Detection of Philadelphia Chromosome in Chronic Neutrophilic Leukemia

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferativedisorder, differentiated from chronic myelogenous leukemia byseveral features. A case of CNL which was found by long-termculture to involve the Philadelphia chromosome is reported.     

Moment analysis of hepatic local disposition of allopurinol and oxipurinol: metabolism kinetics from allopurinol to oxipurinol in the rat isolated perfused liver

Abstract— Drug metabolism in the liver was examined by the rat isolated perfused liver using the single-pass bolus-input technique. The test compounds, allopurinol and its metabolite oxipurinol, were independently introduced into the liver from the portal vein, and the concentration profiles in the venous outflow were monitored and kinetically analysed by moment theory. The recovery ratios of allopurinol and oxipurinol after the individual administration of each drug were estimated to be 0·17 (±0·08 s.d.) and 1·03 (± 0·02 s.d.), respectively. The outflow recovery ratio of oxipurinol as the metabolite after allopurinol administration was estimated to be 0·80 (±0·07 s.d.). These results indicate that the combined outflow recovery of the precursor and the metabolite after allopurinol administration is almost 100% in the rat liver.     

Pathological effects of neoadjuvant hormonal therapy help predict progression of prostate cancer after radical prostatectomy

BACKGROUND: It is not clear whether pathological changes following neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy have any value as predictors of progression in prostate cancer. METHODS: We conducted a study of 100 patients with prostate cancer who underwent radical prostatectomy following NHT. We used the Japanese general rule as the criterion to assess the biochemical recurrence rate and pathological changes after NHT. RESULTS: In terms of preoperative risk factors, the probability of recurrence was significantly higher for patients with more than 20 ng/mL of pretreatment serum prostate-specific antigen (PSA) and/or a Gleason score of 7 or higher for biopsy specimens. We defined these pretreatment findings as high-risk factors. Among 65 patients with high-risk factors, patients with a post-NHT pathological effect of grade 3 according to the Japanese general rule showed no recurrence, whereas patients with a grade 0 had a poor prognosis. Patients with a PSA nadir 0.5 ng/mL or less tended to have a better prognosis. CONCLUSION: Despite preoperative high-risk factors, patients showing good pathological effects after NHT tend to have a favorable prognosis after radical prostatectomy. Therefore; assessment of the pathological effects of NHT using the Japanese general rule as the criterion proved to be useful for the prediction of biochemical recurrence.     

Emergence of basophils at sites of local allergic reactions using a skin vesicle test

Vesicular exudate, produced by the application of cantharides plaster over normal skin and sites of intradermal allergen injection, was examined for the presence of basophils and eosinophils in normal subjects and patients with bronchial asthma. In comparison with the normals, the asthmatic group demonstrated a high rate of basophil appearance in vesicular fluid derived from areas of untreated skin. Basophil appearance was even more prominent in vesicular fluid from skin injected intradermally with various allergens. Modest numbers of basophils appeared at skin sites injected with house dust, but relatively large numbers appeared in areas injected with Candida, ragweed or tuberculin extracts. Patients with severe, intractable asthma frequently demonstrated large numbers of basophils in vesicular exudates. Intradermal injections of anti-IgE caused the greatest number of basophils to appear in the vesicular fluid, The numbers of eosinophils migrating into such vesicular lesions were not statistically significant though their numbers were proportional to those of the basophils. A significant correlation was shown to exist between both basophil and eosinophil blood counts and the numbers of these cells appearing in cutaneous vesicular fluid. This study demonstrates that basophil leukocytes, together with eosinophils, migrate from blood into extravascular tissues at sites of allergic reaction—especially reaginic hypersensitivity. The skin vesicle technique described is simpler than the skin window technique and may be of use in detection of allergens and evaluation of allergic disease states.     

The role of dermal blood vessels in the pathogenesis of malignant atrophic papulosis (Degos'' disease)

The role of dermal blood vessels in the histopathogenesis of malignant atrophic papulosis has been investigated in two patients using enzyme histochemical, tissue fibrinolysis and electron-microscopic techniques. In the earliest papules the normal enzymatic reactions of the endothelium and fibrinolytic activity of affected blood vessels were markedly impaired or absent. The endothelial cells were swollen and showed minor degenerative changes, but no cytoplasmic inclusions suggestive of virus particles could be detected. The results of intradermal skin tests and lymphocyte transformation cultures did not suggest the presence of any immunological defect. It is suggested that the skin lesions of malignant atrophic papulosis could be secondary to the slow occlusion of deeper arterioles.     

Primary testicular leiomyosarcoma

We report a case of primary testicular leiomyosarcoma. A 76-year-old man, who complained of left scrotal swelling for 6 months, underwent radical orchiectomy. Microscopic examination revealed intratesticular leiomyosarcoma. The patient received no adjuvant therapy and at 12 months after surgery, there had been no recurrence. Primary leiomyosarcoma of the testis is extremely rare; this is the 9th case recorded worldwide.     

Effectiveness of percent free prostate specific antigen as a predictor of prostate cancer detection on repeat biopsy

BACKGROUND: The aim of this study was to identify predictors that can increase the accuracy of detecting prostate cancer on subsequent biopsies. METHODS: Between 1998 and 2003, a total of 235 men with prostate specific antigen (PSA) levels between 4.0 and 20 ng/mL underwent one or more systematic needle biopsies of the prostate. Of these men, 73 (31.1%) underwent one repeat biopsy and 26 (11.1%) underwent two or more repeat biopsies. We evaluated the results of prostate biopsies in relation to the morbidity of prostate cancer detected on repeat biopsies. RESULTS: Of the 73 men who underwent repeat biopsy, 16 (21.9%) had prostate cancer. Twenty-six men with one negative re-biopsy underwent two or more repeat biopsies, and five of these patients were found to have early stage prostate cancer. On repeat biopsy, there was a significant difference in percent free PSA between the cancer-detected group and the no-cancer-detected group (P < 0.01). A receiver operating characteristics (ROC) curve gave an optimal cut-off value for percent free PSA of 11%, demonstrating a significant difference in the cancer detection rate on repeat biopsy (P = 0.0009). Analysis of the data for re-biopsies showed that cancer-detected cases showed a raised PSA value and a simultaneously reduced percent free PSA (these differences were statistically significant). CONCLUSIONS: A low percent free PSA level increased the probability of a positive result in repeat biopsy. An increase in the accuracy of detecting cancer, especially on repeat biopsy, will promote the detection of more early stage prostate cancer.     

Development of a Colon Delivery Capsule and the Pharmacological Activity of Recombinant Human Granulocyte Colony-stimulating Factor (rhG-CSF) in Beagle Dogs

A peroral dosage form was examined to deliver recombinant human granulocyte colony-stimulating factor (rhG-CSF) to the colon in beagle dogs. A new gelatin capsule with its inside surface coated with ethylcellulose was prepared for this purpose. RhG-CSF was dissolved with propylene glycol and was filled in the capsule. Several kinds of ethylcellulose-gelatin capsules with an ethylcellulose layer of thickness 46 to 221 mm were used. The capsule was filled with propylene glycol solution containing fluorescein as an absorption marker, castor oil derivative and citric acid. The hardness of the capsule was tested after the gelatin layer was dissolved using a hardness tester and was dependent on the thickness of the ethylcellulose layer of the capsule. The time, T_max, at which plasma fluorescein level reaches its maximum following oral administration of ethylcellulose capsules was used as a parameter for the in-vivo disintegration time of the ethylcellulose capsule into the colon. Capsules of thickness 84 mm with a T_max of 4–6 h were filled with rhG-CSF solution containing fluorescein and were administered to dogs. After administration, blood samples were collected for 96 h and the blood total leucocyte (BTL) counts were measured as a pharmacological index of rhG-CSF. The maximum BTL count appeared at 10 h then gradually decreased and returned to its normal level at 48 h. These results suggest the usefulness of ethylcellulose capsules for the delivery of rhG-CSF to the colon and the possibility of a new oral rhG-CSF dosage form has been elucidated.