Platelet consumption in thrombocythemia complicated by erythromelalgia: reversal by aspirin.

The involvement of platelets in the pathogenesis of erythromelalgia, a frequent and characteristic microvascular thrombotic manifestation in patients with primary thrombocythemia and polycythemia rubra vera, was investigated by measuring the survival and turnover of 51Cr labeled autologous platelets in 10 patients with thrombocythemia complicated by erythromelalgia, in 10 asymptomatic thrombocythemia patients and in 6 subjects with reactive thrombocytosis. The mean platelet survival time of the erythromelalgia patients was 4.2 +/- 0.2 days, which is significantly decreased as compared with asymptomatic thrombocythemia patients (6.6 +/- 0.3 days, p < 0.001) and patients with reactive thrombocytosis (8.0 +/- 0.4 days, p < 0.001). The mean platelet survival time of asymptomatic thrombocythemia patients was significantly decreased (p < 0.01) as compared with reactive thrombocytosis patients. Treatment of erythromelalgia with aspirin increased the mean platelet survival time from 4.0 +/- 0.3 days to 6.9 +/- 0.4 days (p < 0.001) and was associated with an elevation of the platelet count of 216 +/- 30 x 10(9) platelets per liter (p < 0.001). Coumadin failed to improve platelet survival or symptoms caused by erythromelalgia. The increased platelet consumption in erythromelalgia is attributed to the formation of platelet thrombi in the arterial microvasculature. This conclusion is supported by the ability of aspirin to interrupt platelet consumption and clinical features of erythromelalgia.

Erythromelalgia in essential thrombocythemia is characterized by platelet activation and endothelial cell damage but not by thrombin generation.

Erythromelalgia, a characteristic aspirin-responsive microvascular thrombotic complication in essential thrombocythemia (ET), may develop despite oral anticoagulant treatment or treatment with heparin, suggesting that the generation of thrombin is not a prerequisite for its development. To study this, a cross-sectional comparison of the plasma levels of thrombomodulin (TM), platelet factor 4 (PF4), beta-thromboglobulin (beta-TG), prothrombin fragment 1 + 2 (F1 + 2) and total degradation products of fibrin(ogen) (TDP) was made between 5 ET patients suffering from erythromelalgia, 16 asymptomatic ET patients and 20 control subjects, and after treatment with aspirin, respectively. Furthermore, 2 ET patients with a history of erythromelalgia were studied at regular time intervals after discontinuation of aspirin until erythromelalgia recurred. As compared with asymptomatic ET patients and control subjects erythromelalgia was characterized by significantly higher beta-TG and TM levels but no significant differences were detected in either F1 + 2 or TDP levels. Treatment of erythromelalgia with aspirin resulted in disappearance of erythromelalgic signs and symptoms, which was paralleled by a significant decrease of beta-TG and TM levels. Histopathologic and immunohistochemical analysis of biopsies derived from erythromelalgic skin areas of 2 ET patients showed that erythromelalgic thrombi stained positively for von Willebrand factor opposed to only a weak fibrin staining. Our data suggest that erythromelalgia is caused by the intravascular activation and aggregation of platelets with subsequent sludging or occlusion of the acral arterial microvasculature. The generation of thrombin appears not to be essential for the formation of these platelet thrombi, thereby giving a plausible explanation for the inefficacy of coumadin derivatives and heparin in the prevention and treatment of erythromelalgia in essential thrombocythemia.

Impact of influenza on mortality in relation to age and underlying disease, 1967-1989.

Based on data from the Dutch Central Bureau of Statistics, the impact of influenza on mortality in The Netherlands was estimated for a 22.5-year period (1967-1989) in four age groups and three entities of disease, using Poisson regression techniques. Our analysis suggests that, on average, more than 2000 people died from influenza in The Netherlands each year, but in only a fraction of these deaths was influenza recognized as the cause of death. For each case of death registered as caused by influenza (registered influenza mortality), 2.6 additional cases of death registered as due to causes other than influenza, nevertheless, were influenza-related (non-registered influenza mortality). Therefore, the overall impact of influenza on mortality is estimated to be greater than registered influenza mortality by a factor of 3.6. Those under 60 years of age accounted for 5% of all non-registered influenza deaths, whereas people aged 60-69, 70-79 years and > 80 years accounted for 12%, 29% and 54% of such deaths, respectively. When extrapolating the figures for the Dutch population of 1989, we could attribute, on average per season-year, 82 deaths per 100,000 people > 60 years, 143 in people > 70 years, and 280 in people > 80 years. Of all non-registered influenza cases of death, 47% were estimated to occur in people with heart disease as a primarily reported cause of death, 23% in those with lung disease, and 30% in those with other diseases. This study stresses the serious effects of influenza, mainly in the elderly (95% of non-registered influenza mortality).(ABSTRACT TRUNCATED AT 250 WORDS)

The determination of reference values for hematologic parameters using results obtained from patient populations.

Reference values for hematologic parameters are determined using data from patient populations of a whole year. As a consequence, the authors are not dependent on a limited selected population and can determine reference values for all age and sex groups. It turns out that from the possible compilation technics the gamma distribution gives the best fit. If the results are compared with values stated in the literature, it is remarkable that the total number of leukocytes for men older than 50 years is higher than for women; both the absolute and relative amount of monocytes and eosinophilic granulocytes are higher for men than for women. The platelets are lower for men than for women from the age of 15 years on.

Human small airway smooth muscle responses in vitro; actions and interactions of methacholine, histamine and leukotriene C4.

The in vitro contractile responses to methacholine, histamine and leukotriene C4 (LTC4) were measured in human bronchiolar strips obtained after surgery. LTC4 was approximately 100 times more potent than both methacholine and histamine (mean pD2 values were 8.01, 6.18 and 5.87 respectively). All three agonists produced the same maximum contractile response (Tmax) and no difference was found in the time course of methacholine-, histamine- and LTC4-induced responses. When methacholine, histamine and LTC4 were applied in succession on one airway preparation, no interactions between these agonists were demonstrated for pD2. However, interactions were found concerning Tmax. The sensitivity (pD2) could be measured accurately and reproducibly and showed a relatively small within-patients variation (coefficients of variation 4-5%). In contrast, Tmax showed a considerable within-patients variation (coefficients of variation 47-91%), which limits its usefulness when small numbers of airway preparations are studied.

Short-term efficacy of tricyclic antidepressants revisited: a meta-analytic study.

The original data from the placebo-arms and the tricyclic-arms of all parallel randomized controlled three-arm studies, which had been conducted in the period 1979-1991 for a drug under development in order to obtain marketing authorization for the indication major depression, were included in a meta-analysis. Thirty-two placebo-controlled studies including 4314 patients were analyzed. The intention to treat analysis resulted in 46% responders (at least 50% improvement on the Hamilton Depression Rating Scale) in the tricyclic antidepressant group and 31% in the placebo-group (CI(95%-difference) 11.5-17.1%). The number needed to treat for responders was 7 (CI(95%) 5-8). In 10 out of 32 studies, a statistically significant difference in favor of tricyclic antidepressant compared to placebo was found for responders. The responder rate in the placebo-group varied from 6 to 52%. We conclude that tricyclic antidepressants are efficacious in the short-term treatment of major depression. However, the magnitude of the effect is rather modest. Because 69% of the placebo-controlled studies with a tricyclic antidepressant did not show a statistically significant difference in favor of tricyclic antidepressant and the placebo rate varied considerably from study to study, equivalence studies with tricyclic antidepressant as comparator without a placebo-control are not sufficient for demonstrating efficacy. Therefore in major depression, placebo-controlled studies are still necessary to demonstrate efficacy.

Is irradiation a justifiable treatment of choroidal melanoma? Analysis of published results.

Analysis of the literature shows that dissemination of choroidal melanomas generally occurs after the 7 mm diameter stage, that doubling times of uveal melanomas vary from 30 to 365 days, and that death from metastases occurs 30-40 doubling times after dissemination. Tumour related death within three years after therapy is caused by pre-existing metastases. Survival rates for less than four years after therapy are therefore irrelevant in evaluating the efficacy of therapeutic regimens. Considerably higher postirradiation than postenucleation death rates after a mean 10-year follow-up period have been reported, and this difference can be explained by a reported mean clinical tumour regression rate of 31% two years after irradiation and histopathological studies which revealed that 42 out of 43 irradiated melanomas contained viable tumour, while only 50% showed necrosis. The doubtful value of preserving vision does not justify the high risk of avoidable death from metastases in irradiated patients.

Lung function and bronchial responsiveness in children who had infantile bronchiolitis.

A number of studies have shown that children who had infantile bronchiolitis are at increased risk of recurrent episodes of wheezing. A genetic predisposition to atopy is mentioned in some studies and is contested by others. Lung function abnormalities and increased bronchial responsiveness (BR) have been described after infantile bronchiolitis. We investigated children who had had the clinical syndrome of bronchiolitis during infancy and compared them with asthmatic and healthy children of the same age regarding bronchial caliber, smooth muscle tone, and responsiveness to histamine. Lung function was measured by forced oscillometry. We found that most children with current symptoms had either decreased baseline bronchial caliber, increased bronchial smooth muscle tone, or increased BR. These patients are comparable to mild asthmatics. The children without current symptoms are comparable to healthy children in these respects. Recurrent respiratory symptoms after bronchiolitis should be regarded as mild asthma and treated as such.

Urinary C-peptide: a useful tool for evaluating the endogenous insulin reserve in cohort and longitudinal studies of diabetes in childhood.

Increasing research into the remission phase of type I diabetes mellitus stresses the importance of a non-traumatic and reliable method for the evaluation of endogenous insulin production. We compared 24-h urinary C-peptide excretion (UCE) with plasma C-peptide values before and after stimulation with 1 mg glucagon in 24 type I diabetic children. Fasting plasma C-peptide values and stimulated plasma C-peptide values showed a linear correlation with 24 h UCE. Mean plasma C-peptide levels correlated inversely with the exogenous insulin dose. A slightly better correlation was found between the exogenous insulin dose and 24 h UCE. Control data of 24 h UCE were obtained from healthy siblings. A linear correlation with age was found up to 10 years of age above which UCE values seem to reach a plateau. This effect of age, as well as the frequency of sampling was taken into account in the derivation of 95% reference intervals for UCE. The measurement of 24 h UCE appears to be a useful parameter to assess endogenous insulin production in diabetic children, provided that age is taken into account.

Improved reproducibility of measurements with the nerve fiber analyzer.

PURPOSE: This study was undertaken to assess and improve the repeatability and reproducibility of nerve fiber layer (NFL) measurements using the Nerve Fiber Analyzer (NFA I), a scanning laser polarimeter. METHODS: The repeatability of two subsequent measurements was determined in 100 healthy eyes. Four methods of image evaluation were performed. Polarimetric measurements of retinal NFL were obtained along a peripapillary band at the superior and inferior poles of the optic disk and analyzed in a one-pixel band of absolute retardation values (method 1) and relative to the nasal segment (method 2). Method 3 used measurements obtained in a 10-pixel band along the same peripapillary band. Method 4 comprised measurements in selected areas outside the peripapillary band, which did not contain blood vessels. The repeatability (r) and relative reliability coefficient (Rel) were assessed as indices of agreement of repeated measurements. In addition, the reproducibility (R) from day to day for methods 3 and 4 was assessed by taking 10 images on 10 consecutive days from each of 10 subjects. RESULTS: The 95% critical value for r in the superior and inferior segments improved from about 30% for methods 1 and 2, to 23% for method 3, and to 11% for method 4. For the superior and inferior segments, the fourth method of image evaluation yielded a Rel of 98%, as compared with 54% in method 1, 80% in method 2, and 87% in method 3. The 95% critical value for R was 23% for method 3 but only 15% for method 4. CONCLUSIONS: The improved reproducibility of measurements has made the NFA I a promising device. An improved reproducibility (smaller limit for detecting change) does not necessarily indicate good sensitivity and specificity for any instrument. The role of the scanning laser polarimeter in clinical practice requires further study.

Why leg crossing? The influence of common postures on abdominal muscle activity.

STUDY DESIGN: Abdominal muscle activity is recorded in the supine position, unconstrained standing, and in the sitting position on an office chair with the use of backrest and armrests, with and without crossed legs. OBJECTIVES: To assess the role of oblique abdominal muscles in relation to the stability of lumbar spine and pelvis in commonly adopted unconstrained postures. SUMMARY OF BACKGROUND DATA: Cross-legged sitting is very common for men and women. No solid evidence exists for either a beneficial or a detrimental effect of this posture. No electromyographic study deals with the activity of abdominal muscles in this commonly adopted unconstrained posture. METHODS: In healthy subjects, electromyographic activity of the rectus abdomini and external and internal oblique abdominals was recorded bilaterally during commonly adopted unconstrained postures. RESULTS: The activity of the internal oblique muscle was significantly higher in the sitting position than in supine position. For the external and internal oblique abdominals, the activity was significantly higher in the standing position than in the sitting position. When sitting, the activity of the oblique abdominals is significantly lowered by crossing the legs in the preferred way (either upper legs cross or ankle on knee). In contrast, the activity of the rectus abdominis is not significantly altered by leg crossing. CONCLUSIONS: From these remarkable findings, we conclude that leg crossing is physiologically valuable. It should be studied whether leg crossing can be implemented in the design of the workplace.

Evaluation of techniques for the presentation of laboratory data: support of pattern recognition.

Two tabular and two graphical techniques for the presentation of laboratory test results were compared in a reaction-time experiment with 22 volunteers. The experimental setup was designed to determine whether one or more of the presentation techniques facilitated the recognition of four predefined combinations of abnormal test results. Using a conventional, tabular presentation technique as a reference, faster median response times were obtained with each of the other three presentation techniques, irrespective of pattern. The effect on accuracy was less clear, possibly due to the small number of errors made.

Evaluation of techniques for the presentation of laboratory data. I: Time needed for interpretation.

Four tabular and two graphical techniques for the presentation of laboratory test results were evaluated in a reaction-time experiment with 25 volunteers. Artificial variables and values were used to represent sets of 12 laboratory tests to eliminate the possible effects of clinical experience. Analyses focused on reaction times for correctly classified sets of data. For comparable data sets, Presentation Techniques (PT) that use color, always allow faster interpretation than PTs that do not use color, or use only a simple marker. Color-coded tables yielded an improvement in median reaction time of approximately six times or better, as compared to the reference PT (a tabular PT without any hints). For the color-coded graphs, the improvement rate was approximately 2.5 or better.

Evaluation of techniques for the presentation of laboratory data. II: Accuracy of interpretation.

Four tabular and two graphical techniques for the presentation of laboratory test results were evaluated in a reaction time experiment with 25 volunteers. Artificial variables and values were used to represent sets of 12 laboratory tests to eliminate the possible effects of clinical experience. Analyses focused on four types of errors in interpretation. Color-coded tables and one of the color-coded graphs greatly (2.8 times or better) reduced the number of incorrectly classified test results, as compared to the reference presentation technique. This was mainly due to a reduction of the number of abnormal test results that were not noticed by the subjects when using these presentation techniques.

Allogeneic transplantation of the radial side of the hand in the rhesus monkey: I. Technical aspects.

Since allogeneic transplantation of extremities can only be considered if uneventful long-term survival and functional recovery can be achieved, a series of 12 transplantations of the radial side of the hand were performed in rhesus monkeys so that these factors could be assessed. The transplant incorporated the first ray of the hand in conjunction with the radial forearm flap. Graft survival times varied from 21 to 179 days. Ten of 12 transplants showed rejection. In 2 of the 10, rejection could be reversed. Immunosuppressive therapy consisted of cyclosporin A, prednisone, monoclonal antibodies, and preoperative third-party blood transfusions. Monitoring of the microcirculation of the allograft could not provide a predictive value for transplant rejection. The first clinical signs of sensory and motor function recovery were detected after an average of 42 and 44 days, respectively. Indefinite uneventful allograft survival could not be established. Major complications such as sepsis, shock, and lymphoma development leading to death were encountered. The model, however, is technically feasible, and the results for functional recovery under immunosuppression are promising.

The effect of cigarette smoking on the survival of free vascularized and pedicled epigastric flaps in the rat.

Microsurgeons suspect that cigarette smoking reduces the survival of free vascularized flaps and replantations, but this has never been proven. This experimental study investigates the effect of smoking on free-flap survival. A fasciocutaneous epigastric flap was used in 30 rats as a free flap and in 30 rats as a pedicled flap. Of each group, 10 rats were smoked 6 weeks before and 2 weeks after surgery, 10 rats were smoked only 6 weeks before surgery, and 10 rats underwent the sham smoking procedure. Also, a distally based dorsal skin flap was cut in all rats, representing a random vascularized flap. Vitality and size of both flaps and patency of the vascular anastomoses were assessed 14 days after surgery. The epigastric flaps were monitored by laser Doppler flowmetry and thermometry during the experiment. Survival of the free vascularized epigastric flaps was significantly lower in smoking rats. All pedicled flaps except one survived. The epigastric flaps only necrosed or survived completely, exactly correlating to the patency of the vascular anastomoses. The mean surviving area of the dorsal flaps was best for nonsmoking rats, worse for only preoperatively smoking rats, and worst for preoperatively and postoperatively smoking rats. The differences were statistically significant. Postoperative laser Doppler flow differed significantly between surviving and dying flaps, affirming the value of laser Doppler flow monitoring in microvascular surgery. In conclusion, this study proves that smoking of cigarettes is detrimental to the survival of free vascularized flaps.

Liver and renal function after volatile induction and maintenance of anesthesia (VIMA) with sevoflurane versus TIVA with sufentanil-midazolam for CABG surgery.

We compared liver and renal function after volatile induction and maintenance of anesthesia (VIMA) with sevoflurane and minimal dose sufentanil versus total intravenous anesthesia (TIVA) with moderate dose of midazolam and sufentanil in patients undergoing CABG surgery. Eighty nine patients were studied retrospectively after VIMA (44 patients) or after TIVA (45 patients). Liver and renal function were measured before (T0), then 1 (T1), 2 (T2), 5 (T3) days and 6 weeks (T4) after the operation. Serum levels of aspartate aminotransferase (ASAT) and lactate dehydrogenase (LDH) increased in both groups at T1, T2 and T3 and the highest levels were at T1. Levels of total bilirubin (TBil) increased at T1 only in the TIVA group. Levels of g-glutamyl transpeptidase (GGT) and alanine aminotransferase (ALAT), increased in both groups at T3. Serum levels of creatinine (Cr) were high in both groups on T1 and T2. Blood urea nitrogen (BUN) was high in both group at T2, and T3 with the peak levels in T2. Six weeks after the operation all liver and renal functions were normal in both groups. We concluded that VIMA with sevoflurane during cardiac surgery has no untoward effects on liver or renal functions. The transient reversible elevation was comparable in the VIMA and TIVA groups which was most probably due to the effect of the operation itself.

Differences between arterial and venous occlusion in microvascular surgery.

Between November 1985 and November 1988 11 patients developed arterial occlusion after microvascular anastomoses, 10 patients venous occlusions and five combined arterial and venous occlusions. We undertook a retrospective study to see whether colour, capillary refill, thermometry, or laser Doppler measurements could distinguish arterial and venous occlusions. Neither skin thermometry nor total backscattered light intensity change and flow band width (laser Doppler measurements) were significantly different (p > 0.05) between arterial and venous occlusions, but there were significant differences in colour (p = 0.006), capillary refill (p = 0.007), and laser Doppler flow (p = 0.02). The values obtained from cases with combined arterial and venous occlusions were like those of a venous occlusion or of an arterial occlusion or somewhere in between. Although none of the variables was diagnostic, we advise that the suspect vascular anastomosis should first be checked during reoperation. If an occluded anastomosis is found, one should also check the other anastomosis because occlusion of both artery and vein cannot be reliably detected.