Tumor necrosis factor-alpha in whole blood cultures of preeclamptic patients and healthy pregnant and nonpregnant women.

OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) is recognized as a likely mediator of the excessive endothelial activation and injury that is a key pathogenetic mechanism of preeclampsia. We used whole blood cell cultures from 12 patients with severe preeclampsia and from 12 healthy pregnant and nonpregnant women to determine the release of TNF-alpha by unstimulated leukocytes as a measure of their state of activation, and their response to stimulation with lipopolysaccharide (LPS) as an indicator of their state of priming. METHODS: Blood was cultivated without and with LPS, and TNF-alpha release was measured after six and 24 hours of cultivation by enzyme-linked immunoassays. Differential leukocyte counts were performed, and TNF-alpha values calculated per 10(5) monocytes. RESULTS: In unstimulated whole blood cultures, TNF-alpha release after six hours of cultivation was similar in all three groups; but after 24 hours, TNF-alpha concentrations in culture supernatants from preeclamptic patients were significantly higher than were values obtained in blood from normotensive pregnant women. In LPS-stimulated blood cultures with a maximum of TNF-alpha release at six hours cultivation time, TNF-alpha concentrations were significantly lower in preeclamptic women than they were in both control groups. We showed in an additional experiment that a strong LPS challenge following preactivation with high doses of LPS resulted in reduced release of TNF-alpha compared with release of TNF-alpha following preactivation with low doses of LPS. CONCLUSIONS: The observed high capacity for spontaneous TNF-alpha release by leukocytes in preeclampsia indicates activation of TNF-alpha producing leukocytes by the disease process. Preactivation and exhaustion of leukocytes by leakage of TNF-alpha could lead to the reduced response to TNF-alpha inducer LPS as observed in blood cultures from preeclamptic patients.     

Effects of a monoclonal antibody raised against nerve growth factor on skeletal pain and bone healing after fracture of the C57BL/6J mouse femur.

A closed femur fracture pain model was developed in the C57BL/6J mouse. One day after fracture, a monoclonal antibody raised against nerve growth factor (anti-NGF) was delivered intraperitoneally and resulted in a reduction in fracture pain-related behaviors of approximately 50%. Anti-NGF therapy did not interfere with bone healing as assessed by mechanical testing and histomorphometric analysis. INTRODUCTION: Current therapies to treat skeletal fracture pain are limited. This is because of the side effect profile of available analgesics and the scarcity of animal models that can be used to understand the mechanisms that drive this pain. Whereas previous studies have shown that mineralized bone, marrow, and periosteum are innervated by sensory and sympathetic fibers, it is not understood how skeletal pain is generated and maintained even in common conditions such as osteoarthritis, low back pain, or fracture. MATERIALS AND METHODS: In this study, we characterized the pain-related behaviors after a closed femur fracture in the C57BL/6J mouse. Additionally, we assessed the effect of a monoclonal antibody that binds to and sequesters nerve growth factor (anti-NGF) on pain-related behaviors and bone healing (mechanical properties and histomorphometric analysis) after fracture. RESULTS: Administration of anti-NGF therapy (10 mg/kg, days 1, 6, and 11 after fracture) resulted in a reduction of fracture pain-related behaviors of approximately 50%. Attenuation of fracture pain was evident as early as 24 h after the initial dosing and remained efficacious throughout the course of fracture pain. Anti-NGF therapy did not modify biomechanical properties of the femur or histomorphometric indices of bone healing. CONCLUSIONS: These findings suggest that therapies that target NGF or its cognate receptor(s) may be effective in attenuating nonmalignant fracture pain without interfering with bone healing.     

Management of older patients presenting after a fall--an accident and emergency department audit.

BACKGROUND: It is common for older patients to present to accident and emergency (AE) departments after a fall. Management should include assessment and treatment of the injuries and assessment and correction of underlying risk factors in order to prevent recurrent falls. OBJECTIVES: To determine management of older patients presenting after a fall to the AE department of Groote Schuur Hospital in Cape Town, South Africa. METHOD: Hospital records were reviewed for a random sample of 100 patients aged 65 years and older presenting to the AE department after a fall, between December 2001 and May 2002. RESULTS: The mean age of the sample was 78.6 years (range 65-98 years); 72% of subjects were female. History of a previous fall, and history of drug or alcohol intake, were recorded in less than 20% of cases. Blood pressure and pulse rate were recorded in approximately 90% of cases, and pulse rhythm and postural blood pressure in 2%. Examination of the musculoskeletal system was done in 86% of cases and that of other systems in less than 50%; cognitive assessment was conducted in less than 30%. Radiological investigations were performed in 89% of cases, glucose and haemoglobin in 32%, renal profile and electrocardiogram in 5%, and urinalysis in 4%. Three-quarters of the patients were referred for further management: 52% to orthopaedic surgery, 12% to other surgical subspecialties, 6% to the general medical department, and 6% to other hospitals and clinics. No referrals were made to geriatric medicine, physiotherapy or occupational therapy. CONCLUSIONS: In managing elderly patients after a fall, the AE department focused on injuries sustained. Little effort was made to establish and manage risk factors, hence to prevent recurrent falls. Guidelines are needed for the management of such patients in AE departments.     

A Randomized Pilot Study of Behavioral Treatment to Increase Calorie Intake in Toddlers With Cystic Fibrosis

This pilot study examined a behavioral treatment to increase calorie intake in toddlers with cystic fibrosis. Eight toddlers were randomly assigned to behavioral plus nutrition (BEH) or nutrition intervention (NTR) conditions. Calorie intake and weight were measured at pre- and posttreatment. The BEH group showed a trend for changes in calorie intake pre- to posttreatment (p = .07; 40% increase). Results for the BEH and NTR groups did not differ significantly. Most participants achieved weight gains consistent with normal growth. Seventy-five percent had not shown this pattern during the year prior to intervention. These results support the feasibility and potential for behavioral interventions in this age group.     

The Relationship Between Daily Life Stress and Gastrointestinal Symptoms in Women with Irritable Bowel Syndrome

Research on irritable bowel syndrome (IBS), a functional disorder of the gastrointestinal (GI) system, has linked GI symptoms to stress. This study examined the relationship between daily stress and GI symptoms across women and within woman in IBS patients (n = 26), IBS nonpatients (IBS-NP; n = 23), and controls (n = 26), controlling for menstrual cycle phase. Women (ages 20–45) completed daily health diaries for two cycles in which they monitored daily GI symptoms and stress levels. The Life Event Survey (LES) was used as a retrospective measure of self-reported stress. The across-women analyses showed higher mean GI symptoms and stress in the IBS and IBS-NP groups relative to controls but no group differences in LES scores. The within-woman analyses found a significant and positive relationship between daily stress and daily symptoms in both the IBS-NP and the IBS groups. Controlling for menstrual cycle had no substantial impact on the results.     

Short term effect of diltiazem on portal hypertension in patients with non-cirrhotic portal fibrosis

Fourteen patients of non-cirrhotic portal fibrosis (NCPF) with portal hypertension were put on oral diltiazem hydrochloride (90 mg/day) or placebo on a prospective, randomised, single blind basis for 15 days. Predrug hemodynamic and biochemical status were similar in both groups. Diltiazem produced significant reduction (p less than 0.001) in mean intrasplenic pressure: from 41.88 (SD +/- 6.18) to 21.5 (+/- 7.91) cm of normal saline as against 45.56 (+/- 9.45) to 43.33 (+/- 8.27) in the placebo group. Mean arterial pressure (MAP), heart rate and cardiac output (CO) did not change in either group. Thus, the calcium channel blocker diltiazem reduces portal pressure in patients with NCPF, independent of reduction in MAP and CO; this is advantageous in situations where compromised cardiac hemodynamics may prove deleterious.     

Painful sensory symptoms in neuroleptic-induced extrapyramidal syndromes.

OBJECTIVE: The authors tested the hypothesis that neuroleptic-induced extrapyramidal syndromes are associated with painful sensations objectively conforming to the characteristics of primary sensory symptoms as reported in idiopathic and postencephalitic parkinsonism. METHOD: The frequency of subjective painful sensory symptoms and their relation to neuroleptic-induced extrapyramidal syndromes were examined in a consecutive series of 107 psychiatric patients newly admitted to acute care units at a teaching hospital. Patients without illnesses or conditions likely to be associated with pain were included in the study if they had a diagnosis other than organic mental syndromes and were receiving psychotropic medications as prescribed by their treating physicians. Structured interviews with a modified version of the McGill Pain Questionnaire to assess sensory complaints and neurological examinations for neuroleptic-induced extrapyramidal syndromes (parkinsonism and akathisia) were conducted independently by two raters blind to each other's findings and patients' medication status. RESULTS: Fourteen (23%) of 60 patients receiving neuroleptics reported experiences of spontaneous pain subjectively attributed to pharmacological treatment, compared with only one (2%) of 47 patients receiving psychotropic medications other than neuroleptics. There was no difference between these two groups in subjective complaints of paresthesia (8% versus 9%). Twelve (55%) of the 22 patients with neuroleptic-induced extrapyramidal syndromes reported pain, compared with only two (5%) of the 38 patients who received neuroleptics but did not experience extrapyramidal syndromes. CONCLUSIONS: Although consonant with the study hypothesis, these results should be regarded as preliminary and interpreted conservatively in the light of the methodological limitations of the study.     

Observation on serum prolactin in hepatic cirrhosis.

Serum prolactin assays in patients of hepatic cirrhosis were analysed. Patients with cirrhosis had higher values of serum prolactin (27.2 +/- 5.1 ng/ml in males and 38.4 +/- 4.1 ng/ml in females) as compared to control subjects (p less than 0.05). Majority of patients of cirrhosis with suspected portal-systemic encephalopathy had significantly higher serum prolactin than those without encephalopathy (p less than 0.05). Significantly higher values of serum prolactin on admission had positive correlation with mortality (p less than 0.01). Clinico-biochemical severity of hepatic dysfunction was directly correlated with level of serum prolactin. The present study reveals the possibility of diagnostic and prognostic values of serum prolactin in cirrhosis, specially in clinical/sub-clinical subsets of portal-systemic encephalopathy.