Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein for patients with chronic hepatitis B and C: a comparative study.

We compared Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP) levels between patients with chronic hepatitis B (n=249) and chronic hepatitis C (n=386) based on the degree of liver fibrosis. We examined WFA+ -M2BP levels in patients with F4 (cirrhosis), F3 or more (advanced fibrosis) and F2 or more (significant fibrosis) in the two groups. We further examined the relationship between five fibrosis markers and the degree of fibrosis. The WFA+ -M2BP values ranged from 0.25 cut-off index (COI) to 12.9 COI in patients with hepatitis B and 0.34-20.0 COI in patients with hepatitis C (P<.0001). The median WFA+ -M2BP values in F4 in the two groups were 2.83 COI in patients with hepatitis B and 5.03 COI in patients with hepatitis C (P=.0046). The median WFA+ -M2BP values in F3 or more in the two groups were 1.79 COI in patients with hepatitis B and 3.79 COI in patients with hepatitis C (P<.0001). The median WFA+ -M2BP values in F2 or more in the two groups were 1.49 COI in the hepatitis B cohort and 3.19 COI in the hepatitis C group (P<.0001). Among five liver fibrosis markers, WFA+ -M2BP had the highest correlation coefficient (rs =.629) in terms of correlation with the degree of fibrosis in the patients with hepatitis C and had the second highest rs value (.415) in the hepatitis B group. Although WFA+ -M2BP could be a useful indicator of liver fibrosis, WFA+ -M2BP levels in the two groups significantly differed even in the same degree of fibrosis. Individual cut-off values in each aetiology for the degree of fibrosis should be determined.

Anti-interferon-α neutralizing antibody is associated with nonresponse to pegylated interferon-α plus ribavirin in chronic hepatitis C.

Pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV) treatment fails to achieve a sustained virological response (SVR) in approximately 20-50% of patients with chronic hepatitis C virus (HCV) infection. We assessed the contribution of an anti-IFN-α neutralizing antibody (NAb) on the nonresponse to treatment. NAbs were detected using an antiviral assay that assessed the neutralizing effects of serum samples against IFN. Serum samples were obtained at the end of the treatment and evaluated for the presence of NAbs using recombinant IFN-α as a standard. We studied 129 PEG-IFN-α/RBV-treated patients. In the 82 end-of-treatment responders, no NAbs were detected. Of the 47 patients who did not respond, seven (15%) were positive for NAbs. We also examined an additional 83 patients who had not responded to PEG-IFN-α treatment, and detected 12 with NAbs. Patients with good IFN-responsive characteristics, including HCV genotype 2/3 and major allele homozygotes for interleukin-28B, were included in the 19 patients with NAbs. No NAbs interfered with the antiviral activity of natural human IFN-ß (nIFN-ß) and re-treatement of patients with NAbs with nIFN-ß/RBV achieved SVR. Our analyses revealed that the emergence of anti-IFN-α NAbs was a candidate causal factor of PEG-IFN-α-treatment failure. Therefore, these antibodies should be assayed in patients who do not respond to PEG-IFN-α therapy, and if detected, other effective treatments, i.e., medications that are not neutralized by anti-IFN-α NAbs, should be considered.

[A role of visiting nurses in providing the terminal patients with their desirable life-discussion regarding the place of death of the patients who were registered for visiting nurse system].

AIM: To evaluate the prognosis of the patients who had visiting nurse service and discuss the place of death (life at the terminal stage). To determine the roles of visiting nurses in providing the patients at a terminal stage with their desirable life till death. METHODS: A total of 180 patients, who were registered for their home healthcare service in our Shonan Kamakura General Hospital and died between January 2000 and February 2001, were subjected to the study. All the subjects were classified into 3 groups according to the places of their death, 1) death at home, 2) death in the hospital and 3) death upon arrival after the admission to the hospital. Moreover, the following items were also surveyed and analyzed: 1) diagnosis (name of diseases), 2) cause of death, 3) age, 4) family structure, 5) whether their primary care physicians explained the prognosis and possible expected conditions to the patients and their family before hand, and 6) how the visiting nurses interact with the patients and their family members. RESULTS: Sixty-six patients died at home, 105 in the hospital and 9 upon arrival at the hospital. During this survey period, there were a total of 5,274 and 5,574 visits by primary care physicians and visiting nurses, respectively. The patients who died at home were more often observed in the patients whose primary care physicians explained their conditions to them and whose visiting nurses closely related to them. Moreover, the patients with malignant tumor also more often died at home. On the contrary, there were very few patients with chronic diseases, with whom death at home was accepted and agreed before hand, and there were some cases with chronic diseases who died inside of the ambulance transported on the way to the hospital after a sudden change in their conditions. DISCUSSION AND CONCLUSION: In order to have the patients live their desirable life till their death, it is required for the caretakers to prepare their mind for the day of the patient's death in addition to the patient's own wishes. For the patients with malignant tumor, it is easy to predict their prognosis, thus the caretakers can get prepared for the day of the patient's death. On the contrary, in case of the patients with chronic diseases, it is more difficult for the caretakers to experience an indefinite time with the patients since their prognosis is generally longer but the sudden change in their conditions may give the caretakers a high anxiety. Thus, it is essential for the visiting nurses to play a role as a mediator to interact between the patients and their family members, and their primary care physicians, and to establish a trustful relationship with the patients while their conditions are still stable. Moreover, similar to the malignant patients, the visiting nurses should explain the situations to the patients with chronic diseases, that they can choose the place of their own death and specific medical treatment at emergency and can decide the detail for their terminal stage with their family members. Thus, it was considered to be very important that the visiting nurses should frequently confirm these issues with the patients and their family according to their conditions.

[Serum antibodies to rubella virus in healthy individuals with indirect immunofluorescent method].

To investigate sensitivity to rubella virus (RV) in healthy individuals, we examined levels of antibodies to RV in sera by an indirect immunofluorescence assay (IFA) and compared levels of antibodies by IFA with those by a hemagglutination inhibition (HI) assay. Of 114 healthy individuals, we detected antibodies to RV in serum specimens from 103 (90.3%) by IFA and in those from 109 (95.6%) by HI assay. The peak value of levels of antibodies by HI assay was 4 fold higher than that by IFA. When levels of antibodies by IFA were less than 32, levels of antibodies by HI assay ranged from < 8 to 1024. We did not detect anti-rubella antibodies of IgM class in all serum specimens and detected anti-rubella antibodies of IgA class in serum from only 1 individual by IFA. We detected antibodies to rubella in sera from 51 (94.4%) by IFA and in sera from 52 (96.3%) by HI assay of 54 individuals who reported having had rubella, and in sera from 23 (88.5%), by IFA and in sera from 26 (100%) by HI assay of 26 individuals reported having been vaccinated. Also, we detected anti-rubella antibodies in sera from 13 (76.5%) by IFA and in sera from 15 (88.2%) by HI of 17 individuals who reported having had neither rubella nor vaccination. In serum from 1 individual who reported having had rubella, we detected antibodies to rubella by IFA but not by HI assay. In serum specimens from 2 individuals who reported having had rubella vaccination, from 3 having had vaccination, from 2 having had neither rubella nor vaccination, we detected anti-rubella antibodies by HI assay but not by IFA. On the other hand, by both assays, we detected antibodies to RV in all sera of individuals who reported having had rubella and been vaccinated. The serodiagnosis, at least, by two methods is necessary to prevent individuals from rubella virus infection, because of following results: 1) influence of an inhibitor in serum specimens was thought to be variable. 2) The results measured by IFA were differed from those by HI assay in some individuals. 3) It is difficult in diagnosis of rubella from clinical symptoms alone. Also, it might be required to use vaccine to the individual who lacks detectable antibodies to rubella in serum by any method to prevent rubella infection.

Study on freezing process of killifish egg: utilizing the undercooled state for cryopreservation.

The purpose of this study is to find the feasibility of preservation of large cell and tissue by maintaining the undercooled state in a freezing process, leading to avoiding the growth of ice crystals in the intracellular space, which causes destruction of cell and tissue. The fertilized killifish egg was employed to test biological tissue. The cooling system was equipped with Peltier devices and able to decrease the temperature of the test section to -50 degrees C. The cooling rate could be regulated by the electric current supplied to the Peltier devices. In the temperature range 0 to -40 degrees C, the morphology of fertilized killifish egg was observed under a microscope with a cooling rate from 0.1 to 10 degrees C/min. The damage rate to the egg in the intracellular undercooled state was evaluated by hatching rate. As a result, intracellular undercooled states were observed in the freezing process with the extracellular undercooling and the extracellular freezing. Extracellular undercooling proves to preserve the egg, and extracellular freezing frequently damages the egg. Thus the cryopreservation of biological material is achieved by maintaining the undercooled state until the temperature of -40 degrees C, then is instantly frozen by the liquid nitrogen to avoid the growth of ice crystals. The maintaining of the stable undercooled state of biological material is requisite for the initial phase in the freezing process. Therefore, dehydration or maintaining the extracellular stable undercooled state should be desirable to maintain the intracellular undercooled state for cryopreservation of biological material.

[The usefulness of the emergency hepatobiliary scintigraphy to rule out acute cholecystitis--43 patients report].

We studied emergency hepatobiliary scintigraphy in the 43 patients to rule out acute cholecystitis. After injection of 185-222 MBq (5-6 mCi) of 99mTc-EHIDA or 99mTc-HIDA, serial static scintigraphic images were obtained up to 7 hours in maximum. Of 43 patients in this study, 20 had a normal scan and finally in all of them cholecystitis was ruled out. Of the 43 patients, 14 had an abnormal scan (nonvisualized gall bladder). In 10 of them the diagnosis of acute cholecystitis was confirmed after emergency cholecystectomy. The other 9 patients of 43 had an incomplete scan mainly due to liver dysfunction. Four of them had acute cholecystitis in the cholecystectomy. These results indicate that acute cholecystitis can be excluded by the findings of gall bladder visualization in hepatobiliary scintigram. We concluded that emergency hepatobiliary scintigraphy is very useful to rule out acute cholecystitis.

[Clinical usefulness of scintigraphy with 99m technetium phosphates in rhabdomyolysis].

We performed bone scans with 99mTechnetium phosphates in 15 cases of clinically suspected rhabdomyolysis admitted to Chigasaki Tokushukai Hospital. Whole body scans were performed within 5 days from the onset of illness or admission. Accumulation of the radioactivity in the skeletal muscle was revealed in 13 of the 15 cases and the involved muscle groups were visualized vividly. Etiologies of rhabdomyolysis were diverse, ranging from malignant syndrome to sepsis. Myocardial concentration was absent in all of the cases. Renal concentration of the isotope was seen in cases where the degree of rhabdomyolysis was higher and renal impairment was present. We conclude that 99mTechnetium phosphate bone scan is useful in clinically suspected rhabdomyolysis as a diagnostic test and as a test to localize and quantitate the muscular involvement.

A large degenerated subserous leiomyoma of the uterus: uncommon scintigraphic and ultrasonographic findings.

Bone imaging is commonly used as a sensitive indicator of metastatic bone diseases or other bone pathology. Furthermore, it is now generally known that technetium-99m (99mTc) phosphonates tend to concentrate in various tissues other than bones. Ultrasonography is also widely used for the evaluation of pelvic masses. Ultrasonography is especially useful for detecting a cystic mass. We present a case where the uptake of 99mTc phosphonate compounds occurred in the entire abdomen, and ultrasonography suggested a diagnosis of pseudomyxoma peritonei, but the condition was later proven to be degeneration of giant subserous leiomyoma of the uterus. We have found two interesting features in this case. One is the 99mTc phosphonate concentration in the large cystic and hyaline degeneration of subserous leiomyoma of the uterus without calcification, and the other is the sonographic finding of a large echogenic mass with innumerable small anechoic areas. To our knowledge, no cases of 99mTc phosphonate concentration in non-calcified leiomyoma of the uterus have been demonstrated.

Bactericidal activity of M14659 enhanced in low-iron environments.

The bactericidal activity of M14659 against Escherichia coli in low-iron environments was investigated and compared with that of ceftriaxone and ceftazidime. The bactericidal activity of M14659 against E. coli in Mueller-Hinton broth was enhanced 30- to 20,000-fold by addition of transferrin, which is an iron-binding protein, whereas the activity of ceftriaxone or ceftazidime was much less strongly affected. This enhancement by transferrin was completely inhibited by saturating the iron-binding capacity of transferrin with FeCl3. M14659 was taken up markedly into bacterial cells in the presence of transferrin, and its uptake was inhibited by the protonophore dinitrophenol, which inhibits active-transport systems coupled to an energized membrane such as the iron transport systems of E. coli. The bactericidal activity of M14659, which chelates Fe3+, was also enhanced in the presence of other iron-binding compounds such as lactoferrin and alpha,alpha'-dipyridyl or in iron-deficient Mueller-Hinton broth (Fe3+ concentration, less than 2 nM) supplemented with FeCl3 at 0.1 to 1.0 microM, but not in unsupplemented iron-deficient Mueller-Hinton broth. The E. coli used in this study was confirmed to derepress iron transport systems in the presence of transferrin, lactoferrin, and alpha,alpha'-dipyridyl and in the iron-deficient Mueller-Hinton broth supplemented with FeCl3 at 0 to 1.0 microM. M14659 also showed an excellent antibacterial activity in vitro against other gram-negative bacteria in the low-iron environments. These findings indicate that M14659 may be actively taken up with Fe3+ into bacterial cells, probably through the iron transport systems under conditions of low iron and, thus, kills bacteria effectively.

Role of angiotensin II in the pathogenesis of hyperdipsia in chronic renal failure.

The relation of thirst to the renin-angiotensin system was examined in 38 patients with chronic renal failure receiving hemodialysis treatment. They were classified into three groups, ie, group 1 (19 patients), no or modest thirst; group 2 (13 patients), moderate thirst; and group 3 (six patients), excessive thirst. The plasma renin activity, plasma angiotensin II levels, and interdialytic weight gains of groups 1 to 3 significantly increased in a progressive manner with intensity of thirst. The hyperdipsia experienced by four patients in group 3 ameliorated after administration of an angiotensin-converting-enzyme inhibitor. The hyperdipsia of some patients with chronic renal failure therefore appears to be mediated by increased production of endogenous angiotensin II.