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Biomedical subjects

C Schramm

Publications and source records attributed to C Schramm.

At least 19 recordsLinked to original sources

Multiplex neuritis in a patient with autoimmune hepatitis: a case report.

A 37-year old woman presented with a 9-year history of hepatitis of unknown origin and aminotransferases within a 3-fold upper limit of normal. Autoimmune hepatitis (AIH) was diagnosed on the basis of elevated aminotransferases, soluble liver antigen/liver pancreas (SLA/LP) autoantibodies and characteristic histology. Immunosuppressive therapy led to rapid normalization of aminotransferases. Two years later, the patient developed left sided hemisensory deficits under maintenance therapy of prednisolone and azathioprine (AZT). Later she developed right foot drop and paraesthesia in the ulnar innervation territory on both sides. Magnetic resonance imaging (MRI) and cerebral panangiography suggested cerebral vasculitis. Neurological investigation and electromyography disclosed multiplex neuritis (MN) probably due to vasculitis. Consistent with this diagnosis, autoantibodies to extractable nuclear antigens were detectable in serum. Immunosuppression was changed to oral 150 mg cyclophosphamide (CPM0) per day. Prednisolone was increased to 40 mg/d and then gradually tapered to 5 mg. Oral CPM was administered up to a total dose of 40 g and then substituted by 6 times of an intervall infusion therapy of CPM (600 mg/m(2)). Almost complete motoric remission was achieved after 3 mo of CPM. Sensibility remained reduced in the right peroneal innervation territory. Follow-up of cranial MRI provided stable findings without any new or progressive lesions. This is the first report of multiplex neuritis in a patient with autoimmune hepatitis.

Adult↗

Octreotide hardens the pancreas.

BACKGROUND AND AIMS: Leakage from pancreaticojejunostomy and development of pancreatic fistulas are the major postoperative complications in patients undergoing duodenopancreatectomy. The risk of developing these complications is higher when surgery is performed on a soft pancreas. A recent report suggests that octreotide hardens the pancreas when given intraoperatively. The present study aims at verifying this observation by measuring tissue hardness of the pancreas by a commercially available durometer in pigs with and without octreotide pretreatment. METHODS: Three groups of pigs were investigated: Group 1 (n=6) received no treatment; group 2 (n=6) was treated with 3x100 microg octreotide for 1 day; group 3 (n=6) for 5 days. Thereafter, animals were killed and the pancreas was harvested for performing measurements: Tissue hardness was assessed by a commercially available durometer, and a suture holding test was performed using a Newton dynamometer. RESULTS: There was a significant increase in tissue hardness between untreated control animals [26.3+/-2.5 S.U. (shore units)] and animals with 1 day octreotide pretreatment (29.8+/-2.6 S.U.; p=0.04) as well as between the groups treated for 1 and 5 days (34.8+/-2.8 S.U.; p=0.01). Suture holding capacity was higher in animals treated for 5 days. CONCLUSION: The present study agrees with a recent report suggesting that octreotide hardens the pancreas. Octreotide pretreatment may therefore be an advantage when performing surgery on a soft pancreas, i.e., in patients scheduled for duodenopancreatectomy for ampullary carcinomas or circumscript pancreatic tumors not associated with chronic pancreatitis.

Animals↗

[Primary sclerosing cholangitis is a premalignant condition].

Primary sclerosing cholangitis is a chronic cholestatic liver disease of unknown aetiology. The course of the disease is usually progressive with the development of liver cirrhosis leading to death or liver transplantation within an average of 12 years. To date it is well known that the development of hepatobiliary malignancies and the rate of colonic mucosal dysplasia and carcinoma in patients with concomitant ulcerative colitis are greatly enhanced in patients with PSC. PSC can therefore be regarded as a premalignant condition. The following review will focus on the development of cholangiocellular carcinoma in patients with PSC and the associated diagnostic and therapeutic challenges.

Biliary Tract Neoplasms↗

Involvement of distal airways in a chronic model of experimental asthma.

BACKGROUND: Bronchial asthma is characterized by chronic airway inflammation and airway remodelling which occurs in both proximal and distal airways. These changes are associated with development of airway hyper-responsiveness and airflow limitation. OBJECTIVE: This study was aimed to analyse whether chronic inhalative allergen challenges in mice lead to morphological and physiological changes comparable with this phenotype. METHODS: For this purpose, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed by aerosol allergen challenges on 2 consecutive days per week for 12 weeks. RESULTS: In chronically challenged mice, tissue inflammation in proximal as well as distal airways was observed with a predominance of lymphocytes within the cellular infiltrate. In contrast, inflammation in the airway lumen decreased over time. These changes were associated by a shift in bronchoalveolar lavage-cytokine levels from IL-4, IL-5 and TNF-alpha production (during the acute phase) towards markedly increased levels of TGF-beta during the chronic phase. Goblet cell hyperplasia and subepithelial fibrosis occurred throughout the airway tree. In terms of lung function, chronically challenged mice developed persistent bronchial hyper-responsiveness and progressive airflow limitation. Six weeks after OVA aerosol discontinuation, airway inflammation still persisted although lung function was normalized. CONCLUSION: These data indicate that our model of chronic aerosol allergen challenges leads to a phenotype of experimental asthma with participation of distal airways and persistence of inflammation thereby resembling many morphological and physiological aspects of human bronchial asthma.

Administration, Inhalation↗

[Autoimmune liver disease: diagnosis and therapy].

Autoimmune Hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and overlap syndromes of these three disease entities are regarded as autoimmune liver diseases. These conditions are important differential diagnoses of elevated liver function tests as about 10 % of liver transplantations in Europe and North America are for these indications. The diagnosis is often difficult but can be facilitated by sequential measurement of relevant autoantibodies, exclusion of other liver disease, ultrasound, ERCP and liver histology. In AIH immunosuppressive therapy has been shown to prevent or stop the development of cirrhosis and improve the prognosis of the patients decisively. In other autoimmune liver diseases this evidence is missing making individual therapeutic decisions necessary. Ursodesoxycholic acid (UDCA) seems to slow disease progression in particular in early stages of PBC.

Adult↗

Sustained suppression of HCV replication and inflammatory activity after interleukin-2 therapy in patients with HIV/hepatitis C virus coinfection.

OBJECTIVE: There is increasing evidence that coinfection of hepatitis C (HCV) with HIV is associated with accelerated progression of liver cirrhosis. The aim of this pilot study was to investigate toxicity and efficacy of interleukin-2 (IL-2) for treatment of affected patients. DESIGN: Because low-dose, daily IL-2 therapy is well tolerated and can elevate CD4 cell counts and improve immune functions, patients were treated with 1-2 million units (MU) IL-2 subcutaneously daily. METHODS: This pilot trial included 7 HIV/HCV-coinfected individuals. During therapy, clinical, virologic, and laboratory parameters were closely monitored. RESULTS: All patients responded to IL-2 therapy with either improvement of either CD4 cell counts or liver function test results. In 2 patients, HCV-RNA in serum became negative 2 and 4 months, respectively, after cessation of therapy. HCV-RNA has remained undetectable in these 2 patients for 18 and 24 months, respectively. Therapy was well tolerated and no grade III or IV toxicities were observed. CONCLUSIONS: Low-dose, daily IL-2 therapy can improve both CD4 cell counts and liver function test results in patients with HIV/HCV coinfection and may in some cases lead to sustained suppression of viremia of HCV.

Adult↗

[Identification and surgical anatomy of the external branch of the superior laryngeal nerve].

Injury to the external branch of the superior laryngeal nerve (EBSLN) during thyroid surgery can cause serious consequences for patients who depend on control of pitch and a clear and forceful voice, like singers or professional speakers. We used the Neurosign 100(R) nerve monitor to identify 157 nerves in 108 patients undergoing thyroid surgery. The EBSLN was successfully identified in 98.7 % of cases. The recording electrode could be placed either into the cricothyroid muscle or the vocal cord. The latter position proved superior if the recurrent laryngeal nerve had to be identified as well. 16 percent of the nerves crossed the branches of the superior thyroid artery at or below the upper pole of the gland, posing a "high risk" for intraoperative lesions. Our data confirm the results of smaller studies reporting this type of nerve course in 12 % to 14 % of patients. The present findings show a significant number of EBSLN to be in danger of injury when the superior thyroid artery is ligated during thyroid surgery. Neuromonitoring proofed to be a reliable method to identify the nerve, which is an important element in concepts to prevent its injury.

Electromyography↗

The budding yeast proteins Spc24p and Spc25p interact with Ndc80p and Nuf2p at the kinetochore and are important for kinetochore clustering and checkpoint control.

Here, we show that the budding yeast proteins Ndc80p, Nuf2p, Spc24p and Spc25p interact at the kinetochore. Consistently, Ndc80p, Nuf2p, Spc24p and Spc25p associate with centromere DNA in chromatin immunoprecipitation experiments, and SPC24 interacts genetically with MCM21 encoding a kinetochore component. Moreover, although conditional lethal spc24-2 and spc25-7 cells form a mitotic spindle, the kinetochores remain in the mother cell body and fail to segregate the chromosomes. Despite this defect in chromosome segregation, spc24-2 and spc25-7 cells do not arrest in metaphase in response to checkpoint control. Furthermore, spc24-2 cells showed a mitotic checkpoint defect when microtubules were depolymerized with nocodazole, indicating that Spc24p has a function in checkpoint control. Since Ndc80p, Nuf2p and Spc24p are conserved proteins, it is likely that similar complexes are part of the kinetochore in other organisms.

Amino Acid Sequence↗

Congenital pulmonary lymphangiectasia: a case report of thoracic duct agenesis.

We present a 17-year-old Caucasian male with congenital pulmonary lymphangiectasia and an absent thoracic duct. This patient is unique as he did not present with the disorder until age 9.5 years. Since his initial presentation he has had recurrent chylothoraces and has been treated symptomatically. We discuss the possible implications of his disorder as well as some of the limited treatment that is available.

Adolescent↗

Autoimmune hepatitis in the elderly.

OBJECTIVES: Autoimmune hepatitis (AIH) is widely believed to be a disease of young women and menopause. Little is known about the frequency and clinical characteristics in patients aged > or =65 yr. METHODS: We reviewed charts of 120 consecutive outpatients with known AIH to identify patients who were diagnosed at the age of 65 or older. These 20 patients (median age, 69 yr) were compared to the same number of younger patients (median age, 24 yr) with well-documented AIH from the same cohort. RESULTS: Seventeen percent (20/120) of our patients were > or =65 yr at the time of diagnosis. In the older patients median time to diagnosis was significantly longer than in the younger patients (8.5 vs 3.5 months). Patients most commonly presented with an acute icteric hepatitis. Complete remission was achieved to a similar extent (18/20 and 17/20 patients). Fewer older patients expressed human leukocyte antigen A1-B8 (p = 0.005). CONCLUSIONS: Diagnosis of AIH often seems to be delayed in the elderly, presumably because AIH is erroneously considered to be a disease of young age. Presentation with acute icteric hepatitis is similar to that of younger patients, supporting the assumption that beneficial effects of hormonal changes associated with menopause are not as pronounced in AIH as in other autoimmune diseases. Human leukocyte antigen type seems to have an influence on the age of onset of AIH. Prognosis is excellent, and AIH should be considered in the older patient to avoid delayed initiation of immunosuppressive therapy.

Aged↗

Determination of cotton-bound glyoxal via an internal cannizzaro reaction by means of high-performance liquid chromatography.

Glyoxal, a non-formaldehyde cross-linking agent, was applied in combination with aluminum sulfate hexadecahydrate to impart durable-press properties to cellulosic materials. The cotton fabric was impregnated with a pad bath formulation containing 6% (w/w) glyoxal and 4.5% (w/w) aluminum sulfate hexadecahydrate. The curing process was conducted at 140 degrees C for 3 min, thus affecting a cross-linkage between the cellulose chains. For the first time, a chromatographic method is presented that enables both qualitative and quantitative analysis of the portion of glyoxal that has reacted with the cellulosic material. For this purpose, the glyoxal-treated fabric was treated with an NaOH solution (c = 4 mol L(-1)) at 100 degrees C for 20 min. As a result, glyoxal was extracted from the cellulosic sample and converted into glycolate via an internal Cannizzaro reaction. Subsequently, the glycolate was analyzed chromatographically using the strong cation-exchange column Aminex HPX-87H as the stationary phase and sulfuric acid as the mobile phase. The detection limit was 1.87 mg L(-1) (UV detection). The recovery was 85%. Dry crease wrinkle recovery measurements gave evidence that the cross-linkage was removed completely. The application of the analytical technique developed in the present study demonstrated that the amount of glyoxal that had reacted with the cellulose was 15.7 +/- 0.72 mg/g of fabric. In addition, glycolate thus formed was well separated from non-formaldehyde durable-press finishing agents based on polycarboxylic acids such as 1,2,3,4-butanetetracarboxylic acid or citric acid.

Carbohydrate Sequence↗

The Bbp1p-Mps2p complex connects the SPB to the nuclear envelope and is essential for SPB duplication.

In budding yeast, microtubules are organized by the spindle pole body (SPB), which is embedded in the nuclear envelope via its central plaque structure. Here, we describe the identification of BBP1 in a suppressor screen with a conditional lethal allele of SPC29. Bbp1p was detected at the central plaque periphery of the SPB and bbp1-1 cells were found to be defective in SPB duplication. bbp1-1 cells extend their satellite into a duplication plaque like wild-type cells; however, this duplication plaque then fails to insert properly into the nuclear envelope and does not assemble a functional inner plaque. This function in SPB duplication is probably fulfilled by a stable complex of Bbp1p and Mps2p, a nuclear envelope protein that is also essential for duplication plaque insertion. In addition, we found that Bbp1p interacts with Spc29p and the half-bridge component Kar1p. These interactions are likely to play a role in connecting the SPB with the nuclear envelope and the central plaque with the half-bridge.

Fungal Proteins↗

Rapid development of Epstein-Barr virus-associated Hodgkin's disease after cessation of foscarnet therapy in an HIV-infected patient.

Epidemiological features suggest a link between Hodgkin's disease (HD) and Epstein-Barr virus (EBV) infection. Indeed, EBV genome and expression of latent antigens can be found in Reed-Sternberg cells. In the majority of cases HD in HIV patients seems to be EBV-associated. We report on a 51-year-old HIV-infected patient in whom EBV-positive HD of mixed cellularity rapidly developed within one month after cessation of treatment with intravenous foscarnet.

Antiviral Agents↗

Combined therapy with azathioprine, prednisolone, and ursodiol in patients with primary sclerosing cholangitis. A case series.

BACKGROUND: No established medical therapy alters the progressive course of primary sclerosing cholangitis. OBJECTIVE: To explore the potential usefulness of combined therapy with azathioprine, steroids and ursodeoxycholic acid (UDCA) in primary sclerosing cholangitis. DESIGN: Case series. SETTING: University hospital in Mainz, Germany. PATIENTS: 15 patients with primary sclerosing cholangitis. INTERVENTION: Azathioprine (1 to 1.5 mg/kg of body weight per day), prednisolone (1 mg/kg per day initially, tapering to 5 to 10 mg per day) and UDCA (500 to 750 mg per day). MEASUREMENTS: Clinical and laboratory evaluation, liver biopsy, and endoscopic retrograde cholangiography (a >30% change in stenosis was considered significant). RESULTS: After a median observation period of 41 months (range, 3 to 81 months), liver enzyme levels declined significantly in all patients. Six of 10 patients with follow-up liver biopsies showed histologic improvement. Significant radiographic deterioration was seen in only 1 of 10 patients who had endoscopic retrograde cholangiography. In 7 patients previously treated with UDCA alone, liver enzyme levels declined significantly only after immunosuppressive therapy was added. Adverse drug reactions led to the withdrawal of study medications in 2 patients. CONCLUSIONS: Combined immunosuppressive therapy may alter the progression of primary sclerosing cholangitis. Our observations suggest a benefit from adding immunosuppressive drugs to UDCA therapy. A randomized trial is warranted.

Adult↗

Thiamine for the treatment of nucleoside analogue-induced severe lactic acidosis.

Nucleoside analogue-induced lactic acidosis is an often fatal condition in patients with HIV. There is only one report of successful treatment with riboflavin. We describe a 30-year-old female with AIDS and nucleoside analogue-induced lactic acidosis that exacerbated shortly after introducing total parenteral nutrition and reversed within hours after the addition of thiamine. Successful treatment of nucleoside analogue-induced lactic acidosis with a high dose of thiamine supports the hypothesis that vitamin deficiency is an important cofactor in the development of this rare and unpredictable condition in patients with HIV. We suggest that high dose B-vitamins should be given to any patient presenting with lactic acidosis under nucleoside analogue treatment.

Acidosis, Lactic↗

Expression of major histocompatibility complex class II molecules in rat T cells.

The expression of major histocompatibility complex (MHC) class II molecules in murine T cells has been controversial. We therefore reexamined the transcription, synthesis and surface expression of MHC class II determinants in rat T cells both in vivo and in vitro. In naive rats, a large proportion of small CD4+8+ and mature CD4+8-/CD4-8+ thymocytes was found to be MHC class II positive. At least some of the MHC class II molecules found on thymocytes were actively synthesized. The synthesis of MHC class II proteins was detected in peripheral T cells activated in vivo during induction of experimental allergic encephalomyelitis (EAE). A proportion of T cells from the inflammatory lesion of EAE exhibited MHC class II on the surface. A panel of helper T cell lines and clones was shown to synthesize MHC class II proteins. In a prototypic clone, a weak constitutive expression of MHC class II was observed. During activation, the rate of endogenous MHC class II synthesis increased and passive absorption of surface MHC class II from other cells occurred. Our data demonstrate the expression of MHC class II molecules in rat T cells in both the thymus and periphery. Since the primary function of MHC class II molecules is the presentation of peptide epitopes to T cells, these results call attention to the possible role of MHC class II molecules in T-T interactions during T cell maturation and activation.

Animals↗