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Biomedical subjects

M Greenberg

Publications and source records attributed to M Greenberg.

At least 181 records · Page 10Linked to original sources

Temporal clustering of homicide among urban 15- to 24-year-old white and black Americans.

Temporal clustering of homicides among 15- to 24-year-old black and white Americans was studied in 22 heavily urbanized counties in the United States from 1979 through 1985. Thirty-eight million people, including 37% of black Americans and 14% of white Americans, lived in these densely developed countries. The pattern of white male homicide deaths was cyclical--that is, statistically significant excesses were observed on weekends and on national holidays. The pattern of black male homicide deaths was much less cyclical. But homicide deaths of black males were disproportionately likely to occur in a pattern of single days with multiple homicides as well as in periodic spikes, lasting less than a week, during which many homicides occurred. Implications for research and policy are discussed.

Adolescent↗

Perinatal outcome after multifetal reduction to twins compared with nonreduced multiple gestations.

The outcomes of twins resulting from multifetal reduction were analyzed to examine whether the outcome was improved over that of triplet and quadruplet pregnancies and similar to that of twin pregnancies not involving multifetal reduction. Maternal and perinatal outcomes were examined retrospectively in 62 infertile women who conceived multiple gestations with ovulation induction. The mean gestational age at birth of quadruplets was significantly less than that of twins reduced from quadruplets (24.8 versus 31.0 weeks; P less than .001), and there was appreciable neonatal mortality in the nonreduced quadruplets (62%). In twins selectively reduced from triplets as compared with nonreduced triplets, the mean gestational age at birth, though statistically significant, differed by an average of only 1.7 weeks (34.8 versus 33.1 weeks; P less than .05), and the mean gestational birth weight differed only by 380 g (2305 versus 1924.7 g; P less than .05). Triplets required a longer average stay in the neonatal intensive care unit than did twins resulting from multifetal triplet reduction (20.7 versus 8 days; P less than .001). Although five sets of triplets (20%) were born before 32 weeks, there were only two neonatal deaths, with the remainder of the 58 infants eventually discharged home. The mean gestational age of twins selectively reduced from triplets or quadruplets was significantly less than that for nonreduced twins (32.6 versus 35.3 weeks; P less than .001), and the groups differed by 1605 g in mean birth weight (1841.8 versus 2447.5 g; P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗

Outdoor advertising of addictive products.

Billboards in black and hispanic neighborhoods in four selected New Jersey cities disproportionately contain advertisements for tobacco and alcohol products and are designed with images of sex, youth, and affluence to promote the use of addictive products.

Advertising↗

Systemic exposure to mercaptopurine as a prognostic factor in acute lymphocytic leukemia in children.

BACKGROUND: Despite a success rate of more than 90 percent in inducing remission in children with acute lymphocytic leukemia, 30 to 40 percent of such children relapse. Maintenance therapy during remission usually includes oral mercaptopurine and methotrexate. Recently, wide variability in the bioavailability of oral mercaptopurine has been demonstrated, and there is concern that this may affect the risk of relapse. METHODS: To investigate whether lower systemic exposure to mercaptopurine may increase the risk of relapse in acute lymphocytic leukemia, we prospectively studied 23 children receiving maintenance therapy. On the basis of disease features, 11 were classified as being at low risk of relapse, and 12 at standard risk. Those who relapsed (n = 10) did not differ from those who did not in their mean age, hemoglobin level, mean daily dose of mercaptopurine and weekly dose of methotrexate, or the total number of days during which mercaptopurine and methotrexate therapy was interrupted. RESULTS: There was a significant difference in the mean (+/- SEM) area under the mercaptopurine concentration-time curve achieved by a dose of 1 mg of mercaptopurine per square meter of body-surface area: 1636 +/- 197 nmol per liter x minutes in those who relapsed, as compared with 2424 +/- 177 nmol per liter x minutes in those who did not (P less than 0.005). This caused a significantly lower total daily systemic exposure to mercaptopurine in those who relapsed (104,043 +/- 12,812 nmol per liter x minutes) than in those who did not (168,862 +/- 18,830 nmol per liter x minutes) (P less than 0.005). An identical tendency prevailed when patients at low risk and patients at standard risk were analyzed separately. Kaplan-Meier analysis revealed that children in whom an area under the curve of less than 1971 nmol per liter x minutes was achieved by a dose of 1 mg of mercaptopurine per square meter had a significantly poorer prognosis than those with larger areas under the curve (P less than 0.01). Similarly, those with a total daily systemic exposure of more than 137,970 nmol per liter x minutes had a significantly better prognosis than those with a lower exposure (P less than 0.005). CONCLUSIONS: Low systemic exposure to oral mercaptopurine during maintenance therapy for acute lymphocytic leukemia in childhood adversely affects prognosis. Children should be studied at the beginning of maintenance therapy to establish the pharmacokinetics of mercaptopurine, and the dose should be tailored to achieve an appropriate systemic exposure.

Antineoplastic Combined Chemotherapy Protocols↗

Diurnal variation in the pharmacokinetics and myelotoxicity of mercaptopurine in children with acute lymphocytic leukemia.

During their maintenance therapy, children with acute lymphoblastic leukemia are treated with a daily dose of mercaptopurine for several years. A recent retrospective analysis has suggested that administration of the drug in the evening results in a better prognosis. We compared the disposition pharmacokinetics of mercaptopurine administered in the morning vs in the evening in 13 children with acute lymphoblastic leukemia. Elimination half-life of mercaptopurine was significantly longer in the evening than during the day (423 +/- 142 minutes vs 176 +/- 22 minutes, mean +/- SEM). The area under the concentration-time curve (AUC0-infinity) was significantly larger in the evening (24,713 +/- 3536 ng/mL per minute vs 17,120 +/- 1474 ng/mL per minute). These differences were even more pronounced when comparing the area under the curve of the postdistributive phase (AUC300 min-infinity, 7724 +/- 2955 ng/mL per minute in the evening vs 2597 +/- 712 ng/mL per minute during the day). In a second study, 12 children with acute lymphoblastic leukemia receiving mercaptopurine in the morning had their medication administration switched to the evening. Within 2 weeks there was a sharp fall in peripheral white blood cell counts in all patients (from 4.1 x 10(9)/L to 2.2 x 10(9)/L) mainly due to a drop in polymorphonuclear lymphocytes (from 2.78 x 10(9)/L to 1.05 x 10(9)/L). We conclude that the diurnal variations of mercaptopurine disposition result in clinically important myelotoxicity of the drug.

Antineoplastic Combined Chemotherapy Protocols↗

Pediatric onset of Behçet's syndrome with myositis: case report and literature review illustrating unusual features.

We report a case of Behçet's syndrome with myositis in a pediatric patient, emphasizing the importance of muscle involvement in the differential diagnosis of calf pain and swelling in Behçet's syndrome. A review of the English-language literature from 1965 to the present suggests that the clinical picture of Behçet's syndrome in children differs from that in adults, in that there is a lower frequency of ocular disease, and unusual manifestations appear to be more common.

Adolescent↗

Hodgkin's disease in children: treatment with MOPP and low-dose, extended field irradiation without laparotomy. Late results and toxicity.

The 10 year results of a trial of bimodal treatment of Hodgkin's disease in children with 6 cycles of MOPP and low-dose extended field irradiation, without staging laparotomy, were for 57 children in all stages as follows: survival 85%, relapse-free survival 80%, and survival-free of second relapse 86%. There were three fatal toxic events, two due to viral infection and one to a second malignant tumor (NHL). Three other patients developed a second malignant tumour, and one developed a thyroid adenoma. No patient developed acute leukemia. These results are compared with the results of treatment of surgically staged children by extended field irradiation alone, with bimodal treatment reserved for relapse or advanced disease at diagnosis. Initial bimodal treatment improved the overall 10 year survival free from a second relapse rate by 20% (86% vs. 66%). No major difference in treatment toxicity between these two groups has emerged during the first 10 years of follow-up. We conclude that, except for favourable CS-1 presentations, children with Hodgkin's disease confined to the lymphatic system should be given bimodal treatment, but that the least morbid effective combination remains to be determined.

Adolescent↗

Pineal region germinomas in childhood treatment considerations.

From 1967-1986, 21 children were treated for pineal germinoma, including 16 biopsy-proven, 2 biopsy non-diagnostic, and 3 metastatic unbiopsied (marker negative) patients. Ten of 18 (56%) biopsied patients underwent partial or sub-total tumor resection. Twenty patients were irradiated, 19 of whom are alive. No irradiated patient died of progressive germinoma, but two patients relapsed in the spinal cord and required treatment intensification for salvage. Long-term survivors have significant morbidity. Determination of the minimum effective treatment remains the chief therapeutic challenge.

Adolescent↗

Posterior fossa medulloblastoma in childhood: treatment results and a proposal for a new staging system.

Seventy-two children with posterior fossa medulloblastoma were diagnosed at the Hospital for Sick Children, Toronto, from 1977 to 1987 and treated by standard methods. The 5- and 10-year survival and disease-free survival rates were 71% and 63%, and 64% and 63%, respectively. Total tumor resection, as determined by the surgeon was the most significant favorable prognostic factor. Post-operative meningitis, a residual enhancing mass lesion on the post-operative, pre irradiation CT scan and dissemination to the brain or cord at diagnosis were unfavorable factors. These four easily definable factors were used to define a staging system with prognostic significance. Five-year disease-free survival rates were for Stage I (total resection, no adverse factor) 100%, Stage II (total resection with one or more adverse factor or less than total resection with no other adverse factor) 78%, and Stage III (less than total resection with one or more adverse factor) 18%. Evaluation of treatment results in medulloblastoma requires that these prognostic factors be known.

Adolescent↗

Detecting disease clusters: the importance of statistical power.

A variety of methods and models have been proposed for the statistical analysis of disease excesses, yet rarely are these methods compared with respect to their ability to detect possible clusters. Evaluation of statistical power is one approach for comparing different methods. In this paper, the authors study the probability that a test will reject the null hypothesis, given that the null hypothesis is indeed false. They present a discussion of some considerations involved in power studies of cluster methods and review two methods for detecting space-time clusters of disease, one based on cell occupancy models and the other based on interevent distance comparisons. The authors compare these approaches with respect to: 1) the sensitivity to detect disease excesses (false negatives); 2) the likelihood of detecting clusters that do not exist (false positives); and 3) the structure of a cluster in a given investigation (the alternative hypothesis). The methods chosen, which are two of the most commonly used, are specific to different hypotheses. They both show low power for the small number of cases which are typical of citizen reports to health departments.

Clinical Protocols↗

Understanding mass media coverage of disease clusters.

The responsibility of informing the general public about disease clusters belongs to health investigators. In the majority of instances the investigators must send their messages through the mass media. The authors analyzed nightly network television news coverage of disease clusters during the period 1978-1987, and newspaper coverage of four disease clusters. Formal content analysis of about 600 stories showed that the mass media focuses on human interest, conflicting information, blame, and political symbolism in their coverage of clustered health events. The authors offer suggestions to health practitioners about improving their communications with journalists.

Disease Outbreaks↗

Pulmonary malacoplakia in a child.

Pulmonary malacoplakia is a rare condition with only five previously reported cases in the literature, all occurring in adults. We describe a case of malacoplakia of the lung in a 6-year-old female with acute lymphoblastic leukemia in remission and a Rhodococcus equi pneumonia and septicemia. The case demonstrates that pulmonary malacoplakia can occur in immunocompromised pediatric patients and that malacoplakia should, therefore, be added to the list of causes of nodular lung infiltrates in immunocompromised children.

Child↗

Hemiballismus: study of a case using positron emission tomography with 18fluoro-2-deoxyglucose.

A 64-year-old man had right-sided persistent hemiballismus. Cerebral computed tomography (CT) and 0.5-T magnetic resonance imaging (MRI) showed no abnormalities, but 1.5-T MRI showed decreased signal intensity of the putamina, greater on the left than on the right. The subthalamic area was normal on CT and MRI. Positron emission tomography with 18fluoro2-deoxyglucose showed marked hypometabolism of the left putamen (60% of the right) and hypermetabolism of the left parietal lobe (138% of the right). The decreased metabolism of the left putamen may indicate a reduction in neuronal firing. The pathophysiology of the hemiballismus in this case may be loss of tonic inhibition of the lateral globus pallidus from the putamen, leading in turn to greater inhibition of the subthalamic nucleus, less excitation of the medial globus pallidus, and less inhibition of the thalamus and motor cortex, and thus allowing expression of the ballistic movements.

Adolescent↗

Disposition of oral methotrexate in children with acute lymphoblastic leukemia and its relation to 6-mercaptopurine pharmacokinetics.

We studied the disposition pharmacokinetics of methotrexate (MTX) given orally to 16 children with acute lymphoblastic leukemia (ALL) and its relation to the pharmacokinetics of 6-mercaptopurine (6MP) in the same children. There was an eightfold variability in area-under-concentration time-curve (AUC) of MTX achieved by the same dose. Excellent correlation existed between peak concentrations and AUC0----infinity (r = 0.95, P less than 0.001). Elimination T1/2 was between 1.34 and 5 hours (mean 2.16 +/- 0.23 hr, mean +/- SE). A weak correlation existed between AUC achieved by 1 mg/m2 MTX and patients' age or body weight. Weak but significant correlation existed between AUC achieved by 1 mg/m2 of MTX vs. 6MP (r = 0.54, P less than 0.05). In 13/16 patients peak concentrations were achieved at 60 minutes. There was a significantly larger AUC of 6MP achieved by a standardized dose in longer therapy (greater than 15 mo) vs. short therapy (less than 12 mo) (462 +/- 75 and 246 +/- 58 ng.ml-1.min.mg-1.m2, P less than 0.025). No statistical differences in AUC of MTX were found between short and long therapy. The large interpatient variability in MTX pharmacokinetics supports the possibility that differences in absorption and/or clearance of the drug may affect the clinical response. Because of the excellent correlation between peak and AUC of MTX, and because 3 measurements, at 30, 60, and 90 minutes will almost invariably identify the peak, this measurement can be used to estimate AUC for purpose of correlation with clinical outcome.

Administration, Oral↗

Rhabdomyosarcoma of the prostate in childhood: current challenges.

Since 1978, six boys with prostatic rhabdomyosarcoma have been treated at our institution. Three had localized disease and were managed by initial biopsy, vincristine, actinomycin-D, and cyclophosphamide (VAC) chemotherapy, and bladder-sparing surgery with or without irradiation. Further combination chemotherapy ("pulse" VAC, Adriamycin, VP-16, cisplatin, and ifosfamide) was continued for 20 to 22 months following the induction course. Two boys had microscopic residual disease undetected by frozen section and unresponsive to radiotherapy. Subsequent total cystectomy 4 and 7 months later resulted in eradication of disease. In one patient, preservation of the bladder was achieved at the age of 3 months for 8 years. Artificial sphincter inserted to cure his urinary incontinence failed because of ischemia secondary to cuff compression and scar tissue. He is alive today with a modified Koch pouch urinary diversion. Of the 50% who had metastatic disease at presentation, two were dead within 12 months despite aggressive chemotherapy and irradiation. The third is currently on treatment. Although chemotherapy has markedly improved the prognosis, surgery is still necessary in most cases for cure. Bladder salvage is a desirable goal; however, residual microscopic disease, difficulty with frozen-section disease detection, and poor tissue vascularization for subsequent sphincter replacement remain significant obstacles.

Adolescent↗