Clinical significance of elevated serum interferon- inducible protein-10 levels in hepatitis C virus carriers with persistently normal serum transaminase levels.

The aim of this study was to assess the immunological profile in hepatitis C virus carriers with persistently normal serum transaminase levels. Forty-two serum HCV RNA positive patients with persistently normal serum transaminase levels (22 natural 'asymptomatic HCV carriers' and 20 biochemical responders to IFN therapy) and 23 complete responders to IFN therapy were enrolled. The HCV genotypes and serum HCV RNA levels were determined before IFN therapy in treatment responders, and at entry in the others. The serum levels of IFN-inducible protein-10 (IP-10) (a protein mainly induced by IFN-gamma), interleukin (IL)-10, and IL-4 were measured in all patients while the serum transaminase levels were normal. The serum transaminase levels and platelet counts were then monitored for the next 4 years and the changes in liver fibrosis were assessed. The serum levels of IP-10 in infected and biochemically normal patients were significantly higher than the levels in complete responders to therapy, whereas the serum levels of IL-10 and IL-4 did not vary significantly among the different groups. During the 4-year follow-up period, 10/20 (50%) biochemical responders and 12/22 (55%) asymptomatic carriers had an elevation of the serum transaminase levels. A significant (P=0.0370) increase in platelet count after 4 years and improvement in liver fibrosis were noted in treatment responders but not in infected patients. The weak but significant residual immune response as reflected by the increased serum IP-10 level may underlie the outcome of HCV carriers with persistently normal serum transaminase levels.

Gastric pneumatosis associated with duodenal stenosis and malrotation.

Pneumatosis intestinalis, which is linear or cystic gas within the bowel wall, is usually found in premature babies in association with necrotizing enterocolitis. Gastric pneumatosis defined as intramural gas of the stomach is a rare sign during infancy. We report an infant with Down's syndrome and a duodenal web with obvious gastric pneumatosis.

Retreatment with interferon-alpha at dosages or period increased by 1.3 times is effective for treatment for transient responders and non-responders in chronic hepatitis C patients.

The objectives of retreatment with interferon (IFN) in chronic hepatitis C (CH-C) patients are sustained response and a reduction in the risk of hepatocellular carcinoma (HCC). However, it is still unclear, as to which patients are candidates for retreatment with IFN. Eighteen transient responders (TRs) and 15 non-responders (NRs) to IFN therapy in CH-C received retreatment with IFNalpha. Of the 18 TRs, five showed sustained disappearance of hepatitis C virus, two showed sustained biochemical response, 10 continued as TR and one was a NR. Of the 15 NRs, six showed a TR while nine continued as NRs. Responsive cases, which included the virologically or biochemically sustained and transient responders, received either a dose of IFN 1.3 times greater or were treated for a period of 1.3 times longer in the retreatment than the original treatment. We submit that IFN treatment consisting of either a time period or a dosage 1.3 times those of the original IFN administration may be beneficial in the case of TR and NR in chronic hepatitis C patients.

Diagnosis of carotid artery atheroma by magnetic resonance imaging.

Atheroma appears as a very low signal intensity area on 2-dimensional time-of-flight (TOF) magnetic resonance (MR) images, and its components have various signal intensities on spin-echo (SE) images. The present study investigated atheroma of the carotid arteries in 37 subjects with risk factors (63+/-10 years of age; 19 men) by magnetic resonance imaging (MRI). On 2-dimensional (2D) TOF images, the carotid arteries were clearly demonstrated in all cases and atheroma was detected in 23 patients. The most common location of atheroma was at the origin of the internal carotid artery. There was vascular remodeling in all patients with atheroma. 2D-TOF images showed 97% agreement with ultrasonography. SE images clearly demonstrated atheroma in all 23 patients with atheroma. All patients with atheroma showing high signal intensity on T1-weighted images had hyperlipidemia. These findings indicate that the 2D-TOF imaging method is useful for detecting atheroma and SE-images are useful for its characterization.

[Comparison of positivity rates for antibodies against measles, rubella, chickenpox and mumps by assays].

Our previous study found mistakes by some doctors in the choice of an assay for determining antibodies in Japan. To compare the positivity rates for antibodies by assays, we measured the antibodies of measles, rubella, chickenpox and mumps from the same sera using such methods as the EIA, HI and CF assays. The subjects were 175 nursing students. The positivity rates for measles, chickenpox and mumps by the EIA assay were 96.6%, 93.7%, and 83.3%, respectively. Those for rubella by the HI and CF assays were 92.0% and 10.1%. The sensitivity rates for measles, chickenpox and mumps by the HI and CF assays, based on the results of the EIA assay, were 75.1%, 102.4% and 69.2% in the HI assay, and 20.6%, 38.7% and 8.0% in the CF assay, respectively. Our previous study showed that the sensitivity of the HI assay for rubella antibody is same as that of the EIA assay in Japan. Currently an EIA assay should be chosen for these antibodies and the HI assay or IAHA assay should be possible selections for rubella and chickenpox. However, international comparison of the cutoff titers for these antibodies should be considered.

[Measures against hospital infection for students in medical schools in Japan--a survey by questionnaires].

We sent questionnaires to 80 medical schools in Japan to know what the problems in hospital infection for students in medical schools are. Seventy-one % were sent back to us. There have been hospital infection from patients to students in 12% of the medical schools, included 3 cases each of measles, chickenpox and mumps, 2 cases each of rubella, hepatitis B and tuberculosis. Fourteen % of the medical schools had reports about the past history of infection and vaccination from students, 70% of the schools determined their antibodies and the 28% did nothing. Ninety-three%, 25%, 23%, 18%, and 15%, of the schools determined antibodies for hepatitis B, rubella, measles, chickenpox and mumps, respectively. Some assays of the measurement were low in sensitivity. The cost for the determination was fully paid in 48% of the schools, but only partially supported in 35%. Tuberculin reaction was performed in 40% of the schools and then BCG was done in 57%. Vaccination was recommended in 40% of the schools. The cost of vaccination was all paid in 38% of them, which was only for hepatitis B, and partially supported in 15% of them.

[Comparison of cost and benefits of each model for rubella immunization in Japan].

MMR (measles-mumps-rubella) immunization in Japan was suspended in 1993 due to the high incidence of mumps meningitis as a complication. As a result, immunization coverage for rubella still remains at the 50-60% level in Japan. One way to increase the coverage rate is to increase the frequency of immunization. We calculated the predicted positivity rate of the antibody and cost and the benefits is three models of double vaccination, i.e., vaccination twice. The first model consists of simply two identical vaccinations. The second model consists of two vaccinations with mass vaccination at school for the second immunization. The third model consists of two vaccinations with screening of the urinary antibody for rubella in the second immunization. To calculate the predicted values we used coefficients from Ibara City. The predicted positivity rates and cost increases ranged from 60% to 90% and from 7.3 billion to 12.8 billion yen from the first to third models, respectively. Screening for the urinary antibody should be much cheaper than the presumed price because more than a million subjects will be screened. Since it would cost less than half the price, the third model should be best for the positivity rate of the antibody and cost and benefits. Therefore, we think that third model is the best correction until MMR immunization can be reintroduced.

[Accumulative vaccination rate of rubella and positive antibody rate in an area of Japan--future problems with rubella].

The rubella vaccination rate remarkably decreased in Japan after a revised vaccination law was passed in 1994, as a result of which individual vaccination replaced mass vaccination at each school. We investigated the rubella antibody of 887 students and the accumulative rubella vaccination rate in an area of Okayama. The vaccination rate in Ibara, where children were inoculated individually, was 22.8%. In contrast, in Yoshii, where the vaccination was done as mass at each school, the rate was 89.8%. After 2003, when the transit period of the law ends, children 12-90 months of age will be the subjects for rubella vaccine. We presume that the vaccination rate in the future will reach 40-50% through accumulative vaccination. Such a rate of vaccination cannot prevent rubella epidemics and congenital rubella syndrome. In addition, an individual's rubella vaccination is generally done once during lifetime. We doubt whether the immune response induced by a vaccine can be maintained for more than 20 years without boosting. We think that a second vaccination is necessary for at least young girls, and this should be performed as mass at each school.

Serum insulin-like growth factor-I (IGF-I) in normal Japanese adults.

To evaluate surgical and medical treatment of GH-producing pituitary tumors and GH supplement to GH-deficient patients, we determined the reference values for serum IGF-I in Japanese adults. The serum IGF-I concentration in 454 apparently healthy subjects (246 men aged 21-70 years and 208 women aged 21-72 years) was measured with a commercial RIA kit after acid-ethanol extraction. The concentration of serum IGF-I decreased with age in both sexes. The IGF-I in females was significantly higher than that in males in the group aged 21-30 years and lower in the group aged 61-72 years. We conclude that an age- or sex-related standard is necessary for comparing IGF-I values in patients.

An analysis of bacteraemia in a university hospital in Japan over a 10-year period.

Details of positive blood cultures obtained from 357 inpatients attending the Toyama University Hospital were collected over a 10-year period in order to document changes in microbiological and clinical features of bacteraemia. Fifty-one per cent of patients were over 60 years old, 48% had intravascular catheters in-situ, and 17% had had surgical procedures within 30 days prior to the isolation of organisms from the blood. The proportion of underlying diseases other than malignancies increased over the 10-year period (42-60%, P < 0.05). Patients from surgical departments other than the Academic Department of Surgery increased over the study period (16-55%, P < 0.05). Staphylococcus aureus bacteraemia increased significantly (29 to 49%, P < 0.05) as did pseudomonas and anaerobic bacteraemia. Most bacteria showed no significant changes in their antibiotic sensitivity pattern over the 10 years. Clinical features in patients with bacteraemia varied with the infective organisms and the underlying disease. Mortality was high in patients with haematological malignancy, usually in association with Pseudomonas aeruginosa.

An analysis of intravenous hyperalimentation (IVH) catheter-related infection in a university hospital in Japan over a ten year period (1982-1991).

In order to follow changes in clinical characteristics of IVH catheter-related infections, 183 patients were analyzed in whom microorganisms had been isolated from the tips of IVH catheters over a ten year period (1982-1991) in our university hospital. In 183 patients, the male to female ratio was 2.4, the internal medicine departments (Int. Med. Depts.) to surgical departments (Surg. Depts.) ratio was 0.49, 58% of the patients were over 60 years old, 27% had surgical procedures within 30 days before isolation of organisms, and 44% died before discharge. Malignancies were the highest in number for underlying diseases. The same strains of microorganisms as tip cultures were isolated from blood in around 48% of cases in which blood cultures were employed. In the first 5 years (n = 71) and the latter 5 years (n = 112), the proportion of patients form the Int. Med. Depts. increased from 21 to 40% (p < 0.01), and the proportion of Gram positive bacteria from 44 to 64% (p < 0.01). Their antibiotic sensitivity was, as a whole, slightly lower in the latter 5 years. Among Gram-negative bacteria, P. aeruginosa has shown a tendency to increase (11 to 35%). Clinical features were different depending on the kinds of organisms or types of underlying diseases. Measures against IVH catheter-related infections are discussed.

Fine needle aspiration cytology of clear cell sarcoma. Report of a case with immunocytochemical, immunohistochemical and ultrastructural studies.

Cytologic findings of clear cell sarcoma obtained by fine needle aspiration (FNA) of a tumor are described. The tumor probably originated in the retroperitoneal tissue, and the diagnosis was confirmed histologically by open biopsy. Percutaneous needle aspirates of the intraabdominal tumor and touch preparations obtained from the open biopsy specimen revealed numerous atypical cells with an extremely hyperchromatic nucleus, prominent nucleoli and clear cytoplasm. The cytoplasm was rich in glycogen. The immunocytochemical technique demonstrated S-100 protein and neuron-specific enolase in the cytoplasm, both of which were exhibited also in the histologic specimen. Clear cell sarcoma is a rare tumor of soft tissue, and to our knowledge, detailed cytologic appearances of this tumor obtained by FNA have not been reported. In addition, the present tumor was unique in location. It is possible to diagnose clear cell sarcoma accurately on an FNA cytologic specimen if the periodic acid-Schiff stain and immunocytochemical technique are utilized in addition to the routine Papanicolaou method.

Gastric mucosal microcirculation measured by laser Doppler velocimetry in patients with gastric ulcer.

In order to evaluate the role of gastric mucosal blood flow in patients with gastric ulcer, we applied laser Doppler velocimetry to the human gastric mucosa to study the regional microcirculatory mechanism. We measured 5 spots each in 34 control stomachs, and in 47 patients with gastric ulcer at the angle and antrum of the stomach, 2 additional spots around the ulcer. During the healing process, mucosal blood flow around the gastric ulcer increased as compared to that of the active or scarring stages. Compared with that of surrounding mucosa, mucosal blood flow around the gastric ulcer increased significantly during healing stage. Mucosal blood flow at the ulcer margin in healing stage (H1 stage) was 52% more than in the active stage. The increase in mucosal blood flow in the ulcer margin during healing stages (H1 and H2 stage) was 45% in cases with initial ulcer and 22% in cases with recurrent ulcer. It was concluded that increased blood flow in the ulcer margin during healing stages promotes healing of the ulcer. Laser Doppler velocimetry is useful in measuring mucosal blood flow sequentially in various stages of gastric ulcer, and also provides effective evaluation of medical treatment.

[Evaluation of proposed criteria of disk susceptibility testing for tosufloxacin and lomefloxacin in NCCLS guidelines and WHO standards].

Disk diffusion zone diameter breakpoint criteria for Tosufloxacin and Lomefloxacin were tentatively established by correlating MICs with 1-, 5- and 10 micrograms of Tosufloxacin disk inhibitory zone diameters and with 10 micrograms of Lomefloxacin disk of those to 418 clinical isolates representing 32 species. We recommend 5 micrograms disks for Tosufloxacin with the following breakpoints: Susceptible (MIC, less than or equal to 0.5 microgram/ml), greater than or equal to 22 mm; intermediate, 17 to 21 mm; and resistant (MIC, greater than or equal to 2.0 micrograms/ml), less than or equal to 16 mm. We recommend 10 micrograms disks for Lomefloxacin with the following breakpoints: Susceptible (MIC, less than or equal to 2.0 micrograms/ml), greater than or equal to 21 mm; intermediate, 16 to 20 mm; and resistant (MIC, greater than or equal to 8.0 micrograms/ml), less than or equal to 15 mm. Using these criteria for Tosufloxacin and Lomefloxacin, the occurrence rate of major errors in judging susceptibility and resistance was 0.48%.

A case of spontaneous mesenteric hematoma and a review of 17 cases in Japan.

A 47 year-old male was admitted to Miyazaki Medical college Hospital for further evaluation of an abdominal mass in the left upper quadrant. Abdominal ultrasound (US) and abdominal computed tomography (CT) showed two cystic masses in the mesenterium, which were suspected to be hematomas, but were not related to the pancreas, kidney or spleen. Superior mesenteric artery angiography and gallium (GA)-scintigraphy showed no definite findings. The patient underwent laparotomy on a suspicion of mesenteric hematoma. Two 4 x 3 x 3 cm soft tumors were found in the small intestinal mesenterium. These masses were histopathologically hematomas and surrounded by thick collagenous granulation tissue. The patient had no recent history of abdominal trauma, taking drugs capable of producing bleeding tendency, and/or vascular disease. The case was diagnosed as spontaneous mesenteric hematoma.

[Susceptibility of clinically isolated bacterial strains to imipenem/cilastatin sodium].

In vitro antibacterial activities of imipenem/cilastatin sodium (imipenem) and other beta-lactams against clinically isolated 353 bacterial strains were investigated. The results obtained in this study are summarized as follows: 1. Imipenem (IPM) showed potent antibacterial activities against Gram-positive cocci such as Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus agalactiae. 2. IPM had inferior or equivalent antibacterial activities to beta-lactams against clinically isolated Enterobacteriaceae, that is, Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, Serratia marcescens, Enterobacter cloacae, Enterobacter aerogenes and Proteus spp. 3. IPM showed potent antibacterial activities against clinically isolated Pseudomonas aeruginosa, Acinetobacter anitratus but not against Xanthomonas maltophilia.

[Susceptibility of clinically isolated strains to aztreonam].

In vitro antibacterial activities of aztreonam (AZT) and cephems against clinically isolated 334 strains were investigated. The results obtained in the study are summarized as follows: 1. AZT showed excellent antibacterial activities against clinically isolated 334 strains. 2. AZT showed potent activities against Escherichia coli, Klebsiella pneumoniae, Proteus spp., Enterobacter aerogenes and Citrobacter freundii. 3. Antibacterial activities of AZT were superior against Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa to those of cephems.

Immunological and clinical effects of interferon-gamma on Crohn's disease.

Five patients with Crohn's disease (CD) confined to the small intestine were studied to determine whether intravenous administration of interferon (IFN)-gamma to normalize immunological imbalance produces clinical improvement. A daily dose of 12 million IU of IFN-gamma was intravenously infused for four weeks. Laboratory data, immunological responses, clinical and radiologic findings were evaluated after administration. Laboratory data showed no significant change after treatment. Immunological studies also failed to demonstrate any significant change except for a significant increase of natural killer (NK) cell activity after IFN-gamma infusion. Clinical assessment by Crohn's disease activity index as well as radiologic findings disclosed no definite improvement. This study suggests that enhancement of NK cell activity or augmentation of immunological imbalance induced by IFN-gamma does not play an important role in the pathogenesis of CD.

A case of generalized juvenile gastrointestinal polyposis associated with gastric carcinoma.

A case of generalized juvenile gastrointestinal polyposis associated with gastric adenocarcinoma is described. A 31-year-old male patient developed polyposis of the stomach complicated by gastric carcinoma and multiple polyps in the colon. Polyps of the stomach and colon were pathologically consistent with juvenile polyp, but adenomatous changes were also present in a very small percentage of the juvenile polyps. This case strongly suggests the possibility of carcinoma developing in patients with generalized juvenile gastrointestinal polyposis.