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Biomedical subjects

C A Müller

Publications and source records attributed to C A Müller.

At least 19 recordsLinked to original sources

[Scapho-capitate fracture syndrome of both hands--first description of a bilateral occurrence of a rare carpal injury].

The scapho-capitate fracture syndrome is a rare but severe injury of the carpus. It is characterized by a rotation of the proximal fragment of the capitate bone of 90 or 180 degrees and a fracture of the navicular bone in the intermediate third. This injury is caused by a fall on the outstretched and dorsiflected hand. The scapho-capitate fracture syndrome was firstly described in 1956 by Fenton. There are 31 cases described in literature but none of these involves both hands. Here we describe the first case of scapho-capitate fracture syndrome in both hands, in a 21 year old woman who jumped out of a window with suicidal intentions. She was treated operatively by Herbert-screws and K-wires.

Adult↗

Hanle effect in coherent backscattering.

We study the shape of the coherent-backscattering (CBS) cone obtained when resonant light illuminates a thick cloud of laser-cooled rubidium atoms in the presence of a homogenous magnetic field. We observe new magnetic field-dependent anisotropies in the CBS signal. We show that the observed behavior is due to the modification of the atomic-radiation pattern by the magnetic field (Hanle effect in the excited state).

Journal Article↗

[Esophageal perforation. Etiology, diagnosis, therapy].

METHOD: Between 10/1997 and 2/2000 we treated eight patients (-66.5 y, 31-92 y, 5 male, 3 female). These cases were analyzed retrospectively. RESULTS: In one case the the perforation was located in the cervical part, in three cases in the intermediate part, and in four cases in the distal part oesophagus. In seven cases the perforation was caused by endoscopic and one acid burn in suicidal intention. Surgical treatment was performed in seven cases (87.5%), five of them with primary suture, two with primary esophageal resection. The mortality rate was 50%. There was no insufficiency of the suture, but two patients died because of pulmonary complications, one patient with known hepatic cirrhosis (Child C) because of an uncontrollable bleeding of his fundus and esophageal complications 5 days after successful surgical treatment, and one patient because of fulminant sepsis after dislocation of an enteral catheter. Three of the patients were operated within 12 hours after perforation, seven of them were operated within less than 24 hours. CONCLUSIONS: Surgical treatment of esophageal perforation within 24 hours after perforation shows good results. The outcome of the treatment depends on whether there are postoperative pulmonary complications and concomitant diseases. Enteral nutrition should be avoided in cases of primary esophageal resection to facilitate the surgical reconstruction at the second operation.

Adult↗

Serum levels of procarboxypeptidase B and its activation peptide in patients with acute pancreatitis and non-pancreatic diseases.

BACKGROUND: Carboxypeptidase B from the pancreatic gland may exist in three different molecular and immunoreactive forms: the proenzyme, the active enzyme, and the activation peptide. AIMS: To investigate levels of procarboxypeptidase B (proCAPB) and its activation peptide in serum in acute pancreatitis to test the accuracy of these two variables as markers for the diagnosis of acute pancreatitis and for prediction of pancreatic necrosis. To elucidate whether leakage of proenzymes and activation of proenzymes reflect two different pathophysiological events in acute pancreatitis. METHODS: Sera from patients with acute pancreatitis (n=85) and acute abdominal pain of non-pancreatic origin (n=53) were analysed for proCAPB and its activation peptide. Patients with pancreatitis were divided into necrotising (n=33) and oedematous attacks (n=52) using contrast enhanced computed tomography. Accuracy was determined using receiver operating characteristic curve analysis. RESULTS: Immunoreactive carboxypeptidase B activation peptide (ir-CAPAP) concentration in serum on admission was 0.7 nmol/l (0-18.1) in patients with oedematous pancreatitis compared with 5.8 nmol/l (1.9-34) in patients with later development of pancreatic necrosis. Elevated levels of the activation peptide on admission correlated with an accuracy of 92% to later development of pancreatic necrosis. Ir-proCAPB concentration in serum on admission was 16.0 nmol/l (1.4-50.5) in all patients with acute pancreatitis versus 0.3 nmol/l (0-3.6) in patients with non-pancreatic acute abdominal disorders. Cases with oedematous pancreatitis had ir-proCAPB levels of 15.4 nmol/l (1.4-50.5) versus 19.1 nmol/l (2.7-36.1) in cases with later development of pancreatic necrosis. Measurement of the proenzyme can thus be useful for the diagnosis of acute pancreatitis (accuracy 99%) but levels did not correlate with later development of pancreatic necrosis (accuracy 56%). CONCLUSION: Leakage of proenzymes occurs in acute pancreatitis, irrespective of severity, while development of pancreatic necrosis occurs only when there is activation of the proenzymes.

Abdominal Pain↗

Second German consensus on immunogenetic donor search for allotransplantation of hematopoietic stem cells.

The present paper summarizes the results of the second German consensus meeting on immunogenetic donor search for allotransplantation of hematopoietic stem cells held in Essen in November 1999 under the auspices of the German Society for Immunogenetics (DGI) and the German Working Party for Blood and Marrow Transplantation (DAG-KBT). Immunogeneticists and transplant physicians from all over the country agreed to update the national standards for: (1) search strategy including the role of unrelated and extended family donor search after unsuccessful core family donor search, (2) histocompatibility loci to be typed, (3) histocompatibility typing techniques to be used (HLA serology vs DNA-based HLA typing, cellular tests, serum cross-match), and (4) acceptable HLA mismatches in the context of a defined underlying disease, donor type, and conditioning regimen.

Aging↗

Pancreatic infection in severe pancreatitis: the role of fungus and multiresistant organisms.

HYPOTHESIS: Recent controlled clinical studies suggest a positive effect of early antibiotic treatment on late morbidity and mortality in severe acute pancreatitis. However, widespread use of antibiotics may lead to an increased number of fungal infections and multiresistant bacteria, thereby worsening the outcome of the disease. DESIGN: Single-center prospective study. SETTING: University hospital, gastrointestinal surgical service. PATIENTS: One hundred three patients with necrotizing pancreatitis seen consecutively in our service. INTERVENTIONS: In addition to standard treatment, patients with proven necrotizing pancreatitis received a prophylactic intravenous antibiotic treatment. Pancreatic infection was regarded as an indication for surgery. MAIN OUTCOME MEASURES: Pancreatic infection, microbiological findings, drug resistance, fungal infections. RESULTS: Thirty-three patients (32%) had infected necrosis. Gram-negative organisms were isolated from 19 patients (58%), Gram-positive organisms were isolated from 18 patients (55%), fungal organisms were isolated from 8 patients (24%), and multiresistant organisms were isolated from 3 patients (9%). In 7 patients (21%), the organisms cultured from the pancreatic tissue were resistant to the antibiotics given in for prophylaxis. Infection with multiresistant organisms or organisms resistant to the antibiotic used for prophylaxis, but not with fungal infection or Gram-positive or Gram-negative infection, was correlated with a negative outcome. CONCLUSIONS: Fungal infection under adequate treatment is not associated with a negative outcome. The occurrence of multiresistant organisms seems to be a rare finding (3 of 103 patients). Antibiotic prophylaxis is effective in preventing infection in necrotizing pancreatitis, but optimal choice and duration of administration of the antibiotic agent(s) need to be carefully determined to avoid the sequelae of multiresistant organisms.

Adult↗

[Esophageal perforation by osteosynthesis material after ventral spondylodesis of the cervical spine].

Esophageal perforation after cervical spine surgery is a rare complication. Based on the case of a 77-year-old female patient with a late, asymptomatic esophageal perforation after a ventral spondylodesis of the cervical spine, the symptoms, diagnostics, and therapy of this complication are discussed. The therapy of choice is the operation. Nonoperative therapy should only be chosen--like in our case--for special indications. An esophageal perforation with symptoms should be treated operatively. Our patient was treated conservatively in consideration of her age and missing symptoms.

Aged↗

Comparative analysis of the association of HLA-B*51 suballeles with Behçet's disease in patients of German and Turkish origin.

The distribution of the different HLA-B*51 suballeles among patients with Behçet's disease (BD) of German (n=33) and Turkish (n=92) origin in comparison to their presence in the respective ethnically matched healthy control groups (German: n=325, Turkish: n=93) was studied. HLA-B*51x was significantly increased in both patient groups in comparison to the controls (Germans: 58% vs. 12%, OR 9.76, P<0.001; Turkish: 75% vs. 25%, OR 9.13, P<0.001). Molecular subtyping of B*51x revealed HLA-B*51011 and B*5108 as the predominant suballeles in both patient groups and controls although with a slightly increased frequency of HLA-B*5108 in the diseased individuals. HLA-B*5105 was the only further HLA-B*51x subtype detected in one Turkish patient heterozygous also for HLA-B*5101. HLA-B*5107 although present in a Turkish as well as German control was absent in the patient groups. There was also a tendency towards a higher degree of homozygosity for HLA-B*51x in both patient groups versus the matched controls (Germans: 10% in patients vs. 2,5% in controls; Turkish: 27% in patients vs. 13% in controls). Our study further supports previous hypothesis of an association of BD with B51 suballeles which share amino-acid residues at positions 63 and 67 as well as at positions 77-83 for specific peptide binding and natural killer (NK)-cell interactions. This applies to HLA-B*5101 and B*5108, but not to HLA-B*5107 different at position 67, which could be negatively associated with BD.

Alleles↗

Late mortality in patients with severe acute pancreatitis.

BACKGROUND: Mortality due to severe or necrotizing acute pancreatitis most often results from multiorgan dysfunction syndrome (MODS) occurring either early (within the first 14 days) or 2 weeks or more after the onset of symptoms due to septic complications. The aim of this study was to analyse the course of the disease in patients who died from severe acute pancreatitis. METHODS: Between January 1994 and August 2000 details of 263 consecutive patients with acute pancreatitis were entered prospectively into a database. All patients were treated in an intermediate or intensive care unit. RESULTS: The overall mortality rate was 4 per cent (ten of 263 patients). The mortality rate was 9 per cent (ten of 106) in patients with necrotizing disease. No patient died within the first 2 weeks of disease onset. The median day of death was 91 (range 15-209). Six patients died from septic MODS. Ranson score, Acute Physiology and Chronic Health Evaluation (APACHE) II score during the first week of disease, pre-existing co-morbidity, body mass index, infection and extent of necrosis were significantly associated with death (P < 0.01 for all parameters). However, only infection of the necrotic pancreas was an independent risk factor in the multivariate analysis. CONCLUSION: Early deaths in patients with severe acute pancreatitis are rare, mainly as a result of modern intensive care treatment. Nine of the ten deaths occurred more than 3 weeks after disease onset. Infection of pancreatic necrosis was the main risk factor for death.

APACHE↗

Sporadic cerebellar ataxia associated with gluten sensitivity.

A total of 104 patients with sporadic cerebellar ataxia were tested for antigliadin and antiendomysium antibodies. Twelve individuals (11.5%) with gluten sensitivity underwent duodenal biopsy and extensive clinical, electrophysiological, neuropsychological, radiological and laboratory investigations including human leucocyte antigen (HLA) typing. Two patients showed typical changes of gluten-sensitive enteropathy with crypt hyperplasia and mucosal flattening. In five patients, the intraepithelial lymphocyte count was elevated. Sporadic ataxia with gluten sensitivity was found to be tightly linked to the HLA DQB1*0201 haplotype (70%). Neurological symptoms were not related to hypovitaminosis or inflammatory CSF changes. The clinical syndrome was dominated by progressive cerebellar ataxia with ataxia of stance and gait (100%), dysarthria (100%) and limb ataxia (97%). Oculomotor abnormalities were gaze-evoked nystagmus (66.7%), spontaneous nystagmus (33.3%), saccade slowing (25%) and upward gaze palsy (16.7%). Extracerebellar features also included deep sensory loss (58.3%), bladder dysfunction (33.3%) and reduced ankle reflexes (33.3%). In accordance with clinical findings, electrophysiological investigations revealed prominent axonal neuropathy with reduced amplitudes (50%) and abnormal evoked potentials (58.3%). On neuropsychological testing, patients presented with moderate verbal memory and executive dysfunction. All patients had evidence of cerebellar atrophy on MRI. We conclude that sporadic ataxia may be associated with positive antibodies against gliadin. Nevertheless, mucosal pathology does not represent an obligatory condition of ataxia with gluten sensitivity. The fact that the disease is strongly associated with the same HLA haplotypes found in coeliac disease not only demonstrates coeliac disease and ataxia with gluten sensitivity to be part of the same disease entity but supports the hypothesis of an immunological pathogenesis of cerebellar degeneration.

Adult↗

Thrombolytic effect of lonomin V in a rabbit jugular vein thrombosis model.

Thrombolytic efficacy of lonomin V (LV), a protein isolated from Lonomia achelous caterpillars haemolymph, administered either as a single intravenous bolus or as a continuous infusion, was evaluated in a rabbit jugular vein thrombosis model, and compared with those of single-chain tissue-type plasminogen activator (sct-PA) and two-chain urokinase-type plasminogen activator (tcu-PA). As a bolus LV, at doses of 100 000 IU/kg body weight (bw) produced an activator-induced thrombolysis (AIL) of 50.94% +/- 12.4 compared with 14.4% +/- 10.8 for tcu-PA at the same dose. As a continuous infusion at doses of 200 000 IU/kg bw LV produced an AIL of 45.8%, whereas sct-PA and tcu-PA produced an AIL of 69.9 and 33.7%, respectively. Fibrinogen, plasminogen and alpha-2-antiplasmin levels decreased significantly with the higher doses of LV, sct-PA, and tcu-PA. Factor XIII levels were significantly reduced in a dose-dependent manner only with LV. In conclusion, LV produces a dose-dependent thrombolysis in combination with a decrease in factor XIII activity.

Animals↗

N-cadherin is developmentally regulated and functionally involved in early hematopoietic cell differentiation.

The cadherins, an important family of cell adhesion molecules, are known to play major roles during embryonic development and in the maintenance of solid tissue architecture. In the hematopoietic system, however, little is known of the role of this cell adhesion family. By RT-PCR, western blot analysis and immunofluorescence staining we show that N-cadherin, a classical type I cadherin mainly expressed on neuronal, endothelial and muscle cells, is expressed on the cell surface of resident bone marrow stromal cells. FACS analysis of bone marrow mononuclear cells revealed that N-cadherin is also expressed on a subpopulation of early hematopoietic progenitor cells. Triple-color FACS analysis defined a new CD34(+) CD19(+) N-cadherin(+) progenitor cell population. During further differentiation, however, N-cadherin expression is lost. Treatment of CD34(+) progenitor cells with function-perturbing N-cadherin antibodies drastically diminished colony formation, indicating a direct involvement of N-cadherin in the differentiation program of early hematopoietic progenitors. N-cadherin can also mediate adhesive interactions within the bone marrow as demonstrated by inhibition of homotypic interactions of bone-marrow-derived cells with N-cadherin antibodies. Together, these data strongly suggest that N-cadherin is involved in the development and retention of early hematopoietic progenitors within the bone marrow microenvironment.

Bone Marrow Cells↗

Dysregulated L-selectin expression on lymphocytes in patients with chronic venous insufficiency.

In this study we analysed blood samples taken from the dorsalis pedis vein and a brachial vein of 11 healthy test persons and 8 patients with venous leg ulcer under experimental venous hypertension in order to examine changes in the expression of leukocyte adhesion molecules (LFA-1 (CD11a), Mac-1 (CD11b), p150,95 (CD11c), CD18, VLA-4 (CD49d) and L-selectin (CD62L)) which are involved in the adhesion steps of leukocytes to endothelial cells for transmigration into tissues. Under orthostatic stress, lymphocytes in controls collected at the foot level showed a significant reduction in the expression of L-selectin (p=0.002), compared to those of patients. This finding suggests that venous stasis negatively influences the expression of L-selectin on leukocytes only in healthy volunteers. Patients with chronic venous insufficiency seem to suffer from a specific defect in the regulation of L-selectin shedding under orthostatic stress.

Adult↗

Characterization and functional analysis of laminin isoforms in human bone marrow.

Laminins are a family of disulfide-linked heterotrimeric proteins consisting of 3 different subunits termed alpha, beta, and gamma chains. Combinations of 11 characterized laminin subunits (alpha 1-alpha 5, beta 1-beta 3, and gamma 1-gamma 3) generate at least 12 laminin isoforms, which can serve different functions. Although expression of laminin in the hematopoietic microenvironment has been known for many years, the nature of the laminin isoforms present in the human bone marrow is poorly characterized. The present study attempts to clarify this issue. Reverse transcriptase-polymerase chain reaction analysis of human bone marrow stromal cells suggested the expression of many laminin isoforms in the marrow. Northern blot and immunoblot analysis, however, showed that laminin-8/9 and laminin-10/11 are the most abundant laminin isoforms synthesized by human bone marrow stromal cells. Other isoforms, if present, certainly play a minor role in the hematopoietic microenvironment. Functionally, laminin-10/11 preparations showed strong adhesive interactions with human CD34(+) cell lines. Antibodies against the beta 1 integrin subunit inhibited these interactions. Other laminin isoforms, especially laminin-1 and laminin-2/4, showed only weak or no adhesive interactions with the hematopoietic cell lines tested, explaining former negative results. In addition to its adhesion-mediating properties, laminin-10/11 preparations also showed a mitogenic activity for human hematopoietic progenitor cells. Taken together, these data suggest that laminin in the bone marrow plays a hitherto unexpected important function in the development of hematopoietic progenitor cells. (Blood. 2000;96:4194-4203)

Blotting, Western↗

[Indications for surgical therapy and operative technique in acute pancreatitis].

Eighty to eighty-five percent of all episodes of acute pancreatitis are mild and self-limiting, subsiding within a few days. In the remaining 15 to 20% of cases, however, severe necrotizing disease complicated by multiple organ dysfunction syndrome (MODS) develops. Early stratification according to disease severity is a cornerstone in the management of patients with acute pancreatitis. Patients suffering from mild disease do not need to be operated upon unless specific conditions such as bile duct stones, a tumour at the papilla of Vater or in the head of the pancreas are present. Patients suffering from severe disease are best managed by early intensive care treatment, including antibiotics penetrating into the pancreas in order to prevent infection of the necrotic tissue. Despite such a treatment infection occurs in up to one third of necrotizing cases, asking for surgical treatment. The latter consists of an organ preserving procedure, combined with a continuous postoperative lavage of the retroperitoneum. In 75% of our patients treated operatively, one surgical intervention was sufficient. Overall mortality in patients with necrotizing pancreatitis ranges, according to the current literature, between 6 and 50% and reaches 8% in our own series.

Critical Care↗

Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids.

Reports of spontaneous regressions of metastases and the demonstration of tumor-reactive cytotoxic T lymphocytes indicate the importance of the host's immune system in controlling the devastating course of metastatic renal cell carcinoma. Recent research indicates that immunization with hybrids of tumor and antigen presenting cells results in protective immunity and rejection of established tumors in various rodent models. Here, we present a hybrid cell vaccination study of 17 patients. Using electrofusion techniques, we generated hybrids of autologous tumor and allogeneic dendritic cells that presented antigens expressed by the tumor in concert with the co-stimulating capabilities of dendritic cells. After vaccination, and with a mean follow-up time of 13 months, four patients completely rejected all metastatic tumor lesions, one presented a 'mixed response', and two had a tumor mass reduction of greater 50%. We also demonstrate induction of HLA-A2-restricted cytotoxic T cells reactive with the Muc1 tumor-associated antigen and recruitment of CD8+ lymphocytes into tumor challenge sites. Our data indicate that hybrid cell vaccination is a safe and effective therapy for renal cell carcinoma and may provide a broadly applicable strategy for other malignancies with unknown antigens.

Aged↗

Risk factors for treatment failures in patients receiving PCR-based preemptive therapy for CMV infection.

PCR-based preemptive therapy with ganciclovir has been shown to reduce the incidence of CMV disease after BMT. Failures of this treatment strategy are CMV disease and secondary non-viral infections. Eighty-six consecutive patients at high risk for CMV disease who received PCR-based preemptive therapy with ganciclovir were assessed for treatment failures and possible risk factors. Ganciclovir was initiated in 57 of 86 patients (66%). Only 28 of 86 (32%) patients received 4 or more weeks of ganciclovir. Recurrence of CMV infection after successful treatment was more frequent among recipients of a BMT from an unrelated compared to a sibling donor (P = 0.004). Three (3.5%) patients developed non-fatal early onset CMV disease and seven of 68 (10.3 %) late onset CMV disease (>100 days post transplant). Risk factors for late onset CMV disease were cGVHD (P = 0.0017) and duration of prior antiviral therapy >4 weeks (P = 0. 0073). The incidence of secondary non-viral infections was 28% with the duration of antiviral treatment being a significant risk factor for secondary bacterial (P = 0.0045) and invasive fungal infections (P = 0.006). Thus, PCR-based preemptive treatment with ganciclovir reduces early onset CMV disease, but the duration of antiviral therapy prior to day +100 is a significant risk factor for late onset CMV disease as well as secondary non-viral infections.

Adolescent↗

Acute necrotizing pancreatitis: treatment strategy according to the status of infection.

OBJECTIVE: To determine benefits of conservative versus surgical treatment in patients with necrotizing pancreatitis. SUMMARY BACKGROUND DATA: Infection of pancreatic necrosis is the most important risk factor contributing to death in severe acute pancreatitis, and it is generally accepted that infected pancreatic necrosis should be managed surgically. In contrast, the management of sterile pancreatic necrosis accompanied by organ failure is controversial. Recent clinical experience has provided evidence that conservative management of sterile pancreatic necrosis including early antibiotic administration seems promising. METHODS: A prospective single-center trial evaluated the role of nonsurgical management including early antibiotic treatment in patients with necrotizing pancreatitis. Pancreatic infection, if confirmed by fine-needle aspiration, was considered an indication for surgery, whereas patients without signs of pancreatic infection were treated without surgery. RESULTS: Between January 1994 and June 1999, 204 consecutive patients with acute pancreatitis were recruited. Eighty-six (42%) had necrotizing disease, of whom 57 (66%) had sterile and 29 (34%) infected necrosis. Patients with infected necrosis had more organ failures and a greater extent of necrosis compared with those with sterile necrosis. When early antibiotic treatment was used in all patients with necrotizing pancreatitis (imipenem/cilastatin), the characteristics of pancreatic infection changed to predominantly gram-positive and fungal infections. Fine-needle aspiration showed a sensitivity of 96% for detecting pancreatic infection. The death rate was 1.8% (1/56) in patients with sterile necrosis managed without surgery versus 24% (7/29) in patients with infected necrosis (P <.01). Two patients whose infected necrosis could not be diagnosed in a timely fashion died while receiving nonsurgical treatment. Thus, an intent-to-treat analysis (nonsurgical vs. surgical treatment) revealed a death rate of 5% (3/58) with conservative management versus 21% (6/28) with surgery. CONCLUSIONS: These results support nonsurgical management, including early antibiotic treatment, in patients with sterile pancreatic necrosis. Patients with infected necrosis still represent a high-risk group in severe acute pancreatitis, and for them surgical treatment seems preferable.

Adolescent↗