Lumbar Spinal Stenosis: Therapeutic Options Review

Lumbar spinal stenosis (LSS) functionally impacts significant numbers of Americans per year. Current estimates place the number of Americans suffering from senescent lumbar spinal stenosis at 400,000. The prevalence of this disorder in patients ranging from 60 to 69 years of age is very high. Forty‐seven percent of this age group have mild to moderate stenosis, and 19.7% have severe stenosis. As the baby boomer generation gets older, 10,000 individuals attain the age of 65 years every day in United States. LSS is becoming very common and will be a major healthcare issue as the population ages. Although LSS is not life threatening, it can cause substantial disability with limitations to performing daily activities, and thus, the associated negative impact on quality of life (QOL). This article reviews the pathophysiology and current treatment options for LSS, focusing on evidence‐based treatment options.     

Safety and efficacy of epinephrine added to bupivacaine for lumbar epidural analgesia in obstetrics

The effects of epidural bupivacaine with and without 1:300,000 epinephrine on uterine activity, progress of labor, fetal heart rate, maternal blood pressure and heart rate, newborn Apgar scores, neonatal acid-base status, and Neurologic and Adaptive Capacity Scoring System (NACS) were compared in 32 parturients during labor and delivery. Patients in group I (n = 16) received 0.5% bupivacaine with 1:300,000 epinephrine and those in group II (n = 16) received 0.5% bupivacaine alone. Addition of epinephrine to bupivacaine had no significant effects on uterine activity, duration of first or second stages of labor, fetal heart rate and variability, or the incidence of abnormal fetal heart rate patterns. Maternal hypotension occurred less frequently in group I than in group II patients (P less than 0.05). Apgar scores, neonatal acid-base status, and the NACS were equally good in the two groups. Duration of analgesia was significantly longer in group I than in group II (186.8 +/- 11.6 vs 85.3 +/- 6.1 (mean +/- SEM) min, P less than 0.001). It is concluded that adding epinephrine to bupivacaine during epidural anesthesia in the normal parturient has no adverse effects on either mother, fetus, neonate, or the progress of labor; and that it significantly prolongs the duration of anesthesia and decreases the incidence of maternal hypotension.     

Amyloid precursor protein mRNA levels in Alzheimer's disease brain

Insoluble beta-amyloid deposits in Alzheimer's disease (AD) brain are proteolytically derived from the membrane bound amyloid precursor protein (APP). The APP gene is differentially spliced to produce isoforms that can be classified into those containing a Kunitz-type serine protease inhibitor domain (K(+), APP(751), APP(770), APRP(365) and APRP(563)), and those without (K(-), APP(695) and APP(714)). Given the hypothesis that Abeta is a result of aberrant catabolism of APP, differential expression of mRNA isoforms containing protease inhibitors might play an active role in the pathology of AD. We took 513 cerebral cortex samples from 90 AD and 81 control brains and quantified the mRNA isoforms of APP with TaqMan real-time RT-PCR. After adjustment for age at death, brain pH and gender we found a change in the ratio of KPI(+) to KPI(-) mRNA isoforms of APP. Three separate probes, designed to recognise only KPI(+) mRNA species, gave increases of between 28% and 50% in AD brains relative to controls (p=0.002). There was no change in the mRNA levels of KPI-(APP 695) (p=0.898). Therefore, whilst KPI-mRNA levels remained stable the KPI(+) species increased specifically in the AD brains.     

Evaluation of the effects of VKORC1 polymorphisms and haplotypes, CYP2C9 genotypes, and clinical factors on warfarin response in Sudanese patients

Objective

African populations, including the Sudanese, are underrepresented in warfarin pharmacogenetic studies. We designed a study to determine the associations between the polymorphisms and haplotype structures of CYP2C9 and VKORC1 and warfarin dose response in Sudanese patients, one of the most genetically diverse populations in Africa.

Material and methods

The effect of the CYP2C9 polymorphisms (*2, *3, *5, *6, *8, *9, and *11), 20 VKORC1 tag SNPs and haplotypes, and clinical covariates were comprehensively assessed in 203 Sudanese warfarin-treated patients.

Results

Patients with the CYP2C9*2,*5,*6, or *11 variant required a daily warfarin dose that was 21% lower than those with CYP2C9*1/*1 (4.7 vs 5.8?mg/day, P?VKORC1 and POL3S genes were divided into two haplotype blocks in Sudanese populations. According to multiple linear regression results, rs8050984, rs7294, and rs7199949 in the VKORC1 and POL3S genes (P?<0.001, <0.001, <0.001, respectively), CYP2C9 genotype (*2, *5, *6, *11; P?P?=?0.04), target INR (P?=?0.007), and concurrent medications (P?=?0.029) could explain about 36.7% of the total warfarin dose variation.

Conclusion

Our data revealed that VKORC1 and CYP2C9 polymorphisms are important factors that influence warfarin dose response in Sudanese patients. Our data suggest that combinations of the SNPs may improve predictions of warfarin dose requirements.     

Split course pelvic irradiation and a boost for carcinoma of the prostate

Fifty nine patients with prostatic cancer treated by definitive external irradiation were retrospectively evaluated. The true pelvis and prostate gland were irradiated by a split course technique for 48-50 Gy and 68-70 Gy in 7 weeks with a booster dose of 20 Gy delivered in the rest period (after 24-26 Gy) to the prostate via small ports. The overall 3 and 5 year actuarial survival was 83% and 75%, respectively. Only four patients had persistent local disease and two of these (Stage D) died with local disease and distant metastases. Acute mild diarrhea or mild cystitis occurred in 26 patients whereas two patients developed chronic diarrhea lasting for 2 and 12 months after therapy. There were no long-term complications requiring interventional surgery. Sexual potency did not seem to be affected. These results indicate that carefully performed external radiotherapy with a booster dose delivered half-way through whole pelvic radiation is very well tolerated without affecting the local control rate.