Erythroid crisis caused by parvovirus B19 transmitted via red blood cell transfusion

A 41-year-old man with hairy cell leukemia developed erythroid crisis after the transfusion of red cell concentrate. He was diagnosed with Parvovirus B19 infection based upon the presence of B19-specific IgM antibody and viral DNA in the sera. The repository sample from the corresponding red cell concentrate was negative for B19 antigen by red cell hemo-agglutination method, but was found to contain B19 virus DNA. Furthermore, a genomic PCR direct sequencing showed that B19 in both patient's sera and repository sample were identical. This is the first report directly demonstrating the transmission of B19 through B19 antigen-negative red cell concentrate transfusion. Further accumulation of the cases is warranted to estimate its incidence and to reconsider the screening methods of blood products.     

Hepatic natural killer and natural killer T cells markedly decreased in two cases of drug-induced fulminant hepatic failure rescued by living donor liver transplantation

The human liver contains significant numbers of innate immune cells, such as natural killer (NK) cells and natural killer T (NKT) cells, which express both T-cell receptors and NK-cell receptors simultaneously. It has been suggested that the innate immune system plays a crucial role in the liver. In this report, the distribution of NK and NKT cells in the liver and peripheral blood of two patients with drug-induced fulminant hepatic failure (FHF) who had undergone living donor liver transplantation was examined. In both the liver and peripheral blood, the proportions of NK and NKT cells markedly decreased compared with those in healthy donors. It was also revealed that, unlike murine NKT cells, human CD56(+) T cells and CD57(+) T cells did not constitutively express CD28, which is one of the important costimulatory molecules on T cells. Additionally, the residual CD56(+) T cells and CD57(+) T cells in the patients expressed more CD28 than in controls. This result suggests that NKT cells might be more activated in FHF. Although the accumulation of further cases is required, it is suggested that both NK and NKT cells might be involved in hepatic injury in FHF.     

Accelerated reaction by loop-mediated isothermal amplification using loop primers

Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method that amplifies DNA with high specificity, efficiency and rapidity under isothermal conditions using a set of four specially designed primers and a DNA polymerase with strand displacement activity. We have developed a method that accelerates the LAMP reaction by using additional primers, termed loop primers. Loop primers hybridize to the stem-loops, except for the loops that are hybridized by the inner primers, and prime strand displacement DNA synthesis. Although both inner and loop primers react via the loops, they do so by different mechanisms. The LAMP method presented here uses loop primers to achieve reaction times of less than half that of the original LAMP method. Since the total time of analysis including detection is less than 1h, this new method should facilitate genetic analysis, including genetic diagnosis in the clinical laboratory.     

Recurrent cellulitis due to Helicobacter cinaedi after chemotherapy for malignant lymphoma

A 62-year-old man with diffuse large B-cell lymphoma received five courses of R-CHOP chemotherapy. The patient developed cellulitis in the bilateral lower extremities without fever, and blood culture yielded Helicobacter cinaedi after five-day culture. Although the response to tazobactam/piperacillin (TAZ/PIPC) was prompt, cellulitis recurred immediately after discontinuation of the drug. Even after two months of treatment with PIPC plus amikacin followed by amoxicillin, it recurred again soon after stopping the antibiotics. H. cinaedi reportedly causes bacteremia and cellulitis in immunocompromised patients mostly in patients with acquired immunodeficiency syndrome. Only sporadic cases have been reported in association with hematological malignancies. Physicians should be aware of H. cinaedi as one of the causative pathogens of bacteremia and cellulitis in patients with hematological malignancies. Longer incubation period of blood culture is needed to detect the microbe and long-term use of antimicrobials is required to prevent recurrent cellulitis.     

Post-transplant consolidation therapy using thalidomide alone for the patients with multiple myeloma: a feasibility study in Japanese population

In order to test for improved survival following autologous transplantation (ASCT), we conducted a prospective clinical trial of post-ASCT thalidomide therapy in Japanese patients with multiple myeloma (MM). Twenty-five newly diagnosed patients received double or single ASCT with high-dose melphalan (200?mg/m²). Two months after stem cell infusion, if the patients failed to achieve a near-complete response, thalidomide was administered at 200?mg/day until disease progression or occurrence of intolerable adverse events. Seventeen patients were in partial response or minimal response after ASCT and received thalidomide alone. Their median progression-free survival (PFS) from ASCT was 17.4?months, and the median overall survival (OS) was 42.9?months. Some patients with normal karyotype experienced durable disease stabilization for over 5?years. Five patients who exhibited high-risk chromosomal changes such as t(4;14) or deletion of chromosome 13 or 17 showed very short PFS and OS compared with those who did not. Observed grade 3 or 4 toxicities included infection in three patients, hematological toxicities in three, and gastrointestinal toxicities in two, but there was no grade 3 or higher peripheral neuropathy, probably due to appropriate dose modifications. This long-term prospective study is the first to demonstrate the feasibility of post-ASCT thalidomide therapy in Japanese patients with MM.     

Prediction of Effect of Interferon on Chronic Hepatitis C

Clinical, pathological, and virological analysisincluding hypervariable region-1 of hepatitis C virus(HCV) was performed to predict the effect of interferon(IFN) on 41 patients with chronic hepatitis type C. The low virus load, low frequency ofthe mutation in the hypervariable region-1 as the changeof amino acid and high level of serum aminotransferasemake one estimate the good effect of IFN on patients with HCV. Mutation in the hypervariableregion-1 of HCV measured by fast assay fluorescencesingle-stranded conformational polymorphism was morefrequent in nonresponders to IFN than responders. Themost frequently mutated position was amino acidnumber 406. This indicates that the specific mutationsite might affect the response of IFN.     

Laparoscopic cholecystectomy in gallstone patients with acute cholecystitis

It remains controversial whether patients with gallstones with acute cholecystitis should be operated on early, or whether surgery should be delayed until the acute phase subsides. To help resolve this question, we retrospectively studied 109 patients with acute cholecystitis, 56 of whom underwent laparoscopic cholecystectomy after acute cholecystitis had subsided (delayed group) and 53 of whom underwent early laparoscopic cholecystectomy—within 7 days after admission (early group). On admission, the inflammatory findings in the two groups were very similar; however, at operation, the inflammatory findings were alleviated in the delayed group, while they remained unchanged in the early group. The mean operative time for the two groups was very similar. As for intraoperative complications, there was no conversion to laparotomy in either group, and there were no major complications in either group. The total hospital stay was 37.7 ± 14.4 days for the delayed group and 12.7 ± 2.0 days for the early group, showing a highly significant difference (P < 0.001). Early laparoscopic cholecystectomy seems to be better than delayed treatment for patients with gallstones with acute cholecystitis. Received: April 27, 1998/Accepted: November 27, 1998     

The role of laparoscopic US and laparoscopic US-guided aspiration biopsy in the diagnosis of multicentric hepatocellular carcinoma.

BACKGROUND: Detection of small hepatocellular carcinomas has become possible with improvements in various diagnostic imaging techniques. However, intraoperative US can detect lesions not visualized by any preoperative imaging study in which case it is difficult to determine whether the lesion is a hepatocellular carcinoma. METHODS: Nodular lesions detected by laparoscopic US in 186 patients with hepatocellular carcinoma were examined and we evaluated the diagnostic ability of laparoscopic US to detect multicentric hepatocellular carcinoma. RESULTS: One hundred thirty-four new nodular lesions were detected by laparoscopic US in 64 (34.4%) of 186 patients. Aspiration biopsy under laparoscopic US guidance was performed on the 134 nodules, and 28 nodules in 23 (12.4%) of the 186 patients were histologically diagnosed as hepatocellular carcinoma. Of these 23 patients, 18 had been diagnosed with solitary hepatocellular carcinoma before laparoscopic US. One hundred six of the newly detected lesions were initially diagnosed as noncarcinomatous nodules, but the diagnosis of 10 of these lesions was changed to hepatocellular carcinoma during follow-up that was as long as 96 months. CONCLUSIONS: Laparoscopic US is useful in the initial diagnosis of hepatocellular carcinoma and impacts treatment selection by more accurately defining the presence of multicentric hepatocellular carcinomas.     

Dietary orotic acid enhances the incidence of {gamma}-glutamyltransferase positive foci in rat liver induced by chemical carcinogens

Feeding male Fischer F-344 rats for 5 weeks a diet containing1% orotic acid, a precursor for pyrimidine nucleotide biosynthesis,resulted in an increased incidence of -glutamyltrans-ferase(EC 2.3.2.2 [EC] ) positive foci induced by chemical carcinogens including1,2-dimethylhydrazine, diethylnitrosamine, benzo[a]pyrene, andaflatoxin B₁. This unique effect of orotic acid can be accentuatedby supplying a liver cell proliferative stimulus. The enzymealtered hepatocytes have a higher labelling index (4.4%) comparedwith that of the hepatocytes in the surrounding liver (0.26%).The effect of orotic acid on the increased incidence of focicannot be attributed to either the induction of liver cell proliferationor the imposition of a preferential inhibitory effect on theproliferation of normal hepatocytes while permitting the carcinogen-modifiedhepatocytes to respond to an endogenous or exogenous liver cellproliferative stimulus and grow to form foci. Orotic acid alsodid not behave like some of the promoters of liver carcinogenesissuch as phenobarbital and polychlorinated biphenyls in thatit did not induce either the phase I or phase II componentsof hepatic drug metabolizing enzyme systems. Some of the possiblemechanisms by which orotic acid enhances the incidence of -glutamyltransferasepositive foci by carcinogens are discussed.     

Redifferentiation as a basis for remodeling of carcinogen-induced hepatocyte nodules to normal appearing liver

A system is described for the detailed study of the remodeling of hepatic nodules that appear regularly during liver carcinogenesis with chemicals. With the use of the resistant hepatocyte model and by focusing on the caudate lobe, it has been possible to label with [3H]thymidine all the hepatocytes in hepatocyte nodules without any significant degree of labeling of the surrounding hepatocytes. Through such a model, the persistence of the label, in relation to the organization and appearance of the hepatocytes in the nodules, has been followed for 26 weeks. Nodules do not "disappear" to any significant degree by regression or by replacement with hepatocytes from the surrounding liver. Rather, nodule hepatocytes undergo differentiation to an adult liver phenotype. Thus, differentiation ("redifferentiation") of a carcinogen-induced altered hepatocyte population is seen regularly during carcinogenesis despite the irreversible nature of some of the changes induced by a chemical carcinogen during initiation.