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Biomedical subjects

C Ulrich

Publications and source records attributed to C Ulrich.

At least 55 records · Page 3Linked to original sources

Necrotising fasciitis-cryptogenic infection following posttraumatic immunopathy?

Even in the era of broad-spectrum antibiotics, necrotising fasciitis is still a life-threatening disease. It occurs not only after direct skin laceration but also in contused areas with secondary hematogenic infection. Early diagnosis and immediate surgical intervention are imperative to improve the survival rate. This disease often leads to secondary multiorgan, (particularly renal) failure. A pathophysiological pathway based on an immunological disorder of the host is presented in relation to a case report.

Adult↗

Physical activity and cancer etiology: associations and mechanisms.

OBJECTIVES: This paper reviews the epidemiologic data of associations between physical activity and cancer risk, describes potential mechanisms for a physical activity cancer link, and proposes future directions for research. METHODS: We reviewed English-language published papers on physical activity and cancer through Medline searches for epidemiologic studies, and through references on individual reports. We reviewed general texts on effects of exercise on human biology and applied the concepts to the biology of cancer in humans to describe potential mechanisms for a physical activity-cancer association. RESULTS: Considerable epidemiologic evidence has accrued linking increased physical activity with reduced occurrence of cancers of the breast and colon. The association between physical activity and cancers of other sites is unclear. Potential mechanisms for the association between physical activity and reduced risk for breast and colon cancer are varied: they range from bias due to physical activity's strong correlations with other health factors (e.g., diet, smoking, alcohol use, use of medications) to the metabolic effects resulting from increased physical activity and fitness, such as reduced obesity, hormonal and reproductive effects, mechanical effects, and enhancement of the immune system. CONCLUSIONS: The elucidation of biologic mechanisms for an association between physical activity and cancer may provide biological support for the association. It will contribute information to determine the type, frequency, and duration of exercise needed to maximize protection. This information will be needed before large-scale community interventions are begun, in order to choose the correct interventions for the desired effect of reduced incidence of the most common cancers.

Adult↗

Anthropometric and hormone effects of an eight-week exercise-diet intervention in breast cancer patients: results of a pilot study.

To assess the feasibility of an exercise-diet intervention in sedentary, overweight breast cancer patients, we conducted a pilot 8-week intervention. Recruitment letters and interest surveys were sent to 99 stage 1 or 2 breast cancer patients, ages 25-75 years, who were identified through two Seattle breast surgery practices and the University of Washington Breast Clinic. Ten patients were eligible and interested and were enrolled in the intervention, which consisted of thrice-weekly monitored aerobic exercise sessions and a low-fat (20% of calories from fat) diet. Nine patients completed the program; all adhered well to the intervention and data collection protocol. The patients, ages 40-74 years, lost, on average, 2.6 pounds of body weight, 3.4 cm in waist circumference, 4.6 cm in hip circumference, 2.3% body fat, 3.3 systolic blood pressure points, 0.67 diastolic blood pressure points, and 4.0 pulse beats/min, and they gained an average of 2.3% lean mass. Slight, nonsignificant decreases were observed in serum concentration of total and free estradiol, estrone sulfate, total testosterone, androstenedione, and dehydroepiandrosterone. These pilot data indicate that breast cancer patients are highly motivated to join and adhere to an intense exercise-diet intervention and can experience significant measurable changes in anthropometric and fat mass measures.

Adult↗

[Seidel humerus intramedullary nailing. Clinical results of 100 surgeries].

Between 01.01.88 and 30.07.94 we treated 81 traumatic and 19 pathologic humeral shaft fractures with the Seidel humeral locking nail (HLN). The majority of the 100 patients (60 women, 40 men) were older than 60 years of age. The dominant fracture type according to AO was type A. Operative stabilization was considered indicate because of fracture distraction during functional bracing in most cases. In general, patients choose surgical intervention in preference to conservative management. Radiological consolidation was observed within 10 weeks. In 48 cases sonography revealed motor disturbances between the gliding sheath of the rotator cuff, but there was no correlation between this and the shoulder mobility. In 7 cases an additional fracture was created during introduction of the nail. This complication can be avoided by using the right technique. There were no cases of non-union or radial nerve lesion. There were 2 patients who developed an infection, which disappeared after removal of the nail and introduction of antibiotic-loaded beads. Functional results were recorded in 63 patients: 53 patients (84%) had an excellent or satisfactory result (NEER score > 80). Among the others, problems at the site of nail insertion predominated. In our view, the Seidel humeral locking nail is an implant that provides exercise stability without intraoperative positioning problems or risk of injury to nerves or vessels. Nevertheless, this method needs a skilled surgeon with special training to handle typical technical nailing problems.

Adult↗

Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis.

BACKGROUND & AIMS: We recently identified a single R117H mutation in the cationic trypsinogen gene in several kindreds with an inherited form of acute and chronic pancreatitis (HP1), providing strong evidence that trypsin plays a central role in premature zymogen activation and pancreatitis. However, not all families studied have this mutation. The aim of this study was to determine the disease-causing mutation in kindreds with hereditary pancreatitis that lack the previously identified mutation. METHODS: Clinical features of the HP1 kindreds were compared with those of the new kindreds (HP2), and genetic linkage analysis, screening for mutations through DNA sequencing, and screening an unaffected population were performed. RESULTS: The onset of symptoms was delayed and hospitalizations were fewer in HP2 compared with HP1 (P < 0.05). Linkage of the disease gene to chromosome 7q35 was established (logarithm of the odds, 3.73). Mutational screening identified a single A to T mutation resulting in an asparagine to isoleucine transition mutation at position 21 (N21I) in cationic trypsinogen. The mutation was absent in 94 unrelated individuals, representing 188 unique chromosomes. CONCLUSIONS: The identification of a second mutation in the cationic trypsinogen gene (HP2) suggests a dominant role of trypsin in premature protease activation-mediated forms of acute pancreatitis. The pathogenesis of hereditary pancreatitis also suggests that chronic pancreatitis may result from recurrent acute pancreatitis.

Acute Disease↗

Molecular and functional heterogeneity of cholangiocytes from rat liver after bile duct ligation.

Cholangiocytes, the epithelial cells that line intrahepatic bile ducts, participate in bile secretion via basal and agonist-stimulated transport of solutes and water. On the basis of subtle structural differences between cholangiocytes lining small vs. large bile ducts, as well as known phenotypic variations among transporting epithelia in other organs, we demonstrated that cholangiocytes are functionally heterogeneous along the intrahepatic biliary tree of normal rats. In studies reported here, we confirm and extend the concept of functional heterogeneity of cholangiocytes by employing the bile duct-ligated (BDL) rat model of cholestasis associated with selective cholangiocyte proliferation. Using novel isolation and separatory techniques, we prepared subpopulations of pure small, medium, and large cholangiocytes from BDL rats and compared them with regard to gene expression and basal or agonist-responsive transport activities. Although transcripts for gamma-glutamyl transpeptidase and cytokeratin 19, two cholangiocyte-specific proteins, and glyceraldehyde-3-phosphate dehydrogenase, a housekeeping gene, were in all three subpopulations, genes for several proteins involved in solute transport [Cl-/HCO3- exchanger, cystic fibrosis transmembrane conductance regulator (CFTR), and secretin receptor] were expressed only in medium and large cholangiocytes. Consistent with these findings, secretin increased intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) and 36Cl- efflux rates in medium and large cholangiocytes but not in small cholangiocytes. Also, forskolin/8-(4-chlorophenylthio)-cAMP stimulated 36Cl- efflux rates only in medium and large cholangiocytes, consistent with selective functional expression of CFTR in these subpopulations. These results support the molecular and functional heterogeneity of cholangiocytes within the intrahepatic biliary ductal system and are consistent with the notion that hormone-regulated transport of solutes after BDL occurs principally in medium and large cholangiocytes in a fashion similar to that observed in normal rat liver.

Animals↗

Critical illness polyneuropathy in multiple organ dysfunction syndrome and weaning from the ventilator.

BACKGROUND: Acute axonal polyneuropathy has been found in patients with multiple organ dysfunction syndrome. This 'critical illness polyneuropathy' (CIP) has been associated with difficult weaning from the ventilator in retrospective studies. OBJECTIVE: To test the hypothesis that CIP is related to the degree and number of organ dysfunctions, and to weaning problems. DESIGN: Prospective study of 18 months. SETTING: A multidisciplinary intensive care unit in a general hospital SUBJECTS: Thirty-eight patients under 75 years of age who had been mechanically ventilated for more than 7 days, without previous signs of or risk factors for polyneuropathy. MEASURES: Organ dysfunctions were quantified using a dynamic scoring system (0-12 points). Electromyography studies were performed during mechanical ventilation to identify patients with and without CIP. RESULTS: CIP was present in 18 out of 38 patients and associated with an increased organ dysfunction score (5.3 +/- 1.8 vs. 3.6 +/- 1.5; p = 0.003) and number of organs involved [median (range): 4 (3-5) vs. 2 (1-4); p = 0.009], in particular cardiovascular (p = 0.003), renal (p = 0.04), and hematopoietic failure (p = 0.04). Patients with polyneuropathy were ventilated longer, but this was not clearly due to more difficult weaning [median: 16.5 (1-48) vs. 9.5 (1-38) days; p = 0.26]. Polyneuropathy was present in 2 of 4 patients with normal weaning. CONCLUSIONS: Axonal polyneuropathy is related to the severity of multiple-organ-dysfunction syndrome. Its presence does not necessarily implicate difficult weaning from artificial ventilation.

APACHE↗

A gene for hereditary pancreatitis maps to chromosome 7q35.

BACKGROUND & AIMS: Hereditary pancreatitis (HP) is an autosomal-dominant disorder with incomplete penetrance characterized by recurrent bouts of severe epigastric pain with onset usually at 5-10 years of age. A genetic linkage study was designed to identify the HP gene. METHODS: A 500-member pedigree was constructed from a U.S. kindred centered in eastern Kentucky and western Virginia. A genome-wide search strategy was employed using a 36-member subset of this family to determine the genetic locus for HP. Testing for linkage to microsatellite loci was performed at 20-cM intervals. RESULTS: Linkage was established between the HP phenotype and chromosome 7q in this subset of the family. Modeled as an autosomal dominant disorder with 80% penetrance, a maximal multipoint logarithm of the odds score of 4.3 was obtained using a four-point analysis consisting of markers D7S684, D7S661, D7S505, and the HP locus. Two microsatellite markers, D7S661 and D7S505, that correspond to the 7q35 region of chromosome 7 spanning a 6-cM region did not evidence obligate recombinations with HP. The centromeric and telomeric limits are defined by recombinations at D7S684 and D7S483, respectively, which generates a 19-cM locus for HP. Utilizing family members from the extended pedigree, a break in the high-risk haplotype between D7S684 and D7S661 was observed, which suggests it may be possible to exclude an additional 8 cM from the HP locus. A maximal pairwise logarithm of the odds score of 4.73 at a recombination fraction of theta at D7S684 was obtained with the addition of these extended family members. CONCLUSIONS: Linkage of HP to 7q35 represents a major advancement in our understanding of the genetic basis of this disorder.

Chromosome Mapping↗

Process improvement plan for the reduction of nosocomial pneumonia in patients on ventilators.

Pneumonia is a frequently occurring nosocomial infection that often results in serious illness and death of the patient. In one hospital, after the discovery of a ventilator-associated nosocomial infection rate that was higher than the national standard, a multidisciplinary team was formed. The team followed the FOCUS-PDCA model of quality improvement to identify methods to improve the nosocomial pneumonia infection rate for mechanically ventilated patients. Three areas of potential improvement were identified: trial of a closed suction system, policies and procedures for cleaning of ventilators, and staff education. Additionally, a research project was conducted to identify predictors of ventilator-associated nosocomial pneumonia. These projects resulted in a reduction of the ventilator-associated nosocomial pneumonia infection rate to 8.3/ 1,000 ventilator days and a cost savings of more than $580,000.

Adult↗

Treatment with the platelet-activating factor antagonist TCV-309 in patients with severe systemic inflammatory response syndrome: a prospective, multi-center, double-blind, randomized phase II trial.

In a prospective randomized, double-blind, placebo-controlled clinical study, the safety and efficacy of the platelet-activating factor antagonist TCV-309 in the treatment of systemic inflammatory response syndrome was studied. In total 29 patients were treated with 1.0 mg/kg TCV-309 twice daily during 7 days or with placebo. Study parameters were as follows: adverse events, 28 and 56 day all cause mortality, multi-organ failure scores, and the inflammatory mediators tumor necrosis factor, interleukin 6, interleukin 8, and soluble E-selectin. There was no difference in number and severity of adverse events between TCV-309- and placebo-treated patients. Day 28 and day 56 mortality was similar in both groups (day 56: 7/12 TCV-309 vs. 9/16 placebo, NS). Pulmonary and hematological failure scores improved significantly in TCV-309-treated patients (p < .05). There was no difference in inflammatory mediator levels between TCV-309- and placebo-treated patients. Treatment with TCV-309 appears to be safe in patients with systemic inflammatory response syndrome and does improve organ failure significantly.

Adult↗

[Craniocerebral trauma in fall from bicycles--what is the effect of a protective helmet?].

A prospective study was performed to analyze the particular injuries of 76 cyclists who required in-patient treatment in our department in 1994. There were 50 male and 26 female cyclists, with a median age of 33 years (range: 4-87 years). The most frequent diagnosis, in 50% (n = 38), was head injury. The series included 63 cyclist (83%) who had not been wearing helmets, and 33 of these sustained a head injury; in the helmet group head injury was found in only 38% (5 out of 13). It is remarkable that more serious head injuries did not occur in the helmet group. In 24 of these 33 head-injured patients (73%) without helmets additional intra- and extracranial diagnoses were made: pathologic EEG in 18 patients (55%), skull fracture in 13 patients (39%), intracerebral haemorrhagic contusion in 4 patients (12%) and an increase in intracerebral pressure (edema) in 3 patients (9%). In contrast to these findings, only 2 of the 5 head-injured patients (40%) in the helmet group showed slight changes in the EEG. In our opinion the bicycle helmet can reduce the incidence and the grade severity of head injuries significantly, particularly as we had 2 deaths in the non-helmet group and none in the helmet group. The use of a bicycle helmet is therefore strongly advocated.

Adolescent↗

Detection of disturbed autoregulation of the peripapillary choroid in primary open angle glaucoma.

BACKGROUND AND OBJECTIVE: This study is concerned with perfusion-pressure videoangiographic investigations, performed by combining oculo-oscillo-dynamography and videoangiography. Perfusion-pressure videoangiography permits an evaluation of local vascular resistance in the choroid relative to ciliary perfusion pressure. PATIENTS AND METHODS: Twelve healthy subjects, 21 patients with primary open angle glaucoma (POAG), and 27 patients with ocular hypertension were examined. RESULTS: Perfusion-pressure videoangiograms revealed that the peripapillary choroid (nasal main ciliary artery) filled at distinctly lower perfusion pressures than the paramacular region (temporal main ciliary artery) in all 12 healthy subjects, with a perfusion pressure difference of 12.5 +/- 4.9 mm Hg. In the 21 patients with POAG, the perfusion pressure difference between the beginning of peripapillary and paramacular perfusion was as small as 3.7 +/- 4.5 mm Hg. In the 27 patients with ocular hypertension, the perfusion pressure difference between the two circulatory regions was almost as high as in the healthy subjects. CONCLUSIONS: These examinations showed that (1) there exists efficient autoregulation in the peripapillary choroids of healthy subjects, (2) autoregulation is diminished or even absent in POAG, and (3) autoregulation is normal, increased, or slightly reduced in ocular hypertension.

Adolescent↗

[Ultrasound imaging of the anterior cruciate ligament. Possibilities and limits].

We carried out sonography of the femoral origin of the anterior cruciate ligament in the dorsal cross section with a 7.5-MHz linear scanner in 25 test subjects with healthy knee joints. A physiological difference between the sides in the size of the hypoechoic region of the origin could be defined on the basis of the measurements obtained in both knee joints. Values outside a reference range which could be evaluated from this difference were rated as pathological in terms of an anterior cruciate ligament rupture. The reliability of this method in definitively diagnosing an anterior cruciate ligament rupture was analysed statistically as compared to the golden standard of arthroscopy on 65 patients by means of the two-by-two frequency table test. The femoral origin of the cruciate ligament in 25 test subjects had a median width of 3.1 mm (range 1.7-5.8 mm) on the right and 3.4 mm (range 1.7-4.4 mm) on the left. The median difference between the sides is 0.4 mm (range 0-1.8 mm). If the 3rd to the 97th percentile is selected as the reference range, our data show a physiological difference between the sides of 0-1.5 mm. The median age of the 65 patients was 31 years (range 14-74 years). Two thirds of all patients were men. A rupture of the anterior cruciate ligament was diagnosed sonographically in 19 patients. The result was confirmed arthroscopically in 15 patients. In 4 patients, there was a false positive sonographic finding. Forty-six patients did not fulfil the sonographic criteria of a rupture of the anterior cruciate ligament. Of these, 38 showed an intact anterior cruciate ligament on arthroscopy. Eight patients had a false-negative sonographic finding. The corresponding statistical analysis showed sensitivity of 65%, specificity of 90% and precision of 79%. Accordingly, the diagnostic reliability of knee joint sonography in diagnosing a rupture of the anterior cruciate ligament appears to be unsatisfactory, since old ruptures, above all, cannot be imaged with certainty (sensitivity 65%). On the other hand, a positive sonographic finding points with relative certainty to a rupture of the anterior cruciate ligament even before the operation (precision 79%). Histological analysis of the cruciate ligament preparations obtained intraoperatively showed that in particular the fresh anterior cruciate ligament rupture can be imaged sonographically. Retrospectively, knowledge of the history is thus crucial for interpretation of the sonographic image. After acute trauma to the knee, a side difference in the femoral region of origin of the anterior cruciate ligament of more than 1.5 mm, as revealed sonographically, is a certain indication that the anterior cruciate ligament is ruptured. When there is a positive sonographic finding, ligament strain, synovial bleeding and partial ruptures of the anterior cruciate ligament as well as plica ruptures must be considered as possible diagnoses.

Adolescent↗

[Advantage of load-bearing osteosynthesis of pertrochanteric fractures in geriatric traumatology].

The problems experienced by most patients with trochanteric fractures are caused by their advanced age, particularly multimorbidity and osteoporosis, and due to this early postoperative functional treatment is only possible with full weight-bearing ability. To avoid perforation of the femoral head by overstress and collapse of the weak cancellous bone, any stabilizing device should be designed with an H-beamed blade, providing a large load-bearing surface. In our experience the 130 degrees-Double-T-blade-Plate is an effective implant for the treatment of pertrochanteric fractures, offering high stability, a large load-bearing surface, comparable complications with those known in other devices, easy and fast implantation, and low costs.

Aged↗

Molecular cloning and functional expression of a human pancreatic secretin receptor.

Through binding to high affinity receptors, secretin is the major hormonal stimulant of ductular bicarbonate secretion in the pancreas, contributes toward enzyme secretion from pancreatic acinar cells, and has been implicated as a pancreatic growth factor. In this work, we utilized hybridization screening of a human pancreatic cDNA library to clone a 1.8-kb cDNA encoding a 440 amino acid protein 81% identical to the rat pancreatic secretin receptor. COS-7 cells transfected with this cDNA bound secretin with a high affinity, and vasoactive intestinal peptide with a lower affinity, appropriate for a secretin receptor. Receptor-bearing COS-7 cells also exhibited an increase in cyclic AMP generation in response to secretin stimulation. Studies analyzing the role of this receptor in human pancreatic physiology and pathophysiology are currently underway in our laboratory.

Amino Acid Sequence↗