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K M Rieger

Publications and source records attributed to K M Rieger.

8 recordsLinked to original sources
PubMed2000

Results of modern therapy for patients with mediastinal nonseminomatous germ cell tumors.

BACKGROUND: The aim of this study was to determine the effects of independent prognostic variables, such as prechemotherapy tumor markers, the extent of disease at diagnosis, the tumor markers postchemotherapy (PC), and the pathology of the PC residual mass on the overall survival of patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCT). METHODS: The authors undertook a retrospective review of 39 patients with PMNSGCT between 1983 and 1997 who received their initial chemotherapy at Indiana University and 36 additional patients referred for PC resection. All patients received chemotherapy based on the combination of cisplatin and etoposide. The median follow-up was 22 months (range, 12-144 months). RESULTS: The prechemotherapy tumor markers did not affect overall survival. Extent of disease (mediastinal only vs. visceral metastases) was an important prognostic factor for survival in univariate analysis (P = 0.042). Sixty-two of 75 patients underwent PC resection of residual disease. Fifteen of the 62 patients achieved a CR with chemotherapy alone, as the PC resection revealed only necrosis. Fourteen of these 15 patients continuously had no evidence of disease (NED). Forty-seven of the 62 patients had NED with chemotherapy and PC resection, including 31 with teratoma and 16 with carcinoma. However, 11 of 31 with teratoma and 11 of 16 with carcinoma subsequently relapsed. Although 18 patients had elevated tumor markers at the time of PC resection, 6 of 18 had only necrosis and 4 had teratoma. The PC tumor markers did not affect survival. The pathology of the resected specimen was the most significant predictor of survival in multivariate analysis (P < 0.001). CONCLUSIONS: Twenty-eight of 39 patients (71.8%) with PMNSGCT treated at Indiana University achieved NED status, but only 16 (41%) continuously had NED. Twenty of 36 (55.5%) referred for resection continuously had NED. Disease confined to the mediastinum and necrosis in the PC specimen were important prognostic factors for survival.

Adolescent↗
PubMed2000

Norepinephrine and N(G)-monomethyl-L-arginine in hyperdynamic septic shock in pigs: effects on intestinal oxygen exchange and energy balance.

OBJECTIVES: To compare the effects of norepinephrine (NOR) and the nonselective nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), on intestinal blood flow, oxygen exchange, and energy metabolism over 24 hrs of hyperdynamic, normotensive porcine endotoxic shock. DESIGN: Prospective, randomized, experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Twenty-seven pigs were divided into three groups: seven animals received no vasopressor therapy (ETX) during endotoxic shock; ten animals were treated with NOR; and ten animals were treated with L-NMMA. INTERVENTIONS: Pigs were anesthetized, mechanically ventilated, and instrumented. Eight hours later, endotoxic shock was initiated by an infusion of Escherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch directed to maintain the intrathoracic blood volume and a mean arterial pressure (MAP) of >60 mm Hg. Twelve hours after the start of the endotoxin infusion, NOR or L-NMMA was administered for 12 hrs in the treatment groups to maintain a MAP at preshock levels. MEASUREMENTS AND MAIN RESULTS: ETX caused a continuous fall in MAP, despite a sustained increase in the cardiac output achieved by fluid resuscitation. NOR maintained MAP at preshock levels because of a further rise in cardiac output, whereas hemodynamic stabilization during L-NMMA resulted from systemic vasoconstriction. NOR increased portal venous blood flow concomitant with decreased intestinal oxygen extraction, whereas L-NMMA influenced neither portal venous blood flow nor intestinal oxygen extraction. Mean capillary hemoglobin oxygen saturation of the ileal mucosa as well as the frequency distributions reflecting microcirculatory oxygen availability remained unchanged as well. Nevertheless, portal venous pH similarly decreased and portal venous lactate/pyruvate ratios increased in all three groups. The arterial-ileal mucosal PCO2 gap progressively increased in the ETX and L-NMMA groups, whereas NOR blunted this response. CONCLUSIONS: Neither treatment could reverse the ETX-induced derangements of cellular energy metabolism as reflected by the increased portal venous lactate/pyruvate ratios. The NOR-induced attenuation of ileal mucosal acidosis was possibly caused by a different pattern of blood flow redistribution compared with L-NMMA.

Animals↗
PubMed1999

Primary mediastinal nonseminomatous germ cell tumors: the influence of postchemotherapy pathology on long-term survival after surgery.

OBJECTIVES: The treatment of nonseminomatous germ cell tumors with cisplatin-based chemotherapy followed by aggressive surgical resection of residual disease is one of the most successful models for multimodality cancer therapy. We reviewed the case histories of 91 patients treated at our institution from 1981 to 1998 with primary mediastinal nonseminomatous germ cell tumors to evaluate variables that may influence survival after surgery. METHODS: Twelve of the 91 patients did not undergo postchemotherapy resection because of progressive disease. Seventy-nine of them underwent 82 thoracic surgical procedures and are the basis of this review. The majority (71/75) had elevated serum tumor markers, 75% (n = 50) of which returned to normal levels after first- or second-line chemotherapy. RESULTS: There were 3 operative deaths and 1 late death, attributed to pulmonary complications. Twenty-four patients died of recurrent disease and 3 of leukemia, for an overall survival of 61% after an average follow-up of 48 months. The pathologic findings of complete tumor necrosis (n = 19) and benign teratoma (n = 28) in the surgical specimen predicted excellent and good long-term survival, respectively, which was statistically better than that of patients having persistent nonseminomatous germ cell tumors (n = 24) or carcinomatous/sarcomatous degeneration (n = 8). CONCLUSIONS: Primary nonseminomatous germ cell tumors of the mediastinum can be cured with a multimodality therapy, particularly in the subset of patients with postchemotherapy pathologic findings of tumor necrosis and teratoma. Survival is poor but possible in patients with unfavorable pathologic findings after chemotherapy, currently justifying an aggressive surgical approach in patients with otherwise operable disease.

Adolescent↗
PubMed1999

Norepinephrine and nomega-monomethyl-L-arginine in porcine septic shock: effects on hepatic O2 exchange and energy balance.

We compared the effects of norepinephrine (NOR; n = 11) and the nonselective nitric oxide synthase inhibitor Nomega-monomethyl-L-arginine (L-NMMA; n = 11) on hepatic blood flow (Q liv), O2 exchange, and energy metabolism over 24 h of hyperdynamic, normotensive porcine endotoxic shock. Endotoxin (ETX; n = 8) caused a continuous fall in mean arterial pressure (MAP) despite a sustained 50% increase in cardiac output (Q) achieved by adequate fluid resuscitation. NOR maintained MAP at preshock levels owing to a further rise in Q, while the comparable hemodynamic stabilization during L-NMMA infusion resulted from systemic vasoconstriction, increasing the systemic vascular resistance (SVR) about 30% from shock level after 6 h of treatment concomitant with a reduction in Q to preshock values. Whereas NOR also increased Q liv and, hence, hepatic O2 delivery (hDO2), but did not affect hepatic O2 uptake (hVO2), L-NMMA influenced neither Q liv nor hDO2 and hVO2. Mean capillary hemoglobin O2 saturation (HbScO2) on the liver surface as well as HbScO2 frequency distributions, which mirror microcirculatory O2 availability, remained unchanged as well. Neither treatment influenced the ETX-induced derangements of cellular energy metabolism reflected by the progressive decrease in hepatic lactate uptake rate and increased hepatic venous lactate/pyruvate ratios. ETX nearly doubled the endogenous glucose production (EGP) rate, which was further increased with NOR, whereas L-NMMA nearly restored EGP to preshock levels. Nevertheless, despite the different mechanisms in maintaining blood pressure neither treatment influenced ETX-induced liver dysfunction.

Animals↗
PubMed1998

Effect of increased cardiac output on liver blood flow, oxygen exchange and metabolic rate during longterm endotoxin-induced shock in pigs.

We investigated hepatic blood flow, O2 exchange and metabolism in porcine endotoxic shock (Control, n = 8; Endotoxin, n = 10) with administration of hydroxyethylstarch to maintain arterial pressure (MAP)>60 mmHg. Before and 12, 18 and 24 h after starting continuous i.v. endotoxin we measured portal venous and hepatic arterial blood flow, intracapillary haemoglobin O2 saturation (Hb-O2%) of the liver surface and arterial, portal and hepatic venous lactate, pyruvate, glycerol and alanine concentrations. Glucose production rate was derived from the plasma isotope enrichment during infusion of [6,6-2H2]-glucose. Despite a sustained 50% increase in cardiac output endotoxin caused a progressive, significant fall in MAP. Liver blood flow significantly increased, but endotoxin affected neither hepatic O2 delivery and uptake nor mean intracapillary Hb-O2% and Hb-O2% frequency distributions. Endotoxin nearly doubled endogenous glucose production rate while hepatic lactate, alanine and glycerol uptake rates progressively decreased significantly. The lactate uptake rate even became negative (P<0.05 vs Control). Endotoxin caused portal and hepatic venous pH to fall significantly concomitant with significantly increased arterial, portal and hepatic venous lactate/pyruvate ratios. During endotoxic shock increased cardiac output achieved by colloid infusion maintained elevated liver blood flow and thereby macro- and microcirculatory O2 supply. Glucose production rate nearly doubled with complete dissociation of hepatic uptake of glucogenic precursors and glucose release. Despite well-preserved capillary oxygenation increased lactate/pyruvate ratios reflecting impaired cytosolic redox state suggested deranged liver energy balance, possibly due to the O2 requirements of gluconeogenesis.

Alanine Transaminase↗
PubMed1995

Increased incidence of p53 mutations is associated with hepatic metastasis in colorectal neoplastic progression.

Within a panel of 15 colon carcinoma cell lines we have characterized the p53 gene status using immunocytochemistry (ICC), SSCP and direct sequence analysis. Extension of this analysis to the use of ICC on 104 colonic lesions, representative of different stages of colonic neoplastic progression, showed an absence of detectable p53 nuclear staining in preneoplastic polyp lesions (20 cases) with staining of 52% (25/48) of primary colon carcinomas and 81% (29/36) of hepatic metastases, suggestive of an increased incidence of p53 mutations in late stage lesions of colonic cancer. To address this issue more directly, we analysed 18 primary colon carcinomas and hepatic metastases excised coincidentally from the same patients. In ICC, p53 nuclear staining was recorded in matching lesions from eight individuals where direct sequencing revealed identical mutations in each case. In four individuals no ICC staining was detected in either lesion and molecular analysis revealed wild type sequence in exons 4-9. In six individuals p53 nuclear staining was observed in the hepatic metastases of patients but not the primary lesion. Molecular analysis revealed point mutation events in hepatic metastases from these patients which were not detected in the primary tumor. The point mutations identified in colon carcinomas were predominantly transition events (83%) located in previously characterized colon hotspot regions. These results demonstrate an increased incidence of p53 mutations associated with secondary lesions of colorectal tumors suggestive of a role for p53 in the establishment of colorectal hepatic metastases.

Amino Acid Sequence↗
PubMed1995

Human bladder carcinoma cell lines as indicators of oncogenic change relevant to urothelial neoplastic progression.

Analysis of human tumour-derived cell lines has previously resulted in the identification of novel transformation-related elements and provided a useful tool for functional studies of different genes. To establish the utility of such cell lines as indicators of change relevant to urothelial cancer, we have characterised the expression of five genes (p53, MDM2, Rb, E-cadherin, APC) within a panel of human bladder carcinoma cell lines. Using single-strand conformation polymorphism (SSCP) and direct sequencing, p53 mutations were identified in 7/15 (47%) cell lines reflecting events reported in bladder tumours. Immunohistochemical analysis of p53 in cultured cells and in paraffin-embedded sections of xenografts from the cell line panel revealed discordant results. An absence of p53 nuclear staining was associated with an exon 5 mutation in EJ and with multiple p53 mutations found in J82. Two cell lines positive for p53 staining in the absence of detectable mutation displayed overexpression of MDM2 (PSI, HT1197) in Western blot analysis. Loss or aberrant Rb expression was recorded in 5/15 (TCCSUP, SCaBER, 5637, HT1376, J82) cell lines. Absence of E-cadherin was recorded in 5/15 cell lines (TCCSUP, EJ, KK47, UM-UC-3, J82) with loss of alpha-catenin in immunoprecipitated E-cadherin complexes of CUBIII. Western blot analysis of APC revealed a truncated protein in 1/15 (CUBIII) cell lines. The characterisation of oncogenic events within this panel of human bladder carcinoma cell lines establishes a representation of change observed in bladder tumours and better defines the genotypic background in these experimental human cell models of neoplastic progression.

Base Sequence↗