Large deletion causing the TSC2-PKD1 contiguous gene syndrome without infantile polycystic disease.
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Adolescent↗
Biomedical subjects
Y M Smulders
Publications and source records attributed to Y M Smulders.
[Unexpectedly high mortality rate after acute hospital admission of elderly patients without a medical history].
OBJECTIVE: To determine whether having no medical history is a favourable or unfavourable predictor of the relative risk of post-admission mortality for elderly patients acutely admitted to hospital. DESIGN: Descriptive, retrospective. METHODS: The records of all patients > or = 75 years old who were acutely admitted to the Department of Internal Medicine at the Amsterdam Academic Medical Centre between 1 January 1998 and 31 December 1999 were studied. Age, sex, complete medical history, admission diagnosis, and survival status at discharge were registered. RESULTS: Of the 460 patients studied (201 men and 259 women; age: 74-100 years; median: 82), 25 (5.4%) had no medical history. The total admission-related mortality was 17% (80/460). Patients with no medical history had a mortality rate of 48% (12/25) and patients with a medical history a mortality rate of 16% (68/435). Therefore the difference in mortality rate was 32% (95% CI: 14-51; p = 0.001) to the detriment of patients without a medical history. The age and sex-adjusted odds ratio for mortality associated with having no medical history was 4.0 (95% CI: 1.7-9.4). CONCLUSION: It seems that not having a medical history is an unfavourable prognostic sign for acutely admitted elderly patients.
Acute Disease↗
Contribution of pulmonary vasoconstriction to haemodynamic instability after acute pulmonary embolism. Implications for treatment?
Acute pulmonary embolism with haemodynamic instability has a high mortality rate. Death results from an acute increase in right ventricular afterload, and the commonly held view is that mechanical obstruction of the pulmonary vascular bed is largely responsible for this increase. In accordance, recent treatment guidelines for severe pulmonary embolism focus exclusively on interventions aimed at relieving this mechanical obstruction, either by thrombolysis or (catheter) embolectomy. However, there is evidence to indicate that vasoconstriction is a very important contributor to the initial increase in pulmonary vascular resistance after pulmonary embolism. This is consistent with the observation that the degree of mechanical obstruction correlates at best poorly with haemodynamic manifestations. Thromboxane A(2) and serotonin are probably mainly responsible for pulmonary vasoconstriction. Cyclooxygenase inhibitors and serotonin antagonists have been shown in animal experiments to attenuate the haemodynamic response to acute pulmonary embolism and to reduce mortality. In addition, reports of a favourable response to pulmonary vasodilators in animals and in humans with acute severe pulmonary embolism have been published. In this paper, it is argued that we may need to reconsider our current therapeutic approach to patients with acute severe pulmonary embolism. Antagonising pulmonary vasoconstrictive mediators or administering pulmonary vasodilators may prove to be life-saving interventions in these patients.
Animals↗
Rapid progression of albumin excretion is an independent predictor of cardiovascular mortality in patients with type 2 diabetes and microalbuminuria.
OBJECTIVE: In patients with type 2 diabetes, microalbuminuria is associated with an increase in predominantly cardiovascular mortality. Considerable interindividual variability in the rate of progression of microalbuminuria exists. The prognostic significance of rate of progression of microalbuminuria with regard to cardiovascular and renal clinical end points is, however, unknown. The purpose of this study was to determine the prognostic significance of rate of progression of microalbuminuria for cardiovascular end points and renal function. RESEARCH DESIGN AND METHODS: In a previous prospective cohort study, progression of microalbuminuria (expressed as mean yearly change in albumin-to-creatinine ratio) was assessed in 58 patients with type 2 diabetes. During a median follow-up of 7 years after progression of microalbuminuria was determined, we registered all-cause mortality and coronary heart disease mortality as primary end points and coronary heart disease (fatal or nonfatal), peripheral vascular disease, ischemic stroke, retinopathy, macroalbuminuria, and change in serum creatinine as secondary end points. RESULTS: Seven subjects died during the study; five of these subjects died of coronary heart disease. Cox's regression analysis identified progression of microalbuminuria as a significant predictor of all-cause mortality (hazard ratio 1.46 per point increase in albumin-to-creatinine ratio per year, P < 0.001), coronary heart disease mortality (hazard ratio 2.32, P = 0.006), and macroalbuminuria (hazard ratio 1.79, P < 0.001). Adjustment for multiple cardiovascular risk factors did not affect these results. Identical analyses for baseline level of microalbuminuria instead of progression rate of microalbuminuria did not show significant hazard ratios. In addition, progression of microalbuminuria significantly predicted an increase in serum creatinine (r = 0.29, P = 0.04). CONCLUSIONS: In patients with type 2 diabetes and microalbuminuria, the rate of progression of albumin excretion seems to be a powerful independent predictor of mortality caused mainly by coronary heart disease.
Aged↗
Pathophysiology and treatment of haemodynamic instability in acute pulmonary embolism: the pivotal role of pulmonary vasoconstriction.
Acute massive pulmonary embolism has a high mortality rate. Fatal haemodynamic deterioration is caused by an acute increase in pulmonary vascular resistance. Traditionally, the degree of mechanical obstruction of the pulmonary vasculature by the embolic thrombus is considered to be the major determinant of this increase in right ventricular afterload. However, there is evidence to suggest that another factor plays an important role, since there is a marked discrepancy between the haemodynamic manifestations of acute pulmonary embolism and the degree of mechanical obstruction. Historic studies indicate that this discrepancy is largely explained by pulmonary vasoconstriction caused by vasoactive mediators, released mainly by activated platelets. Thromboxane-A(2) and serotonin are probably the two most important pulmonary vasoconstrictors in this context. Antagonising their effects dramatically increases tolerance to experimental pulmonary embolism in animals. In humans, this concept should eventually find its way into clinical practice. In the future, acute massive pulmonary embolism could be treated with antagonists to pulmonary vasoconstrictors, or with direct pulmonary vasodilators.
Acute Disease↗
The (non-)sense of the methionine loading test for detecting hyperhomocysteinaemia.
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Cardiovascular Diseases↗
Cardiovascular autonomic function is associated with (micro-)albuminuria in elderly Caucasian sujects with impaired glucose tolerance or type 2 diabetes: the Hoorn Study.
OBJECTIVE: To determine whether impaired cardiovascular autonomic function correlates with albuminuria in an age-, sex-, and glucose tolerance-stratified sample of an elderly (50-75 years of age) Caucasian population and to determine whether this association is independent of other determinants of albuminuria. RESEARCH DESIGN AND METHODS: We studied 536 subjects, 256 with normal glucose tolerance, 143 with impaired glucose tolerance (IGT), and 137 with type 2 diabetes. Microalbuminuria was defined as an albumin-to-creatinine ratio of > or =3.0 and < or =30 mg/mmol in an early morning urine sample. We used the deep-breathing test and the lying-to-standing test to obtain 4 measurements of cardiovascular autonomic function: 1) the heart rate (HR) variability during deep breathing, 2) the maximum HR within 15 s after standing up minus the mean HR before standing, 3) the maximum R-R interval between 15 and 30 s after standing up divided by the minimum R-R interval within 15 s after standing up, and 4) the systolic blood pressure in response to standing up. These 4 measurements were summarized in a single cardiovascular autonomic function score (CAFS). RESULTS: A total of 38 subjects with microalbuminuria and 3 subjects with macroalbuminuria (>30 mg/mmol) were grouped as having albuminuria. In bivariate analyses, albuminuria was associated with age, waist-to-hip ratio, systolic and diastolic blood pressure, calculated glomerular filtration rate, and glucose tolerance status. The mean CAFS was higher in subjects with versus without albuminuria (7.5 vs. 5.9, P<0.001). Multiple logistical regression analyses revealed that the CAFS was independently associated with albuminuria in subjects with IGT or type 2 diabetes with an odds ratio (95% CI) of 1.19 (1.02-1.39) per point increase in the CAFS. CONCLUSIONS: Impaired cardiovascular autonomic function is independently associated with (and thus a possible contributor to) the presence of albuminuria in subjects with IGT or type 2 diabetes.
Aged↗
Is plasma homocysteine related to albumin excretion rate in patients with diabetes mellitus?
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Albuminuria↗
Fasting and post-methionine homocysteine levels in NIDDM. Determinants and correlations with retinopathy, albuminuria, and cardiovascular disease.
OBJECTIVE: The increased cardiovascular risk in subjects with NIDDM is partly explained by an association with established risk factors like hypertension, dyslipidemia, and obesity. Mild hyperhomocysteinemia has emerged as a new risk factor for cardiovascular disease. The purpose of this study was to assess its role in NIDDM. RESEARCH DESIGN AND METHODS: We studied predictors of homocysteine levels and correlations between homocysteine and (micro-)albuminuria, retinopathy, and history of cardiovascular disease in normotensive NIDDM subjects under stable metabolic control. This was done in 85 NIDDM subjects by measuring fasting and post-methionine-loading homocysteine levels together with blood pressure, BMI, serum cholesterol, triglyceride, HDL cholesterol, folate, vitamin B12, pyridoxal-5-phosphate, HbA1c, and (micro-)albuminuria and creatinine clearance in triplicate 24-h urine samples. The relationship between micro- and macrovascular complications and fasting homocysteine only was studied in an additional 65 subjects, giving a total of 150 subjects. RESULTS: In multiple regression analysis, significant (P < 0.05) predictors of fasting homocysteine were low-normal values of creatinine clearance (threshold effect at < 80 ml.min-1 .1.73 m-2), folate (< 20 nmol/l), and vitamin B12 (< 350 pmol/l), and postmenopausal status in women. Determinants of post-methionine homocysteine were pyridoxal-5-phosphate levels < 80 nmol/l, creatinine clearance, and sex (higher levels in women). Hyperhomocysteinemia did not cluster with other cardiovascular risk factors, like hypertension, obesity, or dyslipidemia. Regarding cardiovascular complications, fasting homocysteine, but not post-methionine homocysteine, was higher in subjects with a history of cardiovascular disease. There was a stepwise increase in the prevalence of subjects with cardiovascular disease with increasing fasting homocysteine. The prevalence of cardiovascular disease was 19.4% in the bottom quartile of fasting homocysteine, versus 55.0% in the top quartile (P for trend < 0.01). Neither fasting homocysteine nor post-methionine homocysteine correlated with (micro-)albuminuria or with retinopathy. CONCLUSIONS: The findings suggest that homocysteine levels in NIDDM rise even with modest deterioration of renal function and when vitamin status is in the low to low-normal range. Fasting homocysteine correlates with macrovascular disease, but we found no evidence of a correlation with retinopathy or (micro-)albuminuria. Post-methionine homocysteine levels do not show a correlation with micro- or macrovascular complications.
Administration, Oral↗
Trimethoprim and fasting plasma homocysteine.
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Adult↗
Short-term variability and sampling distribution of various parameters of urinary albumin excretion in patients with non-insulin-dependent diabetes mellitus.
We determined the degree of variability and sampling distribution of several commonly used parameters of microalbuminuria in patients with non-insulin-dependent diabetes mellitus (NIDDM) and proposed a sampling strategy for estimating the level of albuminuria. Four patients with NIDDM with previously documented microalbuminuria collected 30 consecutive split (overnight and daytime) 24-hour urine samples (experiment A). These samples were analyzed for total 24-hour albumin excretion; daytime, overnight, and 24-hour albumin concentration; and daytime, overnight, and 24-hour albumin-to-creatinine ratio. In a second experiment (B), 10 patients collected 10 consecutive overnight urine samples. Finally, a total of 300 separate triplicate urine samples were analyzed for the variability of 24-hour albumin excretion (100 samples) and albumin-to-creatinine ratios in 24-hour urine (100 samples) and overnight urine (100 samples). We found that the sampling distribution shape of all parameters of albuminuria is positively skewed, without consistent evidence of log-normality. When two methods were used for quantifying day-to-day variability (the interquartile range/median ratio and the chance of a single measurement being >50% off the actual value of albuminuria), the overnight albumin-to-creatinine ratio is the least-variable parameter of albuminuria, scoring 0.38% and 10% on both methods, respectively, in experiment A. Collecting multiple samples of overnight urine improves accuracy. The largest gain in precision in estimating the actual value of albuminuria is obtained for sample sizes of three and five and does not increase with nonconsecutive sampling of urine. Based on the combined data from experiments A and B, the expected mean deviation of the median of three and five overnight samples from the actual level of the overnight albumin-creatinine ratio is 17.9% and 12.1%, respectively. An analysis of variability in three sets of 100 triplicate 24-hour urine samples shows that the overnight albumin-to-creatinine ratio is a significantly more-constant parameter of microalbuminuria than the amount of albumin excreted in 24 hours or the albumin-to-creatinine ratio in 24-hour urine (p < 0.05). We concluded that the parameters of diabetic albuminuria have positively skewed, non-log-normal sampling distributions. The overnight albumin-to-creatinine ratio is the least-variable parameter of microalbuminuria. We recommend collecting three consecutive early morning urine samples, using the median value of the albumin-to-creatinine ratio in these samples for quantifying albuminuria.
Aged↗
HIV-related thrombotic thrombocytopenic purpura: report of 2 cases and a review of the literature.
Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterised by the clinical pentad of microangiopathic haemolytic anaemia (MAHA), thrombocytopenia, renal failure, fluctuating neurologic signs, and fever. The aetiology of TTP is unknown, but associations with various underlying diseases, infections and drugs have been identified. One of these associations is with HIV infection. We describe the clinical picture, the laboratory results and the response to plasma therapy of two cases of HIV-associated TTP. In both patients, a longitudinal semiquantitative assessment of the numbers of schistocytes in blood was made, which correlated well with the more traditional parameters of disease activity. Since 1987, at least 49 patients with HIV-associated TTP have been reported. A case-analysis of the 38 patients who were described in sufficient detail and a review of the literature in the setting of HIV infection is presented. The most important conclusions from these combined data are: (1) TTP usually seems to occur in patients with a CD4+ lymphocyte count < 250 x 10(6).l(-1); (2) more than 50% of the patients present with TTP soon after or during an infectious or malignant disease; (3) plasma exchange is the therapy of choice, still resulting in mortality of 22%; (4) higher initial platelet count and creatinine level are correlated with an adverse outcome.
Adult↗
Can reduction in hypertriglyceridaemia slow progression of microalbuminuria in patients with non-insulin-dependent diabetes mellitus?
The objective of this study was to investigate whether reduction in hypertriglyceridaemia is associated with a slower rate of progression of microalbuminuria in patients with non-insulin-dependent diabetes mellitus (NIDDM). Fifteen normotensive NIDDM patients with hypertriglyceridaemia (> 2.5 mmol L-1) and microalbuminuria were randomly selected to receive either placebo (eight patients) or gemfibrozil 600 mg b.i.d. (seven patients). Progression of microalbuminuria was assessed during a 12-month follow-up period with measurements, consisting of blood tests and triplicate 24-h urine collections, at 1, 3, 6, 9 and 12 months. All but one patient in the treatment group showed a favourable response (> or = 20% reduction) of hypertriglyceridaemia to gemfibrozil. One patient in the placebo group showed a spontaneous reduction in triglyceride levels. Progression of microalbuminuria was lower, although not statistically significantly so, in the treatment group (36%) than in the placebo group (65%). In the group with > or = 20% reduction in triglyceride levels, progression of MA was significantly lower than in the group with stable or increasing triglyceride levels (+1%, range -56% to +49% vs. +97%, range -35% to +202% respectively) (P = 0.03). Continued follow-up data of patients switching from placebo to gemfibrozil after the trial further support the role of serum triglyceride reduction in stabilizing albumin excretion. In conclusion, the results indicate that, in microalbuminuric NIDDM patients, effective treatment of dyslipidaemia could be associated with stabilization of urinary albumin excretion.
Adult↗
Determinants of progression of microalbuminuria in patients with NIDDM.A prospective study.
OBJECTIVE: To assess the degree of interindividual variation in the rate of progression of microalbuminuria and to identify determinants of progression of microalbuminuria in patients with NIDDM. RESEARCH DESIGN AND METHODS: In a prospective cohort study, 58 microalbuminuric NIDDM patients were followed for a period of at least 24 months. During this period, the level of microalbuminuria in these patients was assessed in triplicate 24-h urine samples on at least four separate visits. All patients had stable metabolic control and controlled blood pressure during follow-up. Microalbuminuria was defined as an albumin-to-creatinine ratio in 24-h urine of between 3 and 30 mg/mmol. The individual rates of progression of microalbuminuria were calculated from linear regression analysis. At baseline, the following data were collected for all patients: age, sex, ethnicity, time since diagnosis of NIDDM, smoking habits, drug use, blood pressure, BMI, HbA1c, serum creatinine, cholesterol, triglyceride, and HDL cholesterol concentrations. RESULTS: Microalbuminuria was found to progress linearly in time. Considerable differences in rates of progression of microalbuminuria were found, the absolute yearly change in albumin-to-creatinine ratio ranging from -5.2 to 12.9 mg/mmol. In bivariate analyses, serum triglyceride concentration, use of ACE inhibitors, mean arterial blood pressure, HDL cholesterol, and time since diagnosis of NIDDM correlated with progression of microalbuminuria (P < or = 0.05). In stepwise multiple regression analysis, a high triglyceride-to-HDL cholesterol ratio at baseline (P = 0.006) and the use of ACE inhibitors (P = 0.007) were identified as the only independent predictors of progression of microalbuminuria. CONCLUSIONS: The rate of progression of microalbuminuria in NIDDM differs considerably between subjects. Diabetic dyslipidemia (high serum triglyceride and low HDL cholesterol) is a predictor of more rapid progression of microalbuminuria in patients with well-controlled blood pressure.
Albuminuria↗
Hypovitaminosis D in immigrant women: slow to be diagnosed.
Hypovitaminosis D osteopathy should be considered in immigrant women with musculoskeletal pain.
Adult↗
Bacille Calmette-Guérin (BCG) meningitis in an AIDS patient 12 years after vaccination with BCG.
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AIDS-Related Opportunistic Infections↗
Intraoperative assessment of the mitral valve: transesophageal Doppler echocardiography vs. left ventricular filling of the flaccid heart.
Several methods can be used for the intraoperative assessment of residual mitral regurgitation (MR) following reconstruction of the mitral valve. The aim of this study was to compare the reliability of two of these methods: left ventricular filling of the arrested heart with saline (LVF) and intraoperative transesophageal Doppler echocardiography (TEE). Reliability was assessed by comparing LVF and TEE to postoperative left ventricular angiography (LVA) in 27 patients. LVF, TEE and LVA grading of MR was 0-4. Correlations, as measured by the Kappa statistic, were as follows: LVF-LVA: K = 0.33 (95% confidence interval (CI): 0.06-0.59), TEE-LVA: K = 0.48 (95% CI: 0.20-0.77), LVF-TEE: K = 0.43 (95% CI: 0.20-0.67). Considering LVF and TEE as predictors of LVA gradings above 2, sensitivities were 0.4 and 0.6, respectively. Specificities were 1.0 for each method. In conclusion, we found TEE in the beating heart not to be significantly more reliable in the prediction of residual MR than LVF in the flaccid heart.
Adult↗
[No consequences of prolonged drainage following open heart surgery on the incidence of postoperative pericardial effusion].
Pericardial effusion (PE) frequently occurs after cardiac surgery and, in some cases, complicates the postoperative course. This study was performed in order to assess if prolongation of the postoperative drainage period may result in a decreased incidence of PE. For this purpose we studied 100 patients, randomised into two groups. In group I (50 patients) standard drainage of the thorax was performed. In group II (50 patients) the drainage period was prolonged by 24 hours. The amount of fluid drained during the additional period did not correlate with preceding fluid production. Echocardiography performed on the sixth postoperative day revealed a virtually equal incidence of PE in both groups: 26 patients in group I, 29 patients in group II. None of the observed effusions resulted in clinical signs of cardiac tamponade. PE occurred more frequently in patients with more than 60 ml of additional drainage volume (p less than 0.01). We conclude that: (1) prolonging the duration of postoperative drainage does not result in a lower incidence of postoperative PE and (2) the aetiological process causing PE in a number of patients is probably already active during the early postoperative course.
Adult↗