Is access to medical care associated with receipt of HIV testing and counselling?

Lack of timely HIV testing leads to missed prevention opportunities and poor prevention counselling may be related to further disease spread. We examined the association of self-reported access to medical care with receiving HIV testing and preventive counselling services among a sample of patients with HIV disease prior to hospitalization. We conducted a cross-sectional interview of 217 Los Angeles patients hospitalized with HIV-related illness between 1992 and 1993 and abstracted clinical data from the medical record. Eighty-four per cent of patients received HIV testing prior to hospitalization, but only 33% received preventive counselling services. Only 48% of all patients rated outpatient medical care as somewhat or very easy to obtain. Controlling for severity of illness, better access to outpatient medical care (OR = 1.48; 95% CI = 1.02-2.15), having a regular source of care (OR = 3.40; 95% CI = 1.29-8.97) and non-homosexual mode of HIV transmission (OR = 0.31; 0.12-0.83) were associated with receiving HIV testing services prior to hospitalization. Having a regular source of care (OR = 3.55; 95% CI = 1.37-9.22), being VA (Veterans' Administration) insured (OR = 6.16; 1.46-26.05), older age (OR = 0.95; 95% CI = 0.90-0.99) and having a CD4 count between 101-200 (OR = 0.19; 95% CI = 0.06-0.63) were associated with receiving HIV counselling. Limited self-reported access to medical care is associated with fewer patients receiving HIV testing and counselling. Improving timeliness of HIV testing may require removing the barriers to medical care.     

Effect of evaluator and resident gender on the American Board of Internal Medicine evaluation scores

OBJECTIVE: To examine the effects of resident and attending physician gender on the evaluation of residents in an internal medicine training program. DESIGN: Cross-sectional study. SETTING: Large urban academic internal medicine residency program. PARTICIPANTS: During their first 2 years of training, 132 residents (85 men, 47 women) received a total of 974 evaluations from 255 attending physicians (203 men, 52 women) from 1989 to 1995. MEASUREMENTS: The primary measurements were the numerical portions of the American Board of Internal Medicine evaluation form. Separate analyses were performed for each of the nine evaluation dimensions graded on a scale of 1 to 9. The primary outcome was the difference in the average scores received by each resident from male versus female attending physicians. RESULTS: Compared with female trainees, male residents received significantly higher scores from male attending physicians than from female attending physicians in six of the nine dimensions: clinical judgment, history, procedures, relationships, medical care, and overall. Similar trends, not reaching conventional levels of statistical significance, were observed in the other three categories: medical knowledge, physical exam, and attitude. These differences ranged from 0.24 to 0.60 points, and were primarily due to higher grading of male residents by male attending physicians than by female attending physicians. CONCLUSIONS: In one academic training program, we found a significant interaction in the grading process between the gender of internal medicine residents and the gender of their attending evaluators. This study raises the possibility that subtle aspects of gender bias may exist in medical training programs.     

Use of bedside activated partial thromboplastin time monitor to adjust heparin dosing after thrombolysis for acute myocardial infarction: results of GUSTO-I. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries

Multiple five-day testing of rats in the open field and elevated plus-maze revealed a regressive dynamics of the integral characteristics of the exploratory behavior. The integral quantitative indices of searching activity in Henderson's test of extrapolation deliverance (modified by N. A. Bondarenko) and in active shock avoidance in N. R. Grigor'ev's problem box, on the contrary, displayed a progressive dynamics, like quantitative characteristics of cognitive activity. We established the differences between the determinants and control mechanisms of exploratory behavior and searching activity. This allowed us to differentiate these forms of behavior as different functional states.     

Environmental effects on cellular photosensitization: correlation of phototoxicity mechanism with transient absorption spectroscopy measurements

The presence of actin in eukaryotic nuclei and chromosomes, and especially in higher plant nuclei and chromosomes, has not been well established. We detected actin in meristematic cells of Allium cepa with indirect immunofluorescence technique and observed bright fluorescence in the intact nuclei and chromosomes, indicating that actin is present in the nuclei and chromosomes of the higher plant. We labeled sections of the meristematic cells of A. cepa with immunogold technique, gold particles were found over the whole nuclei and a number of gold particles were concentrated in condensed chromatin and nucleoli, confirming the results of the immunofluoresence observations. We treated the nuclei and chromosomes of A. cepa with DNase I and 2M NaCl and obtained DNA- and histone-depleted nuclei and chromosomes. Indirect immunofluorescence tests showed that the DNA- and histone-depleted nuclei and chromosomes reacted positively with the anti-actin antibodies. These results demonstrate that actin exists not only in intact nuclei and chromosomes, but also in DNA- and histone-depleted nuclei and chromosomes of the plant. In addition, our immuno-fluorescence tests indicate that tropomyosin is present in the nuclei and chromosomes of A. cepa.     

Nanoliter chemistry combined with mass spectrometry for peptide mapping of proteins from single mammalian cell lysates

A nanoliter-chemistry station combined with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry was developed to characterize proteins at the attomole level. Chemical reactions including protein digestion were carried out in nanoliter or subnanoliter volumes, followed by microspot sample deposition of the digest to a MALDI-TOF mass spectrometer. Accurate mass determination of the peptides from the enzyme digest, in conjunction with protein database searching, allowed the identification of the proteins in the protein database. This method is particularly useful for handling small-volume samples such as in single-cell analysis. The high sensitivity and specificity of this method were demonstrated by peptide mapping and identifying hemoglobin variants of sickle cell disease from a single red blood cell. The approach of combining nanoliter chemistry with highly sensitive mass spectrometric analysis should find general use in characterizing proteins from biological systems where only a limited amount of material is available for interrogation.     

Neuroendocrine differentiation is an independent prognostic factor in chemotherapy-treated nonsmall cell lung carcinoma

BACKGROUND: Neuroendocrine differentiation can be identified in 10-30% of patients with nonsmall cell lung carcinoma (NSCLC) by immunohistochemical or electron microscopic techniques. However, its clinical significance is not well established. METHODS: Tumors from 107 patients with Stage IIIA, IIIB, and IV NSCLC treated with cisplatin/etoposide with or without hydrazine in the North Central Cancer Treatment Group and Mayo Clinic protocols were analyzed immunohistochemically with antibodies to chromogranin A (CGA), Leu 7 (CD 57), and synaptophysin (SY). These results were compared with clinical outcomes. RESULTS: Keratin AE1/AE3, used as a control, was positive in 99.1% of cases; 34.6% had positive staining for at least 1 neuroendocrine marker, and 11.3% had positive staining for 2 or more markers. CGA was positive in 4.7%, Leu 7 in 18.7%, and SY in 24.3% of cases. A significant increase in survival was seen in patients with tumors expressing any one neuroendocrine marker or any combination of neuroendocrine markers (P < or = 0.01). There was no correlation between the presence of neuroendocrine differentiation and either response to chemotherapy or time to disease progression (P > 0.3), nor was there any correlation between chemotherapy response, time to progression, or survival with staining intensity or percent of cells positive per case. CONCLUSIONS: Neuroendocrine differentiation may be of prognostic significance in patients with advanced stage NSCLC treated with chemotherapy.     

Design and construction of a realistic digital brain phantom

1. The effect of diltiazem on isolated sarcoplasmic reticulum (SR) from rabbit skeletal muscle was studied. To observe calcium movement into and out of the SR, a fluorescent chelate probe technique with chlortetracycline (CTC) as a reagent was employed. 2. Tris-ATP-induced calcium accumulation by the isolated SR was associated with a rise in the CTC fluorescence. The effect of ATP was dose dependent. 3. Diltiazem (6 x 10(-4)M, 2 x 10(-3)M) prevented ATP-induced calcium accumulation by the SR. 4. Addition of EGTA to the media chelates external calcium and caused calcium release that can be reversed by further addition of calcium chloride. Similarly diltiazem caused a rapid release of accumulated calcium from the SR, which is not reversed by the addition of calcium chloride. 5. It seems that the effect of diltiazem may be related to SR membrane-bound calcium being available for release.     

Identification of high-affinity binding sites for the insulin sensitizer rosiglitazone (BRL-49653) in rodent and human adipocytes using a radioiodinated ligand for peroxisomal proliferator-activated receptor gamma

A radioiodinated ligand, [125I]SB-236636 [(S)-(-)3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]3-[125I]i odo phenyl]2-ethoxy propanoic acid], which is specific for the gamma isoform of the peroxisomal proliferator activated receptor (PPARgamma), was developed. [125I]SB-236636 binds with high affinity to full-length human recombinant PPARgamma1 and to a GST (glutathione S-transferase) fusion protein containing the ligand binding domain of human PPARgamma1 (KD = 70 nM). Using this ligand, we characterized binding sites in adipose-derived cells from rat, mouse and humans. In competition experiments, rosiglitazone (BRL-49653), a potent antihyperglycemic agent, binds with high affinity to sites in intact adipocytes (IC50 = 12, 4 and 9 nM for rat, 3T3-L1 and human adipocytes, respectively). Binding affinities (IC50) of other thiazolidinediones for the ligand binding domain of PPARgamma1 were comparable with those determined in adipocytes and reflected the rank order of potencies of these agents as stimulants of glucose transport in 3T3-L1 adipocytes and antihyperglycemic agents in vivo: rosiglitazone > pioglitazone > troglitazone. Competition of [125I]SB-236636 binding was stereoselective in that the IC50 value of SB-219994, the (S)-enantiomer of an alpha-trifluoroethoxy propanoic acid insulin sensitizer, was 770-fold lower than that of SB-219993 [(R)-enantiomer] at recombinant human PPARgamma1. The higher binding affinity of SB-219994 also was evident in intact adipocytes and reflected its 100-fold greater potency as an antidiabetic agent. The results strongly suggest that the high-affinity binding site for [125I]SB-236636 in intact adipocytes is PPARgamma and that the pharmacology of insulin-sensitizer binding in rodent and human adipocytes is very similar and, moreover, predictive of antihyperglycemic activity in vivo.     

CD4+ lymphocytes provide MUC1-specific tumor immunity in vivo that is undetectable in vitro and is absent in MUC1 transgenic mice

A C57BL/6 mouse transgenic for human MUC1 (MUC1.Tg) was developed to evaluate MUC1-specific tumor immunity in an animal that expresses MUC1 as a normal self protein. Previous studies showed that MUC1.Tg mice, challenged with syngeneic tumors expressing MUC1 (B16.MUC1), developed progressively growing MUC1-positive tumors, whereas wild-type C57BL/6 (wt) mice developed MUC1-negative tumors at a significantly slower rate. The results of a limiting dilution CTL frequency assay were not informative, in that similar numbers of MUC1-specific CTL precursors (CTL) were detected in MUC1.Tg and wt mice. Tumor immunity in vivo was characterized by an adoptive transfer method to evaluate the degree of MUC1 or non-MUC1 tumor immunity in wt or MUC1.Tg mice. The results revealed that wt mice developed protective tumor immunity mediated by MUC1-specific CD4+ lymphocytes, while MUC1.Tg mice were functionally tolerant to MUC1 in vivo. The potential of adoptive immunotherapy to provide immunity to tumors expressing MUC1 and to produce undesirable autoimmunity in recipient MUC1.Tg mice expressing MUC1 as a self Ag was evaluated. Adoptive transfer of immune cells from wt mice primed in vivo with B16.MUC1 tumor cells into MUC1.Tg recipients resulted in significant increases in the survival of MUC1.Tg recipients compared with unmanipulated control MUC .Tg mice challenged with B16.MUC1 tumor cells. This response was specific for MUC1 since control tumors developed at equivalent rates in recipient or control MUC1.Tg mice. No gross or histologic evidence of autoimmunity was observed in recipient MUC1.Tg mice, indicating that tumor immune responses mediated by MUC1-specific CD4+ lymphocytes spare nontransformed epithelia-expressing MUC1.