Clinical use of the artificial heart, indications and results

Clinical experience with the artificial heart now comprises 520 cases. 390 patients had to be supported mechanically when they could not be weaned off cardiopulmonary bypass. 177 (45%) subsequently had their assist devices removed and 100 (25.4%) were discharged. Good functional results were achieved, since 30 of 36 long-term survivors are in NYHA class I or II. 140 underwent two-stage cardiac transplantation. Of 63 patients implanted with a ventricular assist device (VAD) 71% were transplanted and 51% survived. A total artificial heart (TAH) was used in 77 cases, 81% were transplanted and 47% survived. Five patients received TAH implantations as a permanent replacement of the failing heart. Though the clinical courses were complicated by strokes and infections and the patients were tethered to bulky drive units, it was proven that the TAH may sustain human life for up to 622 days, much longer than so far achieved in animal experiments. Improvements of the atrial connectors and valve holding components and of the biocompatibility of the blood contacting surfaces should overcome the complication of thromboembolism. Fully implantable devices which are currently being developed will avoid the problem of drive-line infections and provide fuller mobility to the patient.     

Prediction of the prognosis of liver cirrhosis in Japanese using Cox's proportional hazard model

Data on 155 patients with liver cirrhosis were analyzed, using Cox's proportional hazard model. Twenty variables were screened, using a multiple linear regression analysis in a stepwise manner and 6 were considered to reflect the prognosis of cirrhotics. Three of the 6 variables were significantly prognostic, i.e. ascites, atrophy of the right lobe of the liver seen on liver scintigram and the concentration of serum albumin. The prognostic index (PI) for each patient was calculated by adding all the products of scores of these three variables with the corresponding coefficient: PI = 0.895 X ascites (absent = 0, present = 1) + 0.983 X atrophy of right lobe of the liver on the liver scintigram (absent = 0, present = 1) + (-0.561) X serum albumin (g/dl). According to the PI, the subjects were separated into three groups; group 1: PI less than -1.9, group 2: -1.9 less than or equal to PI less than -0.6, group 3: PI greater than or equal to -0.6. The global 5- and 10-year survival rates of each group were 80% and 65% in group 1, 50% and 30% in group 2 and 12% and 0% in group 3, respectively. Four of the 14 deaths in group 1, 8 of 47 in groups 2 and 10 of 24 in group 3 were caused by hepatocellular carcinoma. Our observations suggest that advanced stage cases of cirrhosis are at a high risk concerning development of hepatocellular carcinoma.     

The effect of docosahexaenoic acid on bone microstructure in young mice and bone fracture in neonates

Background

As low bone mineral density is a risk factor for fracture in childhood, optimizing age appropriate bone mass is recommended and might lower the impact of bone loss related to age. Consumption of omega-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic and docosahexaenoic (DHA) acids have been shown to beneficially modulate bone metabolism. The objective of this study was to determine the incidence of fracture in neonates receiving a fish compared with soybean oil–based intravenous lipid emulsion and evaluate the effect of varying dietary omega-3 PUFA consumption on growing bone in young mice.

Materials and methods

Eligibility criteria for the clinical study included gestational age ≤37 wk and parenteral nutrition–dependence for ≥4 wk. Radiographs were reviewed after lipid initiation to identify radiologic bone fracture. The animal study evaluated female C57/Bl6 mice randomized into one of five groups from age 3–12 wk, at which time femurs were harvested for micro–computed tomography and light microscopy analysis.

Results

A lower incidence of bone fracture was found in neonates maintained on fish compared with soybean oil. In the animal study, findings suggest the DHA diet provides the best protection against trabecular bone loss as evidenced by increased bone volume fraction, increased trabecular number, and decreased trabecular separation on micro–computed tomography. These protective effects appeared to affect the bone microstructure alone.

Conclusions

The lower fracture risk observed in fish oil fed neonates in combination with the protective effects of DHA observed in the femurs of young C57/BL6 mice suggest an important role for omega-3 PUFAs on bone growth.     

Initial Evaluation of AF78: a Rationally Designed Fluorine-18-Labelled PET Radiotracer Targeting Norepinephrine Transporter

Molecular Imaging and Biology - Taking full advantage of positron emission tomography (PET) technology, fluorine-18-labelled radiotracers targeting norepinephrine transporter (NET) have potential...     

Early stage clear cell adenocarcinoma of the colon examined in detail with image-enhanced endoscopy: a case report

Primary clear cell adenocarcinoma (CCA) of the colorectum is a rare tumor. We report on a 48-year-old man with early stage CCA in the descending colon who underwent detailed examination with image-enhanced endoscopy, such as magnifying endoscopy with narrow-band imaging and crystal violet staining. The tumor was treated successfully with endoscopic mucosal resection at our hospital.     

Reduced α-adrenoceptor responsiveness and enhanced baroreflex sensitivity in Cry-deficient mice lacking a biological clock

To reveal the role of clock genes in generating the circadian rhythm of baroreflexes, we continuously measured mean arterial pressure and baroreflex sensitivity in free-moving normal wild-type mice, and in Cry -deficient mice which lack a circadian rhythm, in constant darkness for 24 h. In wild-type mice the mean arterial pressure was higher at night than during the day, and was accompanied by a significantly enhanced baroreflex sensitivity of −13.6 ± 0.8 at night compared with −9.7 ± 0.7 beats min⁻¹ mmHg⁻¹ during the day ( P < 0.001). On the other hand, diurnal changes in arterial pressure disappeared in Cry -deficient mice with remarkably enhanced baroreflex sensitivity compared with wild-type mice ( P < 0.001): −21.9 ± 1.6 at night and −23.1 ± 2.1 beats min⁻¹ mmHg⁻¹ during the day. Moreover, the mean arterial pressure response to 10 μg kg⁻¹ of phenylephrine, an α₁-adrenoceptor agonist, was severely suppressed in Cry -deficient mice regardless of time, while that for the wild-type mice was 10.1 ± 1.9 mmHg in the night, significantly lower than 22.0 ± 3.5 mmHg in the day ( P < 0.01). These results suggest that CRY genes are involved in generating the circadian rhythm of baroreflex sensitivity, partially by regulating α₁-adrenoceptor-mediated vasoconstriction in peripheral vessels.     

Analysis on allelic variation of the HLA-DMB gene in Japanese by PCR-RFLP as well as direct DNA sequencing and identification of a new DMB allele, DMB*0105

In the HLA-D region, one of the class II genes, DMA and DMB have been identified between the DQ and DP genes, and four allelic polymorphisms in each of the DMA (DMA*0101–0104) and DMB (DMB*0101–0104) genes have been so far recognized. Several recent studies suggested that the DM molecule is required for class II antigen presentation pathway especially by promoting the binding of antigenic peptides to the classical HLA class II molecule. In this study, we have analyzed genetic polymorphism and allelic variation of the DMB gene in a Japanese population by the direct DNA sequencing technique and also by the polymerase chain reaction — restriction fragment length polymorphism (PCR-RFLP) method, and could recognize DMB*0101 (49.3%), DMB*0102 (23.2%), DMB*0103 (23.2%), and DMB*0104 (0.4%). Further, a new DMB allele, DMB*0105 characterized by the presence of Val and Iie at two polymorphic sites, codons 144 and 179, respectively was identified. Strong linkage disequilibria were found between DMB*0101 and DRB1*0101, DPB1*0402 and DRB1*1502, and also between DMB*0103 and DRB1*1501 and DQB1*0602. HLA-DMB genotyping using the PCR-RFLP method established here will provide accurate evaluation of the effects of sequence allelism in the DMB gene on the HLA class II disease associations.     

Expression of Phaseolus vulgaris leukoagglutinin-binding oligosaccharides in oral squamous cell carcinoma: Possible association with the metastatic potential

The expression of -GlcNAcβ1–6Man-(β1–6) branched oligosaccharides In carcinoma cells has been considered to influence their metastatic potentials. In the present paper, the lectin histochemistry of oral squamous cell carcinomas obtained in biopsy from 34 patients with Phaseolus vulgaris leukoagglutinin (L-PHA), which potentially binds to N-glycosidic carbohydrates with β1–6 linked lactosamin antennae, was studied in order to analyze the relationship between their staining patterns and metastases. The L-PHA-binding oligosaccharides of the carcinomas were expressed on the cell surface in the following patterns: (i) all cells were positive for the staining ('positive'); (ii) some cells were positive but the rest of the carcinoma cells were negative ('weakly positive'); and (iii) all were negative ('negative'). Statistical analysis revealed that the incidence of the metastasis to regional lymph nodes in the 'positive' cases was significantly higher than that in the 'negative' cases. Moreover, the number of the CD14 positive cells including macrophages in the Stroma adjacent to the cardnomas in the 'positive' cases was less than that in the 'negative' or 'weakly positive' cases. The expression of L-PHA-binding oligosaccharides in oral squamous cell carcinoma may be responsible for their metastatic potential to regional lymph nodes, possibly Including their ability to escape macrophage recognition.