Comparative evaluation of serum acid phosphatase, urinary cholesterol, and androgens in diagnosis of prostatic cancer.

Serum acid phosphatase activity, urinary total cholesterol, and ratio of deoxy to oxy urinary 17-ketosteroids were measured in a group of 42 patients with prostatic carcinoma and in a group of 14 age-matched normal healthy individuals. Our purpose was to evaluate whether or not the simultaneous determinations of these tests would increase the rate of detection obtained by the single assay alone. The results of single assay revealed for the following detection rate: 67 per cent (28 of 42 patients) for serum acid phosphatase, 62 per cent for urinary total cholesterol, and 22 per cent for ratio of 17-ketosteroids. A significant increase of detection rate was observed when simultaneous determinations of two assays were performed; 86 per cent for serum acid phosphatase activity and total urinary cholesterol; 74 per cent for serum acid phosphatase and ratio of 17-ketosteroids; and 74 per cent for total urinary cholesterol and ratio of 17-ketosteroids. A detection rate of 88 per cent (37 of 42 patients) was obtained as all three assays were analyzed, though it was not significantly different from a ratio of 86 per cent for simultaneous assays of acid phosphatase and total cholesterol. It was concluded that simultaneous determinations of serum acid phosphatase activity, urinary total cholesterol, and androgens are of values in diagnosis for patients with prostatic neoplasia.     

ECOG phase II trials of MGBG, chlorozotocin, COM multidrug therapy in advanced measurable colorectal cancer

The Eastern Cooperative Oncology Group (ECOG) entered 326 patients with advanced measurable colorectal cancer into four phase II drug or drug combination trials. Previously treated and chemotherapy-naive patients were eligible. Chlorozotocin was administered to 83 patients (51 previously treated), methyl-glyoxal-bis-guanylhydrozone (MGBG) to 90 patients (58 previously treated), and two regimens of the three-drug combination of cyclophosphamide, vincristine, and methotrexate (COM) to 153 patients (120 previously treated). The multidrug regimen had been developed specifically for previously treated patients. In this trial, chemotherapy-naive patients were no more likely to respond than were members of the previously-treated group. Even among previously untreated patients, response rates did not exceed 10% in any of these phase II programs. They are not recommended for further trials in patients with colorectal cancers.     

Differences in glycosylation patterns of heat shock protein, gp96: implications for prostate cancer prevention

Heat shock protein gp96 induces a tumor-specific protective immunity in a variety of experimental tumor models. Because the primary sequences of the glycoprotein, gp96 are identical between tumor and normal tissues, the peptides associated with gp96 and/or the posttranslational modifications of gp96, determine its immunogenicity. Gp96-associated peptides constitute the antigenic repertoire of the source tissue; thus, purified gp96-peptide complexes have clinical significance as autologous cancer vaccines. However, the role of altered glycosylation and its contribution in the biological as well as immunologic activity of gp96 still remains uncharacterized. We examined the cancer-specific glycosylation patterns of gp96. To this end, monosaccharide compositions of gp96 were compared between normal rat prostate and two cancerous rat prostate tissues, nonmetastatic/androgen-dependent Dunning G and metastatic/androgen-independent MAT-LyLu, as well as two human nonmetastatic prostate cancer cell lines, androgen-dependent LnCaP and androgen-independent DU145. Marked differences were observed between the gp96 monosaccharide compositions of the normal and cancerous tissues. Furthermore, gp96 molecules from more aggressive cellular transformations were found to carry decreasing quantities of several monosaccharides as well as sum total content of neutral and amino sugars. We believe that the unique glycosylation patterns contribute to cellular phenotype and that the posttranslational modifications of gp96 may affect its functional attributes.     

Effects of a caregiver intervention on negative caregiver appraisals of behavior problems in patients with Alzheimer's disease: results of a randomized trial

Behavioral problems are among the most challenging aspects of caring for a person with Alzheimer's disease. A sample of 406 spouses-caregivers of patients with Alzheimer's disease was randomized to an active multicomponent counseling and support intervention condition or to a usual care condition. Caregivers reported on the frequency of troublesome patient behaviors and their reactions to them at baseline and at regular follow-up interviews. Random-effects regression models over the first 4 years after randomization revealed that, although the intervention did not affect the frequency of patient behavioral problems, it did significantly reduce caregivers' reaction ratings. Because caregiver appraisals have been found to mediate the impact of caregiving stress on depression and to predict nursing home placement rates, they deserve greater attention as an important target of intervention services.     

A hypocalcemic child with a novel activating mutation of the calcium-sensing receptor gene: successful treatment with recombinant human parathyroid hormone

CONTEXT: Persistent hypercalciuria, with the attendant risk of nephrocalcinosis and eventual renal failure, is common in hypoparathyroid patients, especially those with activating mutations of the calcium-sensing receptor (CASR) gene, being treated with oral calcium and calcitriol. Treatment with replacement PTH may be warranted, although this has yet to be evaluated in children. OBJECTIVES: The objectives of this study were to identify the cause of the disorder in a young hypocalcemic patient and to assess the efficacy of treatment of the patient with recombinant human PTH(1-34). SUBJECT: An infant presenting with hypocalcemia at 3 wk of age was studied. METHODS: CASR gene mutation analysis was performed on genomic DNA of the proband and family members. The patient was treated with twice-daily administration of recombinant human PTH(1-34) over a 17-month period. RESULTS: The proband was heterozygous for a de novo novel missense mutation (L727Q), on the border between transmembrane helix 4 and intracellular loop 2 of the CASR. When transiently expressed in a human embryonic kidney 293 cell line, the mutant receptor demonstrated a significant leftward shift in the extracellular calcium/intracellular signaling dose-response curve vs. that for the wild-type receptor [EC(50); mutant, 2.59 +/- 0.11 mm (mean +/- se) vs. wild-type, 3.78 +/- 0.12 mm, P < 0.001]. During treatment with PTH(1-34), the patient had no further serious hypocalcemic episodes, and his urinary calcium excretion declined remarkably. CONCLUSION: PTH should be evaluated further as a treatment of autosomal dominant hypocalcemia in young patients.     

Preliminary data on Pemphigus vulgaris treatment by a proteomics-defined peptide: a case report

Background

A functional blood supply is essential for tumor growth and proliferation. However, the mechanism of blood vessel recruitment to the tumor is still poorly understood. Ideally, a thorough molecular assessment of blood vessel cells would be critical in our comprehension of this process. Yet, to date, there is little known about the molecular makeup of the endothelial cells of tumor-associated blood vessels, due in part to the difficulty of isolating a pure population of endothelial cells from the heterogeneous tissue environment.

Methods

Here we describe the use of a recently developed technique, Expression Microdissection, to isolate endothelial cells from the tumor microenvironment. The methylation status of the dissected samples was evaluated for GSTP1 and RARβ2 promoters via the QMS-PCR method.

Results

Comparing GSTP1 and RARβ2 promoter methylation data, we show that 100% and 88% methylation is detected, respectively, in the tumor areas, both in epithelium and endothelium. Little to no methylation is observed in non-tumor tissue areas.

Conclusion

We applied an accurate microdissection technique to isolate endothelial cells from tissues, enabling DNA analysis such as promoter methylation status. The observations suggest that epigenetic alterations may play a role in determining the phenotype of tumor-associated vasculature.     

Impact of the reduction of environmental and equipment contamination on vancomycin-resistant enterococcus rates

More than 1,500 perirectal swab cultures and 552 environmental and equipment cultures were collected during the study period. Enterococcus faecium was the most frequent species isolated, being responsible for 71% of the positive cultures. Fifty infections were documented, with bloodstream infections (18, 36%) being the most frequent, followed by urinary tract infection (15, 30%). An educational intervention was given to 136 healthcare workers (HCWs), and a questionnaire regarding vancomycin-resistant enterococcus (VRE) transmission was also performed pre- and post-intervention. Overall, 858 opportunities of patient care were evaluated. The compliance with contact precautions did not improve; however, in general, the proportion of correct answers regarding VRE increased significantly when comparing pre- and post-intervention periods (p < 0.05). On the other hand, the proportion of environmental and equipment contaminated by VRE decreased significantly from pre- (23.2%) to post-intervention (8.2%) (p < 0.001) and was associated with a significant decrease in VRE infection from 7.7 to 1.9 when comparing the pre- and post-intervention periods. The use of vancomycin (defined daily dose [DDD]) did not change significantly over the study period (p = 0.970), and the use of teicoplanin increased (p < 0.001). Seventy-six percent of E. faecium belong to type and subtype A by pulsed-field gel electrophoresis (PFGE). This predominant type was found in the environment and caused colonization and infection. In conclusion, the present study showed that reduction of the proportion of environmental and equipment contamination was associated with a decrease of colonization and infection due to VRE, and that the strategy to control VRE dissemination should be based on local problems.     

DETECTION OF EUBACTERIA IN INTERSTITIAL CYSTITIS BY 16S rDNA AMPLIFICATION

Objective

To determine what role non-culturable microorganisms play in the etiology of interstitial cystitis (IC).

Materials and Methods

Thirty patients fulfilling NIH criteria for the diagnosis of interstitial cystitis and sixteen control patients with culture negative urine gave written informed consent and underwent bladder biopsy. Polymerase chain reaction (PCR) using two sets of universal primers for bacterial 16S rDNA was performed on urine from the cystoscope and on a cold cup bladder biopsy specimen. Of the PCR positive bladder biopsies, three patients with interstitial cystitis and three controls were randomly selected and cloned. Ten clones from each were sequenced and putative taxonomic assignments made.

Results

12/26 (46%) IC and 5/12 (42%) control urine specimens and 16/30 (53%) and 9/15 (60%) bladder biopsies were PCR positive, respectively. The bacterial populations in the two patient groups tested appeared to be different based upon analysis of the 16S rRNA sequences.

Conclusions

Both IC and control patients had non-culturable bacteria in their bladders. A random sampling of the two populations revealed that the bacterial populations are different, suggesting a possible link between one or more bacterial species and IC.     

Predicting the extent of prostate cancer using the combination of systematic biopsy and serum prostate-specific antigen in Japanese men

OBJECTIVE: To determine the utility of systematic biopsy alone or combined with an assay of serum prostate-specific antigen (PSA) level to predict the extent of prostate cancer in Japanese men. PATIENTS AND METHODS: Thirty-two patients who were diagnosed as having clinically organ-confined prostate cancer and who underwent prostatectomy were evaluated retrospectively for the results of systematic biopsy (percentage of positive biopsy cores and cancer location), serum PSA and the pathological stage of whole-mount sections of the prostatectomy specimens. RESULTS: The incidence of extraprostatic disease (pT3N0M0 or N+) in patients with >/= 8 ng/mL of serum PSA and cancer in bilateral lobes was significantly higher than in those with <8 ng/mL PSA and cancer in one lobe (83% vs 30%, P=0.020). In those with more than half the biopsy cores positive, extraprostatic disease was significantly more common than in those with less than half positive (93% vs 44%, P=0.0075); moreover, in patients with more than half the cores positive and >/= 8 ng/mL serum PSA, it was significantly more common than in those with less than half positive and <8 ng/mL of serum PSA (93% vs 27%, P=0.0021). However, the incidence of extraprostatic disease predicted by three variables (cancer location, percentage positive biopsy cores and serum PSA) was not significantly better than that predicted by two variables (percentage positive cores and serum PSA). CONCLUSIONS: The combination of systematic biopsy and serum PSA may be useful in predicting extraprostatic cancer. Patients with >/= 8 ng/mL serum PSA and more than half the biopsy cores positive could avoid a prostatectomy because there is a high probability that they have extraprostatic disease.