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Biomedical subjects

K Mason

Publications and source records attributed to K Mason.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effects of haemoglobin normalization on quality of life and cardiovascular parameters in end-stage renal failure.

BACKGROUND: The optimal haemoglobin concentration ([Hb]) for patients with end-stage renal failure is uncertain. In particular, it is unclear whether Hb normalization may be an advantage to such patients who are otherwise well. METHODS: A prospective, randomized, double-blind cross-over study was completed in 14 haemodialysis patients (12 male) aged between 23 and 65 years over a period of 18 months, using a variety of measures to examine the effect of epoetin at target [Hb] of 10 g/dl ([Hb](10)) and 14 g/dl ([Hb](14)). Patients were randomized to maintain one or other of the target levels for 6 weeks before being crossed over to the alternative [Hb]. Baseline data (mean [Hb]: 8.5+/-0.2 g/dl) were also included selectively. Six patients were known to be hypertensive. Comparisons were made between 24-h ambulatory blood pressure levels (ABP), echocardiographic findings and estimates of blood volume (BV), plasma volume (PV) and Hb mass. Quality of life estimates were obtained using the Sickness Impact Profile (SIP), and epoetin dosage requirements at target [Hb] were assessed. RESULTS: Daytime and nocturnal ABP (systolic and diastolic) were not different at the respective target [Hb], although nocturnal diastolic levels were higher compared with baseline (73+/-4 mmHg) at both [Hb](10) (83+/-3, P:<0.01) and [Hb](14) (81+/-6, P:<0.05). Significant reductions in cardiac output (5.2+/-0.3 vs 6.6+/-0.5 l/min, P:<0.01) and left ventricular end-diastolic diameter (4.8+/-0.2 vs 5.2+/-0.2 cm, P:<0. 001) were found at [Hb](14) compared with [Hb](10). Left ventricular mass index was correlated with both PV (P:<0.001) and BV (P:<0.01), but not with Hb mass. The PV decreased as the [Hb] rose (P:<0.001) but BV remained unchanged. Quality of life was significantly improved at [Hb](14) compared with [Hb](10) for both total score (6. 5+/-1.7 vs 13.4+/-3.0, P:=0.01) and psychosocial dimension score (5. 4+/-1.9 vs 15.4+/-4.0, P:<0.01). The maintenance weekly dose of epoetin required was 80% higher at [Hb](14) compared with [Hb](10) (P:<0.001). CONCLUSION: These data suggest there may be a significant haemodynamic and symptomatic advantage in maintaining a physiological [Hb] in haemodialysis patients. Although untoward effects were not identified in this study at [Hb](14), a substantially higher dose of epoetin is required to maintain this level.

Adult↗
PubMed2000

Profiles in courage: evolution of Florida's quality improvement and performance measurement system.

As public health begins to embrace performance standards, it is important to critically examine state and local health department quality improvement and performance measurement systems. In this article, Florida's decade-long evolution of quality improvement and performance measurement as well as their integration are described. Lessons for other states are discussed along with implications for implementing performance standards for state and local health departments.

Adolescent↗
PubMed2000

"Broken windows" and the risk of gonorrhea.

OBJECTIVES: We examined the relationships between neighborhood conditions and gonorrhea. METHODS: We assessed 55 block groups by rating housing and street conditions. We mapped all cases of gonorrhea between 1994 and 1996 and calculated aggregated case rates by block group. We obtained public school inspection reports and assigned findings to the block groups served by the neighborhood schools. A "broken windows" index measured housing quality, abandoned cars, graffiti, trash, and public school deterioration. Using data from the 1990 census and 1995 updates, we determined the association between "broken windows," demographic characteristics, and gonorrhea rates. RESULTS: The broken windows index explained more of the variance in gonorrhea rates than did a poverty index measuring income, unemployment, and low education. In high-poverty neighborhoods, block groups with high broken windows scores had significantly higher gonorrhea rates than block groups with low broken windows scores (46.6 per 1000 vs 25.8 per 1000; P < .001). CONCLUSIONS: The robust association of deteriorated physical conditions of local neighborhoods with gonorrhea rates, independent of poverty, merits an intervention trial to test whether the environment has a causal role in influencing high-risk sexual behaviors.

Analysis of Variance↗
PubMed2000

In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody.

Overexpression of epidermal growth factor receptor (EGFR) has been correlated with tumor resistance to cytotoxic agents, including radiation (T. Akimoto et al., Clin. Cancer Res., 5: 2884-2890, 1999), and thus is a candidate target for anticancer treatment. This study investigated whether treatment with C225 anti-EGFR antibody would improve tumor response to radiotherapy. Nude mice bearing 8-mm-diameter A431 tumor xenografts in the hind leg were treated with C225 antibody, 18 Gy of single-dose local tumor irradiation, or both. C225 was given i.p. at a dose of 1 mg/mouse 6 h before irradiation or 6 h before and 3 and 6 days after irradiation. Delay in tumor growth was the treatment end point. C225 dramatically improved the efficacy of local tumor irradiation, particularly when multiple injections of C225 were administered. Tumor radioresponse was enhanced by a factor of 1.59 by a single dose and by a factor of 3.62 by a doses of C225. Histological analyses of tumors revealed that C225 caused a striking increase in central tumor necrosis associated with hemorrhage and vascular thrombosis when combined with radiotherapy. In addition, C225 induced heavy tumor infiltration with granulocytes, increased tumor cell terminal differentiation, and inhibited tumor angiogenesis. We conclude that C225 anti-EGFR antibody enhances tumor radioresponse by multiple mechanisms that may involve direct and indirect actions on tumor cell survival.

Animals↗
PubMed1999

Association of increased radiocurability of murine carcinomas with low constitutive expression of p21(WAF1/CIP1) protein.

PURPOSE: The study investigated whether basal, constitutive levels of p21(WAF1/CIP1) protein in murine carcinomas are related to in vivo tumor radioresponse. The study is based on recent observations demonstrating that in vitro cancer cell lines are resistant to cytotoxic drugs when they express high basal levels of p21(WAF1/CIP1) protein, and that the loss of the p21 gene in the HCT116 human colorectal cancer cell line results in increased radioresponse of xenografts derived from that cell line. METHODS AND MATERIALS: Protein levels of p21(WAF1/CIP1), p53, bax, and bcl-2 were determined in 8 carcinomas (3 mammary carcinomas designated MCa-4, MCa-29, and MCa-35, 2 squamous cell carcinomas designated SCC-IV and SCC-VII, ovarian adenocarcinoma OCa-I, hepatocarcinoma HCa-I, and adenosquamous carcinoma ACa-SG) syngeneic to C3Hf/Kam mice using Western blot analysis. The tumors, growing in the right hind legs of mice, were 8 mm in diameter at the time of analysis. These tumors greatly differ in their radioresponse, assessed by TCD50 assay, and in their susceptibility to radiation-induced apoptosis. RESULTS: Protein levels of these oncogenes varied among tumors, with p21(WAF1/CIP1) showing the greatest variation: its mean densitometric value ranged from 1 to 19. Bcl-2 levels also showed broad variation in densitometric values, from 1 to 10. In comparison, bax and p53 (7 of 8 tumors contained wild-type p53) varied much less among different tumor types; their variation was within a 5-fold range, and the level of p53 was similar in 6 of 8 tumors. Tumor radioresponse correlated significantly (R = 0.77, p = 0.02) only with the magnitude of p21(WAF1/CIP1)expression: tumors with high levels of p21(WAF1/CIP1)were less radiocurable than those with lower levels. Tumor radiocurability showed a significant positive correlation (p = 0.02) with the extent of radiation-induced apoptosis, indicating that tumors that responded to radiation with higher percentages of apoptosis were more curable by radiation. Despite a strong trend to correlation, (p = 0.15), p21(WAF1/CIP1) expression did not correlate significantly with radiation-induced apoptosis, which suggested that p21(WAF1/CIP1) influenced tumor radioresponse by mechanisms beyond that of apoptosis induction. CONCLUSION: Our findings showed that murine tumors exhibit wide variation in constitutive levels of p21(WAF1/CIP1) which had a significant relationship with tumor radioresponse: tumors with high levels of p21(WAF1/CIP1) were less radiocurable than those with lower levels. These findings support the concept that p21(WAF1/CIP1) is a major determinant of tumor radioresponse in vivo, and may have important clinical implications. The pretreatment assessment of p21(WAF1/CIP1) protein could serve as a useful predictor of radiotherapy outcome and may assist in selecting an effective treatment modality.

Animals↗
PubMed1999

Enhancement of tumor radioresponse in vivo by gemcitabine.

Gemcitabine, 2'2'-difluoro-2'-deoxycytidine, is an inhibitor of DNA synthesis and has been shown previously in vitro and in vivo to enhance the cytotoxic activity of radiation as well as some chemotherapeutic agents. Because gemcitabine has shown clinical activity on its own in several solid tumors traditionally treated with radiotherapy, it was of interest to optimize the combination of gemcitabine and radiation. To determine the optimal gemcitabine dose to combine with irradiation and to determine the effect of gemcitabine on tumor growth, mice bearing SA-NH tumors were treated with 2.5 to 600 mg/kg gemcitabine, and subsequent tumor growth was determined. At low doses, gemcitabine induced transient growth delay, whereas higher doses showed both cytotoxic and cytostatic activity. Flow cytometric, histological, and mitotic analyses of irradiated tumors showed that gemcitabine induced a dose-dependent inhibition of DNA synthesis and induction of apoptosis of cells in S phase. DNA synthesis recovered in cells at the G1-S boundary of the cell cycle in a dose-dependent manner, and a parasynchronous movement of cells through the cell cycle ensued. To determine the optimal schedule for gemcitabine administration in relation to irradiation, tumor-bearing mice were given a single 50 mg/kg dose of gemcitabine at various times before or after irradiation. Gemcitabine enhanced radioresponse in a time-dependent fashion. The highest enhancement factors for tumor growth delay (1.68-2.03) were observed when gemcitabine was administered 24-60 h before irradiation. Although gemcitabine reduced the radiation tumor control dose at all administration times used, the greatest enhancement of tumor radiocurability occurred when gemcitabine was administered 24 h before irradiation (dose modification factor of 1.54). Moreover, gemcitabine decreased the lung metastatic rate in mice with local tumor control from 73% in mice receiving radiation alone to 40% in mice receiving the combination (all combination times included). These results suggest that gemcitabine has strong radioenhancing properties and that the greatest interaction occurs when gemcitabine administration precedes irradiation by 24-72 h. Preliminary studies indicate that normal tissues recover more quickly than tumor tissues from gemcitabine treatment; thus, optimized scheduling of gemcitabine and irradiation may serve to improve the therapeutic ratio of the combination.

Animals↗
PubMed1999

Trauma systems and major injury centres for the 21st century: an option.

Trauma, especially involving accidents and falls is now the leading cause of death in the UK in the first four decades of life. This paper looks at the existing pattern of Accident and Emergency Units and suggests that because it has grown up in a fragmented and poorly co-ordinated fashion and because it is subjected to demands that it was not designed for, it is inadequate in dealing with the most severe injury cases. Following collaborative work with researchers at the North Staffordshire Hospital, the authors propose a system of thirty major trauma centres to cover the whole of the UK. Each would deal with the most severe accident cases from surrounding hospitals. Using data from the census and from health authorities, analysed within a GIS environment, a locational pattern for these centres is suggested and their catchment areas are outlined.

Adolescent↗
PubMed1999

Physical performance and associated electrolyte changes after haemoglobin normalization: a comparative study in haemodialysis patients.

BACKGROUND: To determine the effects of different haemoglobin (Hb) levels on exercise performance and associated electrolyte changes, a prospective, randomized, double-blinded crossover study was completed in 14 haemodialysis patients. METHODS: Performance and changes in arterial [K+] and lactate were compared at rest and during a maximal incremental cycling exercise at a Hb concentration ([Hb]) of 10 g/dl ([Hb]10) and 14 g/dl ([Hb]14) following an initial baseline test (Hb: 8.3 +/- 0.2 g/dl, mean +/- SEM). Ages ranged from 23 to 65 years and patients were divided into younger (age 23-45 years, n = 9) and older (aged 55-65 years, n = 5) groups. RESULTS: Peak work rate and VO2 peak were higher at [Hb]14 than at [Hb]10. 145 +/- 9 vs 134 +/- 9 W, mu +/- SEM, P < 0.01, and 1.90 +/- 0.11 vs 1.61 +/- 0.11 l/min, P < 0.01, respectively. Improvements were demonstrated in both younger and older groups at the higher target [Hb], with an improved aerobic performance evident particularly in younger patients. However, performance remained below that predicted for comparable sedentary controls. Resting plasma [K+] was raised at both [Hb]10 and [Hb]14 compared with baseline (P < 0.01) although the change in [K+] from rest to peak exercise (delta[K+]) was similar at each level. The delta[K+] per unit work performed (used as a marker of K+ regulation) was, however, inversely related to the [Hb] (baseline: 80 +/- 12 micromol/l/kJ vs [Hb]10, 61 +/- 8, P < 0.01, vs [Hb]14. 49 +/- 7, P < 0.05). Exercise induced a significant but similar rise in lactate concentration at both target [Hb] (P < 0.001), which remained markedly elevated for at least 10 min after exercise in both younger and older groups. CONCLUSIONS: These data demonstrate that a physiological [Hb] improves, but does not normalize, exercise performance in end-stage renal failure. Both younger and older patients appear to benefit similarly from the enhanced oxygen transport. Impaired K+ regulation is apparently related to [Hb] and could well contribute to the observed limitations in performance.

Adult↗
PubMed1999

Inverse relationship between epidermal growth factor receptor expression and radiocurability of murine carcinomas.

The study investigated whether a relationship exists between the extent of epidermal growth factor receptor (EGFR) expression and in vivo radiocurability of murine tumors. EGFR expression was determined in nine carcinomas (four mammary carcinomas, designated MCa-4, MCa-29, MCa-35, and MCa-K; two squamous cell carcinomas, designated SCC-IV and SCC-VII; an ovarian adenocarcinoma, OCa-I; a hepatocarcinoma, HCa-I; and an adenosquamous carcinoma, ACa-SG) syngeneic to C3Hf/Kam mice using Western blot analysis. These tumors greatly differed in their radioresponse, assessed by TCD50 assay, and in their susceptibility to radiation-induced apoptosis. Likewise, the expression of EGFR greatly varied, by as much as 21-fold, and the magnitude of the EGFR expression positively correlated with increased tumor radioresistance. The levels of EGFR inversely correlated with radiation-induced apoptosis, suggesting that the lack of sensitivity to apoptosis induction was a major mechanism responsible for radioresistance of tumors with high EGFR. This correlation was highly significant only for wild-type p53 carcinomas. Radiation activated EGFR autophosphorylation and increased the activity of protein tyrosine kinase, but only in tumors with high EGFR expression. Thus, EGFR expression was a major determinant of tumor radioresponse in vivo. The pretreatment assessment of EGFR expression could predict radiotherapy outcome and may assist in selecting an effective treatment modality.

Animals↗
PubMed1998

Selective uncoupling of RGS action by a single point mutation in the G protein alpha-subunit.

Heterotrimeric G proteins function as molecular relays, shuttling between cell surface receptors and intracellular effectors that propagate a signal. G protein signaling is governed by the rates of GTP binding (catalyzed by the receptor) and GTP hydrolysis. RGS proteins (regulators of G protein signaling) were identified as potent negative regulators of G protein signaling pathways in simple eukaryotes and are now known to act as GTPase-activating proteins (GAPs) for G protein alpha-subunits in vitro. It is not known, however, if Galpha GAP activity is responsible for the regulatory action of RGS proteins in vivo. We describe here a Galpha mutant in yeast (gpa1(sst)) that phenotypically mimics the loss of its cognate RGS protein (SST2). The gpa1(sst) mutant is resistant to an activated allele of SST2 in vivo and is unresponsive to RGS GAP activity in vitro. The analogous mutation in a mammalian Gqalpha is also resistant to RGS action in transfected cells. These mutants demonstrate that RGS proteins act through Galpha and that RGS-GAP activity is responsible for their desensitizing activity in cells. The Galphasst mutant will be useful for uncoupling RGS-mediated regulation from other modes of signal regulation in whole cells and animals.

Animals↗
PubMed1998

Multiplex display polymerase chain reaction amplifies and resolves related sequences sharing a single moderately conserved domain.

We present a technique, multiplex display polymerase chain reaction (MD-PCR), that amplifies and resolves coding sequences from messenger RNAs sharing only a single moderately conserved domain encoding eight or nine amino acids. The technique, a form of single-sided PCR, allows detection of known and novel genes in a family by using one degenerate primer complementary to a gene family-specific domain. A second common primer is complementary to an oligonucleotide ligated to a nearby restriction enzyme cleavage site. Uniquely, restriction enzyme digestion of single-stranded cDNA, a technique never previously performed to useful advantage, is used to increase the specificity and sensitivity of the technique. Up to several hundred bases of coding sequence are amplified simultaneously from many (potentially from all) genes in a specific family, yielding products of different sizes from different genes, and allowing amplified products to be resolved electrophoretically. Typically, more than 50% of the amplified sequences are from the targeted gene family and many of the amplified products are novel sequences. mRNAs representing less than 1 in 100,000 messages can be detected. The method allows the focused yet open-ended examination of genes in families known to be important in both normal cellular homeostasis and the etiology of many diseases.

Animals↗
PubMed1998

The anxiogenic agents, yohimbine and FG 7142, disrupt the noradrenergic response to novelty.

Whether or not abnormal noradrenergic transmission can be a causal factor in anxiety is controversial. The present experiments examined this question by comparing the effects of two anxiogenic agents on noradrenaline efflux in the frontal cortex of freely moving rats. A single anxiogenic dose of either yohimbine (2.5 or 5 mg/kg) or FG 7142 (10 or 20 mg/kg) was administered to rats by i.p. injection. Yohimbine increased spontaneous efflux of noradrenaline, but FG 7142 had no effect. However, subsequent exposure of rats to a novel environment increased noradrenaline efflux in vehicle-, but not drug-treated rats. Calculation of the net change in noradrenaline efflux caused by transfer to the novel environment showed that this was reduced by yohimbine, whereas FG 7142 increased it. These two compounds also had different effects on locomotor activity in the novel environment. The results suggest that anxiety is unlikely to be invariably associated with increased noradrenergic transmission, in the frontal cortex at least. However, it remains possible that any disruption of the noradrenergic response to stress could be an underlying feature of anxiety.

Adrenergic alpha-Agonists↗
PubMed1998

Expression of novel potassium channels in the chick basilar papilla.

Ionic currents are critical for the functioning of the inner ear auditory sensory epithelium. We set out to identify and molecularly clone the genes encoding the channels responsible for several currents in the chick basilar papilla. Here we describe an inward-rectifying K+ channel, cKir2.3, present in both hair cells and support cells in the apical end of the chick basilar papilla. The biophysical properties of the human ortholog, hKir2.3, are similar to those of an inward-rectifying channel found in the apical end of the chick basilar papilla, suggesting that this channel may contribute to the corresponding current. Additionally, we describe two new members of the Kv6 subfamily of putative regulatory voltage-gated K channels, cKv6.2 and cKv6.3. Both are expressed in hair cells in the apical end of the chick basilar papilla; cKv6.2 is also strongly expressed in support cells and in the brain.

Amino Acid Sequence↗
PubMed1997

A prospective, randomized study of open vs laparoscopic inguinal hernia repair. An assessment of postoperative pain.

OBJECTIVE: To compare postoperative pain after laparoscopic hernia repair and conventional open hernia repair. DESIGN: Prospective, randomized study. SETTING: Veterans Affairs Medical Center. PATIENTS: Sixty-two patients scheduled for elective inguinal hernia repair. INTERVENTIONS: Patients were randomized in the operating room to have a laparoscopic hernia repair (30 patients) or a conventional open hernia repair (32 patients). All operations were performed while the patient was under general anesthesia to avoid anesthesia as a confounding variable. MEASURES: Postoperative pain following laparoscopic hernia repair and open hernia repair were compared using the McGill Pain Score, the McGill Visual Analogue Pain Scale score, and the number of acetaminophen with 30-mg codeine sulfate (Tylenol 3) tablets needed for pain during the first and second 24-hour periods postoperatively. All of the patients were interviewed and the postoperative pain was evaluated by a special study nurse (P.M.L.) who was blinded to the repair technique. RESULTS: At 24 hours, the patients with laparoscopic hernia repair had 26% less pain by the McGill Pain Score (P = .02) and 31% less pain by the McGill Visual Analogue Scale (P = .006) than those who underwent an open hernia repair. At 48 hours the patients who underwent laparoscopic hernia repair had 28% less pain by the McGill Pain Score (P = .03), 42% less pain by the McGill Visual Analogue Scale (P = .002), and used 42% fewer analgesic tablets (P = .004). CONCLUSION: Patients with a laparoscopic hernia repair had significantly less pain postoperatively than those with standard open hernia repairs.

Aged↗
PubMed1997

Effects of chronic ethanol exposure on GABA receptors and GABAB receptor modulation of 3H-GABA release in the hippocampus.

Chronic ethanol treatment (CET), sufficient for decreasing long-term potentiation (LTP) in rats, also enhances 3H-GABA release from hippocampal slices in these same animals. The mechanism for an increase in GABA release may involve changes in presynaptic receptors. Therefore, we characterized presynaptic autoreceptor modulation of 3H-GABA release in hippocampal slices from control and CET rats. The effects of a GABAB receptor agonist (baclofen) and antagonist [2-hydroxy (OH)-saclofen] were tested for their ability to modulate electrically stimulated 3H-GABA release from superfused hippocampal slices. Baclofen decreased stimulated release in a dose-dependent manner and 2-OH-saclofen increased release consistent with the existence of presynaptic GABAB autoreceptors in hippocampus. The GABAA antagonist bicuculline did not significantly modulate basal or stimulated release. When the effects of baclofen and 2-OH-saclofen were measured in animals 48 hr after withdrawal from CET, presynaptic modulation of release by baclofen and 2-OH-saclofen was decreased. In addition, we examined the density of 3H-baclofen and 3H-bicuculline binding in the hippocampal formation using quantitative autoradiographic techniques. We found that the density of 3H-baclofen binding sites was not affected by CET, whereas the density of 3H-bicuculline binding sites was increased by 28% in ethanol-treated rats. These data may explain how CET increases presynaptic regulation of GABA release from hippocampus that may contribute to the decrease in LTP seen in rats after CET.

Alcoholism↗