Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options

Background

Adenosine kinase deficiency is a recently described defect affecting methionine metabolism with a severe clinical phenotype comprising mainly neurological and hepatic impairment and dysmorphism.

Methods

Clinical data of 11 additional patients from eight families with adenosine kinase deficiency were gathered through a retrospective questionnaire. Two liver biopsies of one patient were systematically evaluated.

Results

The main clinical symptoms are mild to severe liver dysfunction with neonatal onset, muscular hypotonia, global developmental retardation and dysmorphism (especially frontal bossing). Hepatic involvement is not a constant finding. Most patients have epilepsy and recurrent hypoglycemia due to hyperinsulinism. Major biochemical findings are intermittent hypermethioninemia, increased S-adenosylmethionine and S-adenosylhomocysteine in plasma and increased adenosine in urine. S-adenosylmethionine and S-adenosylhomocysteine are the most reliable biochemical markers. The major histological finding was pronounced microvesicular hepatic steatosis. Therapeutic trials with a methionine restricted diet indicate a potential beneficial effect on biochemical and clinical parameters in four patients and hyperinsulinism was responsive to diazoxide in two patients.

Conclusion

Adenosine kinase deficiency is a severe inborn error at the cross-road of methionine and adenosine metabolism that mainly causes dysmorphism, brain and liver symptoms, but also recurrent hypoglycemia. The clinical phenotype varies from an exclusively neurological to a multi-organ manifestation. Methionine-restricted diet should be considered as a therapeutic option.

     

Deep Vein Thrombosis and Pulmonary Embolism in Cirrhosis Patients

Background and Aims It is a commonly held notion that patients with cirrhosis do not suffer from deep vein thrombosis (DVT) or pulmonary embolism (PE) because they are naturally anticoagulated. However, to date, no studies have been carried out that objectively address this issue. We conducted a study to examine the relationship between cirrhosis and DVT/PE events. Methods A case–control study of patients seen at a tertiary care hospital was performed. Cases were hospitalized patients with biopsy and/or imaging plus clinical evidence of cirrhosis. Well-matched patients with no known evidence of cirrhosis served as controls. The DVT/PE events were identified by the international classification of disease-9 (ICD-9) codes and confirmed with radiographic/nuclear imaging. The Charlson Index was calculated to determine the comorbidity. The incidence of DVT/PE in cirrhotic patients was also compared to patients with chronic kidney disease (CKD), congestive heart failure (CHF), and solid organ cancers. Results This study consisted of 963 cirrhotics and 12,405 controls. Both the incidence of DVT/PE (1.8 vs. 0.9%, P = 0.007) and Charlson Index scores (3.2 ± 1.8 vs. 0.9 ± 1.5, P < 0.001) were higher in cirrhotics than in the controls. However, in the multivariate analysis, the presence of cirrhosis was not associated with DVT/PE [odds ratio (OR) 0.87, P = 0.06]. Partial thromboplastin time (PTT; OR 0.88, P = 0.04) and serum albumin (OR 0.47, P = 0.03) were the independent predictors of DVT/PE. The incidence of DVT/PE in cirrhotics (1.8%) was lower than that in patients with other medical illnesses: 7.1% in CKD, 7.8% in CHF, and 6.1% in cancers. Conclusion Patients with cirrhosis do not have a lower risk of DVT/PE than non-cirrhotic controls without other significant co-morbidities, such as CHF, CKD, and solid organ cancers. Partial thromboplastin time and serum albumin were found to be independently predictive of DVT/PE in cirrhotic patients.     

Nationwide trends in molecular epidemiology of methicillin-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>, Finland, 1997–2004

Background  

In Finland, the annual number of MRSA notifications to the National Infectious Disease Register (NIDR) has constantly increased since 1995, and molecular typing has revealed numerous outbreak isolates of MRSA. We analyzed the data on MRSA notifications of the NIDR, and MRSA isolates were identified mainly by pulsed-field gel electrophoresis (PFGE) at the National Reference Laboratory (NRL) in Finland during 1997–2004. One isolate representative of each major PFGE type was further characterized by multilocus sequence (MLST)-, staphylococcal cassette chromosome mec (SCCmec)-, and Panton-Valentine leukocidin (PVL)-typing.     

Hygienic safety of reusable tap water filters (Germlyser<Superscript>®</Superscript>) with an operating time of 4 or 8 weeks in a haematological oncology transplantation unit

Background  

Microbial safe tap water is crucial for the safety of immunosuppressed patients.     

Detection of K-<Emphasis Type="Italic">ras</Emphasis> mutations in the plasma DNA of pancreatic cancer patients

Background In pancreatic cancers, K-ras mutations have been found frequently (80%–100%), and they could be a good marker to detect tumor DNA in the plasma. Several studies have indicated that polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) analysis of K-ras mutation was a useful method for the detection of hepatic and lymph node metastasis of pancreatic cancer. However, this method sometimes exhibited false-positive results, and the rate of K-ras mutation might thus be overestimated in these tissues. To diagnose pancreatic cancer correctly at an early stage, we attempted to detect tumor DNA in the plasma of pancreatic cancer patients using a more sensitive and specific method.Methods We examined 28 pancreatic cancer patients using a sensitive mutation-specific mismatch ligation assay for K-ras gene mutations in primary tumors and paired plasma samples.Results K-ras gene mutations were detected in 26 of the 28 (93%) pancreatic cancers. We also found the same mutations in 9 of these 26 (35%) patients in their plasma DNA. This mutation was found even in the plasma of patients with TNM stage II cancer.Conclusions Genetic alterations present in the tumors of pancreatic cancer patients can be detected in their plasma, and this approach is potentially applicable for cancer screening and the monitoring of this deadly disease.     

Rhythmusstörungen während der Remodelingphase nach Herzinfarkt

BACKGROUND: The effect of mechanical on electrical remodeling or electrical instability of the heart shows that it is essential for the prevention of sudden death to avoid or delay mechanical remodeling and neurohumoral activation after myocardial infarction. In other words, patients after myocardial infarction prone to neurohumoral activation need to be treated with ACE inhibitors or perhaps AT1-receptor blockers and beta blockers to maintain electrical stability. ICD INDICATION: MADIT I and MUSTT study showed that patients with severe ventricular dysfunction after myocardial infarction are at high risk of sudden death, especially in presence of electrical instabilities indicated by ventricular arrhythmias. These patients certainly need an automatic implantable cardioverter defibrillator (ICD). It is not clear so far whether or not the indication needs to be extended according to the MADIT II study. In other words, need all postmyocardial infarction patients with reduced pump function an ICD? There is no doubt that many patients with an ejection fraction below 30% have ventricular arrhythmias and fulfil therefore the inclusion criteria for the MADIT I or MUSTT study. In MADIT I, a run of three ventricular premature beats force was sufficient to fulfil the inclusion criteria. CONCLUSION: Another important consequence of the temporal correlation between mechanical and electrical remodeling is that specific attention must be directed to these interrelations in patients after myocardial infarction. Patients who die of sudden death show in comparison to surviving patients a substantial dilatation of the left ventricular during 6 months of observation which parallel the increasing incidence of ventricular premature beats. The consequence for therapy would be that in patients who present with left ventricular dilatation during 6 months after myocardial infarction, electrical instability is present and a high risk of sudden death exists. These patients probably will benefit from an ICD.     

Patient-centered diabetes self-management education

Diabetes self-management education (DSME) has been shown to improve health outcomes. Yet, relatively little is known about how DSME has its effects. Literature reviewed from the past 3 years indicates that if DSME is to become more effective interventions need to be theory-based, to increase patient involvement in their care, and to encompass a broader array of evidenced-based outcomes. Outcomes reviewed go beyond knowledge and glycemic control to include prevention of diabetes, quality of life, and reduction of cardiovascular risk. The ability of practitioners and health care systems to implement, adopt, and maintain patient-centered interventions over time is discussed. By linking theory to behavior, and broadening the outcomes examined, advances can continue to be made in closing the gap between the scientific base for the treatment of diabetes, and the care and outcomes patients experience. Further research on patient-centered approaches that promote self-management is seen as critical in closing this gap.     

Treatment of hepatitis C

Hepatitis C virus infection accounts for 40% of chronic liver disease in the United States and is the most common indication for liver transplantation. Estimates suggest that 4 million people, or 1.8% of the American population, have or have had hepatitis C virus infection. Pegylated interferon and ribavirin are the current standard of care for treatment. Recent studies have suggested that ribavirin dose and duration of therapy may be adjusted based on genotype. The goals of therapy are to slow disease progression, improve hepatic histology, reduce infectivity, and decrease the risk of hepatocellular carcinoma. Sustained virologic response, which generally implies the absence of viremia 6 or more months following completion of therapy, is increasingly being regarded as a cure, with evidence of slowing or even regression of fibrosis on follow-up liver biopsy. Assessment by liver biopsy of disease severity and evaluation of comorbidities and possible contraindications to therapy should be weighed in the decision to begin treatment. Counseling patients regarding transmission, natural history, and drug and alcohol abstinence should also be included in management. Close monitoring should be done during treatment for interferon and ribavirin side effects, including depression, bone marrow suppression, and hemolytic anemia.     

Interventional endoscopic ultrasound in pancreatic disease

The use of endoscopic ultrasound (EUS) in pancreatic disease is rapidly evolving as the field moves from a primarily diagnostic role to one of therapeutic intervention. Therapeutic EUS includes techniques such as the celiac block and transmural pseudocyst drainage. Newer techniques include EUS-guided fine-needle injection therapy in which a variety of agents are being investigated for the treatment of pancreatic cancer. Novel EUS-guided techniques are being devised to drain and alleviate pancreaticobiliary and gastroduodenal obstruction.