Clinical characteristics of thrombotic microangiopathy following ABO incompatible living donor liver transplantation.

Thrombotic microangiopathy (TMA) may develop after living donor liver transplantation (LDLT), but the mechanism is not fully understood. We retrospectively analyzed all patients undergoing LDLT at our center, including TMA patients, to elucidate the clinical characteristics and presentation and to determine which patients have a higher risk of occurrence of TMA. In all, 57 adult patients were reviewed after LDLT at our institution. TMA was diagnosed by sudden and severe thrombocytopenia, followed by hemolytic anemia with fractionated erythrocytes in the blood smear. Clinical features were compared between the TMA group and the non-TMA group. Of the 57 patients, 4 were diagnosed with posttransplantation TMA. ABO blood group (ABO)-incompatibility, cyclophosphamide (CPA), and recipient blood group (type O) were closely correlated with the occurrence of TMA. Thrombocytopenia appeared 1 to 5 days before hemolytic anemia. Coagulative function markers stayed at the same level after TMA, while marked elevation was shown in fibrinolytic function markers such as plasminogen activator inhibitor type 1 (PAI-1). TMA occurred at a higher prevalence in ABO-incompatible graft recipients. Additional factors associated with ABO-incompatible transplantation, such as an overdose of immunosuppressants, may affect the likelihood of TMA. Sudden and severe thrombocytopenia presented before hemolytic anemia and the serum levels of PAI-1 correlated well with the clinical course of TMA. In conclusion, early recognition of thrombocytopenia and elevation of PAI-1 is crucial to diagnose TMA especially in ABO-incompatible LDLT.     

Associations of brachial-ankle pulse wave velocity and carotid atherosclerotic lesions with silent cerebral lesions.

Silent cerebral lesions are increasingly found in mass screenings using MRI and magnetic resonance angiography (MRA). The purpose of this paper is to assess the usefulness of two non-invasive clinical tests-carotid ultrasound examination and brachial-ankle pulse wave velocity (baPWV) measurement-for predicting silent cerebral infarction (SCI) and silent intracranial arterial stenosis. Data were collected on 480 asymptomatic adult subjects who participated in a brain screening program at a single hospital between April 2003 and March 2006. All participants underwent baPWV measurement, B-mode ultrasonography of carotid arteries, MRI, and MRA. Data on 476 (99.1%) subjects were included in the analysis. Among these, 273 (57.4%) were male and the mean age was 51.5 years; 161 (33.8%) had carotid plaque; 33 (6.9%) had increased intima-media thickness (IMT); 99 (20.8%) had SCI; and 7 (1.5%) had intracranial arterial stenosis. The multivariate analysis showed that age (odds ratio [OR]: 1.12; 95% confidence interval [CI]: 1.08-1.17), carotid plaque (OR: 2.69; 1.59-4.56), increased IMT (OR: 2.40; 1.02-5.65), and a history of hypertension treatment (OR 2.22; 1.11-4.43) were significantly associated with SCI. Also, increased IMT (OR 9.70: 1.48-63.71) was related to intracranial arterial stenosis. Brachial-ankle PWV was related to SCI (p<0.01) and intracranial stenosis (p=0.01) in univariate analysis but not in multivariate analysis. The presence of carotid plaque and that of increased IMT on ultrasound examination are useful for assessing the risk of SIC. Increased IMT is also predictive of intracranial arterial stenosis.     

Tricuspid annuloplasty and right ventricular function in mitral valve disease

From 1985 to 1987, we examined relationship between the lesion of tricuspid valve and right ventricular function in 31 patients (male: 9, female: 22) with mitral valve disease. The median age at operation was 52 years (range 37-69 years). Group I consisted of 17 patients (MS: 10, MSR: 5, MR: 2) accompanied with tricuspid regurgitation (TR) and Group II 14 patients (MS: 12, MSR: 2) without TR. In all cases of Group I tricuspid annuloplasty (TAP) were performed correctly. De Vega methods were done in 12 cases and Carpentier rings were used in 5 cases. Cardiac catheterization was done before and after operation. And right ventricular volume was measured by right ventricular angiography. In both groups pulmonary capillary wedge pressure, pulmonary artery pressure and cardiac index were improved postoperatively. Pulmonary artery resistance (PAR) and total pulmonary resistance (TPR) in Group I were significantly higher before operation but there were no difference between two groups postoperatively. Right ventricular end-diastolic volume index (RVEDVI) and right ventricular end-systolic volume index (RVESVI) in Group I were significantly improved postoperatively, but in Group II these were within normal range both pre- and postoperatively. Preoperative PAR was correlated inversely with postoperative right ventricular ejection fraction (RVEF). It means that patients with severe pulmonary vascular lesion had postoperative lower right ventricular function. In both groups, RVESVI was in inverse correlation with RVEF pre- and postoperatively. In both groups, there was an inverse correlation between the per cent change of RVESVI and that of RVEF. This means that RVESVI influenced right ventricular pump function.     

Chemo-endocrine therapy in patients with stage D2 prostate cancer

There have only been a few studies of chemo-endocrine therapy compared with endocrine therapy alone in newly diagnosed prostate cancer patients. We assessed the effects of these two therapies by comparing long-term survival rates. One hundred and twenty-nine patients were entered in this study between November 1977 and March 1992. Seventy-seven patients were treated with endocrine therapy alone. Other 52 patients received chemo-endocrine therapy, which included orchiectomy and/or diethylstilbestrol diphosphate (DES-DP) plus Cisplatin, with or without other cytotoxic agents. All patients had bone metastasis at the beginning of the study. There was a significant difference in survival between patients who received endocrine therapy and chemo-endocrine therapy (P = 0.0078). That is, survival rate was superior for the chemoendocrine therapy patients throughout the entire follow-up period. These data suggest that early chemo-endocrine therapy containing Cisplatin, with or without maintenance chemotherapy, is a potentially effective treatment for newly diagnosed metastatic prostate cancer and is worth further investigation via a randomized trial.     

Internalization of Mycobacterium bovis Bacillus Calmette-Guérin into Osteoblast-Like MC3T3-E1 Cells and Bone Resorptive Responses of the Cells against the Infection

Mycobacterium bovis BCG (BCG) is a live vaccine used worldwide against tuberculosis. However, it has unfavourable side effects such as osteitis or osteomyelitis, and these sometimes lead to vertebral caries in some patients as a result of bone resorption. Osteoblasts might play a role in the bone resorption caused by BCG infection, because they are central cells in bone metabolism. Cultured osteoblast-like cell lines (MC3T3-E1) derived from C57BL mice susceptible to BCG infection cells were infected with BCG at several doses. Interestingly, internalization of BCG-enveloped phagosome-like membrane in osteoblast-like cells were observed by transmission electron microscopy (TEM). Owing to infection, the proliferation and alkaline phosphatase activity of the osteoblast-like cells were reduced in a dose-dependent manner. On the other hand, interleukin (IL)-6 production was considerably enhanced by infection. These results suggest that BCG infects osteoblasts, suppressing their proliferation and differentiation and inducing bone resorption, which may be related to osteitis/osteomyelitis and bone caries caused by BCG infection.     

Physiological abnormalities in hereditary hyperekplexia.

Five patients from a kindred with hereditary hyperekplexia had physiological testing. The surface-recorded electromyographic pattern of audiogenic muscle jerks was identical to that of the normal acoustic startle reflex. Testing at graded stimulus intensities indicated an increase in the gain of the acoustic startle reflex. Nose-tap stimuli resulted in short-latency generalized electromyographic bursts that were similar to the R1 component of the blink reflex. Electrical stimulation of peripheral nerves elicited a pattern of generalized muscle jerks that was similar to that of the acoustic startle reflex. Somatosensory evoked potentials, brainstem auditory evoked potentials, and cortical auditory evoked potentials were normal. The primary physiological abnormality in hereditary hyperekplexia is widespread elevated gain of vestigial withdrawal reflexes in the brainstem and possibly the spinal cord, most likely resulting from increased excitability of reticular neurons.     

Ganglioglomerular nerves respond to moderate hypoxia independent of peripheral chemoreceptors in the cat

The responses of the ganglioglomerular nerve (GGN) to transient changes and steady-state levels of paO2 at a constant paCO2 were studied in 12 anesthetized and spontaneously breathing cats before and after bilateral section of aortic (AN) and carotid sinus nerves (CSN). In two of these cats carotid chemoreceptor activity was monitored simultaneously. Onset of moderate hypoxia, down to paO2 of about 50 Torr, stimulated GGN activity and withdrawal of the hypoxic stimulus promptly eliminated the responses both before and after CSN section. CSN section, however, significantly raised the baseline activity and slightly delayed the GGN response to the onset of hypoxia. These responses to hypoxia are qualitatively similar to the characteristic responses of peripheral chemoreceptors. Thus, the basic oxygen chemosensing mechanism appeared to be present in the sympathetic nervous system, and is expressed in the postganglionic GGN activity. This property allows the sympathetic nervous system to perform physiologically important functions independent of the peripheral chemoreceptors.     

Geographic patterns of urban trauma according to mechanism and severity of injury

The purpose of this study was to investigate the distribution of various mechanisms of injury and the relative severity of such injury cases throughout the different geographic zones of a large urban area using a computerized emergency medical services (EMS) dispatch/patient record database. The study city (population, 2 million residents) was divided into 156 geographic grids (each 4.5 by 3 miles) and the incidence and relative severity of various injury mechanisms were determined for each zone. Results: In one year (1988), there were more than 115,000 separate EMS incidents involving more than 150,000 patients, 26,000 of whom were transported for injuries incurred in 10,064 motor vehicle accidents, 4,587 falls, 4,015 lacerations/stabwounds, 1,796 beatings, 1,270 gunshots, and 952 auto-pedestrian accidents. Analysis of the 156 zones showed a disproportionate number of EMS responses in the city center with two centralmost grids accounting for about 25% of all responses. Call volume then progressively diminished toward the periphery of the city. However, with some very minor exceptions, the relative incidence and severity of the various injury mechanisms remained proportionally uniform within each zone, regardless of geographic location. Therefore, contrary to popular notoriety, the incidence and associated severity of any given injury type generally was not necessarily predicted by any particular neighborhood predilection for it, but rather by the overall demand for EMS in that zone of the city.     

Synthesis and antiviral activity of sulfonamidobenzophenone oximes and sulfonamidobenzamides

To find antiviral agents, various sulfonamidobenzophenone oximes (II) were synthesized from the appropriate m-sulfonamidobenzophenones by hydroxylamine reaction. The reaction products were generally obtained as syn/anti mixtures which were separable by fractional crystallization. The anti isomer had more potent antipoliovirus activity than the syn isomer. Various sulfonamidobenzamides (III) which were structurally related to II were synthesized by the reactions of amino-substituted benzamides with sulfuryl chloride or amines with (aminosulfonyl)benzoyl chloride. Antiviral activity was examined by the plaque-inhibition test. Compounds 5, 36, and 69 exhibited strong antipicornavirus activity. The structure-activity relationships are discussed.