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Biomedical subjects

P Klein

Publications and source records attributed to P Klein.

At least 109 records · Page 6Linked to original sources

Is local excision of pT1-ampullary carcinomas justified?

We propose that local excision of carcinomas of the ampulla of Vater is justifiable under the following conditions: when the tumour is limited to the ampulla of Vater as diagnosed by pre-operative endoluminal sonography (uT1) and UICC-staging (pT1); and when it is graded G1 or G2 and there is no lymphatic infiltration and the tumour is completely resected (R0). Under these conditions peri-operative morbidity and mortality were significantly reduced compared with more extensive surgery. There was no local recurrence of tumour in our study and long-term survival rates were comparable with Whipple's procedure. This implies that lymphatic spread is limited in localized disease and the feasibility of the proposed procedure may therefore be analogous to localized resections in other malignant tumours, e.g. carcinoma of the rectum.

Adult↗

Use of the DAF assay to assess the functional properties of polyclonal and monoclonal RhD antibodies.

The mechanism whereby passive Rh (D) immunoglobulins suppress the fetomaternal alloimmunization is still unclear. New in vitro tests are needed to better characterize the functional properties of polyclonal anti-Ds. The DAF assay was developed to monitor the antibody-dependent cell-mediated cytotoxicity (ADCC) and the phagocytosis of anti-Rh (D)-sensitized RBCs by effector cells. The principle of this test is based on the oxydization of the 2,7-diaminofluorene (DAF) by the pseudoperoxidase activity of free hemoglobin. The reaction is proportional to the hemoglobin concentration. This test was performed to determine and emphasize the efficacy of different polyclonal anti-D immunoglobulin preparations to mediate lysis and phagocytosis of sensitized RBCs by human peripheral mononuclear cells. The functional properties of different human RhD monoclonal antibodies were also analyzed and compared. The test was found to be convenient to perform and allowed the avoidance of radioactive labelling of RBCs for ADCC studies. It is mainly useful for the direct quantitation of phagocytosis.

Antibody-Dependent Cell Cytotoxicity↗

Comparative clinical efficacy and tolerability of oxerutins and horse chestnut extract in patients with chronic venous insufficiency.

Oxerutins (O-(beta-hydroxyethyl)rutosides, HR, Venoruton) and horse chestnut extract (HCE) are active principles of first priority for the pharmacological treatment of chronic venous insufficiency (CVI). The efficacies of both compounds were shown in numerous, double-blind, randomized, placebo controlled clinical trials. Besides the direct comparison of the two compounds the aim of the study was to investigate the initial dose/maintenance dose concept for HR. 137 female, postmenopausal patients with CVI II finished the study according to protocol. Following one week placebo run-in the patients were treated either with 1000 mg/d HR, 600 mg/d HCE or 1000 mg/d for 4 weeks and than with 500 mg/d HR within the initial dose/maintainance dose concept for 12 weeks and observed for further 6 weeks. A main confirmative criterion was the volume reduction of the leg. Subjective criteria were descriptively evaluated. HR (1000 mg/d) was proven to be equivalent or better, reducing the leg volume (AUB0-18) by -5273 +/- 11418 ml.d compared to -3187 +/- 10842 ml.d under HR (1000 mg/d and 500 mg/d), and -3004 +/- 7429 ml.d under HCE-treatment. Both compounds exhibit a substantial carry-over effect. The maintenance posology of HR is able to stabilize the therapeutic obtained under initial dose conditions.

Aged↗

["As much as possible"--an outdated concept in advanced neuroblastoma?].

Complete tumor resection is often impossible in disseminated stages of neuroblastoma. Therefore, the role of primary tumor resection in neuroblastoma patients of stage III and IV will be discussed here. Between 1972 and 1995, 66 neuroblastoma patients were operated in our department of pediatric surgery, 41 of whom were treated before 1989 and are the subject of retrospective study. Eight children belonged to stage III, 15 to stage IV and two to stage IV-S. Primary tumor resection was carried out in 19 of 25 patients with disseminated tumor stages. Total resection (RO) was achieved in three cases (16%). Microscopic tumor remains (R1) were present in four, with macroscopic remains in 12 cases. Three disseminated neuroblastomas received preoperative chemotherapeutic treatment, followed by a delayed complete operative tumor resection in two cases. Temporary tumor remission after an incomplete primary operation (R2) was achieved with adjuvant postoperative chemo- and radiotherapy in six of 12 patients. The mortality rate was high (stage III: n = 5/8, stage IV: n = 14/15, stage IV-S: n = 2/2). We recommend preoperative chemotherapy in cases of infiltrative tumor growth of stage III and generally in stage IV. This therapeutic regime improves the rate of complete tumor resection with less intraoperative complications.

Adolescent↗

Histological, histochemical, and ultrastructural investigations on the gastrointestinal system of Antarctic seals: Weddell seal (Leptonychotes weddellii) and crabeater seal (Lobodon carcinophagus).

The morphology of the principal sections of the gastrointestinal system of two Antarctic seals with different dietary habits, namely, the Weddell seal (Leptonychotes weddellii) and the crabeater seal (Lobodon carcinophagus), has been investigated. Histologically examined by light microscopy, the tissue layers of the gastrointestinal tract of both seals are almost identical to those observed in most other mammals and no major differences in principle organization could be found between the two seal species. The ultrastructure of the gastric and intestinal epithelial cells has been examined and is also closely comparable to that of these cells in other mammals; however, Paneth cells have not been found in our material. In general, therefore, adaptations of the gastrointestinal tract to the aquatic environment or the diet are not obvious at the morphological levels of organization studied. Histochemical differences are found between the two closely related species; mucins of the surface epithelium in the stomach of Weddell seals are highly sulfated, while those in the crabeater seal are not. Mucous neck cells in Weddell seals contain acid mucosubstances, while those of crabeater seals contain neutral ones. Goblet cells in the small and large intestine in Weddell seals contain both neutral and acid mucosubstances. Both mucin types are detected in the crabeater seal; however, the mucins of the colon in the crabeater seal are more highly sulfated than those in the Weddell seal. The ratio of goblet cells to enterocytes in the large intestine of crabeater seals is higher than that in Weddell seals.

Acclimatization↗

[Chronic hepatitis C in type-II cryoglobulinemia and cutaneous vasculitis].

Over a period of 2 years recurrent erysipelas-like skin eruptions developed over both lower legs of a 77-year-old woman. On examination there was a vasculitic purpura which histologically was like leukocytoclastic vasculitis. Further tests revealed a positive rheuma factor, a mixed type II cryoglobulinaemia of monoclonal IgM-kappa paraprotein and polyclonal IgG, as well as chronic hepatitis C with viral replication and demonstration of hepatitis C virus-RNA in the cryoprecipitates, diagnostic of chronic hepatitis C with mixed type II cryoglobulinaemia. Treatment was begun with prednisone, 25 mg/d orally, and cyclophosphamide, 100 mg/d orally. Once hepatitis C had been diagnosed, treatment was continued with interferon alpha-2b (initially 3 x 5 mill. IU, later 3 x 3 mill. IU, each weekly subcutaneously). The vasculitis quickly healed and the cryoglobulinaemia had disappeared within 5 weeks. So far, during the treatment of 9 months, the vasculitis has not recurred, but cryoglobulins have again been demonstrated. The signs and symptoms of hepatitis C were not affected by the interferon treatment.

Aged↗

Effects of P-glycoprotein expression on cyclic AMP and volume-activated ion fluxes and conductances in HT-29 colon adenocarcinoma cells.

The tissue distribution of P-glycoprotein (Pgp) and the structurally related cystic fibrosis transmembrane conductance regulator (CFTR) is apparently mutually exclusive, particularly in epithelial; where one protein is expressed the other is not. To study the possible function(s) of Pgp and its potential effects on CFTR expression in epithelia, HT-29 colon adenocarcinoma cells, which constitutively express CFTR, were pharmacologically adapted to express the classical multidrug resistance (MDR) phenotype (Pgp+). Concomitant with the appearance of Pgp and MDR phenotype (drug resistance, reduced drug accumulation and increased drug efflux), CFTR levels and cAMP-stimulated Cl conductances were markedly decreased compared to wild-type HT-29 (Pgp-) cells (as shown using the whole cell patch clamp technique). Removal of drug pressure led to the gradual decrease in Pgp levels and MDR phenotype, as evidenced by increased rhodamine 123 accumulation (Pgp-Rev). Concomitantly, CFTR levels and cAMP-stimulated Cl- conductances increased. The cell responses of Pgp/Rev cells were heterogeneous with respect to both Pgp and CFTR functions. We also studied the possible contribution to Pgp to hypotonically activated (HCS) ion conductances. K+ and Cl- effluxes from Pgp- cells were markedly increased by HCS. This increase was twice as high as that induced by the cation ionophore gramicidin; it was blocked by the Cl- channel blocker DIDS (4,4'-disothiocyano-2,2'-disulfonic stilbene) and required extracellular Ca2+. In Pgp+ cells, the HCS-induced fluxes were not significantly different from those of Pgp- cells. Verapamil (10 microM), which caused 80% reversal of Pgp-associated drug extrusion, failed to inhibit the HCS-evoked Cl- efflux of Pgp+ cells. Similarly, HCS increased Cl- conductance to the same extent in Pgp-, Pgp+ and Pgp-Rev cells. Verapamil (100 microM), but not 1,9-dideoxyforskolin (50 and 100 microM), partially inhibited the HCS-evoked whole cell current (WCC) in all three lines. Since the inhibition by verapamil was not detected in the presence of the K+ channel blocker Ba2+ (3 mM), it is suggested that verapamil affects K+ and not Cl- conductance. We conclude that hypotonically activated Cl- and K+ conductances are similar in HT-29 cells irrespective of Pgp expression. Expression of high levels of Pgp in HT-29 cells confers no physiologically significant capacity for cell volume regulation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[The Longmire gastrectomy in the animal model: postoperative changes in fat resorption and the hormones cholecystokinin and secretin].

In this animal study we investigated the absorption of free fatty acids and triglycerides after gastrectomy. The levels of the hormones cholecystokinin and secretin were measured in response to a controlled enteral fat load (Lipofundin 20% MCT emulsion). We studied fat absorption in three groups of animals: the gastrectomy group in which lipid emulsion was administered in the duodenum, and two groups of controls that received the same infusion in the duodenum or stomach, respectively. Infusing the fat load directly into the duodenum, rather than the stomach, resulted in delayed absorption of fatty acids. In the gastrectomized animals there was, in addition, increased absorption of triglycerides. Medium- and long-chain fatty acids were found to be an adequate stimulus for secretion of the gastrointestinal hormones cholecystokinin (CCK) and secretin. In the gastrectomized group, higher baseline levels of both CCK and secretin were observed. CCK showed no response to the lipid stimulus, whereas a secretin response was observed over and above the raised baseline level. The gastrectomized animals showed a markedly restricted growth rate, as measured by body weight; however, they continued to gain weight in a linear fashion up to the end of the study period. No alterations in morphology of CCK-secreting cells were found.

Animals↗

[Congenital duodenal stenosis in adulthood].

A high-grade duodenal stenosis in adults can, in rare cases, be congenital, and its cause is found in an intraduodenally sited membrane. The anamnesis reveals growth disorders with vomiting and meteorism and abdominal complaints. A perforation opening in this membrane is the reason for survival into adulthood. The X-ray appearance and deep duodenoscopy make the diagnosis easy. Volvulus in cases of malrotation, Ladd's ligaments, annular pancreas, and compression of the duodenum by mesenteric vessels must be considered in the differential diagnosis. When the intraduodenal membrane is resected it is most important to expose the papilla Vateri, since this not uncommonly ends in the area of the septum. If necessary, a duodenoduodenostomy is performed. If the windsock web abnormality is present the duodenum should be opened at the point of attachment of the diaphragm. The construction of a gastrojejunostomy should be avoided.

Adult↗

Ca(2+)- and swelling-induced activation of ion conductances in bronchial epithelial cells.

The present study was performed to examine Ca(2+)-dependent and cell-swelling-induced ion conductances in a polarized bronchial epithelial cell line (16HBE14o-). Whole-cell currents were measured in fast and slow whole-cell patch-clamp experiments in cells grown either on filters or on coated plastic dishes. In addition the transepithelial voltage (Vte) and resistance (Rte) were measured in confluent monolayers. Resting cells had a membrane voltage (Vm) of -36 +/- 1.1 mV (n = 137) which was mainly caused by K+ and Cl- conductances and to a lesser extent by a Na+ conductance. Vte was apical-side-negative after stimulation. Equivalent short-circuit (Isc = Vte/Rte) was increased by the secretagogues histamine (0.1 mmol/l), bradykinin (0.1 - 10 mumol/l). and ATP (0.1 - mumol/l). The histamine-induced Is was blocked by either basolateral diphenhydramine (0.1 mmol/l, n = 4) or apical cimetidine (0.1 mmol/l, n = 4). In fast and slow whole-cell recordings ATP and bradykinin primarily activated a transient K+ conductance and hyperpolarized Vm. This effect was mimicked by the Ca2+ ionophore ionomycin (1 mumol/l, n = 11). Inhibition of the bradykinin-induced Isc by the blocker HOE140 (1 mumol/l, n = 3) suggested the presence of a BK2 receptor. The potency sequence of different nucleotide agonists on the purinergic receptor was UTP approximately ATP > ITP > GTP approximately CTP approximately [beta, gamma-methylene] ATP approximately 2-methylthio-ATP = 0 and was obtained in Isc measurements and patch-clamp recordings. This suggests the presence of a P2u receptor. Hypotonic cell swelling activated both Cl- and K+ conductances.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Antihypertensive efficacy of cilazapril 2.5 and 5.0 mg once-daily versus placebo on office blood pressure and 24-hour blood pressure profile.

In a double-blind, randomized, multicenter study the antihypertensive efficacy of cilazapril 5.0 and 2.5 mg once daily vs. placebo was examined on 180 ambulatory hypertensive subjects with supine diastolic office blood pressure (OBP) > or = 95 and < or = 115 mm Hg: a 4-week, single-blind, placebo period was followed by a 4-week double-blind treatment period. At the beginning and end of the latter, OBP measurements and ambulatory 24-h BP monitoring (ABPM) were both carried out on two different days (3 +/- 1), whereby each time two 24-h BP recordings were made using SpaceLabs 90202. Measurements were made every 30 min, and actual waking and sleeping phase evaluation was done using diary entries. White coat hypertensive patients were excluded by the ambulatory BP (ABP) inclusion criterion: mean diastolic 24-h BP > or = 85 mm Hg, or frequency of measurements > 90 mm Hg > or = 35%. One-hundred eighty patients were included in the study. Safety was evaluated in 170 of these patients, and efficacy on OBP in 162. Twenty-four-hour BP recordings that were amenable to analysis were available in the case of 146 patients (average age 56 +/- 10 years, 56 women, 90 men). The results of the main target variable for OBP, namely responder rates, were in the three treatment groups: placebo, 39.6%; cilazapril 2.5 mg, 55.6%; and cilazapril 5.0 mg, 65.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Tibial bypass grafting for limb salvage with ringed polytetrafluoroethylene prostheses: results of primary and secondary procedures.

PURPOSE: In advanced peripheral ischemia, tibial artery prosthetic bypass grafting is virtually the last chance for limb salvage when conservative treatment and other methods of revascularization have failed. METHODS: For this study we reviewed our 7 years of experience with below-popliteal artery polytetrafluoroethylene grafts implanted for limb salvage. RESULTS: All results regarding graft patency and limb salvage were computed by actuarial methods and were presented in the form of life-table analysis. There were 211 grafts in 184 patients (195 limbs). Two and 5 years after the operation, primary patency rates were 37% and 23% and secondary patency rates were 45% and 25%, respectively. The main negative predictive factors for patency rate were an occluded primary plantar arch artery and poor vessel runoff. Primary bypass procedures had markedly better success rates than secondary (repeat) procedures, with primary patency rates of 52% at 2 years and 42% at 4 years, whereas the corresponding rates for secondary procedures were 22% and 14%, respectively. The 5-year cumulative limb salvage rate was 51% for the total series. CONCLUSIONS: Although the patency of prosthetic grafts is not as satisfactory as that of autologous vein grafts, the limb salvage rate justifies an aggressive approach to infrapopliteal bypass grafting with polytetrafluoroethylene prostheses when the limb is threatened and vein is not available.

Aged↗

O3-(2-carbomethoxyallyl) ethers of opioid ligands derived from oxymorphone, naltrexone, etorphine, diprenorphine, norbinaltorphimine, and naltrindole. Unexpected O3-dealkylation in the opioid radioligand displacement assay.

O3-(2-Carbomethoxyallyl) ether derivatives of some phenolic 4,5-epoxymorphinan opioid ligands have been prepared in a simple one-step procedure, and their behavior in the radioligand receptor assay was compared to their phenolic precursors. These O3-ether ligands appeared to show significant affinity for opioid receptors, about 2-fold less than the parent phenols, and their receptor selectivities were similar. However, on close examination of the stability of a representative ether 2b in the radioligand displacement assay, considerable O3-dealkylation was observed. The dealkylation process occurred even after denaturation of the proteins of the membrane preparation, and it occurred in the presence of model nucleophiles imidazole and thiophenol. Thus, what apparently was unusual activity is explained by O3-dealkylation to the parent phenol (e.g., 2a). Saturated ether analog 2c was not dealkylated under the conditions of the radioligand displacement assay and was a very weak opioid ligand. We conclude that the conversion of the O3(2-carbomethoxyallyl) ether electrophilic ligands to their parent phenols accounts for their activity in the opioid radioligand displacement assay.

Alkylation↗