Effects of valsartan and amlodipine on home blood pressure and cardiovascular events in Japanese hypertensive patients: a subanalysis of the VART

The Valsartan Amlodipine Randomized Trial (VART) was performed to compare the beneficial effects of valsartan and amlodipine on cardiovascular events in Japanese hypertensive patients. In this subanalysis of the VART, we assessed the relationship between home blood pressure (HBP) levels and cardiovascular events in the enrolled patients. We enrolled 1021 patients with mild-to-moderate hypertension in the VART. The participants were allocated randomly to either the valsartan group or the amlodipine group. The primary end point was a composite of all-cause death, sudden death, cerebrovascular events, cardiac events, vascular events and renal events. A total of 621 patients (valsartan group: 305 and amlodipine group: 316) completed the measurements of HBP (morning and evening) throughout the trial. Both the agents evenly and significantly lowered morning HBP and evening HBP throughout the trial. There was no significant difference in the primary end point between the two groups. However, we observed significant decreases in the left ventricular mass index and urinary albumin to creatinine ratio in the valsartan group but not in the amlodipine group. There were no significant differences in HBP levels and the main outcome of the cardiovascular events between the valsartan and amlodipine groups. However, in the valsartan group, significant improvements in left ventricular hypertrophy and microalbuminuria were observed.     

Grooved pegboard test as a biomarker of nigrostriatal denervation in Parkinson's disease

Recent pharmacotherapy trials in Parkinson's disease (PD) using dopaminergic neuroimaging as outcome parameter failed to show significant relationships between imaging and clinical results. One possible explanation is that there is a non-linear relationship between striatal denervation and motor performance reflecting a statistical "floor" effect in the imaging data with advanced disease. Both the motor manifestations and the striatal dopamine denervation of idiopathic PD, however, are typically asymmetric and more meaningful associations may be found by comparing data from the least denervated striatum with motor performance in the corresponding body side. PD patients (n=28) underwent [11C]beta-CFT dopamine transporter (DAT) positron emission tomography (PET) and grooved pegboard testing. Voxel-based analysis of DAT PET and bimanual pegboard scores demonstrated significant correlation clusters within the bilateral striata (P<0.001). However, findings were most prominent in the least denervated striatum. There was a significant inverse correlation between pegboard scores of the least affected arm and DAT binding of the least denervated striatum (Rs=-0.69, P<0.0001) but no significant correlation between pegboard scores of the clinically most affected arm and DAT binding of the most denervated striatum (Rs=-0.15, ns). These data indicate that the robustness of the grooved pegboard test as a biomarker for nigrostriatal denervation in PD mainly reflects the relationship between test performance of the clinically least affected limb and the least denervated striatum. These findings indicate that there is both a statistical "floor" and "ceiling" effect for the most affected striatal and body sides that must be considered when employing imaging as an outcome measure in clinical trials in PD.     

Spinal cord injury following aortic arch replacement

Surgery Today - Postoperative spinal cord injury is a devastating complication after aortic arch replacement. The purpose of this study was to determine the predictors of this complication. A group...     

Usefulness of laparoscopic subtotal cholecystectomy with operative cholangiography for severe cholecystitis

Purpose

Cholecystectomy can become hazardous when inflammation develops, leading to anatomical changes in Calot’s triangle. We attempted to study the safety and efficacy of laparoscopic subtotal cholecystectomy (LSC) to decrease the incidence of complications and the rate of conversion to open surgery.

Methods

Patients who underwent LSC between January 2005 and December 2008 were evaluated retrospectively. The operations were performed laparoscopically irrespective of the grade of inflammation estimated preoperatively. However, patients with severe inflammation of the gallbladder underwent LSC involving resection of the anterior wall of the gallbladder, removal of all stones and placement of an infrahepatic drainage tube. To prevent intraoperative complications, including bile duct injury, intraoperative cholangiography was performed.

Results

LSC was performed in 26 elective procedures among 26 patients (eight females, 18 males). The median patient age was 69 years (range 43–82 years). The median operative time was 125 min (range 60–215 min) and the median postoperative inpatient stay was 6 days (range 3–21 days). Cholangiography was performed during surgery in 24 patients. One patient underwent postoperative endoscopic sphincterotomy for a retained common bile duct stone that was found on cholangiography during surgery. Neither complications nor conversion to open surgery were encountered in this study.

Conclusions

LSC with the aid of intraoperative cholangiography is a safe and effective treatment for severe cholecystitis.     

Dose‐dependent,saturable occupancy of the metabotropic glutamate subtype 5 receptor by fenobam as measured with [11C]ABP688 PET imaging

Fenobam is a negative allosteric modulator of the metabotropic glutamate receptor subtype 5 (mGluR5) with inverse agonist activity and is expected to contribute to the treatment of neuropsychiatric disorders involving dysfunction of mGluR5 including Fragile X syndrome. This study examined whether [¹¹C]ABP688, an antagonist PET radioligand, competes with fenobam for the same binding site in the nonhuman primate brain and would allow examination of occupancy‐plasma concentration relationships in the evaluation of the drug for target disorders in the human brain. Four paired PET studies with [¹¹C]ABP688 were performed in baboons at a baseline condition and after intravenous treatment with fenobam at different dose levels (0.3–1.33 mg/kg). Total distribution volume (V_T) and binding potential (BP_ND) using the cerebellum as a reference region were obtained by the plasma reference graphical method. Then it was examined whether occupancy follows a dose‐dependent, saturating pattern that was predicted by a modified first‐order Hill equation in individual regions. Baseline regional V_T and BP_ND values agreed with previously published data. Occupancy showed dose‐dependent and saturating patterns in individual regions, reaching >90% occupancy at 1.33 mg/kg dose of fenobam in the majority of regions. To our knowledge, this is the first use of PET to characterize the mGluR5 therapeutic drug fenobam. This study demonstrates a proof of principle for determining the in vivo occupancy of fenobam in primates. The results indicate that [¹¹C]ABP688 and PET may be useful for examination of occupancy of mGluR5 by fenobam, which should prove to be useful for designing future studies and treatment of human disease states. Synapse 68:565–573, 2014 . © 2014 Wiley Periodicals, Inc.     

Serotypes and antibiotic sensitivity of hemolytic streptococci isolated from clinical specimens in Hiroshima Prefecture, 1987-1989

The grouping, the typing and the drug-sensibility of hemolytic streptococci isolated from the clinical specimens taken from 4 medical centers in Hiroshima Prefecture have been examined and reviewed during the past 3 years 1987-1989. The results were summarized in this report. 1. Of 1572 strains of hemolytic streptococci, 844 strains (53.7%) were group A; 539 strains (34.3%), group B; 14 strains (0.9%), group C; 82 strains (5.2%), group G; and 93 strains (5.9%), the others. We found that group A and group B were predominant, and the incidence rate of group B was higher than it used to be. 2. The prevalent types were T-4 (37.9%), T-1 (13.6%), T-12 (12.0%), and T-28 (10.7%) in group A, while Ia (26.2%), M9 (provisional type 18.4%), and III (14.5%) in group B. 3. As far as the detection data of each month is concluded, during the summer season we could hardly detect group A which peak of occurrence during the winter season. These findings were really consistent with the occurrence pattern of those patients who suffered from streptococcal infectious disease. But this occurrence pattern couldn't be found in group B. 4. In our study, the positive frequency was throat swab greater than urine greater than sputum greater than vaginal swab greater than pus greater than ear secretion in order. Group A was mainly isolated from throat swab, while group B, from several specimens including urine. 5. We found that there was a high drug-sensibility to the beta-lactam drugs in all strains except for 3 strains of group B which were resistant to CEX.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of probucol on repeat revascularization rate after percutaneous transluminal coronary angioplasty (from the Probucol Angioplasty Restenosis Trial [PART])

To address the issue of whether probucol reduces clinical events after percutaneous transluminal coronary angioplasty (PTCA), we surveyed clinical status at 1 year after PTCA of 101 patients who had entered the Probucol Restenosis Angioplasty Trial. Repeat angioplasty at index lesions were required in 5 patients in the probucol group and in 12 in the control group, suggesting that probucol administered beginning 4 weeks before PTCA reduces repeat revascularization rates for 1 year.     

Lactate rise detected by 1H NMR in human visual cortex during physiologic stimulation.

Brain lactate concentration is usually assumed to be stable except when pathologic conditions cause a mismatch between glycolysis and respiration. Using newly developed 1H NMR spectroscopic techniques that allow measurement of lactate in vivo, we detected lactate elevations of 0.3-0.9 mM in human visual cortex during physiologic photic stimulation. The maximum rise appeared in the first few minutes; thereafter lactate concentration declined while stimulation continued. The results are consistent with a transient excess of glycolysis over respiration in the visual cortex, occurring as a normal response to stimulation in the physiologic range.