Sjögren's Syndrome with Chronic Pancreatitis, Sclerosing Cholangitis, and Pulmonary Infiltrations

We report a patient with Sjögren's syndrome and multiple gastrointestinal manifestations who successfully responded to therapy with ursodeoxycholic acid. Our patient had sialoadenitis with dry mouth, dry eyes, arthralgia, chronic pancreatitis, sclerosing cholangitis, and pulmonary inflitrations. The first signs of disease were the symptoms of chronic pancreatitis followed by icterus, caused by extrahepatic bile duct obstruction. Sclerosing cholangitis was diagnosed by liver biopsy and endoscopic retrograde cholangiography. Sialoadenitis, causing dry mouth, was verified by buccal biopsy. Pulmonary infiltrations were seen on standard chest x-ray, and also shown by high-resolution computed tomography examination. Obstructive icterus and even pulmonary infiltration responded successfully to treatment with ursodeoxycholic acid.     

Pouchitis--recurrence of the inflammatory bowel disease?

The incidence and characteristics of reservoir inflammation after restorative proctocolectomy for ulcerative colitis were studied in a series of 179 patients. The median follow up time was 27 months (range 6-80). Pouchitis occurred in 36 patients (20%) and nine of these (5%) developed a chronic, persisting pouchitis. There were no pouch failures as a result of pouchitis and no significant adverse effect on longterm functional outcome. The overall cumulative risk to develop pouchitis four years after surgery was 23%. The risk of pouchitis is unpredictable on clinical grounds except that there were significantly less patients with left sided colitis in the group who subsequently developed pouchitis. Morphological and histochemical studies showed a greater degree of colonic metaplasia in the pouch mucosa in patients with pouchitis and patients with a chronic pouchitis had the highest degree of changes. The results support the view that pouchitis is a novel manifestation of inflammatory bowel disease in ileal mucosa that has changed slowly to a colon like mucosa.     

Design, spectrum measurements and simulations for a 238Pu alpha-particle irradiator for bystander effect and genomic instability experiments.

Design, spectrum measurements and simulations for an alpha-particle irradiator for bystander effect and genomic instability experiments are presented. Measured alpha-particle energy spectra were used to confirm the characteristics of the source of the irradiator specified by the manufacturer of the source. The spectra were measured in vacuum with a high-resolution spectrometer and simulated with an AASI Monte Carlo code. As a next step, we simulated alpha-particle energy spectra at the target plane of the irradiator for three different source-to-target distances. In these simulations, helium was used as the medium between the source and the exit window of the irradiator; its pressure and temperature corresponded to those of the ambient air. Mean energies and full-widths at half-maximum (FWHM) were calculated for the three different helium gas tracks.     

Expression of vascular endothelial growth factor in human adrenals

Angiogenesis is an important component in many biological processes and also in pathologic conditions including neoplastic diseases. Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific growth factor, which is induced by tissue hypoxia and is angiogenic in vivo. Adrenal gland is a well-vascularized organ, and the roles of VEGF in normal adrenal and in adrenal tumorigenesis is not well characterized. We therefore investigated VEGF mRNA expression in normal human adrenals and in cultured adrenocortical cells. VEGF mRNA was constantly expressed in normal adrenals as well as in cultured adrenocortical cells. The mRNA levels were increased after 24h stimulation with either ACTH or cAMP. The effect of cAMP was dose-dependent. This suggests that ACTH-induced VEGF mRNA expression is mediated via protein kinase A dependent pathway.     

Apolipoprotein E polymorphism is associated with both carotid and coronary atherosclerosis in patients with coronary artery disease

Background and aimsApolipoprotein E (apoE) polymorphism plays a significant role in the development of atherosclerosis and cardiovascular disease. Therefore, the aim of the present study was to examine the association between apoE polymorphism and carotid intima-media thickness (IMT), and severity and extent of coronary artery disease (CAD).Methods and resultsB-mode ultrasound and quantitative coronary angiography (QCA) were used to assess carotid, and coronary artery atherosclerosis in 91 patients with clinically suspected CAD referred for cardiac catheterization. Two apoE phenotype groups were defined: apoE3 (E3/E3) and apoE4 (including E4/E3, E4/E4 phenotypes). Maximum IMT was higher in the apoE4 group than in the apoE3 group (p = 0.022). The global atheroma burden index was similarly higher in the apoE4 group than in the apoE3 group (p = 0.033). ApoE4 subjects had higher levels of apolipoprotein B (apoB) (p = 0.008), triglycerides (p = 0.006), remnant lipoprotein-cholesterol (RLP-C) (p = 0.023), and lipoprotein(a) [(Lp(a)] (p = 0.041) than apoE3 subjects. The mean LDL particle size was smaller in the apoE4 group than in the apoE3 group (p = 0.041).ConclusionsApoE polymorphism was associated with both carotid and coronary atherosclerosis. Patients with the apoE4 isoform had an increased carotid IMT and a more severe and extensive CAD than patients with the apoE3 isoform.     

Self-warming blanket versus forced-air warming blanket during total knee arthroplasty under spinal anaesthesia: A randomised non-inferiority trial

Background

Arthroplasty patients are at high risk of hypothermia. Pre-warming with forced air has been shown to reduce the incidence of intraoperative hypothermia. There is, however, a lack of evidence that pre-warming with a self-warming (SW) blanket can reduce the incidence of perioperative hypothermia. This study aims to evaluate the effectiveness of an SW blanket and a forced-air warming (FAW) blanket peri-operatively. We hypothesised that the SW blanket is inferior to the FAW blanket.

Methods

In total, 150 patients scheduled for primary unilateral total knee arthroplasty under spinal anaesthesia were randomised to this prospective study. Patients were pre-warmed with SW blanket (SW group) or upper-body FAW blanket (FAW group) set to 38°C for 30 min before spinal anaesthesia induction. Active warming was continued with the allocated blanket in the operating room. If core temperature fell below 36°C, all patients were warmed using the FAW blanket set to 43°C. Core and skin temperatures were measured continuously. The primary outcome was core temperature on admission to the recovery room.

Results

Both methods increased mean body temperature during pre-warming. However, intraoperative hypothermia occurred in 61% of patients in the SW group and in 49% in the FAW group. The FAW method set to 43°C could rewarm hypothermic patients. Core temperature did not differ between groups on admission to the recovery room, p = .366 (CI: −0.18–0.06).

Conclusions

Statistically, the SW blanket was non-inferior to the FAW method. Yet, hypothermia was more frequent in the SW group, requiring rescue warming as we strictly held to the NICE guideline.

Trial Registration

Clinicaltrials.gov identifier: NCT03408197.     

Mitochondrial genome mutations in hypertensive individuals

Human essential hypertension (HTN), a polygenic, multifactorial, and highly heterogeneous disorder of unknown etiology, has been shown to have excess maternal transmission in several studies, suggesting a possible mitochondrial involvement. In an effort to assess the contribution of the mitochondrial genome to HTN we initiated a systematic, extended screening of hypertensive individuals to identify potentially pathogenic mtDNA mutations. We applied our newly developed novel class of tests for the detection of mitochondrial mutation involvement in complex diseases to the hypertension data set from 350 pedigrees of white ethnicity and 98 of African American ethnicity ascertained at HTN clinics associated with Boston Medical Center, and we identified families with a likely mitochondrial involvement. We analyzed the sequence of the entire mitochondrial genome in probands from 20 such pedigrees, consisting of 10 African American and 10 white families. Comparison with the reference "Cambridge" sequence revealed a total of 297 base changes, including 24 in the ribosomal RNA (rRNA) genes, 15 in the transfer RNA (tRNA) genes, and 46 amino acid substitutions, with the remainder involving the noncoding regions or synonymous changes. Among the coding region mutations, 30 are novel, with 13 hypertensive probands carrying at least one novel variant, usually in combination with the previously described common polymorphisms, several of which are associated with cardiovascular and renal pathologies. These data will serve as a starting point for large-scale case-control association studies.     

Gastric air tonometry during laparoscopic cholecystectomy: a comparison of two PaCO2 levels

PURPOSE: Pneumoperitoneum can cause disturbances in acid-base balance and splanchnic perfusion. We studied the effect of ventilation on acid-base balance and gastric mucosal tonometric values in patients undergoing laparoscopic cholecystectomy. METHODS: Twenty-four patients (ASA I-II) were randomly allocated into two groups. In the fixed ventilation group, ventilation was constant allowing free increase in PCO2, while in the constant CO2 group end-tidal PCO2 was fixed with ventilatory adjustment. Intraabdominal pressure was limited to 12 mmHg. Arterial acid-base balance, automated air tonometric variables and gastric mucosal to arterial PCO2 gap were determined frequently from anesthesia induction until three hours postoperatively. RESULTS: During pneumoperitoneum, in the fixed ventilation group arterial PCO2 changed from 5.0 +/- 0.2 to 6.6 +/- 0.4 kPa and pH from 7.43 +/- 0.03 to 7.33 +/- 0.04, tonometric PCO2 from 5.1 +/- 0.5 to 6.9 +/- 0.4 and pH from 7.44 +/- 0.04 to 7.33 +/- 0.04. In the constant CO2 group these variables remained at control levels (P < 0.01 between groups). The PCO2 gap remained unchanged without any differences between the groups. In the recovery room all measured variables were within normal range in both groups. CONCLUSION: Despite inter-group differences in arterial and tonometric PCO2 and pH values during CO2 pneumoperitoneum, the patients did not develop splanchnic hypoperfusion detectable by air tonometric method, as indicated by normal PCO2 gap in both groups throughout the study.     

Regulation of neuropeptide Y mRNA expression in cultured human pheochromocytoma cells.

The expression of the neuropeptide Y (NPY) gene varies considerably in human pheochromocytomas, but the mechanisms for this variation have not been clarified. To investigate the regulation pattern of the NPY gene in human pheochromocytomas, we screened 16 pheochromocytomas and 9 normal adrenal tissues with Northern blots. The expression level of NPY mRNA in normal adrenal medulla was low and relatively constant, while the pheochromocytomas showed a very wide variation in NPY mRNA levels in both malignant and benign tumors. This indicates that NPY gene expression is not correlated with malignancy in pheochromocytomas. In primary cultures of human pheochromocytoma cells, nerve growth factor treatment (causing neuronal differentiation) increased NPY mRNA accumulation 2- to 5-fold (P < 0.05). NPY mRNA levels were also induced by protein kinase modulators (Bu)(2)cAMP and staurosporine in the cultures (P < 0.05). In contrast, treatment with dexamethasone and IGF-II (causing or linked with chromaffin differentiation) reduced NPY mRNA accumulation (P < 0.05). These data show that the regulation pattern of NPY mRNA expression in cultured human pheochromocytoma cells is different from that previously described in rat pheochromocytoma PC12 cells. Regulation of NPY mRNA expression in primary cultures by these differentiating factors suggests that the expression of NPY mRNA in pheochromocytoma tissues may be associated with the neuronal differentiation of the tumor cells affected by multiple factors.