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Biomedical subjects

A H Zwinderman

Publications and source records attributed to A H Zwinderman.

At least 91 records · Page 5Linked to original sources
PubMed2001

Pravastatin and endothelium dependent vasomotion after coronary angioplasty: the PREFACE trial.

OBJECTIVE: To test the hypothesis that the 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor pravastatin ameliorates endothelium mediated responses of dilated coronary segments: the PREFACE (pravastatin related effects following angioplasty on coronary endothelium) trial. DESIGN: A double blind, randomised, placebo controlled, multicentre study. SETTING: Four hospitals in the Netherlands. PATIENTS: 63 non-smoking, non-hypercholesterolaemic patients scheduled for elective balloon angioplasty (pravastatin 34, placebo 29). INTERVENTIONS: The effects of three months of pravastatin treatment (40 mg daily) on endothelium dependent vasomotor function were studied. Balloon angioplasty was undertaken one month after randomisation, and coronary vasomotor function tests using acetylcholine were performed two months after balloon angioplasty. The angiograms were analysed quantitatively. MAIN OUTCOME MEASURES: The efficacy measure was the acetylcholine induced change in mean arterial diameter, determined in the dilated segment and in an angiographically normal segment of an adjacent non-manipulated coronary artery. RESULTS: Increasing acetylcholine doses produced vasoconstriction in the dilated segments (p = 0.004) but not in the normal segments. Pravastatin did not affect the vascular response to acetylcholine in either the dilated segments (p = 0.09) or the non-dilated sites. Endothelium dependent vasomotion in normal segments was correlated with that in dilated segments (r = 0.47, p < 0.001). There were fewer procedure related events in the pravastatin group than in the placebo group (p < 0.05). CONCLUSIONS: Endothelium dependent vasomotion in normal segments is correlated with that in dilated segments. A significant beneficial effect of pravastatin on endothelial function could not be shown, but in the dilated segments there was a trend towards a beneficial treatment effect in the pravastatin group.

Acetylcholine↗
PubMed2001

Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch pedigree.

Hereditary non-polyposis colorectal cancer (HNPCC) is the most common genetic susceptibility syndrome for colorectal cancer. HNPCC is most frequently caused by germline mutations in the DNA mismatch repair (MMR) genes MSH2 and MLH1. Recently, mutations in another MMR gene, MSH6 (also known as GTBP), have also been shown to result in HNPCC. Preliminary data indicate that the phenotype related to MSH6 mutations may differ from the classical HNPCC caused by defects in MSH2 and MLH1. Here, we describe an extended Dutch HNPCC family not fulfilling the Amsterdam criteria II and resulting from a MSH6 mutation. Overall, the penetrance of colorectal cancer appears to be significantly decreased (p<0.001) among the MSH6 mutation carriers in this family when compared with MSH2 and MLH1 carriers (32% by the age of 80 v >80%). Endometrial cancer is a frequent manifestation among female carriers (six out of 13 malignant tumours). Transitional cell carcinoma of the urinary tract is also relatively common in both male and female carriers (10% of the carriers). Moreover, the mean age of onset of both colorectal cancer (MSH6 v MSH2/MLH1 = 55 years v 44/41 years) and endometrial carcinomas (MSH6 v MSH2/MLH1 = 55 years v 49/48 years) is delayed. As previously reported, we confirm that the pattern of microsatellite instability, in combination with immunohistochemical analysis, can predict the presence of a MSH6 germline defect. The detailed characterisation of the clinical phenotype of this kindred contributes to the establishment of genotype-phenotype correlations in HNPCC owing to mutations in specific mismatch repair genes.

Adult↗
PubMed2001

Biophysical properties of the normal-sized aorta in patients with Marfan syndrome: evaluation with MR flow mapping.

PURPOSE: To investigate the feasibility of magnetic resonance (MR) flow mapping in the assessment of aortic biophysical properties in patients with Marfan syndrome and to detect differences in biophysical properties in the normal-sized aorta distal to the aortic root between these patients and matched control subjects. MATERIALS AND METHODS: Seventy-eight patients with Marfan syndrome with aortic root dilatation and 23 matched control subjects underwent MR flow mapping in four locations in the normal-sized aorta (1, ascending aorta; 2, thoracic descending aorta; 3, descending aorta at the level of the diaphragm; and 4, abdominal descending aorta). Distensibility at each location and flow wave velocity between locations were calculated. RESULTS: Compared with the control subjects, patients with Marfan syndrome had decreased aortic distensibility at three of the four locations (levels 1, 2, and 4; P <.05) and increased flow wave velocity between all locations (P <.05) in the aorta. In patients with Marfan syndrome, flow wave velocity was also significantly increased along the entire aortic tract beyond the aortic root (from level 1 to level 4). CONCLUSION: MR imaging reveals abnormal biophysical properties of the normal-sized aorta in patients with Marfan syndrome. Monitoring of these properties is relevant for evaluating disease progression and treatment options.

Adolescent↗
PubMed2001

Psychopathology in patients with severe asthma is associated with increased health care utilization.

Severe asthma accounts for the majority of health costs for this disease, which is mainly related to the treatment of failed control. Several psychosocial factors have been associated with poor asthma control, but the question remains whether psychiatric disorder in patients with severe asthma predisposes for increased health care utilization. In the present study we compared outpatients with severe asthma with and without psychological dysfunctioning with respect to health care utilization. All patients used high dose inhaled corticosteroids and long-acting bronchodilators for more than 1 yr, and had difficult-to-control asthma, requiring one or more courses of corticosteroids during the past year or maintenance therapy with prednisone. Medical history was taken and health care utilization questionnaires were completed. The General Health Questionnaire (GHQ) was used to identify psychiatric cases (GHQ-12 score of > or = 6). There were no differences between the psychiatric cases (n = 21) and the noncases (n = 77) with respect to demographic and objective disease characteristics. However, the psychiatric cases had increased odds ratios (OR) for frequent visits to GP (OR = 5.9), frequent emergency visits (OR = 5.3), frequent exacerbations (OR = 12.4), and frequent hospitalizations (OR = 4.8) as compared with the nonpsychiatric patients. The present findings suggest that the morbidity and costs of asthma might be related to the level of psychological dysfunctioning in patients with severe asthma rather than to asthma severity per se, thereby identifying an area of potential intervention.

Adult↗
PubMed2001

Diabetics with hypertension not controlled with ACE inhibitors: alternate therapies.

If hypertension in patients with diabetes mellitus type II is not adequately controlled by angiotensin-converting enzyme inhibitors (ACE-i), a beta-blocker is frequently added as second-line therapy. Recently, large randomized trials demonstrated the beneficial effect of second-generation dihydropyridine calcium-channel blockers in these patients. These compounds are increasingly being used to replace beta-blockers. Withdrawal of beta-blockers may influence diabetic control and may cause rebound hypertension. Any rebound hypertension from beta-blocker withdrawal may not occur if the beta-blocker is replaced with a calcium-channel blocker. A calcium-channel blocker will influence vascular resistance (VR) and blood pressure differently than a beta-blocker. Thirty-four patients with diabetes mellitus type II and a resting diastolic blood pressure above 90 mm Hg despite enalapril 10 mg daily (or equipotent dosages of other ACE-i) for at least 3 months were treated in an open label sequential comparison with the same ACE-i in combination with the beta-blocker metoprolol 100 mg for 3 months, and, subsequently for 3 more months with the same ACE-i in combination with the dihydropyridine calcium-channel blocker lercanidipine 10 mg once daily. After 6 weeks, patients with a diastolic blood pressure above 90 mm Hg were titrated up to 200 mg metoprolol or 20 mg lercanidipine once daily. Patients were examined every 6 weeks during the trial, and after 2 weeks while receiving lercanidipine. In addition to blood pressure measurements, VR was measured by iridium strain gauge plethysmography and expressed in units (1 unit = 1 mm Hg/mL blood/100 mL tissue per minute). Two of 34 patients did not complete the protocol because of non-compliance with the lercanidipine treatment in the first 2 weeks of treatment. Their data are included in the analysis. No rebound hypertension 14 days after the change-over of therapies was observed. (Mean arterial pressures [MAPs] were not significantly different from the point of withdrawal of the beta-blockers.) However, heart rate rose from 69+/-7 to 94+/-10 beats/min (p < 0.001). After 3 months on lercanidipine, MAP fell by 6+/-10 mm Hg (p = 0.002) compared to the point of withdrawal of the beta-blocker. Vascular resistance fell by 6.28+/-11.91 units (p<0.01), while glucosylated hemoglobin (HbA1c) rose by 0.4+/-0.5% (p<0.001) and body weight rose by 0.6+/-0.6 kg (p < 0.01). Multiple regression analysis revealed significant associations between decrease in VR, increase in HbAlc, and decrease in MAP, and partial dependence of these variables on one another. In hypertensive patients with diabetes type II, replacement of ACE-i and metoprolol with ACE-i and lercanidipine does not appreciably influence metabolic control and does not cause rebound hypertension. Lercanidipine was more effective than metoprolol as a second-line antihypertensive drug in these patients. At least two mechanisms may be involved: withdrawal of a pressor effect from the beta-blocker, and calcium-channel-mediated vasodilation.

Adrenergic beta-Antagonists↗
PubMed2001

Evaluation of voice quality in adductor spasmodic dysphonia before and after botulinum toxin treatment.

In this prospective study, the efficacy of botulinum toxin (Botox) injections in patients with adductor spasmodic dysphonia (AdSD) was assessed by 3 different modalities: perceptual and acoustic analyses and subjective self-assessment. This was done by comparing AdSD patients' pretreatment and posttreatment values and comparing these values with those of normal control speakers. In contrast to most other studies, the posttreatment status was defined as the optimal voice quality as judged by the patient. The aim of the study was to assess to what extent Botox injections actually improve voice quality and function. The AdSD subjects rated a significantly improved voice quality and function after Botox treatment. However, the results were never within normal limits. Perceptually, the characteristic and severely impaired AdSD voice improved, but another "type" of pathological voice was detected after Botox treatment. Acoustic analyses demonstrated a significant improvement, as well. Nevertheless, the "optimally" treated AdSD voice still remained significantly deviant as compared to normal voice production. Currently, Botox injection is the therapy of first choice for AdSD. Although significant improvement could be measured in our study perceptually, acoustically, and subjectively, the optimal voice that was achieved never fully matched normal voice quality or function.

Adult↗
PubMed2001

Beta-blockers and heart failure: meta-analysis of mortality trials.

BACKGROUND: Four large double-blind placebo-controlled studies have been performed to address mortality as a primary endpoint in patients with heart failure treated with beta-blockers. Unfortunately, 2 of the studies were stopped in the interim stage, and so these trials may be somewhat underpowered for the estimation of the secondary endpoint, type of death. This endpoint is important, because if patients die for reasons other than progression of heart failure, e.g. arrhythmias, then alternative antiarrhythmic agents may serve equally well or better than beta-blockers and with fewer side effects. OBJECTIVES AND METHODS: We assessed hazard ratios of all-cause-deaths, sudden deaths, death due to progressive heart failure and serious adverse effects leading to discontinuation of double-blind treatment. Hazard ratio = risk of death in treatment group/risk of death in placebo group. RESULTS: The pooled results showed a significant reduction in all-cause-deaths of 35% (p < 0.0001). The risk reduction of sudden death, reflecting the occurrence of fatal arrhythmias, similarly, showed a significant risk reduction of 37% (p < 0.0001). However, the risk reduction of death due to progression to heart failure was small (13%) and statistically non-significant, indicating that progression of heart failure, as estimated by numbers of deaths, was not beneficially influenced by the beta-blocker therapy. Finally, the risk of serious adverse effects leading to discontinuation of treatment with beta-blockers, was not significantly different from that for placebo. CONCLUSIONS: Beta-blockers do not reduce the risk of death due to progression of heart failure. The beneficial effect of beta-blockers is mainly due to a reduced risk of fatal arrhythmias. The risk of serious adverse effects of beta-blockers is not different from that of placebo and so there is little argument to withhold this treatment, even if it does not influence the progression of heart failure.

Adrenergic beta-Antagonists↗
PubMed2001

Risk factors of cyclosporine nephrotoxicity after conversion from Sandimmune to Neoral.

BACKGROUND: In 1995 - 1996, we switched from a once-daily Sandimmune dose to a twice-daily dose regimen of Neoral. Concurrent with the switch we changed our target trough level from 100 microg/l at 24 hours to the generally accepted 12-hour level of 150 microg/l. We performed a retrospective cohort study to assess cyclosporine toxicity following this switch and to identify risk factors for nephrotoxicity. PATIENTS AND METHODS: Of 212 patients with a stable graft function pre-conversion clinical parameters at 1 and 12 months post-conversion were compared with those at time of conversion. Cyclosporine nephrotoxicity was defined as a significant decline of the reciprocal of the serum creatinine concentration over time post-conversion in the absence of other obvious causes for declining graft function. Risk factors of cyclosporine nephrotoxicity were assessed using logistic regression analysis. RESULTS: The mean cyclosporine trough level rose from 87 microg/l at the time of conversion to 139 microg/l at 12 months post-conversion whereas the daily drug dose increased over the same period from 233 mg to 252 mg. Mean serum creatinine increased by 10% from 135 to 148 micromol/l (p < 0.001). Cyclosporine nephrotoxicity was present in 42 patients (20%). Cyclosporine dose and trough level did not predict nephrotoxicity but beta-blockers (OR 0.35, 95% CI 0.17-0.72) and calcium channel blockers (OR 0.35, 95% CI 0.19-0.82) reduced the risk of nephrotoxicity, independent from an effect on blood pressure. CONCLUSION: 20% of stable renal transplant patients experienced chronic cyclosporine nephrotoxicity after conversion from a once-daily Sandimmune regimen to a twice-daily Neoral regimen with dose adjustments to a trough level of 150 microg/l. beta-blockers and calcium channel blockers reduced the risk of nephrotoxicity.

Adrenergic beta-Antagonists↗
PubMed2001

Global estimation of myelination in the developing brain on the basis of magnetization transfer imaging: a preliminary study.

BACKGROUND AND PURPOSE: In the developing brain, myelination occurs in an orderly and predetermined sequence. The aim of this study was to determine whether such changes can be tracked using volumetric magnetization transfer imaging. METHODS: Three-dimensional magnetization transfer imaging was performed in 50 children (age range, 0.6-190 months) with no evidence of developmental delay or structural abnormalities. Volumetric magnetization transfer ratio (MTR) parameters generated of the whole brain were mean MTR and height and location of the MTR histogram peak. Relationships between volumetric MTR parameters and age were assessed using nonlinear regression analysis. RESULTS: With age, all volumetric MTR parameters changed exponentially in a way that was best expressed by the function y = a + b.exp(-x/c) (P < .0001). The peak height of the MTR histogram was the parameter that changed most predictably and that continued to change for the longest period of time. CONCLUSION: With this preliminary study, we show that by using volumetric MTR analysis, it is possible to monitor changes in the developing brain, presumably the myelination progress. This method has a potential role for detecting myelination disorders in the pediatric population, for studying the natural history of these diseases, and for monitoring the effects of treatment.

Adolescent↗
PubMed2001

The value of a continuous ambulatory activity monitor to quantify the amount and intensity of daily activity in patients with rheumatoid arthritis.

OBJECTIVE: To examine the reliability, validity, and responsiveness of a continuous ambulatory activity monitor in patients with rheumatoid arthritis (RA). METHODS: Forty-one patients with RA, participating in a randomized controlled trial examining the effect of an intensive exercise program, were assessed by means of the Dynaport ADL (activities of daily living) monitor (AM). The time spent on activities (locomotion, standing, and active sitting) during 24 hours and the intensity of trunk movement during these activities were recorded. To determine test-retest reliability 20 patients were reassessed with the AM one week after the first assessment. Construct validity of the AM was determined by comparing the AM results with physical fitness measures (muscle strength, endurance, joint mobility), disease activity, and functional status. As well, 37 patients were assessed 18 months after the first assessment to determine responsiveness. RESULTS: All AM measurements showed satisfactory test-retest reliability (ICC 0.63-0.76). AM measures were significantly associated with physical fitness, functional status, and disease activity, indicating construct validity of the AM. The AM could discriminate between patients with improvement and deterioration in physical fitness, indicating sufficient responsiveness of AM variables. CONCLUSION: This study shows the value of an ambulatory activity monitor to quantify both the amount and intensity of physical activity of patients with RA during a day in their own environment. The ambulatory activity monitor seems to be a promising instrument for research into rehabilitation of patients with RA.

Activities of Daily Living↗
PubMed2001

Clinical risk factors as predictors of postmenopausal osteoporosis in general practice.

BACKGROUND: Case-finding strategies to identify women with high risk for osteoporotic fractures have recently been proposed, but little information about such an approach in general practice is known. AIM: To study the validity of the proposed case-finding strategy for osteoporosis. DESIGN OF STUDY: Survey using case-finding strategy. SETTING: Seven hundred and twelve women aged between 55 and 84 years, randomly selected from a general practice in The Netherlands. METHOD: Of the 712 randomly selected women, 449 women participated. Information was obtained from a questionnaire, direct questioning, and computerised patients files. Bone mineral density of the femoral neck was measured by dual energy X-ray absorptiometry and vertebral morphometry was performed on lateral X-rays of the spine. Osteoporosis was defined by a bone mineral density T-score of less than 2.5 and/or the presence of severe vertebral deformities. Sensitivity, specificity, and predictive values were calculated for the whole set of risk factors; those significantly associated with osteoporosis and in logistic models. RESULTS: Clinical risk factors were present in 55% of the women and identified 68% of the women with osteoporosis. Three risk factors--a low body mass index, fragility fractures, and severe kyphosis and/or loss of height--were associated significantly with osteoporosis; they were present in 33% of the women and identified 60% of those with osteoporosis. A logistic model based on age and fragility fractures selected 32% of the women and identified 76%. CONCLUSION: No single risk factor could assist in identifying women with osteoporosis. A simplified case-finding strategy using only three risk factors, that is suitable for primary care, reduces the number of women to be evaluated by two-thirds; however, this is at the cost of missing the diagnosis in 40% of the women with osteoporosis. Addition of spine radiographs to the case-finding approach helped to obtain a better risk profile of the women and had also practical consequences for the management of some. We propose that radiographs should be included in any case-finding strategy.

Aged↗
PubMed2000

Diagnostic strategies for the histological examination of muscle biopsy specimens for the assessment of vasculitis in rheumatoid arthritis.

For the diagnosis of rheumatoid vasculitis (RV), histological examination of a blindly-taken muscle biopsy is advocated. If fibrinoid necrosis (FN) is observed in one or more tissue sections of the biopsy the diagnosis of RV is confirmed. The diagnostic value of such histological investigation depends on the prevalence of FN in biopsies of RV patients, the number of tissue sections that are investigated, and the sampling design with which the tissue sections are obtained from the biopsy. In this paper we determine the mathematical relation between the sensitivity of the RV diagnosis and these three factors for four different models for the FN distribution in RV biopsies. The goodness-of-fit of these models was assessed by analysing 18 829 tissue sections of the biopsies of 56 patients, among which were 24 (otherwise histologically proven) RV patients. It appeared that the sensitivity was moderate: FN was observed in only 14 out of 24 (58 per cent) muscle biopsies of the RV patients. The prevalence of FN in the tissue sections of those 14 biopsies was low, about 17 per cent according to the best fitting model. We proved that the sampling design, maximizing the minimum distance between tissue sections (equidistant sampling) was optimal, and that with such optimal sampling, examination of about 20 tissue sections was sufficient. With practical sampling designs, however, considerably more tissue sections had to be inspected. FN appeared to cluster in the RV biopsies, and a first-order Markov model satisfactorily described the (auto)correlation between adjacent tissue sections in RV biopsies.

Arthritis, Rheumatoid↗
PubMed2000

[Surgical treatment of early stage cervical carcinoma at Leids University Medical Center, 1984-1996: depth of invasion, number and bilaterality of metastatic lymph nodes prognostic for recurrence].

OBJECTIVE: To analyse local tumour parameters of early cervical cancer that might be of prognostic significance for tumour relapse in the pelvis. DESIGN: Retrospective. METHOD: Data were collected from 308 patients who underwent radical hysterectomy and pelvic lymphadenectomy in the years 1984-1996 in the Leiden University Medical Centre, the Netherlands. Treatment policies and operating staff were the same during the study period. The existence of relapse was studied by physical, gynaecological, laboratory and, if indicated, radiological examination. RESULTS: Data on 294 patients were available for analysis. Their mean age was 45 years (range: 21-82). Postoperative radiation treatment was given to 119 patients (40%). Mean follow-up duration was 36 months (range: 1-136). Recurrences had developed in 46 patients (15.6%), 29 of whom had died. The calculated overall 5-year survival rate was 83%; 91% for those with negative and 53% for those with positive pelvic nodes. The calculated recurrence-free-5-year survival rate was 75% for the entire group, 83% for the patients without and 47% for those with lymph node metastases. When more than one lymph node region was affected, 5-year disease free survival was 19% and when lymph node metastasis occurred bilaterally, it was 22%. Multivariate analysis revealed that lymph node involvement (hazard ratio: 4.4), parametrial involvement (5.5), tumour size > 30 mm (4.6) and depth of invasion > 10 mm (5.1) were independent factors of prognostic significance for disease free survival. The current indications for adjuvant treatment might be extended with infiltration depth. The number and the bilaterality, if any, of affected lymph node stations might be indication for additional adjuvant therapy.

Adult↗
PubMed2000

Lipoprotein lipase activity is associated with severity of angina pectoris. REGRESS Study Group.

BACKGROUND: Raised triglyceride-rich lipoproteins significantly increase the risk for cardiovascular disease. Variation in the activity of the enzyme lipoprotein lipase (LPL), which is crucial in the removal of these lipoproteins, may therefore modulate this risk. METHODS AND RESULTS: Postheparin levels of LPL activity and mass were measured in a large cohort of male coronary artery disease patients participating in the Regression Growth Evaluation Statin Study (REGRESS), a lipid-lowering regression trial. In addition, the relationships between LPL activity and mass and severity of angina pectoris according to the NYHA classification and silent ischemia on 24-hour ambulatory ECG monitoring were assessed. Patients in different LPL activity quartiles and mass had different severities of angina; a total of 47% of patients in the lowest LPL quartile reported class III or IV angina. In contrast, only 29% in the highest activity quartile (P:=0.002) had severe angina. These parameters were supported by ambulatory ECG results, for which the total ischemic burden in the lowest LPL activity quartile was 36. 5+/-104.1 mm x min compared with 14.8+/-38.8 mm x min in the highest quartile of LPL activity (P:=0.001). LPL activity levels were strongly correlated with LPL mass (r=0.70, P:<0.0001). A significant association between the LPL protein mass and NYHA class (P:=0.012) was also demonstrated. CONCLUSIONS: We have demonstrated a significant relationship between LPL mass and activity and severity of ischemia as defined by angina class and ambulatory ECG. These results suggest that LPL influences risk for coronary artery disease by both catalytic and noncatalytic mechanisms.

Aged↗
PubMed2000

Pravastatin reduces restenosis two years after percutaneous transluminal coronary angioplasty (REGRESS trial).

The Regression Growth Evaluation Statin Study (REGRESS) is a placebo-controlled multicenter study designed to assess the effect of 2-year treatment with pravastatin on the progression and regression of angiographically documented coronary artery disease. One of the secondary end points was the occurrence of 2-year restenosis in the percutaneous transluminal coronary angioplasty (PTCA) block. We randomly assigned eligible patients to receive pravastatin 40 mg once daily or placebo. The end point was the percent diameter stenosis of the target lesion at 24 months, as assessed by (semi)quantitative coronary angiography. Two hundred twenty-one patients underwent scheduled PTCA, which was considered successful in 201 patients. One hundred seventy-eight patients underwent angiographic restudy (89%). The patients in the pravastatin group (n = 109) and placebo group (n = 112) were similar at baseline. Percent diameter stenosis before angioplasty was 78 +/- 14% (mean +/- SD) in the pravastatin group and 80 +/- 14% in the placebo group (p = 0.46). At follow-up, the percent diameter stenosis was 32 +/- 23% in the pravastatin group and 45 +/- 29% in the placebo group (p < 0.001). Clinical restenosis was significantly lower in the pravastatin group (7%) compared with the placebo group (29%) (p < 0.001). Risk reduction for all events was 58%. We conclude that treatment with pravastatin reduces 2-year clinical and angiographic restenosis.

Angioplasty, Balloon, Coronary↗
PubMed2000

Fentanyl, a upsilon-opioid receptor agonist, phase shifts the hamster circadian pacemaker.

The phase-shifting effects of the mu-opioid receptor agonist fentanyl on the circadian timing system were investigated in the hamster. Fentanyl injections during the mid-subjective day induced phase advances of the hamsters' wheel-running activity rhythm. The shifts were not accompanied by an increase in locomotor activity but instead a decrease of activity was often observed. A dose-response curve indicated that with increasing dosage, the response probability increased, while the magnitude of the induced shift remained stable. The present data suggest that there is some role for opioid regulation of the circadian system.

Analgesics, Opioid↗
PubMed2000

Estimation of growth rate in patients with head and neck paragangliomas influences the treatment proposal.

BACKGROUND: Extraadrenal paragangliomas of the head and neck are tumors with variable clinical behavior. Because tumor growth as well as surgery can cause disabling loss of function, knowledge of the natural history of paragangliomas is important for the development of treatment strategies. METHODS: The tumor volume, growth rate, and tumor doubling time of 48 paragangliomas at different anatomic locations in the head and neck region were estimated retrospectively using sequential radiologic imaging. RESULTS: During a mean follow-up period of 4.2 years, a volume increase of > 20% was observed in 60% of the paragangliomas. In these cases the median growth rate was 1.0 mm/year and the median tumor doubling time was 4. 2 years. More growing tumors were observed in intermediate size tumors than in very small or large paragangliomas, suggesting a biphasic growth pattern. CONCLUSIONS: The majority of head and neck paragangliomas have a very low growth rate. Although management of paragangliomas also is determined by other parameters, preoperative estimation of the tumor doubling time may influence the treatment proposal. A "wait and scan" policy must be considered in all cases.

Adult↗