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Biomedical subjects

D Grossman

Publications and source records attributed to D Grossman.

At least 19 recordsLinked to original sources
PubMed2001

Inhibition of melanoma tumor growth in vivo by survivin targeting.

A role of apoptosis (programmed cell death) in tumor formation and growth was investigated by targeting the apoptosis inhibitor survivin in vivo. Expression of a phosphorylation-defective survivin mutant (Thr(34)-->Ala) triggered apoptosis in several human melanoma cell lines and enhanced cell death induced by the chemotherapeutic drug cisplatin in vitro. Conditional expression of survivin Thr(34)-->Ala in YUSAC2 melanoma cells prevented tumor formation upon s.c. injection into CB.17 severe combined immunodeficient-beige mice. When induced in established melanoma tumors, survivin Thr(34)-->Ala inhibited tumor growth by 60-70% and caused increased apoptosis and reduced proliferation of melanoma cells in vivo. Manipulation of the antiapoptotic pathway maintained by survivin may be beneficial for cancer therapy.

Amino Acid Substitution↗
PubMed2000

Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin.

The interface between apoptosis (programmed cell death) and the cell cycle is essential to preserve homeostasis and genomic integrity. Here, we show that survivin, an inhibitor of apoptosis over-expressed in cancer, physically associates with the cyclin-dependent kinase p34(cdc2) on the mitotic apparatus, and is phosphorylated on Thr(34) by p34(cdc2)-cyclin B1, in vitro and in vivo. Loss of phosphorylation on Thr(34) resulted in dissociation of a survivin-caspase-9 complex on the mitotic apparatus, and caspase-9-dependent apoptosis of cells traversing mitosis. These data identify survivin as a mitotic substrate of p34(cdc2)-cyclin B1 and suggest that survivin phosphorylation on Thr(34) may be required to preserve cell viability at cell division. Manipulation of this pathway may facilitate the elimination of cancer cells at mitosis.

Amino Acid Sequence↗
PubMed2000

Ionization and photoelectric smoke alarms in rural Alaskan homes.

OBJECTIVE: To compare rates of nuisance alarms and disconnection between ionization and photoelectric smoke alarms. DESIGN: A prospective cohort study. SETTING: Four Inupiat Eskimo villages in the Northwest Arctic Borough region of Alaska, 48 km (30 mi) above the Arctic Circle. SUBJECTS: Households in 4 communities with similar populations, number of homes, mean income, size of household, and square footage per home. INTERVENTION: Two villages had photoelectric alarms installed (58 homes), and 2 other villages had ionization alarms installed (65 homes) in standard locations. Follow-up household surveys were conducted after 6 months to determine rates of false alarms and detector disconnection. All of the households that could be contacted 104/123 agreed to participate in the follow-up surveys. Main outcome measures The proportion of households experiencing false alarms and the proportion of disabled alarms in households in each of the test communities. RESULTS: Homes with ionization alarms had more than 8 times the rate of false alarms as those with photoelectric alarms. Eleven of the ionization alarms (19%) were disconnected compared with 2 of the photoelectric devices (4%). CONCLUSIONS: In small rural residences, photoelectric smoke alarms have lower rates of false alarms and disconnection. Photoelectric alarms may be the preferred choice for dwellings with limited living space or frequent false alarms.

Alaska↗
PubMed2000

The effect of imaging guidelines on the number and quality of outpatient radiographic examinations.

OBJECTIVE: A significant percentage of outpatient diagnostic radiology is performed by nonradiologists. Studies have shown nonradiologists have higher utilization and cost, as well as quality problems. We sought to determine if, in a managed care environment, a set of guidelines limiting imaging privileges of nonradiologist physicians could decrease imaging costs while ensuring that equipment and personnel providing imaging were of the highest quality. MATERIALS AND METHODS: We determined the number and type of radiographic imaging studies performed the year after these guidelines were set in place (1997) and compared these findings with those of the year before the guidelines were established (1995) and with preguideline trends. We established quality criteria and, based thereon, inspected imaging offices. RESULTS: The number of radiographic examinations per 1000 enrollees decreased 20-25% from the previous trend. Nonradiologists' share of the total fell from 39% to 15%. No deficiencies were found in the inspection of five radiologists' offices, whereas significant deficiencies of equipment, equipment maintenance, or documentation of the examinations performed were found in 78% of nonradiologists' offices. None of the quality indicators monitored by the health plan showed significant change. CONCLUSION: Specific guidelines can effect change in the location and number of radiologic examinations performed, with an improvement in the quality of the studies and a decrease in radiation dose and cost. No decline in quality of care appears to result, despite claims by opponents to such changes that widespread serious quality impairment would occur.

Ambulatory Care↗
PubMed1999

A randomized controlled trial of laminaria, oral misoprostol, and vaginal misoprostol before abortion.

OBJECTIVE: To compare the efficacy and acceptability of oral misoprostol, vaginal misoprostol, and laminaria tents for cervical dilation before surgical abortion. METHODS: We conducted a randomized, double-blind, placebo-controlled trial comparing oral misoprostol 400 microg, vaginal misoprostol 400 microg, and one medium laminaria for dilating the cervix over 4 hours before surgical abortion. The study sample consisted of 106 women at 7-14 weeks' gestation who presented to San Francisco General Hospital requesting abortion. The primary outcome was the amount of cervical dilation measured by Pratt dilators. Secondary outcomes were the proportion of subjects needing further manual dilation, difficulty of dilation, duration of the procedure, blood loss, and side effects. RESULTS: The vaginal-misoprostol group had a significantly greater mean dilation (28.0 mm) than the oral misoprostol group (24.2 mm; P < .05) and a greater mean dilation than the laminaria group (25.9 mm), although this difference did not reach significance. Women who received laminaria reported significantly more pain at the time of placement (85.7% reported at least "a little" pain) compared with women who received misoprostol by either route (28.9% of oral-misoprostol and 34.0% of vaginal-misoprostol subjects reported "a little" pain; P < .01). The proportion of subjects who required further manual dilation, ease of dilation, duration of the procedure, and blood loss were not significantly different among the groups. There was no difference in side effects during the 4-hour waiting period among the three groups, and gastrointestinal side effects were rare in all groups. CONCLUSION: Vaginal misoprostol is superior to oral misoprostol and is an acceptable alternative to laminaria tents for cervical dilation before surgical abortion in pregnancies of 7-14 weeks' gestation. It is inexpensive and easy to administer, and achieves equal or greater dilation with less pain on insertion and no increase in side effects compared with laminaria.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

Expression and targeting of the apoptosis inhibitor, survivin, in human melanoma.

The newly described apoptosis inhibitor survivin is expressed in many human cancers and appears to play a critical part in both apoptosis regulation and cell cycle progression. Its potential role in malignant melanoma is unknown. In a panel of 30 malignant melanomas, survivin was strongly expressed in all cases (15 of 15) of metastatic malignant melanomas and 13 of 15 cases of invasive malignant melanomas by immunohistochemistry. In invasive malignant melanomas, survivin was also expressed in the in-situ component of the lesion. Survivin expression was found in all cases (11 of 11) of nevi, but not in melanocytes in sections of normal skin. The apoptosis inhibitor bcl-2 was expressed in 26 of 30 cases, but generally at lower levels than that of infiltrating lymphocytes. The mitotic index, as assessed by MIB-1 staining, was consistently higher in metastatic than invasive malignant melanomas. Assessment of apoptotic index by in situ end-labeling revealed extremely low rates of apoptosis in most malignant melanomas. Survivin expression by western blotting was detected in four human metastatic malignant melanoma cell lines but not in cultured normal human melanocytes. Transfection of both YUSAC-2 and LOX malignant melanoma cells with green fluorescence protein-conjugated survivin anti-sense or green fluorescence protein-conjugated survivin dominant negative mutant (Cys84Ala) [corrected] resulted in increased apoptosis in the absence of other genotoxic stimuli. Two-color flow cytometry confirmed that YUSAC-2 cells transfected with survivin anti-sense expressed less endogenous survivin and exhibited an increased fraction of cells with sub-G1 DNA content. These data demonstrate that apoptosis inhibition by survivin may participate in the onset and progression of malignant melanomas, and suggest that therapeutic targeting of survivin may be beneficial in patients with recurrent or metastatic disease.

Adult↗
PubMed1999

Expression of the apoptosis inhibitor, survivin, in nonmelanoma skin cancer and gene targeting in a keratinocyte cell line.

The recently described apoptosis inhibitor survivin is expressed in many human cancers, thus potentially contributing to disease progression and resistance to therapy. Its potential role in nonmelanoma skin cancer is unknown. By immunohistochemistry, survivin was expressed in 81% (17 of 21) of basal cell carcinomas (BCC) of both nodular and morpheaform subtypes, and in 92% (24 of 26) of cutaneous squamous cell carcinomas (SCC). Survivin was also expressed in 19 premalignant lesions of Bowen's disease (SCC in situ) and hypertrophic actinic keratosis (HAK), suggesting that its appearance occurs early during keratinocyte transformation. Survivin expression was detected by Western blotting in a model keratinocyte cell line, HaCat. Transfection of HaCat cells with green fluorescent protein (GFP)-conjugated survivin antisense or GFP-conjugated survivin dominant negative mutant (Cys84Ala) resulted in spontaneous apoptosis in the absence of other genotoxic stimuli. In GFP-conjugated survivin antisense transfectants, a decreased level of endogenous survivin was confirmed by flow cytometry. This was associated with a five-fold increase in the sub-G0/G1 fraction corresponding to apoptotic cells and a decrease in proliferating cells with 4N DNA content. These data demonstrate that apoptosis inhibition by survivin may participate in the onset and progression of both BCC and SCC, and suggest that therapeutic targeting of survivin may be beneficial in patients with recurrent or advanced disease.

Apoptosis↗
PubMed1998

Noonan-like phenotype in monozygotic twins with a duplication-deficiency of the long arm of chromosome 18 resulting from a maternal paracentric inversion.

We report on newborn monozygotic twins with a Noonan-like phenotype, and multiple congenital anomalies due to a monocentric recombinant chromosome 18. The mother carried a paracentric inversion of the long arm of chromosome 18, inv(18)(q21.1q22.3). Cytogenetic, fluorescent in situ hybridization, comparative genomic hybridization and DNA marker analyses allowed the delineation of the deleted (18q22.3-qter) and duplicated (18q12.1-q21.1) chromosomal regions in the recombinant chromosome 18, and suggest that this duplication-deletion chromosome 18 resulted from breakage of a dicentric recombinant chromosome 18 with subsequent reconstitution of telomeric sequences on the long arm. Marked variability is observed in the phenotypic expression of the same chromosomal anomaly in these monozygotic twins. The clinical findings of these patients are compared with those reported in proximal 18q-duplication and distal 18q-deletion patients. The clinical features of both infants are compatible with Noonan syndrome, suggesting that a locus for this syndrome may be located on the long arm of chromosome 18.

Chromosome Deletion↗
PubMed1998

Hospital charges to injured drinking drivers in Washington State: 1989-1993.

The Washington State Patrol Crash Database and computerized hospitalization records for 1989-1993 were used to determine total hospital charges billed for motor vehicle collision injuries to drivers whose crash reports contained any indication of alcohol use. In this population-based study, total hospital charges were summed, and mean charges and lengths of stay were computed within alcohol use and insurance coverage status categories in an attempt to evaluate the hospital charges billed to public funding and private insurance. Of the total hospital charges for drivers with injuries from motor vehicle collisions for which a police-reported indicator of alcohol use status was available, 43% (U.S.$64.8 million) were for drivers who reportedly had been drinking. At the time of discharge, Medicaid was identified as the payor for 47% of these hospitalizations. The mean hospital charge billed per collision was greater for drinking (U.S.$18,258) than nondrinking drivers (U.S.$14,181). Drinking drivers also had longer hospital stays, even after adjustment for patient age, gender and injury severity. During this time in Washington state, the average annual amount billed at discharge for initial inpatient care of injuries to drivers who reportedly had been drinking at the time of the motor vehicle collision was U.S.$13 million. This includes only the amount assessed by the hospital at the time of discharge for treatment of the initial injury and does not include other related medical charges for rehabilitation or outpatient care, or for doctors' or laboratory fees. As increasing pressures of managed and capitated care lead to a shift of financial risk from the federal government and insurers to states and providers, the financial burden of specific, potentially preventable conditions such as this will receive greater attention.

Accidents, Traffic↗
PubMed1998

Cultural diversity in Florida nursing programs: a survey of deans and directors.

To determine how nursing programs in the state of Florida promote and integrate cultural diversity, a survey of deans and directors was conducted. Of 90 deans and directors surveyed, 46 (51%) responded. The ethnic composition of students and faculty in the respondents' programs was examined in comparison with that of the Florida population. Hispanics, Blacks, and Asians were found to be underrepresented in nursing faculty as compared with their proportion in the state population. The majority of deans and directors ranked the goal of promoting cultural diversity of moderate importance. The two most critical issues perceived by the respondents were the lack of cultural knowledge, sensitivity, and awareness, and the academic problems and educational deficits of minority students. In 50% of the programs surveyed, culture content was integrated throughout the curriculum. Other programs either integrated culture content in specific classes or offered a course in transcultural nursing. Although numerous approaches are currently being employed to recruit ethnically diverse faculty and students, the data suggest that more extensive and innovative efforts are needed to overcome existing barriers. As nursing faces the challenge of caring for a multicultural society in the 21st century, nursing leaders and organizations must collaborate to resolve the issues and problems revealed in this survey.

Cultural Diversity↗
PubMed1997

The effect of payer status on utilization of hospital resources in trauma care.

OBJECTIVE: To determine the effect of payer status on outcome and resource utilization in motor vehicle-related trauma patients. DESIGN: Retrospective cohort analysis that assessed the effect of payer status on outcome and resource utilization. SETTING: The single level I trauma center in a regionalized statewide system. PATIENTS: Consecutive patients (N = 3141) who were hospitalized after a motor vehicle crash during a 3-year period. MAIN OUTCOME MEASURES: The mortality rate, disposition, total hospital length of stay (LOS), total intensive care unit LOS, and total hospital charges were examined for 2 categories of payers: "commercial insurance" (commercial, labor and industry, and contract pay) and "noncommercial insurance" (Medicaid and self-pay). RESULTS: After controlling for age, sex, race, and the Injury Severity Score, the payer status had no overall effect on the mortality rate, disposition, total hospital charges, total hospital LOS, or total intensive care unit LOS. However, there was a significantly (11.4%; P < .05) longer LOS for those patients with noncommercial insurance who required transfer to another facility for rehabilitation or long-term care. CONCLUSIONS: The utilization of hospital trauma care resources in a level I facility in a regionalized system was not associated with insurance status. Patients with noncommercial insurance who required transfer to elective long-term care facilities had a longer LOS due to delays in obtaining subsequent access. Health care policy should provide appropriate reimbursement for all aspects of regionalized trauma care systems to ensure maintenance of an egalitarian approach to care.

Accidents, Traffic↗
PubMed1997

The complications of trauma and their associated costs in a level I trauma center.

OBJECTIVES: To estimate the expected costs for acute trauma care, to quantify the costs associated with the development of complications in injury victims, and to determine the deficit incurred by patients in whom complications develop. DESIGN: A retrospective, cohort design. SETTING: A referral trauma center. PATIENTS: A total of 12,088 patients admitted to a single regional trauma center during a period of 5 years. INTERVENTIONS: This is an observational study, and no interventions specific to this study are included in the design. MAIN OUTCOME MEASURES: (1) The expected costs for injury victims based on readily available clinical data. (2) The costs associated with the most important complications of trauma. (3) The effect of complications on inadequate reimbursement for trauma care. RESULTS: The expected costs were estimated using a linear model incorporating demographic variables and measures of injury severity. The expected costs averaged $14,567, and the observed costs averaged $15,032. Six complications were important predictors of cost. These included adult respiratory distress syndrome, acute kidney failure, sepsis, pneumonia, decubitus ulceration, and wound infections. For 1201 individuals with these complications, the predicted costs averaged $23,266 and the observed costs averaged $47,457. The mean excess costs for a single complication ranged from $6669 to $18,052. Multiple complications led to greater increases in excess cost, averaging $110,007 for the 62 patients with 3 or more complications. Costs exceeded reimbursement to a much greater degree in those in whom any of the 6 complications developed. CONCLUSION: Expected hospital costs can be estimated using admission clinical data. Each of 6 complications was associated with enormous increases in costs, indicating their importance as a cause of avoidable expenditures in injury victims and identifying situations in which reimbursement may not be adequate.

Cohort Studies↗
PubMed1997

Activated protein C resistance and anticardiolipin antibodies in patients with venous leg ulcers.

BACKGROUND: Hypercoagulable states, which include the presence of anticardiolipin antibodies (ACAs), have been associated with skin ulceration. Resistance to activated protein C (APC), resulting from the factor V Leiden mutation, is a common risk factor for venous thrombosis. Its prevalence among patients with venous leg ulcers is not known. OBJECTIVE: Our purpose was to determine the prevalence of factor V Leiden and ACA in patients with venous leg ulceration. METHODS: Twenty-nine consecutive patients with venous leg ulcers were studied. Resistance to APC was first determined by functional assay based on the partial thromboplastin time. Patients with an abnormally low APC ratio were then subjected to molecular analysis for confirmation of factor V Leiden. Measurements of ACA were performed by enzyme-linked immunosorbent assay. RESULTS: APC resistance was detected in 11 of 26 patients. However, only 2 of these 11 patients (7.7% overall) were found to be heterozygous for the factor V Leiden mutation. ACA was present in neither patient with the Leiden mutation but was found in 6 of 21 patients tested (29% overall). CONCLUSION: The factor V Leiden mutation, unlike ACA, may not be more prevalent in patients with venous leg ulcers than in the general population. Our results emphasize the importance of molecular analysis for factor V Leiden in patients with APC resistance.

Adult↗