Trial geography, pharmacogenetics, and global drug development.

Drug development is increasingly global. The benefits of multiregional trials include worldwide evaluation of safety and efficacy. However, clinical practice, environmental, and genetic factors can vary across geographic regions, significantly influencing trial outcomes within a specific geographic region or the global population relative to the United States (US). Genomic technologies and research discoveries continue to advance at a remarkable pace, offering opportunities to explore intrinsic factors that could account for regional variability in drug pharmacokinetics or response.

Effects of a Deca Iron Triathlon on body composition: a case study.

We investigated energy balance and change of body composition in one athlete in a multistage triathlon, the World Challenge Deca Iron Triathlon 2006, where athletes had to perform one Ironman triathlon of 3.8 km swimming, 180 km cycling and 42.195 km running per day for ten consecutive days. In one well-experienced male ultra-endurance triathlete, we measured body mass, skinfold thicknesses and perimeters of extremities, in order to calculate skeletal muscle mass, fat mass and percentage of body fat. Energy intake was measured by analysis of nutrition, and energy expenditure was calculated using a portable heart rate monitor. This was performed to quantify energy deficit. In addition, bio-impedance measurements were performed to determine fluid metabolism. The athlete finished the race in 128 hours, 22 minutes and 42 seconds in 3rd position. Body mass decreased by 1 kilogram, skeletal muscle mass decreased by 0.9 kilograms and calculated fat mass decreased by 0.8 kilograms. Total body water increased by 2.8 liters. Total energy expenditure for the Deca Iron was 89,112 kilocalories and a total energy deficit of 11,480 kilocalories resulted. We presume that energy deficit was covered by consumption of adipose subcutaneous tissue as well as skeletal muscle mass; the degradation of muscle mass seems to lead to hypoproteinemic edemas.

[A 12 hour indoor cycling marathon leads to a measurable decrease of adipose subcutaneous tissue]. / Ein 12-stunden-Indoor-Cycling-Marathon führt zu einem messbaren Abbau des subkutanen Fettgewebes.

In a 12 hour indoor cycling marathon, an athlete has lost 0.4 to 1.2 kg of body mass depending on the time of measurement. Fat mass has decreased by 0.9 kg independent of the time of measurement. Calculated skeletal muscle mass increased by 0.27 to 0.67 kg - depending on the time of measurement. Due to the specific weight of urine, a possibly minimum dehydration was objectified, whereas specific weight right after exercise and 24 h after exercise had the same value. We assume that there was a substantial loss of fat mass, since repeated measurements after exercise showed an increasingly lower body weight and a constantly lower fat mass after exercise independent of the time of measurement. Increase of calculated muscle mass is considered to be due to an intramuscular oedema. In order to confirm results obtained in a case study, a larger number of athletes would have to be analyzed. A possible oedema would have to be objectified by a bioelectrical impedance analysis.

[A rare cause of diffuse pulmonary hemorrhage in a 45 year-old man]. / Seltene Ursache einer diffusen alveolären Hämorrhagie bei einem 45-Jährigen.

Diffuse pulmonary hemorrhage denotes a diffuse bleeding into the alveoli as a result of severe damage of the alveolocapillary membrane. Autoimmune diseases, toxic injury and hemodynamic changes are the most frequent causes. A 45 year old male patient presented with diffuse alveolar hemorrhage. An Immunoglobulin A (IgA) paraprotein secreting myeloma was found to be the underlying cause. Immunohistochemistry revealed dense pericapillary and perivascular deposits of IgA, indicating a paraprotein mediated damage of the alveolocapillary membrane. The predominantly vascular pattern of damage was regarded as the most likely cause of the pulmonary hypertension in this patient. The diffuse pulmonary bleeding stopped after initiation of treatment consisting of vincristine, adriamycine and dexamethasone.

[Differential diagnosis of diffuse pulmonary haemorrhage]. / Differenzialdiagnostik der diffusen alveolären Hämorrhagie.

Diffuse alveolar haemorrhage (DAH) denotes a diffuse intra-alveolar bleeding from small vessels as a result of severe damage of the alveolocapillary membrane of the lungs. These are comparatively rare, but than often life threatening events. The differential diagnosis is broad and comprises immunologic as well as toxic, infectious, hemodynamic, neoplastic and physical causes. DAH may be a manifestation of systemic diseases, as well as a result of an injury restricted to the lungs. The most frequent systemic diseases, that cause DAH are the so-called small vessel vasculititis-microscopic polyangiitis and Wegener's granulomatosis. More rarely Goodpasture's syndrome and systemic lupus erythematosus are causal. Alongside the immunologic processes mainly diseases with increased left-ventricular preload, infections and side effects of drugs have to be kept in mind. This review summarizes the differential diagnostic spectrum and the diagnostic workup of patients with DAH. Because early aggressive treatment can be life-saving, early and aimed diagnostics is essential.

[Immunosuppression by parenteral lipid emulsions in a model of defined immunostimulation]. / Inmunosupresión de las emulsiones lipídicas parenterales en un modelo de inmunoestimulación definida.

The immunosuppressive effect of intravenous fat emulsions with different n-3/n-6 fatty acid ratio was studied in the heterotopic rat heart allotransplant model. Twenty percent emulsions of safflower oil (n-3/n-6 = 1/370), fish oil (7.6/1), soybean oil (1/6.5) and a 1:1 mixture of safflower and fish oil (1/2, 1; oil control group) were continuously infused (9 g fat/Kg b.w./day; n = 10 each group) after transplantation until rejection. Graft survival time, subpopulations of infiltrating and circulating immunocompetent cells and Interleukin-6 release of circulating monocytes were analyzed. In the safflower oil, fish oil and soybean oil groups graft survival was prolonged to 13.3, 12.3 and 10.4 days vs. 6.7 days in the oil control group and 7.8 days in the saline control group (p < 0.01). In the two groups with the highest prolongation of graft survival the number of infiltrating cells was reduced by up to 50 percent and the peripheral blood monocyte interleukin-6 release by up to 45 percent. Beyond that, circulating T-cells were reduced in the fish oil group. Intravenous fat emulsions show a varying immunomodulatory effect in dependence of the n-3/n-6 fatty acid ratio. Both n-6 and n-3 fatty acids, if applied as main fatty acid source, exert immunosuppressive effects by a diminished infiltration, mobilisation and cytokine release of immunocompetent cells. Soybean oil with a more balanced n-3/n-6 fatty acid ratio than safflower is significantly less immunosuppressive than safflower oil and fat emulsions with a n-3/n-6 fatty acid ratio of 1/2 are immunologically neutral.

[The MRI in pre- and postnatal diagnosis of congenital sacrococcygeal teratoma]. / Die MRT in der prä- und postnatalen Diagnostik von konnatalen Steissbeinteratomen.

INTRODUCTION: The main tasks of imaging methods on the evaluation of relatively rare and potentially malignant connatal sacrococcygeal teratomas (SCT) are to depict the extent, structure and relationship to surrounding systems. METHODS: Two cases with SCT were studied with pre- and postnatal MRI and findings were compared with the ultrasound and clinical data. RESULTS: Before delivery, MRI permits depiction of the size and structure of teratomas and the integrity of the serum. After delivery, evaluation of the rectum, urinary tract and levator muscles is important to facilitate surgical reconstruction.

[Effects of lumbar peridural anesthesia on tissue pO2 of the large intestine in man]. / Einflüsse der lumbalen Periduralanästhesie auf den Gewebe-PO2 des Dickdarms beim Menschen.

AIM: The aim of this study was to investigate the effect of 15 ml bupivacaine 0.25%, given via an epidural catheter, on the tissue-PO2 of the colon wall in humans. METHODS: Nine patients were studied during elective colorectal surgery. The tissue-PO2 was measured by polarography, using a multiwire surface probe. RESULTS: There was no significant change in cardiac index and arterial oxygen delivery after the injection of bupivacaine. At the serosal side of the colon wall the tissue-PO2 increased from 34 to 51 mmHg after epidural bupivacaine, which is statistically significant. Spinal nerve block produces sympathetic denervation of the bowel with an increase of regional nutritive blood flow. CONCLUSION: It is concluded that epidural bupivacaine has a favourable effect on tissue oxygenation of the colon during colorectal surgery.

[Diagnosis and treatment of adnexa tumors in childhood and adolescence]. / Diagnose und Behandlung von Adnextumoren im Kindes- und Jugendalter.

From 1968 to 1988, 47 children and adolescents, their ages ranged from a few days to 21 years, were treated for tumors of the ovary in the hospital for children and adolescents and the surgical department of the University of Erlangen-Nürnberg. In 33 cases ovarian cysts were found, 14 patients suffered from a neoplasm of the ovary. 8 of the neoplasms were benign cystic and solid teratomata, 4 were of epithelial origin and 2 identified as juvenile granulosa cell tumors. There was a follow up in all patients with tumors ranging up to 19 years.

[A need for surgical treatment in necrotizing enterocolitis?]. / Notwendigkeit der operativen Behandlung bei NEC?

Based on the experience with 57 neonates with NEC, the significance of diagnostic methods (especially ultrasonography, paracentesis, intraoperative photometry) for treatment and results is discussed.

[Chronic atelectasis--an indication for lung resection in early childhood?]. / Chronische Atelektase--eine Indikation zur Lungenresektion im frühen Kindesalter?

Between 1980 and 1989, 69 children underwent lung resection in our department. 45 of them (25 boys, 20 girls, age 0-9 years) presented with atelectatic areas of the lung parenchyma, which had been demonstrated preoperatively in only 76%. Resections were performed for bronchial malformations (n = 7), sequestration (6), cysts (6), aspiration (1), pyocele following pulmonary artery ligation (1), upper lobe torsion (1), chronic pneumonia and/or bronchiectasis (14) and lobar emphysema with lung compression (10). The overall mortality was 4/45. Indications are discussed with special reference to the persistent or recurrent atelectasis.

[Surgical treatment of distal humerus fractures in children]. / Die chirurgische Behandlung distaler Humerusfrakturen im Kindesalter.

From 1955 to 1987 414 children with supracondylar fractures of the humerus were treated at the surgical department of the University of Erlangen. Most important for the choice of treatment in supracondylar fractures was the classification of Baumann. 33 children concerning stage I were treated with cuff and collar or cast. Out of 381 patients with stage II and III Baumann's extension was used in 352 children; 29 had to be operated. The operation was indicated in a further 56 children. 20 of these had a lesion of the condylus radialis, 18 of the epicondylus ulnaris, 8 children showed diacondylar, 3 transcondylar lesions, 3 children had injuries of the condylus ulnaris and 4 more children showed splintered fractures. In 234 patients a follow-up was carried out according to the scheme of Morger. In 91% there was an ideal or good late result, in only 2% of the patients the result was unsatisfactory. The majority of distal fractures of the humerus can be treated conservatively with good results; operative treatment does not improve the functional and cosmetic results. It is indicated in complicated forms of fracture, in which satisfying results are not to be expected by conservative treatment.

[Surgical intervention on the thymus in children and adolescents]. / Operative Eingriffe am Thymus bei Kindern und Jugendlichen.

Our group of 17 thymus operated patients--aged between 2 months and 18 years--consisted of 4 girls and 13 boys. All 5 patients whose operations were connected with a treatment for myasthenia gravis showed clinical improvement. In 3 children with malignant tumours the extent of surgery determined their subsequent prognosis. In 9 patients thoracotomy was performed because of space-occupying growth, or for the purpose of ensuring diagnostic safety.

[7/8th pancreas resection in nesidioblastosis?]. / 7/8 Pankreasresektion bei Nesidioblastose?

UNLABELLED: The extent of pancreatectomy for the treatment of nesidioblastosis is open to dispute. Recurrent hypoglycaemia, insulin-dependent diabetes mellitus, or exocrine insufficiency may result. CASE REPORTS: 1) A female twin presented with hypoglycaemia, insulin response inappropriate for glucose levels, marked leucine sensitivity, low ketones, underwent 7/8 pancreatectomy for multifocal adenomatosis at the age of 13 months. 2) A boy of 7 months of age had a 95% resection including the uncinate process. Focal adenomatosis combined with diffuse nesidioblastosis proved by immunohistological examination. OUTCOME: Both remained asymptomatic and normoglycaemic. DISCUSSION: The prognosis seems to depend on the primary extent of resection.

[Death rate on a heart surgery waiting list]. / Tod auf der herzchirurgischen Warteliste.

Of 2398 patients on a waiting list for aorto-coronary bypass operation 42 (1.8%) died before operation during an average waiting time of four months. Comparing the diagnostic data of those who died on the waiting list and those after operation, there was an increased frequency of indicators to further progression of the coronary heart disease (angina at rest, three-vessel disease, main stem stenosis, left ventricular contraction abnormalities) in the group of those patients who had died on the waiting list. The significance of these various indicators was further high-lighted in their prognostic significance when taking into account different waiting periods of the various sub-groups.

[Resection of the valvula bauhini and its effect on the metabolism. An experimental study in animals (author's transl)]. / Die Resektion der Valvula Bauhini und ihre Stoffwechselfolgen. Eine tierexperimentelle Studie.

In animal experiments (20 mongrel dogs) malabsorption was induced by resection of 100 cm ileum. Subsequently the influence of the ileocoecal valve (Valvula Bauhini) in absorption was studied. In one group of animals intestinal continuity was reestablished by ileoileostomy, in a second by ileocolostomy. The results of the absorption studies were compared with a healthy control group. After ileoileostomy animals do not lose weight, serum cholesterol and protein remain normal. Oral tolerance tests with Triolein-iodine-131 and Cyanocobalamine show results identical with those of the control group. After ileocolostomy all these parameters are lowered--partially to a pathological level. It is concluded that in all operations in the area of the terminal ileum and colon the Valvula Bauhini should be retained if possible.