Morphine-6beta-glucuronide modulates the expression of inducible nitric oxide synthase

The immunomodulatory effects of morphine are well established; however, suprisingly little is known about the immunomodulatory properties of the major metabolites of morphine. The present study tests the hypothesis that expression of inducible nitric oxide synthase (iNOS) is modulated by the administration of the morphine metabolite, morphine-6-glucuronide. The initial study using rats shows that morphine-6-glucuronide administration (0, 1.0, 3.163, 10 mg/kg s.c.) results in a pronounced reduction in lipopolysaccharide (LPS)-induced expression of iNOS (inducible nitricoxide synthease) in spleen, lung, and liver tissue as measured by western blotting. Morphine-6-glucuronide also produces a reduction in the level of plasma nitrite/nitrate, the more stable end-product of nitric oxide degradation. In a subsequent study, administration of the opioid receptor antagonist, naltrexone (0.1 mg/kg) prior to the injection of morphine-6-glucuronide (10 mg/kg) blocks the morphine-6-glucuronide induced reduction of iNOS expression and plasma nitrite/nitrite levels indicating that the effect is mediated via the opioid-receptor. This study provides the first evidence that morphine-6-glucuronide alters the expression of iNOS.     

Expression of five viral antigens in cells infected with wild-type and SSPE strains of measles virus: Correlation with cytopathic effects and productivity of infections

Summary Cells infected with four strains (LEC, Biken, IP-3 and DR) of subacute sclerosing panencephalitis (SSPE) virus were compared with wild type measles virus (Edmonston) with respect to titers of extracellular virus, morphology of the cytopathic effect (CPE) and occurrence of different measles virus antigens within infected cells as determined by immune fluorescence. Murine monoclonal antibodies with specifities for the nucleocapsid (NP), polymerase (P), matrix (M), hemagglutinin (H), and fusion (F) proteins as well as specific hyperimmune sera prepared in rabbits against the NP, H and M proteins were used in immune fluorescence analyses of the various strains. All of the strains produced large amounts of NP and P. Only the NP antigen occurred in nuclei of cells. The Edmonston and LEC strains also showed bright fluorescence with the antibodies against the H, F, and M antigens. Immune fluorescent intensity was variably reduced in cells infected with the Biken, IP-3, and DR strains labelled with anti M, H, or F antibodies. The Biken strain produced moderate titers of extracellular virus and moderate amounts of M, H, and F antigens whereas the DR strain produced no extracellular virus and contained no detectable M or F and only trace amounts of H antigen. The IP-3 strain was intermediate both in antigen expression and in production of extracellular virus.     

Dental Care Utilization of Hospitalized Persons Living with HIV and Substance Use

Journal of Community Health - People living with HIV (PLWH) who use drugs experience worse health outcomes than their non-using counterparts. Little is known about how often they seek dental care...     

Effects of a Brief Case Management Intervention Linking People With HIV to Oral Health Care: Project SMILE

Objectives. Although people with HIV experience significant oral health problems, many consistently identify oral health as an unmet health care need. We conducted a randomized controlled trial to evaluate the impact of a dental case management intervention on dental care use.Methods. We evaluated the intervention according to self-reported dental care use at 6-, 12-, and 18-month follow-ups. Multivariable logistic models with generalized estimating equations were used to assess the effects of the intervention over time.Results. The odds of having a dental care visit were about twice as high in the intervention group as in the standard care group at 6 months (adjusted odds ratio [OR] = 2.52; 95% confidence interval [CI] = 1.58, 4.08) and 12 months (adjusted OR = 1.98; 95% CI = 1.17, 3.35), but the odds were comparable in the 2 groups by 18 months (adjusted OR = 1.07; 95% CI = 0.62, 1.86). Factors significantly associated with having a dental care visit included frequent physician visits and dental care referrals.Conclusions. We demonstrated that a dental case management intervention targeting people with HIV was efficacious but not sustainable over time. Barriers not addressed in the intervention must be considered to sustain its use over time.In the era of antiretroviral therapy, people with HIV are living longer and the treatment of associated medical and oral manifestations of the disease has shifted to a chronic disease model.1 Previous studies have shown that a person living with HIV/AIDS is more likely than a person without the disease to experience oral health problems.2–5 Furthermore, the oral health problems of individuals with HIV can be more severe and difficult to treat than those of the general population and may also contribute to the onset of opportunistic infections.5The oral health complications associated with HIV are well documented,2–6 and oral manifestations are increasingly being recognized as markers for monitoring treatment efficacy and predicting treatment failure.7 Oral manifestations, including Kaposi’s sarcoma, necrotizing ulcerative periodontitis, oral hairy leukoplakia, and candidiasis, may be present in up to 50% of people with HIV and 80% of people diagnosed with AIDS,5,6 and may predict low CD4 counts.8 In addition, individuals living with HIV/AIDS may experience difficulty in maintaining adequate salivary flow, which affects chewing, swallowing, and the ability to take medication.4 Chronic use of highly active antiretroviral therapy can also contribute to diminished salivary flow as well as an increased risk of oral candidiasis and oral hairy leukoplakia.9Throughout the 1990s, a series of study findings highlighted the unmet needs for dental care among people with HIV infection.10–14 This gap in oral health care services was corroborated by findings from the oral health component of the HIV Cost and Services Utilization Study,15 which demonstrated that unmet dental needs were twice as common as unmet medical needs among HIV-positive adults16,17 and led to a national call to action to improve access to oral health care.18 That study also showed that approximately half of people living with HIV had dental insurance, and those without dental insurance had greater unmet needs for dental services.17,19,20Recently published findings suggest that an unmet need still persists. One example is an initiative, funded by the Health Resources and Services Administration, that included 2469 people living with HIV who had not received dental care during the preceding year. Nearly half of these individuals (48%) reported an unmet dental need since their HIV diagnosis, 52% had not seen a dentist in more than 2 years, and 63% rated the health of their teeth and gums as fair or poor.21,22 An earlier investigation involving baseline data from the study presented here showed that oral health problems and symptoms were very prevalent among our study population, with 63% of participants having experienced an oral health impact very often or fairly often in the preceding 4 weeks.23Barriers to dental care use among individuals living with HIV include fear of dental care, HIV-specific stigma, fear of disclosing their HIV status to health care providers, perceived cost barriers, and poor adherence to medical guidance.20,22,24–31 Compounding patient access barriers, dental care providers may be reluctant to treat patients with HIV owing to fears of HIV transmission and associated stigma.32–36Previous research conducted in Florida revealed that more than one third of people with HIV do not discuss oral health with their primary care providers.37 Although clinical guidelines recommend that HIV care providers examine the oral cavity during initial and interim physical examinations of people living with HIV, this still may not be a regular clinical practice.37 To address underuse of oral health care services among individuals with HIV, we evaluated the efficacy of an intervention that linked individuals to dental care. The sample comprised a population of HIV-positive individuals in south Florida who had received HIV primary care but had not received oral health services in the preceding 12 months.     

Factors predisposing to seizures in seriously ill infected patients receiving antibiotics: experience with imipenem/cilastatin

Observations on 1,754 patients treated with imipenem/cilastatin in phase III dose-ranging studies in the United States were reviewed to determine risk factors for seizures. The patients were moderately to severely ill with numerous background disorders known to be associated with an increased risk of seizures. Fifty-two patients (3 percent) had seizures and in 16 (0.9 percent) of them the seizures were judged by the investigators to be possibly, probably, or definitely related to imipenem/cilastatin. An incidence of seizure of 2 to 3 percent was noted among patients treated with other antibiotics (usually including a beta-lactam in the regimen) at times when imipenem/cilastatin was not being given. The average time of onset of seizures for patients receiving imipenem/cilastatin was seven days after start of therapy. As with other beta-lactam antibiotics, central nervous system lesions and disorders including seizures and renal insufficiency were found to be strong risk factors for seizures. Imipenem/cilastatin dosages in excess of those currently recommended by the manufacturer, particularly in patients with renal insufficiency, were also associated with an increased risk of seizures. There was an association with Pseudomonas aeruginosa infection that remained statistically significant even after controlling for imipenem/cilastatin dosage as well as for the other factors indicated. A high background incidence of seizures in general in a group of severely ill patients makes it both difficult to assess the etiology of a seizure and important to consider the risk factors when choosing the appropriate dose of an antibiotic. Guidelines are presented for appropriate dosing of imipenem/cilastatin in relation to renal function, body weight, and infecting pathogen.     

Human herpesvirus 6 and multiple sclerosis: systemic active infections in patients with early disease.

By means of immunohistochemical staining, cells actively infected with human herpesvirus 6 (HHV-6) were found in central nervous system tissues from 8 (73%) of 11 patients with definite multiple sclerosis (MS). Interestingly, 17 (90%) of 19 tissue sections showing active demyelination were positive for HHV-6-infected cells compared with only 3 (13%) of 23 tissue sections free of active disease (P<.0001). Central nervous system tissues from 2 of 28 normal persons and patients with other inflammatory demyelinative diseases were positive for HHV-6-infected cells (P<.0001), and the 2 positive cases were diagnosed as having HHV-6 leukoencephalitis. By use of a rapid culture assay, blood samples from 22 (54%) of 41 patients with definite MS were found to contain active HHV-6 infections, compared with 0 of 61 normal controls (P<.0001). No significant difference was found between HHV-6 viremia-positive and HHV-6 viremia-negative MS patients with respect to type of disease (relapsing/remitting or progressive). In contrast, patients with active HHV-6 viremia were significantly younger and had shorter durations of disease than did HHV-6 viremia-negative patients.     

Acute compartment syndrome of the upper extremity in children: diagnosis, management, and outcomes

Purpose

Acute compartment syndrome (ACS) of the upper extremity is a rare but serious condition. The purpose of this study was to determine the etiology, diagnosis, treatment, and outcome of ACS of the upper extremity in a pediatric population.

Methods

We performed a retrospective chart review of all patients who underwent a decompressive fasciotomy for ACS of the upper extremity. Data collected included demographics, injury details, presenting symptoms, compartment measurements, time to diagnosis, time to treatment, and outcomes at the latest follow-up.

Results

Twenty-three children underwent fasciotomies for ACS of the forearm (15) and hand (8), at an average age of 9.3 years (range 0–17.8 years). The most common etiologies were fracture (13) and intravenous (IV) infiltration (3). The most common presenting symptoms were pain (83 %) and swelling (65 %). Compartment pressures were measured in 17/23 patients, and all but two patients had at least one compartment with a pressure >30 mmHg. The final two patients were diagnosed and treated for ACS based on clinical signs and symptoms. The average time from injury to fasciotomy was 32.8 h (3.7–158.0 h). Long-term outcome was excellent for 17 patients (74 %) and fair for 5 (22 %), based on the presence of loss of motor function, stiffness, or decreased sensation. One patient with brachial plexus injury and poor baseline function was excluded from functional outcome scoring. There was no association between the time from diagnosis to fasciotomy and functional outcome at the final follow-up (p = 1.000).

Conclusions

Although ACS of the upper extremity in children is often associated with a long delay between injury and fasciotomy, most children still achieve excellent outcomes. The majority of patients presented with pain and at least one additional symptom, but treatment was often delayed, implying that ACS of the upper extremity in children is a difficult diagnosis to establish and may be associated with a prolonged clinical time course.