Biomedical subjects

A H Zwinderman

Publications and source records attributed to A H Zwinderman.

At least 163 records · Page 9Linked to original sources

PubMed1998

Pretreatment serum lactate dehydrogenase as additional staging parameter in patients with small-cell lung carcinoma.

PURPOSE: At present the standard staging procedure in patients with small-cell lung cancer (SCLC) is extensive, expensive and time-consuming. Furthermore, the predictive and prognostic value of the current staging system is poor. To determine the value of pretreatment clinical and biochemical parameters to predict tumour stage and to assess prognosis, a retrospective study was performed of 121 consecutive patients with newly diagnosed SCLC. METHODS: On the basis of routine diagnostic procedures, 51 patients were staged as having limited disease and 70 patients as having extensive disease. During follow-up, data on tumour progression and survival were gathered. These data and the tumour stage were correlated with lactate dehydrogenase (LDH), alkaline phosphatase, liver enzymes, leucocyte count, protein, albumin, calcium, age and gender. RESULTS: Follow-up ranged from 1 week to 96 months, during which 110 patients died. In all patients with LDH levels above 400 U/l (n = 31), metastases were found at the initial stage, whereas all patients initially staged as having limited disease and LDH levels above 240 U/l showed tumour progression. Bone and liver were found to be the most commonly involved sites, whereas the incidence of brain metastases increased during follow-up. In patients initially staged as having limited disease, no differences in survival were found between those showing local recurrence and those developing metastases during follow-up (P = 0.67). Compared to the patients initially staged as having extensive disease, the survival of both groups was significantly better (P < 0.001). Significant independent variables of survival were LDH, albumin, initial stage and gender, but LDH was the best overall predictor (P < 0.001). CONCLUSION: These results suggest that pretreatment LDH may be used as an additional staging parameter in SCLC, which can identify prognostic subgroups before treatment.

Carcinoma, Small Cell↗

PubMed1998

Depressed heart rate variability is associated with events in patients with stable coronary artery disease and preserved left ventricular function. REGRESS Study Group.

BACKGROUND: Little is known about the value of heart rate variability in patients with symptomatic coronary artery disease with a preserved left ventricular function. We hypothesized that in these patients heart rate variability might be a helpful adjunct to conventional parameters to predict clinical events. METHODS: In a prospective 2-year follow-up study ambulatory electrocardiographic recordings were performed in 263 consecutive male patients (mean age 56+/-8 years) with stable angina pectoris and a mean left ventricular ejection fraction of 71%+/-12%. Clinical events consisted mainly of coronary events such as percutaneous transluminal angioplasty or coronary artery bypass graft operation. RESULTS: Low measures of standard deviation of normal R-R intervals, standard deviation of the mean R-R intervals of 5 minutes, and two spectral components of heart rate variability were found in patients who had had an event compared with patients with no event. Adjusted for severity of angina, the presence of a previous myocardial infarction, and the use of beta-blockers in a logistic regression model this relation remained statistically significant for SDNN. Healthy volunteers appeared to have the highest measures of heart rate variability. CONCLUSION: In patients with ischemic heart disease and normal or near normal ventricular function decreased heart rate variability is associated with adverse clinical events.

Adrenergic beta-Antagonists↗

PubMed1998

The diagnostic value of the EEG in Angelman and Rett syndrome at a young age.

We determined the diagnostic value of the EEG in young children with Angelman syndrome (AS) and Rett syndrome (RS). EEGs, recorded before 5 years of age, of 10 patients with AS, 10 with RS and 10 with mental retardation of other origin were studied blindly by two examiners for the presence of the following items: (A) 4-6 Hz rhythmic activity of over 200 microV; (B) 2-3 Hz frontal activity of 200-500 microV; (C) posterior spikes; (D) triphasic frontal waves; (E) central and/or centro-temporal spike-wave complexes; and (F) other epileptic discharges. Based on these items the EEGs were scored as AS (A-D); RS (E-F); or other. Examiners never made a mistake between AS and RS. One examiner labeled 6 of 10 AS cases correctly, the other 5; 4 (5) were characterized as 'other.' In RS cases 5 were labeled as 'other' by the first examiner and 3 by the second one. We conclude that EEG patterns of AS and RS are sufficiently different to help differentiate between AS and RS at a young age, which has a bearing on genetic counseling.

Angelman Syndrome↗

PubMed1998

Pretreatment serum LDH as additional staging parameter in small-cell lung carcinoma.

BACKGROUND: In patients with limited disease staged small-cell lung cancer (SCLC), overall survival is still poor. Therefore, a retrospective study was carried out of 48 patients with limited disease staged SCLC to select a parameter which can identify prognostic subgroups at the time of diagnosis. MATERIALS AND METHODS: Follow-up varied from 3 to 96 months during which 38 patients died. Based on clinical outcome, patients were clustered into three groups: complete remission (CR) (n = 16); local recurrence (LOC) (n = 7); and distant recurrence (DIS) (n = 25). Age, gender and pretreatment biochemical parameters were correlated with clinical outcome and survival. RESULTS: No differences in survival were found in patients with LOC (14% 2-year survival) and DIS (16% 2-year survival) (P = 0.67). Patients with complete remission demonstrated a significantly better survival (75% 2-year survival). LDH was found to be the only significant correlate of both tumour progression and survival. All patients with pretreatment LDH levels > 240 IU/l (n = 13) demonstrated tumour recurrence. The survival rate of patients with LDH levels < 240 IU/l (41% 2-year survival) was much better than that of patients with LDH levels > 240 IU/l (8% 2-year survival) (P = 0.0001). CONCLUSION: LDH may be used for the identification of prognostic subgroups in limited disease SCLC. Patients showing pretreatment LDH levels > 240 IU/l have an extremely high risk of tumour recurrence, whereas survival is poor. In patients with LDH levels, < 240 IU/l survival is significantly better.

Adult↗

PubMed1998

Variance components analysis of carotid and femoral intima-media thickness measurements. REGRESS Study Group, Interuniversity Cardiology Institute of The Netherlands, Utrecht, The Netherlands. Regression Growth Evaluation Statin Study.

B-mode ultrasound intima-media thickness (IMT) measurements of carotid and femoral arterial walls are used in atherosclerosis studies. In this study, the components contributing to IMT measurement variability in males with coronary artery disease were investigated by means of repeated B-mode ultrasound scans and repeated off-line video image analyses. For statistical analysis, a mixed-model analysis of variance was used. From sonographer data, it was shown that human subjects and their arterial wall segments contributed 75% of the total IMT measurement variability in this population. Inter-sonographer variance contributed 25%. The intra-sonographer variance was negligible (<1%). In off-line image analysis, variance components due to subjects and segments, inter-analyst variance, and residual fluctuation were 88%, < 1% and 11%, respectively. Intra-analyst variance was negligible (<1%). The major source of B-mode ultrasound IMT measurement variability finds its origin in subjects and their arterial walls. Although sonographers proved a lesser source of variability, in comparative studies they should enter a study well trained and should be randomly assigned to subjects. Follow-up examinations should preferably be done by the same sonographer. Off-line image analysis contributed little to IMT measurement variability.

Adult↗

PubMed1998

B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: a report of the Regression Growth Evaluation Statin Study (REGRESS).

OBJECTIVES: In this B-mode ultrasound study we assessed pravastatin treatment effects on carotid and femoral artery walls and investigated the correlations between the state and evolution of peripheral and coronary atherosclerosis. BACKGROUND: The Regression Growth Evaluation Statin Study (REGRESS) was an 11-center, 2-year, double-blind, placebo-controlled, prospective study of 885 men with coronary artery disease (CAD) (total cholesterol 4 to 8 mmol/liter). The study primarily investigated pravastatin treatment effects on the coronary lumen. This report focuses on the 255 patients who participated in the REGRESS ultrasound study. METHODS: Carotid and femoral artery walls were imaged at baseline and at 6, 12, 18 and 24 months. Pravastatin treatment effect was defined as the difference in progression of the combined intima-media thicknesses (IMT) between treatment groups. RESULTS: Pravastatin treatment effects were highly significant (combined IMT: p = 0.0085; combined far wall IMT: p < 0.0001; common femoral artery far wall IMT: p = 0.004). Correlations between the IMTs of the arterial wall segments ranged from -0.17 to 0.81. Baseline correlations between IMT and percent coronary lumen stenoses ranged from 0.23 to 0.36. Baseline IMT correlated with the mean coronary segment diameter (r = -0.32, p = 0.001) and minimal coronary obstruction diameter (r = -0.27, p = 0.005). There were no individual correlations between IMT and coronary lumen variables (p > 0.30). CONCLUSIONS: Pravastatin treatment effects on carotid and femoral artery walls were observed. B-mode ultrasound imaging studies of peripheral arterial walls could not describe the state and evolution of the coronary lumen in the individual patient, but proved to be a highly suitable tool for the assessment of antiatherosclerotic properties of agents.

Anticholesteremic Agents↗

PubMed1998

Effects of the bisphosphonate olpadronate in patients with carcinoma of the prostate metastatic to the skeleton.

Prostate cancer is predominantly associated with osteoblastic bone metastases, but an increase in bone resorption has been demonstrated consistently, both histologically and biochemically. For this reason, bisphosphonates, which effectively suppress bone resorption, have been used in patients with prostate cancer metastatic to the skeleton. We studied clinical and biochemical responses 5 days and 3 months after administration of the new, potent bisphosphonate, olpadronate, in 28 patients with prostate cancer and bone metastases. All patients received 4 mg of olpadronate intravenously daily for 5 days. No additional treatment was given to the first 12 patients, while treatment was continued with oral olpadronate 200 mg daily in the following 16 patients. Serum alkaline phosphatase (ALP) activity was elevated in 93% of the patients and was positively correlated to urinary hydroxyproline excretion (r = 0.81, p < 0.0001), suggesting a coupling between bone formation and resorption. A rapid and significant suppression of bone resorption was observed in all patients after intravenous treatment. This was sustained for 4-6 weeks in all patients, but reversed thereafter in patients not receiving oral maintenance therapy. No significant changes in serum ALP activity were observed in either group during the 3 months of follow-up. At the start of treatment all patients had severe bone pain and 82% and 36% were using NSAIDs and/or opiates, respectively. Although clinical response was not a primary objective of the study, we observed that intravenous therapy was associated with a decrease in bone pain in 76% of patients and a reduction in the use of analgesics. At 3 months this response was generally sustained only in those patients who were maintained on continuous oral therapy (p < 0.05 compared with the group treated with intravenous olpadronate only). The clinical response thus appeared to parallel the biochemical changes in bone resorption.

Administration, Oral↗

PubMed1998

Neuropsychological performance and plasma cortisol, arginine vasopressin and oxytocin in patients with major depression.

BACKGROUND: The aim of the study was to search for the existence of, and define, a possible relationship between performance in neuropsychological tests and baseline concentrations of plasma cortisol, vasopressin and oxytocin in medication-free patients with a major depressive episode. METHODS: Measures of depression and anxiety were obtained and a neuropsychological battery was presented. Blood for neuropeptide analysis was drawn by venepuncture at 8.00, 16.00 and 23.00 h. RESULTS: The melancholic patients performed less well on the neuropsychological battery than did the non-melancholic patients, but these differences could be accounted for by the severity of the illness. Global intellectual functioning was negatively correlated with mean baseline plasma concentrations of cortisol. Patients with high mean plasma vasopressin concentrations remembered more auditory presented words in the delayed recall test and produced more intrusions in the visual word learning list than did patients with low or normal mean plasma vasopressin concentrations. No association was found between neuropsychological performance and plasma concentrations of oxytocin. CONCLUSIONS: Our findings support the hypothesis that elevated baseline plasma cortisol concentrations are related to cognitive impairment in depressed patients and the hypothesis that the neuropeptide vasopressin independently enhances memory, directly or indirectly through increasing arousal and attention.

Adult↗

PubMed1998

Three- to 5-year prospective follow-up of outcome in major depression.

BACKGROUND: A Dutch cohort of predominantly out-patient DSM-III-R major depressive patients was followed for 3 to 5 years after start of treatment in a psycho-neuro-endocrinological prediction study. The study design permitted description of the course of remissions, relapses and recurrences. METHODS: Pharmacological treatment was standardized, psychotherapy was tailored to the needs of the patient, follow-ups were done monthly until 3 years or more after the initial recruitment. RESULTS: After 9 months 49% of the patients had reached full remission and 45% were in partial remission. During the following 3 to 5 years 82% of the patients had reached a period of full remission. Sixteen per cent of the patients needed 2 years or more before full remission. A relapse or recurrence rate of 41% within 5 years was found. Patients with residual symptoms relapsed particularly in the first 4 months after remission, while patients without residual symptoms recurred mainly after 12 months after remission. Previous depressive episodes and psychoticism predicted relapse. Psychomotor retardation at inception predicted a longer time to partial remission. CONCLUSION: In most cases, major depression is a seriously impairing episodic disease. This is also true for a sample of predominantly out-patients treated at a university clinic.

Adult↗

PubMed1998

Tc-99m tetrofosmin myocardial SPECT perfusion imaging: comparison of rest-stress and stress-rest protocols.

AIM: The purpose of this study was to evaluate the diagnostic value of Tc-99m tetrofosmin SPECT myocardial perfusion scintigraphy rest/stress and stress/rest protocols for the assessment of coronary artery disease (CAD). METHODS: 65 patients underwent both rest and stress SPECT imaging in a one-day protocol and coronary angiography within 2 months before or after scintigraphy. Scintigraphic data was obtained according to two different protocols; 1) rest-stress (n = 18) and 2) stress-rest (n = 47). RESULTS: Scintigraphic evidence for myocardial ischaemia was found in 36 patients (55%). The overall sensitivity to detect CAD (> 50% luminal stenosis) was 94% (34/36), specificity 66% (19/24), positive predictive value 77%, negative predictive value 90%. The sensitivity to detect CAD for protocols 1 and 2 were 100% and 93%, specificity 56% and 70%, positive predictive value 69% and 81% and negative predictive value 100% and 88%, respectively. The left anterior descending coronary artery showed a sensitivity (overall, protocol 1 & 2) of 78%, 75% (3/4) and 79% (15/19) and a specificity of 71%, 64% (9/14) and 75% (21/28). The right coronary artery showed a sensitivity (overall, protocol 1 & 2) of 91%, 100% (6/6) and 88% (14/16) and a specificity of 70%, 92% (11/12) and 61% (19/31). The left circumflex coronary artery showed a sensitivity (overall, protocol 1 & 2) of 50%, 67% (2/3) and 46% (6/13) and a specificity of 94%, 100% (15/15) and 91% (31/34). CONCLUSION: Tc-99m tetrofosmin appears to be a valuable tool in predicting significant CAD. The sensitivity and the positive predictive value are high, making this test highly appropriate for the diagnosis of CAD. The diagnostic value of the individual coronary arteries is high to moderate. No significant differences were found between both protocols.

Adult↗

PubMed1998

Proposed synergistic effect of calcium channel blockers with lipid-lowering therapy in retarding progression of coronary atherosclerosis.

Lipid-lowering therapy now has undoubtedly proven to be an effective therapeutic modality to retard the progression of coronary atherosclerosis. An additional approach for prevention of the progression of atherosclerosis is calcium channel blocker (CCB) treatment. Evidence indicating that CCBs inhibit atherosclerosis is less unequivocal than the clear evidence for lipid-lowering therapy. Many investigations support the view that a number of key processes in atherosclerosis may be influenced by CCBs. From the "negative" and "positive" studies with CCBs performed in animals and humans we must conclude that apparently some, but not all, types or stages of the atherosclerotic process are inhibited by CCBs. To assess whether lipid-lowering therapy and CCB treatment may have an additive or synergistic beneficial effect on human atherosclerosis, which is conceivable because their anti-atherosclerotic properties differ, data from the angiographic lipid-lowering trial REGRESS (pravastatin vs. placebo) were reviewed. In REGRESS, patients in the pravastatin group had significantly less progression if cotreated with CCBs as compared with those with no CCB cotreatment, whereas in the placebo (no pravastatin) group no effect of CCB treatment was observed. With respect to angiographic new lesion formation, in the pravastatin group there were 50% less patients with new angiographic lesions if cotreated with CCBs as compared with no CCB cotreatment, whereas in the placebo (no pravastatin) group, again, no significant effect of CCB treatment was observed. No beneficial effects of CCB treatment on clinical events were observed during the 2-year study follow-up. In view of the correlation between angiographic progression and subsequent clinical events as demonstrated in several large trials, it is not unrealistic to also anticipate in this population, a beneficial effect on clinical events with longer follow-up. Although the REGRESS trial was not designed to evaluate combination therapy, the results suggest that addition of CCBs to HMG-CoA reductase inhibitor therapy (pravastatin) acts synergistically in retarding the progression of established coronary atherosclerosis. These results appear to warrant prospective randomized trials to determine in a more definitive manner the merits of this combination in the prevention of progression of coronary atherosclerosis. Currently a number of studies in these fields are being designed or are already underway.

Anticholesteremic Agents↗

PubMed1998

Distribution of T cells and signs of T-cell activation in the rheumatoid joint: implications for semiquantitative comparative histology.

A prerequisite for comparative histology of synovial tissue by means of biopsies is insight into the distribution of a marker under study. This investigation focuses on the variation in the presence of T cells and signs of T-cell activation within the rheumatoid joint. For this purpose, multiple slides from several pieces of synovial tissue from different parts of a joint were stained and scored for the expression of CD3, CD25, HLA-DR, Ki67 and interferon-gamma. The variation in scores for the presence of T cells and markers of activation was more pronounced in slides prepared from different pieces of tissue than in slides from one piece of tissue. Based on multiple analysis of variance, methods are suggested to establish a reliable overall score for the expression of a certain marker within a joint. Following validation, such methods may prove to be useful by allowing semiquantitative histology of synovial tissue for studies on arthritis.

Arthritis, Rheumatoid↗

PubMed1998

Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline.

Depression is a common cause of sexual dysfunction, but also antidepressant medication is often associated with sexual side effects. This article includes two related studies. The first double-blind, placebo-controlled study was conducted in men with lifelong rapid ejaculation and aimed to assess putative differences between the major selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, fluvoxamine, paroxetine, and sertraline) with regard to their ejaculation-delaying effect. Sixty men with an intravaginal ejaculation latency time (IELT) of 1 minute or less were randomly assigned to receive fluoxetine 20 mg/day, fluvoxamine 100 mg/day, paroxetine 20 mg/day, sertraline 50 mg/day, or placebo for 6 weeks. During the 1-month baseline and 6-week treatment periods, the men measured their IELT at home using a stopwatch. The trial was completed by 51 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was constant at approximately 20 seconds. Analysis of variance revealed a between-groups difference in the evolution of IELT delay (p = 0.0004); in the paroxetine, fluoxetine, and sertraline groups there was a gradual increase to about 110 seconds, whereas in the fluvoxamine group, IELT was increased to only approximately 40 seconds. The paroxetine, fluoxetine, and sertraline groups differed significantly (p < 0.001, p < 0.001, p = 0.017, respectively) from placebo but the fluvoxamine group did not (p = 0.38). Compared with baseline, paroxetine exerted the strongest delay in ejaculation, followed by fluoxetine and sertraline. There was no clinically relevant delay in ejaculation with fluvoxamine. In men with lifelong rapid ejaculation, paroxetine delayed ejaculation most strongly, whereas fluvoxamine delayed ejaculation the least. The second double-blind, placebo-controlled study was carried out in men with lifelong rapid ejaculation (IELT < or = 1 minute) and in men with lifelong less-rapid ejaculation (IELT > 1 minute) to investigate whether data about SSRI-induced delayed ejaculation in men with rapid ejaculation may be extrapolated to men with less-rapid ejaculation. After measurement of IELT at home (using a stopwatch) during a 1-month baseline assessment, 32 men with an IELT of 1 minute or less (group 1) or more than 1 minute (group 2) were randomly assigned to receive paroxetine 20 mg/day or placebo for 6 weeks in a double-blind manner. Patients continued to measure their IELTs at home during the 6 weeks of the study. At baseline, 24 patients consistently had IELTs of one minute or less (group 1), and eight patients had IELTs of more than 1 minute (group 2). The geometric mean IELT was 14 seconds in group 1 and 83 seconds in group 2. Twelve patients in group 1 and five in group 2 were randomized to the paroxetine 20 mg/day. The percentage increase in the geometric mean IELT compared with baseline in patients treated with paroxetine was 420% (95% confidence interval [CI], 216-758%) in group 1 and 480% (95% CI, 177-1,118%) in group 2 (p = 0.81). After 6 weeks of treatment with paroxetine, the geometric mean IELT was 92 seconds in group 1 and 602 seconds in group 2 (p < 0.001). Therefore, the paroxetine-induced percentage increase in IELT seems to be independent of the baseline IELT. This suggests that ejaculation-delaying side effects of some SSRIs investigated in men with lifelong rapid ejaculation may be generalized to men with less-rapid ejaculation.

Adolescent↗

PubMed1998

The diagnostic value of perivascular infiltrates in muscle biopsy specimens for the assessment of rheumatoid vasculitis.

OBJECTIVE: To determine the diagnostic value of perivascular infiltrates (PVI) in randomly obtained muscle biopsy specimens for the assessment of rheumatoid vasculitis (RV). METHODS: The number and size of PVIs, defined as the presence of mononuclear or polymorphonuclear cells around > or = 50% of the circumference of a vessel wall, as well as the presence of fibrinoid necrosis were determined in frozen sections of muscle samples of RV patients with histologically confirmed vasculitis in fixed muscle tissue (n = 12). The findings were compared with those observed in frozen sections of muscle biopsy specimens of rheumatoid arthritis (RA) patients not suspected of vasculitis (n = 14) and patients with osteoarthritis (OA) (n = 11). The presence of PVIs and of fibrinoid necrosis were sought in four frozen sections of the muscle biopsy specimen. RESULTS: PVIs were observed in 75% of the RV patients, which was significantly (p < 0.05) higher than the frequency found in RA (14%) or OA (18%) patients. PVIs with > or = three cell layers were found in 67% of the RV patients and in none of the RA and OA patients (p < 0.05). Fibrinoid necrosis was found in least one of four frozen section in 33% of the RV patients. There was a good intra-observer and inter-observer concordance on the presence of fibrinoid necrosis and of PVIs with > or = three cell layers. CONCLUSIONS: The assessment of PVIs with > or = three cell layers in a muscle biopsy specimen is a specific and reliable test in discriminating RV from RA without vasculitis. The demonstration in muscle of PVIs with > or = three cell layers is more sensitive than that of fibrinoid necrosis in the diagnosis of RV.

Aged↗

PubMed1998

-455G/A polymorphism of the beta-fibrinogen gene is associated with the progression of coronary atherosclerosis in symptomatic men: proposed role for an acute-phase reaction pattern of fibrinogen. REGRESS group.

Increased plasma fibrinogen levels have been identified as a risk indicator for myocardial infarction, stroke, and thrombosis. Both environmental and genetic factors make an important contribution to plasma fibrinogen levels in humans. In the present study we evaluated, in patients with serum cholesterol levels between 4 and 8 mmol/L, the relation of plasma levels and polymorphisms of fibrinogen with coronary artery disease (CAD), cross-sectionally at baseline and after a 2-year follow-up period in which they received either a placebo or pravastatin. Higher plasma fibrinogen levels (3.9 g/L) were observed at baseline in patients with the -455AA genotype than in patients with the -455GA (3.2 g/L) and -455GG (3.1 g/L) genotypes of the -455G/A fibrinogen beta gene polymorphism (P<.05). Plasma levels of fibrinogen were not related to the baseline angiographic variables (mean segment diameter [MSD] and minimum obstruction diameter [MOD]), nor to the quantitative changes in these angiographic variables. However, in the placebo group, patients with the -455AA genotype had more progression of CAD, expressed by a significantly greater decrease of the MSD and MOD, after the 2-year follow-up period than patients with the other genotypes. The -455G/A polymorphism was related to the progression of CAD, and pravastatin therapy seemed to offset this deleterious effect. We hypothesized that the -455A allele may promote a stronger acute-phase response in fibrinogen and that the resulting higher fibrinogen levels may form the pathogenetic basis for the stronger progression of coronary atherosclerosis. Experiments to verify this hypothesis are being proposed and advocated, in view of the possibility of identifying a genetic marker that can recognize a subgroup of patients with an increased risk who may benefit from early treatment with lipid-lowering or anticoagulant drugs.

Aged↗

PubMed1998

Reduction by paroxetine of suicidal behavior in patients with repeated suicide attempts but not major depression.

OBJECTIVE: Suicidal behavior has been associated with reduced central serotonergic function. Because selective serotonin reuptake inhibitors (SSRIs) enhance serotonergic function, the authors studied the efficacy of an SSRI, paroxetine, in the prevention of recurrent suicidal behavior. METHOD: They conducted a 1-year double-blind study comparing paroxetine (40 mg/day) and placebo in 91 patients who had recently attempted suicide for at least a second time. None of the patients had experienced a major depressive episode or had any other major DSM-III-R axis I diagnoses. At least one cluster B personality disorder was present in 74 patients. RESULTS: With adjustment for the number of previous suicide attempts, paroxetine showed significant efficacy in the prevention of recurrent suicidal behavior. Among the patients who had attempted suicide fewer than five times, 12 (36%) in the placebo group (N = 33) and five (17%) in the paroxetine group (N = 30) made a subsequent suicide attempt. Paroxetine was also significantly more effective in patients who met fewer than 15 criteria for cluster B personality disorders than in those who met more than 15 criteria. Overall, paroxetine was not significantly different from placebo in its effect on depressive mood, hopelessness, and anger. However, the data suggest that paroxetine may have some temporary effect in reducing anger. CONCLUSIONS: This study indicates that enhancing serotonergic function with an SSRI may reduce suicidal behavior in a subgroup of patients who have attempted suicide more than once but who do not suffer from major depression.

Adult↗

PubMed1998

Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin.

Fatigue is an important symptom of a disturbed circadian rhythm. To date, no studies of circadian rhythms in patients with chronic fatigue syndrome (CFS) have been published. The objectives of the study were to study rhythms of heart rate and systolic and diastolic blood pressure in patients with chronic fatigue syndrome compared with age-matched normotensive controls and to study the effects of melatonin and inopamil on such rhythms. Ambulatory blood pressure (ABP) measurements (Space Lab, Inc, validated) of 18 patients with CFS were made according to the 1987 U.S. Center for Disease Control Criteria, and measurements of 12 age-matched normotensive controls were used in a cosinor analysis of the two groups. The effects of melatonin and inopamil on ABP were studied subsequently in four patients in an 8-week open-label evaluation. One patient was hypertensive (diastolic blood pressure > 90 mm Hg at least once every 4 hours), and was, therefore, excluded. The data of the remaining 17 patients (15 women, 2 men) revealed a significant 12-hour rhythm in heart rate and 24-hour rhythm in systolic and diastolic blood pressure with 95% confidence intervals not significantly different from sinusoidal patterns. Although these rhythms were synchronous with the control group rhythms, their amplitudes were not and showed, respectively, 2.8, 2.8, and 9.0 times the size of the control group rhythms (p < 0.001, p < 0.001, and p < 0.0001, respectively). Systolic blood pressures in the patients with CFS were consistently below 100 mm Hg during the nighttime. In a subsequent pilot study of four patients from the study population treated with melatonin 4 mg daily and inopamil 200 mg daily for 4 weeks, inopamil reduced nighttime hypotension (p < 0.05), whereas melatonin increased nighttime hypotension (p < 0.02). Patients with CFS have increased amplitudes of circadian rhythms and systolic blood pressures consistently below 100 mm Hg during the nighttime. Positive inotropic compounds may be beneficial in such patients, but melatonin may not be.

Adult↗

PubMed1998

Combination therapy in recent onset rheumatoid arthritis: a randomized double blind trial of the addition of low dose cyclosporine to patients treated with low dose chloroquine.

OBJECTIVE: To investigate whether there is interaction between chloroquine and cyclosporine (CyA) at the level of efficacy and toxicity in patients with recent onset rheumatoid arthritis (RA). METHODS: Eighty-eight patients with recent onset RA, who had shown a suboptimal clinical response on low dose chloroquine monotherapy, were randomly assigned to additional treatment with placebo, CyA 1.25 mg/kg/day, or CyA 2.50 mg/kg/day (fixed doses) for another 24 weeks. The tender joint count was the primary outcome assessment of efficacy and the serum creatinine of toxicity. The 1995 preliminary ACR response criteria for improvement were applied to evaluate individual clinical responses. RESULTS: Two patients in the placebo group (n = 29), 7 patients in the CyA 1.25 mg group (n = 29), and 8 patients in the CyA 2.50 mg group (n = 30) (p = 0.06) discontinued study medication prematurely for inefficacy or adverse events. The intention-to-treat analysis revealed that the tender joint count decreased 2.2 +/- 6.1 (mean +/- SD) joints in the placebo group, 2.2 +/- 6.6 joints in the CyA 1.25 mg group, and 5.0 +/- 5.8 joints in the CyA 2.50 mg group (p = 0.04). The 1995 preliminary ACR response criteria for clinical improvement were met by 8 (28%) patients in the placebo group, 10 (34%) patients in the CyA 1.25 mg group, and 15 (50%) patients in the CyA 2.50 mg group (p = 0.07). The serum creatinine increased 2 +/- 7 micromol/l in the placebo group, decreased 1 +/- 8 micromol/l in the CyA 1.25 mg group, and increased 10 +/- 15 micromol/l in the CyA 2.50 mg group (p < 0.001). CONCLUSION: The addition of low dose CyA is moderately effective in patients with early RA already treated with low dose chloroquine, but results in statistically significant renal function loss.

Adolescent↗