Long-term use of the female condom among couples at high risk of human immunodeficiency virus infection in Zambia

A comparison of course and outcome in schizophrenics and patients with unipolar affective disorders revealed significant differences not only between the two groups but also between first hospitalized and rehospitalized patients within each group. While schizophrenics fared worse in almost all parameters at the end of the 14-year follow-up period, within each group overall course and outcome were also poorer for rehospitalized versus first hospitalized patients. The poorest course was shown by rehospitalized schizophrenics. Future studies on course and outcome should differentiate between first and rehospitalized patients.     

Influence of the heterogeneity of P-glycoprotein expression on technetium-99m-MIBI uptake in breast cancer

We prospectively studied a total of 30 patients with breast cancer to evaluate the relationship between the degree of accumulation of 99mTc-sestamibi (MIBI) and the heterogeneity of p-glycoprotein expression in tumor tissues. METHODS: Twenty patients during initial presentation and 10 patients during post-therapy evaluation underwent contemporaneous 99mTc-MIBI imaging and surgery or biopsy. Immunohistochemical studies were performed on multiple nonconsecutive sections of the same tumor using a p-glycoprotein-specific monoclonal antibody, JSB-1. Tumor-to-background (T/B) ratios were correlated with the level and heterogeneity of p-glycoprotein expression determined by immunohistochemical studies. RESULTS: The T/B ratios were lower for those tumors with strong p-glycoprotein expression (Group 1) than those with strong-to-weak expression (Group 2) or those with weak-to-no expression (Group 3) (1.32 +/- 0.19 and 1.85 +/- 0.56 and 2.86 +/- 1.06, respectively). There was statistically significant difference in T/B ratios between all 3 groups (p < 0.005). Although T/B ratios for Group 1 and Group 3 were clearly distinct from one another with no overlapping values, the values for Group 2 overlapped with those of Group 1 and Group 3. When we evaluated the entire patient group with excluding those with strong-to-weak expression, although the p value remained the same (p < 0.001), we obtained a stronger correlation between T/B ratios and p-glycoprotein expression (r = 0.808 versus 0.735). CONCLUSION: Due to the heterogeneous expression of p-glycoprotein, both immunohistochemistry and 99mTc-MIBI scintigraphy may yield confounding results by contrasting with one another if the presence or absence of p-glycoprotein is not extensively explored. Although our data confirmed that 99mTc-MIBI imaging is useful in the determination of the presence of multidrug resistance in patients with breast cancer, the issue of heterogeneous expression of the antigen should be further investigated when unexpected results are obtained.     

Heterocyclic nucleoside analogues by cycloaddition reactions of 1-vinylthymine with 1,3-dipoles

1,3-Dipolar cycloaddition of 1-vinylthymine to azides, nitrile oxides, nitrones and nitronates has been investigated as a route to heterocyclic nucleoside analogues in which the nucleoside ribose moiety has been replaced by an alternative heterocycle. Reaction of 1-vinylthymine with highly reactive nitrile oxides affords 1-(isoxazolin-5-yl)thymine products in excellent yield at room temperature. The less reactive nitrone dipoles undergo cycloaddition to 1-vinylthymine at elevated temperature to afford 1-(isoxazolidin-5-yl)thymine cycloadducts in good-to-moderate yields, but show a tendency to eliminate thymine from the cycloaddition products over long reaction times. Azide cycloadditions to 1-vinylthymine proceed only under forcing conditions to which the fragile triazoline products are unstable.     

Estimation of unit risk for coke oven emissions

We are investigating the hypothesis that biotin multimers can be used with streptavidin and monoclonal antibody conjugates in cancer pretargeting protocols to provide a method of increasing the amount of radioactivity bound on cancer cells in patients. As part of that investigation, a series of biotinylated Starburst dendrimers (BSBDs) have been prepared and evaluated in vitro and in vivo. In this study, a new biotinidase-stabilized, water-solubilizing biotinylation reagent was prepared and reacted with Starburst (PAMAM) dendrimers, generations 0, 1, 2, 3, and 4. The reaction conditions employed resulted in perbiotinylation of generation 0 (four biotin moieties conjugated), generation 1 (eight biotin moieties conjugated), generation 2 (16 biotin moieties conjugated), and generation 3 (32 biotin moieties conjugated). With generation 4, incomplete biotinylation was achieved resulting in the largest portion of that BSBD having 51 biotin moieties (of 64 possible) conjugated. The ability of each BSBD to cross-link streptavidin (SAv) was examined in an in vitro assay. In that assay, an assessment was made of the quantity of [125I]SAv bound with polystyrene-bound SAv after treatment with the synthesized BSBDs. All BSBDs cross-linked the polystyrene-bound SAv with [125I]SAv; however, the amount of [125I]SAv bound varied with the different BSBDs. Roughly 1 equiv of [125I]SAv was bound when Starburst dendrimers containing three or four biotin moieties (generation 0) were used. Two equivalents were bound with BSBD generation 1, and 4 equiv were bound with BSBDs generations 2, 3, and 4. To assess the distribution of BSBDs generations 0, 1, and 2 in mice (at 4 h postinjection), a method was developed for radioiodinating them using the NHS ester of p-[125I]iodobenzoate ([125I]PIB). It was found that the radioiodinated BSBDs had low blood concentrations (i.e., 0.13-0.20% ID/g) at the 4 h time point. In fact, most tissues examined had low concentrations of biotinylated dendrimers, except kidney and liver. Kidney had the highest concentration of [125I]-labeled BSBDs, and its concentration increased with increasing size and charge of dendrimer (e.g., 8-48% ID/g). On the basis of the increased radioactivity observed in the in vitro assay and the rapid clearance from blood in mice, additional in vivo studies with perbiotinylated Starburst dendrimer, generation 2, are planned.     

The fetal-pelvic index has minimal utility in predicting fetal-pelvic disproportion

OBJECTIVE: Our purpose was to evaluate the fetal-pelvic index in our patient population and to determine whether it would be predictive of route of delivery. STUDY DESIGN: One hundred seventy-six patients with a previous history or clinical findings in the current pregnancy suggestive of fetal-pelvic disproportion participated in this Human Investigation Committee-approved study. All underwent fetal ultrasonographic examinations and modified digital radiography before labor. Fetal head and abdominal circumferences and maternal inlet and midpelvic circumferences were determined, and the fetal-pelvic index was calculated. RESULTS: Ninety-one patients fulfilled all aspects of the study, including rigorous criteria pertaining to labor management. Thirty of these patients underwent cesarean delivery and 61 were delivered vaginally. The fetal-pelvic index value for the vaginal delivery group was -5.4 +/- 5.3, as opposed to -2.4 +/- 5.8 in the cesarean delivery group (P <.02). Notwithstanding this difference, the fetal-pelvic index had a low overall ability to predict fetal-pelvic disproportion (0.65) and had associated sensitivity and specificity of 0.27 and 0.84, respectively. Predictive thresholds other than zero were tested, but optimal predictive ability, at a fetal-pelvic index cutoff of 2, was only 70% (sensitivity 0.20, specificity 0.95). CONCLUSION: In our patient population the fetal-pelvic index was only moderately predictive of fetal-pelvic disproportion. Factors other than those assessed by the fetal-pelvic index are probably important in determining the route of delivery. Further studies are indicated.     

Evidence of acute stress disorder after diagnosis of cancer

Cancer patients frequently have symptoms of anxiety and depression after diagnosis. Often these symptoms are apparent to the physician. We report the case of a cancer patient who appeared to her physician to be coping relatively well but was actually having psychologic symptoms that met criteria for acute stress disorder (ASD). Cancer patients who have psychologic trauma at diagnosis and meet criteria for ASD may appear to be coping better than they are. Mental health interventions for cancer patients are recommended.     

Coagulation initiated on herpesviruses

Herpesviruses have been previously correlated to vascular disease and shown to cause thrombogenic and atherogenic changes to host cells. Herein we show that even in the absence of cells, purified cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) can initiate thrombin production. Functional assays demonstrated that purified HSV-1 and HSV-2 provide the necessary phospholipid (proPL) for assembling the coagulation factors Xa and Va into prothrombinase, which is responsible for generating thrombin. These observations are consistent with our earlier studies involving CMV. The presence of proPL on all three herpesviruses was confirmed directly by flow cytometry and electron microscopy by using annexin V and factor Va, respectively, as proPL-specific probes. Of equal importance, we found that CMV, HSV-1, and HSV-2 were also able to facilitate factor Xa generation from the inactive precursor factor X, but only when factor VII/VIIa and Ca2+ were present. Monoclonal antibodies specific for tissue factor (TF), the coagulation initiator, inhibited this factor X activation and, furthermore, enabled identification of TF antigen on each virus type by flow cytometry and electron microscopy. Collectively, these data show that CMV, HSV-1, and HSV-2 can initiate the generation of thrombin by having essential proPL and TF activities on their surface. Unlike the normal cellular source, the viral activity is constitutive and, therefore, not restricted to sites of vascular injury. Thus cell-independent thrombin production may be the earliest event in vascular pathology mediated by herpesviruses.