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Biomedical subjects

M Caldwell

Publications and source records attributed to M Caldwell.

At least 19 recordsLinked to original sources

Stump appendicitis: a rare but important entity.

A case of right lower quadrant pain in a 35-year-old male who underwent an appendicectomy 14 years previously is presented. Recurrent appendicitis with perforation was noted in an appendiceal stump on exploratory laparotomy. Although rare, inlammation of the appendiceal stump can occur and is still an important clinical entity. It is difficult to diagnose pre-operatively. A wide spectrum of causes in the differential diagnosis of right lower quadrant pain of the abdomen and a previous appendicectomy in a patient's history may delay the diagnosis. Knowledge of the condition should permit the physician to make an early diagnosis and, thus, limit the resultant morbidity.

Adult↗

Anatomical perspectives on adult neural stem cells.

The concept of stem cells within the adult brain is not new. However, only recently have scientific techniques become sufficiently advanced to identify them although this remains problematic and the technology is still developing. Nevertheless, it is now generally recognized that stem cells are restricted to two germinal regions within the intact brain. From here they can migrate to specific destinations where they integrate with existing circuitry. Their identity remains controversial but a growing body of evidence suggests it may have an astrocytic phenotype. Within the germinal regions the stem cells are confined to a niche environment and are capable of responding to environmental signals generated locally in an autocrine or paracrine fashion. The niche environment is also modulated by more generalized systemic and physiological activity. These observations are exciting in their own right and form the basis of this review. They are also beginning to alter how we think about neural injury and disease and to impact on the development of novel therapies.

Adult↗

Pneumococcal immunizations at flu clinics: the impact of community-wide outreach.

This study examined the effectiveness of a community-wide outreach campaign to promote the use of pneumococcal vaccine at public flu immunization clinics, and assessed whether this intervention was more effective than simply making pneumococcal vaccination available at such clinics. In 1997, a community-wide outreach campaign promoting pneumococcal and influenza immunizations was launched in a 17 zip code area of Dutchess County, NY. The campaign was aimed at 7,961 Medicare beneficiaries urging them to obtain pneumococcal immunization from local flu clinics. Medicare reimbursement data were used to assess the countywide pneumococcal vaccination rate, and to analyze differences between rates for beneficiaries in the target area and elsewhere in the county. Between 1996 and 1997 there was a 94% increase in pneumococcal vaccination billed to Medicare beneficiaries in Dutchess County. The 1997 annual rate of pneumococcal immunization in the target area reached 16.3% versus 12.2% elsewhere in the county (p < 0.001), with an increase over the previous year of 8.7% and 5.6%, respectively. Nearly all of the increase is accounted for by pneumococcal vaccination delivered at flu clinics. It is possible to significantly increase the use of pneumococcal immunization by linking its delivery to community-based flu clinics and by developing local outreach strategies. The outreach campaign has a significant additive effect over simply making PPV available at flu shot clinics. Additional community-wide outreach can further improve pneumococcal immunization utilization rates.

Aged↗

Murine phospholipid hydroperoxide glutathione peroxidase: cDNA sequence, tissue expression, and mapping.

Phospholipid hydroperoxide glutathione peroxidase (PHGPx), also known as glutathione peroxidase 4 (GPX4), is a 19-kDa, monomeric enzyme that protects cells from lipid peroxide-mediated damage by catalyzing the reduction of lipid peroxides. PHGPx is synthesized in two forms, as a 194-amino acid peptide that predominates in gonadal tissue and localizes to mitochondria, and as a 170-amino acid protein that predominates in most somatic tissues and localizes to the cytoplasm. With the rapid amplification of cDNA ends (RACE) procedure, an 876-bp PHGPx cDNA was amplified from mouse testis, and a 767-bp PHGPx cDNA was amplified from mouse heart. The cDNA sequences were identical except that the testis cDNA contained an additional 109 bp at its 5' end. With a partial cDNA with complete homology to both the testis and myocardial PHGPx cDNAs, the murine tissue distribution of PHGPx mRNA expression was determined by Northern blotting. Highest level of PHGPx expression was found in the testis, followed by the kidney, heart and skeletal muscle, liver, brain, lung, and spleen. Northern blotting performed with a cDNA specific for the longer PHGPx transcript demonstrated that this longer PHGPx transcript was present only in the testis. A 1.4-kb PHGPx genomic fragment was amplified from murine kidney DNA and used to map the PHGPx gene by linkage analysis of restriction fragment length variants (RFLVs). The murine PHGPx gene (Gpx4) was mapped to a region of murine Chromosome (Chr) 10, located 43 cM from the centromere, that is syntenic with the human locus, which is located at the terminus of the short arm of human Chr 19. This information may be valuable in characterizing the role of PHGPx in modulating susceptibility to lipid peroxide-mediated injury in inbred murine strains and for targeted disruption of the gene.

Amino Acid Sequence↗

Long-term functional status and quality of life after lower extremity revascularization.

OBJECTIVE: The objective of this study was to assess the longer term (up to 7 years) functional status and quality of life outcomes from lower extremity revascularization. METHODS: This study was designed as a cross-sectional telephone survey and chart review at the University of Minnesota Hospital. The subjects were patients who underwent their first lower extremity revascularization procedure or a primary amputation for vascular disease between January 1, 1989, and January 31, 1995, who had granted consent or had died. The main outcome measures were ability to walk, SF-36 physical function, SF-12, subsequent amputation, and death. RESULTS: The medical records for all 329 subjects were reviewed after the qualifying procedures for details of the primary procedure (62.6% arterial bypass graft, 36.8% angioplasty, 0.6% atherectomy), comorbidities (64% diabetics), severity of disease, and other vascular risk factors. All 166 patients who were living were surveyed by telephone between June and August 1996. At 7 years after the qualifying procedure, 73% of the patients who were alive still had the qualifying limb, although 63% of the patients had died. Overall, at the time of the follow-up examination (1 to 7.5 years after the qualifying procedure), 65% of the patients who were living were able to walk independently and 43% had little or no limitation in walking several blocks. In a multiple regression model, patients with diabetes and patients who were older were less likely to be able to walk at follow-up examination and had a worse functional status on the SF-36 and a lower physical health on the SF-12. Number of years since the procedure was not a predictor in any of the analyses. CONCLUSION: Although the long-term mortality rate is high in the population that undergoes lower limb revascularization, the survivors are likely to retain their limb over time and have good functional status.

Activities of Daily Living↗

Mouse glycosylphosphatidylinositol-specific phospholipase D (Gpld1) characterization.

Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is an 110-kDa monomeric protein found in the circulation that is capable of degrading the GPI anchor utilized by dozens of cell-surface proteins in the presence of detergent. This protein is relatively abundant (5-10 microgram/ml in human serum), yet its sites of synthesis, gene structure, and overall function are unclear. It is our purpose to use the mouse system to determine its putative roles in lipid transport, pathogen control, and diabetes. We have isolated murine full-length cDNA for GPI-PLD from a pancreatic alpha cell library. The deduced amino acid sequence shows 74% homology to bovine and human GPI-PLD. There is a single structural gene (Gpld1) mapping to mouse Chromosome (Chr) 13, and among nine tissues, liver showed the greatest abundance of GPI-PLD mRNA. Genetic differences in serum GPI-PLD activity were seen among four mouse strains, and no correlation was seen between GPI-PLD activity and circulating levels of high density lipoproteins in these mice. This is the first report of map position and genetic regulation for Gpld1. This information will enable us to further study the expression and function of GPI-PLD in normal and pathological conditions.

Amino Acid Sequence↗

Weight training increases fat-free mass and strength in untrained young women.

OBJECTIVE: To examine the effects of a weight training program on the resting metabolic rate, fat-free mass, strength, and dietary intake of untrained young women. DESIGN: A 12-week weight training program was completed by 20 previously untrained women aged 19 through 44 years. SUBJECTS: Twenty-three study subjects and 14 control subjects were recruited on a volunteer basis. Twenty study subjects and 10 control subjects completed the study. INTERVENTIONS: Study subjects participated in a 12-week moderate-intensity, progressive resistance weight training program consisting of 2 supervised sessions per week with 6 types of lifting exercises per session. Resting metabolic rate, fat-free mass, strength, and dietary intake were measured before and immediately after the study. STATISTICAL ANALYSES: Repeated measures analysis of variance and t tests (unequal variance and paired) were used to determine interaction effects and differences within and between groups. RESULTS: The study group increased their fat-free mass (mean+/-standard deviation) from 44.2+/-5.4 kg to 46.2+/-6.0 kg (P<.001). Elbow flexion, elbow extension, and knee flexion strength all increased from 28.9+/-5.3 to 34.5+/-3.8, 16.9+/-4.9 to 22.1+/-5.3, and 39.5+/-8.6 to 48.6+/-7.3 ft-lb, respectively (P<.001). Percent body fat decreased from 29.8+/-2.8 to 27.2+/-2.6 (P<.001) without a significant change in body weight. Resting metabolic rate did not change significantly (P>.05). APPLICATION: A moderate-intensity weight training program increased strength and fat-free mass and decreased body fat in normal-weight young women. Favorable changes in body composition were obtained without restricting food intake. The increase in fat-free mass did not increase resting metabolic rate significantly.

Adult↗

Swimming-associated haemorrhagic colitis due to Escherichia coli O157:H7 infection: evidence of prolonged contamination of a fresh water lake.

We describe an Escherichia coli O157:H7 outbreak associated with a fresh water lake at a county park. Campers were surveyed for diarrhoeal illness within 10 days of their visit, and a case-control study of day visitors was conducted. A confirmed case was a symptomatic person with a stool culture positive for E. coli O157:H7 and a probable case was a person with bloody diarrhoea. Clinical isolates of E. coli O157 were subtyped by pulsed field gel electrophoresis (PFGE). In the camper survey, 12 (38%) of 32 swimmers had a diarrhoeal illness (relative risk [RR] = 12.4; 95% confidence interval [CI] = 1.7-89.7). For the case-control study, the 12 cases were more likely than controls to have purposefully ingested lake water (odds ratio [OR] = 6.9, 95% CI = 0.9-55.8). The PFGE patterns of six clinical isolates were indistinguishable. This report further demonstrates that contaminated fresh-water lakes can be the source of community outbreaks of E. coli O157:H7.

Adolescent↗

NG-nitro-L-arginine methyl ester protects against lipid peroxidation in the gerbil following cerebral ischaemia.

The aim of this study was to assess the role of nitric oxide (NO) in lipid peroxidation following 5 min of bilateral carotid occlusion in the Mongolian gerbil. The study consisted of 4 experimental groups (n = 10). Animals were either sham operated, subjected to bilateral carotid occlusion or administered the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg i.p.) 30 min, 6, 24 and 48 h following sham operation or 5 min bilateral carotid occlusion. Animals were killed 96 h post surgery and changes in the concentrations of malonaldehyde and 4 hydroxyalkenals (the main decomposition products of peroxides derived from polyunsaturated fatty acids and related esters) were measured in the hippocampus and cortex using the LPO-586 colorimetric method. The results showed a significant increase in the concentrations of both decomposition products following 5 min of bilateral carotid occlusion. L-NAME administered to sham operated controls had no effect, but in those animals subjected to 5 min of bilateral carotid occlusion L-NAME significantly decreased the levels of both decomposition products. These results suggest that inhibition of NO synthase activity decreases lipid peroxidation in the gerbil model of cerebral ischaemia.

Animals↗

The sigma receptor ligand JO 1784 (igmesine hydrochloride) is neuroprotective in the gerbil model of global cerebral ischaemia.

To assess the effects of the novel sigma receptor ligand JO 1784 ((+)-N-cyclopropyl-methyl-N-methyl-1,4-diphenyl-1-yl-but-3-en-1-ylami ne, hydrochloride or igmesine hydrochloride) on behavioural and histological changes following cerebral ischaemia, the gerbil model of cerebral ischaemia was used. Two experiments were carried out. In the first animals were either sham operated, subjected to 5 min of bilateral carotid occlusion or administered JO 1784 (25, 50, 75 or 100 mg/kg p.o.) 1, 24 and 48 h after 5 min bilateral carotid occlusion and histological evaluation carried out 96 h after surgery. In the second experiment the effects of JO 1784 administered at a dose of 100 mg/kg i.p. 30 min, 6, 24 and 48 h post-surgery on home cage activity and nitric oxide (NO) synthase activity in the cortex, hippocampus, cerebellum and brain stem 4 days after surgery was examined. Extensive neuronal death was observed in the CA1 region of 5 min occluded animals. JO 1784 (50, 75 and 100 mg/kg) provided significant protection against this ischaemia-induced cell death (P < 0.03-0.005). In the second experiment a large increase in home cage activity was observed for 5 min occluded animals for 12 h after surgery (P = 0.0018-0.02). A large increase in NO synthase activity was observed in all brain regions for 5 min occluded animals. Post-administration of JO 1784 attenuated the ischaemia-induced hyperactivity and increased NO synthase activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of 2-amino-3-phosphonopropionic acid (AP-3) in the gerbil model of cerebral ischaemia.

The effect of 2-amino-3-phosphonopropionate (AP-3), a metabotropic glutamate receptor antagonist on behavioral and histological changes following global ischaemia was investigated on the Mongolian gerbil. Ischaemia was induced by bilateral carotid occlusion for 5 min. AP-3 was administered i.p. (25 or 250 mg/kg) 30 min before and 24 h after surgery. Significant neuroprotection was observed 96 h after surgery to cells in the CA1 region of the hippocampus in drug treated animals. AP-3 (250 mg/kg) significantly attenuated the increase in locomotor activity measured 72 h after surgery. These results suggest that metabotropic glutamate receptors play a role in the neurodegeneration seen following ischaemia.

Alanine↗

NG-Nitro-L-arginine protects against ischaemia-induced increases in nitric oxide and hippocampal neuro-degeneration in the gerbil.

To assess the effects of the nitric oxide synthase inhibitor NG-Nitro-L-arginine on behavioural, biochemical and histological changes following global ischaemia, the Mongolian gerbil was used. Ischaemia was induced by bilateral carotid occlusion for 5 min. NG-Nitro-L-arginine was administered i.p. at either 1 or 10 mg/kg 30 min, 6, 24, and 48 h after surgery. 5 min bilateral carotid occluded animals were hyperactive 24, 48 and 72 h after surgery. NG-Nitro-L-arginine caused some attenuation in this hyperactivity. The activity of nitric oxide synthase was increased in the cerebellum, brain stem, striatum, cerebral cortex and hippocampus of 5 min bilateral carotid occluded animals. NG-Nitro-L-arginine reversed the increase in nitric oxide synthase activity in all brain regions. Extensive neuronal death was observed in the CA1 layer of the hippocampus in 5 min bilateral carotid occluded animals 96 h after surgery. NG-Nitro-L-arginine significantly protected against the neuronal death of cells in the CA1 layer.

Amino Acid Oxidoreductases↗

Blunt injury augments interleukin-6 but not tumor necrosis factor in isolated, perfused rat hindlimbs.

An isolated, perfused hindlimb model in rats was used to examine the immediate inflammatory response after blunt tissue injury. A femur-fracture degloving model was used in isolated rat hindlimbs perfused with a modified Kreb's buffer (pH 7.4) containing albumin, washed human red blood cells (RBCs), amino acids, and glucose at 37 degrees C. Arterial and venous perfusate was sampled at 5, 20, and 80 minutes of perfusion. Initial experiments were conducted in perfusate void of white blood cells (WBCs), group 1 (-inj/-WBC, n = 6) and group 2 (+inj/-WBC). Subsequent experiments were conducted in perfusate containing activated WBCs, group 3 (-inj/+WBC, n = 6) and group 4 (+inj/+WBC, n = 7). Hindlimb muscle was analyzed for adenylate energy charge (EC) and lactate-to-pyruvate ratios (LPR) at the end of each perfusion. This preparation appeared metabolically stable in that oxygen consumption and lactate remained stable during the 80-minute perfusion and muscle EC and LPR indicated aerobic metabolism. Tumor necrosis factor (TNF) and thromboxane B2 (TXB2) were measured in all four groups while prostaglandin F (PGF1 alpha), IL-6, myeloperoxidase, and 8-isoprostane were measured in groups 3 and 4. Initial perfusions in the -WBC hindlimbs indicated no change in TNF release after injury. The TXB2 level increased during perfusion irrespective of injury. The PGF1 alpha was elevated at 80 minutes in both groups 3 and 4, however at 20 minutes PGF1 alpha levels were higher in group 4 compared with group 3. Interestingly, the IL-6 level was significantly elevated at 80 minutes in group 4 but not in group 3.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Regulation by nutritional status of lipids and apolipoproteins A-I, A-II, and A-IV in inbred mice.

This study illustrates that genetic strain and feeding status can markedly influence tissue lipid concentrations and mRNA levels of apolipoprotein genes. C57BL/6 and BALB/c mice were maintained for 2 weeks on four test diets differing in amount of cholesterol and type of fat, and fasted for 4 h or 16 h prior to collection of tissues. For both strains, the primary effect of fasting from 4 h to 16 h was to paradoxically elevate triglyceride levels in plasma and liver, and to elevate hepatic apoA-IV mRNA levels. Triglyceride secretion rates, estimated after the injection of Triton WR-1339, suggested that elevations in plasma triglyceride levels were due to reduced clearance of very low density lipoproteins. Although plasma glucose levels decreased with fasting time for both strains, insulin levels decreased for BALB/c but not C57BL/6 mice regardless of diet. This suggests that factors thought to be mediated by insulin, (e.g., plasma free fatty acid concentrations; hepatic apoA-IV mRNA levels) may be influenced by local changes in insulin sensitivity, which are controlled genetically and are not reflected by plasma insulin levels. In summary, nutritional status influences a constellation of factors involved in lipid transport that also show strong genetic components and may influence subsequent analyses of gene expression in the mouse system.

Animals↗

Clinical indicators for oncology, cardiovascular, and surgical patients: report of the ADA Council on Practice Quality Assurance Committee.

Clinical indicators were developed as an ADA project for use by the membership and the Joint Commission on Accreditation of Healthcare Organizations as part of its Agenda for Change. This 3-year project involved three clinical indicator task forces who developed clinical indicators for oncology, cardiovascular, and surgical adult acute-care setting patient populations. The task forces developed clinical indicators that were revised after an extensive field review and validation by field test. The following indicators were recommended: Cardiovascular--Patients at high risk for impaired nutritional status receive nutrition intervention within 5 days of admission or within consecutive 5 days on clear liquid diet/nothing by mouth; Patients make food choices consistent with therapeutic diet. Oncology--No patient is on clear-liquid diet/nothing by mouth without nutrition support for more than 5 days; All patients at moderate or high risk are identified by screening and assessed within 72 hours of admission; Patients at moderate or high risk are able to implement nutrition care plan at discharge. Surgery--No patient is on clear-liquid diet/nothing by mouth without nutrition support for more than 7 days; No patient has weight loss greater than 10% of admission weight at discharge; calorie and protein and/or volume goals for patients on enteral or parenteral nutrition are documented in the medical record; Patients on enteral or parenteral nutrition receive at least 1,000 kcal/day by the fourth day after an operation.

Cardiovascular Diseases↗

Anesthetic care during thiopental tests to evaluate epileptic patients for surgical therapy.

A thiopental test 2 weeks after insertion of intracranial electrodes may be used to evaluate patients with refractory epilepsy for surgical therapy. Barbiturates normally produce beta activity on the electroencephalogram. The absence of this response in a monitored brain region implies focal cerebral dysfunction. We describe a technique used to perform this test and the resultant morbidity. The thiopental test consists of intravenous injection of thiopental, 25 mg, every 30 s until either corneal reflexes are abolished, 1,000 mg of thiopental has been administered, or adverse events occur. In children, the dose is adjusted to approximately 0.3 mg/kg of thiopental every 20 s. A retrospective chart review was performed on 104 patients who underwent thiopental tests at the University of Pittsburgh Epilepsy Center. Records were systematically reviewed for thiopental dose, mean arterial blood pressure, heart rate, oxygen saturation in arterial blood, time to responsivity, need for airway intervention, and occurrence of nausea or vomiting. Thirty-six patients developed upper airway obstruction which required jaw lift maneuver, six patients were given 1,000 mg of thiopental without loss of corneal reflexes, and one patient briefly sustained an arterial saturation of 67%. Five patients exhibited electrographic seizures with clinical seizures evident in two patients. No permanent effects were evident in any patient as a consequence of the test. We conclude, with appropriate monitoring and personnel, that the thiopental test, as described, can be performed safely with acceptable morbidity.

Adolescent↗