Prevention of extrahepatic disease during intraarterial floxuridine of colorectal liver metastases by simultaneous systemic 5-fluorouracil treatment? A prospective multicenter study

Fifty-two (52) patients with nonresectable hepatic-only metastases from colorectal carcinoma (tumor volume less than 75%) were treated by intraarterial FUdR, 0.2 mg/kg/d x 14 days/month (IA) using implantable pumps (Infusaid). They were randomized either for IA or for IA + systemic 5-FU 700 mg/m2/d x 3 days/month (IA/IV). Forty-six (46) patients were evaluable (26 IA; 20 IA/IV). Both groups were comparable in respect to primary tumor stage, age, liver function tests, tumor markers and extent of tumor infiltration. Twenty-six (26) patients (56%) demonstrated a complete (CR) or partial response (PR) with at least a 50% decrease in CEA levels and a significant tumor volume reduction (IA 50%; IA/IV 65%). Quality of response was significantly correlated with median survival (MS) time of 25 months for CR and PR. Approximate MS for IA and IA/IV was 16 and 19.5 months, respectively, and approximate median survival time to extra- and/or intrahepatic progression was 9 months (IA) and 11 months (IA/IV). Incidence of extrahepatic recurrence was not influenced by any treatment (IA 62%; IA/IV 60%). Overall approximate median time to occurrence of extrahepatic disease was 12.5 months (IA 13; IA/IV 10). Liver disease progression was observed in 38 patients (IA 85%; IA/IV 80%). A median time of 8 months to diagnosis of liver disease progression was calculated for IA, and IA/IV was 11.5 months. Incidence of chemical hepatitis for IA and IA/IV was 54 and 45%, while biliary sclerosis occurred in 15% and 10% of the cases, respectively, and did not correlate with response rates. Systemic side effects (25%) were only observed in the IA/IV group and induced significantly more interruptions of therapy than in the IA group. It is concluded from this study that additional systemic 5-FU treatment does not prevent the occurrence of extrahepatic disease under local chemotherapy of the liver.     

Comparison of the Effects of the Neurotrophins on the Morphological Structure of Dopaminergic Neurons in Cultures of Rat Substantia Nigra

The effect of the various neurotrophin family members on the morphological structure of dopaminergic neurons was compared in dissociated cultures of embryonic rat ventral mesencephalon. Cultures were maintained in vitro in the presence of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4/5), nerve growth factor (NGF) or no added growth factors. Three-dimensional reconstructions of 48 neurons were made in each of the experimental groups following immunocytochemical staining for tyrosine hydroxylase to detect dopaminergic neurons. In addition [³H]mazindol binding analyses were carried out in replicate cultures in order to quantify the effects of the neurotrophins on the number of dopamine uptake sites. Among the neurotrophins tested, NT-4/5 influenced the proximal morphological parameters most, as determined by a 36% increase in the soma profile area and 35% in the number of stem neurites. Analysis of neuritic size and complexity in these cultures revealed that combined neuritic length and number of segments/cell were increased by 45 and 40% respectively. A change in neurite complexity in the NT-4/5 treated cultures was further confirmed using Scholl's concentric sphere analysis. In addition, relative to the control, NT-4/5 increased the neuronal differentiation as evidenced by increases in varicosity density and [³H]mazindol binding by 114 and 101% respectively. BDNF and, to a lesser extent, NT-3 also increased both proximal parameters and parameters of differentiation, but were without effect on parameters of neuritic size and Complexity. No effects on neuronal structure were observed in NGF treated cultures. These findings demonstrate that BDNF, NT-3 and NT-4/5 influence the morphological differentiation of dopaminergic neurons in vitro , suggesting they may play a role in the structural development and plasticity of these neurons in the mesencephalon.     

Taste thresholds in man are differentially influenced by hydrocortisone and dexamethasone

The present study focused on sensory processing (taste threshold) in healthy young men given different cortisol doses within the normal physiological range. It aimed to differentiate the effects of dexamethasone, a synthetic pure glucocorticoid, compared to hydrocortisone, which has both glucocorticoid and mineralocorticoid properties. In a double-blind, cross-over design, 18 male subjects participated in three sessions. Subjects were pretreated orally with hydrocortisone (50 mg), dexamethasone (2 mg) or placebo. Taste detection was tested by a forced-choice three stimulus drop technique to determine detection acuity and a signal detection procedure to determine the ability to detect differences in NaCl concentration. Cortisol concentrations were determined in blood and saliva.

Hydrocortisone and dexamethasone had opposite effects on taste detection acuity. With the highest cortisol levels after intake of hydrocortisone, subjects made more errors is detection trials with respect to stimuli close to the absolute taste detection threshold than after intake of dexamethasone. Detection of differences was impaired by both glucocorticoids. This type of behavioral study in man may help clarify the roles of heterogenous corticosteroid receptor systems within the human brain.     

Status of clinical pancreas transplantation

Since 1977 and especially within the latest 5 years there was a volatile development in the pancreas transplantation. If we had only 60 transplants between 1966-1977, prevalent duodeno-pancreas-transplants, the cases rose to 215 up to 1982 and to 447 transplantations between 1983 to 1985. Altogether there were 722 pancreas transplants, up to November, 15, 1985 registered. Before 1977 only 2 patients had a 1 year function rate of the transplant and of the 447 transplantations within the latest 3 years 201 transplants functioned more than 12 months. That was a 1-year function rate of 45% in contrast to 3% before 1977. The clear improvement of the results in pancreas transplantation can be attributed to operative aspects and to the employment of Cyclosporine A. The segmental pancreas transplantation with duct occlusion and intestinal or external drainage of the duct system were the most sure operative procedures. The combination of Azathioprine and Cyclosporin A brought with a 1-year function rate of 54% better results in comparison to the singular application of Azathioprine (22%) and Cyclosporin A (41%). The simultaneous pancreas-kidney transplantation had a 1-year function rate of 39%, the pancreas transplantation after kidney of 31% and the pancreas transplantation alone of 20%.     

Safety of celecoxib in patients with ulcerative colitis in remission: a randomized, placebo-controlled, pilot study.

BACKGROUND & AIMS: The safety of selective cyclooxygenase-2 inhibitors in patients with ulcerative colitis in remission is unknown. METHODS: We performed a placebo-controlled pilot trial to evaluate the safety of celecoxib in patients with ulcerative colitis in remission who had a present or past history of nonspecific arthritis, arthralgia, or other condition amenable to nonsteroidal anti-inflammatory drug therapy. A total of 222 patients with ulcerative colitis in remission were randomized to receive oral celecoxib 200 mg or placebo twice daily for 14 days. Remission was defined as a total Mayo Clinic score of 2 points or less and an endoscopic score of 1 point or less. Disease exacerbation was defined as a total Mayo Clinic score of 5 points or more and an increase in the endoscopic score of 1 point or more. The primary analysis was disease exacerbation through day 14 among patients who underwent randomization, had at least 1 dose of study drug, and had both endoscopy and Mayo Clinic disease activity index scores at the baseline and final assessments. RESULTS: Three percent of patients in the celecoxib group experienced disease exacerbation through day 14, as compared with 4% in the placebo group (P = .719). Eleven percent of patients in each group experienced a bowel-related adverse event (P > .20). CONCLUSIONS: Therapy with celecoxib for up to 14 days did not have a greater relapse rate than placebo in patients with ulcerative colitis in remission who had a present or past history of nonspecific arthritis, arthralgia, or other condition amenable to nonsteroidal anti-inflammatory drug therapy.     

Immunenzymatische AB0-blutgruppenbestimmung am einzelhaar

Zusammenfassung Untersucht wurden markhaltige Einzelhaare von 168 Personen bekannter serologischer Blutgruppenkonstellationen (Blutgruppe A₁: n=58; A₂: n=11; B: n=28; 0: n=46; A₁B: n=16; A₂B: n=9). Die immunenzymatische Darstellung der AB0-Blutgruppensubstanz gelang fehlerfrei in allen Fällen am Markkanal des Haares durch Inkubation mit monoklonalen Antikörpern sowohl nach einer Variante des Sternberger-Verfahrens als auch bei Verwendung eines monoklonalen APAAP-Komplexes als Markerenzym. Die Untersuchungen wurden parallel an kunststoffeingebetteten Haarquer- und Haarlängsschnitten und im Flotationsverfahren durchgeführt. Mit der Immunenzymtechnik steht eine zweite unabhängige Methode neben dem serologischen Nachweis nach Yada und seinen Modifikationen zur AB0-Blutgruppenbestimmung am Haar zur Verfügung.Ein Teil der Ergebnisse der PAP-Technik sind Bestandteil der Dissertation von Herrn K. Lorenz     

Pancreatic donor operation for islet cell isolation and transplantation

Preservation of B-cells, following organ collection and cold ischaemia, was defined on 19 donor organs by means of histological tests and testing for insulin content in pancreatic tissue. The degree of preservation declined by 50 per cent after two hours of cold ischaemia. The Velcro technique and uncrushed organ digestion were used for isolation. Islet yield was calculated by determination of insulin levels in isolated tissue (nmol/ml) and in the islet (pmol/islet). The average islet yield was 2 076 islets to one gram pancreas, that is ten per cent of the original amount. Studies conducted into in-vitro insulin secretion from isolated islets have revealed damage to organs due to handling, especially to organs which had undergone extended cold ischaemia.     

Patient satisfaction of primary care for musculoskeletal diseases: A comparison between Neural Therapy and conventional medicine

Background  

The main objective of this study was to assess and compare patient satisfaction with Neural Therapy (NT) and conventional medicine (COM) in primary care for musculoskeletal diseases.     

Clinical relevance of a dosage device for laser photocoagulation

Fundus reflectometry constitutes a procedure with which dosage can be precisely regulated during the coagulation process. During retinal coagulation, for example, it is possible with this method to administer coagulations of uniform intensity regardless of variations in either the quality of the fundus image or the absorption of the pigmented structures. This can be useful for coagulation procedures which have to be confined for the most part to the pigment epithelium, as for example in the treatment of central serous retinopathy or in panretinal photocoagulation, where the functional therapeutic principle is still not clearly understood. Another area of application for reflectometric laser coagulation will be laser trabeculoplasty, in which barely detectable lesions have to be placed in the trabecular meshwork.     

Synthesen von N-Lost-Derivaten, 2. Mitt. Reaktion von N-Bis(2-Chlorethyl)phosphorsäureamid-dichlorid mit 1-Aminopropan-2,3-diol

Synthesis of N-Lost Derivatives, II: Reaction of N,N-bis(2-Chloroethyl)phosphoramidic dichloride with 1-Aminopropane-2,3-diol The reaction between the phosphoramidic dichloride 1 and 1-aminopropane-2,3-diol ( 3 ) affords the five membered ring 9 and not the desired 5-hydroxycyclophosphamide 8 . The structural assignment was based on an independent synthesis of 9 via the benzyl ether 14 .