Trends in the incidence of basal cell carcinoma by histopathological subtype

Background As a result of the high prevalence, basal cell carcinoma (BCC) causes a significant and expensive health care problem. Objective In this study, we evaluate the proportional increase in BCC by histological subtype over the last two decades. Methods We retrospectively reviewed all primary histological confirmed BCCs diagnosed in the Maastricht University Medical Centre in The Netherlands in the years 1991, 1999 and 2007. Results An annual increase of the number of BCCs of 7% for both genders was shown. The age‐standardized incidence rates for BCC increased between 1991 and 2007 from 54.2 to 162.1 per 100 000 men and from 61.7 to 189.8 per 100 000 women. The proportion of superficial BCC increased significantly from 17.6% to 30.7%. Conclusion The incidence of BCC is continuing to increase this century. The observed shift to the superficial histological subtype, which can be treated non‐surgically, might reduce the workload in the busy dermatologists practice.     

Vasodilator agents and supracollicular transection fail to inhibit cortical spreading depression in the cat

It remains an open question as to whether cortical spreading depression (CSD) is the pathophysiological correlate of the neurological symptoms in migraine with aura. In the experimental animal, CSD is an electrophysiological phenomenon mainly mediated via NMDA receptors. However, according to case reports in humans, visual aura in migraine can be alleviated by vasodilator substances, such as amyl nitrite and isoprenaline. There is also circumstantial evidence that brainstem nuclei (dorsal raphe nucleus and locus coeruleus) may play a pivotal role in the initiation of aura. In this study, CSD was elicited in alpha-chloralose anesthetized cats by cortical needle stab injury and monitored by means of laser Doppler flowmetry. Topical application of isoprenaline (0.1-1%) and amyl nitrite (0.05%) onto the exposed cortex had no effect on the elicitation or propagation of CSD. Also, after supracollicular transection, subsequent CSDs showed no differences in the speed of propagation and associated flow changes. We conclude from these data that--given CSD probably exists in humans during migraine--spreading neurological deficits during migraine aura are independent of brainstem influence and have a primarily neuronal rather than vascular mechanism of generation.     

Neuropeptides in migraine and cluster headache

The cerebral circulation is invested by a rich network of neuropeptide Y (NPY) and noradrenaline containing sympathetic nerve fibers in arteries, arterioles and veins. However, the nerve supply of vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) containing fibers is sparse. While noradrenaline and NPY cause vasoconstriction, VIP, SP and CGRP are potent vasodilators. Stimulation of the trigeminal ganglion in cat and man elicits release of SP and CGRP. Subjects with spontaneous attacks of migraine show release of CGRP in parallel with headache. Cluster headache patients have release of CGRP and VIP during bouts. Treatment with sumatriptan aborts headache in migraine and cluster headache as well as the concomitant peptide release.     

Confirmation of hepatitis C infection: a comparison of five immunoblot assays

BACKGROUND: Recently, new immunoblot assays for the detection of antibodies to hepatitis C virus (HCV) became available. STUDY DESIGN AND METHODS: The performance of five confirmatory anti-HCV immunoblot assays was studied with samples with known HCV antibody and HCV RNA status. The assays were a third-generation strip recombinant immunoblot assay (RIBA-3, Chiron Corp., Emeryville, CA), a second-generation HCV blot (DB-2 blot, Diagnostic Biotechnology, Singapore), the Wellcozyme HCV Western blot (Murex blot, Murex Diagnostics, Dartford, UK), an immunodot HCV assay (Matrix, Abbott Laboratories, Chicago, IL), and the third-generation HCV line immunoassay (Liatek-III, Organon Teknika, Boxtel, The Netherlands). RESULTS: Sensitivity on samples from 48 HCV RNA-positive, second-generation RIBA (RIBA-2)-positive persons and specificity on samples from 31 low-risk donors was 96 percent or better for all assays. The sensitivity on 31 HCV RNA-positive, RIBA-2- indeterminate samples was as follows: Liatek-III, 94 percent; RIBA-3, 90 percent; Murex blot, 61 percent; Matrix, 55 percent; and DB-2 blot, 39 percent. In testing 39 HCV RNA-negative, RIBA-2-indeterminate donor samples, the percentage found to be negative was Liatek-III, 77 percent; RIBA-3, 67 percent; Murex blot, 49 percent; DB-2 blot, 33 percent; and Matrix, 15 percent. The order of sensitivity on four HCV seroconversion series was (from high to low): RIBA-3, Liatek-III, DB-2 blot, Murex blot, and Matrix; the differences were small. CONCLUSION: Detection of HCV antibodies was not refined by the addition of new HCV antigens (NS5, E2/NS1), but by improved classical antigens (core, NS3, NS4). Replacement of the commonly used RIBA-2 will resolve the status of a high proportion of RIBA-2-indeterminate samples.     

Soluble urokinase-type plasminogen activator receptor levels in patients with burn injuries and inhalation trauma requiring mechanical ventilation: an observational cohort study

Introduction  

Soluble urokinase-type plasminogen activator receptor (suPAR) has been proposed as a biologic marker of fibrinolysis and inflammation. The aim of this study was to investigate the diagnostic and prognostic value of systemic and pulmonary levels of suPAR in burn patients with inhalation trauma who need mechanical ventilation.     

The role of previously unmeasured organic acids in the pathogenesis of severe malaria

IntroductionSevere falciparum malaria is commonly complicated by metabolic acidosis. Together with lactic acid (LA), other previously unmeasured acids have been implicated in the pathogenesis of falciparum malaria.MethodsIn this prospective study, we characterised organic acids in adults with severe falciparum malaria in India and Bangladesh. Liquid chromatography-mass spectrometry was used to measure organic acids in plasma and urine. Patients were followed until recovery or death.ResultsPatients with severe malaria (n=138), uncomplicated malaria (n=102), sepsis (n=32) and febrile encephalopathy (n=35) were included. Strong ion gap (mean±SD) was elevated in severe malaria (8.2 mEq/L±4.5) and severe sepsis (8.6 mEq/L±7.7) compared with uncomplicated malaria (6.0 mEq/L±5.1) and encephalopathy (6.6 mEq/L±4.7). Compared with uncomplicated malaria, severe malaria was characterised by elevated plasma LA, hydroxyphenyllactic acid (HPLA), α-hydroxybutyric acid and β-hydroxybutyric acid (all P<0.05). In urine, concentrations of methylmalonic, ethylmalonic and α-ketoglutaric acids were also elevated. Multivariate logistic regression showed that plasma HPLA was a strong independent predictor of death (odds ratio [OR] 3.5, 95 % confidence interval [CI] 1.6–7.5, P=0.001), comparable to LA (OR 3.5, 95 % CI 1.5–7.8, P=0.003) (combined area under the receiver operating characteristic curve 0.81).ConclusionsNewly identified acids, in addition to LA, are elevated in patients with severe malaria and are highly predictive of fatal outcome. Further characterisation of their sources and metabolic pathways is now needed.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-1023-5) contains supplementary material, which is available to authorized users.     

High-dose atorvastatin therapy in severe heterozygous familial hypercholesterolaemia

Lipid targets can be difficult to attain in familial hypercholesterolaemia. To compare atorvastatin with simvastatin- fenofibrate and simvastatin-cholestyramine therapy, we studied 54 patients with familial hypercholesterolaemia over periods of 2-6 months on each therapeutic regimen. The atorvastatin regimen reduced total cholesterol by 41.2 +/- 11.2%, LDL by 45.6 +/- 15.5%, triglycerides by 33.8 +/- 24.8%, and increased HDL by 2.3 +/- 37.0%. Simvastatin- fenofibrate therapy achieved reductions of 33.9 +/- 8.5% in cholesterol, 42.0 +/- 12.2% in LDL, 34.7 +/- 38.3% for triglycerides, and a 25.4 +/- 55.1% increase in HDL. Simvastatin-cholestyramine gave a reduction of 31.3 +/- 11.8% in cholesterol, 36.0 +/- 14.4% in LDL, 13.7 +/- 36.3% in triglycerides, and a 1.1 +/- 30.3% rise in HDL. The atorvastatin regimen was marginally but not significantly better than simvastatin-fenofibrate in improving the LDL:HDL ratio, LDL:apoB and and apolipoprotein B:A1 ratios. Eleven patients (20.4%) had side- effects: two discontinued atorvastatin due to side-effects; two patients had rashes; six had myalgia and two had diarrhoea. Gastrointestinal side-effects were described in 16 (30.1%) patients on simvastatin-cholestyramine therapy and four cases of myalgia (11.2%) were seen with simvastatin-fenofibrate. In nine patients on atorvastatin (20.4%) a 30% or greater fall in HDL was observed, compared to five patients with resin therapy (9.2%) and two with fibrate therapy (5.5%). There were no significant differences in liver or muscle biochemistry between the regimens, but atorvastatin did raise transaminase and creatine kinase concentrations significantly compared to pre-treatment values (p = 0.001). Atorvastatin significantly improves the lipid profile in most patients compared with other regimens. It has a comparable incidence of side-effects to combination therapy regimens.      

The provision of renal replacement therapy for adults in England and Wales: recent trends and future directions

We assessed the level of provision of renal replacement therapy for adults in England and Wales. All autonomous main renal units in England (n = 52) and Wales (n = 5) were surveyed in 1996. Data for England were compared to the 1993 National Renal Review. The acceptance rate in England 1995 was 82 (80-85) per million population (p.m.p.) compared with 67 (65-70) p.m.p. in 1991-2. The rate in 1995 in Wales was 109 (98- 122) p.m.p. The prevalence rate in England was 476 p.m.p. at end-1995 compared to 393 p.m.p. in 1993, in Wales it was 487 p.m.p. The number of main renal units in England did not rise between 1993 and 1995; capacity was increased by use of more treatment shifts and temporary haemodialysis stations, and by opening more satellite units. The main growth was in hospital haemodialysis. There was an uneven geographical distribution of services. Patients accepted were older with more comorbidity. The use of better-quality processes of dialysis increased. The steady-state position for RRT will not be reached for over a decade. Health authorities will face continued pressure to fund increases in quantity and quality improvements. A stronger evidence base of the effectiveness of therapies, and a national registry to monitor the equity and cost-effectiveness of services are needed.