Neuropathic pain in end-stage hip and knee osteoarthritis: differential associations with patient-reported pain at rest and pain on activity.

OBJECTIVE: We investigated whether pain at rest and pain on activity were differentially associated with neuropathic pain scores in individuals with end-stage hip and knee OA. DESIGN: Study participants were 843 patients with hip or knee OA scheduled for total joint arthroplasty. In pre-surgery questionnaires, measures of socio-demographics, health status, medication use, neuropathic pain (painDETECT), pain at rest and pain on activity (WOMAC pain items), depression (HADS) and pain catastrophizing (PCS) were collected. Multivariable linear regression models were estimated for men and women separately to examine the association between neuropathic pain scores (outcome) and study measures, entered in blocks. RESULTS: Sample mean age was 65.1 years (SD: 9.6); 57.1% were women. Mean painDETECT scores were significantly higher (P ≤Ö¹ 0.001) for women (11.2 ± 6.6 out of 38) than men (9.3 ± 7.0), with 35.6% of women and 27.7% of men meeting cut-offs for possible or likely neuropathic pain. In the final regression model for women, the coefficients for both types of pain were statistically significant, although the coefficient for pain at rest was 1.6 times greater than that for pain on activity. For men, only pain at rest was significantly associated with neuropathic pain scores. CONCLUSIONS: Findings support that possible neuropathic pain is experienced by a notable proportion of patients with end-stage hip and knee OA and is more strongly associated with pain at rest than pain on activity, particularly in men. Clinical presentation of pain at rest may warrant more thorough evaluation for potential neuropathic pain and have implications for appropriate pain management.

Systemic inflammation and painful joint burden in osteoarthritis: a matter of sex?

OBJECTIVE: We investigated the association between serum levels of C-reactive protein (CRP) and the extent of multijoint pain among individuals with hip/knee osteoarthritis (OA) and determined whether the association differs by sex. DESIGN: Serum CRP and cartilage oligomeric matrix protein (COMP) were determined by enzyme-linked immunosorbent assay (ELISA) in 189 individuals (101 female, 88 male) scheduled for total hip/knee arthroplasty for OA. Patients indicated on a homunculus all painful joints; a summed count was derived. A series of negative binomial regression models was used to investigate the cross-sectional association between painful joint count (outcome) and serum CRP concentrations, adjusting for age, sex, body mass index (BMI), comorbidity count and COMP. An interaction between sex and these biomarkers was tested. RESULTS: Mean age: 66 among women, 65 among men. Women had higher mean joint count (3.7 vs 2.5, P < 0.01; 4+ joint count reported by 37% women, 25% men). Median CRP concentration was higher in women (15.4 mg/l vs 9.3, P = 0.07). From adjusted analyses, the effects of both ln(CRP) and ln(COMP) were modified by sex (P < 0.05). Increasing ln(CRP) was associated with greater painful joint count among women, but not men. CONCLUSIONS: There may be a dose-response association between painful joint burden in OA and systemic inflammation, and it appears the association is sex-specific, which may in part explain inconsistent findings in the literature. Our results underline the importance of showing sex-specific associations in OA, especially when studying the influence of inflammation.

Multiple joint involvement in total knee replacement for osteoarthritis: Effects on patient-reported outcomes.

OBJECTIVE: To determine whether symptomatic (painful/problematic) joints pre-total knee replacement (TKR) surgery influence 1) pre- and 12-month post-TKR patient-reported outcomes (pain, physical function, and mood [fatigue, anxiety, and depression]) and 2) postsurgical pain and function mediated through mood. METHODS: A total of 494 participants completed the patient-reported outcome measures pre- and 12-months post-TKR. Symptomatic (painful/problematic) joints affected by arthritis were indicated on a homunculus presurgery. Covariate data included age, sex, educational attainment, body mass index, and comorbidity. Pre- and postsurgical outcome scores were regressed on symptomatic joint sites and covariates using linear regression analyses; postsurgical scores additionally were regressed on presurgery scores. Path analyses examined whether the effects of symptomatic joint sites on postsurgical pain and function were mediated through mood. RESULTS: The age range was 35-88 years (mean 65 years) and 65% were women. Forty-six percent reported ≥4 symptomatic joints (other than the surgical knee). Pre- and postsurgery, worse outcome scores were observed with increasing joint count. Adjusted for covariates, individuals reporting symptomatic ankles/feet/toes, neck, and spine/lower back had worse presurgery fatigue and anxiety. Adjusted for covariates and presurgery status, worse fatigue for the neck and spine/lower back and worse depression, pain, and function for the ankles/feet/toes and neck were observed postsurgery. The influence of symptomatic ankles/feet/toes on postsurgical pain and function was in part direct and partially mediated through depression. Full mediation was found for the neck through fatigue, anxiety, and depression, and for the spine/lower back through fatigue. CONCLUSION: Findings suggest that a comprehensive approach to osteoarthritis management/care is warranted, and identify important associations between symptomatic joints and mood that negatively impact post-TKR pain and physical function.

The role of brain-gut peptides in the control of sodium appetite.

Ingestion of food and fluid stimulates release of a number of peptides from the gastrointestinal system. These peptides are recognized to act as neurotransmitters/neuromodulators and act at both peripheral and central receptors. Many studies indicate that these peptides are important signals in terminating meals. Recent studies suggest that bombesin, a peptide related to gastrin-releasing peptide, suppresses sodium appetite. We have investigated the role of cholecystokinin (CCK) in the control of sodium appetite. Our studies indicate that CCK is effective at reducing saline intake. We found that exogenous, intraperitoneal CCK octapeptide suppresses saline intake. Moreover, administration of trypsin inhibitor to stimulate endogenous CCK release resulted in suppression of saline intake. Finally, intraperitoneal administration of the CCK receptor antagonist lorglumide resulted in increased saline intake. These observations extend the potential role of gastrointestinal peptides in the modulation of ingestive behavior.

Benzodiazepine use in pregnancy and major malformations or oral cleft: meta-analysis of cohort and case-control studies.

OBJECTIVE: To determine if exposure to benzodiazepines during the first trimester of pregnancy increases risk of major malformations or cleft lip or palate. DESIGN: Meta-analysis. SETTING: Studies from 1966 to present. SUBJECTS: Studies were located with Medline, Embase, Reprotox, and from references of textbooks, reviews, and included articles. Included studies were original, concurrently controlled studies in any language. INTERVENTIONS: Data extraction and quality assessment were done independently and in duplicate. MAIN OUTCOME MEASURES: Maternal exposure to benzodiazepines in at least the first trimester; incidence of major malformations or oral cleft alone, measured as odds ratios and 95% confidence intervals with a random effects model. RESULTS: Of over 1400 studies reviewed, 74 were retrieved and 23 included. In the analysis of cohort studies fetal exposure to benzodiazepine was not associated with major malformations (odds ratio 0.90; 95% confidence interval 0.61 to 1. 35) or oral cleft (1.19; 0.34 to 4.15). Analysis of case-control studies showed an association between exposure to benzodiazepines and development of major malformations (3.01; 1.32 to 6.84) or oral cleft alone (1.79; 1.13 to 2.82). CONCLUSIONS: Pooled data from cohort studies showed no association between fetal exposure to benzodiazepines and the risk of major malformations or oral cleft. On the basis of pooled data from case-control studies, however, there was a significant increased risk for major malformations or oral cleft alone. Until more research is reported, level 2 ultrasonography should be used to rule out visible forms of cleft lip.

Characterization of the surface polypeptides of Strongyloides ratti: a comparison of homogonic and heterogonic strains.

Surface iodination, extraction and SDS-PAGE analysis techniques were employed to characterize and compare the surface polypeptides of two strains of Strongyloides ratti. Third stage infective larvae and parasitic adults of homogonic and heterogonic strains were studied using a variety of surface labelling procedures and detergents for the extraction of labelled molecules. Profiles obtained from SDS-PAGE analysis demonstrated that homogonic and heterogonic strains of S. ratti have identical surface antigens.

Detection of human papillomavirus type 16/18 DNA in cervicovaginal cells by fluorescence based in situ hybridization and automated image cytometry.

Automatic fluorescence image cytometry (AFIC) is a fast, sensitive, and reliable approach for screening slide-based clinical specimens. In this study, we applied AFIC to identify cancer-associated human papillomavirus (HPV) genotypes 16 and 18 in individual cells of cervical smears using a sensitive fluorescence based in situ hybridization (FISH) assay. HPV sequences were labeled by FISH and the cells imaged using an epi-fluorescence microscope coupled to a low-light color CCD camera. Before application to clinical specimens, AFIC was assessed using fluorescent calibration beads and cervical cancer cell lines containing known numbers of integrated HPV genomes per nucleus. Assessment showed that our AFIC had a linear response, was quantitatively accurate, and had the sensitivity to detect one HPV genome per nucleus. After acquisition of images, computer algorithms identified every cell nucleus (via a fluorescent DNA counterstain) and quantified the FISH signal per nucleus. AFIC was employed to screen 27 patient specimens for HPV 16/18, of which 12 were positive. The HPV status of the specimens positively correlated with the pathological diagnosis, and since AFIC automatically and correctly located every cell, it was possible to directly compare morphology and HPV status in the same cell. In conclusion, the combination of FISH and AFIC is a sensitive and quantitative method to detect high risk HPV sequences in cervical smears.

Attenuation of 8-OH-DPAT induced feeding after lesions of the area postrema/immediately adjacent nucleus of the solitary tract.

Rats with lesions of the area postrema/immediately adjacent nucleus of the solitary tract (AP/mNTS-lesions) have an attenuated feeding response after several manipulations that induce food intake in intact control rats. In this study we examined the ingestive response of rats with AP/mNTS-lesions after treatment with 8-OH-DPAT, a 5-HT1A agonist. Rats with AP/mNTS-lesions failed to increase their food intake after treatment with 8-OH-DPAT at doses that stimulated food intake in intact rats. These data suggest that altered serotonergic function may contribute to the attenuation of feeding observed in rats with AP/mNTS-lesions after treatment with some orexigenic stimuli.

Rapid-onset "need-free" sodium appetite after lesions of the dorsomedial medulla.

Previous studies indicate the dorsomedial hindbrain is important in the maintenance of fluid balance. Lesions centering on the area postrema (AP) result in enhanced ad libitum intake of concentrated saline solutions on a 24-h basis as well as enhanced excretion of water and electrolytes. Additionally, rats with lesions of the AP are reported to have an exaggerated behavioral response to dipsogenic challenges that mimic depletion of the extracellular fluid compartment. In the studies reported here, we have observed that rats with lesions of the AP and immediately adjacent nucleus of the solitary tract consume large quantities of concentrated saline solutions within minutes of presentation. This intake does not appear to be related to sodium loss or depletion because the lesioned rats are in a positive sodium balance and the appetite persists after bilateral nephrectomy. These data, in conjunction with earlier studies, suggest that the dorsomedial medulla, including the AP, acts to prevent overconsumption of water and sodium that could result in increased extracellular fluid volume.

Impact of an intermediate care area on ICU utilization after cardiac surgery.

We compared utilization of a 14-bed respiratory ICU before and after establishing an intermediate care area (ICA) for patients recovering from cardiac surgery. Availability of the four-bed ICA significantly reduced the duration of ICU stay in patients who had undergone aortocoronary bypass or valvular cardiac surgery, and no potentially preventable deaths resulted from early ICU discharge. Use of an ICA should also decrease ICU utilization for other low-risk monitored patients.

Elective cesarean hysterectomy: a 5 year comparison with cesarean section.

Elective cesarean sections performed on the obstetric service at the University of Arkansas Medical Center were reviewed for the period January 1, 1970, through December 31, 1974. The purpose of the review was to compare operative and postoperative complications of cesarean section, cesarean section and tubal ligation, and cesarean section and elective hysterectomy. A total of 1,255 cesarean sections were performed of which 207 (17 per cent) were associated with tubal ligation and 242 (18 per cent) with hysterectomy. Elective cesarean hysterectomies were performed for elective sterilization (68 per cent), for medically indicated sterilizations (11 per cent), or for definitive treatment of uterine pathology(21 per cent). All cesarean sections were obstetrically indicated with the exception of 34 primary cesarean hysterectomies performed as definitive treatment of carcinoma in situ of the cervix. The operative procedures were compared in regard to the following characteristics or complications: operating time; incidence of blood transfusions, urinary tract injuries, postoperative bleeding, febrile morbidity, and other postoperative complications; and postoperative hospital days.