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Biomedical subjects

R Stein

Publications and source records attributed to R Stein.

At least 127 records · Page 7Linked to original sources
PubMed1997

Vitamin metabolism in patients with a Mainz pouch I: long-term followup.

PURPOSE: We assessed whether creation of the Mainz pouch I, which requires 24 to 36 cm. of terminal ileum and 12 cm. of ascending colon including the ileocecal valve, leads to metabolic disturbances. MATERIALS AND METHODS: In 137 patients the levels of vitamins A, B1, B2, B6, B12, D and E, folic and bile acids, ammonia, and intracorpuscular vitamin B12 and folic acid were evaluated and a red blood count was performed. Patients were divided into children and adults, and into 3 groups according to number of years after surgery (2 or less, more than 2 to 4 and more than 4). RESULTS: In all patients the levels of vitamins A, B1, B2, B6, D and E, folic and bile acids, and ammonia as well as red blood count were within normal ranges. In the 51 children there was no significant decrease in vitamin B12 postoperatively. In the 86 adults mean serum vitamin B12 plus or minus standard deviation decreased significantly from 402 +/- 182 ng./l. during the first 2 years postoperatively to 292 +/- 204 ng./l. after year 4 (normal 240 to 1,100). There was no significant decrease in intracorpuscular vitamin B12 during this period. CONCLUSIONS: In addition to regular examinations, the determination of vitamin B12 levels 4 years after Mainz pouch diversion is mandatory. It remains unclear whether substitution is necessary. However, substitution is easy to achieve and even less expensive than the regular determination of vitamin B12.

Adult↗
PubMed1997

Advantage of a residualizing iodine radiolabel for radioimmunotherapy of xenografts of human non-small-cell carcinoma of the lung.

UNLABELLED: Attachment of 131I to MAbs through adducts such as dilactitol-tyramine (DLT), which remain lysosomally trapped after catabolism of the labeled MAb, can greatly increase the residence time of the radiolabel at the tumor site. Our previous studies demonstrated a marked increase in accretion of 131I in a human lung-cancer xenograft model, using 131I-DLT in comparison to 131I linked to MAb by the conventional chloramine-T methodology. METHODS: In this study, biodistribution experiments were performed to evaluate the effect of protein dose on the accretion of 131I-DLT-labeled MAb RS11 in tumor and nontumor tissues, and in vivo radioimmunotherapy experiments compared the effect of single injections of 131I-DLT-labeled MAb RS11 to conventional 131I-labeled RS11 and an untreated control group. RESULTS: Dosimetry calculations based on the biodistribution data indicate only small changes in absorbed dose-to-tumor and nontumor tissues with increasing protein dose up to 100 micrograms, with a predicted absorbed dose to tumor of from 21,000 to 25,000 cGy/mCi. A single dose of 100 microCi of 131I-DLT-RS11 was found to cause tumor regression. At 7 wk postinjection of the radiolabeled MAbs, tumor volume in 73% of the animals administered 131I-DLT-labeled RS11 remained smaller than at the time of MAb injection. This is compared to 14% of the tumors in the conventionally labeled 131I-RS11 group and none in the untreated group. CONCLUSION: The use of the residualizing radiolabel DLT provides a therapeutic advantage in comparison to conventional 131I-labeled RS11.

Animals↗
PubMed1997

Manipulation of blood clearance to optimize delivery of residualizing label-antibody conjugates to tumor cells in vivo.

UNLABELLED: We have attempted to improve the therapeutic index of radioimmunotherapy by manipulating the blood clearance rate and the catabolism of the radiolabel. The general strategy is to allow the antibody (Ab) to circulate in the blood for 2-3 days, then to clear it rapidly by a method that delivers the Ab to hepatocytes. In addition, the radiolabel selected has two key properties: it is a residualizing label (which is lysosomally trapped after catabolism), so it is retained well by tumor cells, but is excreted rapidly by hepatocytes into bile. METHODS: In initial experiments, three residualizing radiolabels were tested for their rate of excretion after specific delivery in vivo to either hepatocytes, via galactosylated Ab, or Kupffer cells, via immune complexes. A label showing rapid biliary excretion only after delivery to hepatocytes, (111)In-benzyl-diethylenetriamine tetraacetic acid, was then used for radioimmunodetection in a protocol of delayed rapid blood clearance in which clearance was by hepatocytes. This was achieved by using galactosylated Ab, combined with temporary inhibition of the asialo-glycoprotein receptor on hepatocytes. Ab RS11 and the lung adenocarcinoma Calu-3 xenograft in nude mice were used. Control experiments were performed with a conventional 125I label and with 125I-dilactitol-tyramine. RESULTS: Indium-benzyl-diethylenetriamine tetraacetic acid was identified as a label that was excreted more rapidly from hepatocytes than from Kupffer cells, by biliary excretion. Using this radiolabel with delayed rapid blood clearance, very high tumor/blood ratios were obtained, 166:1 at day 3, but tumor/normal tissue ratios for other tissues were not as high. There appeared to be some uptake of the radiolabel by all normal tissues tested, including the lungs and muscle. Dosimetry calculations suggested that the therapeutic index was no better than with a simple Ab injection. CONCLUSION: Antibody catabolism can be directed towards either hepatocytes or Kupffer cells, and this difference can strongly affect the excretion rate of radiolabels, since only hepatocytes can excrete degradation products into bile. Processing will also depend on the particular radiolabel. These factors are particularly important for protocols involving delayed rapid blood clearance, since liver uptake is so rapid. The methods described should stimulate other approaches of manipulating Ab blood clearance and radiolabel catabolism to achieve improved therapeutic results.

Animals↗
PubMed1997

Pregnancy after Mainz pouch urinary diversion.

PURPOSE: We report on our experience with pregnancies and deliveries in patients with a continent ileocecal reservoir with catheterizable stoma (Mainz pouch). MATERIALS AND METHODS: Six women aged 18 to 33 years (mean age 26.8 years) became pregnant after undergoing urinary diversion. A continent ileocecal reservoir was made comprising 5 umbilical stomas and 1 stoma in the left lower abdominal quadrant. Underlying diseases were bladder exstrophy in 4, meningomyelocele in 1 and urogenital sinus in another patient. Cesarean section was jointly performed by the obstetricians and urologists in all patients. RESULTS: Seven pregnancies occurred in a total of 6 women. Three pregnancies were completely uneventful. Pregnancy complications were ureteral dilatation in 4 cases with pyelonephritis and premature labor in 1 case. A nipple prolapse in the patient with the stoma in the left lower abdominal quadrant was easily corrected during cesarean section. All patients underwent cesarean section without complications. Seven healthy children were born. CONCLUSIONS: In women with Mainz pouch urinary diversion there appears to be no contraindication to pregnancy, while other forms of continent diversion await further evaluation. Urologists and obstetricians should be aware of the potential complications of this high risk pregnancy and delivery, and their interdisciplinary cooperation is essential for successful outcome.

Adolescent↗
PubMed1996

Antibody penetration of tumor GS-7 xenografts in nude mice: a model for mucinous adenocarcinoma of the colon.

A new cell line derived from a human adenocarcinoma of the colon, GS-7, was propagated as a s.c. tumor in nude mice. This tumor histologically is a mucinous adenocarcinoma (also designated mucoid or colloid) with characteristic large mucin pools that are not lined by an epithelial layer but may contain scattered, randomly distributed cancer cells. Ten to 20% of human colorectal adenocarcinomas are of this histological type, but rapidly growing xenografts with this histology have been rarely used experimentally. This tumor, therefore, constitutes a useful model for similar human tumors. The mucin pools contain large amounts of carcinoembryonic antigen and tumor-associated glycoprotein 72, and the cells express epithelial glycoprotein 2 on their surface. The ability of antibodies injected i.v. to penetrate this tumor was investigated, using both biotinylated and radioiodinated antibodies (Abs). The results demonstrate that Abs can effectively penetrate the mucin pools, and that large amounts of Ab can localize there. This tumor type may have advantages as a target for certain forms of experimental immunotherapy.

Adenocarcinoma, Mucinous↗
PubMed1996

Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy.

Patients with myelodysplastic syndromes (MDS) have refractory cytopenias leading to transfusion requirements and infectious complications. In vitro marrow culture data have indicated that granulocyte colony stimulating factor (G-CSF) synergizes with erythropoietin (EPO) for the production of erythroid precursors. In an effort to treat the anemia and neutropenia in this disorder, MDS patients were treated with a combination of recombinant human EPO and recombinant human G-CSF. Fifty-five patients were enrolled in the study of which 53 (96%) had a neutrophil response. Forty-four patients were evaluable for an erythroid response of which 21 (48%) responded. An erythroid response was significantly more likely in those patients with relatively low serum EPO levels, higher absolute basal reticulocyte counts and normal cytogenetics at study entry. Seventeen (81%) of the patients who responded to combined G-CSF plus EPO therapy continued to respond during an 8-week maintenance phase. G-CSF was then discontinued and all patients' neutrophil responses were diminished, whereas 8 continued to have an erythroid response to EPO alone. In 7 of the remaining 9 patients, resumption of G-CSF was required for recurrent erythroid responses. The median duration of erythroid responses to these cytokines was 11 months, with 6 patients having relatively prolonged and durable responses for 15 to 36 months. Our results also indicate that approximately one half of responding patients require both G-CSF and EPO to maintain an effective erythroid response, suggesting that synergy between G-CSF and EPO exists in vivo for the production of red blood cells in MDS.

Adult↗
PubMed1996

Structural and functional diversity of phosphoinositide 3-kinases.

Phosphoinositide 3-kinases (PI3-kinases) have been shown to be recruited to cell surface receptor signal complexes whose formation is triggered by growth factors, cytokines and other ligands. PI3-kinases are also involved in protein sorting phenomena. A number of PI3-kinase isotypes have been characterised in several laboratories. Here the relations between the PI3-kinases, PI4-kinases and PI5-kinases and other potential phosphoinositide kinases are analysed. A study of the relation of structure to function for sequence motifs defined through the use of homology searches and protein modelling techniques is described and used to assign the family of phosphoinositide kinases to subgroups.

Amino Acid Sequence↗
PubMed1996

Continent diversion with the Mainz pouch.

From 1983 until July 1994, 561 patients in 2 urology departments (Mainz and Wuppertal) underwent a Mainz pouch 1 procedure. The Mainz pouch 1 was used for bladder augmentation in 60 patients, for orthotopic bladder substitution in 61 patients, and for continent cutaneous urinary diversion in 440 patients. In the group of continent cutaneous urinary diversion, the continence mechanism applied was an ileal intussusception nipple in 270 patients, an appendix stoma in 146 patients, a submucosal seromuscular bowel-flap tube in 14 patients, and a submucosal full-thickness bowel-flap tube in 10 patients. Indications for urinary diversion were bladder cancer in 339 patients, anatomical or functional loss of bladder capacity in 179 patients, and other primary or secondary malignancies of the bladder or true pelvis in 43 patients. After a mean follow-up period of 57 months (range, 3-127 months), early and late complications were encountered in 12% and 37% of the patients, respectively. In the bladder-augmentation group, 93% of the patients are completely continent day and night. All but three patients, who empty their reservoir by intermittent self-catheterization (CIC), void spontaneously by abdominal straining. In the orthotopic bladder-substitution group, 95% of the patients are continent during the daytime. To prevent urinary leakage, 13% have to empty their reservoirs regularly at 4-h intervals and 13% have to perform CIC to avoid residual urine. Among the patients treated with continent cutaneous urinary diversion, stoma failure occurred in 11%, stoma stenosis was encountered in 13% and required open revision in 2%, endoscopical incision in 10%, and conservative treatment (dilation) in 1% of cases.

Cecum↗
PubMed1996

Social integration, sexual behavior and fertility in patients with bladder exstrophy--a long-term follow up.

UNLABELLED: After primary bladder closure or urinary diversion, other factors apart from the reconstruction itself gain importance for individuals with the exstrophy-epispadias complex: social integration and, after reaching puberty, sexuality and fertility. Between 1968 and July 1994 115 patients with bladder exstrophy or incontinent epispadias underwent surgery at our institution. A total of 104 patients could be followed, 2 of whom died in the meantime. Of the remaining 102 patients 48 attend school, 4 are in college, 40 have completed or are currently undergoing vocational training, 3 are unemployed, 1 lives in a therapeutic centre and 6 are younger than 6 years of age. A total of 95% of the patients with continent urinary diversion are continent day and night, whereas only three of five patients with a sling plasty (incontinent epispadias) or with primary bladder closure followed by a Young-Dees procedure are continent. None of the patients showed deterioration or renal function. In 25 females the external genitalia were reconstructed. Fixation of the uterus was done in 13 to correct or prevent uterine prolapse. Of the 17 women older than 18 years of age with genital reconstruction, 16 are satisfied with the cosmetic result. All adults engage in sexual intercourse. Five women have delivered seven children by Caesarean section. Of the 35 male adults 32 underwent reconstruction of the external genitalia and 34 males achieve erection. One developed necrosis of the penis early in life following primary bladder closure performed at an outside hospital. Penile deviation was present in 11 of the 32 patients with genital reconstruction, which is distressing in only 2. Thirty patients are satisfied with the cosmetic result. After genital reconstruction 9 males developed epididymitis, necessitating two orchiectomies and three vasectomies. No patients with reconstruction of the external genitalia can ejaculate normally or has fathered children, whereas ejaculation was normal in the three men who did not undergo genital reconstruction and in two patients prior to post-pubertal reconstruction. Furthermore, two of these three men have fathered four children. CONCLUSION: Education, occupation and social development of patients with urinary diversion are uneventful. The cosmetic results achieved by genital reconstruction are satisfactory. In female patients, antefixation of the uterus should be performed before or together with an introitusplasty to prevent uterine prolapse. In male patients, however, surgery is performed at the expense of fertility. Detailed discussions with the patients and their patients should include not only the question of primary bladder closure versus urinary diversion, but also the pros and cons of correction of the external and-in females-the internal genitalia.

Adult↗
PubMed1996

Predictability of the clinical potency of NSAIDs from the preclinical pharmacodynamics in rats.

OBJECTIVE AND DESIGN: Relevance of the preclinical pharmacodynamic, toxicity and pharmacokinetic parameters predicting the clinical potency of nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated. MATERIAL: Data for oral potencies of 24 NSAIDs in rats were collected from the literature and from New Drug Applications with respect to the following parameters: antiinflammatory, analgesic, antipyretic, acute ulcerogenic activities, acute toxicity, in vitro inhibition of prostaglandin synthesis, acid dissociation constant (pKa), octanol-water partition coefficient and elimination half-life. TREATMENT: Data for most of the in vivo parameters in rats were collected following single dose administration with the exception of adjuvant arthritis. Single and daily clinical doses were considered. All of these NSAIDs have been approved for marketing although not all have been sold in the USA. METHODS: The preclinical data were compared to human dose (unit or daily doses) using single and multiple stepwise regression analyses. RESULTS: Analyses suggest that NSAIDs are effective in all models of preclinical tests for fever, pain and inflammation, however, carrageenin-induced rat paw edema model is clearly the best predictor of human dose. Rank order of preclinical models for predicting human dose is carrageenin > yeast induced fever > pressure induced pain = adjuvant arthritis in rats. The analysis suggested that the pain and adjuvant arthritis models in rats may also involve a prostaglandin independent mechanism. Of the two physicochemical factors tested, pKa contributed best to the carrageenin model towards predicting the clinical potency of NSAIDs. Mathematical relationships between human dose, carrageenin ED50 and pKa were established that may assist in the future clinical development of NSAIDs. CONCLUSIONS: Carrageenin-induced paw edema model in rats is the most robust predictor of the clinical potency of NSAIDs. Acid dissociation constant (pKa) appears to be a secondary contributor to the potency of NSAIDs. The relevance of the data analyses for developing cyclooxygenase-2 (COX-2) selective NSAIDs is discussed.

Administration, Oral↗
PubMed1996

Colonic conduit in children: protection of the upper urinary tract 16 years later?

PURPOSE: Complication rates of up to 86.6% have been reported after creation of an ileal conduit. In contrast to others, we construct an antirefluxing isoperistaltic colonic for incontinent diversion in children. MATERIALS AND METHODS: Between 1968 and 1989 a colonic conduit was created in 105 patients up to age 20 years for neurogenic bladder (76), bladder exstrophy (16) and other reasons (13). Long-term followup (minimum 5 years, mean 16.3 years, range 5 to 26) was possible in 84 patients (159 renal units). RESULTS: Early and late stenosis at the ureterocolic anastomosis, and stomal stenosis occurred in 7.6 and 15.5% of the cases, respectively. Renal calculi developed in 8.2% of the renal units. Eight kidneys without function after recurrent pyelonephritis, calculi or stenosis at the ureterocolic anastomosis were removed during followup. Compared to preoperative status 3 of the remaining 151 renal units had increased dilatation of the upper urinary tract at the last followup. A total of 31 patients had complications during followup and 18 underwent conversion to continent urinary diversion. CONCLUSIONS: When incontinent urinary diversion is necessary in children, a colonic conduit with the option of continent conversion should be created before deterioration of the upper urinary tract.

Adolescent↗
PubMed1996

Compound motor action potential recording distinguishes differential onset of motor block of the obturator nerve in response to etidocaine or bupivacaine.

The purpose of this investigation was to establish an objective (quantitative) method for determining onset time of motor block induced by different local anesthetics. Twenty-four consenting patients undergoing transurethral surgery during spinal anesthesia were randomized to receive direct obturator nerve block with 10 mL of plain bupivacaine 0.5% (n = 12) or 10 mL of plain etidocaine 1% (n = 12). Another 14 patients (control group) received obturator nerve "block" with saline. After identification of the obturator nerve, patients underwent testing of nerve conduction by recording compound motor action potentials (CMAPs) of thigh adductor muscles in response to stimulation provided by a nerve stimulator at 0.2 to 0.5-mA currents. Testing ended when CMAP amplitudes had returned to their baseline values (control group) or when motor blockade was 90% complete (local anesthetic groups). In all 38 patients, the amplitude of the thigh CMAPs decreased immediately after injection of saline or local anesthetic. While CMAP amplitudes in the control group returned to their initial (baseline) values after 3-6 min, the patients receiving etidocaine or bupivacaine achieved > or = 90% motor blockade after 6 and 13 min, respectively. In the present report, the time to > or = 90% block was significantly faster in patients given etidocaine compared with those given bupivacaine. We conclude that electromyographic recording of CMAPs can be used to compare the ability of different local anesthetics to induce motor block.

Adult↗
PubMed1996

Plasma exchange for dramatic gestational hyperlipidemic pancreatitis.

We describe the response to plasma exchange in a woman with extreme gestational hyperlipidemia and severe pancreatitis. Her serum triglyceride reached an astounding level of 21,300 mg/dl-among the highest concentrations ever recorded. Two consecutive plasma exchanges led to a remarkable reduction in triglyceride levels of 73% and 82%, respectively. Plasma viscosity decreased by 50% after the first plasma exchange. This was associated with an equally dramatic and unexpectedly rapid resolution of severe pancreatitis. Plasma exchange can rapidly and safely resolve extreme hyperlipidemia and be associated with prompt resolution of pancreatitis in women with severe gestational hyperlipidemic pancreatitis.

Acute Disease↗
PubMed1996

Pyeloplasty in hydronephrosis: examination of surgical results from a morphologic point of view.

BACKGROUND: Dilatation of the upper urinary tract is the most common congenital urogenital anomaly. Pyeloplasty is the therapy of choice in those patients with significant obstruction of the ureteropelvic junction. There are not many reports concerning the operative long-term results from a morphologic point of view. Furthermore, little information is available about children with giant hydronephrosis treated without resection of the dilated renal pelvis. METHODS: Between 1973 and 1993, 231 children with 262 renal units (kidney, renal pelvis, ureter) were treated at our institution. Giant hydronephrosis was observed in 52 renal units. The clinical and follow-up data were obtained from the patients' records. The dilatation of the upper urinary tract, confirmed by means of intravenous pyelogram, was divided into 5 grades. RESULTS: In 215 renal units, reconstructive surgery was performed without reduction of the renal pelvis. Revision of the pyeloplasty was necessary in 5 of the 215 renal units. The dilatation of the upper urinary tract improved or remained stable in 99.4% of the renal units during the follow-up period of 4.8 years (range, 1 month to 21 years). CONCLUSION: Surgical reconstruction of the ureteropelvic junction obstruction is a safe and successful procedure. The excision of the dilated pelvis does not seem to be necessary, even in patients with giant hydronephrosis.

Child↗
PubMed1996

Calcium blockage in pulmonary hypertension and hypoxic vasoconstriction.

Both extracellular and intracellular calcium (Ca2+) play important roles in hypoxic pulmonary vasoconstriction (HPV) and the vasoconstrictor responses to endogenous pulmonary vasoconstrictor substances, as evidenced by the effect of calcium-channel blockers on these vasoconstrictor responses and the measurement of changes in Ca2+ flux or intracellular Ca2+ concentrations in isolated cells. The more vasoselective the calcium-channel blocker, the greater its effect on pulmonary vasoconstriction. However, these drugs are not selective for the pulmonary vascular bed and are not as potent as pulmonary vasodilators when compared with other vasodilator drugs, including prostaglandin E1, isoproterenol, prostacyclin, or nitroglycerin. Moreover, the primary effect of vasoselective calcium-channel blockers on pulmonary vascular resistance is secondary to the effects of these agents on systemic vascular resistance and cardiac output. Although there is improvement in oxygen delivery, exercise tolerance, and survival in patients with primary pulmonary hypertension who respond to calcium-channel blockers, the response of individual patients to these drugs is difficult to predict because the extent of reversible versus irreversible changes in the pulmonary vasculature is not known. The use of these drugs in patients with chronic hypoxia-induced pulmonary vasoconstriction may be associated with a worsening of ventilation-perfusion mismatching secondary to inhibition of HPV.

Animals↗