A Cerebrovascular Event After Single-Dose Administration of Recombinant Factor VIIa in a Patient with Esophageal Variceal Bleeding

Upper gastrointestinal bleeding (UGIB) is a life-threatening complication of cirrhosis that develops from esophageal varices in almost 70% of patients. The mortality rate from the bleeding episodes is reported to be 30% [1–4]. Standard management of UGIB of cirrhotic patients is vasoactive therapy combined with endoscopic procedures such as endoscopic sclerotherapy and band ligation [5]. Currently, it is reported that recombinant activated fVIIa (Novoseven, NovoNordisc) can correct the prothrombin time in decompensated cirrhotic patients and also can be used safely in Child's B and C cirrhotic patients with UGIB [6–8]. Herein, we describe the first case report in the literature of a cerebrovascular event after the administration of a single dose of fVIIa in a cirrhotic patient with esophageal variceal bleeding.     

Huffing-Induced Cardiomyopathy: A Case Report

The intentional inhalation of fumes from gasoline or solvents for recreational purposes is commonly known as Huffing, Sniffing or Dusting (Anderson and Loomis in Am Fam Physician 68(5):869–874, 2003). Inhalant abuse is known to be “Cardio-toxic”, causing sudden death and chronic myocardial damage (Meadows and Verghese in South Med J 89(5):455–462, 1996; Anderson and Loomis in Am Fam Physician 68(5):869–874, 2003). We report a 20-year-old white man who presented with altered mental status following ingestion of multiple alprazolam and oxycodone tablets. He was found to have diffused ST-T changes on his EKG. Cardiac enzymes were found to be elevated—CK: 599 U/L, CK-MB: 16.8 ng/mL and Troponin: 0.78 ng/mL. A transthoracic echocardiogram (TTE) revealed global left ventricular (LV) dysfunction with an ejection fraction (EF) of 10–15%. During hospitalization, the cardiac enzymes started trending downward and this was followed by spontaneous resolution of the LV dysfunction. The patient also admitted to inhaling “Dust-Off” spray 2–3 days prior to admission. Inhalant abuse can cause cardiomyopathy and should be considered a probable cause in patients presenting with cardiac dysfunction of unknown etiology, particularly in teenagers and young adults.     

Spontaneous pneumomediastinum secondary to refractory dermatomyositis successfully treated with rituximab

Spontaneous pneumomediastinum has been described in patients with dermatomyositis (DM) and polymyositis (Korkmaz et al., Rheumatology 40:476–478, 2001; Maruoka et al., Mod Rheumatol 16:55–57, 2006; Kono et al., Ann Rheum Dis 59:372–376, 2000; Neves et al., Clin Rheumatol 26:105–107, 2007). Literature reviews suggest that this complication has a mortality of between 27% and 41% ( Kono et al., Ann Rheum Dis 59:372–376, 2000; Neves et al., Clin Rheumatol 26:105–107, 2007; Goff et al., Arthritis Rheum 61:108–118, 2009). This is the first report of rituximab being used successfully as part of the treatment for DM complicated by pneumomediastinum.     

Spousal Intimate Partner Violence is Associated with HIV and Other STIs Among Married Rwandan Women

HIV is a health problem in Rwanda, where the adult HIV prevalence is 3.1% (WHO 2008 in Online database of HIV/AIDS epidemiological data, found at: ); the majority of those infected are women (UNAIDS 2008 in ). Prior studies indicate that intimate partner violence is frequently associated with increased HIV risk in women, often because men who abuse their wives also exhibit riskier sexual behaviors (Silverman et al. in JAMA 300:703–710 2008. Population—based data from the 2005 Rwanda Demographic and Health Survey indicate that women with few, if any, other sexual risk factors who have experienced sexual, physical, or emotional abuse within their marriages are 1.61–3.46 times as likely to test positive for HIV, and 2.14–4.11 times more likely to report another STI. These findings confirm prior clinical studies that indicate that intimate partner violence is a correlate of HIV/STIs in Rwanda. Further research is needed to determine whether Rwandan men that abuse their wives have higher baseline rates of HIV/STI infection.     

Simultaneous deep vein thrombosis and transverse myelitis with negative serology as a first sign of antiphospholipid syndrome: a case report and review of the literature

Transverse myelitis is a rare manifestation of antiphospholipid syndrome, usually secondary to systemic lupus erythematosus (Rheum Dis Clin North Am 20:129–158, 1994). Only about 110 reports of this complication have been reported (Lupus 10:851–856, 2001). A connection has been demonstrated between positive serology for antiphospholipid and transverse myelitis (Lupus 8:109–115, 1999). Herein, we report of a young patient admitted with deep vein thrombosis and neurological manifestations of transverse myelitis with negative serology for systemic lupus erythematosus and antiphospholipid, who developed positive anticardiolipin antibody during pulse therapy with cyclophosphamide and methylprednisolone.     

Therapeutic Endoscopic Ultrasound for Biliary and Pancreatic Disorders

The role of endoscopic ultrasound (EUS) has greatly expanded since the first clinical examination performed nearly 30 years ago. The introduction of linear instruments allowed tissue sampling (Kulesza and Eltoum Clin Gastroenterol Hepatol 5:1248–1254, 2007; Levy and Wiersema Gastrointest Endosc 62:417–426, 2005) and therapeutic interventions applications, including celiac plexus and ganglia blockade and neurolysis (Wiersema and Wiersema Gastrointest Endosc 44:656–662, 1996; Levy and Wiersema Gastroenterol Clin North Am, 35:153–165, 2006; Levy et al. Am J Gastroenterol 103:98–103, 2008), pancreatic fluid drainage (Lopes et al. Arq Gastroenterol 45:17–21, 2008; Norton et al. Mayo Clin Proc 76:794–798, 2001; Kruger et al. Gastrointest Endosc 63:409–416, 2006; Seifert et al.: Endoscopy 32:255–259, 2000), cholecystenterostomy (Kwan et al. Gastrointest Endosc 66:582–586, 2007), and delivery of cytotoxic agents (eg, chemotherapy, radioactive seeds, and gene therapy) (Chang et al.: Cancer 88:1325–1335, 2000; Chang Endoscopy 38(Suppl 1):S88–S93, 2006). The continued need to develop less invasive alternatives to surgical and interventional radiologic therapies drove the development of EUS-guided methods for biliary and pancreatic intervention. This article reviews existing data and focuses on established and emerging EUS techniques for accessing and draining the bile and pancreatic ducts.     

Does acute ingestion of large amounts of alcohol cause pancreatic injury? A prospective study

Summary The contribution of ethanol to the pathogenesis of acute pancreatitis has been questioned for a long time. The authors asked whether acute ingestion of large amounts of alcohol may lead to pancreatic injury, as assessed by serum amylase levels, clinical picture, and abdominal ultrasound. Therefore, all patients (N=112) admitted to our medical emergency ward with the diagnosis of alcohol intoxication were evaluated prospectively during a 12-mo period. Of these, 78 (56 M, 22 F; mean age 36±15) could be evaluated. The other 44 were excluded because of incomplete data (n=18), mixed intoxications (n=8), repeated admission (n=9), incorrect diagnosis on admission (n=7), and chronic pancreatitis (n=2). Serum ethanol, amylase, and GOT were measured. Serum ethanol was 246±122 mg/dL (3–500 mg/dL), amylase 83±44 U/L (27–361 U/L), and GOT 25±37 U/L (5–271 U/L) without significant differences among the genders. No correlation between serum ethanol and serum amylase levels could be detected.     

Recurrent Acute Pancreatitis

Opinion statement  

Nasogastric feeding in severe acute pancreatitis may be practical and safe

Summary Background. Severe acute pancreatitis may be protracted and some form of nutritional support is frequently required to maintain the patient’s nutritional status. Recent work has suggested that enteral feeding via a jejunal route of delivery may reduce the magnitude of the inflammatory response. Insertion of nasojejunal (NJ) tubes in the patient with severe acute pancreatitis involves both delay and inconvenience. We undertook a prospective, feasibility study to assess the safety and practicability of nasogastric (NG) feeding in patients with severe acute pancreatitis. Patients and Methods. Twenty-six patients with objective evidence of severe acute pancreatitis received nasogastric feeding within 48 h of admission to our unit. Results. Etiology was identified as cholelithiasis (18 patients), ethanol (5), and miscellaneous (3). The median Glasgow score was 4 (range 2–7), APACHE II score 10 (4–28), and C-reactive protein concentration 286 mg/L (79–469). Fifteen patients had pancreatic and/or peripancreatic necrosis. Eleven patients developed severe organ failure, necessitating ventilatory support. Six developed multiple organ system failure, requiring inotropic support and/or renal dialysis. There were four deaths (15.3%). Nine patients underwent early, and nine late, ERCP, respectively; six necrosectomy (5 proven infected necrosis, 1 continued deterioration despite maximal support) and 4 patients internal drainage of a pseudocyst. The feed was well-tolerated in 22 patients. In 3 patients gastric stasis proved troublesome. There was no evidence of clinical or biochemical deterioration on commencing nasogastric feeding. Conclusion. It would appear that early NG feeding is usually possible in severe acute pancreatitis. In most patients it appears safe, well-tolerated, and worthy of further study.     

Takotsubo Cardiomyopathy

Background  Takotsubo cardiomyopathy is a novel, yet well-described, reversible cardiomyopathy triggered by profound psychological or physical stress with a female predominance. Objective  This review is designed to increase general clinician awareness about the diagnosis, incidence, pathogenesis, and therapies of this entity. Data Sources  A complete search of multiple electronic databases (Pubmed, EMBASE, Science Citation Index) was carried out to identify all full-text, English-language articles published from 1980 to the present date and relevant to this review. Review Methods  The following search terms were used: takotsubo cardiomyopathy, stress-induced cardiomyopathy, and left ventricular apical ballooning syndrome. Citation lists from identified articles were subsequently reviewed and pertinent articles were further identified. Results  Takotsubo cardiomyopathy is typically characterized by the following: 1) acute onset of ischemic-like chest pain or dyspnea, 2) transient apical and mid-ventricular regional wall-motion abnormality, 3) minor elevation of cardiac biomarkers, 4) dynamic electrocardiographic changes, and 5) the absence of epicardial coronary artery disease. The pathogenesis of the syndrome is unknown but has mostly been associated with acute emotional or physiologic stressors. Dote, Sato, Tateishi, Uchida, Ishihara (J Cardiol. 21(2):203–214, 1991); Desmet, Adriaenssens, Dens (Heart. 89(9):1027–1031, Sep., 2003); Bybee, Kara, Prasad, et al. (Ann Intern Med. 141(11):858–865, Dec 7, 2004); Sharkey, Lesser, Zenovich, et al. (Circulation. 111(4):472–479, Feb 1, 2005) The short and long-term prognosis of these patients is overwhelmingly favorable and often only requires supportive therapy. Conclusion  Whether an emotional or physical event precedes one’s symptoms, it is apparent that takotsubo cardiomyopathy case presentations mimic ST-segment elevation myocardial infarction, and thus is an important entity to be recognized by the medical community.     

Evidence for only two independent pathways for decreasing senescence in <Emphasis Type="Italic">Caenorhabditis elegans</Emphasis>

Cold temperature, dietary restriction, reduced insulin/insulin-like growth factor signaling, and mutations in mitochondrial genes have all been shown to extend the lifespan of Caenorhabditis elegans (Kenyon et al., Nature 366:461–464, 1993; Klass, Mech Ageing Dev 6:413–429, 1977; Lakowski and Hekimi, Science 272:1010–1013, 1996). Additionally, all of them extend the lifespan of mice (Bluher et al., Science 299:572–574, 2003; Conti et al., Science 314:825–828, 2006; Holzenberger et al., Nature 421:182–187, 2003; Liu et al., Genes Dev 19:2424–2434, 2005; Weindruch and Walford, Science 215:1415–1418, 1982). The mechanism by which these treatments extend lifespan is currently unknown, but our study uses an epistatic approach to show that these four manipulations are mainly additive in terms of lifespan. Classical interpretation of this data suggests that these manipulations are independent of each other. However, using a Gompertz mortality rate analysis, the maximum mortality rate doubling time can be achieved through the use of only dietary restriction and cold temperature, suggesting that the mechanisms by which cold temperature and caloric restriction extend lifespan are the only independent mechanisms.     

Acute pancreatitis with diabetic ketoacidosis associated with hypermyoglobinemia,acute renal failure,and DIC

We report a case of acute pancreatitis with diabetic ketoacidosis associated with increased serum myoglobin concentration, acute renal failure, and disseminated intravascular coagulation. A 49-year-old man suffering from diarrhea, vomiting, and somnolence was admitted to the hospital. He had had flu-like symptoms for 4 days prior to the onset of these symptoms. He was a habitual drinker and had been consuming 360 ml–900 ml of the drink “shochu” (distilled spirits containing 28% alcohol) daily for 30 years. Laboratory data on admission revealed elevated serum levels of pancreatic enzymes, including amylase, trypsin, lipase, pancreatic secretory trypsin inhibitor (PSTI), phospholipase A₂ (PLA₂), and elastase-1, as well as elevated levels of glucose (373 mg/dl), ketone bodies (3675 μmol/l), and myoglobin (229.8 ng/ml). Treatment with subcutaneous insulin and intravenous administration of electrolyte fluid and the systemic protease inhibitor, gabexate mesilate, was begun immediately. Early after the initiation of treatment, there was an increase in serum cretinine (4.9 mg/dl), and thrombocytopenia (15000/μl) was observed. The patient completely recovered from renal failure and acute pancreatitis, but required insulin therapy. Alcohol ingestion and dehydration are thought to have played a major role in the triggering of the acute pancreatitis, We examined the relationship among acute pancreatitis, diabetic ketoacidosis, and hypermyoglobinemia in the literature.     

Noonan syndrome and related disorders: Alterations in growth and puberty

Noonan syndrome is a relatively common multiple malformation syndrome with characteristic facies, short stature and congenital heart disease, most commonly pulmonary stenosis (Noonan, Clin Pediatr, 33:548–555, 1994). Recently, a mutation in the PTPN11 gene (Tartaglia, Mehler, Goldberg, Zampino, Brunner, Kremer et al., Nat Genet, 29:465–468, 2001) was found to be present in about 50% of individuals with Noonan syndrome. The phenotype noted in Noonan syndrome is also found in a number of other syndromes which include LEOPARD (Gorlin, Anderson, Blaw, Am J Dis Child, 17:652–662, 1969), Cardio-facio-cutaneous syndrome (Reynolds, Neri, Hermann, Blumberg, Coldwell, Miles et al., Am J Med Genet, 28:413–427, 1986) and Costello syndrome (Hennekam, Am J Med Genet, 117C(1):42–48, 2003). All three of these syndromes share similar cardiac defects and all have postnatal short stature. Very recently, HRAS mutations (Aoki, Niihori, Kawame, Kurosawa, Ohashi, Tanaka et al., Nat Genet, 37:1038–1040, 2005) have been found in the Costello syndrome and germline mutations in KRAS and BRAF genes (Rodriguez-Viciana, Tetsu, Tidyman, Estep, Conger, Santa Cruz et al., Nat Genet, 2006; Niihori, Aoki, Narumi, Neri, Cave, Verloes et al., Nat Genet, 38:294–296, 2006) in the Cardio-facio-cutaneous syndrome. Phenotypic overlap between these genetic disorders can now be explained since each is caused by germline mutations that are major components of the RAS-MAPK pathway. This pathway plays an important role in growth factor and cytokine signaling as well as cancer pathogenesis.     

Human pancreas-specific protein

Summary Conclusion Human pancreas-specific protein (hPASP) is a very sensitive reflector of the extent of pancreatic necrosis on the cellular level, and is of both diagnostic and prognostic value in acute pancreatitis. Furthermore, it allows the estimation of the severity of graft pancreatitis soon after simultaneous renal and pancreatic transplantation. Background Diagnosis of acute pancreatitis (AP) has been improved in the past 15 yr as new methods for the determination of specific pancreatic enzymes have been developed. However, these enzymes have no prognostic implications. In this prospective study, we evaluated the role of human pancreas-specific protein (hPASP) in comparison with pancreatic amylase and C-reactive protein (CRP) in acute pancreatitis and pancreas transplantation. Patients and Methods The study included 40 patients (22 female, 18 male; mean age 51 yr, range 22–88 yr) with AP and 7 patients (2 female, 5 male; mean age 37 yr, range 25–49 yr) with type I diabetes and renal insufficiency who underwent simultaneous kidney and pancreas transplantation. By means of contrast-enhanced computed tomography (CT) and/or intraoperative findings, patients were judged to have edematous-interstitial (AIP,n=20, mean age 55.2 yr, range 24–88 yr) or necrotizing pancreatitis (NP,n=20, mean age 46.3 yr, range 22–81 yr). Serum hPASP concentration was measured daily by a commercial radioimmunoassay technique. In 25 healthy subjects and in several control groups (35 patients with chronic pancreatitis, 20 patients with pancreatic carcinoma and 80 patients with different gastrointestinal diseases) a single blood specimen was taken at hospital admission for the determination of the normal range of hPASP and for specificity analysis. Results The upper normal value for hPASP in healthy subjects was found to be 52 ng/mL. Serum hPASP was elevated in all patients suffering from AP, with a median of 343 ng/mL (lower-upper quartile: 192–478 ng/mL) at hospital admission. In the daily serum monitoring with respect to the onset of symptoms, significantly higher hPASP levels were found in NP compared with AIP after day 2 (p<0.001). In patients with NP, peak values of hPASP correlated significantly with the extent of pancreatic necroses measured by contrast-enhanced CT-scanning, whereas CRP did not. Six patients of the transplantation group had the same serum hPASP course as AIP, with almost normal values on the third postoperative day. One patient had elevated levels throughout the observation period. This patient suffered from necrotizing graft pancreatitis, confirmed by relaparotomy, and died because of subsequent septic complications.     

The Prevalence of Cationic Trypsinogen (PRSS1) and Serine Protease Inhibitor,Kazal Type 1 (SPINK1) Gene Mutations in Polish Patients with Alcoholic and Idiopathic Chronic Pancreatitis

Background  

The main cause of chronic pancreatitis (CP) is excessive alcohol consumption. On the other hand, only 5–10% of heavy drinkers develop chronic pancreatitis. We have only limited information regarding the pathogenic mechanism by which alcohol leads to the disease. Mutations of the PRSS1 and SPINK 1 have been mostly implicated in hereditary and idiopathic CP, but their presence in other types of this disease have also been reported.     

The veteran population: one at high risk for sleep-disordered breathing

Sleep complaints are very common among the general population and are usually accompanied by significant medical, psychological and social disturbances (Redline S, Strohl K, Otolaryngol Clin North Am, 132:303, 1999). A higher prevalence of sleep complaints has been described in the elderly (Vgontzas AN, Kales A, Annu Rev Med, 50:387–400, 1999). It is manifested by breathing disturbances during sleep, loud snoring, difficulties maintaining sleep, fatigue, daytime sleepiness, mood effects and impairment of daily activities (Lugaresi E, Cirignotta F, Zucconi M et al., Good and poor sleepers: an epidemiological survey of the San Marino population, Raven, New York, pp 1–12, 1983; Kales A, Soldatos CR, Kales JD, Am Fam Physician, 22:101–108, 1980). It has been associated with cardiovascular, endocrine and neurocognitive manifestations. Growing interest in early diagnosis and treatment has been noted in recent years based on emerging knowledge about the potential health consequences when the disease goes untreated (Nanen AM, Dunagan DP, Fleisher A et al., Chest, 121:1741, 2002). The veteran population in the mainland has a higher tendency for obesity, high blood pressure (HBP), sleep disorders and chronic alcohol consumption (Mustafa M, Erokwu N, Ebose I, Strohl K, Sleep Breath, 9:57–63, 2005). The Hispanic veteran population has never been studied in detail for sleep disorders and related conditions. We used previously validated screening tools for sleep disturbance breathing. Two hundred and forty-five questionnaires were administered. We found a higher prevalence of Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) in our population compared with data from the mainland (USA). The mean age was 64 years (±11). Ninety seven per cent were males. The mean body mass index was 25 kg/cm²; mean Epworth Sleepiness Scale score was 8. Thirty-four per cent met high-risk criteria for sleep apnea, 53% for insomnia, 13% for symptoms suggestive of narcolepsy and 13% for those suggestive of restless leg syndrome. There were high incidences of alcohol consumption (37.6%), diabetes (32.7%), hypercholesterolemia (31.8%), depression (31.8%), hypertension (39.6%) and post-traumatic stress disorder (PTSD) (9.8%).     

Chronic Alcohol Intake Increases the Severity of Pancreatitis Induced by Acute Alcohol Administration,Hyperlipidemia and Pancreatic Duct Obstruction in Rats

Background: The mechanism of alcoholic pancreatitis is still unknown. It is of special interest why only about 5% of all alcoholics develop an episode of pancreatitis. We evaluated the role of long-term alcohol intake in the pathogenesis of alcoholic pancreatitis in rats. Methods:To evaluate the effect of long-term alcohol intake, rats were fed either a Lieber-DeCarli control diet (CD) or a Lieber-DeCarli alcohol diet (AD) for 6 weeks. Then, rats were infused over 2 h with either Ringer's solution (CO) or ethanol (E). In additional animals, alcoholic pancreatitis was induced by ethanol combined with hyperlipidemia and temporary pancreatic duct obstruction (EFO). Controls received Ringer's solution combined with hyperlipidemia and temporary pancreatic duct obstruction (RFO). Intravital microscopy (pancreatic perfusion and leukocyte adhesion), alcohol concentrations, amylase, lipase, cholesterine and triglyceride levels in plasma, myeloperoxidase activity and histology were evaluated at different time intervals. Results: In those animals which received the Lieber-DeCarli control diet, capillary perfusion was reduced in the E group and further reduced in the EFO group as compared to the controls (CO, RFO; p < 0.01). Leukocyte adhesion was significantly increased in rats receiving E (p < 0.01), and was further increased in the combination group EFO (p < 0.01). EFO induced histologically evident acute pancreatitis. The additional administration of a long-term alcohol diet further increased microcirculatory disturbances and pancreatic injury significantly (EFO-AD > EFO-CD). Conclusions: This study shows that alcoholic pancreatitis is induced by the combination of ethanol and individual cofactors. Chronic alcohol abuse intensifies these changes. Therefore, long-term alcohol intake seems to be a major factor in the pathogenesis of alcoholic pancreatitis.     

Epidemiology of pancreatic diseases in Lüneburg county: A study in a defined German population

Background/Aims: Worldwide, the incidence of pancreatic cancer is very well known, that of acute pancreatitis and chronic pancreatitis not. Our study sought to determine the incidence of all three pancreatic diseases in a well-defined population in Germany. Methods: Records of all patients treated for acute (first attacks only) and chronic pancreatitis as well as pancreatic cancer from 1988 to 1995 and who resided in the county of Lüneburg were evaluated. Results: The crude incidence rates for acute pancreatitis, chronic pancreatitis and pancreatic cancer per 100,000 inhabitants/year were 19.7, 6.4, and 7.8. In acute and chronic pancreatitis the male gender dominated, whereas in pancreatic carcinoma the gender ratio was almost even. Peak incidence for acute pancreatitis was in the age group of 35–44 years, for chronic pancreatitis 45–54, and for pancreatic cancer 6575. Etiology of acute pancreatitis was biliary in 40%, alcohol abuse in 32%, unknown in 20%, and other in 8% of the patients. In chronic pancreatitis alcohol abuse was the etiology in 72% and unknown (idiopathic) in 28%. Conclusion: For the first time, epidemiological data obtained in a well-defined German population are being published relating to all three pancreatic diseases: acute pancreatitis (incidence rate, etiology and severity), chronic pancreatitis (incidence rate and etiology), and pancreatic carcinoma (incidence rate). A peak incidence of chronic pancreatitis occurring in an age group 10 years older than the peak age group for acute pancreatitis suggests that chronic pancreatitis develops during this time-frame following first attacks of acute pancreatitis.