Positive effect of abdominal breathing exercise on gastroesophageal reflux disease: a randomized, controlled study.

OBJECTIVES: The lower esophageal sphincter (LES), surrounded by diaphragmatic muscle, prevents gastroesophageal reflux. When these structures become incompetent, gastric contents may cause gastroesophageal reflux disease (GERD). For treatment, lifestyle interventions are always recommended. We hypothesized that by actively training the crura of the diaphragm as part of the LES using breathing training exercises, GERD can be positively influenced. METHODS: A prospective randomized controlled study was performed. Patients with non-erosive GERD or healed esophagitis without large hernia and/or previous surgery were included. Patients were randomized and allocated either to active breathing training program or to a control group. Quality of life (QoL), pH-metry, and on-demand proton pump inhibitor (PPI) usage were assessed at baseline and after 4 weeks of training. For long-term follow-up, all patients were invited to continue active breathing training and were further assessed regarding QoL and PPI usage after 9 months. Paired and unpaired t-test was used for statistical analysis. RESULTS: Nineteen patients with non-erosive GERD or healed esophagitis were randomized into two groups (10 training group and 9 control group). There was no difference in baseline patient characteristics between the groups and all patients finished the study. There was a significant decrease in time with a pH<4.0 in the training group (9.1±1.3 vs. 4.7±0.9%; P<0.05), but there was no change in the control group. QoL scores improved significantly in the training group (13.4±1.98 before and 10.8±1.86 after training; P<0.01), but no changes in QoL were seen in the control group. At long-term follow-up at 9 months, patients who continued breathing exercise (11/19) showed a significant decrease in QoL scores and PPI usage (15.1±2.2 vs. 9.7±1.6; 98±34 vs. 25±12 mg/week, respectively; P<0.05), whereas patients who did not train had no long-term effect. CONCLUSIONS: We show that actively training the diaphragm by breathing exercise can improve GERD as assessed by pH-metry, QoL scores and PPI usage. This non-pharmacological lifestyle intervention could help to reduce the disease burden of GERD.

Delayed processing of blood samples influences time to positivity of blood cultures and results of Gram stain-acridine orange leukocyte Cytospin test.

We investigated in vitro whether storage of blood samples influences the time to positivity used for the calculation of the differential time to positivity (DTP) and the results of the Gram stain-acridine orange leukocyte Cytospin (AOLC) test. A 24-hour storage of blood samples at room temperature may lead to false-negative DTP and false-positive Gram stain-AOLC test results, whereas storage at 4 degrees C does not.

Detection of catheter-related bloodstream infections by the differential-time-to-positivity method and gram stain-acridine orange leukocyte cytospin test in neutropenic patients after hematopoietic stem cell transplantation.

For febrile neutropenic patients who received hematopoietic stem cell transplantation, the Gram stain-acridine orange leukocyte cytospin (AOLC) test and the differential-time-to-positivity method (DTP) were performed. As a diagnostic tool for catheter-related bloodstream infections in these patients, the Gram stain-AOLC test has a lower sensitivity than does the DTP method but acceptable positive and negative predictive values.

Molecular typing of coagulase-negative staphylococcal blood and skin culture isolates to differentiate between bacteremia and contamination.

In order to determine whether a blood culture positive for coagulase-negative staphylococci (CNS) represents bacteremia or contamination, a prospective study was conducted using molecular typing to analyze CNS blood culture isolates and corresponding CNS skin isolates collected after skin disinfection from 431 subjects. CNS bacteremia was not found in any of the 301 subjects not suspected of having bacteremia. In 130 patients suspected of having bacteremia, the rate of actual CNS bacteremia was 6%. The overall rate of CNS blood culture contamination was 1%. Chart analysis showed good agreement between our microbiological definitions of bacteremia and the clinical definitions previously published. Bacteremia and contamination can be differentiated using pulsed-field gel electrophoresis and molecular typing of CNS isolates obtained from cultures of blood and corresponding skin samples.

Effect of pantoprazole on the course of reflux-associated laryngitis: a placebo-controlled double-blind crossover study.

BACKGROUND: The optimal management of patients with reflux-associated laryngitis is unclear. We performed a placebo-controlled crossover trial in patients with proven reflux disease and associated laryngitis to determine the effect of pantoprazole and to gain information on the natural course of the disease. METHODS: Sixty-two consecutive non-smoking patients with hoarseness and proven laryngitis were examined. Scores with respect to the larynx and for subjective complaints were determined and 24-h pH-metry to assess acid reflux in the lower oesophagus and pharynx was performed. Patients with pathologic reflux were given the chance to enter a double-blinded randomized crossover trial with pantoprazole 40 mg b.i.d. and placebo for a duration of 3 months each, separated by a 2-week washout period. RESULTS: Twenty-four of 62 patients showed pathological reflux; 21 patients were included in the study and 14 concluded all parts of the study. Both pantoprazole and placebo resulted in a marked improvement in laryngitis scores (decrease of 8.0 +/- 1.4 versus 5.6 +/- 2.6; no significant difference between the 2 treatments) and symptoms after the first 3 months (decrease of oesophageal symptom score of 2.2 +/- 1.4 versus 5.4 +/- 2.8; decrease of laryngeal scores of 8.3 +/- 3.6 versus 10.3 +/- 3.9; also no significant difference between the 2 treatments). A second pH-metry 2 weeks thereafter proved the persistence of reflux in most of these patients. Switching to pantoprazole led to a further improvement of scores. In the group switched to placebo there was recurrence only in a minority of patients. CONCLUSIONS: The self-limited nature of reflux-associated laryngitis in non-smokers is largely underestimated. Laryngitis improves despite the persistence of reflux. Pantoprazole may be helpful especially in relieving acute symptoms, but the advantage of long-term treatment over placebo has been greatly overestimated.

Monoclonal and biclonal gammopathy in two patients infected with Bartonella henselae.

Two immunocompetent patients with cat-scratch disease due to infection with Bartonella henselae developed monoclonal and biclonal gammopathy. Neither patient had evidence of any other known cause of plasma cell dyscrasia, and antibiotic eradication of Bartonella henselae infection resulted in the prompt disappearance of the gammopathy. Hence, cat-scratch disease should be added to the list of possible underlying disorders in individuals presenting with monoclonal and biclonal gammopathy.

Metabolic benefits associated with sibutramine therapy.

Sibutramine-induced weight loss and weight maintenance lead to clinically relevant reductions in risk factors associated with the metabolic syndrome. Treatment with the drug decreases visceral fat, improves lipid levels, decreases glycosylated haemoglobin and decreases uric acid concentrations. Sibutramine is effective in achieving weight loss in patients with type 2 diabetes but weight loss occurs more slowly than in non-diabetic patients. The criteria for predicting response to treatment in uncomplicated patients may not be appropriate to those with type 2 diabetes. Furthermore, it is important to set realistic goals for weight loss in type 2 diabetes to avoid the risk of denying effective treatment to patients.

Aborted sudden death in a patient with a structurally normal heart: the Brugada syndrome.

We report a 37-year-old man with documented aborted sudden death. After resuscitation, the patient showed no structural heart disease but the ECG showed a right bundle-branch block with a descending ST segment elevation in leads V(1) and V(2). After transient normalization of the ECG, the administration of ajmaline led to spontaneous development of the distinct descending ST segment elevation in the right precordial leads and therefore to the diagnosis of Brugada syndrome. The incidence of sudden cardiac death among these patients is high. The only treatment is an implantable cardioverter-defibrillator (ICD). The Brugada syndrome should therefore be borne in mind in the differential diagnosis of sudden death.

A case of lung transplantation following Mycoplasma pneumoniae infection.

Reported here is a case of severe necrotizing pneumonia following Mycoplasma pneumoniae infection that occurred in a 55-year-old man. The histological changes of lung parenchyma included granulomas and bronchiolitis obliterans. Mycoplasma infection was diagnosed by repeated antibody determination (complement fixation test) and confirmed using the polymerase chain reaction to detect the pathogen from a tracheal aspirate. Prior to this episode of pneumonia, the patient had been healthy, except for Reiter's disease that had been diagnosed 18 years previously. In addition to severe pulmonary involvement, the patient developed rhabdomyolysis with subsequent acute renal failure, Stevens-Johnson syndrome, biochemical pancreatitis, severe anemia, and an effusion of the right knee. Contrary to the symptoms of pulmonary disease, all of the extrapulmonary manifestations except anemia were transient. Due to persistent respiratory insufficiency and long-term failure to wean the patient from a respirator, a lung transplantation was performed. Five weeks after transplantation the patient died as a result of intrapulmonary hemorrhage. To the best of our knowledge, this is the first report of pneumonia due to Mycoplasma pneumoniae leading to lung transplantation. Furthermore, the multiple extrapulmonary manifestations in this case make it exceptional.

Effect of sildenafil on oesophageal motor function in healthy subjects and patients with oesophageal motor disorders.

BACKGROUND AND AIMS: Sildenafil blocks phosphodiesterase type 5 which degrades nitric oxide (NO) stimulated 3'5'-cyclic monophosphate (cGMP), thereby relaxing smooth muscle cells in various organs. We used sildenafil as a tool to investigate the role of the NO-cGMP pathway in the oesophagus of healthy volunteers and patients with hypercontractile oesophageal motility disorders. METHODS: Six healthy male volunteers participated in a randomised double blind study on two separate days before and one hour after oral intake of either sildenafil 50 mg or placebo. Oesophageal manometry was performed to determine vector volume of the lower oesophageal sphincter (LOS) and pressure amplitudes of the oesophageal body. Four of the volunteers underwent 12 hour ambulatory oesophageal manometry on two separate days, once with sildenafil 50 mg and once with placebo. An activity index for spontaneous swallowing was calculated for every hour of the study. Eleven patients with hypercontractile oesophageal motility disorders took part in an open study of the effect of 50 mg sildenafil on manometric features of their disorder and on the clinical response to sildenafil taken as required. RESULTS: In healthy subjects, sildenafil significantly reduced LOS pressure vector volume and pressure amplitudes in the distal half of the oesophageal body. In three of four subjects the inhibitory effect of sildenafil lasted at least eight hours. In nine of 11 patients, manometric improvement after sildenafil was observed but only four had an improvement in oesophageal symptoms with sildenafil taken as required. Two of these four patients however experienced side effects and did not want to continue treatment. CONCLUSIONS: Sildenafil lowers LOS pressure and propulsive forces in the body of the oesophagus of healthy subjects as well as in patients with nutcracker oesophagus, hypertensive LOS, and achalasia. The effect of sildenafil on the oesophageal body may last for up to eight hours in healthy volunteers. A subset of patients with hypertensive LOS or nutcracker oesophagus may benefit from sildenafil but side effects are a limiting factor.

Role of Candida in antibiotic-associated diarrhea.

To quantitatively assess the role of Candida species in antibiotic-associated diarrhea (AAD), stool samples from a total of 395 patients and control subjects were cultured in differential isolation medium: 98 patients had AAD, 93 patients were taking antibiotics but did not have diarrhea (A(+)D(-)), 97 patients were not taking antibiotics but had diarrhea (A(-)D(+)), and 107 patients were control subjects (A(-)D(-)). In addition, secreted aspartyl proteinase (Sap) production was tested. In AAD patients, Candida positivity (77/98) and Candida overgrowth (62/98) were not different from that among A(+)D(-) patients (75/93 [P= .860] and 52/93 [P= .375], respectively). Candida overgrowth among A(-)D(+) patients (40/97, P= .003) was less frequent than among AAD patients, but Candida positivity was not different (80/97, P= .612). In control subjects, Candida positivity and overgrowth were less common than in all other groups. Production of Sap did not differ between patients with AAD and control subjects (P= .568 and P= .590, respectively). Data indicate that elevated Candida counts are a result of antibiotic treatment or diarrhea rather than a cause of AAD.

Treatment of patients with chronic hepatitis C not responding to interferon with high-dose interferon alpha with or without ribavirin: final results of a prospective randomized trial. Austrian Hepatitis Study Group.

OBJECTIVE: To investigate the efficacy of high-dose interferon alpha (IFN-alpha) with or without ribavirin in interferon (IFN) non-responders. STUDY DESIGN: 304 chronic hepatitis C patients received 5 MU IFN-alpha2b (IntronA, Schering-Plough, Kenilworth, NJ, USA) three times a week for 3 months. Non-responders were randomized either to continue with IFN (IFN 5 MU/TIW followed by 10 MU/TIW, each for 3 months) alone (group A: n = 76, m: f = 54: 22, age 45.7 +/- 12 years, 16% cirrhosis, alanine aminotransferase [ALT] 66 +/- 35 U/l) or in combination with ribavirin (approximately 14 mg/kg/day) (group B: n = 81, m: f = 57: 24, age 48.2 +/- 12 years, 17% cirrhosis, ALT 71 +/- 40 U/l). At the end of treatment, patients were followed for 6 months. MAIN OUTCOME MEASURES: Virological response at end of treatment and 6 months thereafter. SETTING: University hospitals and tertiary referral centres. RESULTS: At the end of treatment, eight (10.8%) and 25 (31.3%, P= 0.0066) patients were HCV-RNA negative, and 51 and 39 were HCV-RNA positive, in groups A and B, respectively. There were 17 drop-outs in each group. Six months after treatment, only one patient in group A (1.3%) and seven patients (8.6%, P= 0.06) in group B had normal ALT and undetectable serum HCV-RNA. CONCLUSIONS: A combination of high-dose IFN with ribavirin induces a short-lasting complete response in about one-third of IFN-non-responders.

Hemoglobin variants and determination of glycated hemoglobin (HbA1c).

Measurement of glycated hemoglobin in diabetic patients is an established procedure for evaluating long-term control of diabetes. The Diabetes Control and Complications Trial (DCCT), as well as the United Kingdom Prospective Diabetes Study (UKPDS), confirmed the direct relationship between the degree of glycemic control as estimated by glycohemoglobin (GHb) determinations and the development and progression of long-term complications in diabetic patients. Samples with known interferences of HbA(1c) determination as hemoglobinopathies are specifically excluded from certification testing and there are no guidelines or requirements for comparability of samples containing hemoglobin (Hb) variants. This paper reviews the interference of Hb variants on determination methods of glycated hemoglobin as they result in false HbA(1c) results.

Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases.

Reduced hepatobiliary transporter expression could explain impaired hepatic uptake and excretion of bile salts and other biliary constituents resulting in cholestasis and jaundice. Because little is known about alterations of hepatobiliary transport systems in human cholestatic liver diseases, it was the aim of this study to investigate such potential changes. Hepatic mRNA levels in hepatobiliary transport systems for bile salts (NTCP, BSEP), organic anions (OATP2, MRP2, MRP3), organic cations (MDR1), phospholipids (MDR3), and aminophospholipids (FIC1) were determined in 37 human liver biopsies and control livers by competitive reverse-transcription polymerase chain reaction (RT-PCR). Transporter tissue distribution was investigated by immunofluorescence microscopy. In patients with inflammation-induced icteric cholestasis (mainly cholestatic alcoholic hepatitis), mRNA levels of NTCP, OATP2, and BSEP were reduced by 41% (P <.001), 49% (P <.005), and 34% (P <.05) compared with controls, respectively. In addition, NTCP and BSEP immunostaining was reduced. MRP2 mRNA levels remained unchanged, but canalicular immunolabeling for MRP2 was also decreased. mRNA expression of MRP3, MDR1, MDR3, and FIC1 remained unchanged. In contrast to the alterations of transporter expression in inflammation-induced icteric cholestasis, transporter expression did not change in anicteric cholestasis caused by primary biliary cirrhosis (PBC) stages I and II. In conclusion, reduced expression of hepatobiliary transport systems for bile salts and other organic anions may contribute to inflammation-induced cholestasis in humans. Reduction of transporter gene expression can occur at the mRNA level as observed for NTCP, OATP2, and BSEP. However, reduced MRP2 immunostaining in the presence of conserved MRP2 mRNA levels suggests an additional role for posttranscriptional/posttranslational mechanisms.

Gastric adenocarcinoma mimicking achalasia in a 15-year-old patient: a case report and review of the literature.

Although adenocarcinoma of the cardia is extremely rare in adolescent patients, the endoscopist should be alert to this disease in patients of any age with dysphagia, even if symptoms, and results of a barium study, upper endoscopy, and esophageal manometry are suggestive of primary achalasia, especially if family history is negative for achalasia. In addition, secondary achalasia should be suspected in patients who do not respond to therapy with botulinum toxin within 2 months. Because none of the mentioned tests can distinguish between primary achalasia and secondary forms due to carcinoma of the cardia, biopsy specimens should be obtained. It appears that, although there is a minimal risk for complications, a diagnostic procedure such as biopsy would be appropriate when the information obtained could be essential. In some cases EUS can be an additional diagnostic tool, because lesions of the submucosa and the surrounding area can be identified by EUS.

Osteomyelitis of the hip joint associated with systemic cat-scratch disease in an adult.

Reported here is the case of a 29-year-old male with cervical lymphadenopathy, fever and weight loss, followed by acute painful osteomyelitis of the left hip joint due to cat-scratch disease. The diagnosis was established by detection of IgG antibodies to Bartonella henselae in serum and histologic examination of a lymph node including a positive polymerase chain reaction test. Treatment consisted of clarithromycin and cefotiam for 2 weeks. Four weeks after discharge, all of the patient's symptoms had completely resolved. Magnetic resonance imaging of the left hip joint showed marked regression of bone inflammation 4 months later and normalization after 8 months. Cat-scratch disease should be considered in the differential diagnosis of osteomyelitis in an adult, especially when lymphadenitis is present.

[Helicobacter pylori and stomach cancer]. / Helicobacter pylori und Magenkarzinom.

A number of epidemiological studies and summaries of such studies in the form of meta-analyses have shown a significant relationship between Helicobacter pylori infections of the gastric mucosa and the incidence of gastric cancer. The risk of developing stomach cancer is on average six times higher in the presence of H.p. In countries such as Austria, some 1% of H.p. positives develop gastric cancer in the course of their lives, while only one per 750 noninfected individuals do so. The molecular basis is unclear, but a defect in the tumor-suppressor gene p53 seems to play an important role. As H.p. infection is common (some 30% of the total population in Austria is infected) and gastric cancer without H.p. eradication has become less common (in 1997 there were 24 new cases per 100,000 population), H.p. eradication is not advised as prophylaxis for gastric cancer. Patients who have a positive family history of gastric cancer and those who have had surgery for gastric cancer should, however, according to the Maastricht recommendations, undergo eradication. An example is given to show that in comparison with other measures for cancer screening or prevention, the cost of 120,000 ATS per prevented gastric cancer would be a very good investment with general eradication of H.p. in all individuals over 50 years of age.

Intra-hepatic haematoma complicating transjugular intra-hepatic portosystemic shunt for Budd-Chiari syndrome associated with anti-phospholipid antibodies, aplastic anaemia and chronic hepatitis C.

Portal venous decompression with transjugular intra-hepatic portosystemic shunt (TIPS) is a new approach in the treatment of Budd-Chiari syndrome. We report on a 31-year-old female with Budd-Chiari syndrome due to anti-phospholipid antibodies with compression of the inferior vena cava treated with TIPS and stenting of the inferior vena cava. TIPS was complicated by massive intra-hepatic haematoma which was managed conservatively. Treatment options and pathogenic mechanisms of Budd-Chiari syndrome under the rare coincidence of aplastic anaemia and anti-phospholipid syndrome are discussed. TIPS may be considered for venous decompression in Budd-Chiari syndrome, but physicians should be aware of potential TIPS' complications in these patients.

Scintigraphic long-term follow-up of a patient with metastatic glucagonoma.

Two years after resection of a pancreatic glucagonoma, scintigraphy with 111indium-labeled octreotide revealed hepatic metastases in a 48-yr-old man. Hepatic metastases were also visualized by CT, whereas an additional lesion in the chest was seen only by scintigraphy. A total of 11 follow-up examinations over 46 months proved somatostatin receptor scintigraphy to monitor reliably somatostatin receptor expression, growth and dissemination of glucagonoma metastases, and to indicate therapeutic readjustment if necessary. The survival time of the patient is now >75 months, in comparison with a mean survival time of 59 months reported for metastatic glucagonoma.