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Biomedical subjects

A Glicksman

Publications and source records attributed to A Glicksman.

At least 19 recordsLinked to original sources

Caregiver and elder experiences of Cambodian, Vietnamese, Soviet Jewish, and Ukrainian refugees.

Our purpose was to describe and compare Cambodian, Vietnamese, Soviet Jewish, and Ukrainian refugee caregivers and elders on life experiences, health status, and knowledge of available services. Detailed interviews were conducted with 105 female caregivers and 52 elders. Similar patterns emerged across all groups with regard to filial obligation, minimal knowledge of services, impact of immigration, and retention of cultural ties. Findings confirmed the special health and social service needs of refugee families in transition.

Aged↗

Fragile X premutation is a significant risk factor for premature ovarian failure: the International Collaborative POF in Fragile X study--preliminary data.

The preliminary results of an international collaborative study examining premature menopause in fragile X carriers are presented. A total of 760 women from fragile X families was surveyed about their fragile X carrier status and their menstrual and reproductive histories. Among the subjects, 395 carried a premutation, 128 carried a full mutation, and 237 were noncarriers. Sixty-three (16%) of the premutation carriers had experienced menopause prior to the age of 40 compared with none of the full mutation carriers and one (0.4%) of the controls. Based on these preliminary data, there is a significant association between fragile X premutation carrier status and premature menopause.

Adolescent↗

Accelerated prenatal diagnosis of fragile X syndrome by polymerase chain reaction restriction fragment detection.

Prenatal diagnosis of fragile X syndrome requires detection of the full FMR1 mutation in chorionic villus or amniotic fluid cell samples. Although analysis of genomic DNA restriction fragment pattern is a highly reliable technique for identification of the full FMR1 mutation, standard Southern blot determination of this pattern requires significantly more genomic DNA than is initially available from a prenatal sample. To overcome this limitation we developed a method that determines the diagnostic pattern of genomic restriction fragments from a fraction of a prenatal specimen. The prenatal DNA sample is first digested with EcoRI and EagI, and after agarose gel electrophoresis, the 2- to 10-kb region of the gel is serially sectioned and amplified by polymerase chain reaction. Analysis of prenatal samples from an unaffected male and from a full mutation male showed that this approach generated a diagnostic pattern comparable with a Southern blot of 100-fold more material. This innovation enables laboratories to prenatally diagnose the full FMR1 mutation sooner than standard techniques.

Blotting, Southern↗

A multidisciplinary study investigating radiotherapy in Ewing's sarcoma: end results of POG #8346. Pediatric Oncology Group.

PURPOSE: To determine if involved field radiation (IF) is equivalent to standard whole bone radiation (SF) in local tumor control; to establish patterns of failure following treatment; and to determine response, event-free survival (EFS), and overall survival rates from multidisciplinary therapy in Ewing's sarcoma. METHODS AND MATERIALS: Between 1983 and 1988, 184 children with Ewing's sarcoma were enrolled onto Pediatric Oncology Group 8346 (POG 8346). A total of 178 (97%) met eligibility criteria; 6 had pathology other than Ewing's sarcoma. Induction chemotherapy of cyclophosphamide/doxorubicin (adriamycin )(C/A) x 12 weeks was followed by local treatment either surgery or radiation therapy and C/A, dactinomycin, and vincristine for 50 weeks. Resection was advised for patients with small primary tumors if accomplished without functional loss. Forty patients were randomized to receive SF, whole bone radiation to 39.6 Gy plus a 16.2 Gy boost (total 55.8 Gy) or IF to 55.8 Gy, and the remainder were assigned to IF radiation. RESULTS: Of 178 eligible patients, 141 (79%) had localized disease and 37 (21%) had metastases at presentation. Their 5-year EFS was 51% (SE 5%) and 23% (SE 7%) respectively. The response rate to induction chemotherapy was 88% (28% complete, 60% partial), but after radiotherapy the response rate increased to 98%. Thirty-seven of the localized patients underwent resection, of whom 16 (43%) required postoperative radiotherapy; the 5-year EFS of these surgical patients was 80% (SE 7%). The remaining 104 localized patients were eligible for randomization or assignment to receive radiotherapy; the 5-year EFS of these patients was 41% (SE 5%), with no significant difference in EFS between those randomized to SF vs. IF. Site of primary tumor correlated with 5-year EFS: distal extremity 65% (SE 8%), central 63% (SE 10%), proximal extremity 46% (SE 8%), and pelvic-sacral 24% (SE 10%) (p=0.004). Initial tumor size did not correlate significantly with EFS. Patterns of failure among the 141 localized patients revealed 23% of patients experienced a local failure, while 40% had a systemic failure. The 5-year local control rate for the surgical patients +/- postoperative radiotherapy was 88% (SE 6%), while for the patients undergoing radiotherapy alone it was 65% (SE 7%). There was no difference in local control between those randomized to SF vs. IF. The 5-year local control rate for the patients with pelvic-sacral tumors was 44% (SE 15%), significantly worse than the local control rates for those with central tumors 82% (SE 8%), distal extremity 80% (SE 8%), or proximal extremity 69% (SE 9%) (p=0.023). However, quality of radiotherapy correlated with outcome. Patients who had appropriate radiotherapy had a 5-year local control of 80% (SE 7%), while those with minor deviations had 5-year local control of 48% (SE 14%), and those with major deviations had a local control of only 16% (SE 15%) (p=0.005). The local failure was within an irradiated volume in 62% of patients, outside the irradiated volume in 24% of cases, while the precise location could not be determined in the remaining 14%. CONCLUSIONS: As most failures in Ewing's sarcoma are systemic, improved EFS requires more effective systemic chemotherapy. Adequate IF radiotherapy requires treatment to appropriate volumes as defined by MRI imaging and full radiation doses. Pretreatment review of radiologic images with a musculoskeletal radiologist to determine appropriate tumor volumes, as well as use of conformal radiotherapy techniques are important for improved outcome.

Adolescent↗

Augmented therapy of extensive Hodgkin's disease: radiation to known disease or prolongation of induction chemotherapy did not improve survival--results of a Cancer and Leukemia Group B study.

PURPOSE: This prospective randomized trial in extensive untreated Hodgkin's disease was undertaken to assess the potential benefit of augmented therapy (12 months chemotherapy or radiation to known disease) compared to standard 6 months chemotherapy. PATIENT AND METHODS: A total of 258 patients, mostly Stage IV, were randomized to four treatment regimens consisting of six cycles of CCNU, vinblastine, procarbazine, and prednisone (CVPP); 12 cycles of CVPP; six cycles of CVPP followed by 25 Gy radiotherapy; or three cycles CVPP, 25 Gy radiotherapy, and three cycles CVPP. RESULTS: Complete remissions were achieved in 65% of all patients. A 58% overall 5-year survival rate was obtained. Relapses in irradiated areas of known disease occurred in only 6% of responding patients. There was, however, no statistical difference in response frequency, disease-free survival, or overall survival among the four regimens. Elderly patients responded less frequently. CONCLUSION: While radiotherapy provided control of local (known) disease, no impact on overall survival was apparent. Likewise, doubling the duration of chemotherapy did not improve response or survival. Augmentation of therapy with either radiotherapy or more chemotherapy in this study was of no benefit compared to the standard 6 months of treatment.

Adult↗

Recurrence patterns with concurrent platinum-based chemotherapy and accelerated hyperfractionated radiotherapy in stage III and IV head and neck cancer patients.

BACKGROUND: Stage III and IV squamous cell cancers of the head and neck are often unresectable at presentation and are associated with poor disease-free and overall survival rates. A phase II study using concurrent cisplatin and radiotherapy in advanced head and neck cancer indicated impressive local-regional control and survival with organ preservation. METHODS: A multicentered phase II study was undertaken consisting of 1.8 Gy fraction radiotherapy for 2 weeks followed by 1.2 Gy BID hyperfractionation to 46.8 Gy. Continuous infusion cisplatin 20 mg/m2 was given on days 1 through 4 and 22 through 25. Biopsy of the primary tumor was done at this point, and patients with clinical and pathologic complete response continued with hyperfractionated radiotherapy to 75.6 Gy plus simultaneous carboplatin 25 mg/m2 BID for 12 consecutive days. Residual disease at 46.8 Gy required curative surgery. RESULTS: Seventy-four patients entered the study, and 73 completed their treatment. Twenty were stage III and 54 were stage IV. Fifty patients had involved regional lymph nodes. Treatment was well tolerated with only one grade IV hematologic toxicity. At 46.8 Gy, biopsy revealed a complete response in 75% of the primary sites and 47% of the nodes. Only 12 patients required resection of the primary lesion. At 4 years (median follow-up is 26 months), 29 patients have recurred. CONCLUSIONS: Accelerated hyperfractionated radiotherapy with concurrent chemotherapy in stage III and IV head and neck cancer yields excellent local-regional control with organ preservation. This protocol is intensive, and some patients have distant failures.

Antineoplastic Agents↗

1457 years of microsurgical experience.

Microsurgery is a relatively new field of surgery involving various methods and practices that are currently evolving. Our goal was to register the current practices employed by the members of the American Society for Reconstructive Microsurgery. A survey was mailed to the 319 members of the society, resulting in a response rate of 33 percent (106 of 319). The data reflect the combined experience of 10,839 free-tissue transfers and 3487 digital and upper and lower extremity replants over a 4-year period between 1990 and 1994. Practices employed, such as pharmacologic adjuvant therapy, monitoring techniques, flap types, and success rates reported by the members of the American Society for Reconstructive Microsurgery, were analyzed.

Anticoagulants↗

Reverse mutations in the fragile X syndrome.

Three females were identified who have apparent reversal of fragile X premutations. Based on haplotype analysis of nearby markers, they were found to have inherited a fragile X chromosome from their premutation carrier mothers, and yet had normal size FMR1 repeat alleles. The changes in repeat sizes from mother to daughter was 95 to 35 in the first, 145 to 43 in the second, and 82 to 33 in the third. In the first family, mutations of the nearby microsatellites FRAXAC2 and DXS548 were also observed. In the other two, only mutations involving the FMR1 repeats were found. We suggest differing mutational mechanisms such as gene conversion versus DNA replication slippage may underlie such reversions. We estimate that such revertants may occur among 1% or less of premutation carrier offspring. Our results indicate that women identified to be carriers by linkage should be retested by direct DNA analysis.

DNA Replication↗

Prenatal diagnosis and carrier screening for fragile X by PCR.

During the past three years, we have conducted fragile X DNA studies for carrier screening and prenatal diagnosis using a previously described PCR protocol that accurately resolves normal FMR1 alleles and premutations and detects most full mutations [Brown et al., JAMA 270:1569-1575, 1996]. A total of 344 pregnant women with a family history of mental retardation of unknown cause were screened and 6 fragile X carriers were identified: two had full mutations, and four had premutations. The mentally retarded relatives of two other women were found to be fragile X positive although the women themselves were not carriers. In all, 6 carriers and 8 fragile X families were identified by this screening. We have also screened 40 pregnant women who were members of previously identified fragile X families, but whose carrier status was unknown. Ten were found to be carriers and were offered prenatal diagnosis. Prospective prenatal testing of 84 carrier women correctly detected 31 fetal samples (19 females, 12 males) with full mutations and 6 with premutations (2 females, 4 males). No false positives but one false negative occurred early on due to undetected maternal cell contamination. In addition, screening of 806 males with developmental delays of unknown cause gave positive results in 33 (4.1%). Potential problems and pitfalls of direct DNA testing are discussed. Because of the proven success of fragile X screening with direct molecular analysis, screening of all undiagnosed individuals with mental retardation and at risk pregnant women should now be considered. The identification of fragile X carriers and prenatal diagnosis of their pregnancies should significantly reduce the prevalence of this syndrome.

Amniocentesis↗

An alternative explanation for the apparent elevated relative mortality and morbidity risks associated with exposure to environmental tobacco smoke.

Insofar as industrial and other blue collar workers are more likely to bring home toxic materials on their person, and also are more likely to smoke than those in other occupations, members of a household are more likely to be subject to paraoccupational exposure and belong to lower socioeconomic strata if the household contains a smoker than if the household does not contain a smoker. Thus observed differences in risk of mortality or morbidity ascribed to ETS on the basis of a comparison of households with and without smokers may be partly or entirely due to differences in paraoccupational exposure and socioeconomic strata. Similarly, differences in mortality and morbidity ascribed to paraoccupational exposure may be partly or entirely due to differences in ETS exposure that are also related to social class and to types of occupation. Unfortunately, there are no data now in existence that could help determine separately the effects of these major confounded variables. There exists, then, a situation in which two explanations are advanced for respiratory diseases among members of a household, each based on similar study populations but focused on different major risk variables: ETS on the one hand, socioeconomic status and paraoccupational exposure on the other. Properly focused investigations need to be initiated.

Confounding Factors, Epidemiologic↗

Mosaicism in fragile X affected males.

Fragile X affected males have an expansion of a CGG repeat and a hypermethylated CpG island 5' to the FMR-1 gene. Mosaic males with both a premutation and full mutation have been noted among the affected individuals. Such mosaic males are most easily identified by the presence of a methylated restriction fragment characteristic of the full mutation and an additional unmethylated fragment in the premutation range in Southern analyses with EcoR I and the methylation-sensitive enzyme Eag I and a probe such as StB12.3. We analyzed a group of affected fragile X males by Southern blotting and found 41% (61/148) to be mosaic. The 148 individuals were divided between 36 pairs of brothers and 76 unrelated males. Little difference in the number of mosaics was seen between the brothers and the unrelated males nor was the expected distribution of mosaicism in brother pairs different from observed. Thus, these data do not suggest a familial basis for mosaicism. Our observation that 41% affected fragile X males were mosaic is significantly higher than previous reports. The difference is likely due to technical modifications which permitted the identification of faint premutation bands in some patients. The high percentage of affected males with mosaicism seen here suggests that the occurrence of such individuals may be a much more frequent event than presently recognized.

Blotting, Southern↗

Exploring the validity of the Affect Balance Scale with a sample of family caregivers.

Open-ended responses of caregiving daughters and daughters-in-law were generated by a modified random probe technique to investigate the construct validity of the two subscales of the Affect Balance Scale (ABS), i.e., the 5-item Positive Affect Scale (PAS) and the 5-item Negative Affect Scale (NAS). A set of criteria were developed to distinguish between responses that did and did not correspond to Bradburn's assumptions concerning affect. While most responses met at least one of the criteria, very few met all. In exploring the nature of affect, we found that positive affect was based to a large extent on personal accomplishments and the recognition of others. The assessment of negative affect was a more interior, or self-focused process. For a significant subset of the sample, a negative response to a closed-ended PAS or NAS item implied disagreement or discontent with the wording or the implications of the item itself, rather than an absence of affect. Not all of the ABS items were equally valid measures of affect.

Affect↗

Prognostic features of Ewing sarcoma on plain radiograph and computed tomography scan after initial treatment. A Pediatric Oncology Group study (8346)

BACKGROUND: The authors studied the short-term changes in the plain radiographic and computed tomography (CT) appearance of Ewing sarcoma for indicators of decreased survival or future disease progression. METHODS: The authors evaluated CT scans and plain radiographs of the primary tumor site from 105 patients with Ewing sarcoma at diagnosis (prebiopsy), after induction chemotherapy (13 weeks), and after radiation therapy (20 weeks). RESULTS: Data suggest an association between postinduction CT findings of medullary involvement, cortical destruction, lysis, permeation, and unhealed pathologic fracture and decreased survival. On the postradiation scans, only medullary involvement was associated with worsened survival. No plain radiographic features were significant at any time. Absolute greatest tumor dimension was not significantly related to survival or tumor progression. The Cox model suggested that fractional change in greatest tumor dimension on CT at the time points studied relative to the prebiopsy CT was correlated to survival. Log-rank testing did not corroborate this finding. All significant associations appeared to result from adverse outcomes in small subgroups. CONCLUSIONS: Our data suggest that CT obtained immediately after induction chemotherapy and radiation may have some limited use in predicting the long-term prognosis of patients with Ewing sarcoma.

Actuarial Analysis↗

Epidemiology of burns in the Tel Aviv area.

Between 1 August 1988 and 31 January 1992, 421 burn patients were admitted to the Burn Unit at Beilinson Medical Center. Name, age, sex, month of the year, cause of burn, area and degree of burn and duration of stay in hospital were recorded. Of these patients, 37 per cent were treated surgically and the remainder were treated conservatively. The male to female ratio was 2:1. Burns occurred most frequently in July and January; the peak average age was the first decade of life. The most frequent cause in children was scalding (domestic burns), and in adults open fires (work accidents). Patients treated by early tangential excision and skin grafting (204 operations on 157 patients) had a shorter stay in hospital than conservatively treated patients. In accordance with others, we suggest that early surgery of burn injuries decreases morbidity and mortality and leads to better aesthetic results and improved motor function. Secondly, burn injury can be prevented in children and the elderly by increasing safety measures at home, and in adults by enforcing strict safety measures at work.

Adolescent↗

Cisplatin, vincristine, and fluorouracil therapy for hepatoblastoma: a Pediatric Oncology Group study.

PURPOSE: To estimate the disease-free survival rate in children with grossly resected hepatoblastoma treated with cisplatin, vincristine, and fluorouracil (CDDP/VCR/FU) and to assess the disease-response rate and disease-free survival (DFS) rate in children with unresectable or metastatic tumors treated with this combination. PATIENTS AND METHODS: Sixty assessable patients with hepatoblastoma received therapy with five (stage I and II) to seven (stage III and IV) courses of CDDP (90 mg/m2), day 1, and VCR (1.5 mg/m2), and FU (600 mg/m2), day 3. RESULTS: Nineteen of 21 patients with stage I or II disease survive free of disease (actuarial survival, 90% at 5 years). Twenty-four of 31 patients with stage III disease achieved a complete remission (CR) after chemotherapy and surgical excision; actuarial DFS at 4 years is 67%. Only one of eight patients with stage IV disease achieved a remission and survives. CONCLUSION: Relatively brief exposure to chemotherapy with CDDP/VCR/FU provided excellent disease control to patients with grossly resected tumors. In patients with initially unresectable disease, this therapy provides a response rate and DFS rate comparable to regimens that contain doxorubicin (DOX).

Actuarial Analysis↗

Cefuroxime prophylaxis in biliary surgery: single versus triple dose.

The standard regimen for prophylaxis in bilary surgery consists of three doses of a first- or second-generation cephalosporin (one pre- and two postoperatively). The purpose of our study was to compare a single dose of cefuroxime (1.5 gi.v. on call to surgery) with the standard regimen (1.5 gi.v. on call to surgery followed by two additional doses of 750 mg i.v. each, 8 and 16 h after surgery). One hundred patients participated in the study, 44 in the single-dose group and 56 in the triple-dose group. These two groups did not differ with regard to sex, risk factors, duration of surgery, etc. The incidence of infection was 9% in the single-dose group and 7% in the triple-dose group. We conclude that one dose of cefuroxime is as effective as three for biliary surgery. This regimen would reduce the risk of side effects and/or suprainfections and the emergence of resistant strains of bacteria. It is also more convenient for the nursing staff and reduces the cost by one-half.

Cefuroxime↗

Chemotherapy can convert unresectable hepatoblastoma.

The surgical evaluation and management of children with hepatoblastoma has changed with recent advances in imaging modalities and preoperative chemotherapy. Pediatric Oncology Group (POG) Study no. 8697 has followed 63 patients with hepatoblastoma from 1986 to 1991. Twenty-six patients underwent primary tumor resection followed by chemotherapy consisting of cisplatin, vincristine, and 5-fluorouracil (group I). Thirty-seven patients with "unresectable" tumors received preoperative chemotherapy. Twenty-nine of these patients responded to chemotherapy and 26 underwent delayed surgical resection (group II). Eight patients had an inadequate response to chemotherapy; two have had successful liver transplantation and six are dead of disease progression. "Unresectable tumor" involved both liver lobes (25 patients), encased the inferior vena cava (2), involved adjacent tissues (1), involved the hepatic veins (2), or was deemed too large for safe resection (7). Two patients had distant metastases. The reason for an unresectable designation was not reported in five patients. The determination for an unresectable designation included exploratory laparotomy in 14 patients, angiogram in 7, computed tomography scan in 20, and magnetic resonance imaging in 3 patients. Operative times and transfusion requirements were similar in both groups. Perioperative complications were higher in patients in group II. There was no mortality and only minor morbidity associated with chemotherapy in each group. In both groups 77% of the patients are in complete remission after 13 to 54 months. Preoperative chemotherapy can allow successful resection of initially "unresectable" hepatoblastoma. Primary resection that may result in exsanguination should be postponed and chemotherapy given.

Antineoplastic Combined Chemotherapy Protocols↗

The role of pain in the last year of life of older persons.

A random sample of 200 decreased older community residents was studied with a focus on the role of pain in the last year of life. Interviews with a surviving close person elicited retrospective reports. Pain increased over the final year; one month before death 66% felt pain frequently or all of the time, substantially higher than a matched comparison group of living persons (24%). For both groups across the year, pain was associated with most measures of behavioral competence, perceived quality of life, and psychological well-being. Hierarchical multiple regressions indicated that background and health variables explained 28% to 32% of the variance of pain over the year. Controlling for background variables and health, pain contributed significantly to lowered happiness and to depression, but had no independent impact on hope and interest in the world. After controlling for physical health, the older old were judged to have less pain than the younger old.

Activities of Daily Living↗