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Biomedical subjects

L Levy

Publications and source records attributed to L Levy.

At least 55 records · Page 3Linked to original sources

Chemotherapy for cervical carcinoma: factors determining response and implications for clinical trial design.

PURPOSE: To identify characteristics that predict response to chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the cervix. PATIENTS AND METHODS: Between January 1986 and May 1996, 190 chemotherapy-naive patients with advanced or recurrent squamous cell carcinoma of the cervix not amenable to curative radiation therapy or surgery were treated on 14 different chemotherapy protocols at M.D. Anderson Cancer Center. Patient's charts were retrospectively reviewed for patient demographics, tumor and treatment characteristics, and patterns of response and survival. RESULTS: Of 190 patients, 22 had advanced or persistent disease and 168 had recurrent disease. Patients were treated with platinum-based (n=95) and non-platinum-based (n=95) regimens. The overall response rate was 20.0% (4.2% complete response; 15.8% partial response), with a median response duration of 4.8 months. Race, socioeconomic class, tumor stage and grade, mode of primary treatment, time from primary diagnosis to disease recurrence, initial performance status, and use of platinum-based therapy were not significant predictors of response. Age at time of chemotherapy (P=.001) and site of recurrence (P=.044) were significant determinants by multivariate analysis. Patients who were older were more likely to respond to therapy, and the response rate for patients in whom disease recurred outside the irradiated field was 25.2%, compared with a 5.3% response rate for patients with recurrent disease limited to a previously irradiated field. CONCLUSION: The site of disease recurrence and patient age should be taken into account when designing chemotherapy trials and also when considering chemotherapy in the patient with recurrent cervix cancer.

Adult↗

Trends in food label use associated with new nutrition labeling regulations.

OBJECTIVES: This study compared use of food labels before and after implementation of new Food and Drug Administration regulations in 1994. METHODS: Data were obtained by random-digit-dial surveys of Washington State residents in 1993 (n = 1001) and 1996 (n = 1450). RESULTS: After implementation of the new regulations, usual label use increased significantly, by 8.5 percentage points in women and 11.3 percentage points in men. More respondents looked for information on fat content and fewer failed to use labels because they "take too much time" or "are too hard to understand. CONCLUSIONS: Use of food labels and satisfaction with their content have increased, but 70% of adults still want labels to be easier to understand.

Adolescent↗

[Intra-mandibular adenoid cystic carcinoma].

A case of mandibular cystic adenoid carcinoma was observed in a 49-year-old man. After slow progression, the diagnosis was directed to mandibular pseudocystic tumor. The treatment was enucleoresection. Histological findings in this exceptionnal lesion led to a discussion of the radioclinical diagnosis and etiopathogenic features of adenoide cystic carcinoma. The origin of this tumor is hypothesized to be heterotopic salivary inclusion although no histologicaly proof can be provided.

Carcinoma, Adenoid Cystic↗

Synthesis and two-dimensional electrophoretic analysis of mixed populations of circular and linear RNAs.

Spontaneous cleavage of the less abundant form of tobacco ringspot virus satellite RNA is readily reversible. Capitalizing on earlier observations by Feldstein and Bruening that small 'mini-monomer' RNAs derived from this molecule and containing little more than covalently attached ribozyme and substrate cleavage products are able to efficiently circularize, we have constructed a series of self-circularizing RNAs of precisely known size. Mixtures of linear and circular RNAs synthesized in vitro and containing 225-1132 nt could be completely resolved using a novel two-dimensional denaturing polyacrylamide gel electrophoresis system. Similar analyses of a complex mixture of coconut cadang-cadang viroid RNAs revealed the presence of relatively large amounts of a previously undescribed 'fast-slow' heterodimeric RNA species in infected palms. Only a single DNA template is required to prepare each pair of circular and linear RNA markers.

Base Sequence↗

Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22.

PURPOSE: The National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a randomized trial (B-22) to determine if intensifying but maintaining the total dose of cyclophosphamide (Cytoxan, Bristol-Myers Squibb Oncology, Princeton, NJ) in a doxorubicin (Adriamycin, Pharmacia, Kalamazoo, MI)-cyclophosphamide combination (AC), or if intensifying and increasing the total dose of cyclophosphamide improves the outcome of women with primary breast cancer and positive axillary nodes. PATIENTS AND METHODS: Patients (N = 2,305) were randomized to receive either four courses of standard AC therapy (group 1); intensified therapy, in which the same total dose of cyclophosphamide was administered in two courses (group 2); or intensified and increased therapy, in which the total dose of cyclophosphamide was doubled (group 3). The dose and intensity of doxorubicin were similar in all groups. Disease-free survival (DFS) and overall survival were determined using life-table estimates. RESULTS: There was no significant difference in DFS (P = .30) or overall survival (P = .95) among the groups through 5 years. At 5 years, the DFS of women in group 1 was similar to that of women in group 2 (62% v 60%, respectively; P = .43) and to that of women in group 3 (62% v 64%, respectively; P = .59). The 5-year survival of women in group 1 was similar to that of women in group 2 (78% v 77%, respectively; P = .86) and to that of women in group 3 (78% v 77%, respectively; P = .82). Grade 4 toxicity increased in groups 2 and 3. Failure to note a difference in outcome among the groups was unrelated to either differences in amount and intensity of cyclophosphamide or to dose delays and intervals between courses of therapy. CONCLUSION: Intensifying or intensifying and increasing the total dose of cyclophosphamide failed to significantly improve either DFS or overall survival in any group. It was concluded that, outside of a clinical trial, dose-intensification of cyclophosphamide in an AC combination represents inappropriate therapy for women with primary breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Intraoperative ketorolac has an opioid-sparing effect in women after diagnostic laparoscopy but not after laparoscopic tubal ligation.

Ketorolac tromethamine (Toradol) is a parenteral, nonsteroidal antiinflammatory drug that is being extensively used to provide postoperative analgesia. This study evaluated whether intraoperative ketorolac would act synergistically with fentanyl to decrease postoperative analgesic requirements in outpatients undergoing gynecologic procedures. The patients studied were adult ASA physical status I or II females scheduled for diagnostic laparoscopy (DL) (n = 80) or laparoscopic tubal ligation (TL) (n = 46). Each patient received fentanyl 2 micrograms/kg intravenously (i.v.) before induction, followed by a standardized propofol anesthetic and 2 mL of saline or ketorolac 60 mg i.v. in a randomized double-blind fashion 30 min before the anticipated end of the operative procedure. Patients were assessed for postoperative pain via a 10-cm visual analog scale (VAS) (0 = no pain; 10 = severe pain) before analgesic treatment in the postanesthesia care unit (PACU). Severe postoperative pain (VAS or 5 or more) was treated with incremental doses of fentanyl, 25-50 micrograms i.v. by a blinded PACU nurse. Ibuprofen or acetaminophen with codeine was administered for pain control once the patient tolerated oral medications. This study showed that intraoperative ketorolac (60 mg i.v.) with fentanyl (2 micrograms/kg i.v.) administered at the induction of anesthesia resulted in significant opioid sparing and a diminution in pain in the DL sample but not in the TL sample. The analgesic regimen was also associated with a lower incidence of nausea and vomiting and resulted in earlier discharge, which was not seen after TL. These results demonstrate that pain after TL is far greater than that after DL, which suggests that these procedures should be considered separately when designing analgesic regimens.

Adult↗

Haemophilia care in Zimbabwe.

OBJECTIVE: To review haemophilia care in Zimbabwe. DESIGN: Retrospective study. SETTING: Cases seen in both central hospitals and health centres in Harare. MAIN OUTCOME MEASURES: Home treatment hospital admission and HIV seroconversion. RESULTS: Of the expected 500 haemophilicacs in a Zimbabwean male population of five million, only 190 had been registered by mid 1993. Home treatment is effective. CONCLUSION: Haemophilia care in Zimbabwe has a good foundation. Home care is effective and needs to be expanded simultaneously with health education for the cases.

Adolescent↗

Cancer in the European population of Harare, Zimbabwe, 1990-1992.

The data presented from the population-based cancer registry in Harare, Zimbabwe, represent the first information on the incidence of cancer in a population of European origin living in Southern Africa for over 30 years. Their cancer pattern is more or less typical of white populations of high socio-economic status living in Europe or North America, with elevated incidence rates of breast cancer, large-bowel cancer and, in women, lung cancer. However, there are also several unusual features, with extremely high incidence rates of skin cancers, including melanomas, and higher rates of liver and bladder cancer than normally seen in white populations.

Adolescent↗

Cancer in the African population of Harare, Zimbabwe, 1990-1992.

The data presented from the population-based cancer registry in Harare, Zimbabwe, represent the first information on the incidence of cancer in Southern Africa for almost 20 years. In the African population in Zimbabwe there are several features in common with other countries in sub-Saharan Africa: high rates of liver, prostate and cervix cancer, low rates of large-bowel cancer and breast cancer. Also, as reported from southern and south-eastern Africa, there are relatively high incidence rates of cancers of the oesophagus, bladder and (in men) lung. The AIDS epidemic has given rise to a striking increase in incidence of Kaposi's sarcoma (now the commonest cancer of African men), but there is not much evidence for an increase in incidence of non-Hodgkin lymphomas nor, although rates are very high, of cervical cancer.

Adolescent↗

Complete sequence (20 kilobases) of the polyprotein-encoding gene 1 of transmissible gastroenteritis virus.

The entire nucleotide sequence of cloned cDNAs containing the 5'-untranslated region and gene 1 of Purdue-115 strain of transmissible gastroenteritis virus (TGEV) was determined. This completes the sequence of the TGEV genome, which is 28,579 nucleotides long. The gene 1 is composed of two large open reading frames, ORF1a and ORF1b, which contain 4017 and 2698 codons, respectively (stop excluded). A brief, three-codon-long ORF is present upstream of ORF1a. ORF1b overlaps ORF1a by 43 bases in the (-1) reading frame. In vitro experiments indicated that translation of the ORF1a/b polyprotein involves an efficient ribosomal frameshifting activity, as previously shown for other coronaviruses. Analysis of the predicted ORF1a and ORF1b translation products revealed that the putative functional domains identified in infectious bronchitis virus (IBV), mouse hepatitis virus (MHV) and human coronavirus 229E (HCV 229E) are all present in TGEV. The amino-terminal half of the ORF1a product exhibits greater divergence than the carboxyl-terminal half, including within the TGEV/HCV229E pair. The ORF1b protein is overall highly conserved among the above four coronaviruses, except a divergent region situated near the carboxy terminus.

Amino Acid Sequence↗

Form and magnitude of beta-sympathetic and parasympathetic influences on pulse transit time.

In this study, we examined autonomic influences on pulse transit time measured from the R-wave of the electrocardiogram (R-PTT). Six subjects received three doses each of isoproterenol and atropine. Isoproterenol produced a significant linear decrease in R-PTT, a significant linear increase in heart rate (HR), and a significant linear decrease in diastolic blood pressure (DBP). Atropine produced a significant linear decrease in R-PTT and significant linear increases in HR and DBP. The R-PTT shortening effect of isoproterenol may reflect positive inotropic effects of beta-sympathetic myocardial stimulation. The R-PTT shortening effect of atropine may reflect reduction of parasympathetic inhibition of ventricular myocardial activity. However, possible vascular contributions to these effects remain to be determined. Nonetheless, the results encourage further examination of R-PTT in research concerning autonomic regulation of cardiovascular activity.

Adult↗

Growth hormone (GH)-releasing hormone tonically inhibits in vitro endogenous somatostatin in human GH-secreting tumors.

We have previously shown that the somatostatin (SRIH) precursor (pro-SRIH) and SRIH are present in the normal human pituitary, whereas mature SRIH is never detected in GH-secreting adenomas associated with high plasma GH levels, and pro-SRIH is absent in 50% of them. Considering the fact that GHRH is present and released in vitro in higher amounts from GH adenomas than from normal human pituitaries, the possibility of a negative control exerted by GHRH on pituitary SRIH was investigated. When GH-secreting adenomas were incubated for 4 h in the presence of GHRH (10(-8) mol/L), the amount of pro-SRIH, quantified after Sephadex G-50 filtration of the acetic acid extracts, was significantly decreased. The percent inhibition was negatively correlated to the amount of endogenously released GHRH measured in the control incubation medium, suggesting a local negative feedback control exerted by pituitary GHRH on pituitary SRIH. This was further demonstrated when adenomas were incubated with a GHRH antibody. Indeed, the presence of the GHRH antibody resulted in a significant increase in the content of pro-SRIH in the adenoma. Similar results were obtained for in vitro SRIH release; exogenous GHRH induced an inhibition of SRIH release from GH-secreting adenomas, and the GHRH antibody had the opposite effect. Using a perifusion system, we showed the concomitance between the increase in GH release and the decrease in SRIH release after GHRH stimulation. Together, these results show in vitro a negative control exerted by GHRH (both exogenous and locally released) on adenomatous pituitary SRIH. This further amplifies the importance of autocrine or paracrine controls in these tumors.

Adenoma↗

Simple and rapid preparation of infected plant tissue extracts for PCR amplification of virus, viroid, and MLO nucleic acids.

A rapid, simple method for preparing plant tissues infected with viruses, viroids, or MLOs using a commercial product known as Gene Releaser is described. The Gene Releaser polymeric matrix method produced plant extracts suitable for PCR amplification without the use of organic solvents, ethanol precipitation, or additional nucleic acid purification techniques. Modification of maceration methods and/or extraction buffers resulted in the PCR amplification of potato spindle tuber, apple scar skin, and dapple apple viroids, as well as, genomic segments of plum pox potyvirus, grapevine virus B, grapevine leafroll-associated virus III, and elm yellows MLO. These pathogens were amplified from tissue of woody and herbaceous hosts such as peach, apricot, apple, grapevine, elm, periwinkle and potato. The application of this product for use with intractable tissue avoids lengthy and laborious extraction procedures. In our hands, about 20 samples could be prepared for PCR or RT-PCR in 1-2 h versus 1-3 days.

Base Sequence↗

Genetic determinants of feline leukemia virus-induced lymphoid tumors: patterns of proviral insertion and gene rearrangement.

The genetic basis of feline leukemia virus (FeLV)-induced lymphoma was investigated in a series of 63 lymphoid tumors and tumor cell lines of presumptive T-cell origin. These were examined for virus-induced rearrangements of the c-myc, flvi-2 (bmi-1), fit-1, and pim-1 loci, for T-cell receptor (TCR) gene rearrangements, and for the presence of env recombinant FeLV (FeLV-B). The myc locus was most frequently affected in naturally occurring lymphomas (32%; n = 38) either by transduction (21%) or by proviral insertion (11%). Proviral insertions were also common at flvi-2 (24%). The two other loci were occupied in a smaller number of the naturally occurring tumors (fit-1, 8%; pim-1, 5%). Examination of the entire set of tumors showed that significant numbers were affected at two (19%) or three (5%) of the loci. Occupation of the fit-1 locus was observed most frequently in tumors induced by FeLV-myc strains, while flvi-2 insertions occurred with similar frequency in the presence or absence of obvious c-myc activation. These results suggest a hierarchy of mutational events in the genesis of feline T-cell lymphomas by FeLV and implicate insertion at fit-1 as a late progression step. The strongest links observed were with T-cell development, as monitored by rearrangement status of the TCR beta-chain gene, which was positively associated with activation of myc (P < 0.001), and with proviral insertion at flvi-2 (P = 0.02). This analysis also revealed a genetically distinct subset of thymic lymphomas with unrearranged TCR beta-chain genes in which the known target loci were involved very infrequently. The presence of env recombinant FeLV (FeLV-B) showed a negative correlation with proviral insertion at fit-1, possibly due to the rapid onset of these tumors. These results shed further light on the multistep process of FeLV leukemogenesis and the relationships between lymphoid cell maturation and susceptibility to FeLV transformation.

Animals↗