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PubMed1988

Pyrogenic reactions associated with the reuse of disposable hollow-fiber hemodialyzers.

We investigated 18 pyrogenic reactions (PRs) that occurred between July 1 and 13, 1987, in 16 patients receiving long-term hemodialysis at one dialysis center in Illinois. We defined a case of PR as the onset of chills or fever (oral temperature, greater than or equal to 37.8 degrees C) in a patient who was afebrile and had no signs or symptoms of infection before a dialysis treatment. Pyrogenic reactions to dialysis sessions during the epidemic period (July 1 through 14) were associated with the use of a reused dialyzer (risk ratio, 6.2; 95% confidence interval, 0.8 to 45). The water used to rinse the dialyzers after use and to dilute the germicide for disinfecting the dialyzers contained high concentrations of endotoxins (greater than 6 ng/mL) and bacteria (greater than 10(4) colony forming units/mL). After reuse of dialyzers was discontinued at the center, the PR rate fell to pre-epidemic levels. We concluded that PRs were associated with reuse of dialyzers, probably contaminated with endotoxins. Active surveillance for PRs among patients undergoing long-term hemodialysis should be routine at all dialysis centers; an increase in PRs should prompt timely review of water treatment and dialyzer reprocessing systems.

Bacteria↗

PubMed1987

Intraoperative outflow resistance as a predictor of late patency of femoropopliteal and infrapopliteal arterial bypasses.

To evaluate the efficacy of intraoperative outflow resistance (OR) measurements in predicting late graft patency rates (PR) for femoropopliteal (FP) and femoroinfrapopliteal (FD) bypasses, we have reviewed 134 such cases performed during the past 3 years at our institution. Of these, 64 bypasses were FP (13 autogenous saphenous vein [ASV] and 51 polytetrafluoroethylene [PTFE]) and 70 were FD (43 ASV and 27 PTFE). Total and distal OR measurements (measured in millimeters of mercury per milliliter per minute) were divided into four groups each for all infrainguinal bypasses combined and for FP and FD bypasses separately. The relationship of PR to total and distal OR measurements were analyzed according to the product limit method. Overall 1- and 2-year PRs were 64% and 56%, respectively. For FP bypasses the same PRs were 78% and 67% whereas for FD bypasses, they were 52% and 45%, respectively. The 1-year PRs for FP and FD bypasses within each respective OR group were analyzed. For FP bypasses in the lowest to the highest total OR groups, the 1-year PRs were 86%, 75%, 78%, and 62% (NS), and for FD bypasses they were 72%, 89%, 23%, and 22% (p less than 0.001). Similar trends were observed when distal OR measurements were analyzed. For infrainguinal PTFE bypasses, both total and distal OR measurements were significant predictors of patency, whereas for those with ASV only distal OR measurements were predictive. These data reaffirm our early experience with OR measurements. Although a trend for predicting graft patency was noted for FP bypasses, OR measurements were highly predictive only for FD bypasses.

Adult↗

PubMed1981

[Transmission of nociceptive information along the spino-cervico-thalamic component of the lemniscal system].

Noxious heating (up to 44-60 degrees) of the skin of the foot facilitated the primary cortical responses (PRs) evoked by threshold stimulation of spinocervical tract (SCT) neurones receiving information from the heated skin area. The facilitation reached its maximal level 3-4 minutes after the beginning of the heating when the amplitude of PRs increased 2-4 times. The facilitation is completely due to an increase in excitability of SCT neurones, since PRs to stimulation of the exons of these neurones in the dorsolateral funiculus did not change. In view of the fact that PRs, at least their early components, are evoked by impulses reaching the cerebral cortex through the lemniscal system, the findings suggest that the lemniscal system transmits not only tactile, as for many years has been generally accepted, but also nociceptive information. When it is considered that the lemniscal system, contrary to the extralemniscal pathways, shows a high degree of topographic organizations, the above suggestion should be viewed as having a paramount importance for understanding the animal's ability for an exact localization of the site of pain stimulation.

Afferent Pathways↗

PubMedDate not supplied

Prevalence of selected pediatric conditions in children with Pierre Robin sequence.

Pierre Robin sequence (PRS) is a congenital abnormality characterized by micrognathia and glossoptosis, with or without cleft palate. Patients with PRS may demonstrate various pediatric conditions such as associated syndromes, respiratory distress, feeding difficulties, or middle ear pathology. The purpose of this study was to determine, by means of a retrospective computerized review of patient records, the presence of these pediatric conditions in a sample of 55 confirmed patients with PRS. Five patients (9.1%) exhibited associated syndromes; 20 (36.4%) had respiratory distress requiring no assistance; and 10 (18.2%) exhibited severe respiratory distress requiring tracheotomy. A total of 30 patients (54.5%) had early feeding difficulties requiring mechanical assistance to maintain adequate nutrition, and 50 (90.9%) had multiple episodes of otitis media. Chi-square analysis revealed a statistically significant relationship between the presence of respiratory difficulties and the need for feeding assistance (P = 0.012); and a highly significant relationship between the presence of otitis media and subsequent myringotomy tube placement (P < 0.001). Pediatric dentists who treat children with PRS should be aware of these relationships when obtaining medical history before establishing strategies to implement a treatment plan.

Bottle Feeding↗

PubMed1994

Review of phase II trials of Taxol (paclitaxel) in patients with advanced ovarian cancer.

The efficacy and safety of paclitaxel in the treatment of advanced ovarian cancer has been assessed in several phase II trials. McGuire and associates at the Johns Hopkins Oncology Cancer reported results from a phase II trial in which paclitaxel-administered as a 24-hour intravenous (i.v.) infusion with premedication to avoid acute hypersensitivity reactions-yielded one complete response (CR) and 11 partial responses (PRs) (overall response rate, 30%) among 40 previously treated patients with ovarian cancer evaluable for response; 25 of the patients had been refractory to cisplatin therapy. Among 30 evaluable patients who took part in a study at the Albert Einstein Cancer Center, paclitaxel (180 to 250 mg/m2 as a 24-hour i.v. infusion every 21-28 days) produced an overall response rate of 20% (1 CR, 5 PRs). Four responding patients were resistant to previous cisplatin therapy. Median survival for responders was 27 months, and 6 months for nonresponders (P = 0.0001). The Gynecologic Oncology Group confirmed the activity of paclitaxel (175 mg/m2 as a continuous 24-hour i.v. infusion) in 41 evaluable cisplatin-resistant patients, among whom 15 (37%) responded (5 CR, 10 PR). A total of 8 of 27 (29%) patients with cisplatin-refractory disease responded (2/27 CR, 6/27 PR). Among 14 patients whose disease progressed more than 6 months following cisplatin therapy, 3 had CRs and 4 had PRs. Finally, the National Cancer Institute Treatment Referral Center protocol enrolled more than 2,000 patients; preliminary analysis of 1,000 patients included 663 evaluable for response with measurable disease. There are 27 CRs and 119 PRs; median time to progression for responding patients is 7 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Cisplatin↗

PubMed2025

Contributions of Common, Rare, and Somatic Genetic Variants to Incidence of Atrial Fibrillation.

IMPORTANCE: Atrial fibrillation (AF) has a complex genetic architecture involving common, rare, and somatic variants. The association between these components requires further investigation. OBJECTIVE: To examine the individual and combined contributions of polygenic, monogenic, and somatic genetic variants to AF incidence, and develop an integrated genomic model (IGM-AF) for improved risk prediction. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used whole-genome sequence data from participants of the UK Biobank, with follow-up for AF events through hospital records, death registries, and self-report. The UK Biobank recruited participants aged 40 to 69 years in the UK between 2006 and 2010. Study data were analyzed from August 2022 to November 2024. EXPOSURES: IGM-AF comprising an AF polygenic risk score (PRS), a composite rare variant gene set (AFgeneset), and somatic variants associated with clonal hematopoiesis of indeterminate potential (CHIP). Clinical AF risk was estimated using the Cohorts for Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) score. MAIN OUTCOMES AND MEASURES: The primary outcome was hazard ratios (HRs) for 5-year incident AF attributable to PRS, AFgeneset, CHIP, and their interactions. The predictive performance of IGM-AF and its components was quantified using HRs, C statistics, and reclassification indices. RESULTS: A total of 416 085 individuals (mean [SD] age, 56.6 [8.0] years; 224 642 female [54.0%]) with 30 797 AF cases were included. The PRS (HR per 1 SD, 1.65; 95% CI, 1.63-1.67; P < 1 × 10-8), AFgeneset (HR, 1.63; 95% CI, 1.52-1.75; P = 1.46 × 10-42), and CHIP (HR, 1.26; 95% CI, 1.15-1.38; P = 1.41 × 10-6) were associated with incident AF. The 5-year cumulative incidence of AF was at least 2-fold among individuals having all 3 genetic drivers (common, rare, and somatic drivers) compared with those with only 1 driver. Integration of IGM-AF with a clinical risk model (CHARGE-AF) showed higher predictive performance (C statistic, 0.80; 95% CI, 0.80-0.80) compared with IGM-AF and CHARGE-AF alone. The classification of the at-risk population for AF was improved when IGM-AF was added to CHARGE-AF (net reclassification index, 0.08; 95% CI, 0.07-0.09). CONCLUSIONS AND RELEVANCE: Results of this cohort study demonstrated the complementary value of common, rare, and somatic variants in shaping genomic AF risk. Leveraging comprehensive genetic information may enhance screening and preventive interventions for AF.

Humans↗

PubMed1999

Intraindividual variability of infant whole-body plethysmographic measurements: effects of age and disease.

The intraindividual variability of whole-body plethysmographic measurements was studied in a large series of consecutive infants (N = 144), divided into two groups: a group of infants born very prematurely (PM, N = 63), with (N = 28) or without (N = 35) a history of bronchopulmonary dysplasia (BPD), and a group of infants with persistent respiratory symptoms (PRS, N = 81), i.e., wheezing (N = 53) or cough (N = 28). The intraindividual variability was determined within each test and between tests, separated by a 10-min interval. In both study groups, the between-test variability was significantly larger than that within tests. Expressed as the median coefficient of variation (CV), the between-test repeatabilities in the PRS group were 8.0% for thoracic gas volume (TGV), 17.5% for airway resistance (Raw), and 18.4% for specific airway conductance (sGaw), and in the PM group, 8.9% for TGV, 20.4% for Raw, and 20.7% for sGaw. However, the individual range of CVs was large, ranging from 3 to 19% for TGV and from 5 to 55% for sGaw. With respect to TGV, the difference between the groups was statistically significant (P = 0.03). In infants with a history of BPD, there was also a significant negative age dependency in CVs of sGaw (r = -0.50, P = 0. 009), showing larger variation among younger individuals. The presenting symptom (wheezing or cough) in the PRS group did not influence the measurement variability significantly, and neither did the degree of bronchial obstruction. We conclude that on a group basis, the repeatability of infant body plethysmographic measurements may be satisfactory for scientific studies demonstrating pharmacodynamic effects; however, the intraindividual measurement variability should be reported for each test conditions and for infant groups in each study. Due to the large range in individual variation and the influence of age and disease processes on the variation, for an individual child there is only questionable benefit from a given measurement, unless the intrasubject, between-test variability is assessed individually before interventions, such as a bronchodilation test.

Bronchopulmonary Dysplasia↗

PubMed1988

Postradiation soft tissue sarcomas. An analysis of 53 cases.

The clinicopathologic features of 53 cases of postradiation soft tissue sarcoma (PRS) were correlated with the physical characteristics of the administered radiation. All but three patients received radiation for malignant processes. Of the secondary sarcomas, malignant fibrous histiocytoma (MFH) accounted for 36 cases (68%), followed by seven extraskeletal osteosarcomas (13%), six fibrosarcomas (11%), two malignant Schwannomas (4%), one extraskeletal chondrosarcoma, and one angiosarcoma. The sex incidence, age of the patient at time of diagnosis, and location of the PRS correlated only with the clinical characteristics of the initial treated condition. The latency period (mean 10 years) showed an indefinite relationship to patient survival but no definite relationship to the patient's age at the time of the initial radiation. There was no difference between patients treated with megavoltage radiation (39 patients) and with orthovoltage radiation (seven patients) in the type of sarcoma, location, or survival, although the orthovoltage group received a lower mean radiation dose (3880 rads) than the megavoltage group (4446 rads). Megavoltage radiation, however, produced deeper tissue radiation changes and was associated with a shorter latency period. Most PRS were poorly differentiated, produced abundant collagen, and had a dismal prognosis.

Adult↗

PubMed1992

Relative effect of steroid hormone receptors on the prognosis of patients with operable breast cancer. A univariate and multivariate analysis of 3089 Japanese patients with breast cancer from the Study Group for the Japanese Breast Cancer Society on Hormone Receptors and Prognosis in Breast Cancer.

In a retrospective multicenter study to investigate the correlation between estrogen (ER) and/or progesterone receptors (PgR) in primary breast cancer with patient prognosis, 3118 patients with operable breast cancer (International Union Against Cancer Stages I, II, and III) were investigated from ten hospitals in Japan who underwent surgery from October 1972 to December 1982; 3089 were evaluable. The ER-positive and PgR-positive cancers were found in 56% and 34% of patients, respectively. The positivities decreased as the tumor size increased but were independent on lymph node metastasis. There were no significant differences in relapse-free survival (RFS) in relation to receptor status (median follow-up, 89 months [ER], 84 months [PgR]). However, in patients with four or more positive nodes, those with PgR-positive cancer had a longer RFS. The patients with ER-positive cancer survived significantly longer than ER-negative ones, with the greatest difference seen in those with four or more positive nodes. There was a significantly longer postrelapse survival (PRS) for patients with ER-positive cancer because of the different distribution of the major metastasis and better responses to first-line and subsequent treatments. Cox's multivariate analysis showed that overall survival but not PRS was affected by ER (and more weakly by PgR) because of the longer PRS in patients with ER-positive cancer.

Adult↗

PubMed1995

Self-esteem and self-efficacy; perceived parenting and family climate; and depression in university students.

This study examined associations among self-esteem and self-efficacy; perceived unfavorable Parental Rearing Style (perceived PRS) and unfavorable family climate in the family of origin; and depression in undergraduates still in frequent contact with their families (N = 186). Unfavorable perceived PRS and family climate were construed as "affectionless control," in which parents and family provide little affection, but excessive control. Constructs were measured by the Self-Esteem Inventory, the Self-Efficacy Scale, the Child Report of Parental Behavior Inventory, the Family Environment Scale, and the Beck Inventory. Perceived "affectionless control" in both PRS and family climate accounted for about 13% of the variance in self-esteem, self-efficacy, and depression. Neither introversion nor depression mediated the relation between family socialization and self-esteem.

Adolescent↗

PubMed1994

PA-IgG on platelet subpopulations of different buoyant densities: high levels on the low density population is an artifact.

We isolated subpopulations of normal blood platelets from platelet rich plasma (PRP) and, in parallel, from platelet rich saline (PRS) on the basis of their buoyant densities. The MPV, being smallest in the lightest subpopulation, correlated significantly with platelet buoyant density (P < 0.002). In agreement with previous reports, we showed that the least dense platelet subpopulation, separated from PRP, had a high level of PA-IgG (3,486 mol/plt). This value was significantly greater (P < 0.02) than PA-IgG in the lightest subpopulation separated from PRS (693 mol/plt). We believe that the procedure of separating platelets from PRP artificially increased PA-IgG in the least dense subpopulation. Our data showed that when subpopulations were prepared from PRS, PA-IgG correlated with platelet buoyant density (P < 0.002), and that the subpopulation with the highest density had the highest level of PA-IgG.

Autoantigens↗

PubMed2003

Phosphoribosylpyrophosphate synthetase overactivity as a cause of uric acid overproduction in a young woman.

Overactivity of phosphoribosylpyrophosphate synthetase (PRS) is an X chromosome-linked disorder of purine metabolism that is characterized by gout with uric acid overproduction and, in some families, neurodevelopmental impairment. We present the case of a 24-year-old Spanish woman with renal colic and hyperuricemia, which first manifested at age 11 years. Results of enzymatic and genetic studies supported the view that accelerated purine nucleotide and uric acid production in this woman resulted from defective allosteric regulation of PRS activity, which is, in turn, a consequence of a mutation in one of the patient's PRPS1 genes: an A-to-T substitution at nucleotide 578, encoding leucine for histidine at amino acid residue 192 of the mature PRS1 isoform. A previous example of disordered regulation of PRS1 activity in a family with a different substitution at the same amino acid residue strengthens this proposed mechanism. This is the first reported instance of PRS overactivity in which the propositus and sole affected family member is a woman.

Adult↗

PubMed2026

Prostate Cancer, Genetic Susceptibility, and Risk of Chronic Non-Urological Complications.

BACKGROUND: Chronic nonurological complications are common among prostate cancer (PCa) survivors; however, their spectrum, magnitude, and genetic contribution remain poorly characterized. METHODS: We evaluated 15 commonly reported nonurological complications and tested their associations with exposure to PCa and disease-specific polygenic risk scores (PRS) in the UK Biobank (UKB; N = 219,133). Analyses were conducted using cause-specific Cox proportional-hazards models within a full-cohort framework with time-updated PCa status, delayed entry at study recruitment, and age as the underlying time scale. RESULTS: After recruitment, incident PCa was diagnosed in 13,780 men, of which 1,656 (12.02%) had metastatic PCa (mPCa). Risks for seven complications were higher among men with PCa, adjusting for genetic background (all p < 0.05), including osteoporosis, venous thromboembolism, depression, and four primary cancers (bladder, kidney, colorectal, and pancreatic). Risks were consistently stronger among men exposed to mPCa than non-mPCa; for example, the hazard ratio (HR) (95% confidence interval) for osteoporosis was 1.88 (1.63-2.18) for any PCa, 4.67 (3.11-7.01) for mPCa, and 1.75 (1.50-2.04) for non-mPCa. Elevated risks for three additional complications (coronary artery disease, type 2 diabetes and chronic obstructive pulmonary disease) were observed only among men with mPCa. The risks for these ten complications were further increased among men with higher disease-specific PRS; for example, the HR for osteoperosis in mPCa patients in the top PRS quartile was 13.57 (8.24-22.34) compared with men without PCa (p < 0.001). CONCLUSION: PCa diagnosis and inherited genetic susceptibility jointly contribute to increased risks of multiple chronic non-urological complications among survivors.

Humans↗

PubMed1997

Potency comparison of peptidomimetic inhibitors against HIV-1 and HIV-2 proteinases: design of equipotent lead compounds.

HIV-1 and HIV-2 proteinases (PR) are responsible for the processing of viral polyproteins, a step that is crucial for the formation of infectious virus particles. PR represents one of the most important targets for antiviral chemotherapy. Inhibitors of HIV-1 PR usually exhibit a 10- to 100-fold weaker affinity for HIV-2 PR. In order to design subnanomolar inhibitors for both HIV-1 and HIV-2 PRs, we prepared a series of compounds varying in the type of scissile bond replacement as well as in the P1, P1', and P2' side chains. While inhibitors containing reduced amide, hydroxyethylamine and statine isosteres had Ki values in the range of 10(-10)-10(-9) M against HIV-1 PR; their activities against HIV-2 PR were several orders of magnitude lower. Glutamic acid was identified to be the optimal P2' residue for both PRs. HIV-2 PR was shown to be more sensitive to P2' Glu-->Gln replacement. Using this data set we were able to design and prepare hydroxyethylene isostere containing inhibitors that were equipotent against both PRs.

Aspartic Acid Endopeptidases↗

PubMed1998

Steroid receptor expression in endometria from women treated with tamoxifen.

Breast cancer patients receiving tamoxifen (Tam) are at an increased risk for developing endometrial carcinomas, possibly due to the partial estrogenic effect of Tam on endometrial cells. Progestational therapy has not routinely been included in Tam regimens. It was our aim to determine the presence of estrogen receptors (ERs) and progesterone receptors (PRs) in normal and abnormal endometria from postmenopausal women with breast cancer who were treated with Tam. Standard immunohistochemical staining of ERs and PRs was performed on paraffin sections from formalin-fixed uterine curettings or hysterectomy specimens from 40 patients who had received 20-40 mg of Tam daily for a minimum of 3 months. For comparison, normal endometria from 20 women who had not received Tam (11 premenopausal, 9 postmenopausal) were also studied for ER and PR expression. Staining was evaluated using semiquantitative immunoreactivity scores (IRS) ranging from 0 (negative) to 12 (strongly positive). In the group of patients receiving Tam, ERs and PRs were detected in the nuclei of glandular cells in 24/24 cases of endometrial atrophy (ER/PR-IRS, 2-12), in 8/8 endometrial polyps (ER-IRS, 6-12; PR-IRS, 4-12), in 4/4 adenomatous endometrial hyperplasias (ER-IRS, 3-8; PR-IRS, 1-12), and in 4/4 well-differentiated endometrioid adenocarcinomas (ER-IRS, 2-12; PR-IRS, 6-8). Of the 11 endometria from premenopausal patients who had not received Tam, 8 were ER+/PR+ (ER-IRS, 1-12; PR-IRS, 1-12), 1 was ER+/PR- (ER-IRS, 3; PR-IRS, 0), 1 was ER-/PR+ (ER-IRS, 0; PR-IRS, 2), and 1 was ER-/PR- (ER/PR-IRS, 0). Among 9 atrophic endometria from women not treated with Tam, 6 were ER+/PR+ (ER-IRS, 4-12; PR-IRS, 3-6), 1 was ER+/PR- (ER-IRS, 4; PR-IRS, 0), and 2 were ER-/PR- (ER/PR-IRS, 0). The consistent finding of ER and PR expression in endometria from postmenopausal women receiving Tam further supports the suspected estrogenic effect exerted by Tam on endometrial cells. Progestational therapy could be beneficial in the prevention of Tam-induced abnormal endometrial proliferations.

Antineoplastic Agents, Hormonal↗

PubMed2001

The role of neurosteroids and nongenomic effects of progestins in the ventral tegmental area in mediating sexual receptivity of rodents.

Progesterone (P(4)) in the ventromedial hypothalamus (VMH) and ventral tegmental (VTA) is important for facilitation of lordosis; however, P(4)'s actions in these brain areas are different. Using lordosis in rodents as in vivo experimental models, we have examined the effects progestins exert in the midbrain and hypothalamus. Localization and blocker studies indicate that P(4)'s actions in the VMH require intracellular progestin receptors (PRs) but in the VTA they do not. Progestins that have rapid, membrane effects, and/or are devoid of affinity for PRs, facilitate lordosis when applied to the VTA. Manipulation of GABA and/or GABA(A)/benzodiazepine receptor complexes (GBRs) in the VTA alter lordosis, which suggests that progestins may interact with GBRs to facilitate receptivity by enhancing the function of GABAergic neurons. Interfering with P(4)'s metabolism to 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP), the most effective endogenous positive modulator of GBRs, or the biosynthesis of the neurosteroid 3 alpha,5 alpha-THP in the VTA attenuates female sexual behavior in rodents. Stimulation of mitochondrial benzodiazepine receptors (MBRs), which enhance neurosteroid production, by infusions of a MBR agonist to the VTA enhances lordosis. 3 alpha,5 alpha-THP is increased in the midbrain of mated > proestrous > diestrous rodents. These data suggest that 3 alpha,5 alpha-THP has a proximate modulatory role on lordosis. In summary, the actions of P(4) in the VTA are different from those in the VMH that involve PRs. In the VTA, P(4) may facilitate lordosis following metabolism to and/or biosynthesis of 3 alpha,5 alpha-THP, which may have subsequent actions at GBRs and/or MBRs to acutely modulate female sexual behavior in rodents.

Animals↗

PubMed1985

Massive peripheral retinal sclerosis. Correlation between light and scanning electron microscopic findings.

Peripheral retinal sclerosis (PRS) is especially massive in cases of high myopia and retinitis pigmentosa. The distribution and configuration of the sclerotic formations in nine such cases were studied and compared by light microscopy and SEM. Different aspects of the sclerotic structures are described. It is shown that no formations of PRS lie isolated within the degenerated retinal tissue as could be supposed by light microscopy. They are always in multiple contact to or originate from the vitreo-retinal border layer and/or peripheral retinal vessels. This leads to the supposition that these preexisting collagenous structures participate in some way in the formation of PRS.

Aged↗

PubMed1993

Phase II study of NK313 in malignant lymphomas: an NK313 Malignant Lymphoma Study Group trial.

Liblomycin (NK313) is a bleomycin analog that has proved to be associated with less pulmonary toxicity and with more potent antitumor activity than bleomycin in animal tumors. In a phase I study, pulmonary toxicity was not observed, whereas myelosuppression was the dose-limiting factor. The maximum tolerated dose was 140 mg/m2 given once a week for 4 weeks. In the present phase II study, patients with malignant lymphomas received liblomycin at 80 or 100 mg/m2 by intravenous infusion over 15 min once a week for 4 weeks. A total of 39 patients were entered, and 31 [4 with Hodgkin's disease (HD) and 27 with non-Hodgkin's lymphoma (NHL)] were evaluable. The median age of the patients was 52 years (range, 22-74 years), and their performance status ranged from 0 to 3. In all, 28 of the patients had a history of intensive anticancer chemotherapy. Responses were evaluated according to WHO criteria. We obtained 1 complete remission and 9 partial remissions (PRs), for an overall response rate of 37%, in the 27 patients with NHL, whereas 1 PR was achieved in the 4 patients with HD. In all, 9 PRs (32.1%) were obtained in patients who had been exposed to prior chemotherapy, including 4 PRs (33.3%) in 12 patients who had previously been treated with bleomycin. Myelosuppression and nausea and vomiting were the major toxicities, which occurred in about 50% of the patients, and myelosuppression was severe in two patients treated at a dose of 100 mg/m2. We concluded that liblomycin demonstrated significant antitumor activity against malignant lymphomas.

Adult↗