Debilitating diarrhoea and weight loss due to colitis in two RA patients treated with leflunomide

Diarrhoea and weight loss are frequently reported adverse events in rheumatoid arthritis (RA) patients receiving the disease-modifying antirheumatic drug (DMARD) leflunomide. According to the available literature these side effects occur mostly during the first 6 months of treatment, are rather mild and rarely lead to treatment withdrawal. In this report, we describe the clinical, endoscopic and histologic findings in two RA patients with severe diarrhoea and important weight loss more than 12 months after starting treatment with leflunomide. In both cases the symptoms were caused by colitis, but one had ulcerative and the other microscopic colitis. Despite treatment with budesonide the complaints only improved after withdrawal of leflunomide, making a causal relationship between this drug and the pathogenesis of colitis probable. The heterogeneous histopathological findings in these two patients, however, do not allow us to draw any definitive conclusions about the mechanism by which leflunomide causes diarrhoea and weight loss in RA patients. We conclude that persistent diarrhoea or weight loss in patients taking leflunomide can be more serious than what is previously reported in the literature. In such cases leflunomide treatment should be stopped and an endoscopic examination of the colon is recommended. Given the long half-life of this drug a washout procedure with cholestyramine should be considered whenever the problem is severe or persistent.     

Tumor M2-Pyruvate Kinase, a New Metabolic Marker for Pancreatic Cancer

An isoenzyme of pyruvate kinase (Tu M2-PK) is overexpressed by tumor cells and can be measured in blood by a specific immunoenzymatic assay. Our objective was to investigate the diagnostic value of Tu M2-PK in comparison with that of CA 19-9 in pancreatic cancer. We studied 265 subjects: 60 with histologically confirmed pancreatic cancer, 43 with benign pancreatic diseases (acute and chronic pancreatitis), 5 with benign cystic neoplasms of the pancreas, 9 with neuroendocrine tumors, 77 with other abdominal malignancies, 47 with benign digestive diseases, and 24 healthy controls. Levels of plasma Tu M2-PK and serum CA 19-9 were determined by commercially available specific immunoassays. The diagnostic sensitivity and specificity of Tu M2-PK for pancreatic cancer were 85 and 41%, respectively, while those of CA 19-9 were 75 and 81%. The combination of the two tests significantly increased sensitivity (97%) but lowered specificity (38%). In discriminating between pancreatic cancer and acute or chronic pancreatitis, Tu M2-PK turned out to be less accurate than CA 19-9. In patients without pancreatic tumor, cholestasis appeared not to affect the values of Tu M2-PK, while CA 19-9 was found to be significantly higher. Tu M2-PK was also abnormally high in the majority of patients with other digestive malignancies or neuroendocrine tumors. The results demonstrate that Tu M2-PK has a satisfactory sensitivity but a poor specificity in the diagnosis of pancreatic cancer. Used together with CA 19-9, the sensitivity increases considerably.     

Effect of pregnancy on autoregulation of cerebral blood flow in anterior versus posterior cerebrum

Endothelin receptor antagonists and phosphodiesterase type 5 inhibitors are used to treat pulmonary arterial hypertension. We tested the hypothesis that a selective endothelin type A receptor antagonist (ambrisentan) and a phosphodiesterase type 5 inhibitor (tadalafil) may act synergistically to relax endothelin-constricted pulmonary arteries. Rat isolated intrapulmonary arterial rings contracted with 8 nmol/L endothelin-1 were relaxed by 10 nmol/L ambrisentan and 30 nmol/L tadalafil alone by 26±3% and 21±1%, respectively, whereas both drugs in combination acted synergistically to relax arterial rings by 83±6%. The nonselective endothelin type A and B receptor antagonists bosentan (100 nmol/L) and macitentan (30 nmol/L) alone relaxed endothelin-contracted rings by 30±5% and 24±3%, respectively. Combinations of 30 nmol/L tadalafil with 100 nmol/L bosentan or 30 nmol/L macitentan relaxed endothelin-contracted rings by 53±5% or 46±7%, respectively; these values are similar to the calculated sums of the individual effects of these compounds. Denudation of endothelium from pulmonary arterial rings abolished the vasodilator response to 30 nmol/L tadalafil and the synergistic vasorelaxant effect of tadalafil with ambrisentan. In the presence of 1 μmol/L BQ-788, a selective endothelin type B receptor antagonist, the vasorelaxant effects of 10 nmol/L ambrisentan and 30 nmol/L tadalafil were additive but not synergistic. These data can be interpreted to suggest that ambrisentan and tadalafil synergistically inhibit endothelin-1-induced constriction of rat intrapulmonary arteries and that endothelin type B receptors in endothelium are necessary to enable a synergistic vasorelaxant effect of the drug combination.     

Proposed guidelines for the management of nodding syndrome

Nodding Syndrome is a poorly understood neurologic disorder of unknown aetiology that affects children and adolescents in Africa. Recent studies have suggested that the head nods are due to atonic seizures and Nodding Syndrome may be classified as probably symptomatic generalised epilepsy. As part of the Ugandan Ministry of Health clinical management response, a multidisciplinary team developed a manual to guide the training of health workers with knowledge and skills to manage the patients. In the absence of a known cause, it was decided to offer symptomatic care. The objective is to relieve symptoms, offer primary and secondary prevention for disability and rehabilitation to improve function. Initial management focuses on the most urgent needs of the patient and the immediate family until ‘stability’ is achieved. The most important needs were considered as seizure control, management of behavioural and psychiatric difficulties, nursing care, nutritional and subsequently, physical and cognitive rehabilitation. This paper summarises the processes by which the proposed guidelines were developed and provides an outline of the specific treatments currently being provided for the patients.     

Comparison of periodontal open flap debridement versus closed debridement with Er,Cr:YSGG laser

Background

Traditional periodontal open flap debridement (OFD) results in reduced pocket depth (PD), clinical attachment loss (CAL), gingival recession (GR) and postoperative pain and discomfort. The quest to overcome these shortcomings has led to research into Er,Cr:YSGG laser assisted pocket therapy (ELAPT). This study was designed to compare the clinical outcomes of ELAPT versus OFD.

Methods

Fifteen patients with a PD of ≥5 mm and ≤8 mm at two sites were selected. Test sites (Group 1) were treated by ELAPT and the control (Group 2) by OFD. Clinical parameters were recorded at baseline, 3 and 6 months and included Plaque Index (PI), Gingival Index (GI), modified Sulcular Bleeding Index (mSBI), PD, CAL and GR.

Results

Both treatments produced a reduction in PI, GI, mSBI and PD, an increase in GR, and a gain in CAL at 3 and 6 months. The mean gain of CAL in Group 1 at 3 and 6 months (1.60 ± 0.78 and 1.80 ± 0.63) was similar (p > 0.05) to the value of Group 2 (1.93 ± 0.88 and 2.00 ± 0.54). GR increased significantly (p < 0.05) only in Group 2 at 3 and 6 months (1.80 ± 0.56 and 1.87 ± 0.64) compared to Group 1 (0.50 ± 0.68 and 0.60 ± 0.74).

Conclusions

ELAPT compared with OFD results in similar CAL gains with less GR and significant reductions in PD, GI and mSBI, and may be considered as an alternative to surgical therapy.     

Thoracic surgical management of colorectal lung metastases: a questionnaire survey of members of the Society for Cardiothoracic Surgery in great Britain and Ireland

Introduction

Distant metastases to liver and lung are not uncommon in colorectal cancer. Resection of metastases is accepted widely as the standard of care. However, there is no firm evidence base for this. This questionnaire survey was carried out to assess the current practice preferences of cardiothoracic surgeons in Great Britain and Ireland.

Methods

An online questionnaire survey was emailed to cardiothoracic surgeons in Great Britain and Ireland. The survey was live for 12 weeks. Responses were collated with SurveyMonkey^®.

Results

Overall, there were 75 respondents. The majority (83%) indicated thoracic surgery as a specialist interest. Almost all (99%) used thoracic computed tomography (CT) for staging; 70% added liver CT and 51% added pelvic CT. Fluorodeoxyglucose positron emission tomography was used by 86%. The most frequent indication for pulmonary resection (97%) was solitary lung metastasis without extrathoracic disease. Video assisted thoracoscopic surgery (VATS) was used by 85%. In addition, thoracotomy was used by 96%. A third (33%) used radiofrequency ablation. Synchronous liver and lung resection was contraindicated for 83% of respondents. Over three-quarters (77%) thought that scientific equipoise exists presently for lung resection for colorectal lung metastases but only 21% supported a moratorium on this type of surgery until further evidence becomes available.

Conclusions

The results confirm that the majority of respondents use conventional cross-sectional imaging and either VATS or formal thoracotomy for resection. The results emphasise the continuing need for formal randomised trials to provide evidence of any survival benefit from pulmonary metastasectomy for colorectal lung metastases.