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Biomedical subjects

P Unger

Publications and source records attributed to P Unger.

At least 19 recordsLinked to original sources
PubMed1995

Seminal vesicle biopsy and laparoscopic pelvic lymph node dissection: implications for patient selection in the radiotherapeutic management of prostate cancer.

PURPOSE: Seminal vesicle biopsies (SVB) and laparoscopic pelvic lymph node dissection (LPLND) are safe surgical staging procedures for prostate cancer that can yield more accurate information than can be obtained by routine clinical means. This information is critical in patient and treatment selection when planning definitive prostate irradiation. An analysis of the procedural findings was undertaken to better define those patients who might benefit from these procedures. METHODS AND MATERIALS: From June 1990 to February 1994, 120 patients with clinical Stage T1b to T2c prostate cancer with negative bone scan and pelvic computerized tomography (CT) scans underwent transrectal ultrasound guided SVB (three from each side). Of these patients, 99 also underwent LPLND. Twelve patients were excluded from analysis of LPLND findings because they were treated with 3 months of hormonal therapy prior to LPLND. During LPLND, 0 to 18 nodes were removed (median-five nodes) from the right side and 0 to 20 nodes (median-five nodes) were removed from the left side. Prostate specific antigen (PSA) values ranged from 1.6 to 190 ng/ml, with a median value of 11.5. Combined Gleason grades ranged from 2 to 9, with a median of 6. RESULTS: A positive SVB was found in 18 patients (15%). A logistic regression analysis was performed to test the effect of grade, PSA, and stage on SVB results. Combined grade and PSA were significant predictors of a positive SVB (p < 0.001 and p = 0.024, respectively). Patients with combined grades of 7 or greater had a higher positive SVB rate of 37.5% (12 out of 32) compared to 7% (6 out of 88) for patients with a lower grade (p < 0.0001). Patients with PSA values greater than 10 had a positive SVB rate of 21% (15 out of 70) compared to 6% (3 out of 50) for patients with values up to 10. There was no morbidity associated with SVB. Laparoscopic pelvic lymph node disection detected positive pelvic nodes in nine patients (10%). The effect of a positive SVB, combined Gleason grade, PSA, and stage on the detection of positive nodes were tested using a stepwise logistic regression analysis. Seminal vesicle biopsy was the most significant predictor of positive nodes (p < 0.0001), while combined grade and PSA were also significant predictors (p = 0.0006 and p = 0.005, respectively). Positive nodes were found in 50% (9 out of 18) of patients with positive SVB compared to 0% (0 out of 69) of patients with a negative SVB (p < 0.0001). Positive nodes were found in 35% (8 out of 23) of patients with a combined grade of 7 or greater compared to 2% (1 out of 64) of patients with a combined grade less than 7 (p < 0.0001). Laparoscopic pelvic lymph node dissection revealed positive nodes in 3% (2 out of 58) of patients with PSA levels < = 20 compared to 24% (7 out of 29) of patients with PSA levels greater than 20 (p = 0.003). Laparoscopic pelvic lymph node dissection was associated with a hospital stay of one night and a minor complication rate of 4%. There were no major complications. CONCLUSIONS: Seminal vesicle biopsy should be performed before treatment in all patients, except those with low risk factors, undergoing radiation therapy for prostate cancer, due to its ability to upstage patients, select patients for LPLND, and alter radiotherapeutic management. Laparoscopic pelvic lymph node dissection should be considered in patients with high risk features, especially in patients with positive SVB where the likelihood of encountering positive nodes is 50%.

Adenocarcinoma↗
PubMed1995

Plasma endothelin and early coronary endothelial dysfunction in recipients of a cardiac transplant.

Serotonin constricts coronary arteries with endothelial dysfunction, possibly through reduced endothelial release of nitric oxide or enhanced production of constricting factors such as endothelin. Because the plasma levels of this peptide are increased in the early months after cardiac transplantation, we assessed whether a coronary hypersensitivity to the vasoconstrictor effect of serotonin is associated with high plasma endothelin levels. One to 3 months after cardiac transplantation, serotonin (1, 10, or 20 micrograms/min for 2.5 min each) was infused into the coronary circulation in 32 patients. Changes in coronary diameters were determined by quantitative angiography. A > or = 40% reduction in coronary diameter for a dose of serotonin < or = 10 micrograms/min was observed in group A (n = 14) whereas in group B (n = 18), this diameter reduction was never reached even for a 20 micrograms/min infusion of serotonin. Plasma endothelin levels were significantly higher (p < 0.01) in the coronary ostium and coronary sinus in group A, at 23.4 +/- 1.3 pg/ml and 24.9 +/- 0.9 pg/ml versus 12.6 +/- 0.9 pg/ml and 13.8 +/- 1.1 pg/ml, respectively, in group B. These endothelin levels did not significantly change after intracoronary infusion of serotonin. A significant correlation was found between plasma endothelin levels in the coronary ostium and peak coronary constriction (percentage diameter reduction) in both groups (r = 0.77 for group A and r = 0.92 for group B). Thus, early after cardiac transplantation, serotonin-induced coronary constriction is a common finding, and the severity of this abnormality seems to be influenced by plasma endothelin levels.

Blood Pressure↗
PubMed1995

Successful treatment of metastatic small cell carcinoma of the bladder with methotrexate, vinblastine, doxorubicin and cisplatin therapy.

A man with metastatic small cell carcinoma of the bladder who was treated with methotrexate, vinblastine, doxorubicin and cisplatin therapy achieved complete remission with disease-free survival of more than 9 years. The nature of this unusual form of bladder carcinoma and the course of the disease in our case are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Doppler echocardiographic diagnosis and follow-up of acquired pulmonary stenosis due to external cardiac compression.

Mediastinal tumors that cause hemodynamic disturbances by compressing the heart are extremely rare. We report the case of a 19-year-old woman who presented right ventricular outflow tract obstruction due to a non-Hodgkin lymphoma. The diagnosis of this complication and its response to chemotherapy can be accurately assessed by transthoracic echocardiography and Doppler.

Adult↗
PubMed1995

Chronic angiotensin-converting enzyme inhibition and endothelial function of rat aorta.

To determine whether chronic angiotensin-converting enzyme (ACE) inhibition produces functional changes in the aorta normotensive rats, four groups of rats were studied in parallel for 6 weeks. Group 1 orally received ramipril and beta 2-kinin antagonist HOE140 500 micrograms/kg per day s.c. by injection for the remaining 2 weeks; group 3, hydralazine 100 mg/kg per day PO for 6 weeks; group 4 (control), subcutaneous injections of saline solution during the last 2 of 6 weeks. In aorta isolated from group 1 the relaxations induced by bradykinin, acetylcholine, and histamine were significantly potentiated compared with those of group 4. In group 3, despite a decrease in systolic blood pressure similar to that induced by ramipril treatment, the responses to these three endothelium-dependent vasodilators were not different from those of group 4. In group 2, bradykinin-induced relaxations were completely abolished whereas acetylcholine-induced and histamine-induced relaxations were to those of group 4. The inhibitory effect of the endothelium on serotonin-induced contractions was significantly increased in preparations of group 1 compared with those of groups 2 through 4. Indirect measurements of nitric oxide formation such as contractions evoked by NG-monomethyl-L-arginine (L-NMMA) and aortic cGMP content were also significantly enhanced in preparations from group 1 compared with those of groups 2 through 4. Moreover, because the relaxations to nitroglycerin and nitroprusside were similar in groups 1, 2, and 4 an alteration of the guanylate cyclase activity by ramipril treatment is quite unlikely. Thus long-term treatment with ramipril potentiates the endothelium-dependent responses in the rat aorta by enhancing nitric oxide availability.

Adrenergic beta-Antagonists↗
PubMed1995

Laparoscopic pelvic lymph node dissection combined with real-time interactive transrectal ultrasound guided transperineal radioactive seed implantation of the prostate.

Laparoscopic pelvic lymph node dissection with real-time interactive transrectal ultrasound guided transperineal radioactive seed implantation is a new method of treatment for localized carcinoma of the prostate. A total of 58 patients with clinically confined prostate cancer and negative seminal vesicle biopsies underwent staging laparoscopic pelvic lymph node dissection immediately followed by prostate implantation: 50 had 125iodine and 8 had 103palladium implants. Mean operating time was 226 minutes (range 120 to 475), mean blood loss was 57 cc (range 5 to 400) and average hospital stay was 2.2 days (range 0.5 to 8). At a mean followup of 12 months (range 6 to 24), complications included proctitis in 1.7% of the cases, dysuria in 24%, nocturia in 21% and outlet obstruction in 17%. Erectile function remained unchanged. Prostate volume decreased to 58.9% of the pretreatment value by 12 months and to 44.3% by 24 months. Mean prostate specific antigen level was 18.4 +/- 26.3 ng./ml. before treatment, 3.4 +/- 3.9 ng./ml. at 6 months, 2.3 +/- 2.3 ng./ml. at 12 months and 4.9 +/- 6.0 ng./ml. at 24 months (1.2 +/- 1.0 ng./ml. for patients with no evidence of disease). Of the patients 15.8% had local failure at 18 to 24 months as determined by positive transrectal ultrasound guided biopsy. Five of 58 patients (8.6%) had persistently elevated prostate specific antigen levels, only 1 of whom had a positive biopsy. Laparoscopic pelvic lymph node dissection with transrectal ultrasound guided implantation is a safe and promising mode of therapy for patients with localized prostate cancer.

Aged↗
PubMed1995

Indications for seminal vesicle biopsy and laparoscopic pelvic lymph node dissection in men with localized carcinoma of the prostate.

PURPOSE: The ability of seminal vesicle biopsy and laparoscopic pelvic lymph node dissection to identify patients with stage T3 or N+ disease before undergoing treatment for localized carcinoma of the prostate was investigated. MATERIALS AND METHODS: A total of 157 patients with clinical stages T1a to T2c prostate cancer underwent ultrasound guided seminal vesicle biopsy (3 on each side) and 130 underwent subsequent laparoscopic pelvic lymph node dissection. RESULTS: Of 157 patients 23 (14.6%) had a positive seminal vesicle biopsy. Predictors of a positive seminal vesicle biopsy were stages T2b to T2c versus T1a to T2a disease (20% versus 4%, respectively, p = 0.005), Gleason score 7 or more versus less than 7 (34% versus 9%, respectively, p < 0.0001) and prostate specific antigen (PSA) 4 to 10 ng./ml., 10 to 20 ng./ml. or more than 20 ng./ml. (9%, 14% and 27%, respectively, p = 0.03). Of 130 patients 14 (10.7%) had a positive laparoscopic pelvic lymph node dissection. Predictors for a positive laparoscopic pelvic lymph node dissection were Gleason score 7 or more versus less than 7 (32% versus 2%, respectively, p < 0.0001), PSA more than 20 ng./ml. or less than 20 ng./ml. (24% versus 4.5%, respectively, p = 0.009) and stage T2b or T2c (15% and 24%, respectively, p = 0.056). Of the patients with a positive seminal vesicle biopsy 48% had a positive laparoscopic pelvic lymph node dissection (p < 0.0001). CONCLUSIONS: All patients with a Gleason score more than 4, PSA more than 10 ng./ml. or clinical stage T2b or more should undergo seminal vesicle biopsy, and those with a positive seminal vesicle biopsy or Gleason score 7 or greater should undergo laparoscopic pelvic lymph node dissection before initiating therapy for localized carcinoma of the prostate.

Aged↗
PubMed1994

Thyroglobulin-induced murine thyroiditis assessed by intrathyroidal T cell receptor sequencing.

Thyroid glands from CBA/J (H-2k) mice, with human thyroglobulin (Tg)-induced thyroiditis, were removed and total cellular RNA was prepared and reverse transcribed as target cDNA for PCRs to detect 17 murine T cell receptor (mTCR) V beta families. Southern analysis of the resulting PCR fragments showed a marked bias in the intrathyroidal expression of mTCR V beta gene families with only 10 detectable V beta gene families of the 17 tested. Four Tg-specific CBA/J T cell lines also showed a biased use of mTCR V beta gene families with only 7 V beta gene families detected of the 17 tested. Sequence analysis showed evidence of oligoclonal expansion of the intrathyroidal T cell populations, and some of the CDR3 sequences found in the thyroid infiltrates were identical, or similar, to examples of the patterns of CDR3 sequences seen in the Tg-specific lines. Overall, however, there was marked N-D-N sequence variation in both the lines and thyroid infiltrates. These data indicated that 1) mTcR V gene analysis of intact thyroid tissue reflected the thyroid Ag-specific T cells infiltrating the thyroid gland; 2) confirmed the phenomenon of oligoclonal expansion in early thyroiditis; 3) showed that certain V beta gene families may be overemployed in the T cell recognition of Tg in the context of H-2k; and 4) revealed, by the varied patterns of the CDR3 sequences, that the V gene itself may be more important in thyroid Ag recognition than N-D-N region motifs.

Amino Acid Sequence↗
PubMed1994

Comparison of the hemodynamic responses to molsidomine and isosorbide dinitrate in congestive heart failure.

To evaluate the mechanisms involved in nitrate tolerance, we randomized 23 patients with congestive heart failure resulting from coronary artery disease to an isosorbide dinitrate or a molsidomine infusion. The drugs were titrated to decrease pulmonary capillary wedge pressure by > or = 30% or > or = 10 mm Hg. Then isosorbide dinitrate, molsidomine, or placebo was infused in a double-blind randomized manner for 24 hours. In all patients, treatment with enalapril was begun > or = 48 hours before the beginning of the protocol and was continued throughout the study to avoid renin-angiotensin activation. The pulmonary capillary wedge pressure remained significantly decreased at 24 hours during molsidomine infusion only. No significant increase in catecholamines occurred. Because molsidomine differs from organic nitrates by its property of directly stimulating guanylate cyclase without depending on thiol group availability, these results suggest that impaired biotransformation of nitrates is involved in tolerance induced by high doses of isosorbide dinitrate in congestive heart failure.

Biotransformation↗
PubMed1994

Effect of narrow, pulsed high voltages on bacterial viability.

BACKGROUND AND PURPOSE: High-voltage pulsed current (HVPC) has been used to promote the healing of decubitus ulcers and surgical wounds. The benefits of HVPC are thought to include an antimicrobial action. This study was undertaken to explore the development of an in vitro system for the systematic evaluation of the effects of HVPC. METHODS: Using agarose-based media, the system allows for examination of the direct effect of HVPC on microorganisms as well as exploration of the possible in situ generation of bacteriostatic or bactericidal factors by the action of HVPC on constituents of the media. The solid media also allow characterization of the spatial extent of the current's effects such as changes in temperature or pH. The system was used to examine the effects of HVPC on four different species of bacteria: Escherichia coli, Klebsiella, Pseudomonas aeruginosa, and Staphylococcus aureus. RESULTS: Both direct and indirect bactericidal effects were observed at either the positive or negative electrode, or both, for each of the organisms, although zones of inhibition varied. Temperature and pH were examined as possible mechanisms for the indirect effect. Temperature changes observed during the application of HVPC were minimal and did not contribute to the antimicrobial effect. Extreme pH changes did not appear to be the major cause of the indirect effect because the zones of inhibition observed were generally larger than the zones of extremely acid or basic pHs. CONCLUSION AND DISCUSSION: High-voltage pulsed current produced antimicrobial effects in this in vitro study. Additional studies are needed to elucidate the mechanisms and to determine whether the mechanisms occur in vivo.

Bacterial Infections↗
PubMed1994

Attenuation of cyclosporine A-induced vascular toxicity by ramipril.

We wished to determine whether chronic inhibition of angiotensin-converting enzyme (ACE) prevents the vascular toxicity of cyclosporine A (Cx). In aortas isolated from rats treated with ramipril [10 mg/kg/day orally (p.o.) for 4 weeks], the endothelium-dependent relaxations to acetylcholine (ACh) were potentiated (the area under the curve (AUC) decreased from 154 +/- 35 to 63 +/- 12, p < 0.05), but contractions induced by phenylephrine (PE) and angiotensin II (AII) were not affected. Therefore, we studied three groups of rats in parallel. Group 1 received ramipril 10 mg/kg/day p.o. for 4 weeks and ramipril 10 mg/kg/day p.o. plus Cx 20 mg/kg/day intramuscularly, in fifth week; group 2 received Cx only (20 mg/kg/day i.m. for 1 week), and group 3 served as control. In group 2, ACh-induced relaxations were reduced as compared with those of the control group (AUC increased from 141 +/- 34 to 240 +/- 32, p < 0.05), whereas in group 1, AUC was not significantly different from that of group 3 (195 +/- 28 vs. 141 +/- 34). In group 2, PE- and AII-induced contractions were enhanced; AUC values for PE and AII were 495 +/- 45 versus 348 +/-38 in group 3 and 424 +/- 28 versus 314 +/- 17 in group 3, respectively (p < 0.05). In group 1, AUCs for PE and AII were not significantly different from those of group 3. After mechanical removal of the endothelium, the increased responsiveness to PE and AII persisted in group 2 whereas AUC values in group 1 were not different from those of group 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Preservation of functioning human thyroid "organoids" in the severe combined immunodeficient mouse. III. Thyrotropin independence of thyroid follicle formation.

The severe combined immunodeficient (scid) mouse allows the in vivo reconstitution of thyroid follicles from thyroid monolayer cells when transplanted sc within an extracellular basement membrane matrix. After 2-3 weeks, these human thyroid organoids show an active microfollicular histology and secrete human thyroglobulin into the murine serum in response to the administration of recombinant human TSH. Furthermore, such organoids survive for more than 3 months in this functional state. To assess whether thyroid follicular reconstitution was TSH dependent, we examined organoid follicular reconstruction in T3-induced hyperthyroid scid mice, in which endogenous murine TSH was presumed to be totally suppressed. By providing water with 12 micrograms/ml T3, we increased the murine serum T3 levels from a mean of 1.9 nmol/liter in controls to greater than 12.0 nmol/liter. After 3 weeks, thyroid cells derived from normal human thyroid monolayers were suspended in an extracellular basement membrane matrix, and the suspension was transplanted sc into scid mice (with or without T3-induced hyperthyroidism) and allowed to reconstitute. Histological examination 4 weeks later showed a similar degree of thyroid follicle formation in mice treated with or without T3, indicating that the hyperthyroid state had caused no interference with thyroid follicle reconstitution. This was further confirmed by transmission electron microscopy, which demonstrated normal human thyroid follicle cell polarity in the organoids of both euthyroid and hyperthyroid mice. In addition, using an extracellular basement membrane preparation with reduced growth factor (epidermal growth factor, insulin-like growth factor-I, and platelet-derived growth factor) levels also allowed normal thyroid follicle formation in T3-fed mice. These data demonstrate that in vivo thyroid follicle formation is TSH independent and that extrathyroidal epidermal growth factor, insulin-like growth factor-I, and platelet-derived growth factor may be relatively unimportant. The factors and molecular mechanisms leading to follicular reorganization of adult human thyroid cells remain to be determined, but are likely to depend largely on intrathyroidal growth factor secretion and cell-cell interaction.

Animals↗
PubMed1994

Engraftment of human lymphocytes and thyroid tissue into scid and rag2-deficient mice: absent progression of lymphocytic infiltration.

To study human autoimmune thyroid disease in an animal model we have investigated the in vivo survival of human thyroid tissues and functionality of human lymphocytes in severe combined immunodeficient (scid) mice and recombination-activating gene (rag2) knockout mice. We found successful engraftment of human thyroid tissues in both scid and rag2-deficient mice. However, when peripheral blood mononuclear cells were transplanted ip, human immunoglobulin production was poor in rag2-deficient mice compared to that in scid mice (mean human immunoglobulin G levels at 6 weeks, 0.2 +/- 0.2 microgram/mL in two of eight rag2-deficient mice compared to 20.8 +/- 7.0 micrograms/mL in seven of nine scid mice; P < 0.05). We, therefore, only pursued the further use of scid mice and transplanted them with thyroid tissue from patients with either Graves' disease (four patients) or Hashimoto's thyroiditis (one patient). At the functional level, we observed transiently increased thyroid hormone levels (T4 peaking at 5.4 +/- 0.2 microgram/dL compared to a normal level of 2.6 +/- 0.2 microgram/dL); human autoantibodies to human thyroglobulin, human thyroid peroxidase, and the human TSH receptor were also detected in thyroid-transplanted mice. In contrast to recent reports, histological examination of the thyroid explants showed no increase in the lymphocytic infiltrate compared to the original donor tissue, nor was there any thyroid follicular destruction observed. In fact, many of the transplants demonstrated a marked diminution in the infiltrates over time, with an absence of HLA-DR antigen expression by both T-cells and thyrocytes. Cotransplanted allogeneic thyroid tissues were unremarkable in terms of lymphocytic infiltrates and showed intact morphology. Taken together, these data point to a relative degree of T-cell inactivity within the thyroid explants from the scid mouse. Hence, a factor(s) present in the patient with autoimmune thyroid disease that activates their thyroid-specific T-cells may be absent in this murine model as presently constructed.

Animals↗
PubMed1993

Nitrate tolerance and aging in isolated rat aorta.

The purpose of this study was to determine whether there are age-related changes in the extent of in vitro-induced nitrate tolerance. Nitroglycerin pre-exposure (10 microM for 30 min) provoked a significant shift to the right of the dose-response curve to nitroglycerin in aortae isolated from rats of 8 weeks, 12 and 18 months. However, this shift to the right was significantly larger at 18 months, both when KCl or phenylephrine were used as contractile agents. On the contrary, nitroglycerin pre-exposure did not significantly alter the dose-dependent relaxation to Sin-1 (3-morpholinosydnonimine, the active metabolite of molsidomine) at 8 weeks, 12 and 18 months. These data indicate that the extent of the in vitro-induced nitrate tolerance is larger when aortae are isolated from senescent rats. This increase in tolerance does not appear to involve desensitization of guanylate cyclase.

Aging↗
PubMed1993

Effects of serotonin on coronary arteries of cardiac transplant recipients.

Serotonin constricts coronary arteries with endothelial dysfunction. To detect early graft artery disease, the responses to intracoronary serotonin were studied 1 month (group A, 14 patients) and 1 year (group B, 13 patients) after orthotopic cardiac transplantation. No patient had evidence of rejection and all had angiographically normal coronary arteries. Serotonin in increasing doses (1, 10 and 20 micrograms/min for 2.5 minutes each) was infused into the coronary circulation. Diameters of proximal, middle and distal segments were measured by quantitative angiography. At the maximal concentration of serotonin, the diameters of the proximal segments decreased to 73 +/- 4% (percentage of the baseline) in group A; the diameters of the middle and distal segments decreased to 67 +/- 5 and 63 +/- 4%, whereas in group B, the diameters of the proximal, middle and distal segments were 90 +/- 6% (p < 0.02 vs group A value), 88 +/- 5% (p < 0.01 vs group A value) and 84 +/- 4% (p < 0.01 vs group A value), respectively. These changes were significantly (p < 0.02) different from those observed in 6 control patients in whom no constriction was induced by intracoronary serotonin. Moreover, coronary plasma endothelin levels were significantly higher in group A than in group B and control patients (5.6 +/- 0.3 vs 4.3 +/- 0.2 fmol/ml in group B and 3.9 +/- 0.3 fmol/ml in control patients). Thus, an abnormal response to intracoronary serotonin seems to occur often in transplant patients, and this abnormality is unexpectedly more pronounced in the early weeks after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗