G. J. Krejs

Post-prandial administration of the insulin analogue insulin aspart in patients with Type 1 diabetes mellitus.

Aims In intensified insulin therapy, the recent development of short‐acting insulin analogues with a very rapid onset of action forces a new discussion in terms of the optimal injection–meal interval. This study evaluated prandial glycaemia in patients with Type 1 diabetes following the subcutaneous injection of soluble human insulin (HI) and the insulin analogue insulin aspart (IAsp) at different injection–meal intervals and investigated whether administration of IAsp after the meal might provide satisfactory metabolic control.

Evaluation of a new DNA test compared with the lactose hydrogen breath test for the diagnosis of lactase non-persistence.

Background and aims Recent publications have found that the CC genotype of the DNA variant −13910 T/C upstream of the LCT gene is associated with lactase non-persistence. We therefore compared the value of DNA testing for this variant (DNA test) with the lactose hydrogen breath test (H2 test), which is the clinical standard for the diagnosis of lactase non-persistence. Patients and methods One hundred and twenty-three consecutive patients with suspected lactose malabsorption were tested for the presence of the −13910 T/C variant by polymerase chain reaction-restriction fragment length polymorphism analysis. These patients also underwent the H2 test after ingestion of 50 g lactose. Results Thirty-seven subjects had a CC genotype of the −13910 T>C polymorphism suggesting lactase non-persistence; 36 (97%) had also a positive H2 test. Eighty-six subjects had either a TC or a TT genotype suggestive of lactase persistence. Seventy-four (86%) of these tested negative on the H2 test, while 12 patients had a positive H2 test. In eight of these 12 patients duodenal biopsies showed no evidence of small bowel disease. One patient carrying a CC genotype had a negative H2 test. In this patient the rise in serum glucose after oral lactose was normal, furthermore H2 non-excretion was also excluded. Conclusions An excellent correlation is observed between a CC genotype and a positive H2 test, whereas the correlation between a TC or TT genotype and a negative H2 test result is less strong. Analysis of the −13910 T/C variant can be considered a good test for predicting the presence of lactase non-persistence in a patient population with suspected lactose malabsorption.

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.

IMPACT OF LONG-TERM HEMODIALYSIS ON NUTRITIONAL STATUS IN PATIENTS WITH END-STAGE RENAL FAILURE

We evaluated the way in which duration of hemodialysis treatment affects nutritional status in 96 end-stage renal failure patients. According to the length of previous hemodialysis treatment patients were divided into the groups: onset hemodialysis (ON-HD), early-stage hemodialysis (ES-HD, 1–8 months), mid-stage hemodialysis (MS-HD, 9–69 months), and advanced-stage hemodialysis (ASHD, 70–207 months). Nutritional status was assessed by laboratory data (serum proteins, total lymphocyte count), intradermal skin antigen testing, anthropometric measurements (body mass index [BMI], infrared interactance), and records of food intake. ON-HD patients on a low-protein diet exhibited abnormally low values for serum total protein, albumin, transferrin, and total lymphocyte count and a high prevalence of anergy to skin antigens (69%). In the ES-HD and MS-HD groups values for serum proteins and total lymphocyte count were in the normal range and significantly higher than in ON-HD patients. In addition, a lower proportion of cutaneous anergy was observed (50% and 27%, respectively). Long-term hemodialysis therapy for 6–17 years (AS-HD) was associated with normal levels for all measured serum proteins. Subnormal levels of total lymphocyte count, significantly lower than in MS-HD patients, were associated with an increase in anergy to skin antigens (46%). Serum prealbumin, complement C3c, BMI, body fat, and lean body mass exhibited normal values in all patients and showed no differences between groups. These results indicate that diminished visceral protein stores, lymphopenia, and anergy to skin antigens are widespread in undialyzed uremic patients with end-stage renal failure but become uncommon after the initiation of regular hemodialysis therapy. Even patients on long term hemodialysis for 6–17 years can maintain their serum protein levels, BMI, body fat, and lean body mass in the normal range. The catabolic stimulus of the dialysis procedure itself does not seem to outweigh its beneficial effect of removing uremic toxins when patients are treated for so many years. The occurrence of lymphopenia and a higher proportion of anergy to skin antigens in AS-HD patients indicates that hemodialysis treatment of very long duration has a depressive effect on immunological functions, but not on nutritional status.

Cell-type specific response of peripheral blood lymphocytes to methotrexate in the treatment of rheumatoid arthritis

The mode of action of methotrexate in the treatment of rheumatoid arthritis is still questionable. Although in vitro results suggest an immunosuppressive effect of methotrexate, several clinical studies have failed to confirm these effects in patients treated with oral low-dose methotrexate. With respect to the highly variable bioavailability of methotrexate, we investigated the effects of an intravenous administration of 15 mg methotrexate per week on peripheral blood lymphocyte subsets in eight patients with rheumatoid arthritis. Methotrexate after 12 weeks significantly (P<0.01) reduced total peripheral blood lymphocytes and led to a pronounced redistribution of lymphocyte subsets with a preferred reductive effect on B-lymphocytes (P<0.005) and T-lymphocytes (P<0.05). Natural killer cells and killer cell-like T cells, on the other hand, were unaffected by the treatment. Our results suggest a cell-type specific effect of intravenously administered low-dose methotrexate on peripheral blood lymphocytes. This effect, in our opinion, may contribute to the mode of action of methotrexate as an immunosuppressive drug in the treatment of rheumatoid arthritis.

Osteomyelitis of the Hip Joint Associated with Systemic Cat-Scratch Disease in an Adult

Abstract 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 patients 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.

A Case of Lung Transplantation Following Mycoplasma pneumoniae Infection

Abstract.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 Reiters 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.

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.

Puumala Virus RNA in Patient with Multiorgan Failure

To the Editor: The hantaviruses (genus Hantavirus, family Bunyaviridae) include human pathogens and occur worldwide (1). In Western and Central Europe, the predominant serotype is Puumala virus (PUUV), which causes epidemic nephropathy. We report the first Austrian patient with reverse transcription–polymerase chain reaction (RT-PCR)–confirmed PUUV infection and, to our knowledge, the first detection of PUUV-specific RNA in bone marrow. On April 27, 2004, a previously healthy 52-year-old bus driver stopped his bus because of visual disturbance, dizziness, headache, and weakness in his legs; he then lost consciousness for a few minutes. He was seen at the neurology emergency service and subsequently admitted to the university hospital in Graz. He smoked tobacco, drank beer on the weekends, and cleaned his bus in the garage daily. The patient showed slight paresis of the right leg, nystagmus, cognitive deficit, and retrograde amnesia. Laboratory tests showed increases in (normal values are shown in parentheses) C-reactive protein (CRP) 40 mg/L ( 3,000 ng/mL, aspartate aminotransferase 368 U/L (<35), alanine aminotransferase 96 U/L (<45), γ-glutamyl transpeptidase 182 U/L (<55), erythrocytes 3.76 × 109/mL, leukocytes 9.09 × 106/mL, thrombocytopenia of 9.2 × 104 platelets/mL, and lymphoplasmacytoid cells on peripheral blood smear. Serum electrophoresis and immunofixation showed an increased γ-globulin fraction with oligoclonal immunoglobulin G (IgG) λ and IgGκ components. A bone marrow biopsy showed hypercellularity and 15% lymphoid cells with plasmocytoid features. Fluorescence-activated cell sorter testing showed 3% reactive B- and T-cell blasts but no signs of a malignant hematologic disease. Culture of bronchoalveolar lavage for bacteria and fungi was negative. Urinary antigen tests for Legionella spp. and pneumococci were negative. Serum antibody tests for Leptospira spp. were negative, but IgM against PUUV was detected by POC Puumala rapid test (Erilab Ltd, Kuopio, Finland) and recomLine Bunyavirus IgG/IgM test (Mikrogen, Martinsried, Germany). PUUV RNA was detectable in serum and in bone marrow by RT-PCR (2). PUUV was confirmed with a bootstrap probability of 99% on phylogenetic analysis (2). On May 1, status epilepticus developed and was treated with clonazepam. On May 2, renal function deteriorated and progressed to a maximum serum creatinine concentration of 4 mg/dL (0.6–1.3) and urea of 244 mg/dL (10–45), which required hemodialysis. CRP increased to 360 mg/L, and blood pressure decreased to 95/65 mmHg. The patient received intensive supportive care including dopamine and norepinephrine. After improvement, the patient was extubated on May 9. Eight days later, fever (temperature up to 40°C), Enterococcus faecalis bacteremia, nosocomial pneumonia from methicillin-resistant Staphylococcus aureus, respiratory failure requiring mechanic ventilation, and renal failure developed in the patient. Despite antimicrobial drug therapy with linezolid, the patient died 19 days after reintubation. In Austria, before this case, PUUV RNA had only been detected by RT-PCR in rodents (2). We report the first Austrian patient with RT-PCR–confirmed PUUV infection. Furthermore, PUUV-specific RNA had never been detected in bone marrow. In animal studies, PUUV induces production of proinflammatory cytokines, such as interleukin (IL)-6 and IL-10 (3). IL-6 constitutes a major growth factor for myeloma and plasma cells, induces immunoglobulin production, and is an active factor in B-cell differentiation (4,5). IL-10 is a differentiation factor for plasma cell formation and immunoglobulin secretion. Since we detected a clear increase of IL-6, IL-10, and tumor necrosis factor α (TNFα) during the acute phase of infection (IL-6 133.0 pg/dL, IL-10 218.0 U/mL, and TNFα 29.7 pg/mL), we assume that lymphoplasmacytoid cells in bone marrow and peripheral blood of our patient and his production of oligoclonal γ-globulins were due to PUUV-induced cytokine release. Epidemic nephropathy usually takes a benign course, but multiorgan failure with cerebral involvement developed in our patient. Whereas neurologic symptoms such as headache (97% of patients), blurred vision (40%), and vomiting (31%) are common in patients infected with PUUV, only a few cases have been reported with severe central nervous system involvement (i.e., meningitis, epileptiform seizures) (6,7). Our patient had visual disturbances, slight paresis of the right leg, nystagmus, cognitive deficit, retrograde amnesia, and status epilepticus. We want to draw attention to the severe course PUUV infections can rarely take. The presence of PUUV in bone marrow explains the marked hematologic changes with lymphoplasmacytoid cells in marrow and peripheral blood.

Are dyspeptic symptoms linked to Helicobacter pylori? A prospective cohort study among medical students

ZusammenfassungEinführungIn Österreich wurde die Prävalenz der Helicobacter pylori (Hp)-Infektion in Zusammenhang mit dyspeptischen Symptomen in einem „gesunden” Kollektiv noch nicht systematisch erhoben. Wir führten eine prospektive Kohorten-Studie bei Medizinstudenten im Praktikum aus Innere Medizin an der Medizinischen Universitäts klinik Graz durch, um festzustellen, ob ein Zusammenhang zwischen Hp-Infektion und dyspeptischen Symptomen existiert. Symptome wurden vor Durchführung des Hp-Tests erhoben, um eine Beeinflussung durch das Testergebnis auszuschließen.MethodenZwischen Februar 2000 und Februar 2001 wurden 242 Medizinstudenten gebeten, an unserer Studie teilzunehmen. Abdominelle Beschwerden wurden mittels Fragebogen erhoben. Dyspeptische Symptome wurden entsprechend den Rom II Kriterien definiert. Sodbrennen wurde demnach nicht als dyspeptisches Symptom gewertet. Um das Ausmaß der Beschwerden zu erheben, verwendeten wir den Glasgow Dyspesia Severity Score (GDSS). Nach der Symptomerhebung wurde ein 13C-Urea-Atemtest durchgeführt.ErgebnisseVon 242 Studenten (103 männlich, 139 weiblich, Altersschnitt 26a, Range 21–39) waren 23 Hppositiv (10%); 34 der Teilnehmer berichteten über dyspeptische Symptome (14%, GDSS-Range 1–11). Vier der symptomatischen Studenten waren Hp-positiv (12%). Von 208 asymptomatischen Studenten waren 19 Hp-positiv (9%). Die statistische Analyse zeigte keinen signifikanten Unterschied in der Frequenz der Hp-Infektion zwischen asymptomatischen Studenten und Studenten, die über dyspeptische Beschwerden klagten.ZusammenfassungDie Hp-Prevalenz bei österreichischen Medizinstudenten ist vergleichbar mit anderen westlichen Ländern. Es zeigte sich kein signifikanter Unterschied in der Hp-Prevalenz zwischen dyspeptischen und asymptomatischen Studenten.SummaryObjective and designIn Austria, the prevalence of Helicobacter pylori (Hp) infection in healthy people with or without symptoms of dyspepsia has not yet been assessed systematically. We conducted a prospective cohort study among medical students during their rotation in internal medicine to determine whether or not dyspeptic symptoms are linked to Hp infection. Symptoms were assessed before testing for Hp so that knowledge of Hp status could not influence symptom-reporting behavior.MethodsFrom February 2000 to February 2001 we invited 242 medical students to participate in this trial. Abdominal symptoms were assessed by a questionnaire. Dyspeptic symptoms were defined according to the Rome II criteria: heartburn was not considered a dyspeptic symptom. Severity of symptoms was assessed using the Glasgow dyspepsia severity score (GDSS). After determination of symptoms, students underwent a13C-urea breath test for Hp.ResultsOf 242 students (103 male, 139 female, mean age 26 years, range 21–39 years), 23 tested positive for Hp (10%). Of 34 participants reporting dyspeptic symptoms (14%, GDSS-range 1–11), four were Hp positive (12%). Of the 208 asymptomatic students, 19 were Hp positive (9%). Statistical analysis did not show a significant difference in the frequency of Hp infection between asymptomatic students and students reporting dyspeptic symptoms.ConclusionHp prevalence in Austrian medical students is similar to that in other western countries. There was no significant difference in Hp prevalence between dyspeptic students and asymptomatic students.