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Biomedical subjects

D Grossman

Publications and source records attributed to D Grossman.

At least 19 recordsLinked to original sources
PubMed2006

Diagnostic accuracy of a point-of-care syphilis test when used among pregnant women in Bolivia.

OBJECTIVE: To evaluate the performance of a point-of-care (POC) syphilis test when used in urban Bolivian maternity hospitals. METHODS: We tested 8892 pregnant women for syphilis using the Abbott Determine Syphilis TP rapid POC test and rapid plasma reagin (RPR) in the laboratory of four large urban maternity hospitals where national statistics reported a syphilis prevalence of at least 3%. Sera were stored and transferred to the national reference laboratory (INLASA) where RPR testing was repeated. When the reference laboratory staff observed a positive RPR result, a Treponema pallidum particle agglutination assay (TPPA) was performed to confirm these findings. We calculated test performance characteristics for the POC test and hospital RPR using RPR performed at the reference laboratory confirmed by TPPA as the reference standard. Participants received treatment during their initial visit based on the POC test results. RESULTS: The sensitivity, specificity, negative predictive value and positive predictive values of the POC syphilis test were: 91.8% (95% confidence intervals 88.4% to 94.5%), 98.5% (98.2% to 98.8%), 71.0% (66.6% to 75.2%), and 99.7% (99.5% to 99.8%), respectively. The RPR values were 75.7% (70.8% to 80.2%), 99.0% (98.9% to 99.3%), 76.9% (72.0% to 81.3%), and 99.0% (98.8% to 99.2%), respectively. CONCLUSION: The Abbott Determine Syphilis TP test proved to be more sensitive than routine RPR and had comparable specificity. POC testing may be a simple way to expand syphilis screening to clinics with no laboratory facilities, improve case detection, and facilitate treatment delivery.

Adolescent↗
PubMed2006

Laparoscopic partial splenectomy.

BACKGROUND: The immunologic function of the spleen and its important role in immune defense has led to splenic-preserving surgery. This study aimed to evaluate whether laparoscopic partial splenectomy is safe. METHODS: Data on consecutive patients presenting with localized benign or malignant disease of the spleen were included in a prospective database. The surgical technique consisted of six steps: patient positioning and trocar placement, mobilization of the spleen, vascular dissection, parenchymal resection, sealing/tamponading of the transected edge, and removal of the specimen. RESULTS: From 1994 to 2005, 38 patients underwent laparoscopic partial splenectomy. The indications included splenomegaly of unknown origin, splenic cysts, benign tumors (hamartoma), and metastasis from ovarian carcinoma and schwannoma. The median operating time was 110 min (range, 65-148 min). The median length of hospital stay was 5 days (range, 4-7 days). There was no postoperative mortality. Postoperative pleural effusion occurred in two patients. There were no reoperations. Three patients required blood transfusions. CONCLUSION: Laparoscopic partial splenectomy is safe for patients with localized benign or malignant disease of the spleen.

Adolescent↗
PubMed2006

Induction of melanoma cell apoptosis and inhibition of tumor growth using a cell-permeable Survivin antagonist.

The inhibitor of apoptosis gene family member Survivin is highly expressed in most tumors, and appears to be a promising target for cancer therapy. Although a variety of Survivin antagonists have been shown to induce apoptosis in malignant cells, the potential utility of these agents is limited by inefficient delivery and cell impermeability. We generated recombinant fusion proteins containing the TAT protein transduction domain and either wild-type Survivin (TAT-Surv-WT) or a dominant-negative mutant (TAT-Surv-T34A). The TAT-Surv proteins were purified by sequential affinity and ion-exchange chromatography, and at 30 nM concentration demonstrated rapid entry into cells at 30 min. Whereas TAT-Surv-WT had minimal effect on YUSAC2 or WM793 melanoma cells, TAT-Surv-T34A induced cell detachment, DNA fragmentation, caspase-3 activation and mitochondrial release of apoptosis-inducing factor at low microM concentrations. Intraperitoneal (i.p.) injection of mice bearing subcutaneous YUSAC2 xenografts with TAT-Surv-T34A (10 mg/kg) was associated with rapid tumor accumulation at 1 h, and increased tumor cell apoptosis and aberrant nuclei formation in situ. Repeated i.p. injection of TAT-Surv-T34A resulted in a 40-50% reduction in growth and mass of established tumors, compared to those similarly injected with saline buffer or TAT-Surv-WT. These studies demonstrate the feasibility of systemic tumor treatment using a cell-permeable Survivin antagonist.

Animals↗
PubMed2004

Pedestrian crashes: higher injury severity and mortality rate for light truck vehicles compared with passenger vehicles.

INTRODUCTION: During the last two decades changes in vehicle design and increase in the number of the light truck vehicles (LTVs) and vans have led to changes in pedestrian injury profile. Due to the dynamic nature of the pedestrian crashes biomechanical aspects of collisions can be better evaluated in field studies. DESIGN AND SETTING: s: The Pedestrian Crash Data Study, conducted from 1994 to 1998, provided a solid database upon which details and mechanism of pedestrian crashes can be investigated. RESULTS: From 552 recorded cases in this database, 542 patients had complete injury related information, making a meaningful study of pedestrian crash characteristics possible. Pedestrians struck by LTVs had a higher risk (29%) of severe injuries (abbreviated injury scale >/=4) compared with passenger vehicles (18%) (p = 0.02). After adjustment for pedestrian age and impact speed, LTVs were associated with 3.0 times higher risk of severe injuries (95% confidence interval (CI) 1.26 to 7.29, p = 0.013). Mortality rate for pedestrians struck by LTVs (25%) was two times higher than that for passenger vehicles (12%) (p<0.001). Risk of death for LTV crashes after adjustment for pedestrian age and impact speed was 3.4 times higher than that for passenger vehicles (95% CI 1.45 to 7.81, p = 0.005). CONCLUSION: Vehicle type strongly influences risk of severe injury and death to pedestrian. This may be due in part to the front end design of the vehicle. Hence vehicle front end design, especially for LTVs, should be considered in future motor vehicle safety standards.

Abbreviated Injury Scale↗
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↗
PubMed2001

Drug resistance in melanoma: mechanisms, apoptosis, and new potential therapeutic targets.

Melanoma is the most aggressive form of skin cancer. Patients with advanced disease, such as lymph node involvement and distant metastases, have 5-year survival rates of 50% and 10-20%, respectively. This poor prognosis largely results from resistance to conventional chemotherapy, namely cytotoxic drugs. The basis for drug resistance in melanoma is most likely dysregulation of apoptosis, although other mechanisms including drug transport, detoxification, and enhanced DNA repair may also play a role. Defects at multiple levels and in both major apoptotic pathways have been described in melanoma. Our laboratory has identified an inhibitor of apoptosis, termed survivin, that is expressed in melanoma and required for maintenance of melanoma cell viability. Targeting of survivin and other apoptotic regulators increases the sensitivity of melanoma cells to cytotoxic drugs, and may provide a promising new therapeutic approach to cancer.

Antineoplastic Agents↗
PubMed2001

Factors influencing the patterns of injuries and outcomes in car versus car crashes compared to sport utility, van, or pick-up truck versus car crashes: Crash Injury Research Engineering Network Study.

BACKGROUND: Data using crash dummies suggest that motor vehicle crashes (MVCs) involving passenger sedans (S) vs sport utility, vans, or light trucks (SUVTs) produce more severe injuries than those involving two sedans (SvS). However, no detailed data regarding pattern of injuries or force mechanisms involved have been presented in real patients. METHODS: The relationship of injury patterns and severities with MVC reconstruction data were obtained in 412 MVC patients, drivers or front seat passengers. Crashes were examined with regard to impact direction, frontal (F) or lateral (L) crashes, vehicle mass ratio, ISS, DELTA V, seat belt use, and airbag deployment (AB). RESULTS: In 309 F-MVC, AB reduced overall ISS (24.3 to 17.9) with a reduction in the mean severity of traumatic brain injury (TBI) GCS < or = 12, from 48% to only 28%. This AB protection from TBI was preserved as DELTA V increased to > 30 mph even though non-AB protected body areas (thorax, lung, liver, and lower extremity injuries) all increased. When vehicles of incompatible size and mass (SUVT) had F-MVC with sedans the incidence of severe TBI rose as did face lacerations despite AB or belt use. In L-MVC between SUVT and sedans compared with SvS MVC, there was a cephalad shift in body injuries with increased thorax, but decreased lower extremity injuries. The incidence of TBI increased. Analysis of injury contact sites (hits) showed more hits and a wider distribution of contract sites in SUVT vs sedan MVC. These appeared due to the greater mass excess and larger mass ratio, hood height, and width in the F-SUVT vs S crashes. All of these factors plus the increased bumper height above the body frame side-door sill were injury causal factors in the L-SUVT vs S MVCs. CONCLUSION: Both F and L crashes between sedans and SUVT with a high mass ratio shift the pattern of injury cephalad with increased thorax and intrathoracic organ injuries, and more severe TBI. These data suggest that improved head and thorax side-impact buffering and design features which transmit MVC forces from the higher front end of the larger mass SUVT to the frame of the sedan may better protect sedan occupants from side-impacts.

Accidents, Traffic↗
PubMed2001

Transgenic expression of survivin in keratinocytes counteracts UVB-induced apoptosis and cooperates with loss of p53.

The inhibitor of apoptosis protein survivin has been implicated in both cell cycle control and apoptosis resistance. To discriminate between these different roles, we used transgenic expression of survivin in the skin as a model for cell proliferation, differentiation, and apoptosis. Transgenic mice expressing survivin under the control of a keratin-14 promoter developed normally, without histologic abnormalities of the skin or hair, epidermal hyperplasia, or developmental abnormalities of basal or suprabasal epidermis. Keratinocyte proliferation assessed under basal conditions, or after ultraviolet-B (UVB) irradiation, or phorbol ester stimulation was unchanged in survivin transgenic mice. In contrast, survivin expression inhibited UVB-induced apoptosis in vitro and in vivo (i.e., sunburn cell formation), whereas it did not affect Fas-induced cell death. When crossed with p53 knockout mice, transgenic expression of survivin in a p53(+/-) background substituted for the loss of a second p53 allele and further inhibited UVB-induced apoptosis. These data provide the first in vivo evidence that survivin inhibits apoptosis and suggest that this pathway may oppose the elimination of cancerous cells by p53.

Animals↗
PubMed2001

On killing. II: The psychological cost of learning to kill.

Military and law enforcement studies reveal that interpersonal combat is a universal human phobia. Physiological responses include forebrain shutdown and sympathetic arousal. A resistance to killing exists in the midbrain of most healthy members of most species, becoming ascendant when the forebrain shuts down, and can prevent soldiers from performing in combat. The U.S. military has increased participation in killing activities from 20% in World War II to 95% in Vietnam by operantly conditioning responses. Conditioning is achieved through training that closely resembles battle situations and inadvertently occurs when children see violence as entertainment. The price of this conditioning is an increase in post-traumatic stress disorder which can be defrayed through debriefing, social acceptance, and prevention of atrocities. Similar techniques may be used to prevent PTSD in civilian populations involved in tragedies like school shootings.

Arousal↗
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↗