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Biomedical subjects

B Rosen

Publications and source records attributed to B Rosen.

At least 73 records · Page 4Linked to original sources

Alkaline phosphatase activity in Penicillium roqueforti and in blue-veined cheeses.

The Penicillium roqueforti mold exhibits alkaline phosphatase activity. Therefore, blue mold-ripened cheeses made from properly pasteurized milk test positive for phosphatase. Because microbial phosphatases are considered to be more resistant to heat than is milk phosphatase, a statutory control test recommends the repasteurization of cheese at 66 degrees C for 30 min to inactivate selectively the native milk enzyme. However, because of thermal lability of Penicillium roqueforti phosphatase, this control test leads to confusion of the fungal enzyme with native milk alkaline phosphatase and does not confirm whether the milk used to make cheese has been pasteurized.

Alkaline Phosphatase↗

The bacterial colicin active against tumor cells in vitro and in vivo is verotoxin 1.

We have identified verotoxin 1 (VT1) as the active component within an antineoplastic bacteriocin preparation from Escherichia coli HSC10 studied over two decades. Recombinant VT1 can simulate the toxicity of anticancer proteins (ACP), and the antineoplastic activity of ACP (and VT1) was abrogated by treatment with anti-VT1 antibody. Similarly, VT1 mimics the protective effect of ACP in a murine metastatic fibrosarcoma model. Prior immunization with VT1 B subunit prevents the effect of VT1 or ACP in this model. The activity of ACP against a variety of human ovarian cell lines was mimicked by VT1, and multidrug-resistant variants were significantly hypersensitive. Primary ovarian tumors and metastases contain elevated levels of globotriaosylceramide compared with normal ovaries, and overlay of frozen tumor sections showed selective VT binding to tumor tissue and the lumen of invading blood vessels. Our contention that VT1 could provide an additional approach to the management of certain human neoplasms is discussed.

Animals↗

Does aggressive therapy improve survival in suboptimal stage IIIc/IV ovarian cancer? A Canadian-American comparative study.

In an effort to determine if differences exist in the treatment and outcome of patients with suboptimally debulked stage IIIc and IV epithelial ovarian cancer between two tertiary-care cancer centers in Canada and the United States, we conducted a comparative study. The records of all patients who underwent treatment for epithelial ovarian cancer at two tertiary-care cancer centers in Canada and the United States between 1987 and 1989 were abstracted onto a common datasheet which was then entered into a computerized database for analysis. Only patients with suboptimally debulked stage IIIc disease (residual tumor diameter > 1 cm) or stage IV were included in the comparative study. There was a total of 129 evaluable patients (61 Canadian, 68 American). There were no statistically significant differences between the centers in mean age, performance status, histology, grade, or stage distribution. During the period of this study there was no statistically significant difference between the two institutions in the proportion of patients in whom optimal debulking was achieved (Canadian 19%, American 26%). The American patients were heavier than the Canadian patients (Quetelet index 27.3 vs 23.8, P < 0.006). Primary chemotherapy included a platin-containing regimen in 98 and 93% of Canadian and American patients, respectively. The average number of laparotomies each patient received during her course of illness was 1.7 and 2.5 at the Canadian and the American centers, respectively (P < 0.0001). Similarly, the American patients received a higher mean number of different chemotherapy regimens and total number of courses of chemotherapy during the course of their disease (3.0 and 12.6) than did the Canadian patients (2.4 and 8.8) (P < 0.01 and P < 0.001, respectively). The median survival was 21 months and 20 months in the Canadian and the American patients, respectively (no significant difference), and the 5-year survival was 10% for the Canadian and 11% for the American patients. Despite significant differences in the overall aggressiveness of treatment between the two centers, there was no difference in the survival of these patients. Until effective salvage agents or treatment strategies are realized, "more is not necessarily better."

Actuarial Analysis↗

Meta-analysis comparing cisplatin total dose intensity and survival.

OBJECTIVE: To determine the relationship between total dose intensity (TDI) of cisplatin/carboplatin, total dose intensity of all chemotherapy drugs (GDI) and median survival (MS) in stage III-IV ovarian cancer patients. METHODS: Over 700 studies from the English literature were reviewed. Prospective clinical trials that had at least one arm treating patients with cisplatin/carboplatin and provided data on both MS and dose and schedule of chemotherapy were included. Dose intensity (DI), TDI, and GDI were calculated for each study arm. To explore possible relationships, several linear regression models were fitted with MS as the dependent variable and DI, TDI, GDI, and other known prognostic factors as the independent variables. RESULTS: Sixty-one study arms were analyzed including 4118 patients. No significant correlation was found between DI and TDI of cisplatin and MS (P = 0.90 and P = 0.11 respectively). Of the 10 variables tested, proportion of patients optimally debulked (%OD), proportion of mucinous tumor, and GDI were found to have a significant correlation to MS. All studies with a GDI less than 20 and %OD < 20 had a MS less than 20 months. On the other hand 77% of studies have a MS greater than 20 months when GDI is > 20 and %OD > 20%. We found single-agent chemotherapy had the worst outcome and there was very little difference between two or more drugs for percentage of studies with > 20 months MS, (56.5% vs 63.3% respectively). CONCLUSIONS: From this meta-analysis we believe that both GDI and %OD are important factors that determine outcome in terms of median survival.

Antineoplastic Agents↗

Linkage analysis of 26 Canadian breast and breast-ovarian cancer families.

We have examined 26 Canadian families with hereditary breast or ovarian cancer for linkage to markers flanking the BRCA1 gene on chromosome 17q12-q21. Of the 15 families that contain cases of ovarian cancer, 94% were estimated to be linked to BRCA1. In contrast, there was no overall evidence of linkage in the group of 10 families with breast cancer without ovarian cancer. A genetic recombinant in a breast-ovarian cancer family indicates a placement of BRCA1 telomeric to D17S776, and helps to define the region of assignment of the cancer susceptibility gene. Other cancers of interest that appeared in the BRCA1-linked families included primary peritoneal cancer, cancer of the fallopian tube, and malignant melanoma.

Adult↗

Insulin response of women athletes in relation to body fat quantified by magnetic resonance imaging.

We report the glucose and insulin response to a 300-min glucose tolerance test among 17 women athletes as compared with 11 normal, nonatheletic controls. Also reported is the relationship of the insulin area under the curve as a function of percentages of total fat (TF), subcutaneous fat, and internal fat of total volume (TV) quantified by magnetic resonance imaging overall and at six regional sites. Athletes had a more sensitive insulin response to the glucose tolerance test as compared with controls. The insulin area under the curve of athletes and controls was significantly (p = 0.05) related to their overall TF/TV%; athletes had significantly less TF/TV% compared with the controls.

Adipose Tissue↗

Medication treatment in first-admission patients with psychotic affective disorders: preliminary findings on research-facility diagnostic agreement and rehospitalization.

The discharge medications of 101 Suffolk County subjects with facility and/or research diagnoses of affective disorder were ascertained. Rehospitalization was recorded for a 6-month follow-up period. Twenty-three of 31 patients (74.2%) with a facility diagnosis of depressive disorder were prescribed antidepressants, and 21 of 36 patients with a facility diagnosis of bipolar disorder (58.3%) were prescribed lithium. When research and facility diagnoses concurred, 84.2% of depressed patients were prescribed antidepressants, and 66.7% of bipolars were given lithium. The percentages were lower when the two diagnoses were discrepant. The results for diagnostic congruence were independent of demographic variables, length of stay, and premorbid functioning. Patients prescribed diagnosis-specific medications had a lower rate of rehospitalization (7.3%) than those not prescribed such medications (22.2%). The findings suggest that such medications are prescribed in the more unambiguous cases of affective disorders and are important (with or without antipsychotic treatment) in preventing rehospitalization.

Adolescent↗

Hereditary and familial ovarian cancer in southern Ontario.

BACKGROUND: Hereditary ovarian cancer may be site specific or may appear in combination with breast cancer or other cancers in a family. The most common hereditary form is the breast-ovarian cancer syndrome. It is estimated that in 100% of these families, there is linkage to a cancer susceptibility gene on chromosome 17q, BRCA1. METHODS: A positive family history of breast or ovarian cancer was reported for 71 of 450 unselected cases of ovarian cancer identified in Southern Ontario. Detailed pedigrees were completed by telephone interview for 48 of the 71 subjects. RESULTS: Nine families were identified with five or more cases of breast or ovarian cancer, 14 families with four cases of cancer, and eight families with three cases. Breast cancer appeared in 80% of the ovarian cancer families. There were 81 healthy first-degree female relatives of the cancer cases considered to be at high risk for ovarian cancer. CONCLUSIONS: It is feasible to use a simple questionnaire on all incident cases of ovarian cancer in a population to identify families with potential hereditary breast-ovarian cancer. Two point nine percent to 6.9% of cases of ovarian cancer appear to be inherited; the majority of the families also will have an excess number of cases of breast cancer.

Adult↗

High-dose methotrexate for gestational trophoblastic disease.

Eighty patients with low-risk and 5 patients with intermediate-risk gestational trophoblastic neoplasia (GTN) (WHO classification) were treated with single-agent high-dose methotrexate with folinic acid rescue (MTX/FAR). By the NCI classification, 65 patients had nonmetastatic GTN, 13 patients had low-risk metastatic GTN, and 7 patients had high-risk metastatic GTN. Seventy-one (84%) patients achieved remission (beta HCG < or = 5 IU/liter) with MTX/FAR, whereas 14 (16%) failed to achieve remission with MTX/FAR alone. All failures were salvaged with second-line therapies. Patients successfully treated with MTX/FAR required a median of 4 courses to achieve remission, and a median of 2 consolidative courses. Factors found predictive of failure with MTX/FAR were pretreatment beta HCG (P = 0.003), prior history of GTN (P < 0.04), and time from termination of antecedent pregnancy to initiation of treatment (P < 0.05). No significant difference was noted between the "success" and "failure" groups with respect to MTX dose or infusion time, the timing and dosage of folinic acid rescue, the number of courses of MTX, or the mean interval between courses. Multivariate analysis revealed that the pretreatment beta HCG (P < 0.01) and short time from termination of antecedent pregnancy to initiation of treatment (P < 0.03) were independently significant for failure. No significant (grade 3/4) hematologic or gastrointestinal toxicity occurred, and no treatment delays or dose reductions were required. This regimen is both effective and well tolerated; however, the theoretical advantages of high-dose methotrexate do not appear to offer any clinical advantage over conventional dose MTX in low- and intermediate-risk GTN.

Biomarkers, Tumor↗

Sensory disturbances after two-portal endoscopic carpal tunnel release: a preliminary report.

Very few complications following endoscopic carpal tunnel release have been reported. We studied the incidence and pattern of sensory disturbances in 53 consecutive cases in which the Chow two-portal technique was used. Persistent sensory disturbances for 4 months or more were noted in six hands. Sensory tests were normal or near normal in all except one case. The disturbance was described by the patients as an uncomfortable tingling sensation or hyperesthesia, and in all cases the ring finger, especially the radial half, was involved. We wish to direct attention to this potential complication and suggest possible mechanisms behind it.

Adult↗

Contrast induced myocardial signal reduction: effect of lanthanide chelates on ultra high speed MR images.

The myocardial MR signal reduction associated with an intravenous bolus of Gd-DTPA and Dy-DTPA was studied in a canine model. Imaging was performed with a high speed echo-planar type imaging system (Instascan, Advanced NMR Systems, Inc.). Gated spin-echo images were obtained with TE of 30 ms, which permits image acquisition in approximately 40 ms. The gated TR was dependent on the heart rate, with an average TR of 2.4 s. After 0.1 mmol/kg of contrast was injected, 70 images were acquired, which showed in an 80-image data set a reduction in myocardial signal with a gradual return to normal. After dipyridamole infusion, the signal loss was significantly more pronounced, and earlier than in the control data set. There was no significant difference between Gd-DTPA and Dy-DTPA in these imaging studies despite the theoretical prediction of better Dy signal reduction, possibly due to physiological variability during the course of a study or between studies. The cause of enhanced contrast effect after dipyridamole infusion is discussed, as is the basis for dipyridamole enhancement, and the possible role of contrast enhanced MR imaging in the detection of cardiac disease.

Animals↗

Alterations in gene expression during mesoderm formation and axial patterning in Brachyury (T) embryos.

The mouse T (Brachyury) deletion causes defective mesoderm formation and notochord morphogenesis, and abnormalities in the caudal neural tube and somites. To investigate the effect of the wild type T gene on concurrently expressed genes, we have compared expression of a panel of such genes in homozygous T mutants with that in wild type and heterozygous T/+ control embryos. Two classes of genes were used in this study: those implicated in primitive streak or mesoderm formation, and those which are differentially expressed in regions of the neural tube and somites. Results of wholemount in situ analysis show that the mRNA levels of Evx-1, Wnt-3a and Wnt-5a decrease in T/T embryos late in gastrulation, although earlier expression patterns are similar to control embryos. In contrast, BMP-4 and Msx-1 expression patterns remain similar throughout the period studied. Pax-3 and Pax-6, which are expressed in specific dorsoventral domains of the neural tube, both have ventrally extended expression domains in caudal T/T neural tube. This is consistent with a missing ventral signal provided by the notochord. However, the expression of Msx-1 in the most dorsal domain of the neural tube is unaltered in T/T embryos. Pax-1 and Pax-3, which are expressed in the sclerotome and dermamyotome respectively, are expressed correctly in anterior T/T somites, although the Pax-3 expression domain is widened ventromedially. This extension into ventromedial somite domains is more pronounced caudally, supporting a function for the notochord in ventralizing somites.

Abnormalities, Multiple↗

[Visits to emergency rooms and hospital ownership categories].

Trends in emergency room (ER) visits in Israeli general hospitals were analyzed and differences were found according to category of hospital ownership, Data for 1986-90 were gathered from 23 hospitals which included 90% of the country's acute care beds. An upward trend in ER visits in the 1970's and early 1980's ended in 1987. Despite a 7% increase in population during 1987-90, total ER visits decreased by 4%. In Jerusalem's public hospitals ER visits decreased by 13%, in government and government-municipal hospitals by 7%, while in Kupat Holim Clalit hospitals there was a 2% increase. The proportion of ER visits resulting in hospital admissions also varied by hospital ownership and also among individual hospitals within any given ownership category. Factors which might influence ER visits include size and composition of populations, development of alternative sources of care in the communities, price of services, changes in hospital admission policies, nature of the competition between hospitals, supply of physicians, and the use of ER's for primary care.

Emergency Service, Hospital↗

Differences in the morbidity of radical hysterectomy between gynecological oncologists.

A multivariate analysis was performed on 405 patients who underwent radical hysterectomy and pelvic lymphadenectomy by eight surgeons for stage IB cervical carcinoma, to determine the influence of primary surgeon on morbidity. Patient characteristics analyzed (mean/proportion) were age (41 years), quetelet index (25.4), American Society of Anesthesiologists classification of physical status (0.5% > 2), previous laparotomies (23%), previous radiation (0.7%), prophylactic antibiotics (95%), prophylactic heparin (67%), tumor size (1.0 cm), histology (68% SCC), grade (68% grades 2 or 3), vascular space involvement (45%), pelvic lymph node metastases (6%), and depth of invasion (6.6 mm). Morbidity characteristics analyzed (mean/proportion) were blood loss (910 ml), operative time (3.0 hr), intra-op complications (5%), post-op infectious (21%) and non-infectious complications (7%), transfusions (35%), post-op hospital stay (9.9 days), time to normal urine residual (9.0 days), and bladder dysfunction at 3 months post-op (21%). Mean tumor size was the only preoperative characteristic that was significantly different among surgeons (P < 0.001). Of the factors evaluated for morbidity, mean blood loss (P < 0.0001), operative time (P < 0.001), and postoperative hospital stay (P < 0.001) varied among physicians as did the incidence of blood transfusion (P < 0.0001) and bladder dysfunction at 3 months postoperatively (P < 0.0001). On multivariate analysis, surgeon was independently significant for blood loss (P < 0.0001), operative time (P < 0.0001), postoperative hospital stay (P < 0.001), incidence of blood transfusion (P < 0.0001), and bladder dysfunction at 3 months postoperatively (P < 0.0001). Despite differences in tumor size, patients appeared similar among the surgeons. Differences in patient morbidity among surgeons do exist and are of significant magnitude. Since the design of surgical trials to assess the therapeutic ratio should include not only measures of efficacy, but also measures of morbidity to be meaningful, intersurgical morbidity between centers/surgeons must continue to be quantified.

Adult↗

On-line measurement of microvascular diameter and red blood cell velocity by a line-scan CCD image sensor.

A line-scan charge-coupled device (CCD) image sensor (256 photo sites) was equipped for on-line measurement and calculation of red blood cell velocity and microvascular diameter. The principle of measurement is based on a sequential readout of the CCD-sensor photo signal at predefined time intervals. The velocity is calculated by a computer by cross correlation of a given set of readouts. Rotation of the sensor into a position perpendicular to the microvessel axis allows measurement of the diameter, which is related to the red blood cell column moving under the sensor. At low magnification (up to 38-fold) diameters up to 80 microns can be measured. Calibration, which was performed by comparing diameters measured in vivo by the CCD-based system with microphotographically obtained measurements, revealed a mean CCD/photo ratio of 0.98 +/- 0.08. Calibration of velocity measurements in glass tubes of different diameters by a calibrated pump with known bulk flow resulted in a mean conversion factor of 1.59 +/- 0.2 (mean +/- SD). The CCD sensor is mounted such that it can freely rotate on the microscope. In conjunction with a programmable scanning table, several vessels can be measured sequentially in one preparation. The interval between two combined measurements and calculations of velocity and diameter is 1.1 sec.

Animals↗