Solitary pulmonary granuloma caused by Mycobacterium avium-intracellulare complex.

OBJECTIVES: To analyse the clinical features and high resolution computed tomography (HRCT) findings of solitary pulmonary granulomas caused by the Mycobacterium avium-intracellulare (MAI) complex. METHODS: We retrospectively analysed a series of 73 consecutive patients with solitary pulmonary granuloma and negative sputum smear and culture results, in whom the diagnosis was established by histological examination of specimens obtained by partial pulmonary resection or lobectomy. We compared the clinical features and HRCT findings of the solitary pulmonary granulomas definitively diagnosed to be caused by the MAI complex with those of granulomas of other causes by univariate and multivariate analyses. RESULTS: In this study series of 24 patients with solitary pulmonary granuloma, the aetiological agent was established as being the MAI complex. According to the results of the multivariate analysis, 'female sex', 'pleural indentation' and 'lobulation' on the HRCT images were significantly associated with solitary pulmonary granuloma caused by the MAI complex. CONCLUSION: This study demonstrated several characteristics of solitary pulmonary granulomas caused by the MAI complex, and suggested that it might be a subtype of pulmonary MAI complex infection without the typical radiographic features of the infection.

Lafutidine can improve the quality of gastric ulcer healing in humans: a randomized, controlled, multicenter trial.

Improving the quality of ulcer healing (QOUH) is one of the valid methods of prevention of relapse of gastric ulcers. We investigated the effect of lafutidine on the QOUH of gastric ulcer compared with famotidine in a randomized, multi-centre controlled trial. Consecutive 80 patients with a gastric ulcer were randomly assigned to receive twice daily either lafutidine (10 mg) or famotidine (20 mg) for 12 weeks. Esophagogastroduodenoscopy was performed to examine the ulcer healing rate and rate of flat type ulcer scars using dye-contrast. The gastric ulcer healing rate was 92.1% in the lafutidine group (35/38) and 94.7% in the famotidine group (36/38). The rate of flat-type ulcer scars was significantly higher in the lafutidine group (68.4%, 26/38) than in the famotidine group (42.1%, 16/38) (P = 0.021). In conclusion, the present study demonstrated that lafutidine, as compared to famotidine, yields a significantly superior QOUH in patients with gastric ulcers in the clinical setting.

Diagnostic accuracy of CT-guided percutaneous cutting needle biopsy for thymic tumours.

AIM: To determine the diagnostic accuracy of computed tomography (CT)-guided percutaneous cutting needle biopsy (PCNB) for thymic tumours in accordance with the World Health Organization (WHO) classification. MATERIAL AND METHODS: We retrospectively analysed a consecutive series of 138 cases in which CT-guided PCNB had been performed for an anterior mediastinal tumour. Its sensitivity and specificity for thymic epithelial tumours were evaluated, and the concordance between the histopathological diagnosis according to the WHO classification of thymic tumours based on PCNB and the diagnosis is based on the surgical specimens was assessed by Kappa statistic. RESULTS: The diagnostic sensitivity and specificity of CT-guided PCNB for thymic tumours were 93.3 and 100%, respectively. The overall concordance between the diagnosis according to the WHO classification established by PCNB specimen and by the surgical specimen was 79.4% (weighted kappa=0.79). CONCLUSION: CT-guided PCNB is a reliable method of diagnosing thymic tumours, and there was good concordance for the WHO classification between the diagnosis based on CT-guided PCNB specimen and that based on the surgical specimen.

Endovascular therapy followed by stereotactic radiosurgery for cerebral arteriovenous malformations.

SUMMARY: Pre-radiosurgical embolization was carried out using cyanoacrylate in seven of 13 patients with cerebral arteriovenous malformations (AVMs) treated by stereotactic radiosurgery (SRS) with a linear accelerator (LINAC). The aim of embolization before SRS was the reduction of AVM volume and/or the elimination of vascular structures bearing an increased risk of haemorrhage. Staged-volume SRS was also performed in two patients because of residual irregular shaped nidus of AVMs even after the embolizations. Complete obliteration of the AVM nidus on angiogram was presented in five patients with embolizations (including one with staged-volume SRS) and in three of six patients with SRS alone, during follow-up periods after radiosurgery. No patients experienced haemorrhagic events after SRS. Although transient neurological symptoms were observed after embolizations in two patients, no permanent neurological deficits were presented in all patients with SRS. Pre-radiosurgical embolization may allow the effective influence on irradiation therapy in relatively large AVMs and promote more frequent obliteration in more small sized AVMs compared to those with SRS alone. However, further study must be needed to determine whether staged-volume SRS provides a high rate of AVM obliteration and its safeness.

Effects of ranitidine on quality of gastric ulcer healing compared with famotidine: a randomized, controlled, multicenter trial.

Ranitidine has been found to have anti-inflammatory action as well as antisecretory action in experimental models. However, there are no reports in human gastric ulcer. The aim of this study was to investigate the effects of ranitidine compared with those of famotidine on the quality of gastric ulcer healing. We randomly assigned 69 consecutive patients with gastric ulcers to ranitidine (n = 34) or famotidine (n = 35) for 12 weeks, with endoscopic assessment of the quality of gastric ulcer healing and histological assessment of gastric mucosa 12 weeks after treatment started. Ulcer healing rates of over 95% were very similar in the two groups. The rates of ulcer scars with a flat pattern (good-quality healing) were significantly higher in the ranitidine group than in the famotidine group (per protocol, 63.0% and 34.5%, p = 0.033). The neutrophil infiltration score in the body mucosa treated with famotidine, but not ranitidine, significantly increased after treatment. In contrast, the mononuclear cell infiltration score in the antral mucosa treated with ranitidine, but not in that treated with famotidine, had significantly decreased. In conclusion, initial therapy with ranitidine significantly improved the quality of gastric ulcer healing and the histological scores of gastric mucosa compared with famotidine.

Interrelation between HeLa-S3 cell transfection and hemolysis in red blood cell suspension using pulsed ultrasound of various duty cycles.

We have studied the in vitro transfection of a plasmid DNA with the lacZ gene to HeLa-S3 cells and hemolysis in a red blood cell (RBC) suspension under pulsed ultrasound with duty cycles gamma of 10, 20 and 30% using a digital sonifier at a frequency of 20 kHz and an intensity of 6.2 W/cm(2) on the surface of a horn tip. Cultured HeLa-S3 cells in suspension were exposed to pulsed ultrasound for an apparent exposure time t' from 0 to 60 s. HeLa-S3 viability decreased as a single exponential function of the total exposure time t = gammat' with a common time constant tau = 3.8 s for three duty cycles. Transfection was evaluated by counting the number of beta-galactosidase(beta-Gal)-positive cells relative to the total number of cells. Pulsed ultrasound provided an enhanced transfer of the beta-Gal plasmid to HeLa-S3 cells, 3.4-fold as compared with that in the case of the control. The optimal transfection efficiencies were 0.75, 0.80 and 0.74% near t = tau with gamma = 10, 20 and 30%, respectively. The number ratio of beta-Gal-positive cells to the surviving cells after exposure increased with t' according to a modified logistic equation. The degree of hemolysis also increased exponentially with t' at a time constant tau' = tau(0)/gamma for the RBC suspension in physiological saline at a hematocrit concentration of 0.5% with tau(0) = 0.9 s. Thus the total exposure time for the optimal transfection efficiency was tau, that is, nearly four times of tau(0). Hemolysis in the RBC suspension may be a useful model for determining optimal transfection by pulsed ultrasound of various duty cycles.

Value of virtual computed tomographic colonography for Crohn's colitis: comparison with endoscopy and barium enema.

BACKGROUND: Crohn's colitis, frequently accompanied by stenosis or narrowing, can be difficult to assess through conventional methods. We evaluated the usefulness of virtual computed tomographic colonography (CTC) for the detection of colonic lesions due to Crohn's disease. METHODS: Forty-two lesions in 33 patients with Crohn's disease were examined by CTC and barium enema (BE). Twenty-two patients also were examined by colonoscopy (CS). The visualization ability of CTC was compared with those of the other two methods. RESULTS: In the visualization of elevated lesions, there was no significant difference between CTC and BE (18 of 20, p = 0.487) or between CTC and CS (15 of 16, p = 0.99); however, ulcerative lesions were less often visualized by CTC. However, CTC enabled identification of serious lesions in the colon proximal to the stenosis in nine patients and was superior to BE and CS in terms of its ability to visualize the proximal site of the stenosis (p = 0.003). CONCLUSION: CTC is clinically useful for the evaluation of Crohn's colitis, especially those with stenotic lesions.

[Pure red cell aplasia developing during the course of primary macroglobulinemia associated with pseudochylothorax and IgA nephropathy].

A 74-year-old man who had undergone artificial pneumothorax therapy for pulmonary tuberculosis 40 years earlier was admitted because of blurred vision, headache, and numbness of the lower limbs in October 1997. He presented with anemia and leukocytopenia with monoclonal gammopathy of IgM (kappa). His bone marrow was diffusely infiltrated with small lymphocytes, plasmacytoid lymphocytes, and plasma cells expressing IgM, kappa surface immunoglobulin. On the basis of these findings, primary macroglobulinemia (PMG) was diagnosed. CT scan of the chest demonstrated pleural effusion of the right lung encapsulated in a thickened pleura, and pseudochylothorax was diagnosed from a specimen of chyliform fluid which contained numerous cholesterol crystals and was positive for Mycobacterium tuberculosis (MT) on PCR assay. The patient's condition was also complicated by chronic renal failure due to IgA nephropathy, which may have been a consequence of the tuberculosis, possibly due to an abnormal IgA-mediated immune response to MT. The patient gradually developed pure red cell aplasia during the course, probably due to an autoimmune mechanism. Later in the course, immunoglobulin gene analysis of the malignant cells of PMG showed that they were derived from antigenically selected cells. In the context of antigenic stimulation, the role of MT antigen in the pathogenesis of PMG was of interest in this patient.

Prevalence of Helicobacter pylori infection and correlation between severity of upper gastrointestinal lesions and H. pylori infection in Japanese patients with Crohn's disease.

BACKGROUND: The prevalence of Helicobacter pylori infection in Crohn's disease (CD) patients was investigated to determine whether the presence and severity of gastroduodenal lesions were related to H. pylori infection. METHODS: Infection rates were compared between CD group (n = 90) and the control group (n = 525). Correlations between endoscopically detected lesions and H. pylori positive rates were investigated. The relationship between drug therapy and the prevalence of H. pylori infection was also analyzed. RESULTS: H. pylori-positive rate of the 90 CD patients attending our clinic was 16.7%, significantly lower than the rate in healthy controls (40.2%) (P = 0.0001). The involvement of H. pylori infection in the gastroduodenal lesions of CD patients was also examined. The prevalence of gastroduodenal lesions in all CD patients was high, 92.2%. The lesions observed included ulcers, erosion, and "bamboo joint-like lesions" of the stomach, and ulcers, erosion, stenosis, and elevated lesions of the duodenum. None of these lesions were found to be related to H. pylori infection. However, H. pylori infection was found to exacerbate gastric ulcers (P = 0.036). The analysis of a possible relationship between a history of drug therapy and the low prevalence of H. pylori infection in CD patients showed that the prevalence of H. pylori infection was significantly lower in patients who had received antibiotics for 2 weeks or more (P = 0.002). CONCLUSIONS: The results suggest that H. pylori infection is essentially unrelated to the gastroduodenal lesions observed in CD. It seems likely, however, that H. pylori infection may exacerbate gastric ulcers and that H. pylori can be eradicated by prolonged use of antibiotics.

Left-side dominance for song discrimination in Bengalese finches (Lonchura striata var. domestica).

Male Bengalese finches are left-side dominant for the motor control of song in the sensorimotor nucleus (the high vocal center, or HVc) of the telencephalon. We examined whether perceptual discrimination of songs might also be lateralized in this species. Twelve male Bengalese finches were trained by operant conditioning to discriminate between a Bengalese finch song and a zebra finch song. Before training, the left HVc was lesioned in four birds and the right HVc was lesioned in four other birds. The remaining four birds were used as controls without surgery. Birds with a left HVc lesion required significantly more time to learn to discriminate between the two songs than did birds with a right HVc lesion or intact control birds. These results suggest that the left HVc is not only dominant for the motor control of song, but also for the perceptual discrimination of song.

Effect of the novel prostaglandin A1 derivative TEI-6363 on ROS17/2.8 cell differentiation in vitro.

The effect of TEI-6363 (5-[E-4-N,N-dimethylaminophenylmethylene]-4-hydroxy-2-[1-methyl imidazole-2-ilthio]-4-[4-phenylbutyl]-2-cyclopentenone), a chemically synthesized prostaglandin A1 derivative, on cell proliferation and osteoblastic differentiation was investigated concurrently. ROS17/2.8 cells (a rat osteosarcoma-derived cell line) were treated with TEI-6363 at two concentrations, 10(-7) and 10(-6) M, and viable cells were counted to assess cytotoxic effects and determine the growth curve. After 96 h of treatment, there was no evidence of any effect of TEI-6363 on cell viability at either concentration. However, a clear inhibitory effect on cell proliferation was observed after treatment with 10(-6) M TEI-6363 for 24 h or longer. A pulse-treatment experiment showed that TEI-6363 induced the inhibition of proliferating ROS17/2.8 cells 24 h after addition. The inhibition of proliferation was associated with G1-arrest demonstrated by flow cytometric analysis, and incorporation of [3H]thymidine by ROS17/2.8 cells was decreased. Osteoblastic differentiation (assessed on the basis of increased alkaline phosphatase activity and collagen synthesis) was induced by TEI-6363 treatment at 10(-6) M following G1-arrest and inhibition of cell proliferation. These results suggest that TEI-6363 arrested the cell cycle of ROS17/2.8 cells at the G1 phase and induced osteoblastic differentiation. These results did not appear to be dependent on a marked cytotoxic effect.

[Participation of pharmacists in the medical team at home].

This report reviews drug consultations at patients' home and collaboration of pharmacists with medical teams over 4 years. The participation of pharmacists is necessary for home care service, because of their pharmaceutical expertise and the demands from the medical team and patients at home.

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 1). Effects of 2-weeks daily administration of estradiol benzoate.

As part of a collaborative project to assess whether a 2-weeks administration period is sufficient to detect testicular toxicity of various compounds, male rats were subcutaneously administered 0, 5, 20, 50 or 100 micrograms/kg of estradiol benzoate (E2B), a known testicular toxicant, daily for 2 or 4 weeks. After 4-weeks, suppression of body weight gain, increase in the weight of the adrenal gland, and gross changes such as decrease in size of the prostate and seminal vesicles, and increase in size of the adrenal gland were observed in the 5, 20, 50 and 100 micrograms/kg groups. On histopathological examination, degeneration/necrosis of Pachytene spermatocytes, atrophy of Leydig cells, mature spermatid retention (Lee, et al., 1993) at stages IX, X and XI, and atrophy of ducts of the epididymides were also observed in the 5, 20, 50 and 100 micrograms/kg groups. After 2-weeks, the same changes were also observed with 20, 50 and 100 micrograms/kg, but not 5 micrograms/kg. These results indicate that the toxic effects of E2B are detectable by administration for 2 weeks at an appropriate dose level.

[High-dose chemotherapy with autologous peripheral blood stem cell transplantation support in a patient with breast cancer metastasis to bone marrow: immunocytochemical monitoring of cancer-cell contamination].

A 32-year-old woman who 1 year earlier underwent a right mastectomy for stage II breast cancer with the histology of invasive ductal carcinoma (scirrhus type) was admitted due to recurrent, metastatic breast cancer in January 1997. She presented multiple metastatic lesions in the skin, lymph nodes, bone, lungs, liver, and spleen, and her bone marrow was replaced almost entirely by tumor cells. The patient was sequentially treated with 5 courses of cyclophosphamide (CPA) and adriamycin (ADM) (CA); 2 courses of CPA, ADM, and 5-fluorouracil; 5 caurses of docetaxel hydrate; and 1 course of CA. After recovery of the normal bone marrow by standard-dose chemotherapies, peripheral blood stem cells (PBSC) were then collected after mobilization with G-CSF. The number of breast cancer cells in bone marrow and PBSC samples was determined by immunocytochemical staining with an anti-cytokeratin monoclonal antibody. The number of tumor cells in PBSC sample was within the level for non-metastatic breast cancer. Complete remission was obtained with high-dose chemotherapy consisting of CPA and Thio-TEPA, and supported by autologous PBSC transplantation.

Prostate specific antigen density for discriminating prostate cancer from benign prostatic hyperplasia in the gray zone of prostate-specific antigen.

Serum prostate specific antigen (PSA) is currently the best blood marker for prostate cancer. However, low specificity for detection of prostate cancer, especially in the gray zone of PSA, is a problem. We evaluated the clinical significance of PSA density (PSAD) in gray zone PSA cases with conversion of serum PSA to a Stanford reference value. In a series of histologically confirmed 63 benign prostatic hyperplasia (BPH) patients and 234 prostate cancer patients, 36 BPH patients and 25 prostate cancer patients had gray zone PSA levels. Serum PSA was measured with the Markit-F or Markit-M PA assay. All data were converted to Stanford reference values. We used transabdominal ultrasound to determine prostate volume. PSAD was determined as the serum PSA/prostate volume ratio. The mean PSA values for BPH and prostate cancer were 6.42 +/- 1.80 and 7.80 +/- 2.15 ng/ml (p = 0.0116), respectively, and prostate volume was 33.4 +/- 14.1 ml and 17.1 +/- 8.2 ml, respectively (p < 0.0001). The mean PSAD for prostate cancer was 0.572 +/- 0.363 while that for BPH was 0.218 +/- 0.085 (p = 0.0001). Cut-off values with sensitivity > 90% were 0.218 for PSAD and 30 ml for prostate volume. At these cut-off values, specificity reached 56% for each marker. In discriminating prostate cancer from BPH in the gray zone of PSA, PSAD demonstrated better performance than PSA.

Comparative study of assays for prostate-specific antigen molecular forms.

BACKGROUND: The detection of prostate-specific antigen (PSA) molecular forms such as free PSA and PSA-ACT and the use of PSA molecular ratios, especially the percentage of free to total PSA, have been reported to improve the diagnostic accuracy of prostate cancer in the patients with slightly elevated serum PSA values. However, the correlation among the values of serum free PSA or PSA-ACT obtained in various assays remains unclear. METHODS: Serum free PSA and PSA-ACT values were detected with the following assays: Hybritech, DPC, EIKEN, Abbott, Roche and Can-Ag for free PSA and Dainippon, Chugai, EIKEN and Bayer for PSA-ACT. The data obtained with each assay were compared with Hybritech (free PSA) and Dainippon (PSA-ACT) as standards. RESULTS: The free PSA data obtained with the Hybritech, EIKEN, Abbott and Can-Ag kits were similar. The values obtained with the DPC and Roche kits showed a linear regression of y = ax + b with those obtained with the Hybritech, with a b value of zero and an a value of 1.20 and 1.57, respectively. The serum PSA-ACT values detected with the Dainippon and Chugai kits were identical. The equation for converting the data obtained with the EIKEN kits to the Dainippon value was 0.7636 x (EIKEN) + 0.1381. CONCLUSIONS: Serum free PSA and PSA-ACT values obtained with various assays were not necessarily the same. Some kits for the assay of free PSA and PSA-ACT gave the same serum values. The free PSA values obtained with the other kits could be converted using appropriate equations. The gamma-Sm values showed wide variations and were not considered suitable as a measurement of free PSA.

[Splenic lymphoma with villous lymphocytes expressing chromosomal abnormalities].

An 88-year-old Japanese woman with splenomegaly, but without lymphadenopathy, was admitted because of epigastric distress. Laboratory data disclosed an RBC of 310 x 10(4)/microliter, Hb of 10.1 g/dl, Ht of 30.6%, Plt count of 9.8 x 10(4)/microliter, and WBC of 4,470/microliter with 38% abnormal lymphocytes. Peripheral blood films revealed lymphocytes with thin, short cytoplasmic villi, condensed nuclear chromatin, and small nucleoli. The lymphocytes stained negative for tartrate-resistant acid phosphatase. Also, immunophenotyping was positive for expression of the cell surface markers CD19, CD20, IgG, kappa and HLA-DR, but not for CD5, CD10, CD11c, CD23, CD25, CD38, or CD103 antigens. Chromosomal analysis of peripheral blood cells disclosed the 46, XX, del(7), (q32) aberration. A splenectomy was performed simultaneously with partial colon resection because of a mucinous carcinoma found in the transverse colon. Histologic examination of resected spleen tissues revealed a distinctive pattern of white pulp infiltration by lymphoma cells. The histologic findings and clinical data were consistent with the features of splenic lymphoma with circulating villous lymphocytes. Our patient exhibited a relatively benign clinical course, and was being followed on an outpatient basis with no additional therapy.

[Non-Hodgkin's lymphoma complicated by recurrent intractable generalized herpes zoster responsive to long-term acyclovir therapy].

A 34-year-old male with a history of chickenpox developed primary abdominal non-Hodgkin's lymphoma (diagnosed in August 1995). Treatment with cyclophosphamide, doxorubicin, vincristine, and prednisolone achieved a partial remission. In July 1996, the disease recurred, and the patient received chemotherapy with carboplatine, etoposide, mitoxantrone, and prednisolone, but no response was noted. Involvement of the central nervous system and meninges was diagnosed on September 12, 1997. Blast cells were detected in the peripheral blood on September 26. Based on these findings, he was diagnosed as having leukemia. On September 27, painless vesicles developed on the left gluteal region. On October 13, the patient was hospitalized because the vesicles had spread over his entire body. Pathologic examination of the roofs of the blisters showed masses of inclusion bodies. Based on this, a diagnosis of varicella-zoster infection was made. Treatment with acyclovir (750 mg/day) for seven days failed to form crusts. New vesicles developed after the drug was discontinued, but crusts formed after acyclovir therapy was resumed. He died of interstitial pneumonia on December 21. Autopsy could not be performed. Histopathologic examination of pulmonary tissue obtained by necropsy did not reveal the presence of inclusion bodies characteristic of herpes simplex or varicella-zoster infection. Varicella-zoster virus (VZV) antigen was negative by an immunochemical staining method using monoclonal antibodies against VZV. Continuous long-term administration of acyclovir has been reported to be effective for non-Hodgkin's lymphoma complicated by recurrent intractable herpes zoster.

Determination of reference values for total PSA, F/T and PSAD according to prostatic volume in japanese prostate cancer patients with slightly elevated serum PSA levels.

BACKGROUND: For screening prostate cancer (CAP) using prostate-specific antigen (PSA), the indications of biopsies for patients showing slightly elevated PSA values are still controversial. Furthermore, the dependence of total PSA, free-to-total PSA ratio (F/T) and PSA density (PSAD) on prostatic volume in gray zone cases is unclear. METHODS: By analyzing 1913 patients with a serum total PSA ranging from 2.0 to 20 ng/ml, we evaluated the correlation between total PSA and age or prostatic volume and positive predictive value (PPV) in each range for total PSA, age and prostatic volume. Then suitable reference values for total PSA, F/T and PSAD were decided according to prostatic volume. RESULTS: There was no close correlation between PSA and age or volume. The PPV was high in the group with a prostatic volume of 10-30 ml. Prostatic volume was categorized into three groups, <20, 20-40 and > or =40 ml, and reference values for obtaining a sensitivity of 90% were proposed. The reference values of total PSA and PSAD were lowered and that of F/T was raised with increase in prostatic volume. The specificity was very low for the > or =40 ml group. The highest specificity of 36% in PSAD was obtained for the <20 ml group. CONCLUSION: The reference values for total PSA, F/T and PSAD must be changed according to prostatic volume in order to maintain a sufficient diagnostic sensitivity of CAP. Of these parameters, PSAD showed a high specificity in the group with a prostatic volume of <40 ml.