Immune responses to Aeromonas hydrophila in cat fish (Heteropneustis fossilis) exposed to cadmium and hexachlorocyclohexane.
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Aeromonas hydrophila↗
Biomedical subjects
W Jones
Publications and source records attributed to W Jones.
Impact of laparotomy finding of significant intraabdominal adhesions on the surgically defined complete response rate to subsequent salvage intraperitoneal chemotherapy.
One possible explanation for the failure of the high concentrations of cytotoxic agents achieved following intraperitoneal (i.p.) drug delivery to produce a favorable response in patients with ovarian cancer is the inability of the drug-containing fluid to be adequately distributed throughout the peritoneal cavity, usually because of intraabdominal adhesion formation. To evaluate the influence of the severity of adhesions, observed at the time of laparotomy performed immediately preceding the initiation of i.p. therapy, on the ability to achieve a surgically defined complete response (S-CR), we retrospectively reviewed the operative reports of 70 patients with small-volume residual ovarian cancer treated on one of three phase-2 salvage i.p. trials at the Memorial Sloan-Kettering Cancer Center. The S-CR rate in the 36 patients with limited adhesion formation observed upon entering the peritoneal cavity was 28%, compared to 35% in the 34 patients with extensive adhesions (P greater than 0.05). In 33 patients treated with a phase-2 cisplatin-based i.p. program, who had previously responded to systemic platinum, 47% (8/17) and 44% (7/16) of those with limited and extensive adhesions, respectively, achieved a S-CR (P greater than 0.05). We conclude that the presence of extensive adhesions observed within the peritoneal cavity at the time of a laparotomy performed immediately prior to the initiation of i.p. therapy does not have a negative impact on the potential to achieve an S-CR, assuming it is technically feasible to lyse all significant adhesions prior to the completion of the operative procedure.
Abdomen↗
Phase 2 trial of chronic low-dose oral etoposide as salvage therapy of platinum-refractory ovarian cancer.
Eighteen previously treated patients with advanced ovarian cancer were entered into a phase 2 trial of chronic low-dose oral etoposide (50 mg/day for 20 days, repeated every 28 days) to determine the activity of this therapeutic strategy in organoplatinum-refractory disease. The treatment program was generally well tolerated, with mild neutropenia the most common side-effect encountered. One patient (6%; 95% confidence interval = 0-17%) achieved a partial response, which lasted for 11 months. Three additional patients (17%), who failed to meet the criteria of a partial response, demonstrated objective evidence of antineoplastic activity. Chronic low-dose oral etoposide administration is associated with definite, although modest, activity in platinum-refractory ovarian cancer.
Carboplatin↗
Association between pretreatment CA-125 levels and surgically documented complete responses in patients with ovarian cancer treated with second-line intraperitoneal therapy.
Approximately 20%-40% of patients with small-volume residual ovarian cancer, following systemically administered platinum-based chemotherapy, will respond to a second-line intraperitoneal treatment regimen. In an effort to improve the selection criteria for patients being considered for this regional therapeutic approach, we retrospectively evaluated the influence of pretreatment CA-125 levels on the ability of a group of 70 patients with small-volume residual ovarian cancer (no tumor mass greater than 1 cm in diameter) to achieve a surgically defined complete response (S-CR) following treatment on one of three phase-2 intraperitoneal chemotherapy trials conducted at the Memorial Sloan-Kettering Cancer Center. Overall, 18/46 (39%) patients with normal pretreatment CA-125 levels (less than or equal to units/ml) achieved a S-CR, compared to only 4/24 patients (17%) with an elevated pretreatment value (chi 2 = 3.7, P greater than 0.5). Despite the lower S-CR rate in patients with elevated CA-125 levels, the duration of response and survival were similar in the two patient populations achieving a S-CR. Thus, we conclude that an elevated pretreatment CA-125 level in a patient with small-volume residual ovarian cancer should not be used by itself to disqualify an individual from consideration for a second-line intraperitoneal treatment regimen, although the finding suggests a reduced likelihood of achieving a S-CR with this therapeutic approach.
Antigens, Tumor-Associated, Carbohydrate↗
Salvage intraperitoneal therapy of small-volume residual ovarian cancer: impact of pretreatment finding of peritoneal carcinomatosis on the surgical complete response rate.
Second-line intraperitoneal (i.p.) therapy has been demonstrated to result in surgically defined complete responses (S-CR) in 25%-40% of patients with small-volume residual ovarian cancer (microscopic disease or largest tumor mass less than 1 cm in diameter). To evaluate the influence of the surgical finding of diffuse peritoneal carcinomatosis on the S-CR rate to salvage i.p. therapy in this patient population, we retrospectively reviewed the operative reports of 70 patients with small-volume residual ovarian cancer treated on one of three phase-2 second-line i.p. trials at the Memorial Sloan-Kettering Cancer Center. Of the 11 patients with diffuse carcinomatosis, none achieved a S-CR compared to a S-CR rate of 37% (22/59) in patients without this surgical finding (chi 2 = 6.0; P less than 0.025). However, of the 7 patients with diffuse carcinomatosis treated on a cisplatin-based i.p. program, the only 2 who had previously responded to systemic platinum also experienced a response (partial) to the i.p. cisplatin regimen. In conclusion, while the surgical finding of diffuse peritoneal carcinomatosis indicates a poor prognosis in patients with small-volume residual ovarian cancer for response to i.p. chemotherapy, patients in this clinical setting with prior evidence of platinum sensitivity may experience some benefit from an i.p. cisplatin-based treatment strategy.
Cisplatin↗
Methods for testing impairment of driving due to drugs.
The Transport and Road Research Laboratory has been concerned for a long time with possible causes of driving difficulties and has developed methods for investigating driving performance. The question addressed here was how applicable these methods are in assessing driving problems arising from the use of drugs which can impair performance, particularly widely-available centrally-acting drugs. We assessed four types of driving-related tests by comparing their sensitivities with two laboratory tests, developed elsewhere, which measure more basic effects of drugs on performance, using drugs known to impair skills. Performances under the influences of ethanol, the benzodiazepine lorazepam, and the antihistamine triprolidine, each given both as a single high dose and a single low dose, were compared with performances after placebo. We used double-blind crossover design, in which subject variability was minimized by studying only women of a limited age range (45-55 y). The driving-related tests detected the effects of the substances used, although they were generally less sensitive than the laboratory tests. The individual sensitivities of the driving test could be improved to match those used for more general assessments.
Automobile Driving↗
Association of cervicovaginal infections with increased vaginal fluid phospholipase A2 activity.
OBJECTIVE: The purpose of this study was to determine if phospholipase A2 was detectable within vaginal fluid and to correlate its presence with the presence of common lower genital tract infection or microbial conditions. STUDY DESIGN: Pregnant women were examined at the first prenatal visit with standard clinical evaluations and microbiologic cultures or tests. Vaginal fluid samples were evaluated for phospholipase A2 activity by means of a standardized enzyme fluorometric assay. Data were stratified to control for coexisting infections. RESULTS: Phospholipase A2 activity was detected among 29.8% of women and was independently associated with the presence of bacterial vaginosis (p < 0.001), Trichomonas. vaginalis (p < 0.04), and Chlamydia trachomatis (p < 0.02). The percentage of women with phospholipase A2 activity and the level of activity was increased in the presence of more than one infection. CONCLUSIONS: Elevated reproductive tract phospholipase A2 concentrations among pregnant women may play roles in the pathogenesis of preterm labor and birth. Identification of pregnant women with increased concentrations in vaginal fluid may allow for development of effective intervention strategies to reduce the risk of preterm birth.
Animals↗
Phenotypic responses of mouse mammary tumours and normal mammary epithelium cultured in collagen gels: correlation with tumour type and progression.
Mammary tumours in female BR6/Icrf mice and the corresponding contralateral normal mammary glands were disaggregated with collagenase and the epithelial structures released ('organoids') separated from other cellular components by filtration. The organoids were established in primary culture in a collagen matrix and the outgrowths obtained were studied by light microscopy and time-lapse cinemicroscopy. The pattern of three-dimensional outgrowths produced was found to be specific to the original tissue. Organoids from normal tissue formed a characteristic outgrowth designated Pattern A. Normal tissue from pregnant mice formed an additional characteristic outgrowth (Pattern A') which has not been described previously. Pregnancy-dependent tumours produced a distinctive phenotypic outgrowth designated Pattern D, whereas pregnancy-independent tumours gave a different distinctive Pattern B as well as a unique specific outgrowth designated Pattern C. Outgrowths of Pattern D from a pregnancy-dependent tumour were removed from culture and implanted into a syngeneic female mouse. Tumours arising in the host were found to be pregnancy-independent and showed phenotypic outgrowths in subsequent culture of pregnancy-independent Patterns B and C. The results show that the type of outgrowths in these cultures correlates with the biology of the tissue in vivo and that changes in tumour progression in vivo are accompanied by alterations in phenotypic outgrowths in culture.
Animals↗
Phase 2 trial of intraperitoneal carboplatin and etoposide as salvage treatment of advanced epithelial ovarian cancer.
To evaluate the efficacy of intraperitoneal (IP) carboplatin-based therapy as salvage treatment of ovarian cancer, 46 patients with persistent or recurrent ovarian cancer following initial systemic chemotherapy were treated with a regimen of carboplatin (200-300 mg/m2) and etoposide (100 mg/m2) administered on a monthly schedule. A maximum of six courses of therapy was delivered, followed by a response laparotomy. The treatment program was well tolerated, except for bone marrow suppression, with one-quarter of patients developing platelet count depressions to < or = 50,000/mm3, and one-third experiencing hemoglobin levels of < or = 8 g/dl during treatment. Twelve (38%) of 32 patients evaluable for efficacy of the treatment program achieved a surgically documented response, including 8 (25%) complete responses. Of 25 patients whose largest tumor mass at the initiation of therapy measured < or = 0.5 cm, 11 (44%) responded, including 8 (32%) complete responses. We conclude that the IP administration of carboplatin can result in surgically documented responses when used in the salvage setting in patients with advanced ovarian cancer. The relative efficacy of carboplatin versus cisplatin when administered by the IP route to patients with ovarian cancer previously treated with platinum-based systemic therapy remains to be defined.
Adult↗
Acute pyogenic Pseudallescheria boydii foot infection sequentially treated with miconazole and itraconazole.
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Acute Disease↗
Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease.
PURPOSE: There is a critical need to find new antineoplastic drugs that are active in platinum-refractory ovarian cancer. We conducted a phase II trial of single-agent ifosfamide with mesna uroprotection in patients with ovarian cancer previously treated with an organoplatinum compound to assess its activity in this clinical setting. PATIENTS AND METHODS: Ifosfamide (1.0 or 1.2 g/m2/d for 5 days, delivered on a monthly schedule) was administered to the 57 patients entered onto this trial. Dose reductions were permitted for unacceptable toxicities. RESULTS: Toxicity included severe bone marrow suppression (WBC count less than 1,000/microL and/or platelet count less than 50,000/microL), renal dysfunction (serum creatinine level greater than 2.0 mg/dL), and reversible CNS dysfunction (disorientation, hallucinations, somnolence, and agitation), which occurred in 20%, 14%, and 12% of patients, respectively. Of 41 patients with strictly defined platinum-refractory ovarian cancer, five (12%) demonstrated a partial (four) or complete (one) response to this treatment program. CONCLUSION: Single-agent ifosfamide has modest but unequivocal activity in platinum-resistant ovarian cancer. Further studies of this drug used as a front-line agent along with an organoplatinum compound or as part of a dose-intensification program with bone marrow, peripheral stem cell, or colony-stimulating factor support are indicated. In addition, single-agent ifosfamide is a reasonable standard second-line treatment strategy in appropriately selected patients with platinum-refractory ovarian cancer.
Acute Kidney Injury↗
Impact on survival of surgically defined favorable responses to salvage intraperitoneal chemotherapy in small-volume residual ovarian cancer.
PURPOSE: To evaluate the impact on survival of the attainment of surgically defined favorable responses (S-R) to salvage intraperitoneal (IP) chemotherapy after initial systemic cytotoxic drug delivery. PATIENTS AND METHODS: We examined the survival of patients who were treated on one of three phase II IP trials that were conducted at the Memorial Sloan-Kettering Cancer Center. A total of 58 patients whose largest residual tumor masses measured less than or equal to 0.5 cm in maximum diameter at the initiation of this salvage therapy were assessable for response, 28 of whom (48%) demonstrated a S-R, which included 19 (33%) who achieved a surgically defined complete response (S-CR). RESULTS: With a median follow-up of 43+ months (range, 33+ to 58+ months) from the initiation of IP therapy, 12 of 19 (63%) have recurred. The median duration of S-CR for the 10 patients with microscopic residual disease was 32 months compared with 15 months for the nine patients with macroscopic residual disease (largest tumor mass less than or equal to 0.5 cm; P greater than .1). For patients with microscopic residual disease who experienced a S-CR (n = 10) after salvage IP therapy, the median overall survival from the initiation of therapy has not been reached, but will exceed 4 years compared with a 25-month median survival for the nonresponding patients (n = 13; P = .004). The median survival for the 18 patients with small-volume macroscopic disease who responded to therapy was 40 months compared with 19 months for the nonresponders (P = .009). CONCLUSION: Although the results of this evaluation are encouraging and suggest that the attainment of a S-R, particularly a S-CR, after IP chemotherapy may result in a clinically meaningful favorable impact on survival, a randomized controlled trial will be required to address definitively this important issue.
Antineoplastic Combined Chemotherapy Protocols↗
Phase I trial of intraperitoneal taxol: a Gynecoloic Oncology Group study.
PURPOSE: To evaluate the safety and pharmacology of the intraperitoneal (IP) administration of the antineoplastic agent taxol. PATIENTS AND METHODS: Twenty-five pretreated patients who were entered onto a phase I clinical trial; 24 had advanced ovarian cancer. Patients were treated with taxol administered IP in 2 L of normal saline every 3 to 4 weeks. The starting dose was 25 mg/m2. There were no intrapatient dose escalations. RESULTS: The dose-limiting toxicity was the development of severe abdominal pain at taxol doses more than 175 mg/m2. Moderate leukopenia (WBC count less than 2,000/mm3) was observed at IP doses of greater than or equal to 175 mg/m2. The exposure of the peritoneal cavity (peak levels and area under the time-versus-concentration curve [AUC]) to taxol after IP delivery exceeded that of the plasma by approximately 1,000-fold. However, concentrations of the agent previously shown to produce cytotoxicity in experimental systems were demonstrated in the systemic compartment after regional delivery, which was considered important. Significant concentrations of taxol persisted within the peritoneal cavity for more than 24 to 48 hours after a single IP installation. Several antitumor responses, which included control of platinum-refractory ascites, were documented. CONCLUSION: Taxol can be delivered by the IP route with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure.
Alkaloids↗
Deficiency of acylpeptide hydrolase in small-cell lung carcinoma cell lines.
During protein biosynthesis, processing of the N terminus of many proteins may occur through acetylation and deacetylation. The enzyme acylpeptide hydrolase is likely involved in deacetylation of nascent peptide chains or of bioactive peptides. The related enzyme, acylase, hydrolyzes the acetyl amino acid product of the acylpeptide hydrolase reaction to acetate and a free amino acid. There is a reciprocal relationship between the substrates for these enzymes (i.e., substrates for one enzyme are competitive inhibitors for the other). In several cultured cell lines, including normal and malignant cells, the ratio of acylpeptide hydrolase to acylase enzyme activities appears to be coordinated and characteristic for a given cell type. Thus, in normal cultured lung cells, hamster ovary cells, hepatoma cells, and lymphocyte cells, nearly equal amounts of these enzymes are expressed, conducive to optimal processing of acetylated N-terminal residues. Four lines of erythroleukemic cell lines were found to express nearly twice as much acylase as acylpeptide hydrolase activity. In the Ehrlich ascites tumor cell line, where 80% of the proteins have been reported to remain acetylated at their N terminus, acylpeptide hydrolase is hardly expressed but acylase activity is not reduced. The 3p21 region of human chromosome 3, which contains the DNF15S2 locus that encodes acylpeptide hydrolase (Jones et al., Proc Natl Acad Sci USA 1991;88:2194), undergoes deletion in some carcinoma cells; the gene that encodes for the acylase is also present on region 3p of the same chromosome. We found that both acylpeptide hydrolase and acylase activities are practically absent in six small-cell lung carcinoma cell lines tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Amidohydrolases↗
Mortality in the slave and white populations of Natchitoches Parish, Louisiana, 1850.
A review of mortality from the 1850 census mortality schedules of Natchitoches Parish, Louisiana has provided a snapshot of the health conditions of African-American slaves. The cause of death was abstracted from the mortality schedule and categorized according to the ninth revision of the Manual of the International Classification of Diseases. Children under the age of 9 accounted for 44% of the total mortality. Sixty-four percent of all deaths recorded occurred in the slave population. Sixty-two percent of the slave deaths occurred in the male population. Leading causes of death were helminthiasis, whooping cough, fever, cholera, and pneumonia. Reports of mortality due to Cachexia Africana (dirt eating) among slaves are discussed.
Black or African American↗
Increased occurrence of exfoliation in the male, Spanish American population of New Mexico.
Exfoliation syndrome was found to occur much more frequently in the male Spanish American population of New Mexico. This was based on a Veterans Administration Medical Center study in Albuquerque, New Mexico. The prevalence of exfoliation in the Spanish Americans was estimated to be from 3-6 percent and this is consistent with many other such studies performed in the United States and other countries. The Spanish American population is 5.8 times more likely to develop exfoliation than the non-Spanish American population of New Mexico. Exfoliation was found on such eye structures as the lens, iris, ciliary processes, posterior capsule, vitreous face, posterior corneal surface, and arterial chamber angle. Glaucoma capsulare was also studied and it was found that there was not a significant difference between the Spanish American and the non-Spanish American population for developing the condition. However, there was a strong association of glaucoma with the presence of exfoliation in both groups. Based on our results, patients with exfoliation are 22 times more likely to develop glaucoma than are their age-matched controls. Also, 40 percent of the exfoliation patients had glaucoma compared with only 5 percent of the age-matched controls (p less than .001). The patients with glaucoma capsulare were found to have a more medically resistant type of glaucoma, which was consistent with other reports of this condition. There are two theories we propose for the existence of exfoliation in the Spanish American population of New Mexico. The first is a geographic climatic theory that relates exfoliation to greater solar radiation levels due to a high overall altitude and sunny weather in New Mexico.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Exploring the use of chronic low-dose oral etoposide in ovarian cancer: is there a role for this "new drug" in the management of platinum-refractory disease?
Despite showing high objective response rates (70% to 80%) to cisplatin- or carboplatin-based chemotherapy, most patients with ovarian cancer ultimately die of complications of their disease. Etoposide, given either as a single agent or in combination with the organoplatinum compounds, has produced disappointingly low response rates in the salvage setting. Based on recent data that suggest chronic administration of oral etoposide is superior to single daily dosing every 3 to 4 weeks, and the failure of previous trials to evaluate etoposide's activity in cisplatin-resistant malignancies, we have begun a phase II trial of chronic, low-dose oral etoposide in patients with clinically defined, platinum-resistant ovarian cancer. Thus far, 11 patients have been entered into the study. Neutropenia, the most prevalent toxicity, has precluded several patients from receiving the full 20-day course of 50 mg/d. No responses to treatment have been observed in nine evaluable patients. The study continues to accrue patients. The final results of this study and other trials should help determine the efficacy of chronic low-dose oral etoposide administration in patients with ovarian cancer.
Administration, Oral↗
Flexible-benefit plans offer savings for employees, employers.
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Cost Control↗