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Biomedical subjects

M de Groot

Publications and source records attributed to M de Groot.

At least 19 recordsLinked to original sources

The active straight leg raising test (ASLR) in pregnant women: differences in muscle activity and force between patients and healthy subjects.

Pregnancy-related low back and pelvic pain (PLBP) is a frequent complication of pregnancy. Although pathological mechanisms underlying PLBP are obscure, dysfunction of the sacroiliac joints (SI-joints) seems to play an important role. A cross-sectional study was performed on 24 pregnant women with and without PLBP. The objective was to determine muscle activation patterns of trunk and leg muscles during the active straight leg raising test (ASLR) and static hip flexion, and to determine maximal hip flexion force at 0 and 20 cm leg raise height. Moreover, the effort to raise the leg was scored. The measurements resulted in several significant differences between the patients and healthy controls; among others (a) patients scored subjectively more effort during ASLR, (b) at both 0 and 20 cm leg raise height patients had less hip flexion force, and (c) patients developed more muscle activity during ASLR. Since pregnant women with PLBP developed a higher muscle activity during ASLR with a significantly lower output at 0 and 20 cm than healthy pregnant women, it could be proposed that the ASLR demonstrates a disturbed load transfer across the SI-joints in this population.

Abdominal Muscles↗

Initial experience with routine administration of etanercept in psoriasis.

BACKGROUND: Etanercept and efalizumab recently became available and reimbursed for routine use in severe psoriasis in the Netherlands. The criteria for reimbursement are Psoriasis Area and Severity Index (PASI) > or = 10 (or Skindex-29 > or = 35 if PASI > or = 8 and < 10) and ineffectiveness of ultraviolet (UV) B/psoralen plus UVA, methotrexate and ciclosporin, or a contraindication to or serious side-effect(s) during these treatments. OBJECTIVES: We hypothesized: (i) that efficacy would be lower than that obtained in published phase II and III studies because (a) resistance to all conventional therapies as a reimbursement condition would select for more resistant cases and (b) inclusion would be more restricted to severe cases (higher PASI), and (ii) that efficacy would be lower in obese patients due to the possible role of adipose tissue in tumour necrosis factor (TNF)-alpha homeostasis. METHODS: We treated 50 patients (38 men, 12 women; mean PASI 15.8) with etanercept 25 mg or 50 mg twice weekly and evaluated in a retrospective analysis the efficacy and safety in comparison with data from published trials. Additionally, we related the clinical effect to the body mass index (BMI), for adipose tissue is thought to have a possible role in TNF-alpha homeostasis. RESULTS: Based on the literature, 30% and 49% of the patients treated with etanercept 25 mg and 50 mg twice weekly, respectively, should have achieved 75% or more improvement in PASI compared with baseline (PASI 75), and 10% and 21%, respectively, should have achieved 90% or more improvement (PASI 90). Our data showed that 21% in the 2 x 25 mg group and 23% in the 2 x 50 mg group achieved PASI 75. PASI 90 was only attained in 7% of patients treated with 2 x 25 mg and 6% of those treated with 2 x 50 mg. Contrary to our hypothesis, the mean initial PASI was comparable with the mean PASI mentioned in the phase II and III clinical trials. Although fatigue is not identified as a side-effect of etanercept, 10% of our patients reported fatigue as an adverse event during etanercept treatment. High BMI, indicating overweight or obesity, was found both in patients with little efficacy and in patients achieving PASI 75 or better. CONCLUSIONS: Use of etanercept in real practice gives impressive results, but these are generally less favourable than those published in clinical trial reports. This is probably due to the stringent conditions for reimbursement, which select for more treatment-resistant patients. Fatigue as a possible side-effect of etanercept should also be an issue for further investigation. Finally, the BMI does not seem to influence the patients' response to etanercept, although further investigations would be needed to confirm this.

Adult↗

Rat islet isolation yield and function are donor strain dependent.

Effective rat islet isolation is pertinent for successful islet transplantation and islet studies in vitro. To determine which rat strain yields the highest number of pure and functional islets, four commonly used rat strains were compared with regard to islet yield, islet purity and islet function. Secretory responses were assessed by stimulation with glucose, and by stimulation with glucose plus 3-isobutyl-1-methylxanthine (IBMX). We show that rat islet function and isolation yield are donor strain dependent. Albino Oxford (AO) rats donated twice as many islets than Wistar, Lewis and Sprague Dawley (SD) rats. Stimulation with glucose plus IBMX resulted in an average five-fold increase of the stimulation index of AO, Lewis, Wistar and SD rats compared to stimulation with glucose only. AO islets had improved secretory responses after a one-week culture period, but required the addition of IBMX to glucose to elicit a distinguished stimulated insulin secretion after 2 days of culture. Islets from SD rats showed inferior results with regard to purity immediately after isolation and with regard to function after short- and after long-time culture. Because Lewis islets possessed the highest secretory response to glucose (without IBMX) immediately after isolation, Lewis rats may be preferred as islet donors for immediate use. The addition of IBMX to glucose for in vitro functional testing is recommended because it elicits high insulin secretory responses of islets regardless of the rat strain. AO rats are preferred for culture experiments since the number of experimental animals is reduced two-fold compared to Lewis, Wistar and SD rats.

1-Methyl-3-isobutylxanthine↗

Response of encapsulated rat pancreatic islets to hypoxia.

Hypoxia contributes to encapsulated pancreatic islet graft failure. To gain insight into the mechanisms that lead to hypoxia-induced graft failure, encapsulated islet function, vitality, and cell replication were assessed after 2 and 5 days of hypoxic (1% O2) and normoxic (20% O2) culture. The mRNA expression levels of Bcl-2, Bax, inducible nitric oxide synthase (iNOS), and monocyte chemoattractant protein 1 (MCP-1) were assessed, as well as the amount of nitrite and MCP-1 in the culture medium. Hypoxia was associated with loss of encapsulated islet function and vitality, but not with an increase in islet cell replication. Loss of vitality was due to necrosis, and only modestly due to apoptosis. Hypoxia was not associated with changes in the Bcl-2/Bax mRNA ratio, but it did increase the expression of iNOS and MCP-1 mRNA. The increased mRNA levels were, however, not associated with elevated concentrations of nitrite nor with elevated levels of MCP-1 protein. The increased iNOS mRNA levels imply a role for NO in the completion of cell death by hypoxia. The increased MCP-1 mRNA levels suggest that encapsulated islets in vivo contribute to their own graft failure by attracting cytokine-producing macrophages. The discrepancy between iNOS mRNA and nitrite is explained by the longer half-life of NO during hypoxia. MCP-1 protein levels are underestimated as a consequence of the lower number of vital cells in combination with a higher proteolytic activity due to necrosis. Thus, strategies to eliminate hypoxia may not only improve islet function and vitality, but may also reduce the attraction of macrophages by encapsulated islets.

Animals↗

Detection of myocardial viability based on measurement of sodium content: A (23)Na-NMR study.

MRI of total sodium (Na) content may allow assessment of myocardial viability, but information on Na content in normal myocardium, necrotic/scar tissue, and stunned or hibernating myocardium is lacking. Thus, the aims of the study were to: 1) quantify the temporal changes in myocardial Na content post-myocardial infarction (MI) in a rat model (Protocol 1); 2) compare Na in normally perfused, hibernating, and stunned canine myocardium (Protocol 2); and 3) determine whether, in buffer-perfused rat hearts, infarct scar can be differentiated from intact myocardium by (23)Na-MRI (Protocol 3). In Protocol 1, rats were subjected to LAD ligation. Infarct/scar tissue was excised at control and 1, 3, 7, 28, 56, and 128 days post-MI (N = 6-8 each), Na content was determined by (23)Na-NMR spectroscopy (MRS) and ion chromatography. Na content was persistently increased at all time points post-MI averaging 306*-160*% of control values (*P < 0.0083 vs. control). In Protocol 2, (23)Na-MRS of control (baseline), stunned and hibernating samples revealed no difference in Na. In Protocol 3, (23)Na-MRI revealed a mean increase in signal intensity, to 142 +/- 6% of control values, in scar tissue. A threshold of 2 standard deviations of the image intensity allowed determination of infarct size, correlating with histologically determined infarct size (r = 0.91, P < 0.0001).

Animals↗

[Contralateral and ipsilateral repetitive transcranial magnetic stimulation in Parkinson patients].

In seven women and two men with Parkinson's disease, Hoehn and Yahr stage 1 or 2, the effect of repetitive transcranial magnetic stimulation (rTMS) was evaluated. Primary endpoint outcome measure was the changing of the motor items of the Unified Parkinson's Disease Rating Scale (subscale III of UP-DRS) 24 h after stimulation. Kinesiologic tests and writing samples were secondary outcome measures. After discontinuing all medication, stimulation was performed with 5 Hz at 90% of the motor threshold over the primary motor cortex of the more affected. There were 2250 stimuli applied, divided into 15 trains at intervals of 10 s. The identical treatment of the opposite side served as control treatment. Only treatment of the more affected side resulted in a significant improvement of the clinical symptoms of 46% as assessed by the UPDRS (p < 0.02). This effectiveness differed significantly from the control treatment (21%, p < 0.02). The kinesiological testing did not show any significant speeding of movements (p > 0.05). Some patients showed a normalisation of the previously disturbed handwriting specimen. These data confirm the previous observation that rTMS of primary motor regions leads to at least temporary clinical improvement of symptoms in patients with Parkinson's disease.

Dominance, Cerebral↗

Temporal fluctuations of myocardia high-energy phosphate metabolite with the cardiac cycle.

This review describes the temporal changes of high-energy phosphate metabolites during the cardiac cycle. Under baseline condition, the extent of cyclical changes ("cycling") of ATP, phosphocreatine and inorganic phosphate varies between 10-15%. Such energy oscillations are not augmented under various forms of metabolic stress including 1) inotropic stimulation, 2) acute hypoxia and 3) failing, chronically infarcted hearts. Thus, the concentrations of high-energy phosphates over the cardiac cycle are a tightly regulated entity, even when energetic needs are substantially augmented.

Adenosine Triphosphate↗

[Acupuncture: complications, contraindications and informed consent].

With the widespread usage of acupuncture, the number of reports about complications of this treatment increases. Harmless disturbances are common and include minor bleedings or haematomas, pain during insertion or after withdrawal of the needle, and skin symptoms. In every second acupuncture treatment, at least one of these complications occurs. Orthostatic dysregulations are relatively rare and can be observed in only 1% of patients. They can be prevented by treating the patient in a lying position, especially in the first treatment session. Stab injuries of internal organs most often affect the lungs, resulting in a pneumothorax. At least 23 cases have been published, 2 of them with fatal consequences. An inquiry of Norwegian doctors even suggests that until 1995 in Norway alone 250 cases of pneumothorax after acupuncture occurred. Stab injuries of other internal organs or the CNS are only described in case reports, but some of them had fatal consequences. Stab injuries of peripheral nerves or large vessels and systemic bacterial infections like sepsis or endocarditis are very rare but serious consequences have been described. The transmission of viral infections due to insufficiently sterilised acupuncture needles loses more and more importance. The incidence of local infections can possibly be influenced, but even in Europe this complication still occurs frequently. The overview of published complications leads to the contraindications of acupuncture. Disturbances of coagulation, immune deficiency, abnormal heart valves or prosthetic valves are the most important ones to name. Suggestions for obtaining informed consent may be helpful while performing clinical trials.

Acupuncture Therapy↗

Depression and poor glycemic control: a meta-analytic review of the literature.

OBJECTIVE: Depression is common among patients with diabetes, but its relationship to glycemic control has not been systematically reviewed. Our objective was to determine whether depression is associated with poor glycemic control. RESEARCH DESIGN AND METHODS: Medline and PsycINFO databases and published reference lists were used to identify studies that measured the association of depression with glycemic control. Meta-analytic procedures were used to convert the findings to a common metric, calculate effect sizes (ESs), and statistically analyze the collective data. RESULTS: A total of 24 studies satisfied the inclusion and exclusion criteria for the meta-analysis. Depression was significantly associated with hyperglycemia (Z = 5.4, P < 0.0001). The standardized ES was in the small-to-moderate range (0.17) and was consistent, as the 95% CI was narrow (0.13-0.21). The ES was similar in studies of either type 1 or type 2 diabetes (ES 0.19 vs. 0.16) and larger when standardized interviews and diagnostic criteria rather than self-report questionnaires were used to assess depression (ES 0.28 vs. 0.15). CONCLUSIONS: Depression is associated with hyperglycemia in patients with type 1 or type 2 diabetes. Additional studies are needed to establish the directional nature of this relationship and to determine the effects of depression treatment on glycemic control and the long-term course of diabetes.

Adult↗

An EGP-2/Ep-CAM-expressing transgenic rat model to evaluate antibody-mediated immunotherapy.

The human pancarcinoma-associated epithelial glycoprotein-2 (EGP-2), also known as 17-1A or Ep-CAM, is a 38-kDa transmembrane antigen, commonly used for targeted immunotherapy of carcinomas. Although strongly expressed by most carcinomas, EGP-2 is also expressed in most simple epithelia. To evaluate treatment-associated effects and side-effects on tumor and normal tissue respectively, we generated an EGP-2-expressing transgenic Wistar rat. To express the cDNA of the EGP-2 in an epithelium-specific manner, the 5' and 3' distal flanking regions of the human keratin 18 (K18) gene were used. EGP-2 protein expression was observed in the liver and pancreas, whereas EGP-2 mRNA could also be detected in lung, intestine, stomach and kidney tissues. In this rat, EGP-2-positive tumors can be induced by injecting a rat-derived carcinoma cell line transfected with the GA733-2 cDNA encoding EGP-2. Transgenic rats were used to study specific in vivo localization of an i.v. anti-EGP-2 monoclonal antibody, MOC31, applied i.v. Immunohistochemical analyses showed the specific localization of MOC31 in s.c. induced EGP-2-positive tumors, as well as in the liver. In contrast, in EGP-2-transgenic rats, MOC31 did not bind to EGP-2-negative tumors, the pancreas, or other normal tissues in vivo. In conclusion, an EGP-2-transgenic rat model has been generated that serves as a model to evaluate the efficacy and safety of a variety of anti-EGP-2-based immunotherapeutic modalities.

Animals↗

Glycemic control and major depression in patients with type 1 and type 2 diabetes mellitus.

The current study evaluated the association of glycemic control and major depression in 33 type 1 and 39 type 2 diabetes mellitus patients. Type 1 patients with a lifetime history of major depression showed significantly worse glycemic control than patients without a history of psychiatric illness (t = 2.09; df = 31, p < 0.05). Type 2 diabetes patients with a lifetime history of major depression did not have significantly worse control than those with no history of psychiatric illness. Findings from this study indicate different relationships between lifetime major depression and glycemic control for patients with type 1 and type 2 diabetes. Treatment implications for glycemic control in type 1 and type 2 diabetes patients are discussed.

Adult↗

Effects of ACE inhibition and beta-receptor blockade on energy metabolism in rats postmyocardial infarction.

Chronic treatment with beta-receptor blockers or angiotensin-converting enzyme (ACE) inhibitors in heart failure can reduce mortality and improve left ventricular function, but the mechanisms involved in their beneficial action remain to be fully defined. Our hypothesis was that these agents prevent the derangement of cardiac energy metabolism. Rats were subjected to myocardial infarction (MI) or sham operation. Thereafter, animals were treated with bisoprolol, captopril, or remained untreated. Two months later, cardiac function was measured in the isolated heart by a left ventricular balloon (pressure-volume curves), and energy metabolism of residual intact myocardium was analyzed in terms of total and isoenzyme creatine kinase (CK) activity, steady-state levels (ATP, phosphocreatine), and turnover rates (CK reaction velocity) of high-energy phosphates (31P nuclear magnetic resonance) and total creatine content (HPLC). Bisoprolol and partially captopril prevented post-MI hypertrophy and partially prevented left ventricular contractile dysfunction. Residual intact failing myocardium in untreated, infarcted hearts showed a 25% decrease of the total, a 26% decrease of MM-, and a 37% decrease of the mitochondrial CK activity. Total creatine was reduced by 15%, phosphocreatine by 21%, and CK reaction velocity by 41%. Treatment with bisoprolol or captopril largely prevented all of these changes in infarcted hearts. Thus the favorable functional effects of beta-receptor blockers and ACE inhibitors post-MI are accompanied by substantial beneficial effects on cardiac energy metabolism.

Adenine Nucleotides↗

Why do microencapsulated islet grafts fail in the absence of fibrotic overgrowth?

The survival of microencapsulated islet grafts is limited, even if capsular overgrowth is restricted to a small percentage of the capsules. In search of processes other than overgrowth contributing to graft failure, we have studied the islets in non-overgrown capsules at several time points after allotransplantation in the rat. All recipients of islet allografts became normoglycemic. Grafts were retrieved at 4 and 8 weeks after implantation and at 15.3 +/- 2.3 weeks postimplant, 2 weeks after the mean time period at which graft failure occurred. Overgrowth of capsules was complete within 4 weeks postimplant, and it was usually restricted to <10% of the capsules. During the first 4 weeks of implantation, 40% of the initial number of islets was lost. Thereafter, we observed a decrease in function rather than in numbers of islets, as illustrated by a decline in the ex vivo glucose-induced insulin response. At 4 and 8 weeks postimplant, beta-cell replication was 10-fold higher in encapsulated islets than in islets in the normal pancreas, but these high replication rates were insufficient to prevent a progressive increase in the percentage of nonviable tissue in the islets. Necrosis and not apoptosis proved to be the major cause of cell death in the islets. The necrosis mainly occurred in the center of the islets, which indicates insufficient nutrition as a major causative factor. Our study demonstrates that not only capsular overgrowth but also an imbalance between beta-cell birth and beta-cell death contributes to the failure of encapsulated islet grafts. Our observations indicate that we should focus on finding or creating a transplantation site that, more than the unmodified peritoneal cavity, permits for close contact between the blood and the encapsulated islet tissue.

Animals↗

Changes of myocardial high-energy phosphates with the cardiac cycle during acute or chronic myocardial stress.

Whether changes of cardiac high-energy phosphate concentrations occur over the cardiac cycle remains controversial. The hypothesis was that such cyclical changes are accentuated during acute or chronic myocardial stress. Isolated rat hearts were perfused under four conditions: (1) control, (2) inotropic stimulation by doubling of perfusate [Ca2+], (3) acute hypoxia (buffer PO2 approximately 150 torr), and (4) failing, chronically infarcted hearts. 31P-MR spectra were obtained at seven time points of the cardiac cycle. Under control conditions, cyclical changes ("cycling") of ATP (11+/-3%*, *P < 0.05) and phosphocreatine (9+/-2%*) were detected, inorganic phosphate cycling did not reach statistical significance. At high [Ca2+] perfusion, cycling of phosphocreatine (9+/-5%*) was not accentuated, cycling of ATP and inorganic phosphate did not reach significance. During acute hypoxia, cycling of ATP (10+/-4%*) and inorganic phosphate (11+/-4%*) occurred, but cyclical changes of phosphocreatine were not significant. In chronically infarcted hearts, the extent of cyclical changes of ATP, phosphocreatine, and inorganic phosphate was not accentuated. Thus, in perfused rat heart, small oscillations of high-energy phosphates during the cardiac cycle are detectable, but such changes are not accentuated during acute or chronic stress. The concentrations of high-energy phosphates over the cardiac cycle are tightly regulated.

Acute Disease↗

Thoracoscopy in undiagnosed pleural effusions.

OBJECTIVE: To review the indications and accuracy of diagnostic thoracoscopy for pleural effusions of unknown origin. DESIGN: Retrospective review of consecutive patients referred for diagnostic thoracoscopy over a 5-year period from 1 January 1989 to 31 December 1993. SETTING: Tertiary referral cardiothoracic unit. PATIENTS: Thirty-four patients referred from either medical or oncology services within a university-affiliated academic complex. INTERVENTIONS: All patients had diagnostic thoracoscopy performed under general anaesthesia. Retrospective data were collected in respect of presenting symptoms, gross findings, final pathological findings, amount of drainage, length of hospital stay and complications of the procedure. In 7 patients (21%), iodised talc was insufflated at the same time to create pleurodesis. MAIN RESULTS: Final diagnoses were: 17 (50%) malignant disease, 6 (18%) tuberculosis and 9 (26%) 'negative' pathology. In 2 (6%), further intervention was required to make a conclusive diagnosis. The diagnostic sensitivity for malignant disease was 89% and the specificity 100%. For pleural tuberculosis both the sensitivity and specificity were 100%. For 'negative' diagnoses the negative predictive value was 82%. A history of fever and sweats had a marked association (P = 0.002) with the final diagnosis of tuberculosis. No association could be identified between the gross observations at the time of thoracoscopy and the final diagnosis. The average length of hospital stay was 6.7 (range 1-25) days. There was 1 in-hospital death (3%), and 9 patients (26%) had major complications related to the procedure. CONCLUSIONS: Diagnostic thoracoscopy is a useful modality for obtaining a diagnosis in effusions of unknown origin where other methods have failed. The presence of symptoms such as fever and sweats is highly associated with a final diagnosis of tuberculosis.

Biopsy, Needle↗