Mapping the rat somatosensory pathway from the anterior cruciate ligament nerve endings to the cerebrum

The anterior cruciate ligament (ACL) serves as the primary restraint to anterior tibial translation. In addition to this biomechanical function, the ACL appears to have a function in neuromuscular control. This hypothesis was formulated after the discovery of mechanoreceptors within the ACL. The full somatosensory pathway from the ACL to the cerebrum has yet to be elucidated. In order to map this sensory pathway, we conducted a viral trans-synaptic tracing experiment using the neurotropic pseudorabies virus (PRV). The pseudorabies virus was injected into the ACL of rats and allowed to replicate and spread trans-synaptically for 6-7 days. The brain and spinal cord of each sacrificed rat was then removed and processed immunohistochemically to detect the presence of PRV. PRV-immunoreactive neurons were found to be localized in several different regions from the spinal cord to the cerebrum. Four nuclei in the reticular formation of the brain stem demonstrated strong positive labeling: the mesencephalic reticular nucleus, magnocellular reticular nucleus, paragigantocellular reticular nucleus, and gigantocellular reticular nucleus. This finding suggests that the nerve endings of the rat ACL project into the cerebrum and that the reticular formation may play an important role in the afferent pathway of those nerve endings.     

A randomized, double-blind, crossover comparison of risperidone and haloperidol in Korean dementia patients with behavioral disturbances.

OBJECTIVE: Behavioral disturbances in dementia are extremely prominent and distressful, and often result in serious physical, social, and economic consequences. The authors compared the efficacy and tolerability of risperidone and haloperidol in the treatment of behavioral and psychological symptoms of dementia (BPSD) in institutionalized elderly Korean patients with Alzheimer disease, vascular dementia, or mixed dementia. METHODS: This was an 18-week double-blind, crossover study involving 120 patients who were randomly assigned to receive flexible doses (0.5-1.5 mg/day) of risperidone or haloperidol. BPSD were assessed using the Korean version of the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD-K), the Korean version of the Cohen-Mansfield Agitation Inventory (CMAI-K), and the Clinical Global Impression of Change scale (CGI-C). Safety and tolerability assessments included the Extrapyramidal Symptom Rating Scale and the incidence of adverse events. RESULTS: Both risperidone and haloperidol were efficacious in alleviating BPSD. However, when receiving risperidone, patients showed significantly greater improvement than when receiving haloperidol in the total and subscale scores of the BEHAVE-AD-K, the total and subscale scores of the CMAI-K, and the scores on the CGI-C scale. Also, risperidone had an additional benefit on aggressiveness and anxieties/phobias. The risk of antipsychotic-induced parkinsonism throughout this study was significantly lower with risperidone than with haloperidol. CONCLUSION: Risperidone had a favorable efficacy and tolerability profile compared with haloperidol in the treatment of BPSD in this patient population.     

Characteristics of teenage mothers and predictors of breastfeeding initiation in the Michigan WIC Program in 1995. Women, Infants, and Children.

Although breast milk is recommended as the optimal source of infant nutrition, breastfeeding initiation is below recommended levels, especially among teenage mothers. Breastfeeding initiation rates among Michigan (US) teenage mothers (12-19 y) were compared by demographics and health behaviors. Multivariate analyses determined which factors were significant independent predictors of breastfeeding initiation among teenage mothers enrolled prenatally in the Michigan Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) program in 1995. Significant predictors independently associated with breastfeeding initiation were race/ethnicity, education, marital status, postpartum anemia status, parity, prenatal trimester of WIC enrollment, and smoking. The strongest predictor of breastfeeding initiation differed for white mothers (positive predictor: education beyond high school [OR = 3.13]) and black mothers (negative predictor: multiparous [OR = 0.25]). Initiation rates for this population of teenage mothers fall below the national average for mothers of all ages and the US Healthy People 2010 goals. Research is needed concerning how breastfeeding support and education can be improved to reach the US national health goals.     

Stereoselective metabolism of lansoprazole by human liver cytochrome P450 enzymes.

The stereoselective metabolism of lansoprazole enantiomers was evaluated by incubation of human liver microsomes and cDNA-expressed cytochrome p450 (p450) enzymes to understand and predict their stereoselective disposition in humans in vivo. The intrinsic clearances (Clint) of the formation of both hydroxy and sulfone metabolites from S-lansoprazole were 4.9- and 2.4-fold higher than those from the R-form, respectively. The sums of formation Clint of both metabolites were 13.5 and 57.3 microl/min/mg protein for R- and S-lansoprazole, respectively, suggesting that S-lansoprazole would be cleared more rapidly than the R-form. The p450 isoform selective inhibition study in liver microsomes, and the incubation study of cDNA-expressed enzymes, demonstrated that the stereoselective sulfoxidation is mediated by CYP3A4 and that the hydroxylation is mediated by CYP2C9 and CYP3A4 as well as by CYP2C19. Total Clint values of hydroxy and sulfone metabolite formation catalyzed by all these p450 enzymes were consistently higher for S-lansoprazole than for the R-form. The CYP3A4 produced the greatest difference of Clint between S- and R-enantiomers, mainly due to a difference of sulfoxidation metabolism (Clint 76.5 versus 10.8 microl/min/nmol of p450, respectively), whereas CYP2C19-catalyzed hydroxylation resulted in a minor difference of Clint between S- and R-enantiomers (179.6 versus 143.3 microl/min/nmol of p450, respectively). However, the affinity of CYP2C19 on hydroxylation was 5.7-fold higher for S-enantiomer than for the R-form (Km 2.3 versus 13.1 microM), suggesting that the role of CYP2C19 on stereoselective hydroxylation would be more prominent at concentrations around the usual therapeutic level. These findings suggest that both CYP2C19 and CYP3A4 are major enzymes contributing to the stereoselective disposition of lansoprazole, but stereoselective hydroxylation of lansoprazole enantiomers is mainly influenced by CYP2C19, especially at the usual therapeutic doses.     

Thymidine labeling index in breast tumors

The relationship between primary tumor proliferative activity and clinical and pathologic characteristics was analyzed in relation to menopausal status in 32 patients with malignant or benign breast disease. The thymidine labeling index (TLI) showed significantly higher median values in the cancer patients (3.48 per cent) than in the patients with benign diseases (1.02 per cent). TLI was not significantly affected by delayed incubation at room temperature for about 1 hour. In the breast cancer patients, TLI did not significantly correlate to tumor size, the presence of axillary lymph node metastasis or pathologic nuclear grading. The only significant difference was limited to the breast cancer patients without axillary lymph node metastasis in relation to menopausal status; the TLI in the premenopausal patients (5.10 per cent) was significantly higher (p<0.05) than that in the postmenopausal patients (2.28 per cent). These data thus suggest that among premenopausal patients without axillary lymph node metastasis, those with a high TLI could be potential candidates for adjuvant chemotherapy.     

A SLAP lesion associated with calcific tendinitis of the long head of the biceps brachii at its origin

Calcific tendinitis is a common condition with characteristic clinical and radiological findings. Although we do not know which condition initiated the pathologic cascade, we present a rare case of calcific tendinitis of the long head of the biceps brachii at its origin, associated with a SLAP lesion. The calcium deposit was removed and the SLAP lesion was repaired with a suture anchor arthroscopically.     

Simple measurement of spinal cord evoked potential: a valuable data source in the rat spinal cord injury model.

Measurement of spinal cord evoked potentials (SCEPs) is proposed as a means of predicting locomotion outcome in the rat spinal cord injury (SCI) model. Using 55 rats, three reproducible peak waves (waves I, II and III) were observed during stimulation at the C7 level with recording at the L1 epidural space. Hemisection at the T13 level showed three wave loss patterns: wave III loss only, loss of both wave II and III, and loss of all three waves. Defining an ideal SCI model as establishment of stable monoparesis or paraparesis, all animals in the wave II-III loss group showed favorable results. Histological data and electrophysiological properties allowed reasonable assumptions of wave origin: wave I from extrapyramidal tracts, wave II from the ventral corticospinal tract, and wave III from the dorsal corticospinal tract. Complete destruction of pyramidal tracts in both dorsal and ventral fibers was essential for long-term impairment of locomotion.