Licorice-induced apparent mineralocorticoid excess causing persistent hypertension and hypokalemia.

Chronic ingestion of licorice is known to cause numerous metabolic and electrolyte disturbances. Severe hyponatremia, hypertension, and hypokalemia as well as metabolic alkalosis are amongst the most common consequences of chronic ingestion resulting in an apparent mineralocorticoid excess (AME). Treatment predominantly consists of cessation of licorice ingestion, potassium replenishment and aldosterone antagonists. Given the potentially lethal effects of chronic licorice ingestion, clinicians should be made aware of the presentation of AME and the proper management. We present the rare case of a 62-year-old male with licorice-induced apparent mineralocorticoid excess secondary to excessive licorice tea intake. Initial presentation included severe hypokalemia of 2.2mmol/L and hypertension of 180/110mmHg, while eunatremic (Na, 144meq/L).

Prokineticin-2 and ghrelin robustly influence the sexual and ingestive behaviors of female Syrian hamsters.

Prokineticins are involved in many physiological processes including circadian rhythms, neurogenesis, angiogenesis, and cancer. Recently, they have been found to play a role in regulating food intake. Historically, proteins that increase feeding behavior in mammals decrease reproductive behavior to prevent pregnancy and lactation when food is scarce. In the current study, prokineticin-2 (PK2) had pronounced effects on reproductive and ingestive behaviors when given to female Syrian hamsters. Administration of PK2 prevented ingestive behaviors induced by food restriction, such as the amount of time spent with food and eating. Hamsters given PK2 preferred to engage in reproductive behaviors, including spending time with a male and lordosis. Furthermore, analysis of blood plasma revealed that changes to behavior persisted despite similar levels of des-acyl ghrelin (DAG) and reduced glucose concentrations in the blood. Additionally, administering 10 mg/kg of acyl ghrelin (AG) to a different cohort of animals significantly decreased the amount of time females spent with a potential mating partner, increased the amount of time females spent with food, decreased the duration of lordosis, and increased the duration of eating. Results from the current study support the need for further research investigating the reproductive and ingestive roles of PK2 and ghrelin.

Treatment of Refractory Gastrointestinal Bleeding in Patients With Portal Hypertension: A Case Series and Treatment Algorithm.

In patients with portal hypertension, ectopic varices can develop at any site along the gastrointestinal tract outside the classically described gastroesophageal location. Like esophageal variceal hemorrhage, bleeding from ectopic varices can be life-threatening. Diagnosis and treatment of ectopic varices can be challenging; to date, no effective treatment algorithm has been described. A systematic teamwork approach to diagnosing and treatment of ectopic varices is required to successfully manage hemorrhage from ectopic varices.

Enhanced risk of illness during the 1918 influenza pandemic after previous influenza-like illnesses in three military populations.

The reasons for the unprecedented mortality during the 1918 influenza pandemic remain poorly understood. We examined morbidity records from three military cohorts from years prior to and during the 1918 pandemic period to assess the effects of previous respiratory illnesses on experiences during the pandemic. Clinical registers and morbidity lists were examined to identify all medical encounters for acute respiratory illnesses in students at two U.S. military officer training academies and Australian soldiers deployed in Europe. Influenza-like illness prior to the major pandemic wave of 1918 predisposed Australian soldiers [relative risk (RR) 1·37, 95% confidence interval (CI) 1·18-1·60, P < 0·0001] and US officer trainees at West Point (RR 3·10, 95% CI 2·13-4·52, P < 0·0001) and Annapolis (RR 2·03, 95% CI 1·65-2·50, P < 0·0001) to increased risks of medically treated illnesses in late 1918. The findings suggest that susceptibility to and/or clinical expressions of the 1918 pandemic influenza virus depended on previous experiences with respiratory infectious agents. The findings are consistent with observations during the 2009 pandemic in Canada and may reflect antibody-dependent enhancement of influenza infection.

Liver transplantation in an adult with adenomatosis and congenital absence of the portal vein: a case report.

Congenital absence of the portal vein (CAPV) is a rare congenital anomaly in which the superior mesenteric veins (SMV) and splenic veins converge and bypass the liver, effectively draining directly into the systemic venous circulation via the inferior vena cava (IVC), or alternatively the renal or iliac vein, creating a native portosystemic shunt. Portosystemic shunting results in clinical manifestations of hepatic encephalopathy as well as a predisposition to focal nodular hyperplasia and tumors, including adenomas, hepatoblastoma, and hepatocellular carcinoma (HCC), by the disruption of enterohepatic blood flow. Historically, CAPV has been thought to be a rare condition found mainly at autopsy, however, in recent years due to advances in radiological techniques, CAPV detection has increased. Herein we describe a patient with known CAPV who initially underwent hepatic resection for HCC. During surveillance, additional masses were discovered and were identified as recurrent HCC. Unfortunately, this patient was not a candidate for further resection or locoregional therapy. We demonstrate that transplantation is a challenging but technically viable option for treatment of HCC complicating adenomatosis-associated CAPV.

Predicting water table response to rainfall events, central Florida.

A rise in water table in response to a rainfall event is a complex function of permeability, specific yield, antecedent soil-water conditions, water table level, evapotranspiration, vegetation, lateral groundwater flow, and rainfall volume and intensity. Predictions of water table response, however, commonly assume a linear relationship between response and rainfall based on cumulative analysis of water level and rainfall logs. By identifying individual rainfall events and responses, we examine how the response/rainfall ratio varies as a function of antecedent water table level (stage) and rainfall event size. For wells in wetlands and uplands in central Florida, incorporating stage and event size improves forecasting of water table rise by more than 30%, based on 10 years of data. At the 11 sites studied, the water table is generally least responsive to rainfall at smallest and largest rainfall event sizes and at lower stages. At most sites the minimum amount of rainfall required to induce a rise in water table is fairly uniform when the water table is within 50 to 100 cm of land surface. Below this depth, the minimum typically gradually increases with depth. These observations can be qualitatively explained by unsaturated zone flow processes. Overall, response/rainfall ratios are higher in wetlands and lower in uplands, presumably reflecting lower specific yields and greater lateral influx in wetland sites. Pronounced depth variations in rainfall/response ratios appear to correlate with soil layer boundaries, where corroborating data are available.

Management of colorectal polyp cancers.

INTRODUCTION: Management of malignant colorectal polyps is controversial. The options are resection or surveillance. Resection margin status is accepted as an independent predictor of adverse outcome. However, the rate of adverse outcome in polyps with a resection margin of <1mm has not been investigated. METHODS: A retrospective search of the pathology database was undertaken. All polyp cancers were included. A single histopathologist reviewed all of the included polyp cancers. Polyps were divided into three groups: clear resection margin, involved resection margin and unknown resection margin. Polyps were also analysed for tumour grade, morphology, Haggitt/Kikuchi level and lymphovascular invasion. Adverse outcome was defined as residual tumour at the polypectomy site and/or lymph node metastases in the surgical group and local or distant recurrence in the surveillance group. RESULTS: Sixty-five polyps (34 male patients, mean age: 73 years, range: 50-94 years) were included. Forty-six had clear polyp resection margins; none had any adverse outcomes. Sixteen patients had involved polyp resection margins and twelve of these underwent surgery: seven had residual tumour and two of these patients had lymph node metastases. Four underwent surveillance, of whom two developed local recurrence. Three patients had resection margins on which the histopathologist was unable to comment. All patients with a clear resection margin had no adverse outcome regardless of other predictive factors. CONCLUSIONS: Polyp cancers with clear resection margins, even those with <1mm clearance, can be treated safely with surveillance in our experience. Polyp cancers with unknown or involved resection margins should be treated surgically.

Pediatric health-related quality of life after intestinal transplantation.

As outcomes after ITx improve, greater emphasis is needed on HRQOL. The primary aims of this study were to (i) assess the feasibility of measuring HRQOL in pediatric ITx recipients, (ii) measure HRQOL using validated instruments, and (iii) compare HRQOL in ITx recipients to healthy normal (NL) children. The CHQ and Pediatric Quality of Life (PedsQL4.0) instruments were administered to both patients and parents at outpatient visits. All 24 eligible patients were enrolled. The median age at study enrollment was 6.0 yr (range: 2-18 yr), and the median time from transplant to study enrollment was 2.8 yr (range: 0.5-11.8 yr). The majority of subjects were male (58%), Latino (58%), and liver-inclusive (92%) recipients. For CHQ and PedsQL4.0, parental responses were significantly lower in multiple categories including physical health and social functioning compared to healthy norms. Patient responses were not different from NL using CHQ but using PedsQL4.0 were significantly lower in the school functioning subcategory and psychosocial health summary score. HRQOL as reported by children and families after ITx is significantly lower in multiple categories compared to NL.

Critical care issues in patients after liver transplantation.

The majority of patients who undergo liver transplantation (LT) spend some time in the intensive care unit during the postoperative period. For some, this is an expected part of the immediate posttransplant recovery period, whereas for others, the stay is more prolonged because of preexisting conditions, intraoperative events, or postoperative complications. In this review, 4 topics that are particularly relevant to the postoperative intensive care of LT recipients are discussed, with an emphasis on current knowledge specific to this patient group. Infectious complications are the most common causes of early posttransplant morbidity and mortality. The common patterns of infection seen in patients after LT and their management are discussed. Acute kidney injury and renal failure are common in post-LT patients. Kidney injury identification, etiologies, and risk factors and approaches to management are reviewed. The majority of patients will require weaning from mechanical ventilation in the immediate postoperative period; the approach to this is discussed along with the approach for those patients who require a prolonged period of mechanical ventilation. A poorly functioning graft requires prompt identification and appropriate management if the outcomes are to be optimized. The causes of poor graft function are systematically reviewed, and the management of these grafts is discussed.

Novel mechanism of increased Ca2+ release following oxidative stress in neuronal cells involves type 2 inositol-1,4,5-trisphosphate receptors.

Dysregulation of Ca(2+) signaling following oxidative stress is an important pathophysiological mechanism of many chronic neurodegenerative disorders, including Alzheimer's disease, age-related macular degeneration, glaucomatous and diabetic retinopathies. However, the underlying mechanisms of disturbed intracellular Ca(2+) signaling remain largely unknown. We here describe a novel mechanism for increased intracellular Ca(2+) release following oxidative stress in a neuronal cell line. Using an experimental approach that included quantitative polymerase chain reaction, quantitative immunoblotting, microfluorimetry and the optical imaging of intracellular Ca(2+) release, we show that sub-lethal tert-butyl hydroperoxide-mediated oxidative stress result in a selective up-regulation of type-2 inositol-1,4,5,-trisphophate receptors. This oxidative stress mediated change was detected both at the transcriptional and translational level and functionally resulted in increased Ca(2+) release into the nucleoplasm from the membranes of the nuclear envelope at a given receptor-specific stimulus. Our data describe a novel source of Ca(2+) dysregulation induced by oxidative stress with potential relevance for differential subcellular Ca(2+) signaling specifically within the nucleus and the development of novel neuroprotective strategies in neurodegenerative disorders.

A pilot study revealing impaired P50 gating in antisocial personality disorder.

The authors investigated preattentive filtering assessed by P50 gating in nine participants with antisocial personality disorder (ASPD) and seven with adult-onset antisocial behavior (AAB). Relative to 15 comparison subjects, gating was impaired in ASPD, suggesting abnormal pre-attentive filtering in pathological impulsivity.

ACP Best practice no 159. Examination of large intestine resection specimens.

Macroscopic examination of large intestinal resection specimens by the surgical pathologist provides important diagnostic and prognostic information. This review summarises current recommended protocols and evidence based guidelines for gross description, dissection, and histological block selection in both neoplastic and non-neoplastic colorectal disease. Specific lesions discussed include colorectal cancer, polypectomies and polyposis syndromes, and inflammatory bowel disease. Microscopic examination is briefly described, with emphasis on certain pitfalls that might be encountered in routine practice. A section covering special techniques for the investigation of occult bleeding is included.

Spindle cell angiosarcoma of the oropharynx.

Angiosarcomas are uncommon malignant tumours of vascular endothelium. In the head and neck, the scalp is the commonest site of origin. A rare case of spindle-cell angiosarcoma of the oropharynx, treated by surgery and post-operative radiotherapy, is reported. We discuss the clinical presentation and histopathological diagnosis of this lesion.

Oesophageal and gastric cancer pathology reporting: a regional audit.

AIM: To audit the information content of pathology reports of oesophageal and gastric cancer resection specimens in Wales. METHODS: All such reports from the 16 NHS histopathology laboratories in Wales in a one year period were evaluated for their information content. Two standards were used: (1) best practice reporting, and (2) a minimum dataset required for informed patient management that included clear statements on histological tumour type, depth of tumour invasion, lymph node involvement, and completeness of excision. RESULTS: 282 reports were audited. Minimum standards were achieved in 77% of gastric resections (156/203) and 53% of oesophageal resections (42/79). All laboratories achieved minimum standards in some gastric cancer reports (range 50-100%); three laboratories did not achieve minimum standards in any oesophageal cancer reports (range 0-100%). Best practice reporting was achieved in only 20% of gastric and 18% of oesophageal cancer reports. Failure to include an explicit statement on completeness of excision or involvement of the oesophageal circumferential resection margin were the most frequent causes of inadequate reporting. Most other data items were generally well reported, but apparent inadvertent omission of just one item was noted in many of the substandard reports. CONCLUSIONS: This audit shows the need to improve the information content of pathology reports in gastric and oesophageal cancer. The widespread implementation of template proforma reporting is proposed as the most effective way of achieving this. Multidisciplinary meetings of clinicians involved in cancer management should provide a forum for greater communication between pathologists and surgeons, and help to maintain standards of pathological practice.

Identification of a novel penicillin-binding protein from Helicobacter pylori.

The Helicobacter pylori genome encodes four penicillin-binding proteins (PBPs). PBPs 1, 2, and 3 exhibit similarities to known PBPs. The sequence of PBP 4 is unique in that it displays a novel combination of two highly conserved PBP motifs and an absence of a third motif. Expression of PBP 4, but not PBP 1, 2, or 3, is significantly increased during mid- to late-log-phase growth.

Comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of acute bacterial sinusitis.

This double-masked, multicenter, randomized clinical trial compared the efficacy and tolerability of cefuroxime axetil and amoxicillin/clavulanate in the treatment of acute bacterial maxillary sinusitis. A total of 263 patients with acute bacterial maxillary sinusitis were randomly assigned to receive 10 days of treatment with either cefuroxime axetil 250 mg twice daily (n = 132) or amoxicillin/clavulanate 500/125 mg 3 times daily (n = 131). Patients' responses to treatment were assessed once during treatment (6 to 8 days after the start of treatment), at the end of treatment (1 to 3 days posttreatment), and at follow-up (26 to 30 days after cessation of treatment). Clinical success, defined as cure or improvement, was equivalent in the cefuroxime axetil and amoxicillin/ clavulanate groups at the end-of-treatment and follow-up assessments. Patients in both groups showed improvements in symptoms of acute sinusitis at the during-treatment visit. Treatment with amoxicillin/clavulanate was associated with a significantly higher incidence of drug-related adverse events than treatment with cefuroxime axetil (29% vs 17%), primarily reflecting a higher incidence of gastrointestinal adverse events (23% vs 11%), particularly diarrhea. Two patients in the cefuroxime axetil group and 8 patients in the amoxicillin/clavulanate group withdrew from the study due to adverse events (P = 0.06). These results indicate that cefuroxime axetil 250 mg twice daily is as effective as amoxicillin/clavulanate 500 mg 3 times daily in the treatment of acute sinusitis and produces fewer gastrointestinal adverse events. cefuroxime axetil, amoxicillin/clavulanate, acute sinusitis.

Granulomatous inflammation in sigmoid diverticulitis: two diseases or one?

AIMS: Histological appearances indistinguishable from Crohn's disease have been described in patients undergoing sigmoid colectomy for complicated diverticular disease. To investigate whether this finding represents coincidental dual pathology or merely a granulomatous colitis confined to the diverticular segment, we undertook clinical follow-up of affected patients. METHODS AND RESULTS: Eight patients (median age 64 years, four males) whose sigmoid colectomy specimens showed acute diverticulitis and granulomatous inflammation were identified. All had a pre-operative diagnosis of diverticular disease and no previous evidence of Crohn's disease. Non-caseating epithelioid granulomas, unrelated to foreign material and usually unrelated to inflamed diverticular were present in the bowel wall of seven cases and in the regional lymph nodes of five. Three had granulomatous vasculitis and two had granulomas in 'background' mucosa. Mural lymphoid aggregates were identified in all cases. However, fissuring ulcers distinct from inflamed diverticula were not identified. On median follow-up of 51 months (range 18-112 months) none of the patients developed evidence of chronic inflammatory bowel disease. Three had died from unrelated causes. CONCLUSIONS: Granulomatous inflammation appears to be part of a spectrum of sigmoid diverticulitis. In this setting, caution should be exercised to avoid an inappropriate diagnosis of Crohn's disease.

Characterization of the lanthanide ion-binding properties of calcineurin-B using laser-induced luminescence spectroscopy.

Calcineurin (CaN) is a Ca2+/calmodulin-dependent protein phosphatase found in brain and other tissues. It is a heterodimer consisting of a catalytic subunit (CaN-A) and a Ca(2+)-binding regulatory subunit (CaN-B). The primary structure of CaN-B indicates that it, like calmodulin, is an EF-hand protein and binds four Ca2+ ions. Eu3+, due to its favorable spectroscopic and chemical properties, has been substituted for Ca2+ in CaN-B to determine the metal ion-binding properties of this "calmodulin-like" protein. Excitation of the 7F0-->5D0 transition of Eu3+ results in a spectrum similar to that of calmodulin, consisting of three peaks. Analysis of the spectral titration curves reveals four Eu(3+)-binding sites in CaN-B. The affinities vary: sites I and II have dissociation constants of 1.0 +/- 0.2 and 1.6 +/- 0.4 microM, respectively; the values for sites III and IV are Kd = 140 +/- 20 and Kd = 20 +/- 10 nM, respectively. Binding of Tb3+ is slightly weaker. Tb3+ luminescence, sensitized by tyrosine, reveals that for lanthanides the highest affinity sites lie in the C-terminal domain. Energy transfer distance measurements between Eu3+ and Nd3+ in sites III and IV reveal a separation of 10.5 +/- 0.5 A, which suggests that these sites are arranged in a typical EF-hand pair. This information indicates that the overall structure of CaN-B is similar to the dumbbell-shaped proteins troponin-C and calmodulin, but is more like TnC in its metal-binding properties.

Beta-lactam antibiotics inhibit agonist-stimulated platelet calcium influx.

beta-lactam antibiotics cause platelet dysfunction with reversible agonist-receptor inhibition, irreversible [14C]-penicillin binding, and inhibition of agonist-stimulated elevation in cytosolic Ca2+ ([Ca2+]i), occurring after 24 h exposure in vitro and after in vivo treatment. We investigated beta-lactam antibiotic-induced inhibition of rises in [Ca2+]i stimulated by thrombin, sodium arachidonate or A23187 to determine whether Ca2+ influx or intracellular release was primarily affected. The mean rise in [Ca2+]i, measured with fura-2-AM, was inhibited 43.7-84.1% by penicillin when the extracellular Ca2+ concentration ([Ca2+]e) was 1 mM, but was significantly less inhibited when [Ca2+]e was < 1 microM. NiCl2 (2 mM), that blocks Ca2+ influx, caused inhibition comparable to penicillin. MnCl2 (1 mM), that quenches the intracellular fura-2 signal, significantly decreased the rise in 1 mM [Ca2+]i when [Ca2+]e was 1 mM, but did not increase the inhibition caused by penicillin. Penicillin did not inhibit the rise in [Ca2+]i stimulated by inositol-1,4,5-trisphosphate or GTP gamma S. Therefore, beta-lactam antibiotics inhibit agonist-induced elevations of [Ca2+]i primarily through inhibition of Ca2+ influx, which probably accounts for the irreversible inhibition of platelet function seen after prolonged in vitro or in vivo treatment.