Clinical features of hepatocellular carcinoma that occur after sustained virological response to interferon for chronic hepatitis C

Background and Aim: This study investigated the clinical features of hepatocellular carcinoma in patients with sustained virological response to interferon for hepatitis C viral (HCV) infection. Methods: A total of 7715 patients with HCV infection were treated with interferon and followed up for more than 1 year after withdrawal of interferon in 64 Japanese hospitals and clinics between July 1988 and August 2001. Sustained virological response was obtained in 2515 (32.6%) patients. Of these 2515 patients, clinical data were collected for 38 patients in whom hepatocellular carcinoma developed. Sustained virological response was defined as HCV RNA negativity more than 6 months after the termination of interferon. Results: All patients were HCV RNA negative at the time of diagnosis of hepatocellular carcinoma. The median period until the detection of hepatocellular carcinoma was 4.7 years (range 1.4–9.0 years). There were significant improvements in hepatic function including serum albumin, aspartate aminotransferase, alanine aminotransferase, indocyanine green test, platelet count and histological activity grade in comparison with those before interferon therapy and at the onset of hepatocellular carcinoma. The maximum tumor size in patients without medical follow‐up for 1 year or more (median: 60 mm) was significantly larger than in patients who were periodically followed up for 6 months or less (median: 25 mm) (P = 0.002). Conclusions: The present findings emphasize the importance of regular medical follow up of patients with HCV infection, as even patients showing a sustained virological response to interferon and in whom hepatic function has improved have the potential to develop hepatocellular carcinoma.     

A Sensitive and Simple Determination of Human α-fetoprotein by Enzyme-electroimmunodiffusion

A simple and sensitive determination method of α-fetoprotein was developed by introducing α-fetoprotein horseradish peroxidase conjugate into electroimmunodiffusion.
The precipitin line formed was directly visualized by staining for peroxidase activities. The sensitivity was 32 ng/ml. Electrophoretic activities of AFP were analyzed by two dimensional electrophoresis applying the present method to the second electrophoresis.
AFP from normal adults and several patients was confirmed to migrate as an α-globulin as AFP of hepatoma, yolk sac tumor and fetuses did.
AFP-like activities were detected in β-γ-globulin region in some samples but these were not due to AFP-anti-AFP interactions.     

Correlation between deletion patterns of SMN and NAIP genes and the clinical features of spinal muscular atrophy in Japanese patients

We conducted molecular analysis of two candidate genes for spinal muscular atrophy (SMA), the survival motor neuron gene (SMN) and the neuronal apoptosis inhibitory protein gene (NAIP), in 16 Japanese patients with SMA and compared the phenotypic features of SMA in these patients with the corresponding genotypes. Exons 7 and/or 8 of SMN were homozygously deleted in 11 SMA type I (Werdnig-Hoffmann disease) patients, two SMA type II patients and one SMA type III patient. Exons 5 and 6 of NAIP were homozygously deleted in six SMA type I patients. No patient had a deletion in NAIP without a deletion in SMN. Mechanical ventilation was required during the first 7 months of life in the SMA type I patients who had a deletion in both SMN and NAIP. Ventilatory support was initiated within 2 years after birth in patients who had a deletion in SMN but not in NAIP. We detected homozygous deletion of exon 5 of NAIP in the unaffected mothers of two SMA type I patients. In these families, the patients exhibited a deletion in both SMN and NAIP. The parents and unaffected siblings of these patients did not have a deletion in SMN. The present findings support the hypothesis that SMN deletion plays an important role in the development of SMA and suggest that combined deletion of both SMN and NAIP may be relevant for determining the disease severity.     

Recent Advances and Future Directions of Hypothermia Therapy for Traumatic Brain Injury

For severe traumatic brain injury (TBI) patients, no effective treatment method replacing hypothermia therapy has emerged, and hypothermia therapy still plays the major role. To increase its efficacy, first, early introduction is important. Since there are diverse pathologies of severe TBI, it is necessary to appropriately control the temperature in the hypothermia maintenance and rewarming phases by monitoring relative to the pathology. Currently, hypothermia is considered appropriate for severe TBI patients requiring craniotomy for removal of hematoma, while induced normothermia is appropriate for severe TBI patients with diffuse brain injury. Induced normothermia is expected to exhibit a cerebroprotective effect equivalent to hypothermia, as well as reduce the complexity of whole-body management and systemic complications. According to the Japan Neurotrauma Data Bank of the Japan Society of Neurotraumatology, the brain temperature was controlled in 43.9% of severe TBI patients (induced normothermia: 32.2%, hypothermia: 11.7%) in Japan. Brain temperature management was performed mainly in young patients, and the outcome on discharge was favorable in patients who received brain temperature management. Particularly, patients who need craniotomy for removal of hematoma were a good indication of therapeutic hypothermia. Improvement of therapeutic outcomes with widespread temperature management in TBI patients is expected.     

Update on Intensive Neuromonitoring for Patients with Traumatic Brain Injury: A Review of the Literature and the Current Situation

Intracranial pressure (ICP) measurements are fundamental in the present protocols for intensive care of patients during the acute stage of severe traumatic brain injury. However, the latest report of a large scale randomized clinical trial indicated no association of ICP monitoring with any significant improvement in neurological outcome in severely head injured patients. Aggressive treatment of patients with therapeutic hypothermia during the acute stage of traumatic brain injury also failed to show any significant beneficial effects on clinical outcome. This lack of significant results in clinical trials has limited the therapeutic strategies available for treatment of severe traumatic brain injury. However, combined application of different types of neuromonitoring, including ICP measurement, may have potential benefits for understanding the pathophysiology of damaged brains. The combination of monitoring techniques is expected to increase the precision of the data and aid in prevention of secondary brain damage, as well as assist in determining appropriate time periods for therapeutic interventions. In this study, we have characterized the techniques used to monitor patients during the acute severe traumatic brain injury stage, in order to establish the beneficial effects on outcome observed in clinical studies conducted in the past and to follow up any valuable clues that point to additional strategies for aggressive management of these patients.     

Pseudomyxoma Peritonei with High Carcinoembryonic Antigen (CEA) Level: Report of Two Cases

Two cases of pseudomyxoma peritonei with high serum carcinoembryonicantigen (CEA) are reported. CEA levels in serum increased incorrelation with the accumulation of ascites. Systemic chemotherapywith anticancer agents such as 5-fluorouraciI (5-FU), cyclophosphamide,mitomycin C (MMC) and chromomycin A_a showed no effect on reducingeither the production of mucinous materials or the CEA level,but repeated intraperi-toneal instillation of large amountsof MMC reduced them in one case. In the other case, the CEAlevel returned to normal after removal of the tumor. These resultssuggest that CEA may be a useful indicator of the effect oftreatment and of the prognosis of pseudomyxoma peritonei.     

DIFFERENTIAL BLOCKING EFFECTS OF TETRODOTOXIN ON DOUBLE-PEAKED VASOCONSTRICTOR RESPONSES TO PERIARTERIAL NERVE STIMULATION IN CANINE ISOLATED, PERFUSED SPLENIC ARTERY

1. In the present study, we investigated the effects of progressive inhibition of neuronal sodium channels by increasing concentrations of tetrodotoxin (TTX; 1-30 nmol/L) on the double-peaked vasoconstrictor responses to electrical periarterial nerve stimulation in the canine isolated and perfused splenic artery. 2. Double-peaked vasoconstrictions (biphasic vasoconstrictor responses) were consistently observed in following electrical stimulation with 30 s trains of pulses at 1-10 Hz. At low frequencies of stimulation (1-3 Hz), a submaximal concentration of 3 nmol/L TTX had no effect on the first phase of the contractile response, but almost completely inhibited the second-phase response. At high frequencies (6-10 Hz), the two vasoconstrictor phases were almost equally inhibited by 50% by 3 nmol/L TTX. A three-fold increase in the concentration of TTX used (10 nmol/L) abolished the second-phase vasoconstriction at all stimulation frequencies tested, whereas this concentration of TTX failed to block the first-phase response. Further increasing the concentration of TTX to 30 nmol/L completely blocked the remaining first-phase response. 3. Treatment with 0.1 mumol/L prazosin did not modify the first-phase response to any of the stimulation frequencies in the presence of 3 nmol/L TTX. Moreover, 0.1 mumol/L prazosin had no affect on the second-phase response at low frequencies (1-3 Hz), while at high frequencies (6-10 Hz) it slightly, but significantly inhibited the second-phase response. The vasoconstrictor responses that persisted after 3 nmol/L TTX and 0.1 mumol/L prazosin were completely suppressed by subsequent application of 1 mumol/L alpha, beta-methylene ATP at all stimulation frequencies (1-10 Hz). 4. In conclusion, progressive inhibition of sodium channels by increasing the concentration of TTX may exert a more preferential inhibition on adrenergic rather than purinergic components, suggesting that TTX-sensitive sodium channels may have a more important role in determining the adrenergic rather than purinergic transmission of sympathetic nerves.     

Persistence of anti-HBs and protective efficacy after administration of hepatitis B vaccine

To evaluate the effect of hepatitis B vaccine on the persistence of anti-HBs and its efficacy in preventing hepatitis type B, anti-HBs and anti-HBc levels were studied over a period of 5.5 years. Plasma-derived hepatitis B vaccine, containing 20 micrograms of HBsAg protein, was injected subcutaneously in 122 healthy medical staff members, followed by two identical injections 1 and 6 months later. Anti-HBs and anti-HBc levels were then measured by radio-immunoassay. The anti-HBs titres were expressed as the sample/negative (S/N) ratios, and an S/N ratio of more than 2.1 was considered positive. The mean (and s.d.) anti-HBs titre peaked 7 months after the first vaccination with an S/N ratio of 153.6 +/- 149.8, after which it decreased with time. The mean anti-HBs titre dropped to an S/N ratio of 8.0 +/- 5.1 5.5 years after the first vaccination. The percentage of vaccinees who were anti-HBs positive also gradually decreased with time after a peak of 84.2% at 7 months following the first vaccination. The percentage of vaccinees who were anti-HBs positive was 38.9% 5.5 years after the first vaccination. The anti-HBc level was not positive in all subjects during the observation period. Five vaccinated volunteers who had developed anti-HBs after the basic vaccination, but whose acquired antibody level became negative within 4.5 years following the first vaccination, were administered a booster dose of 20 micrograms of HBsAg 4.5 years after the first vaccination. Only one of these subjects did not respond to the booster vaccination.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acquired Fatty Replacement of the Body and Tail of the Pancreas Diagnosed by Endoscopic Ultrasonography —A Case Report—

Abstract: A 62-year old female was admitted for a detailed study of a pancreatic abnormality detected by abdominal ultrasonography. A CT and MRI revealed a fat deposition in the body and tail of the pancreas. An ERCP demonstrated the distal main pancreatic duct as 2 fine branches in the head, and accessory pancreatic ducts were visualized. An endoscopic ultrasonography revealed a swelling of the body. In the tail, a membrane-like hyperechoic structure was noted, and probably represented the pancreatic capsule. A angiography demonstrated branches of the dorsal and transverse pancreatic artery, and the diagnosis of acquired fatty replacement of the body and tail of the pancreas was confirmed. Endoscopic ultrasonography appears to be a useful method to confirm fatty replacement of the body and tail of the pancreas.