Biomedical subjects

C B Wallemark

Publications and source records attributed to C B Wallemark.

At least 19 recordsLinked to original sources

PubMed2000

Celecoxib does not significantly alter the pharmacokinetics or hypoprothrombinemic effect of warfarin in healthy subjects.

The objective of this study was to determine the effects of celecoxib, an anti-inflammatory/analgesic agent that primarily inhibits COX-2 and not COX-1 at therapeutic doses, on the steady-state pharmacokinetic profile and hypoprothrombinemic effect of racemic warfarin in healthy volunteers. Twenty-four healthy adult volunteers on maintenance doses of racemic warfarin (2-5 mg daily), stabilized to prothrombin times (PT) 1.2 to 1.7 times pretreatment PT values for 3 consecutive days, were randomized to receive concomitant celecoxib (200 mg bid) or placebo for 7 days in an open-label, multiple-dose, randomized, placebo-controlled, parallel-group study of warfarin pharmacokinetics and PT. Steady-state exposure of S- and R-warfarin (area under the curve [AUC]) and maximum plasma concentration (Cmax) in subjects receiving celecoxib were within 2% to 8% of the warfarin AUC and Cmax in subjects receiving placebo during the concomitant treatment period. In addition, PT values were not significantly different in subjects receiving warfarin and celecoxib concomitantly compared with subjects receiving warfarin and placebo. In conclusion, concomitant administration of celecoxib has no significant effect on PT or steady-state pharmacokinetics of S- or R-warfarin in healthy volunteers.

Adult↗

PubMed1998

Diclofenac/misoprostol compared with diclofenac in the treatment of osteoarthritis of the knee or hip: a randomized, placebo controlled trial. Arthrotec Osteoarthritis Study Group.

OBJECTIVE: Gastric (GU) and duodenal ulcers (DU) are common adverse effects of nonsteroidal anti-inflammatory drugs (NSAID). Endoscopically diagnosed upper gastrointestinal (GI) ulceration occurs in about 24% of longterm NSAID users. Coadministration of misoprostol with the NSAID reduces the incidence of NSAID induced GU and DU and their complications. However, compliance is limited by the different dosing regimens of misoprostol and NSAID and GI symptoms associated with misoprostol at its recommended q.i.d. dose. We compared the efficacy, safety, and incidence of endoscopic upper GI ulceration associated with the administration of 2 combinations of diclofenac (50 or 75 mg) and misoprostol 200 microg (D50/M200 t.i.d., D75/M200 b.i.d.), diclofenac 75 mg b.i.d., and placebo in a 6 week, randomized, double blind study in patients with osteoarthritis (OA) of the knee or hip. METHODS: A total of 572 patients with symptomatic OA of the knee or hip and history of GU, DU. or 10 or more erosions were randomized to receive D50/M200 t.i.d., D75/M200 b.i.d., diclofenac 75 mg b.i.d., or placebo for 6 weeks. Arthritis assessments were performed at baseline, 2, and 6 weeks, and upper GI endoscopies at baseline and end of treatment. RESULTS: All active treatment groups were significantly better than placebo, at all visits, in improving OA symptoms. There were no significant differences in arthritis efficacy between the diclofenac/ misoprostol combinations and diclofenac. However, endoscopically diagnosed GU and/or DU were significantly less frequent in patients receiving D50/M200 t.i.d. (8%), D75/M200 b.i.d. (7%), and placebo (4%) compared to diclofenac 75 mg b.i.d. (17%). Adverse events were not different between the active treatment groups, except for higher incidences of flatulence with D75/M200 and diarrhea with D50/M200. CONCLUSION: Diclofenac 50 mg/misoprostol 200 microg t.i.d. and diclofenac 75 mg/misoprostol 200 microg b.i.d. are as efficacious as diclofenac 75 mg b.i.d. in the treatment of OA, but are associated with a significantly lower incidence of gastric and/or duodenal ulcers.

Adult↗

PubMed1991

Prevalence of mucosal lesions in the stomach and duodenum due to chronic use of NSAID in patients with rheumatoid arthritis or osteoarthritis, and interim report on prevention by misoprostol of diclofenac associated lesions.

We review preliminary findings of the screening and prophylaxis phases of a study of misoprostol in patients with arthritis receiving nonsteroidal antiinflammatory drugs (NSAID). Endoscopic evaluation of over 1,800 patients with rheumatoid arthritis or osteoarthritis, more than 95% of whom qualified for screening on the basis of continuous NSAID use over the prior 6 months, has revealed clinically significant gastroduodenal lesions in 37% and ulceration in 24%. In the prophylaxis phase, patients without significant lesions were randomized to receive misoprostol or placebo and NSAID therapy with diclofenac for 52 weeks. Product-limit and crude incidence analyses of data from patients thus far enrolled indicate that misoprostol is associated with significant protection against the development of gastroduodenal lesions compared with placebo after 12 or 24 weeks of study. No adverse effect of misoprostol administration on underlying arthritis activity has been observed thus far. Definitive conclusions await completion of the study.

Alprostadil↗

PubMed1989

Predictors of outcome in AIDS patients receiving zidovudine.

Fifty-eight AIDS patients who previously had Pneumocystis carinii pneumonia (PCP) were enrolled in an open trial of zidovudine therapy. We analyzed baseline clinical and laboratory parameters to identify predictors of outcome. Fifty-eight patients were followed for a mean of 26.5 weeks. There were 17 deaths; the probability of survival at 24 weeks was 0.81. Forty-one participants had unsuccessful outcomes, which included new opportunistic infections (24), progressive neurologic deterioration (2), and drug toxicity, excluding anemia, necessitating discontinuation of zidovudine (15). Only 24 subjects (41%) were receiving zidovudine at the end of the study period including 17 who had neither opportunistic infection nor toxicity. Low baseline hemoglobin level (p less than 0.001) and poor performance status as measured by the Karnofsky scale (p less than 0.01) independently predicted unsuccessful outcome and early death. Low hemoglobin (p = 0.001), low platelet count (p = 0.016), and increased time since PCP (p = 0.008) predicted development of drug toxicity. Neither CD4 lymphocyte count nor p24 antigenemia correlated with outcome.

Acquired Immunodeficiency Syndrome↗

PubMed1989

Prognostic significance of positive peritoneal cytology in clinical stage I adenocarcinoma of the endometrium.

One hundred fifty-seven consecutive patients with clinical stage I endometrial adenocarcinoma who underwent primary surgical therapy between July 1979 and January 1986 were evaluated prospectively for malignant peritoneal cytology. No treatment was directed specifically for positive peritoneal cytology. Thirty patients (19%) had malignant peritoneal cytology. In univariate statistical analysis, positive cytology was significantly associated with depth of myometrial invasion (P = .02) and histopathology (P less than .025), but not with disease recurrence (P = .33). Recurrence developed in five (17%) of 30 patients with positive cytology and 11 (9%) of 127 patients with negative cytology. Using multivariate analysis, the presence of extrauterine disease spread other than lymph node metastasis was the only variable significantly associated with time to recurrence (P = .009). When patients with poor prognostic factors (grade 3 tumors, deep myometrial invasion, tumors larger than 2 cm, positive lymph nodes, and other extrauterine disease spread) were excluded from analysis, malignant peritoneal cytology still had no influence on time to recurrence. Of the five patients with positive peritoneal cytology who had disease recurrence, only one recurrence arose within the peritoneal cavity. The presence of positive peritoneal cytology in clinical stage I endometrial adenocarcinoma does not appear to have independent prognostic significance and probably should not influence treatment decisions in the absence of other poor prognostic factors.

Adenocarcinoma↗

PubMed1988

Growth disadvantage of 45,X and 46,X,del(X)(p11) fibroblasts.

We have previously shown that cell generation time (CGT) is prolonged in 45,X and certain X-deletion fibroblast lines (Simpson & Le Beau 1981). A consequence of that finding should be that cells with 45,X or an X-structural abnormality are at a competitive disadvantage when cocultivated with 46,XX cells. To test this hypothesis we prepared 15 minutes of cells from combinations of 9 different cell lines: four 45,X; one 46,Xdel(X)(p11); and four 46,XX. Each culture was monitored cytogenetically at frequent passage intervals for the percentage of the two cell lines. Significant differences were found between normal and abnormal lines in culture predominance, in the order predicted by our hypothesis (p less than 0.01). The specific mechanism by which absence of an X chromosome confers growth disadvantage is unknown, but is consistent with prolongation of CGT. Prolongation of CGT could also be responsible for the embryonic lethality, intrauterine growth retardation, short stature, and somatic anomalies commonly observed in individuals with absent or aberrant X chromosomes.

Cell Division↗

PubMed1988

Prognostic usefulness of the Walter Reed staging classification for HIV infection.

We evaluated the usefulness of both the Walter Reed (WR) staging classification and the component criteria used in the system in predicting progression to AIDS. The WR classification was applied to a cohort of 431 men who were seropositive for the human immunodeficiency virus on entry into a prospective study. The WR classification was of limited usefulness, as only 133 men (31%) could be assigned to a WR stage. Among men who could be WR classified, only individuals in WR stage 5 were found to have a significantly more rapid progression to AIDS. The seropositive cohort was also classified based on initial CD4 cell number. Low CD4 counts (less than 400 cells/mm3) were significantly associated with progression to AIDS, and grouping seropositive men by CD4 number alone provided as much prognostic information as the WR classification. Skin test anergy was also a significant predictor for progression to AIDS, but only in individuals with low CD4 counts.

Acquired Immunodeficiency Syndrome↗

PubMed1987

Cisplatin and 5-fluorouracil in the primary management of squamous esophageal cancer.

A combined treatment program consisting of chemotherapy with cisplatin and infusion 5-fluorouracil (5-FU) for three cycles followed by esophagectomy or radiation, or both, has been conducted in 26 patients with squamous cancer of the esophagus localized to the primary site. Eleven patients had objective evidence of partial or complete response to the chemotherapy. Fourteen patients were operated on and ten underwent total esophagectomy. Drug toxicity was considerable with severe mucositis and myelosuppression occurring in 11 and seven patients, respectively. There were no drug-related deaths. Median survival is 17.8 months. Ten patients have lived more than 2 years. Six of these patients have undergone total thoracic esophagectomy after the induction chemotherapy. Determination of the ultimate benefits of combined modality therapy may require prospective randomized trials isolating the major treatment components but our data suggest that chemotherapy contributes to improved results in this disease and that drug therapy is emerging as an integral component of combined therapy.

Aged↗

PubMed1987

Induction of high-grade, high-stage carcinomas in the rat urinary bladder.

The hypothesis that biologic aggressiveness of bladder cancer is determined by carcinogen dose was tested using heterotopically transplanted rat urinary bladders (HTBs). Young male Fischer rats, which were recipients of normal bladders, were divided into three groups; the first group received 0.5 mg of N-methyl-N-nitrosourea (MNU) into HTBs for six doses, a second, 0.05 mg for six doses and the third, 1 mg for three doses. Separately, a group of animals received bladders from rats treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) in drinking water for 4 weeks; the transplanted bladders then were treated with 0.5 mg of MNU for six doses. Treatment with the larger dose of MNU resulted in a significant increase in tumor incidence and frequency of invasive carcinomas. The combination carcinogen treatment induced more invasive carcinomas than the single treatment. The data suggest that deeply invasive carcinomas may develop in two ways: the first is by emergence of a more anaplastic cell population within a pre-existing noninvasive carcinoma and the second is by the de novo development of an invasive carcinoma directly from a severely dysplastic urothelium, which is acceptable as carcinoma in situ. Squamous differentiation was characteristic of deeply invasive carcinomas. The dose of carcinogen(s) is a determinant of aggressiveness of bladder carcinomas.

Animals↗

PubMed1987

Prevalence of antibody to hepatitis B virus in foreign-born hospital employees.

Hepatitis B surface and core antibodies were measured in 512 community hospital employees at increased risk for developing infection with hepatitis B virus. Antibody was detected in 140 (27 percent) participants. Multivariate logistic regression analysis indicated that seropositivity was strongly associated with the prevalence of hepatitis B in an employee's country of birth and with age. These results suggest that reported differences among hospitals in hepatitis B seropositivity may in part be a reflection of the national origin of its employees. These data also indicate that each hospital should assess its own risk for hepatitis B infection and that prevaccination serologic testing is particularly worthwhile in hospitals having large numbers of foreign-born employees.

Carrier State↗

PubMed1987

Tumor size in endometrial cancer: a prognostic factor for lymph node metastasis.

The association of tumor size and lymph node metastasis in endometrial cancer clinically confined to the uterus was evaluated in 91 patients. Other factors possibly associated with lymph node metastasis were also analyzed. Tumor size was independently associated with lymph node metastasis when analyzed by multivariate analysis (P = .022). Patients with tumors less than or equal to 2 cm in diameter had only a 5.7% incidence of lymphatic metastases. When tumors exceeded 2 cm in diameter or involved the entire endometrial surface, metastases occurred in 21.7 and 40.0% of patients, respectively. Measuring tumor size at surgery, or possibly preoperatively by hysteroscopy, will help predict which patients are at increased risk for lymph node metastasis. There were no lymph node metastases in patients with tumors less than or equal to 2 cm in diameter and invasion of less than half of the myometrium. For these patients, extended surgical staging with pelvic and aortic lymph node biopsies may not be indicated.

Female↗

PubMed1987

Prognostic implications of proliferative activity and DNA aneuploidy in colonic adenocarcinomas.

Paraffin-embedded surgical specimens from 120 patients who underwent resections for primary untreated colonic adenocarcinoma were examined for proliferative activity, DNA aneuploidy, DNA index, and the proportion of aneuploid cells by flow cytometry. The results were correlated with survival times and clinical characteristics of the patients. The presence of metastases, both distant and restricted to local lymph nodes, was found to be a more potent adverse prognostic indicator than any DNA flow cytometry-derived parameter. Additional analyses were performed following stratification of patients into two groups on the basis of presence or absence of metastases. Analysis of 60 patients without metastatic involvement revealed a significant correlation between high proliferative activity, defined as more than 20% of cells in S-phase, and DNA aneuploidy. In fact, high proliferative activity was shown to be a more powerful adverse prognostic indicator in relation to survival than DNA aneuploidy in these cases after multivariate analysis. These results suggest that differences in proliferative activity may be an important biologic factor operative in the variable prognosis seen in colonic adenocarcinoma. In addition, they re-emphasize the importance of stratifying patients into groups based on metastatic involvement when evaluating other possible prognostic features in this disease.

Adenocarcinoma↗

PubMed1986

Estramustine affects bone mineral metabolism in metastatic prostate cancer.

A patient with metastatic prostate cancer is described where treatment with Adriamycin (doxorubicin) and estramustine produced severe hypophosphatemia (serum phosphate level, 1.2 mg/dl), which was reversible when treatment was discontinued. Previous studies have shown no effect of Adriamycin on serum phosphate levels. A retrospective study of serial serum chemistry values was done in 15 patients treated with estramustine. A significant fall in the serum phosphate level (mean, 0.8 +/- 0.3 mg/dl) was observed during the first 6 weeks of treatment. When compared with similar patients treated with bilateral orchiectomy, estramustine-treated patients had lower levels of serum calcium, fractional excretion of calcium, serum phosphate, and renal tubular threshold for phosphate reabsorption (TmPO4/GFR). Qualitatively similar but quantitatively smaller effects were also seen in a group of patients treated with diethylstilbestrol (DES) in a dose of 1 to 3 mg daily. Estramustine appears to have significant effects on bone mineral metabolism, particularly on renal phosphate handling resulting in significant hypophosphatemia. This is probably due to an estrogenic effect.

Adenocarcinoma↗

PubMed1986

Emergency administration of radiocontrast media in high-risk patients.

Patients with previous anaphylactoid reactions to radiographic contrast media (RCM) are at increased risk for subsequent reactions on repeat exposure. The most efficacious pretreatment regimens require administration of medications up to 13 hours before the anticipated procedure. Emergency administration of RCM in patients requiring essential procedures precludes prolonged pretreatment. We report results of pretreatment in nine patients requiring emergency administration of RCM. We recommend hydrocortisone, 200 mg intravenously, immediately, and every 4 hours until the procedure is completed, and diphenhydramine, 50 mg intravenously, 1 hour before the procedure. No reactions occurred in these patients, suggesting that this pretreatment regimen may be valuable in prophylaxis for patients requiring emergency administration of RCM who have experienced previous anaphylactoid reactions. Although used in only one additional patient, ephedrine, 25 mg orally, 1 hour before the procedure may also be valuable.

Anaphylaxis↗

PubMed1986

Phenotypic analysis in diffuse, large cell lymphoma. Clinical and histologic associations.

To investigate the possible relationships between immunologic phenotype, histologic subtype, and clinical features in diffuse, large cell lymphoma (DLCL), a computerized registry has been established for the prospective collection of immunologic, histologic, and clinical data. A combination of immunofluorescence and immunoperoxidase technics on single-cell suspensions, frozen tissues, and B5-fixed, paraffin-embedded specimens was used to study the first 33 biopsies. A definitive phenotype was established in all but two cases. Monoclonal antibody reagents reactive in B5-fixed, paraffin-embedded tissue sections helped assign a B-cell lineage in four cases lacking surface or cytoplasmic immunoglobulin, monoclonal light chains, and T-cell markers. There was no statistically significant association between the immunologic phenotype (whether mature B or not) and any clinical or histologic parameter, including response to therapy and survival. Bone marrow involvement was found to be associated significantly with both vague nodularity and a cleaved cell subtype. Through the use of a multifaceted approach to the immunophenotypic analysis of the DLCLs, a distinct lineage and stage of differentiation could be assigned to most biopsy specimens. That such analysis has significant clinical implications for patients with DLCL could not be demonstrated in this series.

Adult↗

PubMed1986

Prognostic implications of ploidy and proliferative activity in diffuse large cell lymphomas.

Paraffin-embedded surgical biopsies from 50 patients with newly diagnosed diffuse large cell lymphoma (DLCL) were examined for proliferative activity and DNA aneuploidy by flow cytometry. These results were correlated with the clinical characteristics of these patients and the course of their disease. High proliferative activity, defined as less than 80% of cells in G0 or G1, was found to be the single most important pretreatment adverse prognostic factor in these patients. This relationship remained significant after correcting for poor performance status and advanced Ann Arbor stage, the other factors found to be associated with a shortened survival. DLCLs with high proliferative activity were more probable to present with extranodal involvement than those with lower proliferative activity. The mitotic count as determined by light microscopy did not correlate with flow cytometry-defined proliferative activity and may be a less accurate method for assessing this important biological characteristic in DLCL. DNA aneuploidy was detected in 62% of cases but did not appear to have any prognostic significance. Biopsies from patients who presented with lymphomatous bone marrow involvement, however, invariably demonstrated an aneuploid stemline. These results suggest that differences in proliferative activity may be an important biological basis for the variable prognosis seen in DLCL.

Adolescent↗

PubMed1985

A phase II study of high-dose estrogens (diethylstilbestrol diphosphate) in prostate cancer.

Twenty-five patients with metastatic prostate cancer resistant to primary hormone therapy, received high-dose intravenous diethylstilbestrol diphosphate (Stilphostrol [Miles Pharm], DES-P) in a Phase II study using established response criteria. Objective response rate was 17%, while 22% of the patients were subjectively improved. Moderate gastrointestinal toxicity was reported in 10 patients (40%). Thromboembolic complications were seen in 2 (8%). The role of high-dose Stilphostrol in the treatment of hormone-resistant prostate cancer is limited.

Acid Phosphatase↗

PubMed1985

Sequential clinical and immunologic abnormalities in hemophiliacs.

We examined 35 patients with hemophilia to determine if there was an association between impaired cell-mediated immunity and the amount of factor concentrate use. There was a significant negative relationship between the logarithm of the helper-suppressor ratio and the logarithm of concentrate use determined over the previous one year, five years, and total lifetime. Similarly, the presence of splenomegaly was significantly associated with the logarithm of concentrate use for each time interval. Hypergammaglobulinemia, anergy, and lymphadenopathy were present in a high proportion of patients. Repeated study of 30 of these patients at eight to 14 months showed no significant changes in their T-cell subsets. At follow-up, 16 patients had lymphadenopathy with or without splenomegaly and four had splenomegaly alone. No significant associations between concentrate use during the study period and changes in T-cell subsets or clinical condition were found.

Adolescent↗