Serum MBP immunoreactivity and immunoglobulin level as markers of tumour type

Summary Forty three patients, admitted to the department of Neurological Surgery for management of central nervous system tumours, were studied pre-operatively for serum myelin basic protein immunoreactivity as a marker of central nervous system lesion and for circulating immunoglobulins and complement (C₃) levels. Myelin basic protein concentration did not appear to correlate with tumour type or grade. Serum immunoglobulin levels were found to be within the normal range but the mean IgM level was significantly higher in the glioma group when compared with meningiomas.     

Informed Consent

There have been significant changes in the doctor patient relationship with the impact of technology in day-to-day practice. More and more patients are aware of their rights and are keen to make free choice and decision on their treatment. This helps them to choose the treatment of their choice from the options available and to select a physician of their choice. Doctor's decisions are being questioned regarding their correctness and there is a need to educate the patient, on what one offers by way of treatment. In some procedures and types of treatment, patient needs to be educated and informed of the merits and demerits of the treatment available. This will help the patient to make appropriate choice and also to accept some adverse outcome of treatment. Towards this end, all countries are looking afresh at the necessity of Informed Consent. Methods adopted by some countries are highlighted to help our physicians practice them in an appropriate way. A lot of remedial work needs to be done to minimize future litigation, as many doctors misunderstand their legal obligations and haven't caught up with the change in judge's thinking.     

Chloride losing diarrhoea and metabolic alkalosis in an infant with cystic fibrosis

A case of hypochloraemic metabolic alkalosis in an infant with chloride losing ileostomy drainage and cystic fibrosis is described. It is speculated that intestinal loss of chloride played a major role in the development of metabolic alkalosis.     

The role of pancreatic venous sampling in the localization of occult insulinomas

The palpation and enucleation of occult insulinomas (less than 15 mm) can be a difficult surgical problem even with good arteriographic localization. In the authors' limited experience, confirmation of arteriographic findings by pancreatic venous sampling provided little additional localizing information. However, if arteriography is negative or equivocal, venous sampling can indicate the segment of pancreas to be "blindly" resected if the adenoma is not palpable. Venous sampling may be misleading in polyendocrine syndromes because of the frequency of multiple adenomas and variable hormone production.     

Fused piperidines as a novel class of potent and orally available transient receptor potential melastatin type 8 (TRPM8) antagonists

The transient receptor potential melastatin type 8 (TRPM8) is a nonselective cation channel primarily expressed in a subpopulation of sensory neurons that can be activated by a wide range of stimuli, including menthol, icilin, and cold temperatures (<25 °C). Antagonism of TRPM8 is currently under investigation as a new approach for the treatment of pain. As a result of our screening efforts, we identified tetrahydrothienopyridine 4 as an inhibitor of icilin-induced calcium influx in CHO cells expressing recombinant rat TRPM8. Exploration of the structure-activity relationships of 4 led to the identification of a potent and orally bioavailable TRPM8 antagonist, tetrahydroisoquinoline 87. Compound 87 demonstrated target coverage in vivo after oral administration in a rat pharmacodynamic model measuring the prevention of icilin-induced wet-dog shakes (WDS).     

Intravenous digital subtraction renal angiography: use in screening for renovascular hypertension

Intravenous digital subtraction renal angiography (DSRA) has been compared with conventional angiography only in small, selected series of hypertensive patients. The authors prospectively examined with intravenous DSRA 94 patients at increased risk for renovascular hypertension and compared these studies with conventional angiography. A stenosis of at least one main renal artery was identified with intravenous DSRA in 22 patients and confirmed in 20 patients. No significant stenoses were seen with conventional angiography in any of the 64 patients in whom lesions were not seen with intravenous DSRA. Since inadequate DSRA studies were considered positive for renal artery stenosis, the sensitivity of intravenous DSRA was 100% (25 of 25); specificity, 93% (64 of 69); positive predictive value, 83% (25 of 30); and negative predictive value, 100% (64 of 64). The authors conclude that intravenous DSRA is a sensitive test for identifying stenosis of the main renal arteries and is appropriate to use as a screening test among patients at increased risk for renovascular hypertension.     

Cyclosporin nephrotoxicity in heart and lung transplant patients

Twenty-two patients with heart, lung or heart and lung transplants maintained on cyclosporin for periods ranging from 3 months to 10 years developed renal insufficiency which was investigated by renal biopsy. The histopathological changes were: (i) severe vascular and glomerular damage due to thrombotic microangiopathy (TM); (ii) a form of focal segmental glomerulosclerosis (FSGS); (iii) glomerular ischaemia. Rather than being separate entities, these changes appeared to represent a spectrum of pathology, some biopsies showing all three forms of glomerular injury. In all cases the glomerular changes were accompanied by arteriolar and arterial pathology, and we identified novel ultrastructural changes in the arteriolar endothelial basal lamina. Tubular atrophy was a consistent feature, the severity of which reflected the severity of the glomerular sclerosis, and which appeared to be a consequence of glomerular loss. Our findings are consistent with the nephrotoxic effects of cyclosporin being mediated chiefly via damage to preglomerular vessels and glomerular capillary endothelium. From an analysis of the clinical aspects of these cases, the effects of cyclosporin appear to be to some extent idiosyncratic, and therefore not entirely preventable, but strict monitoring of blood cyclosporin levels is essential to minimize the risk of permanent renal damage. Monitoring urinary protein in addition to plasma creatinine may detect the onset of FSGS, as proteinuria precedes creatinine elevation.      

How do we transfuse blood components in cirrhotic patients undergoing gastrointestinal procedures?

The liver plays a pivotal role in hemostasis. Consequently, patients with cirrhosis frequently demonstrate abnormal coagulation profiles on routine laboratory tests. These tests mainly reflect decreased procoagulant proteins. However, in cirrhosis, complex changes also occur in anticoagulant and fibrinolytic pathways. Recent evidence demonstrates that patients with cirrhosis exist in a state of hemostatic rebalance. Accordingly, routine tests inadequately represent hemostatic alterations in these patients. Unfortunately, these tests are regularly used to guide the transfusion of blood components with the assumption that they will correct laboratory abnormalities and improve hemostasis in a bleeding patient or prevent excessive bleeding following a procedure. With an absence of both accurate laboratory testing to assess hemostasis and evidence‐based guidelines to direct the transfusion of blood components, management of patients with cirrhosis poses a significant challenge to clinicians. Therefore, we developed multidisciplinary guidelines for the periprocedural transfusion of blood components in patients with cirrhosis based on concurrent evidence and personal experience at our medical center.