Optimal postoperative pain management after VATS lung resection by thoracic epidural analgesia, continuous paravertebral block or single-shot intercostal nerve block (OPtriAL): study protocol of a three-arm multicentre randomised controlled trial.

BACKGROUND: Adequate pain control after video-assisted thoracoscopic surgery (VATS) for lung resection is important to improve postoperative mobilisation, recovery, and to prevent pulmonary complications. So far, no consensus exists on optimal postoperative pain management after VATS anatomic lung resection. Thoracic epidural analgesia (TEA) is the reference standard for postoperative pain management following VATS. Although the analgesic effect of TEA is clear, it is associated with patient immobilisation, bladder dysfunction and hypotension which may result in delayed recovery and longer hospitalisation. These disadvantages of TEA initiated the development of unilateral regional techniques for pain management. The most frequently used techniques are continuous paravertebral block (PVB) and single-shot intercostal nerve block (ICNB). We hypothesize that using either PVB or ICNB is non-inferior to TEA regarding postoperative pain and superior regarding quality of recovery (QoR). Signifying faster postoperative mobilisation, reduced morbidity and shorter hospitalisation, these techniques may therefore reduce health care costs and improve patient satisfaction. METHODS: This multi-centre randomised study is a three-arm clinical trial comparing PVB, ICNB and TEA in a 1:1:1 ratio for pain (non-inferiority) and QoR (superiority) in 450 adult patients undergoing VATS anatomic lung resection. Patients will not be eligible for inclusion in case of contraindications for TEA, PVB or ICNB, chronic opioid use or if the lung surgeon estimates a high probability that the operation will be performed by thoracotomy. PRIMARY OUTCOMES: (1) the proportion of pain scores ≥ 4 as assessed by the numerical rating scale (NRS) measured during postoperative days (POD) 0-2; and (2) the QoR measured with the QoR-15 questionnaire on POD 1 and 2. Secondary outcome measures are cumulative use of opioids and analgesics, postoperative complications, hospitalisation, patient satisfaction and degree of mobility. DISCUSSION: The results of this trial will impact international guidelines with respect to perioperative care optimization after anatomic lung resection performed through VATS, and will determine the most cost-effective pain strategy and may reduce variability in postoperative pain management. Trial registration The trial is registered at the Netherlands Trial Register (NTR) on February 1st, 2021 (NL9243). The NTR is no longer available since June 24th, 2022 and therefore a revised protocol has been registered at ClinicalTrials.gov on August 5th, 2022 (NCT05491239). PROTOCOL VERSION: version 3 (date 06-05-2022), ethical approval through an amendment (see ethical proof in the Study protocol proof).

Randomised controlled trial to estimate reduction in pain after laparoscopic surgery when using a combination therapy of intraperitoneal normal saline and the pulmonary recruitment manoeuvre.

OBJECTIVE: To evaluate the effect of two manoeuvres at the end of gynaecological laparoscopy on postoperative pain. DESIGN: Randomised controlled trial. SETTING: One teaching and one university hospital in the Netherlands. SAMPLE: Women aged between 18 and 65 years, with American Society of Anaesthesiologists (ASA) classification I-II, scheduled for an elective laparoscopic procedure for a benign gynaecological indication. METHODS: Women were randomly allocated to two groups. In the intervention group, carbon dioxide was removed from the abdomen by a combination treatment of intraperitoneal warm saline and performing a pulmonary recruitment manoeuvre. In the control group, carbon dioxide was removed with gentle abdominal pressure. MAIN OUTCOME MEASURES: Frequency and intensity of post-laparoscopic shoulder pain and pain in the upper abdomen at 8, 24, and 48 hours after surgery. RESULTS: A total of 200 women participated, with 100 in each group. No difference was observed in the occurrence of post-laparoscopic shoulder pain during the first 48 hours after surgery between the intervention group (46%) and the control group (55%). The incidence of abdominal pain was not significantly different between the two groups. The mean visual analogue scale (VAS) scores of participants who reported shoulder pain were not statistically different between the groups. The mean VAS score for abdominal pain at 8 hours after surgery was significantly lower in the intervention group compared with the control group (3.2 versus 4.2, P = 0.02). No difference in pain medication between the groups was observed, nor was there any difference in nausea or vomiting. CONCLUSIONS: Combined intervention of intraperitoneal saline and the pulmonary recruitment manoeuvre does not lower post-laparoscopic shoulder pain. FUNDING: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. TWEETABLE ABSTRACT: PRM with intraperitoneal saline does not influence the incidence and intensity of post-laparoscopic shoulder pain.

POstLAparoscopic Reduction of pain By combining intraperitoneal normal salinE And the pulmonary Recruitment maneuver (POLAR BEAR trial). RCT to estimate reduction in pain after laparoscopic surgery when using a combination therapy of intraperitoneal normal saline and the pulmonary recruitment maneuver.

BACKGROUND: Shoulder pain and pain in the upper abdomen are common complaints after laparoscopy, sometimes surpassing the pain at incision sites. The incidence of shoulder pain ranges from 35 to 80%. Post-laparoscopic pain is caused by retention of carbon dioxide in the abdomen, which irritates the phrenic nerve and diaphragm, causing referred pain in the shoulder and in the upper abdomen. A promising strategy to reduce this post-laparoscopic pain is the pulmonary recruitment maneuver, which indirectly increases intraperitoneal pressure and thereby facilitates removal of residual carbon dioxide. An alternative strategy is the infusion of intraperitoneal normal saline. With normal saline infusion, carbon dioxide rises and escapes through the port sites. In addition, normal saline offers a physiologic buffer system to dissolve excess carbon dioxide. METHODS/DESIGN: This multicenter randomized controlled trial is conducted in two teaching hospitals in the Netherlands. Women between 18 and 65 years of age, with an ASA classification of I-II who are scheduled to undergo an elective laparoscopic procedure with benign gynecologic indication can participate. Following informed consent, participants are randomly allocated into two groups at the end of the surgical procedure. In the intervention group, the upper abdomen is filled with normal saline infusion with the patient in the Trendelenburg position. Then the anesthesiologist performs a standardized pulmonary recruitment maneuver with a pressure of 40 cm H2O. The trocar sleeve valves will be left open, so carbon dioxide can escape the abdominal cavity. With the patient in a neutral position the instruments are removed from the abdomen. In the control group, carbon dioxide is removed from the abdominal cavity at the end of surgery, with gentle abdominal pressure and passive exsufflation through the port sites, with open sleeve valves. The primary outcomes are the incidence and intensity of post-laparoscopic pain in the shoulder, upper abdomen and at the operation sites, at 8, 24 and 48 h after surgery. Secondary outcomes are postoperative use of analgesics, nausea, vomiting and pulmonary complications. DISCUSSION: This study may reduce post-laparoscopic pain in women undergoing laparoscopy. TRIAL REGISTRATION: Dutch trial register, number NTR4812 .

Assessment of disease activity in patients with rheumatoid arthritis using optical spectral transmission measurements, a non-invasive imaging technique.

OBJECTIVES: In rheumatoid arthritis (RA), treat-to-target strategies require instruments for valid detection of joint inflammation. Therefore, imaging modalities are increasingly used in clinical practice. Optical spectral transmission (OST) measurements are non-invasive and fast and may therefore have benefits over existing imaging modalities. We tested whether OST could measure disease activity validly in patients with RA. METHODS: In 59 patients with RA and 10 patients with arthralgia, OST, joint counts, Disease Activity Score (DAS) 28 and ultrasonography (US) were performed. Additionally, MRI was performed in patients with DAS28<2.6. We developed and validated within the same cohort an algorithm for detection of joint inflammation by OST with US as reference. RESULTS: At the joint level, OST and US performed similarly inproximal interphalangeal-joints (area under the receiver-operating curve (AUC) of 0.79, p<0.0001) andmetacarpophalangeal joints (AUC 0.78, p<0.0001). Performance was less similar in wrists (AUC 0.62, p=0.006). On the patient level, OST correlated moderately with clinical examination (DAS28 r=0.42, p=0.001), and US scores (r=0.64, p<0.0001). Furthermore, in patients with subclinical and low disease activity, there was a correlation between OST and MRI synovitis score (RAMRIS (Rheumatoid Arthritis MRI Scoring) synovitis), r=0.52, p=0.005. CONCLUSIONS: In this pilot study, OST performed moderately in the detection of joint inflammation in patients with RA. Further studies are needed to determine the diagnostic performance in a new cohort of patients with RA.

Quality of factor XI activity testing in North American Specialized Coagulation Laboratories.

INTRODUCTION: The performance of factor XI activity (FXI) by laboratories in the North American Specialized Coagulation Laboratory Association proficiency testing program was analyzed. METHODS: Over 10 years (2003-2013), 80 samples were distributed; 33-55 laboratories participated per exercise providing 3833 total responses. Analysis was performed on numeric results and qualitative classification of results. RESULTS: The sample FXI levels ranged from 3.8 to 154.0 IU/dL. The overall interlaboratory average coefficient of variation (CV%) was 17.5%; the CV was higher for a sample with low (3.8 IU/dL) FXI. Results were correctly classified as abnormal (100%) for a sample with 3.8 IU/dL FXI and normal/borderline normal (97.7%) for 45 samples with 80 to < 140 IU/dL FXI. The classification was heterogeneous for samples with FXI of 50 to < 80 IU/dL. Six specimens were repeat-tested from 2007 to 2013. The mean FXI was not significantly different in laboratories using the same method on both exercises, suggesting good intralaboratory precision over time. Univariate analysis of data from 2011 to 2012 did not find a consistent significant difference among the activators, analyzers, calibrators, and FXI-deficient plasmas. CONCLUSION: Laboratories generally performed well in assessment of FXI based on interlaboratory precision when FXI >30 IU/dL and on classification of samples with very low or normal FXI.

Factor VII assay performance: an analysis of the North American Specialized Coagulation Laboratory Association proficiency testing results.

The performance of factor VII (FVII) assays currently used by clinical laboratories was examined in North American Specialized Coagulation Laboratory Association (NASCOLA) proficiency tests. Data from 12 surveys conducted between 2008 and 2010, involving 20 unique specimens plus four repeat-tested specimens, were analyzed. The number of laboratories per survey was 49-54 with a total of 1224 responses. Numerous reagent/instrument combinations were used. For FVII > 80 or <40 U/dL, 99.5% of results (859/863) were correctly classified by laboratories as normal/abnormal. Classification of specimens with 40-73 U/dL FVII was heterogeneous. Interlaboratory precision was better for normal specimens (coefficient of variation (CV) 10.7%) than for FVII<20 U/dL (CV 33.1%), with a mean CV of 17.2% per specimen. Intralaboratory precision for repeated specimens demonstrated no significant difference between the paired survey results (mean absolute difference 2.5-5.0 U/dL). For specimens with FVII >50 U/dL, among commonly used methods, one thromboplastin and one calibrator produced results 5-6 U/dL higher and another thromboplastin and calibrator produced results 5-6 U/dL lower than all other methods, and human thromboplastin differed from rabbit by +7.6 U/dL. Preliminary evidence suggests these differences could be due to the calibrator. For FVII <50 U/dL, differences among the commonly used reagents and calibrators were generally not significant.

Preincubation in the Prothrombinase-induced Clotting Time test (PiCT) is necessary for in vitro evaluation of fondaparinux and to be avoided for the reversible, direct factor Xa inhibitor, rivaroxaban.

INTRODUCTION: There is no clear consensus about tests in vitro that are suitable for evaluating various factor Xa inhibitors. The availability of reversible and irreversible inhibitors further complicates the application of available assays. METHODS: We evaluated the suitability of the prothrombinase-induced clotting test (PiCT) for fondaparinux and rivaroxaban, as representatives for irreversible and reversible inhibition of factor Xa, with specific attention to preincubation times prior to re-calcification, in the context of automate program limitations. RESULTS: We demonstrate that the PiCT assay requires a preincubation step to allow inhibitory activity by fondaparinux. Without this step, inhibition in the test is minimal and lacking sufficient dynamic range. In contrast, to measure the reversible inhibition by rivaroxaban, we found any preincubation introduced an artifact in inhibition as exemplified by a biphasic pattern and only the test without a preincubation phase gave informative results. CONCLUSION: It is concluded that PiCT in its format with two steps is suitable for fondaparinux evaluation, while its format without preincubation (the one-addition format) is suitable for reversible inhibitors such as rivaroxaban. Unfortunately, both types of inhibitors cannot be compared in vitro in a single assay format.

A guideline to medical photography: a perspective on digital photography in an orthopaedic setting.

PURPOSE: Quality photographs are essential for clinical documentation, research, and publication in scientific journals and teaching. Oftentimes, non-ideal lighting and a sterile environment restrict the medical photographer, resulting in lower-quality photographs. This article aims to provide a clear and comprehensible guideline for medical photography in an orthopaedic setting. METHODS: This article is based on extensive photographic involvement in operating and laboratory settings, in close collaboration with medical professionals from the Steadman Clinic (Vail, Colorado, USA), Gothenburg University (Göteborg, Sweden) and Erasmus MC (Rotterdam, the Netherlands). Background literature was searched through Google Scholar and PubMed. RESULTS: Three relevant journal articles, and one book on medical photography, were used to write this paper. Seventeen Internet articles were used for background information. CONCLUSION: A relevant, up-to-date and comprehensive guideline to medical photography for medical professionals, with or without photographic experience, is provided. LEVEL OF EVIDENCE: Expert opinion, Level V.

In ECAT veritas?

The laboratory criteria of the antiphospholipid syndrome include one coagulation assay (lupus anticoagulant [LA]) and two solid phase assays (anticardiolipin [aCL] and anti-ß(2)glycoprotein I antibodies [aß(2)GPI]). External quality control (EQC) surveys show that negative and clearly positive LA samples are classified correctly by about 95% of laboratories. For 'weak' LA there is a wide variability in samples' classification. Furthermore, when a weak LA sample is used in two different EQC surveys more than 50% of laboratories classify it differently. In some surveys weak LA samples were found to be positive for aCL and for aß(2)GPI by a majority of laboratories; the main reason for laboratories which classified these samples as LA negative was a negative result in the mixing test. It is likely that, depending on the sensitivity of the assay, a weak LA cannot be detected anymore after 1:1 dilution of the sample with normal plasma. Therefore, we recommend the use of integrated assays, such as screen/confirm ratios, for the detection of weak LA samples.

The factor VIII inhibitor assays can be standardized: results of a workshop.

BACKGROUND: The Bethesda and the Nijmegen assays are commonly used for the measurement of inhibitor levels in hemophilia A patients. Despite test innovations, the between-laboratory coefficient of variation (CVb) of factor VIII inhibitor test data in external quality surveys remains very high (40-60%) with a high degree of false-negative and false-positive results resulting in undesired effects on treatment. OBJECTIVES: Organization of a workshop in order to address the causes of this phenomenon and to suggest ways to improve the assays. METHODS: Fifteen laboratories showing a high CVb in regular surveys and using a variety of methods participated in the wet workshop, which included four different sessions where variables probably contributing to the high CVb (e.g. use of [non-]buffered plasma, FVIII-deficient plasma, sample dilution and APTT reagents) were investigated. RESULTS: The CVb varied from 30% to 70% in the first session of the workshop when the participants used their own test settings and reagents. The use of buffered normal pooled plasma and FVIII-deficient plasma as a reference sample by all participants did not significantly alter the CVb (35-50%) but decreased the number of false positives. However, the use of buffered pooled plasma in combination with standardized sample dilution procedures by all participants showed a significant improvement (CVb, 10-20%). CONCLUSIONS: These results may contribute to improvement of FVIII inhibitor testing. However, improved inter-laboratory comparison of factor VIII inhibitor assay results can only be reached when further local standardization is implemented.

Development of a computerised alert system, ADEAS, to identify patients at risk for an adverse drug event.

INTRODUCTION: Adverse drug events (ADEs) are frequent and pose an important risk for patients treated with drugs. Fortunately, a substantial part of ADEs is preventable, and computerised physician order entry with a sophisticated clinical decision support system may be used to reach this goal. OBJECTIVE: To develop a new automated system that could improve the quality of medication surveillance. The system should focus on detecting patients at risk for an ADE by combining data from the hospital information system and computerised physician order entry (drug prescription data, drug-drug interaction alerts, clinical chemical laboratory parameters, demographic features), using clinical rules. METHODS: The clinical rules were formulated in a multidisciplinary team, based on seven risk categories. The new system was composed in a guideline-based decision support framework consisting of both a guideline development module and a decision support module. A total of 121 clinical rules were built into the system. Validation of the system and a proof of principle test were performed. RESULTS: The adverse drug event alerting system (ADEAS) was developed and validated successfully. The proof of principle test showed that ADEAS has potential clinical usefulness. ADEAS generated alerts and detected additional potential risk situations, which were not generated by the conventional medication surveillance. CONCLUSION: We developed a pharmacy decision support system ADEAS that focuses on the detection of situations prone to lead to an ADE and might help clinicians to take timely corrective interventions and thereby can prevent patient harm.

Cardiac assessment of patients with late stage Duchenne muscular dystrophy.

Background. Duchenne muscular dystrophy (DMD) patients used to die mainly from pulmonary problems. However, as advances in respiratory care increase life expectancy, mortality due to cardiomyopathy rises. Echocardiography remains the standard diagnostic modality for cardiomyopathy in DMD patients, but is hampered by scoliosis and poor echocardiographic acoustic windows in adult DMD patients. Multigated cardiac radionuclide ventriculography (MUGA) does not suffer from these limitations. N-terminal proBNP (NTproBNP) has shown to be a diagnostic factor for heart failure. We present our initial experience with plasma NT-proBNP measurement in the routine screening and diagnosis of cardiomyopathy in adult mechanically ventilated DMD patients.Methods. Retrospective study, 13 patients. Echocardiography classified left ventricular (LV) function as preserved or depressed. NT-proBNP was determined using immunoassay. LV ejection fraction (LVEF) was determined using MUGA.Results. Median (range) NT-proBNP was 73 (25 to 463) ng/l. Six patients had an NT-proBNP >125 ng/l. Seven patients showed an LVEF <45% on MUGA. DMD patients with depressed LV function (n=4) as assessed by echocardiography had significantly higher median NT-proBNP than those (n=9) with preserved LV function: 346 (266 to 463) ng/l versus 69 (25 to 257) ng/l (p=0.003). NT-proBNP significantly correlated with depressed LV function on echocardiogram and with LVEF determined by MUGA.Conclusion. Although image quality of MUGA is superior to echocardiography, the combination of echocardiography and NT-proBNP achieves similar results in the evaluation of left ventricular function and is less time consuming and burdensome for our patients. We advise to add NT-proBNP to echocardiography in the routine cardiac assessment of DMD patients. (Neth Heart J 2009;17:232-7.).

Biological variation in inflammatory and hemostatic markers.

BACKGROUND: Concentrations of inflammatory and hemostatic variables are influenced by biological variation, which is the natural within-subject variation over time. OBJECTIVES: The aim of this study was to determine fibrinogen, C-reactive protein (CRP), platelet aggregation, thrombin generation and prothrombin time (PT): (i) the number of repeated measurements needed to obtain the true habitual concentration of an individual; (ii) the recommended analytical imprecision for diagnosis and monitoring; (iii) the recommended analytical bias; (iv) the contribution of analytical imprecision to test result variability; (v) the index of individuality; (vi) the reference change value; and (vii) the seasonal variation. SUBJECTS AND METHODS: We collected 520 blood samples over a 1-year period from 40 healthy individuals, and determined the between-subject, within-subject and seasonal variation in fibrinogen, CRP, platelet aggregation, thrombin generation and PT. RESULTS: One or two repeated measurements were sufficient to establish the true habitual concentration, except for platelet aggregation and peak thrombin generation, where at least four and nine repeated measurements were needed, respectively. For diagnosis, the maximal recommended coefficient of analytical variation (CV) was 4%-27%, except for CRP (77.7%). For monitoring, these CVs were on average 3% lower. Recommended analytical bias varied between 1.7% and 33.2%. Finally, seasonal variation was observed in concentrations of fibrinogen and thrombin generation, which could explain approximately 11% of their total variation. CONCLUSION: This study provides insights into the biological variability of selected inflammatory and hemostatic markers, which can be used for sample size calculations and to determine the analytical quality specifications for their respective assays.

Diagnosis of factor VIII deficiency.

The correct diagnosis of factor VIII deficiency and the assessment of severity of the disease are essential for a patient-tailored treatment strategy. An optimal diagnostic procedure comprises sensitive and specific screening methods and factor VIII activity assays. Different screening reagents show variable characteristics and receiver operator characteristic curves are presented showing the relation between sensitivity and specificity of eleven activated partial thromboplastin time reagents. The details of the three methods for factor VIII activity assay, one-stage and two-stage assay and chromogenic assays, are discussed. The chromogenic assay seems to be more sensitive than the one-stage assay with regard to the detection of severe haemophilia. Discrepant results obtained with one-stage and two-stage assays are reviewed and discussed.

Dipyridamole enhances ischaemia-induced reactive hyperaemia by increased adenosine receptor stimulation.

BACKGROUND AND PURPOSE: Dipyridamole enhances post-occlusive reactive hyperaemia (PORH) in the human forearm vascular bed. We hypothesize that this effect is completely mediated by increased adenosine receptor stimulation. To test this hypothesis, the effect of caffeine (an adenosine receptor antagonist) on dipyridamole-induced augmentation of PORH was explored. EXPERIMENTAL APPROACH: The forearm vasodilator responses to three increasing periods of forearm ischaemia (2, 5 and 13 min) were determined during placebo infusion. Forty minutes after the last reperfusion period, this procedure was repeated during intra-arterial infusion of dipyridamole (7.4 nmol min(-1) per 100 ml forearm). At least 2 weeks later, this whole procedure was repeated, but now in the presence of caffeine (90 microg min(-1) per 100 ml volume). KEY RESULTS: After 2, 5 and 13 min of ischaemia, the average forearm blood flow increased to 5.6+/-0.7, 9.7+/-1.3 and 34.5+/-2.1 ml min(-1) per 100 ml. After infusion of dipyridamole into the brachial artery, these numbers were significantly increased to 7.7+/-0.8, 12.5+/-1.5 and 41.6+/-3.1 ml min(-1) per 100 ml. This response was abolished by the concomitant infusion of caffeine (6.6+/-0.5, 10.2+/-0.6, 35.1+/-2.2 (caffeine) versus 7.4+/-0.4, 10.5+/-0.6, 33.7+/-2.2 ml min(-1)per 100 ml (caffeine/dipyridamole)). CONCLUSIONS AND IMPLICATIONS: Caffeine prevented the augmenting effect of dipyridamole on PORH. This indicates that dipyridamole-induced augmentation of PORH is mediated via increased adenosine receptor stimulation as a result of elevated extracellular formation of adenosine during ischaemia.

[Summary of the practice guideline 'Atopic dermatitis' (first revision) from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'Constitutioneel eczeem' (eerste herziening) van het Nederlands Huisartsen Genootschap.

The 1996 practice guideline on atopic dermatitis from the Dutch College of General Practitioners has been updated. For diagnosing atopic dermatitis, the use of Williams' criteria is recommended. Testing for food allergy is only useful in case of children under the age of 2 who have other food-related allergic complaints together with dermatitis. In the treatment of atopic dermatitis, keeping the skin in good condition with emollients is essential; furthermore, topical corticosteroids are the therapy of first choice. In case of a severe exacerbation of atopic dermatitis, starting with a class 3 corticosteroid is preferred. In case of frequent recurrences, 'pulse-therapy' is indicated: topical corticosteroids on 2-4 consecutive days per week as maintenance therapy. The role of preparations from tar is marginal. The use of the topical immunomodulators tacrolimus and pimecrolimus in general practice is discouraged.

The harmonization of quantitative test results of different D-dimer methods.

Nowadays D-dimer testing is frequently applied in the diagnosis of venous thromboembolism. However, the test results of different quantitative D-dimer tests can differ significantly. The background of this variability, which is mainly caused by the variety of fibrin degradation products in plasma, the specificity of D-dimer assays, and the calibrators used in the test, is summarized here. Because D-dimer is not a single entity in plasma but a mixture of heterogeneous fibrin degradation products, method standardization is in principle impossible. Efforts undertaken in the past to standardize D-dimer methods are summarized. All these projects failed and it was concluded that only harmonization of D-dimer test results seems to be feasible. The results of a large field study on which a new approach to the harmonization of quantitative D-dimer methods will be based is summarized in this article. This approach seems to be an adequate solution for overcoming the practical problem of variation of test outcome in different D-dimer assays.

[Tetany due to excessive use of alcohol: a possible magnesium deficiency]. / Tetanie bij overmatig alcoholgebruik: mogelijk een magnesiumtekort.

Two alcoholic patients, a woman aged 64 and a man aged 69 years, were admitted with tetany. Both had severe electrolyte disorders, with low plasma levels of calcium, magnesium and potassium. Following mineral supplementation both patients recovered. Hypomagnesaemia plays a central role in the pathophysiology of this syndrome. Chronic alcohol abuse results in hypomagnesaemia in 30% of patients by decreasing renal tubular reabsorption. Hypomagnesaemia leads to suppression of parathyroid-hormone secretion, parathyroid-hormone resistance and vitamin-D suppression, resulting in hypocalcaemia. Hypomagnesaemia also causes kaliuresis leading to hypokalaemia. Supplementation with magnesium is crucial in the treatment of this combined electrolyte disorder.

ATP-induced vasodilation in human skeletal muscle.

1. The purine nucleotide adenosine-5'-triphosphate (ATP) exerts pronounced effects on the cardiovascular system. The mechanism of action of the vasodilator response to ATP in humans has not been elucidated yet. The proposed endothelium-derived relaxing factors (EDRFs) were studied in a series of experiments, using the perfused forearm technique. 2. Adenosine 5'-triphosphate (0.2, 0.6, 6 and 20 nmol dl(-1) forearm volume min(-1)) evoked a dose-dependent forearm vasodilator response, which could not be inhibited by separate infusion of the nonselective COX inhibitor indomethacin (5 microg dl(-1) min(-1), n=10), the blocker of Na(+)/K(+)-ATPase ouabain (0.2 microg dl(-1) min(-1), n=8), the blocker of K(Ca) channels tetraethylammonium chloride (TEA, 0.1 microg dl(-1) min(-1), n=10), nor by the K(ATP)-channel blocker glibenclamide (2 microg dl(-1) min(-1), n=10). All blockers, except glibenclamide, caused a significant increase in baseline vascular tone. The obtained results might be due to compensatory actions of unblocked EDRFs. Combined infusion of TEA, indomethacin and l-NMMA (n=6) significantly increased the baseline forearm vascular resistance. The ATP-induced relative decreases in forearm vascular resistance were 48+/-5, 67+/-3, 88+/-2, and 92+/-2% in the absence and 23+/-7, 62+/-4, 89+/-2, and 93+/-1% in the presence of the combination of TEA, indomethacin and l-NMMA (P<0.05, repeated-measures ANOVA, n=6). A similar inhibition was obtained for sodium nitroprusside (SNP, P<0.05 repeated-measures ANOVA, n=6), indicating a nonspecific interaction due to the blocker-induced vasoconstriction. 3. ATP-induced vasodilation in the human forearm cannot be inhibited by separate infusion of indomethacin, ouabain, glibenclamide or TEA, or by a combined infusion of TEA, indomethacin, and l-NMMA. Endothelium-independent mechanisms and involvement of unblocked EDRFs, such as CO, might play a role, and call for further studies.