persons, perhaps as much as 20% of the adult population, insomnia is a recurring problem for which they may turn to over-the-counter or prescription sleeping pills as a solution. In all but the most extreme cases, however, medication is not necessary and nondrug remedies are sufficient for lulling the patient back to sleep. In this article, Dr Fletcher describes what everyone should know about the complex process of sleep and offers suggestions, including some familiar old-fashioned home remedies, on what to do when sleep is evasive.

Animals↗
PubMed1986

The effects of vagotomy on compensatory ovarian hypertrophy and follicular activation after unilateral ovariectomy.

Following unilateral ovariectomy in the rat, the remaining ovary undergoes rapid compensatory changes including an increase in the number of antral follicles (follicular activation) and an increase in ovarian weight (compensatory ovarian hypertrophy). The ovary is innervated by the vagus nerve (Burden et al., 1983). In the present study, the effects of right and left cervical vagotomy and abdominal vagotomy on follicular activation and compensatory ovarian hypertrophy in the remaining right or left ovary were compared 15 days after unilateral ovariectomy. Neither right nor left cervical vagotomy affected compensatory ovarian hypertrophy of the right or left ovaries but abdominal vagotomy depressed compensatory ovarian hypertrophy in both the right and left ovaries. Left cervical vagotomy did not inhibit follicular activation, but right cervical vagotomy prevented follicular activation in the right but not left ovary. Also, abdominal vagotomy inhibited follicular activation in the right but not the left ovary. In animals with both ovaries which were subjected to the left or right cervical vagotomy or abdominal vagotomy follicular counts in both right and left ovaries were similar. Collectively, these data indicate that the vagus nerve participates in follicular activation after unilateral ovariectomy. The data also indicate that the right ovary is more dependent on vagal influences for follicular activation than the left ovary.

Animals↗