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L R Hill

Publications and source records attributed to L R Hill.

At least 19 recordsLinked to original sources
PubMed1992

Serological alpha 1-antichymotrypsin in Down's syndrome and Alzheimer's disease.

alpha 1-Antichymotrypsin (ACT) is a serine protease inhibitor that is markedly elevated in the serum and cerebrospinal fluid of patients with Alzheimer's disease (AD). Patients with Down's syndrome are known to develop neuropathological changes of AD by age 40 years and many become demented. Therefore, in the present study, we obtained serum ACT levels from patients with Down's syndrome and AD, diagnosed by autopsy or clinically, and healthy control subjects. Newman-Keuls' multiple range test revealed a significantly greater (p less than 0.01) mean ACT level in the Autopsy AD (906.4 +/- 94.64 mg/L) and Clinical AD (745.00 +/- 59.95 mg/L) groups in contrast to the Old Control group (531.00 +/- 23.05 mg/L). The mean ACT level of the Down's Syndrome group (513.33 +/- 14.73 mg/L) was not significantly different from that of the Young Control subjects. Furthermore, we did not observe a positive correlation of ACT levels with age in the Down's Syndrome group, in spite of the age-dependent premature increase in neuropathological changes of AD that are known to occur in patients with Down's syndrome. A positive correlation between serum ACT levels and the density of plaques or tangles, neuropathological hallmarks of AD, in brains of patients with AD also did not exist. Thus, our results suggest that ACT levels may not parallel the development of the classical neuropathological hallmarks of AD.

Adult↗
PubMed1991

Survival of patients with metastatic breast cancer diagnosed between 1955 and 1980.

In order to determine whether current programs for the management of metastatic breast cancer have led to improved patient survival, we determined the median survival times for five-year intervals of 849 patients admitted to the City of Hope National Medical Center with metastatic breast cancer from 1955 to 1980. Survival curves were constructed from the dates of first diagnosis of breast cancer and to the first metastasis for all population subsets and clinical subsets: menopausal status, presence or absence of visceral metastases, length of disease-free interval, and pattern of palliative therapy. In this analysis, the median survival in each successive interval of five years from diagnosis of the primary tumor was 52.1, 45.0, 49.9, 41.1, and 36.0 months, and the survival times from the first metastasis were 31.9, 23.0, 24.2, 23.9, and 18.7 months. Survival times in each of the clinical subsets remained unchanged during the period of observation, regardless of the therapeutic modalities included in the treatment regimens. This study indicates that changes in palliative therapy for metastatic breast cancer during the 25 years of observation have not influenced overall survival. Therefore, it seems appropriate that the therapeutic risk/benefit ratio and impact on quality of life should be reassessed when asymptomatic patients are treated, or when aggressive palliative therapy is used outside a clinical research setting.

Breast Neoplasms↗
PubMed1991

Stephen P. Lapage.

Explore the source record for details and available documents.

Bacteriology↗
PubMed1990

Presurgical imaging with indium-labeled anti-carcinoembryonic antigen for colon cancer staging.

Over a 4-year period, 108 patients with known or suspected colorectal cancer were studied by radioimmunoconjugate scintigraphy prior to operative procedures. Study subjects received 0.2 to 40 mg i.v. of murine anti-carcinoembryonic antigen monoclonal antibody labeled with 2-5 mCi of 111In (Indacea). Resected tissues were analyzed for 111In and carcinoembryonic antigen content. Tumor, liver, and draining lymph nodes had over 10% injected dose/kg compared to less than 2.5% injected dose/kg for other normal tissues. Primary tumors that were successfully imaged were significantly larger and had higher 111In and carcinoembryonic antigen content. In 54 patients, primary tumors were visualized with a sensitivity of 78%. Hepatic metastases (58 patients) were visualized as negative filling defects (sensitivity, 45%). Extrahepatic (intraabdominal) metastases (25 patients) were visualized (sensitivity, 48%) as areas of increased uptake. Extraabdominal metastases were uncommon (10 patients; sensitivity, 80%). Of 56 patients with known or suspected hepatic metastases who presented with no evidence of extrahepatic disease by conventional tests (X-ray, computerized tomographic scan), 20 (36%) were documented to have extrahepatic metastases at exploratory surgery and 10 of these (50%) had the extrahepatic disease localized by the Indacea scan. The management of these 10 patients was, or could have been, modified by the scan findings and unnecessary surgery eliminated.

Adult↗
PubMed1990

Radioimmunotherapy of human colon cancer in nude mice.

Nude mice bearing subcutaneous human colon cancer xenografts (LS174T) were treated with 120 microCi of yttrium 90-labeled anti-carcinoembryonic antigen monoclonal antibodies (specific therapy), 120 microCi of 90Y-labeled anti-melanoma monoclonal antibodies (nonspecific therapy), or phosphate-buffered saline solution (no treatment control). Mean (+/- SD) tumor growth rates (percent increase per day) over the first 30 days of the study were as follows: 0.6% +/- 0.2% per day (specific therapy); 17.7% +/- 5.7% per day (nonspecific therapy); and 30.5% +/- 4.2% per day (control). In all three groups, tumors over 1 g had similar doubling times (5.74 +/- 0.71 d). Specific therapy caused a lag in tumor growth corresponding to a 3-logarithm cell kill. Estimated tumor dose of radiation obtained by tissue analysis was 34 and 14 Gy for specific and nonspecific therapy, respectively. In conclusion, 120 microCi of 90Y-labeled anti-carcinoembryonic antigen monoclonal antibodies was effective in suppressing growth of human colon cancer xenografts. Clinical studies with this preparation are recommended.

Animals↗
PubMed1990

Interlaboratory comparative study of the numerical analysis of one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoretic protein patterns of Campylobacter strains.

Twenty-nine bacterial strains of the genus Campylobacter were examined independently at two collaborating institutes, the National Collection of Type Cultures, London and the Laboratorium voor Microbiologie, Rijksuniversiteit Gent. The one-dimensional polyacrylamide gel electrophoretic protein patterns of the strains were analysed using computerised numerical methods which employed a correlation coefficient and a clustering algorithm. The electrophoretic methods used at the two institutes included both major differences such as gel composition and running conditions and minor differences in buffer composition. Although the algorithm on which similarity and clustering were computed were the same, the detailed treatment of scan patterns differed. The resulting protein patterns in the gels differed markedly in appearance but after numerical analysis the two systems were equally effective in their ability to speciate the strains. There were, however, differences in the relationships between the species defined at the two institutes and these were at least partly due to the different background subtraction methods employed. In conclusion, the portability and reproducibility of the two systems for identification was demonstrated but for definitive classification further standardization may be required.

Bacterial Proteins↗
PubMed1990

Effects of 5-azacytidine in Syrian golden hamsters: toxicity, tumorigenicity, and differential modulation of bronchial carcinogenesis.

5-Azacytidine (AZC) was studied in a lung cancer model in outbred and syngeneic (F1D) hamsters wherein benzol[a]pyrene (BP) from sustained release implants (SRI) induces preneoplastic mucosal changes which progress to bronchogenic cancer. In pilot studies to evaluate AZC toxicity, a dose schedule of 5 mg/kg biweekly was found suitable and was then used for long-term administration in all subsequent studies. Three groups of outbred hamsters were studied: BP SRi alone (n = 60), BP SRI + AZC (n = 60), and AZC alone (n = 54). AZC treatment was begun 3-5 days after SRI placement. Sixty-one days after the start of the experiment, seven or eight hamsters were sacrificed from each group. Later sacrifices were at 3-week intervals in groups receiving BP SRI and at 6-week intervals in the AZC only group. Four groups of F1D syngeneic hamsters were studied: BP SRI alone (n = 50); BP + AZC starting 3-5 days after SRI placement and continuing until death (n = 52); BP + AZC from 3 to 5 days until 75 days after SRI placement (n = 49); BP + AZC starting 80 days after SRI placement and continuing until death (n = 52). Hamsters (n = 9-14) from each group were sacrificed at 120, 150, 180, and 220 days after SRI implantation. AZC alone was not carcinogenic under these conditions. Both outbred and F1D hamsters treated with early or continuous AZC had slower rates of neoplastic change from BP SRI than did animals receiving BP SRIs alone or BP + late AZC. The incidence of epidermoid cancer were the same for all regimens, but the tumors in those receiving AZC early in carcinogenesis were smaller than in those receiving late or no AZC. The incidences of nonepidermoid cancer were lower in those receiving AZC during early carcinogenesis, and larger tumors were noted in the absence of AZC. Thus, within the study period in this unique hamster lung cancer model, AZC given early in carcinogenesis inhibited only the later (promotional) phase of BP epidermoid carcinogenesis, but inhibited all phases of nonsquamous cancer development induced by BP. This differential modulation of bronchial carcinogenesis, which occurs from AZC given during preneoplastic stages, may prove useful for delineating molecular mechanisms underlying specific phenotypic types of bronchogenic cancers.

Animals↗
PubMed1990

A prospective, randomized evaluation of the treatment of colorectal cancer metastatic to the liver.

Over a 4-year period (1982 to 1986), 91 patients with solitary or multiple metastases from colorectal cancer were stratified, based on findings at laparotomy, to one of three groups and then prospectively randomized to one of two treatment arms within each group. Group A patients had solitary resectable metastases, group B patients had multiple, resectable metastases, and group C patients had multiple, unresectable metastases. Patients were randomized to one of two treatment arms within a group: group A-arm A1: resection only, arm A2: resection and continuous hepatic artery infusion (CHAI) of fluorodeoxyuridine (FUdR); group B-arm B1: resection and CHAI, arm B2: CHAI only; group C-arm C1: CHAI, arm C2: systemic fluorouracil followed by CHAI. Median time to failure (TTF) was 31.8, 11.1, and 8.8 months for groups A, B, and C, respectively. Arm A2 had an improved TTF when compared with arm A1 (P = .03). Median survival correlated with extent of disease and was 37.3, 22.4, and 13.8 months for groups A, B, and C, respectively. Survival was not changed by treatment variation (arms) within each group. Two- and 5-year cumulative survivals for groups A, B, and C were 72.7% and 45.4%; 45.8% and 16.7%; and 31.7% and 3.2%, respectively. In patients with multiple metastases (groups B and C), those patients whose original tumor was a Dukes' B had a significantly improved TTF and survival over those patients whose tumor was a Dukes' C (P less than or equal to .02).

Adult↗
PubMed1990

Quantitative DNA alterations during 5-azacytidine-induced differential modulation of benzo(a)pyrene carcinogenesis in hamster bronchi.

Sustained release implants (SRI) containing 10% benzo(a)pyrene (BP) were placed endobronchially into outbred and syngeneic (F1D) hamsters. Randomly selected OB and F1D hamsters also received 5-azacytidine (AZC), 5 mg/kg i.p., twice weekly until death (AZC-CONT); two more groups of F1D hamsters were given the same AZC dose either for the first 75 days of SRI implantation (AZC-EARLY) or from 80 days after SRI placement until death (AZC-LATE). OB Hamsters were sacrificed at regular intervals from 62 to 189 days of SRI exposure. F1D Hamsters were sacrificed in groups after 120, 150, 180, and 220 days of SRI exposure. The bronchial mucosa at the SRI site was examined cytologically and histologically, as were the tumors that developed. Mean quantitative total cellular DNA values (QDNA) were measured by image analysis. For both varieties of hamster given AZC, QDNA values were higher in early carcinogenesis (CG) and lower in the late stage of CG than in hamsters that did not get AZC (P less than 0.001). QDNA values were lower in epidermoid than in non-epidermoid cancers (P less than 0.001); for both types of cancer, QDNA was lower in AZC-treated hamsters (P less than 0.01). Cancers induced under the influence of AZC included more epidermoid cancers (P less than 0.01) and were of a higher degree of differentiation (P less than 0.01) than those induced by BP alone, especially when AZC was given early in CG. There was no consistent relationship between QDNA and degree of differentiation in tumors. These differential effects of AZC given early during CG suggest that 1) for epidermoid bronchial CG, some of the molecular alterations involved in hyperploidy and in differentiation occur early in the sequential progression of carcinogenesis; and 2) for both epidermoid and non-epidermoid bronchial CG, the necessary changes must occur in a fixed sequence instead of as random events, until all needed changes have occurred.

Animals↗
PubMed1990

Quantitative DNA patterns in human preneoplastic breast lesions.

In 12 cases of human mammary carcinoma in which a preneoplastic atypical ductal hyperplasia was also identified, quantitative DNA (QDNA) measurements of thionein-stained samples from both lesions were performed using the Cell Image Analysis 100 system. The QDNA values in the preneoplastic and neoplastic lesions from each case showed concordance (six as euploid and six as aneuploid/hyperdiploid). Such congruence suggests a stable inheritance of the somatic mutation(s) that is involved in carcinogenesis and that affects ploidy. If this relationship between concurrent preneoplasia and neoplasia in the ipsilateral breast is confirmed, it offers the possibilities of (1) identifying individuals at risk for developing neoplasias with defined biologic characteristics and (2) developing therapeutic regimens more appropriate to the risk assessment of each patient. It may be possible to conceive of a rational preventive regimen for cancer of the breast.

Breast↗
PubMed1989

Evaluation of a short-stay program for patients undergoing mastectomy.

Two hundred twenty-eight patients were included in a retrospective study to evaluate the morbidity and feasibility of early discharge after mastectomy. Group I (early discharge, n = 75) patients were given pre- and postoperative instruction related to wound and drain care. Group II (concurrent control, n = 44) was given similar postoperative instruction, but received no preoperative teaching. Group III (historical controls, n = 109) underwent surgery during a period of more liberal hospitalization and discharge policies. The groups were similar in age, cultural background, operations performed, and pathologic diagnosis. Length of stay for groups I, II, and III was 5.5 +/- 0.4, 3.5 +/- 0.2, and 8.6 +/- 0.3 days, respectively. Groups I and II had a significantly shorter stay than group III. There was no difference among the groups for the presence of wound erythema, rate of primary healing, seroma formation, or wound infection. The practice of same-day admission and early discharge to limit length of stay for patients undergoing mastectomy is safe and effective.

Breast Neoplasms↗
PubMed1989

Strain variation in Campylobacter pylori detected by numerical analysis of one-dimensional electrophoretic protein patterns.

A total of 21 clinical isolates of Campylobacter pylori from Peru and the United Kingdom and two reference strains (from Australia), including the type strain (NCTC 11637T), were characterized by high resolution one-dimensional SDS-polyacrylamide gel electrophoresis of cellular proteins. The protein patterns contained more than 40 discrete bands and the approximate molecular weights of the major bands were 22, 27, 46, 57, 60, 65 and 93 kD. The total patterns were used as the basis of numerical analysis. Most strains were clustered in four phenons at 91% similarity with the exception of six ungrouped strains. Overall similarity was high with all strains linked in the phenogram at greater than or equal to 81%. Variation among strains was attributable principally to qualitative and quantitative band differences in the 47 to 56 kD (hypervariable) region of the C. pylori protein profile. From the analysis, ten different electropherotypes (EP-types) were identified. We demonstrated that differences were detectable among isolates from widely separated geographical locations as well as from the same location, although multiple isolates from two Peruvian patients had the same electropherotype. Our results indicate that determination of protein profiles provides the basis of a reproducible method for characterization of C. pylori isolates.

Bacterial Proteins↗
PubMed1989

The effects of tumor mass, tumor age, and external beam radiation on tumor-specific antibody uptake.

The effects of external beam radiation on tumor uptake of radiolabeled monoclonal antibody were investigated. Nude mice bearing carcinoembryonic antigen (CEA)-producing subcutaneous human tumor xenografts (LS174T) were irradiated (60Co) with a single fraction of 0, 2 or 20 Gy, 6 or 11 days after tumor inoculation. An Indium-111 labeled anti-CEA monoclonal antibody (T84.66) was injected 1-2 hrs after irradiation. Biodistribution studies performed at 48 hrs showed a statistically significant (p less than 0.01) inverse correlation between tumor mass and tumor antibody uptake. Tumor age was also a significant factor with 11 day old tumors having significantly less uptake (p less than 0.0001) compared to 6 day old tumors for a given mass. Radiation increased tumor antibody uptake only in those tumors where growth inhibition also occurred. Multiple regression analysis showed that this inverse correlation between tumor mass and antibody uptake was the same for irradiated and nonirradiated tumors. We conclude that, in this model system, radiation does not act independently to enhance tumor antibody deposition. Radiation's primary effect is to reduce tumor mass, with mass reduction then resulting in an increase in antibody uptake. The clinical implications of this study are discussed.

Animals↗
PubMed1989

Small lymphocytic lymphoma: a clinicopathologic analysis of 268 cases.

We analyzed specimens from 268 patients with small lymphocytic lymphoma (SL) to identify prognostic factors significant for survival. These patients were staged and treated according to the protocols of the Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, Southeastern Cancer Study Group, and the Southwest Oncology Group. Univariate analysis showed that a large-cell grade greater than I, WBC greater than 10,000/microL, hemoglobin (Hgb) less than 11 g/dL, age greater than or equal to 55 years, and failure to respond to treatment were all poor prognostic factors. Multivariate analysis showed that large-cell grade, age, degree of capsular invasion, and symptom type were independently associated with survival. Separate analyses of cases with and without leukocytosis indicated differences in survival. In patients without leukocytosis, age, presence or absence of anemia, and treatment response were significant prognostic variables; in patients with leukocytosis, large-cell grade, presence or absence of anemia, symptom type, and treatment response were significantly related to survival. Multivariate analysis showed that age was the only significant independent prognostic variable in patients without leukocytosis; in patients with leukocytosis, symptom type, large-cell grade, and bone marrow involvement were independently associated with survival. We conclude that several parameters, both clinical and pathologic, should be assessed at the initial diagnosis of SL to predict prognosis better.

Age Factors↗
PubMed1988

To boost or not to boost: decreasing radiation therapy in conservative breast cancer treatment when "inked" tumor resection margins are pathologically free of cancer.

A retrospective study was performed to compare local treatment approaches for 108 treated breasts in 105 patients with Stage I or II breast cancer. Six cases with intraductal carcinoma have shown no evidence of recurrence. The other 102 cases had invasive cancer. In 54 treated breasts in 53 patients, the treatment approach involved surgical resection of the primary tumor, pathological determination of tumor-free "inked" specimen margins and 5000 cGy to the whole breast. Local radiation therapy (RT) boosts to the primary site were not given. This approach produced a 100% local control rate (mean follow-up of 38 months). In 28 treated breasts in 27 patients, the treatment approach involved tumor excision without evaluation of specimen margins followed by RT which included a local boost by either interstitial Iridium-192 implant or electron beam. This approach yielded an actuarial local control rate of 87% at 48 months (mean follow-up of 47 months). The difference in local control rate between the two groups was statistically significant (p less than 0.03). Among patients with clear surgical margins who received a local RT boost, 1 of 9 developed a local recurrence. Among those with tumor involving specimen margins who received a local boost, 1 of 8 developed local recurrence. Local recurrence developed more frequently among patients with poorly differentiated cancers (2 of 11 cases) than among those with other invasive cancers (3 of 91 cases). Comparison of treatment approaches was limited since poorly differentiated cancer was present in 25% of cases with unknown specimen margins, as compared with only 2% of those with clear surgical margins who did not receive a local RT boost. Our preliminary findings suggest that when "inked" primary tumor resection margins are pathologically free of cancer, 5000 cGy whole breast RT appears to be highly effective for local tumor control in patients with Stage I or II disease. Our results are inconclusive as to whether patients with poorly differentiated cancers should receive a local RT boost even when surgical margins are clear.

Actuarial Analysis↗
PubMed1988

Total skin electron irradiation for mycosis fungoides: relationship between acute toxicities and measured dose at different anatomic sites.

From June 1978 to June 1986, 50 patients with primary and recurrent mycosis fungoides were treated with total skin electron irradiation (TSEI), using the Stanford technique, to a total dose of 3600 cGy. TSEI was used alone, or in combination with low dose total body photon irradiation, or MOPP. Thermoluminescent dosimeter (TLD) measurements of the prescribed skin dose were obtained on twenty patients. The dorsum of the foot was 24% higher. The axillae, the bottom, and the arch of the foot were significantly underdosed. Frequencies of acute toxicities noted at 2000 cGy were: Skin, Grade I-II (RTOG) 80%. Partial epilation: scalp, 100%; eyebrows and at eyelashes, 20%. Nail dystrophy, 48%. Edema: hands and feet, 44%. Bullae: dorsum of feet, 8%; hands, 4%; and 3600 cGy: Skin, grade III 22%. Total epilation: scalp, 66%; eyebrows and eyelashes, 56%. Nail loss, 38%. Edema: hands and feet, 76%. Bullae: dorsum of feet, 34%; hands, 12%. Conjunctivitis, 4%. Large bullae, were more significant on the dorsum of the feet. Severe moist desquamation occurred in eight patients who had ulcerated lesions on initial presentation. Three patients were hospitalized due to ulceration and skin infection. All patients completed treatment after a short to moderate break. No patient developed skin necrosis, or corneal ulceration. No correlation exists between dose level, degree and onset of toxicity with previous chemotherapy or TBI. We conclude that the overall toxicity of TSEI is well tolerated.

Female↗
PubMed1988

Complications of abdominal operations for malignant disease.

The incidence of morbidity and mortality in 365 consecutive patients with a mean age of 60 years who underwent intraabdominal operation for a variety of cancers involving different organ systems over a recent 2-year period was analyzed. The primary tumor sites were the esophagus (21 patients), gastroduodenum (33 patients), liver and gallbladder (6 patients), pancreas (15 patients), colorectum (101 patients), lymphoproliferative disorders (35 patients), abdominal carcinomatosis (45 patients), genitourinary and gynecologic systems (94 patients), and other sites (15 patients). One hundred eighty-two patients (49 percent) had 1 or more complications (grouped as gastrointestinal, septic, cardiopulmonary, and nonseptic) and 47 patients died (12.9 percent). The 145 patients who underwent a palliative procedure had the highest morbidity and mortality rates (41 percent and 21 percent, respectively). In the 168 patients who had curative resection, the morbidity and mortality rates were 39 percent and 9 percent, respectively, and in 51 patients with a diagnostic laparotomy, 20 percent and 4 percent, respectively. Age was not a contributory factor. The 177 malnourished patients had a significantly higher incidence of complications (72 percent) and postoperative death (23 percent) than the well-nourished patients (29 percent and 4 percent, respectively; p less than 0.001). These differences also existed with each form of complication. Of those patients without complications, the majority resumed consuming 60 percent of their caloric requirements by postoperative day 9. In the majority of patients with complications, resumption of adequate oral intake occurred by postoperative day 20.

Abdominal Neoplasms↗