Biomedical subjects

H T Thaler

Publications and source records attributed to H T Thaler.

At least 55 records · Page 3Linked to original sources

PubMed1992

Expression of Her2/neu oncogene product p185 in correlation to clinicopathological and prognostic factors of gastric carcinoma.

The expression of the Her2/neu gene product p185 was retrospectively analyzed in 58 patients with gastric carcinoma. The results were correlated to various clinicopathological and prognostic factors. Positive membrane staining for p185 could be detected in 38% of the patients (22/58). Membrane staining was significantly greater in well and moderately differentiated tumors of the intestinal type when compared with poorly differentiated lesions and carcinomas of the diffuse type (P less than 0.01). Positive membrane staining did not correlate with site and tumor stage, but T1 lesions had less membrane staining than more advanced primary tumors. Overall survival showed no difference between p185-positive and negative cases. Multivariate analysis defined a subgroup of curatively resected patients with stage III and IV disease that had a statistically significant poorer survival when p185 was overexpressed (P = 0.005). Overexpression of the Her2/neu product p185 appears to be associated with intestinal-type gastric carcinoma and may help in identifying a subset of patients at increased risk for shorter survival.

Adenocarcinoma↗

PubMed1992

A prospective analysis of vascular access device-related infections in children.

To identify significant predictors of device-related infections, we performed a prospective, nonrandomized analysis of our experience with vascular access devices over a 2-year period in a pediatric oncology population. Variables analyzed included: (1) age at placement, (2) sex, (3) underlying disease, (4) type of device used (catheter v port), and (5) total white blood cell count at placement. Quantitative microbiologic criteria were used for diagnosis of bacteremia while clinical and microbiologic criteria were used in diagnosis of tunnel/port/site infections. During the study period a total of 351 devices, comprising 78,159 days in situ, were placed and data for univariate and multivariate analysis were available on 271 (77%). The mean age at placement was 7.2 +/- 4.7 years for catheters and 9.5 +/- 4.8 years for implantable devices (P less than or equal to .01). Significant predictors of device-related infections in univariate analysis were type of device (P less than or equal to .0001) and age (P less than or equal to .002). External catheters and age less than or equal to 7 years were associated with increased risk of infection. Underlying disease had a marginal effect on the infection rate (P = .08). In multivariate analysis, device type (P less than or equal to .0001) and age (P less than or equal to .002) continued to affect infections, whereas underlying disease demonstrated only a borderline effect (P = .14). We conclude that device type and age significantly affect the rate of device-related infections. These data support increased use of implantable devices in pediatric oncology patients.

Catheters, Indwelling↗

PubMed1992

The metabolite morphine-6-glucuronide contributes to the analgesia produced by morphine infusion in patients with pain and normal renal function.

Morphine-6-glucuronide is a metabolite of morphine that binds to the opioid receptor and is analgesic in animals and humans. Although accumulation of morphine-6-glucuronide in patients with renal insufficiency has been implicated in morphine toxicity, the contribution of the metabolite to morphine analgesia in patients with normal renal function has not been established. To evaluate this contribution, we repeatedly sampled blood and assessed effects during and after a loading infusion with morphine (mean duration, 168 minutes) in 14 patients with chronic pain, all of whom had normal serum creatinine levels. Plasma concentrations of morphine and morphine-6-glucuronide were assayed by use of high performance liquid chromatography with electrochemical detection. Patients were divided into three groups on the basis of the molar concentration ratio of morphine-6-glucuronide:morphine from the start of the infusion until 240 minutes later: Group 1 (n = 5) had a mean ratio greater than or equal to 0.7:1; group 2 (n = 4) had a mean ratio less than 0.7:1 but greater than or equal to 0.4:1; and group 3 (n = 5) had a mean ratio less than 0.4:1. Time-effect plots revealed that average and peak relief were greater in group 1 than group 2 and greater in group 2 than group 3. For all patients, mean morphine-6-glucuronide:morphine ratio throughout the study was significantly correlated with mean pain relief (r = 0.611, p less than 0.02). These data suggest that morphine-6-glucuronide contributes to morphine analgesia in patients with normal renal function. The role of the metabolite should be considered when morphine is used clinically.

Adult↗

PubMed1992

Pentoxifylline in cerebrovascular dementia.

OBJECTIVE: To test the effect of pentoxifylline, a hemorheologic agent used to treat intermittent claudication, on the course of vascular dementia. DESIGN: Randomized, double-blind, placebo-controlled, parallel group trial. SETTING: Outpatient tertiary care center. PATIENTS: 64 patients meeting DSM-III criteria for multi-infarct dementia with modified Hachinski ischemic scores greater than or equal to 6, 38 of whom completed the trial. INTERVENTION: Pentoxifylline (Trental) 400 milligram tablets three times daily vs placebo for 36 weeks. MAIN OUTCOME MEASURE: Alzheimer's Disease Assessment Scale (ADAS). RESULTS: Baseline demographic values and psychometric variables were similar in the placebo and control groups; endpoint statistical analysis was used to allow the use of data from all patients in this clinically high-risk group. For the total group, the slowing of deterioration did not reach statistical significance (by 2-tailed t test), as measured by scores on the total ADAS (P = 0.058) or on the cognitive (ADAS items 1-11; P = 0.064) or non-cognitive subscales (ADAS items 12-21; P = 0.234), although it was significant on the cognitive subscales excluding memory (ADAS items 2-6, 8-10; P = 0.036). For the subgroup of 40 patients who had CT and/or MRI evidence of stroke as well as meeting the other inclusion criteria, treatment with pentoxifylline was associated with significantly slower deterioration, as measured by the total ADAS (P = 0.023) and cognitive subscores (P = 0.020) but not non-cognitive subscores (P = 0.118). For the subgroup of 37 patients who had at least one discrete clinical stroke, treatment with pentoxifylline was associated with significantly less deterioration on the total ADAS (P = 0.002) and both the cognitive (P = 0.001) and non-cognitive (P = 0.017) subscores. CONCLUSION: Treatment with pentoxifylline may slow the progression of dementia in patients who meet DSM-III criteria for "multi-infarct dementia" and who also have clinical and neuroradiological evidence of cerebrovascular disease.

Academic Medical Centers↗

PubMed1992

Combined modality therapy for primary CNS lymphoma.

PURPOSE: Primary CNS lymphoma (PCNSL), formerly rare, is being seen with increased frequency among apparently immunocompetent patients. Conventional treatment has consisted of whole-brain radiotherapy (RT) and corticosteroids, with a median survival of 15 to 18 months and a 3% to 4% 5-year survival. Chemotherapy has been useful in the treatment of recurrent PCNSL. In 1985 we began a treatment protocol using chemotherapy and cranial irradiation for the initial therapy of non-AIDS PCNSL. PATIENTS AND METHODS: Thirty-one patients (group A) completed the combined modality regimen. All had placement of an Ommaya reservoir and received pre-RT systemic methotrexate, 1 g/m2, plus six doses of intra-Ommaya methotrexate at 12 mg per dose. A full course of cranial RT (4,000-cGy whole-brain RT plus a 1,440-cGy boost) was followed by two cycles of high-dose cytarabine (ara-C), with each course consisting of two doses of 3 g/m2 ara-C separated by 24 hours and infused over 3 hours. During this period, 16 additional patients (group R) were treated with RT alone, either because patients refused chemotherapy or RT was initiated before our consultation; all would have been eligible to participate in the protocol. Follow-up extended through April 1, 1991. RESULTS: Group A had a significantly prolonged time to recurrence (median, 41 months) compared with group R (median, 10 months; P = .003). Although median survival was doubled from 21.7 months for group R to 42.5 months for group A, this was not statistically significant because of small sample size. More importantly, group R patients received systemic chemotherapy for recurrent PCNSL, which improved survival. CONCLUSION: The addition of chemotherapy to cranial RT for initial treatment of PCNSL significantly improved disease-free survival and contributed to overall survival; all non-AIDS patients with newly diagnosed PCNSL should be considered for combined modality therapy.

Adult↗

PubMed1992

A prospective randomized trial of single versus multiple drains in the axilla after lymphadenectomy.

Increasing duration and amount of postoperative fluid formation after axillary lymphadenectomy delays final healing. We postulated that multiple drains (instead of a single drain) might decrease postoperative fluid accumulation by their greater proximity to points of leakage. We randomized 65 women with clinical stage I or II carcinoma of the breast to single or multiple drains. They were stratified for axillary dissection or modified radical mastectomy. For axillary dissection, randomization to multiple drains meant placement of four catheters in the axilla, and randomized to the single drain, one catheter in the axilla. For modified radical mastectomy, the patients randomized to multiple drains received four catheters in the axilla and one catheter under the inferior flap; the patients randomized to single drains had one catheter in the axilla and one catheter under the inferior flap. All catheters exited separately. The two arms (single versus multiple drains) were determined to be homogeneous in other variables that may affect postoperative fluid formation--age, size of the breast, weight, height, obesity, presence of previous surgical biopsy, excision of pectoralis minor muscle, excision of thoracodorsal complex, level of axillary dissection, number of lymph nodes, number and proportion of positive lymph nodes and whether or not the dominant hand was on the side operated upon. Single versus multiple drains had no clinically significant effect on the amount or duration of drainage, as an inpatient or outpatient, or total. We recommend a single drain to the axilla after lymphadenectomy.

Adult↗

PubMed1991

Treatment of squamous cell carcinoma of the anal canal.

Progress in the prognosis of patients with squamous cell carcinoma of the anal canal has followed the use of multimodality therapy. From 1977 to 1985, 42 patients with squamous cell carcinoma of the anal canal were treated with mitomycin C (15 mg/m2) and 5-fluorouracil (750 mg/m2) on day 1, 5-FU (750 mg/m2/d) alone on days 2 to 5, and radiation therapy (3000 cGy) on days 7 to 28. They were evaluated 4 to 6 weeks after completion of the chemotherapy/radiation therapy protocol and received local excision, abdominoperineal resection, or both. Patient follow-up times ranged from 7 to 161 months, with a mean follow-up time of 71 months. Pathologic examination showed no residual carcinoma in 19 (45%) patients. The authors could not predict, based on clinical evaluation, which patients would have a complete response. Of the patients with a complete clinical response, 44% had tumor in the pathology specimen. Wide local excision was the most common initial operation (23 of 42 patients; 55%), with five of these patients subsequently requiring abdominoperineal resection. Anal continence was retained in 18 of 42 (43%) patients. Eleven patients experienced recurrent disease: six local recurrences, one distant, and four both local and distant. The 5-year overall survival rate was 82% and the 5-year disease-specific survival rate was 87%. There were no treatment related deaths. Preoperative tumor size was the only factor significantly related to survival. Contrary to other reports, tumor in the pathology specimen did not adversely affect long-term survival. Hence, patients should be treated after chemotherapy/radiation therapy with surgical therapy sufficient to control local disease.

Adult↗

PubMed1991

Prognosis of node-positive colon cancer.

The most recent American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system subgroups patients into one to three and four or more positive nodes. However, the Gastrointestinal Study Group and the National Surgical Adjuvant Breast and Bowel Project divides node-positive patients into one to four and five or greater. A Cox multi-variate retrospective analysis was done of the overall survival of node-positive colon cancer patients with the specific objective of determining the most appropriate subcategorization. Data on 306 patients with node-positive colon cancer who underwent potentially curative surgery from 1970 to 1984 were analyzed retrospectively. No patient received adjuvant chemotherapy. Also excluded were patients with synchronous resected metastatic disease or those with rectal primaries. The median follow-up was 6 years, and the median survival for the entire group was 8.6 years. By univariate analysis, the following were significant prognostic features: number of positive nodes (P less than 0.0001), degree of differentiation (P less than 0.0001), colon primary site (P = 0.009), tumor stage (P = 0.001), and tumor size (P less than 0.0001). Lymphatic/blood vessel invasion and a mucinous histology were not significant. By Cox multivariate analysis the number of positive lymph nodes remained the best discriminant of survival (P = 0.0001). The number of positive nodes was related inversely to prognosis with the optimal dichotomization between one to three (66% 5-year survival) and four or greater nodes (37% 5-year survival).

Colonic Neoplasms↗

PubMed1991

Merkel cell carcinoma. Prognosis and management.

Seventy patients with Merkel cell carcinoma were treated at Memorial Sloan-kettering Cancer Center between 1969 and 1989. The overall estimated 5-year survival rate was 64%. Factors predictive of improved survival included head and neck site and negative lymph nodes at presentation. Local recurrence was seen in 18 patients (26%) and did not correlate with patient-, tumor-, or treatment-related variables. Nine patients with local recurrence (50%) were free of disease following aggressive reoperation. Regional nodes were involved at some point during the course of the disease in forty-six patients (66%). Regional lymph node involvement was apparent within 2 years of diagnosis in 40 (87%) of 46 patients in whom it occurred. Systemic disease was nearly uniformly preceded by the appearance of nodal metastases and was uniformly fatal regardless of subsequent therapy. This suggests an orderly "cascade" pattern of spread for this tumor, in which elective regional lymph node dissection may be justified. Our recommendations for treatment include a wide excision of the primary tumor and either elective or early therapeutic regional node dissection. The role of adjuvant radiotherapy or chemotherapy remains unproven.

Carcinoma, Merkel Cell↗

PubMed1991

The importance of clinical staging of minor salivary gland carcinoma.

We reviewed a 45-year experience with 459 patients who had previously untreated minor salivary gland neoplasms, 378 (82%) of which were malignant. Data were adequate for retrospective clinical staging in 353 of the 378 patients with malignant tumors using criteria identical to those for squamous carcinoma in the same sites. Five-, 10-, and 15-year survival rates for the patients with malignant tumors treated after 1966 were 75%, 62%, and 56%, respectively, a significant improvement compared with results reported previously. Multivariate analysis confirms that survival was significantly influenced by the clinical stage and the histologic grade, but the applicability of grading was limited to patients with mucoepidermoid carcinoma or adenocarcinoma. Ten-year overall survival was 83%, 53%, 35%, and 24% for patients with stage I through stage IV, respectively. Results in these patients are similar to those we have recently reported in patients with major salivary gland carcinomas, but we are unable to demonstrate that postoperative radiotherapy improved survival.

Carcinoma↗

PubMed1991

Chronic morphine therapy for cancer pain: plasma and cerebrospinal fluid morphine and morphine-6-glucuronide concentrations.

Morphine-6-glucuronide (M-6-G) is an active metabolite that may contribute to the clinical effects produced by systemic administration of morphine. To help clarify the extent to which M-6-G may cross the blood-brain barrier and exert effects, we employed high-performance liquid chromatography with electrochemical detection to measure the concentrations of M-6-G and morphine in the plasma and either ventricular (three patients) or lumbar (eight patients) CSF of cancer patients receiving chronic morphine therapy. The mean ratio of morphine in ventricular CSF:morphine in plasma was 0.71; the same ratio for M-6-G was only 0.077. The average molar ratio of M-6-G: morphine in ventricular CSF was 0.207, and the average molar ratio in plasma was 1.89. Although sampling problems render the lumbar CSF results less reliable, they were very similar. Thus, plasma contained approximately twice as much M-6-G as morphine, whereas CSF contained only one-fifth to one-third as much. These data confirm that M-6-G in plasma is distributed into CSF, but to a far lesser extent than morphine. They help explain animal data demonstrating much higher potency of M-6-G on administration into CSF than systemic administration and indicate that the degree to which M-6-G contributes to morphine effects in humans remains an unresolved question.

Adult↗

PubMed1990

Direct estimation of serological H-Y antigen by flow cytometry.

This study was undertaken to evaluate the efficiency of flow cytometry in the detection of the serological H-Y antigen, and to survey expression of H-Y in the normal human population. Peripheral blood leukocytes (granulocytes) were reacted with monoclonal H-Y antibody, gw-16, and with FITC-conjugated goat anti-mouse IgG, and then were scored for fluorescence in the flow cytometer. Assigned H-Y phenotype was correlated accurately with sex phenotype in 33 out of 38 women and 62 out of 65 men. Data were evaluated by exploratory data analysis (EDA).

Antibodies, Monoclonal↗

PubMed1990

Factor analysis of the immunophenotypes of astrocytomas and malignant gliomas: correlations with tumor grade and patient survival.

Our previous investigations correlated the degree of cytogenetic and immunophenotypic heterogeneity of cultured normal glia, astrocytomas and malignant gliomas. The possible significance was suggested by the statistical correlation of individual antigens with diagnosis and patient survival. The present study has established the patterns of covariation of titers of monoclonal antibody reactivity with a panel of cell surface antigens among normal glia (8), astrocytomas (4), anaplastic astrocytomas (12), mixed malignant gliomas (8) and glioblastomas (21). A mean aggregate titer across 43 antigens was computed for each culture and then subtracted from the observed individual titers. Factor analysis was performed to determine a small number of Factors, derived as the weighted average of the 43 mean-adjusted antigens, which accounted for a significant proportion of the covariation of immunophenotypic expression in the sample of 53 cultures. Clusters of antigens were found to independently segregate in their deviation from the aggregate phenotype. Adjusting for age and diagnosis, Factors 1 and 4 correlated with patient survival among recurrent and primary neoplasms, respectively. Factor 2 additionally discriminated between primary and recurrent gliomas. Factor 3 was associated with age at diagnosis. Factors 1 and 2 correlated with the histopathologic grade of glial tumor. Scatter plots of Factor 1 vs. 2 revealed the minimal immunophenotypic diversity of the normal glia. Astrocytomas were similar but not identical. Progressive divergence was evident between the immunophenotypes of anaplastic astrocytomas, mixed gliomas and glioblastomas. These data suggest that qualitative and quantitative differences in antigenic heterogeneity may identify stages in glial tumor progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

PubMed1990

The role of radiation therapy following resection of single brain metastasis from melanoma.

From 1972 to 1987, 35 patients underwent resection of a single brain metastasis from melanoma; 19 received postoperative radiation therapy (RT) (group A), and 16 did not (group B). Group A had a longer interval to CNS relapse compared with group B, but survival was similar. However, 4/17 (24%) from group A and 11/13 (85%) from group B died of neurologic causes. We conclude that patients with single brain metastasis from melanoma have improved control of CNS disease when postoperative RT is administered, and survival depends upon control of systemic disease.

Adult↗

PubMed1990

Primary CNS lymphoma: combined treatment with chemotherapy and radiotherapy.

Primary central nervous system lymphoma (PCNSL), an uncommon tumor, is occurring with increasing frequency. Conventional therapy with corticosteroids and cranial radiotherapy (RT) usually gives a dramatic initial response, but median survival is only 10 to 18 months. Chemotherapy is more successful in comparable systemic lymphoma and has been employed for PCNSL at relapse, causing remission but not cure. Between June 1985 and June 1988, we prospectively staged 32 patients with PCNSL at Memorial Sloan-Kettering Cancer Center and treated 28 on a new protocol that combined chemotherapy and radiotherapy at diagnosis. None had occult systemic lymphoma, but 19% had ocular and 69% had definite or probable leptomeningeal lymphoma. There were no complications in 19 stereotactic biopsies, but 4/10 patients who had a complete resection suffered a severe postoperative deficit. Four patients received RT alone, and 28 received chemotherapy and cranial RT, 17 of whom (group A) received a combination regimen using pre-RT systemic (1 g/m2) and intra-Ommaya methotrexate (MTX), 4,000 cGy whole-brain RT with a 1,440 cGy boost, and 2 courses of post-RT high-dose cytosine arabinoside; 5 other patients received an identical regimen but with a decreased dose of MTX (200 mg/m2). Sixty-three percent of assessable patients had a response to MTX independent of corticosteroid and prior to RT. Eighteen of 26 (69%) assessable patients who received combined therapy are alive with a median follow-up of 25.4 months. Twelve of 16 (75%) assessable group A patients are alive in the same period. Chemotherapy-related toxicity was minimal, and no late toxicities have occurred to date.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Expression of transforming growth factor alpha in human gliomas.

Expression of transforming growth factor alpha (TGF alpha) is frequently associated with the development of human and animal tumors. Using a sensitive immunohistochemical assay, which can be applied on formalin-fixed, paraffin-embedded tissue, we have examined the expression of TGF alpha in 71 human gliomas (63 untreated and 8 recurrent tumors). Tumors were graded by a 3-grade-system: grade I = low grade gliomas, grade II = anaplastic gliomas and grade III = glioblastomas. A strong positive correlation between tumor grade and extent of TGF alpha expression was found (P less than 0.0001). Polymerase chain reaction (PCR) was used to amplify the fourth exon of the TGF alpha gene of 8 glioma DNA specimens and increasing amounts of normal human DNA, which served as a standard. No amplification of the TGF alpha gene copy number in tumors could be detected.

Base Sequence↗

PubMed1989

Identification of epidural neoplasm. Radiography and bone scintigraphy in the symptomatic and asymptomatic spine.

Early identification and treatment of epidural neoplasm, before the development of significant neurologic deficits, provides the best opportunity for a favorable outcome. Among the many patients with symptoms, signs, or scintigraphic or radiographic findings suggesting possible epidural disease, a small proportion will have the lesion. The selection of patients for definitive imaging of the epidural space should be based on a determination of the risk of this complication. In this study, the medical records, plain spinal radiographs, bone scintigraphs and myelograms of 43 patients were analyzed retrospectively to assess the risk of epidural disease associated with specific clinical, radiographic, and scintigraphic findings. Cervical, thoracic, and lumbosacral spinal segments were evaluated independently. Symptomatic segments (SS) (N = 41), defined by focal pain or neurologic dysfunction, were distinguished from asymptomatic segments (AS). At SS, epidural disease was found at 86% and 8% of abnormal and normal spinal radiographs, respectively (P less than 0.001), and at 69% and 0% of abnormal and normal scintigrams, respectively (P less than 0.001), whereas at AS epidural disease occurred in 43% and 3% of abnormal and normal spinal radiographs, respectively (P less than 0.001), and 14% and 7% of abnormal and normal scintigrams, respectively (P = NS). Vertebral collapse was highly predictive of an epidural lesion. Epidural disease occurred in 12% of SS and 0% of AS with an abnormal scintigram and normal radiograph, 86% of SS and 45% of AS with abnormalities on both scintigram and radiograph, and at two AS when both were normal. Decision analysis applied to these data yielded a specific conditional probability of epidural disease for each combination of clinical, scintigraphic, and radiographic findings. These data provide a basis for the selection of patients for additional evaluation of the epidural space before neurologic deficits develop.

Adult↗

PubMed1989

Pulmonary function in preterm infants following treatment with intravenous indomethacin.

Pulmonary function tests, including measurements of arterial blood gas levels, total pulmonary compliance, and arterial-alveolar oxygen ratios, were performed in 38 ventilator-dependent preterm infants with respiratory distress syndrome who weighed less than 1500 g at birth. Twenty-seven had a physiologically significant patent ductus arteriosus (PDA). Twelve were assigned at random to receive three doses of intravenous indomethacin, 0.2 mg/kg per dose, on the fourth day of life. This treatment resulted in ductal closure in seven infants by the seventh day of life. Another concurrently observed group of 15 infants with PDA received no indomethacin. A third group of 11 infants lacked evidence of a PDA. Pulmonary function in the infants who received indomethacin did not differ significantly from that in the other two groups.

Ductus Arteriosus, Patent↗