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Biomedical subjects

M Murphy

Publications and source records attributed to M Murphy.

At least 289 records · Page 16Linked to original sources
PubMed1994

Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs.

Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of peptic ulcer complications, but it is not clear whether some drugs are more likely than others to cause such complications. We compared previous use of NSAIDs in 1144 patients aged 60 and older admitted to hospitals in five large cities with peptic ulcer bleeding and in 1126 hospital controls and 989 community controls matched for age and sex. Peptic ulcer bleeding was strongly associated with use of non-aspirin NSAIDs of any type during the 3 months before admission (411 cases, 351 controls; odds ratio 4.5 [95% CI 3.6 to 5.6]). The odds ratios for peptic ulcer bleeding were lowest for ibuprofen (2.0 [1.4-2.8]) and diclofenac (4.2 [2.6-6.8]), and intermediate for indomethacin, naproxen, and piroxicam (11.3 [6.3-20.3], 9.1 [5.5-15.1], and 13.7 [7.1-26.3]). Azapropazone and ketoprofen carried the highest risks (31.5 [10.3-96.9] and 23.7 [7.6-74.2]). Risks also increased with drug dose (low dose 2.5 [1.7-3.8], intermediate 4.5 [3.3-6.0], and high 8.6 [5.8-12.6]) for all drugs combined. Appropriate clinical strategies could prevent many episodes of peptic ulcer bleeding: NSAIDs should be used only in patients who do not respond to other analgesics; the lowest possible doses should be used; and the least toxic NSAIDs should be selected.

Aged↗
PubMed1994

Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation.

Identification of a biocompatible immunoprotective membrane to prevent graft rejection remained elusive until the development of microcapsules formulated in alginate high in guluronic acid. We report insulin independence in a type 1 diabetic patient after encapsulated islet transplantation. Encapsulated human islets were injected intraperitoneally in a diabetic patient with a functioning kidney graft. Insulin independence with tight glycaemic control was demonstrated 9 months after the procedure. These results warrant a trial of a high dose of encapsulated islets in early-onset diabetic patients.

Adult↗
PubMed1994

Leukaemia inhibitory factor rescues motoneurones from axotomy-induced cell death.

The death of spinal motoneurones after axotomy provides a useful model for studying novel factors which prevent motoneurone loss in vivo. Peripheral nerves of newborn rats were unilaterally transected and treated with either a vehicle solution or leukaemia inhibitory factor (LIF). Compared with the vehicle controls, treatment with a gelfoam containing LIF significantly reduced motoneurone loss: from 38% to 22% after 3 days and from 55% to 38% after 7 days. The loss of motoneurones was further reduced by placing the LIF-containing gelfoam inside a silicone chamber: from 39% to 15% after 7 days, which represented a 62% rescue. Thus, LIF is a potential therapeutic agent for preventing the loss of injured or diseased motoneurones.

Animals↗
PubMed1994

Effect of advertising on awareness of symptoms of diabetes among the general public: the British Diabetic Association Study.

OBJECTIVE: To determine the impact of posters advertising symptoms of diabetes on public knowledge of these symptoms. DESIGN: Structured street interviews of members of the general public before, at the end of, and 10 weeks after a campaign advertising the main symptoms of diabetes. SETTING: Basingstoke and Wolverhampton. SUBJECTS: Three samples of 1000 members of the general public were interviewed. Samples were selected randomly but stratified to match the local population's age (20-75), sex, social class, and racial characteristics. MAIN OUTCOME MEASURES: Knowledge of symptoms of diabetes; perceived seriousness of diabetes; and induction of anxiety about symptoms in the target population. RESULTS: Advertising significantly raised knowledge (without prompting) of symptoms: thirst, 245 before v 411 at end of campaign (P < 0.0001) v 341 after (P = 0.0012 v before); polyuria, 72 v 101 (P = 0.0211) v 92 (P = 0.5169); lethargy, 180 v 373 (P < 0.0001) v 298 (P < 0.0001); knowledge of weight loss and visual disturbance was unaffected. The number of subjects lacking knowledge of any symptoms was reduced from 550 to 388 (P < 0.0001). The perceived seriousness of diabetes was unaffected (mean 7.6 in each phase on a scale of 1 (not) to 10 (very). Before advertising, 449 (45%) claimed to have one or more symptoms of diabetes, but this number fell at the end of the campaign (403; P = 0.0419) and 10 weeks afterwards (278; P < 0.0001). CONCLUSIONS: An advertising campaign raised public knowledge of diabetes symptoms without inducing fear of diabetes or anxiety about symptoms. Its potential for achieving earlier detection of non-insulin dependent diabetes should be evaluated.

Adult↗
PubMed1994

Leukemia inhibitory factor prevents the death of axotomised sensory neurons in the dorsal root ganglia of the neonatal rat.

Leukemia inhibitory factor (LIF) has several characteristics of a neurotrophic factor for sensory neurons. Here we have investigated whether LIF also supports the survival of axotomised sensory neurons in vivo. Newborn rat pups received a unilateral sciatic nerve transection and the injury site was treated with gelfoam soaked in phosphate buffered saline (PBS), nerve growth factor (NGF), or LIF. Neuronal nucleoli in the L5 dorsal root ganglia were counted, appropriate corrections applied, and the resultant neuronal loss expressed as a percentage of the contralateral intact side. In animals where LIF was administered neuronal loss was significantly reduced: 2 days after LIF treatment neuronal loss was 19.5% compared to 43% in PBS-treated animals; 3 days after LIF treatment neuronal loss was 20.4% compared to 40.2% in PBS-treated animals; however, 7 days after LIF treatment there was no significant reduction in the number of neurons lost. The degree of rescue of sensory neurons in vivo by LIF was found to be similar to NGF, which was not surprising as both factors supported the survival of a similar population of sensory neurons in vitro. Rescue was not observed when LIF-containing gelfoam was placed away from the axotomised nerve, suggesting that LIF's action may be associated with its retrograde transport or direct signalling at the site of nerve injury.

Animals↗
PubMed1994

Stimulation of DNA synthesis in rabbit bladder wall after partial outlet obstruction and acute overdistension.

Partial outlet obstruction of the rabbit urethrovesical junction (UVJ) has been used to induce pathology in the urinary bladder characteristic of obstructive damage observed in humans. The purpose of the experiments reported here was to compare the 3H-thymidine (3H-TdR) labelling of DNA in urinary bladders of male New Zealand White (NZW) rabbits subjected to partial outlet obstruction or overdistension. A total of 18 animals was used. Two normal controls, and 12 partially obstructed animals (at 1 day [D], 3D, 5D, 7D, 14D, and 21D) were injected (i.v.) with 3H-TdR at a dose of 0.5 microCi/g body weight. An additional 4 were overdistended to volumes 120% of maximum intravesical pressure, immediately emptied via the catheter, and injected with 3H-TdR 24 hr (1D) later. All animals were sacrificed up to 3.5 hr after injection of the label. DNA-associated radioactivity reached a peak at 3D after obstruction and was reduced substantially by 5D, although the level of incorporation remained well above control levels out to 21D. Levels of 3H-TdR incorporation 1D after overdistension bladders were about half of that found 1D following partial obstruction. The distribution of 3H-TdR labelled DNA in tissues was demonstrated by radioautography of histologic sections. One day following obstruction, 3H-Tdr incorporation was localized in the urothelium. Labelling of urothelium subsequent to 1D was reduced but remained above control levels until 21D. Labelled smooth muscle nuclei were observed only in control and 3D bladders, and they were measured at similar frequencies. Labelling of both intrinsic connective tissue (ICT) (mucosal, submucosal, and mural) and extrinsic connective tissue (ECT) (serosal) peaked at 3D after obstruction and declined thereafter but not to control levels. Labelling of ECT was, of course, limited to those bladders in which ECT was present (i.e., 3-21D). While the distribution of labelled cells in radioautograms was more variable 1D after obstruction than 1D after overdistension, the general cellular and biochemical responses to overdistension, as measured by DNA synthesis, are similar to those observed after partial outlet obstruction. Since the first sequela of obstruction is acute distension, these data support the assertion that the initial overdistension of the bladder initiates the cellular response to obstruction.

Animals↗
PubMed1994

3H-thymidine uptake by the rat urinary bladder after partial outflow obstruction.

Partial outflow obstruction induces marked changes in detrusor contractile function and morphology. One common finding in all experimental animal models of outflow obstruction is a significant increase in bladder mass. It is not clear which tissue compartments undergo hypertrophy, hyperplasia, or both. The present study was designed to evaluate the time-related changes in 3H-thymidine uptake and distribution within each tissue compartment induced by partial outflow obstruction using autoradiography. Partial outlet obstruction in rats induced a mild 2-fold increase in mass over a 14 day period. DNA synthesis increased significantly at 1 day following surgery, and remained increased through 7 days. DNA synthesis returned to control levels by 14 days. Distribution studies (using autoradiography) demonstrated a marked increase in the number of labelled urothelium cells at 1 and 3 days after obstruction. Sham surgery also initiated an increase in the number of labelled cells in the urothelium at 1 day. Although both sham and obstructive surgeries induced substantial increases in the labelling of cells within the connective tissue components, the magnitude of the increase in labelled connective tissue cells of the obstructed bladders was greater than that of the sham group. The number of labelled smooth muscle cells of the obstructed bladder increased significantly at 3, 5, and 7 days. However, there were no changes in smooth muscle incorporation of 3H-thymidine by the sham groups. In conclusion, partial outflow obstruction induced time-dependent increases in bladder wall proliferation. The urothelium and connective tissue were the compartments first affected, followed by smooth muscle.

Animals↗
PubMed1994

Effect of cyclosporine A on long-term allograft function in pediatric renal transplant recipients.

There have been concerns regarding long-term adverse effects of cyclosporine A (CSA) on renal allograft function. In a retrospective study, we compared long-term allograft function up to 70 months after renal transplantation in pediatric recipients treated with and without CSA, using iothalamate clearance to assess glomerular filtration rate. Patients received CSA, prednisone, and azathioprine (CSA group, n = 16) or prednisone and azathioprine alone (Pred/AZA, n = 11). At 48 months post transplant, the iothalamate clearances (mean +/- SD) were 57.9 +/- 26.8 ml/min per 1.73 m2 in the CSA group and 68.5 +/- 20.2 in the Pred/AZA group (P > 0.05). The mean of the slopes of individual iothalamate clearances versus time during the first 70 months following transplantation were -0.156 in the CSA group and 0.095 in the Pred/AZA group. Neither slope was statistically different from zero. These data suggest that allograft function is not significantly depressed by CSA at 48 months post transplantation and that there is no greater rate of decline in allograft function up to 70 months post transplantation in patients receiving CSA when compared with the AZA/Pred group.

Adolescent↗
PubMed1994

Strategies for increasing third-party reimbursement for nutrition counseling.

OBJECTIVE AND SETTING: The purpose of this two-phase project was to determine whether specific interventions would affect third-party reimbursement for outpatient nutrition services at the Nutrition Clinic of the Los Robles Regional Medical Center. DESIGN, SUBJECTS, AND INTERVENTION: In phase 1, the baseline reimbursement rate was determined by a questionnaire mailed to 191 clients seen in the clinic from January 1 to September 30, 1989. The survey was completed by 115 clients (60%). In phase 2, two strategies were used to increase reimbursement: instructing clients about how to file claims and providing clients with form letters of medical necessity to submit with their claims. The strategies were applied to 76 new clients from March 15 to July 31, 1991. Five weeks later, 67 of the 76 clients (88%) were interviewed by telephone. OUTCOME MEASURES: The primary outcome measures were submission rates and reimbursement rates. RESULTS: The results showed that in phase 1 (before intervention), 75 of the 115 clients surveyed (65%) submitted claims to their insurance carriers, and 12 of the 74 clients (15%) whose claims were acted on received reimbursement. In phase 2, 47 of the 67 clients (70%) submitted claims, and 15 of the 36 clients (42%) whose claims were acted on received reimbursement. Of the 20 clients who did not submit claims, 8 did not apply because of time constraints, and 5 did not apply because of low expectations of reimbursement. APPLICATIONS/CONCLUSIONS: Form letters of medical necessity increased the reimbursement rate, but client instruction did not increase the submission rate. Most of the clients who did not submit a claim said they did not have time to do so. Therefore, the Nutrition Clinic is attempting to submit insurance forms for the clients after clients have paid for the consultation. Other providers of outpatient nutrition counseling who follow this strategy may increase the reimbursement rate.

Adult↗
PubMed1994

Leukemia inhibitory factor (LIF) infusion stimulates skeletal muscle regeneration after injury: injured muscle expresses lif mRNA.

Leukemia inhibitory factor (LIF) is known to stimulate myoblast growth in culture via direct receptor mediated mechanisms, but it does not suppress myoblast fusion in vitro. We show here that LIF is also effective in vivo, using a muscle crush model. Administration of LIF to the site of the crush results in an increased rate of regeneration of the injured muscle. LIF stimulates an increase in the size of the muscle fibers rather than an increase in total number. Perfusion of 125I-labelled LIF (125I-LIF) at the site of the crush leads to uptake of the great majority of 125I-LIF into the muscle, which suggests that LIF is acting directly at the site of injury. Further, following crush injury LIF mRNA synthesis commences in the muscle. These data provide evidence that LIF is acting as a natural trauma factor in vivo and is actively involved in muscle regeneration.

Animals↗
PubMed1994

Regulation of the early development of the nervous system by growth factors.

Development of the nervous system, although patterned by intrinsic genetic expression, appears to be dependent on growth factors for many of the differentiation steps that generate the wide variety of neurons and glia found in the both the central and peripheral nervous system. By using in vitro assays, including clonal analysis, the precise function of the various growth factors and the differentiation potential of the various neural populations has begun to be described. This review discusses some of the recent findings and examines how neuronal differentiation may result from the interaction of several growth factors.

Animals↗
PubMed1994

Effect of slow and rapid cystometry on in vitro rat urinary bladder DNA synthesis.

1. Partial outflow obstruction induces marked changes in detrusor contractile function and morphology. One common finding in all experimental animal models of partial outflow obstruction is a significant increase in bladder mass. 2. Previous studies have demonstrated that partial outlet obstruction induces a rapid and substantial increase in [3H]thymidine incorporation into virtually all cellular elements of the bladder. 3. The present study was designed to investigate the [3H]thymidine uptake and localization induced by exposure of the in vitro whole rat bladder model to various intravesical pressures and rates of intravesical infusion. 4. The results are as follows: (a) There were no differences in DNA concentration between control and other groups. (b) Slow infusion induced a mild increase in DNA synthesis ([3H]thymidine incorporation) at 0.5 ml and a significantly greater level of DNA synthesis at 1.6 ml. (c) [3H]thymidine incorporation was significantly increased by exposure to 7.5 cm H2O, 15 cm H2O, and 30 cm H2O. (d) Exposure to 60 cm H2O and 90 cm H2O did not initiate an increase in [3H]thymidine incorporation. (e) Autoradiography showed that all tissue elements (urothelium, connective tissue, smooth muscle) participated in the response.

Animals↗
PubMed1994

Absorption of liposome-encapsulated tetracaine versus nonliposome-encapsulated tetracaine from open wounds in rabbits.

The plasma tetracaine concentration versus time profiles for liposome-encapsulated tetracaine (LET) versus nonliposome-encapsulated tetracaine (NLET) were determined after topical application to open wounds in six rabbits (three in LET and three in NLET). H3-tetracaine preparations of LET or NLET were applied randomly to uniform dermal lacerations in anesthetized rabbits. Plasma tetracaine concentrations (ng/mL) of arterial blood samples obtained were measured at predetermined intervals (0.25, 0.5, 1.0, 2.0, and 24 hours) by isotope tracer assay. Results (mean +/- standard deviation) showed the peak plasma tetracaine concentration (Cmax) and the time to Cmax were 40.8 +/- 5.1 ng/mL and 40.1 +/- 7.3 minutes for LET, and 117.8 +/- 9.7 ng/mL and 49.1 +/- 50.2 minutes for NLET. Plasma tetracaine concentrations at all samples times were significantly lower for LET versus NLET. Liposome encapsulation of topically applied tetracaine significantly decreases both the peak and overall plasma tetracaine concentrations compared with the nonencapsulated form. The data suggest that liposome encapsulation of topically applied local anesthetics such as a solution of tetracaine, adrenaline, and cocaine, might reduce the potential systemic toxicity caused by rapid absorption of these compounds.

Absorption↗
PubMed1994

The neurofibromatosis 2 (NF2) tumor suppressor gene encodes multiple alternatively spliced transcripts.

Neurofibromatosis type 2 (NF2) is an autosomal dominantly-inherited disorder predisposing affected individuals to tumors of multiple cell types in the central nervous system, including meningiomas. A candidate tumor suppressor gene for this disorder has recently been cloned; the protein product of this gene has a predicted role in linking integral membrane proteins with the cytoskeleton. Utilizing reverse transcription-polymerase chain reaction (RT-PCR) analyses, we have identified a number of alternatively spliced transcription products encoded by the NF2 gene. These alternative splice variants were detected in RNA isolated from several sources, including primary leptomeningeal tissue and an established line of leptomeningeal cells (LMC). Several of these variants delete previously identified coding regions of this gene. Moreover, two of these splice variants add previously unrecognized exons to the NF2 coding region. These identified splice forms will serve as natural reagents for the functional dissection of the NF2 protein product(s). They also should be considered in studies investigating mutations of this gene in members of NF2 families and in tumor analyses.

Amino Acid Sequence↗
PubMed1994

Administration of recombinant IL-12 to normal mice enhances cytolytic lymphocyte activity and induces production of IFN-gamma in vivo.

IL-12 is a heterodimeric cytokine that has been shown to enhance natural killer (NK) and cytotoxic T lymphocyte (CTL) responses, and to induce IFN-gamma production in vitro. In this study, we have examined the effects in vivo of administering purified murine rIL-12 to normal mice. Daily injections of rIL-12 i.p. (1 ng to 10 micrograms/day) caused dose-dependent enhancement of NK cell lytic activity in the spleens and livers of treated mice. Histologic examination of the livers of IL-12-treated mice revealed focal mononuclear cell infiltrates, and flow cytometry studies indicated that the livers of IL-12-treated mice contained increased numbers of NK cells, CD8+ T cells, and monocytes. Liver and splenic lymphoid cells from IL-12-treated mice, unlike liver and splenic lymphoid cells from control mice, spontaneously secreted IFN-gamma in vitro, suggesting that they had been induced by IL-12 to produce IFN-gamma in vivo. Consistent with this, IFN-gamma could be detected in the serum of IL-12-treated mice. In mice which had been immunized by footpad injection of allogeneic splenocytes, daily administration of rIL-12 i.p. was shown to enhance the specific CTL response in the draining lymph nodes. Thus, these studies demonstrate that IL-12 can enhance NK and CTL activity and induce IFN-gamma production in vivo, as well as in vitro, and suggest possible mechanisms by which IL-12 may exert therapeutic effects in the treatment of some tumors and infectious diseases.

Animals↗
PubMed1994

Role of the carboxy terminus of herpes simplex virus type 1 DNA polymerase in its interaction with UL42.

Several recent reports implicate sequences at or near the C terminus of the catalytic subunit (POL) of herpes simplex virus type 1 (HSV-1) DNA polymerase in its interaction with the accessory protein UL42. We have investigated further the involvement of this region by three different approaches: anti-idiotype antibodies, a competition ELISA and inhibition of the interaction by peptides. Antibodies raised in rabbits to peptides corresponding to regions of POL all reacted in Western blots with POL. Surprisingly, the sera raised against C-terminal peptides (amino acids 1221 to 1235 and 1224 to 1235) also reacted with UL42. The UL42 reactivity was shown to be due to the presence of anti-idiotype antibodies, providing direct evidence for complementarity of the structure of the extreme C terminus of POL to a region of UL42. To measure the contribution of the C terminus of POL to UL42 binding we developed a competition ELISA using POL, a truncated polymerase lacking the carboxyl-terminal 27 amino acids (POLd1) and UL42. UL42 binding to immobilized POL was inhibited approximately four times more effectively by competition, in solution, with POL than with POLd1, indicating that the C-terminal 27 amino acids of POL are responsible for at least 75% of the binding energy. A peptide corresponding to these 27 amino acids (residues 1209 to 1235) inhibited both the POL-UL42 interaction and the stimulation of POL by UL42 and did so more effectively than peptides corresponding to amino acids just away from the C terminus (residues 1195 to 1223 and 1177 to 1195).

Amino Acid Sequence↗
PubMed1994

Lipid peroxidation and antioxidative vitamins under extreme endurance stress.

The aim of this study was to examine whether extreme endurance stress of trained athletes can influence lipid peroxidation and muscle enzymes. A randomized and placebo-controlled study was carried out on 24 trained long-distance runners who were substituted with alpha-tocopherol (400 I.U. d-1) and ascorbic acid (200 mg d-1) during 4.5 weeks prior to a marathon race. The serum concentrations of retinol, ascorbic acid, beta-carotene, alpha-tocopherol, malondialdehyde (TBARS) and uric acid as well as glutathione peroxidase (GSH Px) and catalase were measured 4.5 weeks before (A), immediately before (B), immediately after (C) and 24 h after (D) the course. After competition (C) TBARS serum concentrations of the athletes (n = 22) decreased in both groups (P < 0.0001). The ascorbic acid serum concentration increased significantly in the supplemented group from (A) to (B) (P < 0.01), from (B) to (C) (P < 0.001) and in the placebo group a significant increase from (B) to (C) (P < 0.01) was observed. The alpha-tocopherol serum concentration increased significantly in the supplemented group from (A) to (B) (P < 0.001) and from (B) to (C) (P < 0.05). The enzymes glutathione peroxidase (GSH Px) and catalase measured in erythrocytes as well as the serum selenium levels did not show significant differences at any time. A significant increase of CK concentration was observed from (C) to (D) in the supplemented group (P < 0.01) and in the placebo group (P < 0.001). The increase of CK serum concentration is remarkably lower in the supplemented group compared with the placebo group (P < 0.01). It is concluded that endurance training coupled with antioxidant vitamin supplementation reduces blood CK increase under exercise stress.

Adult↗