Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: The objective of this study was to evaluate the effects of daily dietary supplementation with 1.25 g or 2.5 g of docosahexaenoic (DHA), in the absence of eicosapentaenoic acid (EPA), on serum lipids and lipoproteins in persons with combined hyperlipidemia (CHL) [serum low-density lipoprotein cholesterol (LDL-C) 130 to 220 mg/dL and triglycerides 150 to 400 mg/dL]. METHODS: After a 6-week dietary stabilization period, subjects entered a 4-week single-blind placebo (vegetable oil) run-in phase. Those with adequate compliance during the the run-in were randomized into one of three parallel groups (placebo, 1.25, or 2.5 g/day DHA) for 6 weeks of treatment. Supplements were administered in a triglyceride form contained in gelatin capsules. Primary outcome measurements were plasma phospholipid DHA content, serum triglycerides, high-density lipoprotein cholesterol (HDL-C). LDL-C and non-HDL-C. RESULTS: The DHA content of plasma phospholipids increased dramatically (2 to 3 fold) in a dose-dependent manner. Significant (p < 0.05) changes were observed in serum triglycerides (17 to 21% reduction) and HDL-C (6% increase) which were of similar magnitude in both DHA groups. Non-HDL-C [+1.6 (NS) and +5.7% (p < 0.04)] and LDL-C [+9.3% (NS) and +13.6% (p < 0.001)] increased in the DHA treatment groups. All lipid effects reached an apparent steady state within the first 3 weeks of treatment. CONCLUSION: Dietary DHA, in the absence of EPA, can affect lipoprotein cholesterol and triglyceride levels in patients with combined hyperlipidemia. The desirable triglyceride and HDL-C changes were present at a dose which did not significantly increased non-HDL-C or LDL-C. These preliminary findings suggest that dietary supplementation with 1.25 g DHA/day, provided in a triglyceride form, may be an effective tool to aid in the management of hypertriglyceridemia.     

Cyclic nucleotides attenuate lipid peroxidation-mediated neuron toxicity

Recent studies suggest that increased lipid peroxidation and lipid peroxidation products, such as 4-hydroxynonenal (HNE), contribute to neuronal loss in conditions associated with oxidative stress. The focus of the present study was to determine possible neuroprotective effects of elevated cyclic nucleotide levels against lipid peroxidation and HNE-mediated neural toxicity. Application of 8-bromo derivative analogs of cAMP or cGMP resulted in attenuation of HNE-induced increases in mitochondrial calcium, reactive oxygen species, and neuron loss. Similar results were obtained when neural cells were pretreated with the phosphodiesterase inhibitors zaprinast or isobutylmethylxanthanine (IBMX). These data are consistent with a possible neuroprotective role for elevated cyclic nucleotide levels in disorders associated with increases in lipid peroxidation and HNE.     

Malignancy may adversely influence the quality and behaviour of oocytes

A case series of eight cycles of in-vitro fertilization (IVF) in five women diagnosed with malignant disorders is presented. These patients chose to defer definitive treatment for a chance for preservation of potential fertility. The response of these patients to ovarian stimulation, and the outcome, was compared with 17 IVF cycles in 12 age-matched patients with isolated tubal infertility. An apparent adverse influence of malignant disease on the quality and behaviour of oocytes was observed. Despite a comparable total number of oocytes per cycle in the two groups, a significantly reduced percentage of mature oocytes was retrieved per cycle from patients with malignant diseases. The oocytes from patients with malignant disorders were of a poorer quality and exhibited a significantly impaired fertilization rate compared to the controls. We propose that neoplastic processes, irrespective of the site or cell of origin, may have a detrimental impact on the biology of oocytes, an effect akin to that seen on spermatozoa in men with certain malignancies.     

Immunogenicity of pneumococcal vaccine in persons with spinal cord injury

OBJECTIVE: To determine immunogenicity and optimum timing for administering the 23-valent pneumococcal vaccine after spinal cord injury (SCI). DESIGN: Double-blind, randomized, placebo control study. SETTING: SCI unit in a tertiary care medical center and community. PARTICIPANTS: Eighty-seven persons with recent SCI. INTERVENTION: Participants were randomized to receive either placebo or pneumococcal vaccine at 16 to 18 days versus 4 to 6 months postinjury. MAIN OUTCOME MEASURES: Antibody concentrations were measured prior to intervention and 1, 2, and 12 months afterward to evaluate the immune response to five serotypes of Streptococcus pneumoniae. Effects of demographic and injury-related variables on immune response were also evaluated. RESULTS: Timing of vaccination did not influence mean antibody concentrations for any serotype (p > .05). Ninety-five percent of vaccinated persons had twofold or greater increases in antibody concentration for at least one serotype when measured 1 month after vaccination versus 35% of placebo groups (p < .01). After 12 months, 93% of vaccinated persons in both groups maintained antibody concentrations twofold or greater than baseline values. CONCLUSIONS: Most participants developed an immune response to at least one serotype that was maintained for at least 12 months. Immune response varied according to serotype. Given the favorable immune response and no effect of timing, persons with SCI should receive pneumococcal vaccine during initial hospitalization.     

Inhibitory effect of pulmonary surfactant proteins A and D on allergen-induced lymphocyte proliferation and histamine release in children with asthma

The role of pulmonary surfactant proteins in the pathogenesis of airway inflammation and the impact on asthma has not been elucidated. This study was designed to examine the effect of surfactant proteins A (SP-A) and D (SP-D) on phytohemagglutinin- (PHA) and mite allergen Dermatophagoides pteronyssinus (Der p)-induced histamine release and the proliferation of peripheral blood mononuclear cells (PBMC) in children with asthma in stable condition (n = 21), asthmatic children during acute attacks (n = 9), and age-matched control subjects (n = 7). The results show that SP-A and SP-D were able to reduce the incorporation of [3H]thymidine into PBMC in a dose-dependent manner. In addition to the intact, native SP-A and SP-D proteins, a recombinant peptide composed of the neck and carbohydrate recognition domain (CRD) of SP-D [SP-D(N/CRD)] was also found to have the same suppressive effect on lymphocyte proliferation. This effect was abolished by the presence of 100 mM mannose (for SP-A) or maltose (for SP-D) in the culture medium, which suggested that the CRD regions of SP-A and SP-D may interact with the carbohydrate structures on the surface molecules of lymphocytes. The inhibitory effects of surfactant proteins on PHA- and Der p-stimulated lymphocyte responses were observed in stable asthmatic children and age-matched control subjects, while only a mild suppression (< 25%) was seen in activated lymphocytes derived from asthmatic children with acute attacks. SP-A and SP-D were also found to inhibit allergen-induced histamine release, in a dose-dependent manner, in the diluted whole blood of asthmatic children. We conclude that both SP-A and SP-D can inhibit histamine release in the early phase of allergen provocation and suppress lymphocyte proliferation in the late phase of bronchial inflammation, the two essential steps in the development of asthmatic symptoms. It appears that SP-A and SP-D may be protective against the pathogenesis of asthma.     

Surveillance of non-fatal workplace assault injuries, using police and employers'' reports

BACKGROUND: There is a need to evaluate the effectiveness of laryngeal fracture repair using rigid adaptation plates. METHODS: A retrospective chart review of patients undergoing open repair of laryngeal fractures using metal alloy plates, from 1987 to 1995, was performed. Postoperative airway, deglutition, and voice were assessed. Postoperative follow-up ranged from 1 to 58 months (median, 27 months). All 10 patients sustained blunt or penetrating laryngeal trauma. After patients were resuscitated according to the ABC principles recommended by the American College of Surgeons, each underwent open repair of laryngeal fractures using rigid adaptation plates. RESULTS: Outcome was measured by perceptual analysis of the postoperative airway, swallowing, and voice, as well as biocompatibility. Ten patients underwent repair and stabilization of the larynx using adaptation plates. Nine patients sustained blunt trauma, and one patient sustained penetrating trauma. Voice was subjectively graded as good if it resembled the preinjury status, fair if it differed, and poor if it represented aphonia, whisper, or unintelligible speech. Airway was graded as good if it resembled preinjury status, fair if mild exercise intolerance or aspiration existed, and poor if the patient could not be decannulated. Nine patients had a good airway following repair, and six of seven patients requiring tracheotomy were decannulated. All patients tolerated the plates well and suffered no surgical complications. CONCLUSION: Repair of the laryngeal framework using adaptation plates provides adequate, immediate stabilization with restoration of function and is an alternative to traditional methods of repair.     

Predictors of treatment adherence among asthma patients in the emergency department

N-Nitroso-N-(3-keto-1,2-butanediol)-3'-nitrotyramine (NO-NTA) is a product of model browning system generated in the presence of sodium nitrite. The chemical structure of this compound has been confirmed by UV, mass and nuclear magnetic resonance, and infrared spectroscopy in our previous study. A two-stage transformation protocol was used to chemically transform the mouse embryo fibroblasts C3H10T1/2 cells. To initiate transformation, the cells were treated with benzo[a]pyrene (BaP) (0.1 mg/ml), and NO-NTA (0.01, 0.1 and 1 mg/ml) was employed subsequently to complete the transformation process. Malignant transformed foci were formed in BaP-initiated and NO-NTA promoted C3H10T1/2 cells after 8 wk. Cells treated with NO-NTA alone failed to induce transformation. However, cells initiated with BaP and promoted by cells initiated with BaP and promoted by NO-NTA demonstrated oncogenic properties. Cell lines transformed with NO-NTA-transformed colonies exhibited enhanced growth rate, anchorage independence and tumorigenicity in animals relative to parent cells. These results indicate that NO-NTA is a new tumour promoter and may induce tumour promotion by two-stage oncogenesis. Further studies on the mechanism of action of NO-NTA are now in progress.     

Intrathecal granuloma complicating chronic spinal infusion of morphine. Report of three cases

OBJECTIVE: To assess the frequency of methotrexate (MTX)-induced pancytopenia in rheumatoid arthritis (RA). METHODS: A MEDLINE literature search was conducted to identify articles published during the last 15 years (1980-1995) that presented data on MTX-associated pancytopenia. Two case reports of our own experience are also presented. In addition, articles that examined risk factors associated with MTX-related pancytopenia were identified. RESULTS: A total of 70 patients with pancytopenia related to MTX therapy were identified (68 reported in the literature, 2 from our own experience). Sixty-one of the patients were described in published case reports, 7 patients were from 5 long-term prospective studies. In many of these cases, predisposing factors for the development of pancytopenia were described. The 5 long-term prospective studies reported toxicity data on patients who had been treated with MTX for at least 13 weeks. A total of 511 patients were included in the prospective trials, yielding an overall incidence of pancytopenia of 1.4% (7 of 511). Of the 70 cases reported, 12 patients died (17%). Most of them had impaired renal function, hypoalbuminemia, concurrent infection, and/or concomitant medication with more than 5 drugs. The minimal cumulative MTX dose leading to fatal pancytopenia was 10 mg, observed in one of our patients. CONCLUSION: Pancytopenia is not an uncommon side effect of low-dose pulse MTX therapy in RA. It can lead to serious complications, including death.