Validity of Self-Report in Alcoholism Research: Results of a Veterans Administration Cooperative Study

The validity of self-report in alcoholism treatment research is controversial. Our recently completed Veterans Administration Cooperative Study evaluating the efficacy of disulfiram treatment for alcoholism provided an opportunity to assess the validity of self-report. To assess treatment response, patients and household contacts were interviewed at seven scheduled points during the 1 year of follow-up. Blood specimens also were obtained from the patients at these times and were analyzed for ethanol. Eighty-eight percent of the patient and/or collateral interviews were obtained at 6 months and 90% at 1 year. The mean number of blood and urine specimens collected per patient was 4.3 and 14.4, respectively. Outcome criteria included continuous abstinence during the year and total number of drinking days. Continuous abstinence: If we had had only the patients' self reports, we would have significantly underestimated the percentage of men who drank. By self-report 58.7% (355/605) relapsed whereas the combination of self report, collaterals' reports, and laboratory tests indicated that 72.4% (438/605) drank (p less than 0.001). Using Bayes' theorem, the conditional probability that a patient is continuously abstinent for 1 year when he so claims is 65%. Total drinking days: Of the 213 patient-collateral pairs each of whom provided all seven scheduled interviews, 46.9% (100/213) agreed on the total number of drinking days during the year.(ABSTRACT TRUNCATED AT 250 WORDS)     

Platelet membrane microparticles in blood bank fresh frozen plasma and cryoprecipitate

Cryoprecipitate has been demonstrated to correct the bleeding abnormality of patients with some congenital (storage pool disease) and acquired (uremia) platelet abnormalities, but the reason for this effect is unknown. We found significant platelet contamination in plasma harvested to prepare fresh frozen plasma and cryoprecipitate. The platelet membrane microparticles produced by freezing and thawing of the plasma were highly concentrated in cryoprecipitate and may contribute to its therapeutic effect.     

Risk factors for early termination of breast feeding in Brazil

A prospective study was undertaken to identify possible factors related to the duration of breast feeding. Two hundred and thirty-eight mothers who had delivered normal single babies with birth weights greater than 2.5 kg and had initiated breast feeding were randomly selected at the maternity hospital, Hospital de Clinicas de Porto Alegre, Brazil, and followed by mail questionnaires until termination of breast feeding, or until the end of the first year. If no reply was received, telephone contact or home visits were made. The group of mothers who stopped breast feeding prior to the end of the third month was compared with those who extended breast feeding beyond three months with respect to socioeconomic, biological, environmental, medical and psychological factors. The variables with a significant coefficient of association with early termination of breast feeding were maternal education, past experience with breast feeding, help of a maid, help with housework provided by a relative, breast feeding orientation during prenatal care and encouragement from the husband. These factors act simultaneously, with interactions among them.     

Application of Isoelectric Focusing in Immobilized pH Gradients to the Study of Acetaldehyde-Modified Hemoglobin

We applied the technique of isoelectric focusing (IEF) on immobilized pH gradients (LKB) to determine whether acetaldehyde-modified hemoglobins (Hb) prepared in vitro with unphysiological acetaldehyde concentrations have clinical relevance. This technique separates proteins with pl less than 0.01 and provides detail about hemoglobins not otherwise separable. We performed two kinds of studies. In one kind of study, we incubated red cells from control subjects with acetaldehyde. Products of these incubations were applied to IEF gels either directly or after reduction with sodium cyanoborohydride. Incubation of red cells with acetaldehyde in 1-150 mM concentration without cyanoborohydride reduction yielded hemoglobin bands of decreasing pl the appearance of which coincided with the disappearance of Hb A and Hb A1c. When the products of incubation were reduced with cyanoborohydride before IEF, an additional acidic Hb band appeared which we call the "anodal CNBH band." In a second kind of study, we compared IEF patterns of hemolysates from control subjects and alcoholism detoxification patients, without adding acetaldehyde. Again, samples were applied to IEF gels either directly or after reduction with cyanoborohydride. When samples were run on IEF without reduction, no differences were seen between patients and controls. When samples were reduced before IEF, an anodal CNBH band appeared having the same mobility as the band seen after in vitro incubations with acetaldehyde. These bands were often stronger in samples from patients, but not consistently so. Several experiments, including the use of glycolysis inhibitors, indicated that the anodal CNBH band is an adduct of fructose 1,6-diphosphate with hemoglobin. We suggest that in millimolar concentrations, acetaldehyde may function as an inhibitor of glycolysis at or below the aldolase step.     

Incidence,and Gender,Age and Ethnic Distribution of Sarcomas in the Republic of Suriname from 1980 to 2008

Objective:

We report on the incidence and the gender, age and ethnic distribution of sarcomas diagnosed between 1980 and 2008 in the multi-ethnic Republic of Suriname.

Methods:

Total and average yearly number of cases, crude rates, as well as relevant population data were derived from the records of the Pathologic Anatomy Laboratory and the General Bureau of Statistics, respectively, and stratified according to gender, age groups 0–19, 20–49 and 50+ years, and the largest ethnic groups (Hindustani, Creole, Javanese and Maroons).

Results:

Between 1980 and 2008, 258 sarcomas were diagnosed in Suriname, ie at a frequency of nine per year and an annual rate of two per 100 000. Overall, there was 0.9 male per female, two to four cases per year in each age group, and one to three patients in each ethnic group. Soft-tissue sarcomas comprised approximately 80% of overall cases, with a male/female ratio that was approximately 0.5; almost 90% of patients were older than 20 years; more than one-third was Creole. Leiomyosarcoma, fibrosarcoma and liposarcoma were most frequently encountered (90 cases), particularly above 20 years of age, while leiomyosarcomas seemed, additionally, more common in women and Creoles or Maroons. The most numerous bone tumours were primitive neuroectodermal tumour/Ewing tumour and osteosarcoma (37 cases). They were more common in males, the youngest age group, and Hindustanis and Creoles.

Conclusions:

The incidence of sarcomas in Suriname, and their gender, age and ethnic distribution in general, seemed comparable with international data. The main exception might be leiomyosarcoma which might have a predilection for Afro-Surinamese.     

The RAR-RXR as well as the RXR-RXR pathway is involved in signaling growth inhibition of human CD34+ erythroid progenitor cells

Previous studies have shown that retinoic acid (RA), similar to tumor necrosis factor-alpha (TNF-alpha), can act as a bifunctional regulator of the growth of bone marrow progenitors, in that it can stimulate granulocyte-macrophage colony-stimulating factor (GM-CSF)- or interleukin-3 (IL-3)-induced GM colony formation, but potently inhibit G-CSF-induced growth. The present study, using highly enriched human CD34+ as well as Lin- murine bone marrow progenitor cells, demonstrates a potent inhibitory effect of 9-cis-RA on burst-forming unit-erythroid (BFU-E) colony formation regardless of the cytokine stimulating growth. Specifically, 9-cis-RA potently inhibited the growth of BFU-E response to erythropoietin (Epo) (100%), stem cell factor (SCF) + Epo (92%), IL- 3 + Epo (97%), IL-4 + Epo (88%), and IL-9 + Epo (100%). Erythroid colony growth was also inhibited when CD34+ progenitors were seeded at one cell per well, suggesting a direct action of RA. Using synthetic ligands to retinoic acid receptors (RARs) and retinoid X receptors (RXRs) that selectively bind and activate RAR-RXR or RXR-RXR dimers, respectively, we dissected the involvement of the two retinoid response pathways in the regulation of normal myeloid and erythroid progenitor cell growth. Transactivation studies showed that both the RAR (Ro 13- 7410) and RXR (Ro 25-6603 and Ro 25-7386) ligands were highly selective at 100 nmol/L. At this concentration, Ro 13-7410 potently inhibited G- CSF-stimulated myeloid as well as SCF + Epo-induced erythroid colony growth. At the same concentration, Ro 25-6603 and Ro 25-7386 had little or no effect on G-CSF-induced colony formation, whereas they inhibited 75% and 53%, respectively, of SCF + Epo-stimulated BFU-E colony growth. Thus, the RAR-RXR response pathway can signal growth inhibition of normal bone marrow myeloid and erythroid progenitor cells. In addition, we demonstrate a unique involvement of the RXR-RXR pathway in mediating growth inhibition of erythroid but not myeloid progenitor cells.