Morphological changes in articular cartilage due to static compression: polarized light microscopy study

We studied the deformation of the extracellular matrices in articular cartilage using a new compression-preservation method in histology. A Hoffman clamp was used to compress the tissue, which remained throughout the paraffin procedure and was removed from the embedded tissue block just before microtoming. Then 14 cartilage-bone blocks from 2 canine humeri were compressed for various strain levels from 5% to 65%. The histological sections were studied using a polarized light microscope, which generated a pair of two-dimensional maps of the fibril orientation (angle) and fibril organization (retardance) for each section. Results were 3-fold. One there was little change in the angle and retardance profiles of the tissue for strain levels 0-15% and a significant change in these profiles for strain levels 15% and above. Two for higher compression, more fibrils became aligned parallel to the articular surface; and three at approximately 30% strain, a second "transitional zone" was formed in the deep part of the tissue. We concluded that this novel compression procedure can be used effectively to study the altered architecture of the collagen matrix in compressed cartilage.     

Immunochemical identification and detection of serum fibronectin in liver fibrosis patients with chronic hepatitis C

Serum tests measuring the dynamic processes of fibrogenesis and fibrolysis may reflect the severity of liver disease. Fibronectin plays a role in liver fibrosis. The aim of this study was to assess the diagnostic value of fibronectin in chronic HCV infection among Egyptian patients. Fibronectin was identified using specific monoclonal antibody and Western blot at 90-kDa in sera of HCV infected patients with liver fibrosis. The purified serum fibronectin showed one peak at 8 min when analyzed by capillary zone electrophoresis. Fibronectin was quantified in serum using ELISA. The mean (+/-SD) serum level of fibronectin (mg/L) in liver fibrosis patients were 450.9 (+/-170.3) and 230.5 (+/-90.3) in control individuals, respectively. There was a significant correlation between METAVIR score and serum fibronectin (r=0.401; P<0.0001). The area under the receiver operating characteristic (ROC) curve of fibronectin for discriminating patients with liver fibrosis from those with no fibrosis livers and its p value were 0.78 and P<0.0001. The efficiency of fibronectin for discriminating patients with liver fibrosis from those with non fibrosis livers was 75%. In conclusion, serum fibronectin can differentiate HCV infected patients with liver fibrosis from patients with non fibrosis.     

Opioid Antagonists and the A118G Polymorphism in the μ-Opioid Receptor Gene: Effects of GSK1521498 and Naltrexone in Healthy Drinkers Stratified by OPRM1 Genotype

The A118G single-nucleotide polymorphism (SNP rs1799971) in the μ-opioid receptor gene, OPRM1, has been much studied in relation to alcohol use disorders. The reported effects of allelic variation at this SNP on alcohol-related behaviors, and on opioid receptor antagonist treatments, have been inconsistent. We investigated the pharmacogenetic interaction between A118G variation and the effects of two μ-opioid receptor antagonists in a clinical lab setting. Fifty-six overweight and moderate–heavy drinkers were prospectively stratified by genotype (29 AA homozygotes, 27 carriers of at least 1 G allele) in a double-blind placebo-controlled, three-period crossover design with naltrexone (NTX; 25 mg OD for 2 days, then 50 mg OD for 3 days) and GSK1521498 (10 mg OD for 5 days). The primary end point was regional brain activation by the contrast between alcohol and neutral tastes measured using functional magnetic resonance imaging (fMRI). Secondary end points included other fMRI contrasts, subjective responses to intravenous alcohol challenge, and food intake. GSK1521498 (but not NTX) significantly attenuated fMRI activation by appetitive tastes in the midbrain and amygdala. GSK1521498 (and NTX to a lesser extent) significantly affected self-reported responses to alcohol infusion. Both drugs reduced food intake. Across all end points, there was less robust evidence for significant effects of OPRM1 allelic variation, or for pharmacogenetic interactions between genotype and drug treatment. These results do not support strong modulatory effects of OPRM1 genetic variation on opioid receptor antagonist attenuation of alcohol- and food-related behaviors. However, they do support further investigation of GSK1521498 as a potential therapeutic for alcohol use and eating disorders.     

Impact of Physiological Symptoms and Complications of Colorectal Cancer on the Quality of Life of Patients at King Abdulaziz University Hospital

Colorectal cancer (CRC) is common worldwide. The high prevalence of the disease raises concerns about how CRC influences the health-related quality of life (QoL). To explore the impact of physiological symptoms and complications of CRC on patients’ QoL, we conducted a cross-sectional survey using the FACT-C self-report instrument. The chi-square test was used to compare qualitative data. We found that pain was reported by most of the patients (n?=?31; 77.5 %). Furthermore, male patients were more likely to complain of pain “mostly” as compared with females (P?=?.032). We found no significant differences between genders regarding general health-related questions. A greater proportion of male patients often complained of abdominal cramps (P?=?.542), weight loss (P?=?.086), and diarrhea (P?=?.408). More than half of the patients (n?=?26; 65 %) reported having a good appetite; a greater proportion of males reported having a good appetite “mostly” (P?=?.014). Social and psychological qualities of life were not significantly different between male and female patients. Male and female patients did not differ in their report of disease acceptance (P?=?.420) and ability to enjoy life (P?=?.744). No difference was also found between genders regarding contentment with QoL (P?=?.793) or ability to sleep well (P?=?.695). Furthermore, there were no differences between genders regarding job fulfillment (P?=?.272). Our results add to the growing body of knowledge about the effect of CRC on QoL. Importantly, the differences in self-reported pain and appetite between male and female patients in our study suggest the importance of gender-based treatments in improving patients’ QoL.     

Comparison of propranolol LA 80 mg and propranolol LA 160 mg in migraine prophylaxis: a placebo controlled study

Thirty patients with severe classical and common migraine participated in a double-blind placebo-con-trolled cross-over study of migraine prophylaxis with propranolol LA (long-acting) 80 mg once daily, or propranolol LA 160 mg once daily or placebo. Each treatment was given for two months. There were no significant differences between the three treatment periods in headache frequency, headache severity, nausea frequency or severity. There was a non-significant trend for reduced duration of headache with the two doses of propranolol. The possible reasons for this negative effect are discussed. The safety of propranolol and its lack of serious side effects were demonstrated.     

Autodecremental pacing for the interruption of ventricular tachycardia and atrial flutter

The efficacy and safety of autodecremental pacing (ADP) to interrupt ventricular tachycardia (VT) and atrial flutter was examined. Once tachycardia was recognized, ADP was initiated using a short train of stimuli with gradual shortening (3%) of the interstimulus interval. ADP was applied to 13 consecutive patients during 75 episodes of VT (mostly following induction by ventricular stimulation). Successful interruption of VT occurred in 88% of the episodes. In 6 episodes (8%), ADP resulted in ventricular fibrillation and in 3 episodes VT was unaffected by ADP. The only significant discriminator between the failure or success of ADP was the rate of VT. ADP was also applied to 17 consecutive patients with an atrial flutter that was resistant to conventional antiarrhythmic agents. Successful conversion of atrial flutter to sinus was seen in only 8 patients (47%). A temporary acceleration to atrial fibrillation appeared in 3 patients (18%), and in 6 patients atrial flutter was unaffected by ADP. ADP was successful in 70% (7/10) of patients with type 1 (< 300 beats/min) atrial flutter. The authors conclude that ADP is beneficial in the interruption of VT and atrial flutter in a selected group of patients, especially with a slower rate of tachyarrhythmia (atrial rate during atrial flutter < 300 beats/min and ventricular tachycardia < 180 beats/min).     

Intestinal phosphate transport in spontaneously hypertensive rats and genetically matched controls

Hypophosphatemia has been documented in patients with hypertension and in spontaneously hypertensive rats compared with genetically matched control Wistar-Kyoto rats. However, renal tubular reabsorption is increased in spontaneously hypertensive rats. Therefore, it was hypothesized that decreased serum phosphate levels in spontaneously hypertensive rats may be related to a decrease in the intestinal transport of phosphate. To test this hypothesis, sodium-dependent phosphate uptake by jejunal brush-border membrane vesicles of spontaneously hypertensive rats and genetically matched Wistar-Kyoto rats was determined. Phosphate uptake consisted of two components: sodium-independent passive diffusion across the brush border and sodium-dependent, carrier-mediated uptake. The initial rate of uptake in spontaneously hypertensive and Wistar-Kyoto rats was linear up to 20 seconds. The initial rate and time course of jejunal sodium-dependent phosphate uptake was decreased in adult spontaneously hypertensive rats compared with corresponding mean values in Wistar-Kyoto rats. This decrease was secondary to a decrease in Vmax rather than Km, suggesting tha the number and/or the activity of the sodium-phosphate transporters is decreased. Sodium-dependent phosphate uptake was pH dependent, with greater uptake at pH 6.0 than at pH 7.4. However, uptake values were lower in spontaneously hypertensive rats than in Wistar-Kyoto rats at all pH levels tested. In contrast, sodium-dependent phosphate uptake in weanling rats (prehypertensive state) was not significantly different between spontaneously hypertensive and Wistar-Kyoto rats. Vitamin D deficiency in both spontaneously hypertensive and Wistar-Kyoto rats decreased Vmax and Km of sodium-dependent phosphate uptake, whereas 1,25(OH)2 vitamin D3 administration increased Vmax and Km in both spontaneously hypertensive and Wistar-Kyoto rats. These results suggest that the hypophosphatemia seen in adult spontaneously hypertensive rats is secondary to a decrease in sodium-dependent phosphate uptake compared with controls. The sodium phosphate transporter in spontaneously hypertensive rats is responsive to vitamin D administration.     

In-hospital outcome of elderly patients with acute coronary syndromes treated with platelet glycoprotein Ⅱb/Ⅲa blockers

Background and objective The safety of intravenous glycoproteinⅡb/Ⅲa inhibitors (GPI) in elderly patients admitted with acute coronary syndrome (ACS) has not yet been established. The purpose of this study was to evaluate the safety of GPI in elderly patients with ACS. Methods Ninety consecutive patients≥70 years of age admitted to a county hospital between 1999-2004 were included. All patients had typical ACS symptoms along with high-risk markers. Results There was no difference in the TIMI risk score between patients who received GPI (n=47) and those who did not (n=43). Patients who received GPI had a lower creatinine clearance (40 cc/min vs. 47cc/min, p= 0.04). Patients who received GPI had a lower incidence of death, reinfarction or major bleeding (19% vs. 4%, p=0.03). There was no significant difference in major bleeding between the 2 groups. None of the patients in either group developed thrombocytopenia. Conclusion This retrospective small study suggests that the use of GPI in a selected group of elderly patients with acute coronary syndrome may be safe. (J Geriatr Cardiol 2005; 2(4):203-205 )