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Publications and source records attributed to J Goldsmith.
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The pharmacokinetics, safety, tolerance, and antiviral effects of ganciclovir (Gcv) administered orally were evaluated in 36 children infected with cytomegalovirus (CMV) who were severely immunocompromised by infection with human immunodeficiency virus type 1. In this dose-escalation study, 30 mg/kg of Gcv administered every 8 h produced serum levels similar to the dose (1 g/8 h) effective for maintenance treatment of CMV retinitis in adults. In older children, serum Gcv concentrations were similar after the administration of capsules and suspension. All doses (10-50 mg/kg/8 h) studied were safe and, except for the volume of suspension or number of pills, were well tolerated. Oral Gcv was associated with a decrease in the detection of CMV by culture or polymerase chain reaction. CMV disease occurred in 3 children during the study: one developed Gcv resistance, another had harbored resistant virus at study entry, and a third had wild-type CMV
Chemotherapy, in addition to recombinant growth factors, has been effective in mobilizing stem cells. Unfortunately, the use of chemotherapy for this purpose has resulted in profound myelosuppression and increased morbidity. Docetaxel, the single most active agent in the treatment of advanced breast cancer, was evaluated for its potential to mobilize stem cells when given at conventional doses followed by granulocyte colony-stimulating factor (G-CSF). Sixteen high-risk breast cancer patients were mobilized with a regimen consisting of docetaxel (100 mg/m2) followed by daily G-CSF (10 microg/kg), beginning 72 h after the docetaxel, and continuing until completion of the apheresis. The median white blood cell count (WBC) nadir was 1,000/microl (range 500 to 4000/microl ) occurring a median of 6 days (range 4 to 9 days) after the docetaxel. No patient experienced a neutropenic febrile episode due to the mobilization regimen. The median time interval for initiating the apheresis was 8 days (range 6 to 11 days) following the docetaxel. The median number of apheresis was 2 (range 1 to 3) in each patient. Stem cell recovery as measured by the CD34 cell count x 10(6)/kg was a median of 5.2 (range 1.4 to 15.1). A significant correlation was found between CFU-GM, BFU-E, and CFU-GEMM/kg and CD34 cells/kg (r = 0.891, 0.945, and 0.749, respectively, p < 0.001). When our results were compared to a matched cohort receiving G-CSF alone, the docetaxel group demonstrated a superior CD34 cells/kg yield (p = <0.001). Following myeloablative chemotherapy consisting of thiotepa and cyclophosphamide with or without carboplatinum, the hematopoetic recovery determined by an absolute neutrophil count (ANC) of greater than 500/microl and an unsupported platelet count of > or =20,000/microl for 48 h, was a median of 10 days (range 9 to 14 days) and 10 days (range 8 to 30 days), respectively. The results demonstrate that conventional dose docetaxel, combined with G-CSF, is an effective mobilization regimen with minimal toxicity in high-risk breast cancer patients.
OBJECTIVE: To evaluate the possible association between occupational exposures (risk factors) and male bladder cancer in the Negev region (southern Israel) to enable preventive strategies to be applied. METHODS: A total of 92 male bladder cancer patients, diagnosed at a regional medical center between 1989 and 1993, were studied by interview and compared with 92 males without oncological disease after matching by age and country of origin. A special questionnaire was developed to gather information on demography, life-time occupational history, smoking habits, coffee consumption, and health status. Statistical analysis of the case-referent data was done using the SPSS-5 package for performance of the chi-square test, conditional logistic regression, and multiple classification analysis. RESULTS: Significant associations were found between bladder cancer occurrence and (1) three different groups of occupational exposures [a - solvents (P = 0.002, OR not computed due to the lack of exposed persons among referents), b - dusts (P = 0. 02; OR = 4.67), and c - exposure to multiple chemicals (P < 0.001, OR = 6.25); (2) nephrolithiasis (P = 0.02, OR = 11.00); and (3) cigarette smoking (P = 0.01, OR = 1.87). CONCLUSIONS: Certain types of occupational exposure, different from that to aromatic amines and dyes, may be considered as contributing factors in the epidemiology of bladder cancer. Better identification of these chemicals and the work processes where they are used may help in abating such exposures, thus leading to a reduction in the risk for this relatively common cancer.
OBJECTIVE: To analyze the authors' midterm results (up to 4 years) using endovascular grafts to treat aortoiliac occlusive disease in patients with limb-threatening ischemia. SUMMARY BACKGROUND DATA: Endovascular grafts are being used to manage some aortoiliac lesions formerly treated by aortofemoral or extraanatomic bypass grafts. However, widespread acceptance of these new grafts depends on their late patency and clinical utility. METHODS: Between January 1993 and December 1997, 52 patients with aortoiliac occlusive disease were treated with endovascular grafts. The primary indication for treatment was gangrene or ulceration in 42 patients (81%) and rest pain in 10 patients (19%). Sixteen patients had symptomatic contralateral limbs that were also treated, and 27 (52%) patients required a synchronous infrainguinal bypass. Results up to 4 years were evaluated by life table analysis. RESULTS: Forty-six (88%) of the patients had complete follow-up of 3 to 57 months (median 22 months). Six patients were lost to follow-up at a mean of 20 months after surgery. The 4-year primary and secondary patency rates for the endovascular grafts were 66.1% and 72.3% respectively. Six patients required a major amputation, and the limb salvage rate was 88.7%. Four-year patient survival was 37%, with 23 patients dying during this follow-up period. CONCLUSIONS: Endovascular grafts can often be used when conventional procedures are contraindicated or technically impractical. These grafts are a valuable alternative to extraanatomic and aortofemoral bypasses in high-risk patients with aortoiliac occlusive disease and critical ischemia.
BACKGROUND: Previous reports in the literature have shown that non-steroidal anti-inflammatory drugs (NSAID) may affect osseous tissues by either stimulating or inhibiting bone formation. This effect can be drug specific and different NSAIDs may produce opposite results. There are also reports showing that NSAIDs inhibit bone loss due to inflammatory disease process. The purpose of this randomized, controlled, blinded, clinical investigation was to determine the effect of a one week course of postsurgical naproxen on the osseous healing in intrabony defects. METHODS: Twenty-four vertical osseous defects in 24 patients were treated with either a bioabsorbable membrane plus twice daily postsurgical naproxen 500 mg for one week (test or GPN group) or with a polylactide bioabsorbable membrane alone (control or GA group). Twelve patients were included in each group. Treatment was performed on either 2- or 3-wall or combination defects. All measurements were taken from a stent by a calibrated, blinded examiner and open measurements were repeated at the 9-month second stage surgery. Power analysis to determine superiority of naproxen treatment showed that a 12 per group sample size would yield 87% power to detect a 2.0 mm difference and 64% power to detect a 1.5 mm difference. RESULTS: Open defect measurements from baseline to 9 months showed a statistically significant (P < 0.05) mean defect fill of 1.96 +/- 1.27 mm and 2.04 +/- 1.71 for the GPN and GA groups, respectively. This corresponded to a mean defect fill of 42% and a mean defect resolution of approximately 75% for both groups. The differences between GPN and GA groups were not statistically significant (P > 0.05). Defect fill of > or = 50% was seen in 6 defects (50%) in the GPN group and in 5 defects (42%) in the GA group. CONCLUSIONS: The administration of postsurgical naproxen failed to produce osseous healing that was statistically superior to that obtained with polylactide bioabsorbable membranes alone.
BACKGROUND: The purpose of this randomized, controlled, blinded, clinical investigation was to determine the effect of postsurgical antibiotics on osseous healing in Class II furcation defects. METHODS: Twenty-four Class II furcation defects in 24 patients were treated with either a polylactide bioabsorbable membrane, demineralized freeze-dried bone allograft (DFDBA) plus antibiotics (GBA or test group) or with a polylactide membrane and DFDBA alone (GB or control group). Twelve patients were included in each group. The antibiotic regimen consisted of ciprofloxacin 250 mg twice daily and metronidazole 250 mg tid for 1 week followed by a 7-week regimen of doxycycline hyclate 50 mg daily. Treatment was performed on either mandibular buccal or lingual, or maxillary buccal Class II furcation defects. Defects were randomly selected by a coin toss for treatment and all open and closed measurements were performed by a blinded examiner. Final open and closed measures from a stent were repeated at the 9-month second stage surgery. Power analysis to determine superiority of antibiotic treatment showed that a 12 per group sample size would yield 93% power to detect a 1.5 mm difference and 64% power to detect a 1 mm difference. RESULTS: Mean open horizontal probing depth reductions at 9 months were greater for the GBA group than for the GB group (2.92+/-1.78 versus 2.50+/-1.62 mm); however, these differences were not statistically significant. Seven of 12 furcations (58%) in the GBA group demonstrated >50% vertical defect fill at 9 months compared to 8 of 12 furcations (67%) in the GB group. There were no significant differences in mean open horizontal probing depth reduction between smokers and non-smokers in either the GBA or GB groups. Membrane exposure did not appear to affect regenerative healing in either the GBA or GB groups. CONCLUSIONS: The administration of postsurgical antibiotics did not produce statistically superior osseous healing of Class II furcation defects. This result may be attributable to membrane design which facilitates connective tissue ingrowth, thereby preventing bacterial downgrowth and contamination of the newly regenerated tissues.
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The cardiology unit at the University of Chicago Hospitals developed a cost-saving mechanism in the care of postinterventional cardiology patients, reducing time spent in the coronary care unit. Increased nursing education and training and better identification of patient outcomes made this collaborative effort a cost-saving and effective pilot.
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Clastogenic factors (CFs), as they were described previously in accidentally or therapeutically irradiated persons, in A-bomb survivors and in liquidators of the Chernobyl nuclear power plant, were also detected in the plasma of Chernobyl-exposed children. A high percentage of plasma ultrafiltrates from 170 children, immigrated to Israel in 1990, exerted clastogenic effects in test cultures set up with blood from healthy donors. The differences were highly significant in comparison to children immigrated from 'clean' cities of the former Soviet Union or children born in Israel. The percentage of CF-positive children and the mean values of the adjusted clastogenic scores (ACS) were higher for those coming from Gomel and Mozyr, which are high exposure sites (IAEA measurements), compared to those coming from Kiev. There was no correlation between residual 137-Caesium body burden and presence of CFs. However, both measurements were not done at the same time (in 1990 and 1992-1994, respectively). Also no relationship could be revealed between enlargement of the thyroid gland and CF-positivity. CFs are not only observed after irradiation, but in a variety of chronic inflammatory diseases with autoimmune reactions. They were also described in the congenital breakage syndromes, which are hereditary diseases with the highest cancer incidence in humans. Whether the clastogenic effects continuously produced by circulating CFs represent a risk factor for malignant late effects deserves further study and follow-up. Since CF formation and CF action are mediated by superoxide radicals, prophylactic treatment with antioxidants may be suggested for Chernobyl-exposed children, whose plasma induces a strongly positive CF-test.
OBJECTIVE: To determine if streptococcicidal levels of penicillin G benzathine can be detected in maternal serum 4 weeks after treatment with 4.8 million units. METHODS: Thirty-seven pregnant women with positive group B streptococcus vaginal or urine cultures were each given 4.8 million units of penicillin G benzathine. Maternal blood samples were collected after injection and at delivery. Serum penicillin levels were measured by high-pressure liquid chromatography. Follow-up cultures were done when possible. RESULTS: None of the patients had serum penicillin levels below 0.20 microgram/mL 30 days after treatment. Cord blood levels were approximately 50% lower than maternal levels. In all but three subjects, cord blood levels exceeded 0.06 microgram/mL, the minimal inhibitory concentration for group B streptococcus. The three exceptions were patients who delivered more than 100 days after treatment. Group B streptococcus cultures were negative at the time of delivery in 72% of cases. None of the patients with positive cultures were moderately or heavily colonized. CONCLUSION: In pregnant women, penicillin G benzathine levels are high enough to inhibit the growth of group B streptococcus for more than 4 weeks after injection with 4.8 million units. Further studies are needed to evaluate whether this regimen can prevent neonatal colonization and invasive group B streptococcus disease.
The cardiology unit at the University of Chicago Hospitals developed a cost-saving mechanism in the care of postinterventional cardiology patients, reducing time spent in the coronary care unit. Increased nursing education and training and better identification of patient outcomes made this collaborative effort a cost-saving and effective pilot.
PURPOSE: This study was undertaken to evaluate our results of polytetrafluoroethylene (PTFE) tibial and peroneal artery bypasses done for limb salvage. METHODS: Within a group of patients undergoing infrainguinal limb salvage bypasses at our institution between January 1986 and May 1995, 63 patients faced an immediate amputation, had no autologous vein on duplex examination and operative exploration, and had only a tibial or peroneal artery as an outflow vessel for bypass. Most of these patients (82%) had two or more prior ipsilateral infrainguinal bypasses. These 63 patients underwent 66 PTFE bypasses to a tibial or peroneal artery without a distal anastomotic vein cuff or an adjunctive arteriovenous fistula. Our results were then compared with those reported from infrapopliteal (crural) bypasses performed with alternate autologous vein sources or PTFE in conjunction with various recommended adjuncts. RESULTS: The 3- and 5-year cumulative primary graft patency rates for our PTFE infrapopliteal bypasses were 39%+/-7% and 28%+/-9%, respectively. Secondary graft patency rates were 55%+/-8% and 43%+/-10% at 3 and 5 years, respectively. Limb salvage rates were 71%+/-7% at 3 years and 66%+/-8% at 5 years. Two-year actuarial patient survival rate was only 67%+/-7%. CONCLUSIONS: These results indicate that a PTFE bypass to an infrapopliteal artery remains a worthwhile option in patients without usable autologous vein. The secondary patency and limb salvage rates were acceptable in this setting and were not significantly different from the best results reported with prosthetic tibial/peroneal bypasses with distal vein cuffs or patches (74% at 1 year; 58% at 3 years), arteriovenous fistulas (71% at 1 year) or composite arm vein grafts (39% and 29% at 3 and 5 years, respectively).
The safety, tolerability, pharmacokinetic profile, and preliminary activity of lamivudine (2'-deoxy-3'-thiacytidine), a novel cytidine nucleoside analogue with antiretroviral activity, in human immunodeficiency virus (HIV)-infected children beyond the neonatal period were studied. Ninety children received dosages of 1-20 mg/kg/day. Pharmacokinetic evaluation demonstrated serum and cerebrospinal fluid concentrations that increased proportionally to dose. As of January 1994, 11 children had been withdrawn from study for disease progression and 10 because of possible lamivudine-related toxicity, and 6 had died. CD4 and CD8 cell counts remained stable over 24 weeks in therapy-naive children and decrease slightly in previously treated children. Quantitative immune complex-dissociated p24 antigen and HIV RNA were decreased significantly at 12 and 24 weeks. In vitro resistance to lamivudine was documented in sequential virus isolates from some patients by 12 weeks. Lamivudine was well-tolerated and exhibited virologic activity in children, although future use in children is likely to be in combination antiretroviral regimens.
Tomograms of the temporomandibular joint were digitized in three different formats using a PC-based system. The image resolution for various projections was determined at different camera-film distances. Three series of images were transmitted by telephone, and transmission times were measured. The original radiographs, the digitized images, the transmitted images and the transmitted-and-printed images were presented to 10 observers, who were asked to rate image quality. No difference in image quality was found between the initial digitized and the transmitted images. However, transmitted and transmitted-and-printed images were of significantly lower quality than the original radiographs or the digitized images viewed on a computer monitor. Transmission time was reduced significantly (50%) by cropping the images before transmission. The image quality of individual radiographs was better than radiographs formatted as a series.
OBJECTIVES: Clinical evaluation of a cassette with dual speed screens for cephalometric radiography. METHODS: Two lateral cephalometric radiographs were taken on 20 consenting subjects using the TMJ Orthoceph Slimline Cassette System (TOSCS), incorporating circular Trimax 12 screens in the area adjacent to the temporomandibular joint, and a control cassette (Trimax 8 screens). Ten pairs of radiographs with optimal image quality were randomly presented to 10 observers trained in cephalometric interpretation. Observers rated the overall diagnostic quality of each radiograph and of the TMJ region on an ordinal scale. They then located specific landmarks and traced the TMJ anatomy using acetate overlays. Overlays were digitized by a single operator who repeated tracing placements and digitizations to determine the error of recording method. Landmark variability was compared in the x- and y-axis by the Wilcoxon matched-pairs signed ranks test (p < 0.05). Six repeat tracings were performed and assessed by percentage of repeated observations above the maximum affordable error. Fossa space values were analyzed by the coefficient of variation (CV). The variability of the angular and linear values was also compared. RESULTS: TOSCS image quality was perceived as significantly better than the control. Method error was 0.34 mm in the x-axis and 0.4 mm in the y-axis. Interobserver variability was 2 to 3 times greater than intraobserver. There was less variability with TOSCS for identification of basion (x-axis), center-of-rotation (x-axis) and condyle (posterior) (x-axis). However, this was clinically insignificant. Accurate determination of the fossa space was not possible as CV varied from 23 to 84%. No differences in the variability of angular or linear values variability were found. CONCLUSIONS: While observers preferred TOSCS, no significant clinical differences could be demonstrated between the two systems.