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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 37 records · Page 2Linked to original sources

Predictive Factors for the Removal of "Soft" Femoropopliteal Occlusions with Intraarterial Short-term and High-Dose Urokinase Treatment.

To date, intraarterial lysis is a widely accepted form of treatment for femoropopliteal occlusions. However, the outcome of therapy has been difficult to predict. Therefore, the present study dealt with two parameters likely to influence the occlusion removal rate. These are the outflow condition distal of the occlusion, and the occlusion length. Fifty patients with subacute femoropopliteal occlusions were treated with intraarterial thrombolysis and, in case residual obstructions were left, with subsequent catheter dilation. Only "soft" occlusions that were probed by a guide wire and proved to be penetrable were chosen for treatment. The occlusion age was 3.79 +/- 4.57 weeks with 90% of cases in the range of 1 day to 6 weeks. Fibrinolytic therapy consisted of one to three one-hour series of 300,000 IU urokinase instillation directly into the occlusion material. The complete clearance rate was 34/50 = 68%. In successfully treated patients, both the pressure gradient (difference between systemic and ankle pressure) and the walking distance improved significantly. Most important factors for success or failure of treatment were the quality of calf outflow and the length of obstruction. Thus, patients with at least one calf artery open and an occlusion length of under 10 cm presented with an opening rate of 88.5%, whereas patients with no calf arteries patent and an occlusion length over 20 cm presented with an opening rate of only 20%. The age of the occlusions, all penetrable by a guide wire prior to treatment, did not influence the rate of recanalization. Intraarterial short-term and high-dose urokinase infusion is an excellent form of treatment for subacute femoropopliteal occlusions. Especially good results with a 88.5% clearance rate were achieved in patients who presented with at least one calf artery open and an occlusion length below 10 cm.

Journal Article↗

Cognitive functions and psychopathological symptoms in early-onset schizophrenia.

Type and extent of objectively tested cognitive impairments (attention, verbal fluency, nonverbal reasoning) and their association with self-ratings (Paranoia Depression Scale; Frankfurt Complaint Questionnaire) and clinical assessments (Brief Psychiatric Rating Scale, Scales for the Assessment of Positive Symptoms and Negative Symptoms) of psychopathological symptoms were studied in a sample of 74 adolescents primarily suffering from chronic schizophrenia (DSM-III-R; mean duration of illness = 3.4 years), including 15 patients with a very early onset (< 14 years). Special consideration was given to the differentiation between positive and negative symptoms. In cross-sectional analyses, the schizophrenic adolescents were remarkably impaired in both cognitive functions (attention, reasoning) and psychopathological measures (BPRS, SANS, SAPS). However, factor analysis yielded orthogonal factors for cognitive and psychopathological parameters, and canonical correlation analyses did not find a significant correlation between these two areas. As the degree of objectively measured cognitive impairment in chronic schizophrenic adolescents cannot be predicted by the severity of individual psychopathological symptoms, a multidimensional evaluation of the symptomatology seems to be appropriate. Moreover, premorbid disturbances (motor and/or language developmental disorders) and onset characteristics (age, pattern, subdiagnosis), and their relationship to cognitive impairments were investigated. Premorbid disturbances were confirmed as risk factors for the subsequent occurrence of cognitive impairments.

Adolescent↗

[Inframalleolar bypass in limb salvage. Late results].

STUDY OBJECTIVE: The objective of this retrospective study was to report the long-term results of distal revascularization at the ankle in patients with critical ischemia. PATIENTS AND METHODS: From January 1989 to November 1999, 50 inframalleolar bypasses were performed in 49 patients (35 males and 14 females with a mean age of 75 years [range: 51 to 95 years]). Twenty-five patients (50%) were diabetics. All patients presented with critical ischemia of the lower limb. Distal anastomosis was performed at the retromalleolar posterior tibial artery in 28 cases (56%), pedal artery in 20 cases (40%) and distal fibular artery in two cases (4%). Bypasses were performed using a greater saphenous vein (n = 38), a cryopreserved arterial allograft (n = 9), or a PTFE graft (n = 2). A composite graft with greater saphenous vein and arterial allograft was performed in two cases. RESULTS: There were two early postoperative deaths. One patient presented a blow-out of the distal anastomosis that required bypass ligation and subsequent leg amputation. Early thrombosis of the graft occurred in four cases, leading to major amputation in three cases. No patients were lost to follow-up and mean follow-up was 26.7 months (range: 1 to 86 months). Graft thrombosis occurred in 15 patients and led to amputation in 6 cases. Bypass graft patency rate was 72% and 61% at 1 year and 3 years, respectively, yielding a 80% limb salvage rate at 3 years. The 3-year actuarial survival rate was 53%. CONCLUSION: Inframalleolar bypasses are a valuable tool in patients with critical ischemia. The lower limb salvage rate is satisfactory in this elderly population. Based on this experience, angiography with good run-off and, when necessary, a surgical approach to verify patency of the arteries at the ankle should always be performed before undertaking a major amputation.

Aged↗

Validation of the United States' version of the World Health Organization Quality of Life (WHOQOL) instrument.

In 1991, the World Health Organization initiated a project to simultaneously develop a quality of life (QOL) instrument in 15 countries: The World Health Organization Quality of Life (WHOQOL) instrument. This was intended as a generic QOL tool for use with patients across varying disease types, severities of illness, and cultural subgroups. The objective of the current study was to evaluate the WHOQOL-100 in the U.S., one of the original 15 participating countries. The WHOQOL is a 100-item self-report instrument consisting of 24 subscales within six domains: Physical, Psychological, Independence, Social, Environment, and Spiritual. Four additional items pertain to overall QOL/health. We tested the WHOQOL-100 (U.S. version) in a sample of 443 adults (n = 251 chronically ill, n = 128 healthy, and n = 64 childbearing) in the U.S. to test its reliability (internal consistency, test-retest), construct validity (convergent, discriminant), responsiveness, and factor structure. The WHOQOL-100 (U.S. version) has acceptable internal consistency (alpha range: 0.82-0.95 across domains) and reproducibility (ICC range: 0.83-0.96 at 2-week retest interval). It is responsive to change in clinical conditions, as evidenced by predicted score change (effect size) in women after childbirth. Construct validity was demonstrated by (1) its correlation with the Short Form-36 and Subjective Quality of Life Profile, and (2) its ability to discriminate between the diverse samples in this study. The conceptual structure was confirmed exactly with the exception of four facets that did not correlate most highly with the domains to which they were originally assigned, but these differences were minor. The WHOQOL measurement system is suitable for evaluating the QOL of adults in the U.S. The psychometric properties will be continually evaluated as more data become available in the U.S.

Adult↗

A note on Corballis (1997) and the genetics and evolution of handedness: developing a unified distributional model from the sex-chromosomes gene hypothesis.

A unified, quantitative model for sex, twin, parent, and grandparent influences on handedness is presented. Recent research modeling the evolutionary development of genetic mechanisms for the transmission of handedness on the basis of genotype fitness has appeared to lead to the conclusion that a handedness gene cannot be located on the sex chromosomes. It is shown in this article, however, that this conclusion is not of general validity. The sex-chromosomes hypothesis is developed further, and it is demonstrated that a wide-ranging, detailed, and parsimonious account of the distribution of handedness is obtained when left-handedness is assumed to be associated recessively, and with low penetrance, with genetic variation located on the X chromosome.

Female↗

Mice deficient for delta- and mu-opioid receptors exhibit opposing alterations of emotional responses.

The role of the opioid system in controlling pain, reward and addiction is well established, but its role in regulating other emotional responses is poorly documented in pharmacology. The mu-, delta- and kappa- opioid receptors (encoded by Oprm, Oprd1 and Oprk1, respectively) mediate the biological activity of opioids. We have generated Oprd1-deficient mice and compared the behavioural responses of mice lacking Oprd1, Oprm (ref. 6) and Oprk1 (ref. 7) in several models of anxiety and depression. Our data show no detectable phenotype in Oprk1-/- mutants, suggesting that kappa-receptors do not have a role in this aspect of opioid function; opposing phenotypes in Oprm-/- and Oprd1-/- mutants which contrasts with the classical notion of similar activities of mu- and delta-receptors; and consistent anxiogenic- and depressive-like responses in Oprd1-/- mice, indicating that delta-receptor activity contributes to improvement of mood states. We conclude that the Oprd1-encoded receptor, which has been proposed to be a promising target for the clinical management of pain, should also be considered in the treatment of drug addiction and other mood-related disorders.

Animals↗

Cocaine, but not morphine, induces conditioned place preference and sensitization to locomotor responses in CB1 knockout mice.

The involvement of cannabinoid CB1 receptors in morphine and cocaine motivational effects was investigated using CB1 knockout mice. For this purpose, we evaluated the rewarding effects in the place conditioning paradigm and the sensitization to the locomotor responses induced by these drugs. The hyperlocomotion induced by acute morphine administration (15 mg/kg, s.c.) was preserved, but the sensitization to this locomotor response induced by chronic morphine treatment was abolished in CB1 mutant mice. Morphine (5 mg/kg, s.c.) induced conditioned place preference in wild-type mice but failed to produce any response in knockout mice, indicating the inability of morphine to induce rewarding effects in the absence of CB1 cannabinoid receptors. When the aversive effects of morphine withdrawal were investigated using the place aversion paradigm, no differences between genotypes were observed. Acute cocaine (10 mg/kg, i.p.) induced hyperlocomotor responses in wild-type and knockout mice and a chronic cocaine treatment produced a similar sensitization to this response in both genotypes. In the conditioning place preference paradigm, cocaine (20 mg/kg, i.p.) produced rewarding responses in both wild-type and knockout mice. These results demonstrate that CB1 receptors are essential for adaptive responses produced by chronic morphine but not by chronic cocaine treatment.

Animals↗

Discrimination of sepsis and systemic inflammatory response syndrome by determination of circulating plasma concentrations of procalcitonin, protein complement 3a, and interleukin-6.

OBJECTIVE: To evaluate whether plasma concentrations of procalcitonin (PCT), interleukin-6 (IL-6), protein complement 3a (C3a), leukocyte elastase (elastase), and the C-reactive protein (CRP) determined directly after the clinical onset of sepsis or systemic inflammatory response syndrome (SIRS) discriminate between patients suffering from sepsis or SIRS and predict the outcome of these patients. DESIGN: Prospective study. SETTING: Medical intensive care unit at a university hospital. PATIENTS: Twenty-two patients with sepsis and 11 patients with SIRS. MEASUREMENTS AND MAIN RESULTS: The plasma concentrations of PCT, C3a, and IL-6 obtained < or =8 hrs after clinical onset of sepsis or SIRS but not those of elastase or CRP were significantly higher in septic patients (PCT: median, 16.8 ng/mL, range, 0.9-351.2 ng/mL, p = .003; C3a: median, 807 ng/mL, range, 422-4788 ng/mL, p < .001; IL-6: median, 382 pg/mL, range, 5-1004 pg/mL, p = .009, all Mann-Whitney rank sum test) compared with patients suffering from SIRS (PCT: median, 3.0 ng/mL, range, 0.7-29.5 ng/mL; C3a: median, 409 ng/mL, range, 279566 ng/mL; IL-6: median, 98 pg/mL, range, 23-586 pg/mL). The power of PCT, C3a, and IL-6 to discriminate between septic and SIRS patients was determined in a receiver operating characteristic analysis. C3a was the best variable to differentiate between both populations with a maximal sensitivity of 86% and a specificity of 80%. An even better discrimination (i.e., a maximal sensitivity of 91% and a specificity of 80%) was achieved when PCT and C3a were combined in a "sepsis score." C3a concentrations also helped to predict the outcome of patients. Based on the sepsis score, a logistic regression model was developed that allows a convenient and reliable determination of the probability of an individual patient to suffer from sepsis or SIRS. CONCLUSIONS: Our data show that the determination of PCT, IL-6, and C3a is more reliable to differentiate between septic and SIRS patients than the variables CRP and elastase, routinely used at the intensive care unit. The determination of PCT and C3a plasma concentrations appears to be helpful for an early assessment of septic and SIRS patients in intensive care.

Adult↗

Progression of aortic stenosis in the boxer.

Thirty-five boxers that had been referred to the Royal (Dick) School of Veterinary Studies between 1989 and 1994 with left heart base murmurs and aortic velocities greater than 1.5 m/second on Doppler echocardiography were recalled for clinical examination and Doppler echocardiography between 1995 and 1996. Five dogs (14 per cent) showed an increase in murmur grade on repeat visit. Six dogs (17 per cent) showed an increase in aortic velocity of greater than 20 per cent. Eight dogs (23 per cent) had developed aortic valvular or subvalvular two-dimensional echocardiographic changes that had not been present at the initial visit. Seven dogs (20 per cent) had developed aortic regurgitation, and three dogs (8 per cent) mitral regurgitation.

Animals↗

PMS-601, a new platelet-activating factor receptor antagonist that inhibits human immunodeficiency virus replication and potentiates zidovudine activity in macrophages.

We assessed the anti-human immunodeficiency virus (anti-HIV) activity in vitro of new platelet-activating factor (PAF) receptor antagonists, as PAF and viral replication are thought to be involved in HIV neuropathogenesis. We found that PMS-601 inhibited proinflammatory cytokine synthesis and HIV replication in macrophages and potentiated the antiretroviral activity of zidovudine. These results suggest that PMS-601 is of potential value as an adjuvant treatment for HIV infection.

Anti-HIV Agents↗

Effects of MS-8209, an amphotericin B derivative, on tumor necrosis factor alpha synthesis and human immunodeficiency virus replication in macrophages.

Amphotericin B derivatives, such as MS-8209, have been evaluated as a therapeutic approach to human immunodeficiency virus (HIV) infection. We show that MS-8209, like amphotericin B, increases tumor necrosis factor alpha (TNF-alpha) mRNA expression and TNF-alpha production and consequently HIV replication in human macrophages. These effects confirm the pharmacological risk associated with the administration of amphotericin B or its derivatives to HIV-infected patients.

Amphotericin B↗

Comparative analysis of the mucosal adjuvanticity of the type II heat-labile enterotoxins LT-IIa and LT-IIb.

Cholera toxin (CT) and the heat-labile enterotoxin of Escherichia coli (LT-I) are members of the serogroup I heat-labile enterotoxins (HLT) and can serve as systemic and mucosal adjuvants. However, information is lacking with respect to the structurally related but antigenically distinct serogroup II HLT, LT-IIa and LT-IIb, which have different binding specificities for ganglioside receptors. The purpose of this study was to assess the effectiveness of LT-IIa and LT-IIb as mucosal adjuvants in comparison to the prototypical type I HLT, CT. BALB/c mice were immunized by the intranasal (i.n.) route with the surface protein adhesin AgI/II of Streptococcus mutans alone or supplemented with an adjuvant amount of CT, LT-IIa, or LT-IIb. Antigen-specific antibody responses in saliva, vaginal wash, and plasma were assayed by enzyme-linked immunosorbent assay. Mice given AgI/II with LT-IIa or LT-IIb by the i.n. route had significantly higher mucosal and systemic antibody responses than mice immunized with AgI/II alone. Anti-AgI/II immunoglobulin A (IgA) antibody activity in saliva and vaginal secretions of mice given AgI/II with LT-IIa or LT-IIb was statistically similar in magnitude to that seen in mice given AgI/II and CT. LT-IIb significantly enhanced the number of AgI/II-specific antibody-secreting cells in the draining superficial cervical lymph nodes compared to LT-IIa and CT. LT-IIb and CT induced significantly higher plasma anti-AgI/II IgG titers compared to LT-IIa. When LT-IIb was used as adjuvant, the proportion of plasma IgG2a relative to IgG1 anti-AgI/II antibody was elevated in contrast to the predominance of IgG1 antibodies promoted by AgI/II alone or when CT or LT-IIa was used. In vitro stimulation of AgI/II-specific cells from the superficial lymph nodes and spleen revealed that LT-IIa and LT-IIb induced secretion of interleukin-4 and significantly higher levels of gamma interferon compared to CT. These results demonstrate that the type II HLT LT-IIa and LT-IIb exhibit potent and distinct adjuvant properties for stimulating immune responses to a noncoupled protein immunogen after mucosal immunization.

Adhesins, Bacterial↗

Simultaneous detection of multiplex-amplified human immunodeficiency virus type 1 RNA, hepatitis C virus RNA, and hepatitis B virus DNA using a flow cytometer microsphere-based hybridization assay.

The feasibility of performing a multiplex assay for the detection of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) RNAs and hepatitis B virus (HBV) DNA is demonstrated. This assay is based (i) on the coamplification of a 142-bp fragment from the gag region of the HIV-1 genome and a 142-bp HIV-1 quantitation standard fragment, a 244-bp fragment from the 5' noncoding region of the HCV genome, and a 104-bp fragment from the pre-C and C gene regions of the HBV genome, using three sets of specific primers; (ii) on the capacity of these four biotinylated PCR products to hybridize to their specific oligonucleotide probe-coated microspheres; and (iii) on the ability of the flow cytometer to discriminate between distinct fluorescent-microsphere categories. Absence of cross-hybridization between the unrelated oligonucleotide probes and PCR products generated by the multiplex reverse transcription-PCR (RT-PCR) and the highly sensitive detection method allowed us to assess unambiguously the HIV-1 viral load and the infectious status of 35 serologically well-established clinical samples and 20 seronegative blood donor plasma samples tested. The results indicate that multiplex RT-PCR and flow cytometer microsphere-based hybridization assays, when combined, provide a rapid, sensitive, and specific method for the quantitation and detection of the major viral agents of infectious diseases in a single plasma sample.

Acquired Immunodeficiency Syndrome↗

Isolated hyperthermic liver perfusion with high dose tumor necrosis factor alpha in pigs: an experimental study in preparation of clinical Use.

Isolated hyperthermic perfusion of the liver was performed for 45 min in 27 pigs via hepatic artery and portal vein at mean inflow temperatures between 40.7 and 41.2 degrees C. In two study groups B and C (n = 9 pigs each) 50 microg recombinant human tumor necrosis factor-alpha (rhTNFalpha) per kg body weight were added to the perfusate, whereas in a control group A liver perfusion was done without rhTNFalpha. Before reperfusion the livers were washed out with Ringer's solution in all groups followed by a protein solution in group C. At 30 and 60 min after reperfusion the maximum systemic rhTNFalpha concentrations were significantly higher in group B with 68 and 61 ng/ml compared to 14.5 and 14.9 ng/ml in group C (p < 0. 05). Mean systemic porcine TNFalpha concentration was significantly higher in group B (217 pg/ml) compared to group C (50 pg/ml) 30 min after reperfusion (p = 0.012). Survival was 7/9 in group A and C and only 2/9 in group B with 6/7 pigs dying due to severe cardiopulmonary failure within 12 h after operation. In surviving pigs of group A and C only mild and transient hepatotoxicity was registered. The presented study underlines the feasibility of high dose rhTNFalpha application in an isolated hyperthermic liver perfusion system. Washout of the liver with a protein solution before reperfusion reduces systemic TNFalpha levels as well as associated lethal cardiocirculatory and hepatotoxic side effects.

Animals↗

The 'gender gap' in final examination results at Oxford University.

A lower proportion of women than men obtain first class degrees at British universities (the so-called gender gap). At Oxford University, this difference is not seen in all degree subjects but is found both in some Arts and in some Science subjects. We have used a questionnaire administered under supervision to undergraduates 2 to 3 months before their final examination to assess factors which might be expected to affect examination performance. These included measures of verbal and non-verbal reasoning (Alice Heim AH6 test), self-esteem, motivation, responses to stresses of examinations and of personal relationships, happiness, risk-taking and working patterns. We have also obtained a detailed breakdown of the marks the students were given in the examination. Women scored higher on negative emotions while men scored higher on self-esteem, their perception of their own academic efficacy and on risk-taking strategies, but none of these factors predicted outcome. Verbal reasoning ability did predict outcome but there was no gender difference. Hence, it is concluded that the gender gap is not due to any of these individual differences and is more likely to be related to the nature of the academic assessment system.

Affect↗

Multi-center clinical comparison of combination anorganic bovine-derived hydroxyapatite matrix (ABM)/cell binding peptide (P-15) and ABM in human periodontal osseous defects. 6-month results.

BACKGROUND: Intraosseous periodontal defects present a particular treatment problem. New bone replacement grafts offer promise for improved results. METHODS: The role of a synthetic cell-binding peptide (P-15), combined with anorganic [corrected] bovine-derived hydroxyapatite bone matrix (ABM), was compared to ABM alone in human periodontal osseous defects in a controlled, monitored, multi-center trial. Following appropriate initial preparation procedures, flap surgery with defect and root debridement was performed. Two osseous defects per patient were treated randomly with each procedure after surgical preparation. Appropriate periodontal maintenance schedules were followed, and at 6 to 7 months, re-entry flap surgery was performed for documentation and finalization of treatment. RESULTS: T test and Mann-Whitney U analyses of patient mean values from 33 patients revealed that the combination ABM/P-15 grafts demonstrated significantly better mean defect fill of 2.9 +/- 1.2 mm (72.9%) versus a mean defect fill of 2.2 +/- 1.4 mm (50.67%) for defects treated with ABM (P<0.05). Other hard tissue findings showed similar clinically superior results with the use of ABM/P-15. Relative defect fill results showed 81% positive (50% to 100% defect fill) responses with ABM/P-15 and 67% positive responses with ABM. There were 3.5 times as many optimal results (> or = 90% defect fill) with ABM/P-15 and twice as many failures (minimal response) with ABM. Soft tissue findings showed no significant differences between treatments. CONCLUSIONS: These results suggest that the use of the P-15 synthetic cell-binding peptide combined with ABM yields better clinical results than the ABM alone in intrabony periodontal defects.

Adult↗

Soluble transferrin receptor level: a new marker of iron deficiency anemia, a common manifestation of gastric autoimmunity in type 1 diabetes.

OBJECTIVE: A total of 15-20% of type 1 diabetic patients have parietal cell antibodies (PCAs). PCA+ subjects are at increased risk for iron deficiency anemia and atrophic gastritis. Recently, soluble transferrin receptor (sTfR) levels have proven to be a sensitive indicator for iron deficiency They are, in contrast with ferritin levels, independent of inflammation, liver and hormonal status, and sex. We are the first to evaluate sTfR levels in type 1 diabetes and tested the hypothesis of higher sTfR levels in patients with PCAs and/or autoimmune gastritis. RESEARCH DESIGN AND METHODS: We examined 148 type 1 diabetic patients (85 men and 63 women; 50 were PCA+) and 59 sex- and age-matched control subjects (30 men and 29 women). The main outcome measures were sTfR levels, iron deficiency anemia, and atrophic gastritis. Logistical regression analysis tested risk factors for iron deficiency RESULTS: Iron deficiency was present in 38 subjects. Iron (P<0.0001) and ferritin (P<0.0001) levels but not sTfR levels were lower in women. sTfR levels were similar in diabetic and control subjects but were higher in PCA+ subjects (P = 0.015). In diabetic subjects, iron deficiency anemia was more prevalent in PCA+ than in PCA- patients (odds ratio 3.07, P = 0.013) and was associated with sex (P = 0.0001), age (P = 0.046), and sTfR (P = 0.0008) levels. Atrophic gastritis was present in 15 of 28 PCA+ and in 1 of 11 PCA diabetic subjects (P = 0.014). sTfR levels tended to be higher in patients with atrophic gastritis (P = 0.062). CONCLUSIONS: In type 1 diabetes, sTfR levels can be used to diagnose iron deficiency anemia, which is more prevalent in PCA+ subjects. sTfR levels are higher in PCA+ individuals who are at risk for developing atrophic gastritis.

Adult↗