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The effect of vagus nerve stimulation on migraines.

Vagus nerve stimulation (VNS) inhibits nociceptive behavior in animals. VNS might reduce pain in patients with VNS device implanted for intractable seizures. One case report described possible benefits on migraines. We contacted all patients who received VNS therapy for intractable epilepsy between 1993 and 1999 at Southern Illinois University, Springfield, Illinois. Patients who had concomitant chronic pain were subsequently interviewed. Pain intensity before and after VNS implantation was rated by the patient as average, worst, and least and on numeric rating scale from 1 to 10. Current pain measurements were compared to preimplantation by using Global Pain Relief Rating Scale. Of 62 patients who received VNS, 27 patients were interviewed; 4 patients had common migraine, and no other chronic pain syndromes were identified. All patients with migraine reported reductions in headache frequency and numeric rating scale score for average and least headache intensity. One patient reported complete relief of headaches. Improvement was reported to start 1 to 3 months after initiation of therapy. On Global Pain Relief Rating Scale, 1 patient reported complete pain relief, 2 reported a lot of pain relief, and 1 reported slight pain relief. Concomitant antiepileptic drugs were decreased in 3 patients and slightly increased in 1. VNS might be beneficial for prophylactic therapy of migraine.

Adult↗

Relationship between depression and quality of life in Nigerian outpatients with heart failure.

OBJECTIVE: Our objective was to evaluate the relationship between depression and health-related quality of life (QoL) in Nigerian outpatients with heart failure (HF). METHODS: We used a cross-sectional study in which outpatients with HF (n=100) completed the WHO Quality of Life Scale-Brief Version to assess their subjective QoL. The patients were also assessed for the diagnosis of major depressive disorder (MDD) in accordance with the Diagnostic and Statistical Manual of Mental Health Disorders, Fourth Edition. RESULTS: The factors independently associated with poor QoL include disability due to illness, presence of MDD, younger age, and longer duration of illness. Patients with MDD had worse QoL than patients without MDD on dimensions of physical health, psychological health, and environment. CONCLUSION: Depression adversely affects the QoL of patients with HF. Programs designed to improve the QoL of patients with HF need to incorporate the early identification and treatment of depression. Future studies are warranted to investigate the impact of improved depression management on QoL in patients with HF.

Animals↗

Binding kinetics, uptake and intracellular accumulation of F105, an anti-gp120 human IgG1kappa monoclonal antibody, in HIV-1 infected cells.

The use of targeting moieties is a new and exciting field of scientific research for facilitating the specific delivery of therapeutic agents in HIV-infected patients. The interaction of a potential targeting moiety with its ligand is a crucial factor in the evaluation of a targeted approach for chemotherapeutic intervention. Therefore, we have further characterized the interaction between a potential targeting agent, the monoclonal human antibody F105, and its ligand gp120, a glycoprotein expressed on the surface of HIV-1 infected cells. We demonstrate the specificity of binding and entry of F105 to infected cells. F105 was rapidly taken up into the cell and accumulated in the Golgi apparatus. Kinetic analysis of the F105-gp120 interaction revealed an equilibrium dissociation constant (K(D)) of 0.62 nM, compared with the gp120-CD4 interaction where the K(D) was determined at 35 nM. Consequently, F105 displayed a higher gp120 affinity. This was due to a slower dissociation as compared with the natural ligand. These data further underline the potential of monoclonal antibodies as targeting agents, and offer new insights into the possibility of F105 as a targeting moiety for the delivery of antiretroviral drugs to HIV-1 infected cells.

Acquired Immunodeficiency Syndrome↗

Multidrug resistance in Salmonella enterica serovar typhi isolated from patients with typhoid fever complications in Lagos, Nigeria.

OBJECTIVE: The aim of this study was to determine the prevalence of Salmonella enterica serovar typhi in patients with pyrexia of unknown origin (PUO), and antimicrobial resistance in strains isolated from patients with S. typhi in Lagos, Nigeria. STUDY DESIGN: In total, 103 patients were included in this study, subdivided into two categories. Category A comprised 74 patients presenting with PUO, and Category B comprised 29 patients harbouring S. typhi who did not respond to initial treatment. METHODS: Blood samples were cultured for bacterial isolates and identified by standard procedures. Susceptibility testing was performed according to the National Committee for Clinical Laboratory Standards. Plasmid DNA extraction was performed using the alkaline lysis method with Escherichia coli v517 used as the standard. Conjugation and transformation experiments were performed using standard methods. For the latter, E. coli K12 HB 101 (ara-14, galK2, hsd 520, lacyl, leu, mtl-1, Pro A2, rec A13, rps L20, sup E44, thii xyl-5) was used as the recipient and plasmid PBR 322 was used as the positive control. RESULTS: The prevalence of S. typhi in PUO was 16.2% (12/74). In all, 25 of 41 (61.0%) cases were multidrug resistant (MDR) with phenotypic-resistant patterns: ACoCT, ACTCeS, ACTCoCe and ACTS were commonly encountered among the strains. Interestingly, four of the strains harbouring similar plasmid DNA were isolated from patients with hepatosplenomegaly, and a strain harbouring a large transferable plasmid of 81.2MDa was isolated from a psychosis patient. CONCLUSIONS: Our study confirmed the circulation of MDR S. typhi in Lagos, Nigeria. Periodic review of antibiotics used in hospitals is essential as the efficacies of chloramphenicol, ampicillin and cotrimoxazole are now doubtful. Ciprofloxacin and ofloxacin are effective drugs for treatment of typhoid fever, but with current trends of drug abuse in Nigeria, resistance is likely to develop. These results, therefore, provide an early warning signal for the prudent use of fluoroquinolone antimicrobials to preserve their usefulness.

Anti-Bacterial Agents↗

Experimental workflows for the accurate identification of mitochondrial redox events.

The study of redox biology has been growing constantly since the last decades. Over these years, redox processes have been linked to an extraordinarily wide range of physiological and pathological events, becoming recognized as central mechanisms underlying many of them. In this context, it becomes essential to understand the advantages and limitations of the tools under use, to recognize the specific controls required for each measurement and to accurately distinguish between distinct redox mechanisms. So far, multiple and excellent reviews have dealt with either the tools, the protocols or the mechanisms involved in reactive oxygen species (ROS) production and quenching, a.k.a. redox events. However, a review outlining the workflows to appropriately detect them is still lacking. We define workflow as the combination of tools, methods and mechanistic knowledge that allow the definition of a specific redox event. In this review, we aim to provide an optimal workflow for the research on mitochondrial redox events. To this end, we first summarize the molecular tools available to measure and quench ROS. We then explain the mechanisms of ROS production and scavenging in several of the cellular compartments, with special focus on mitochondria, as well as their implication in physiology and disease. Finally, we use the knowledge in all sections to build a recommended experimental workflow, illustrated by several cases of study. This review will enable the reader to understand how specific mitochondrial redox events can be accurately measured, considering all technical, methodological and mechanistical variables and limitations required for their reliable detection and interpretation.

(Patho)physiology↗

Compound elevated skull fracture: a forgotten type of skull fracture.

BACKGROUND AND OBJECTIVE: We report 4 patients who presented with a rare type of vault fracture. This form of fracture has only been described in few instances in the literature. CASE DESCRIPTION: All the patients presented with elevation of free skull fracture fragments. The etiologies were assault (1 patient), domestic accident (1 patient), and road traffic accident (2 patients). All the fractures were compound as in previously reported cases. Delay in surgery resulted in cerebral abscess in 1 patient. Surgery was performed in all the patients: wound debrident, duroplasty, and reduction of fracture in 3 patients and craniotomy with excision of abscess in 1 patient. Two of the patients did well after surgery. The patients with abscess died 9 days after surgery. Another patient developed CSF fistula after surgery, and died of aspiration while waiting for the closure of the fistula. CONCLUSION: Elevated skull fractures in our series were all compound fractures. Both long, sharp objects as well as blunt objects can cause this injury. Delay in surgery could result in intracranial sepsis. We suggest that this fracture should be included in the classification of skull fractures.

Adult↗

Scleritis.

Scleritis is typically a severe painful inflammatory process centered in the sclera that may involve the cornea, adjacent episclera, and underlying uvea; it poses a significant threat to vision. Careful clinical history taking, detailed ocular examination, appropriate investigation for ocular disease with or without underlying systemic disease, and timely intervention with the use of immunosuppressant drugs when necessary, has improved the long-term outcome for patients with this disease.

Humans↗

Vaccination of mice against intestinal Trichinella spiralis infections by oral administration of antigens microencapsulated in methacrilic acid copolymers.

BALB/c and NIH mice have been successfully vaccinated against the intestinal nematode Trichinella spiralis by oral administration of crude larval extracts (CLE) and excretory-secretory (ES) products derived from first stage T. spiralis larvae (L1) encapsulated in microcapsules made of copolymers of the metacrylic acid (Eudragit L100). Oral vaccination stimulated the secretion of IFN-gamma and inhibited the secretion of IL-4 in spleen and mesenteric lymph nodes (MLN) of BALB/c mice. In vaccinated mice the proportion of CD4+ cells increased (p<0.05) in Peyer's patches (PP) and decreased (p<0.05) in spleen whereas the proportion of CD19+ cells decreased (p<0.05) in both PP and spleen, with regard to unvaccinated controls. No variation was evident for the proportion of CD8+ cells. Oral vaccination elevated the antigen-specific serum IgG1 and IgA (p<0.05) as well as the antigen-specific IgA response in MLN (p<0.05). It is concluded that this way of vaccination induced a concurrent Th1/ Th2 local and systemic responses that are protective and at the same time they may help balancing the strong Th2 response triggered by helminth infections.

Adjuvants, Immunologic↗

Prevalence of and risk factors for anxiety and depressive disorders in Nigerian adolescents with epilepsy.

The emotional response of adolescents to a chronic illness like epilepsy may differ across cultures. This study was aimed at investigating the prevalence of and risk factors for anxiety and depressive disorders in a group of Nigerian adolescents with epilepsy. Adolescents with epilepsy (n=102) aged between 12 and 18 were assessed for anxiety and depressive disorders with the Diagnostic Interview Schedule for Children Version IV (DISC-IV). An anxiety disorder was diagnosed in 32 (31.37%) of the adolescents and a depressive disorder was reported in 29 (28.43%). Predictors of anxiety and depressive disorders by regression analysis include uncontrolled seizures, polytherapy, and felt stigma. Family factors such as parents' psychopathology and family stress are also moderately significant. Results show that emotional disorders in adolescents with epilepsy cut across cultures. Adequate monitoring, education targeted at reducing felt stigma, and family intervention programs are needed for early intervention.

Adolescent↗

Treatment of patients with coexisting epileptic and nonepileptic seizures.

A majority of studies have reported a rate of concurrence of epileptic seizures (ESs) in patients with nonepileptic seizures (NESs) of about 10-18%. We explored the relationship between the two paroxysmal disorders (ESs and NESs) in a series of patients with both, and report a treatment for these patients that proved remarkably effective: reduction of the dose of antiepileptic drug to the minimum required to achieve optimal freedom from seizures. NESs are hypothesized to have a psychobiological basis, and it has been proposed that they be recognized as posttraumatic startle seizures. Excessive suppression of epileptic paroxysmal activity appears to favor the expression of posttraumatic paroxysmal activity in patients with both paroxysmal disorders, and the manifestation of ESs and NESs tends to alternate. Of etiological significance is the finding that the patients commonly have both a personal history of trauma and a family history of epilepsy.

Adult↗

Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo.

Targeted silencing of disease-associated genes by synthetic short interfering RNA (siRNA) holds considerable promise as a novel therapeutic strategy. However, unmodified siRNA can be potent triggers of the innate immune response, particularly when associated with delivery vehicles that facilitate intracellular uptake. This represents a significant barrier to the therapeutic development of siRNA due to toxicity and off-target gene effects associated with this inflammatory response. Here we show that immune stimulation by synthetic siRNA can be completely abrogated by selective incorporation of 2'-O-methyl (2'OMe) uridine or guanosine nucleosides into one strand of the siRNA duplex. These noninflammatory siRNA, containing less than 20% modified nucleotides, can be readily generated without disrupting their gene-silencing activity. We show that, coupled with an effective systemic delivery vehicle, 2'OMe-modified siRNA targeting apolipoprotein B (apoB) can mediate potent silencing of its target mRNA, causing significant decreases in serum apoB and cholesterol. This is achieved at therapeutically viable siRNA doses without cytokine induction, toxicity, or off-target effects associated with the use of unmodified siRNA. This approach to siRNA design and delivery should prove widely applicable and represents an important step in advancing synthetic siRNA into a broad range of therapeutic areas.

Animals↗

A longitudinal study of porcine serological responses to experimental infections with T-1 and T-3 Spanish Trichinella isolates.

Comparison of antibody response and antigen recognition was made by ELISA and western-blot analysis in pig experimental infections by T-1 and T-3 Spanish Trichinella isolates. Two groups of Iberian pigs were experimentally infected with 150 larvae/kg body weight of GM-1 and C-76 Spanish Trichinella isolates as representatives of T-1 and T-3 gene pools respectively. Antibody levels and antigen recognition were measured on days -14, 0, 6, 16, 20, 27, 34, 49, 63 and 82 after infection by ELISA and western-blotting assays. Antibody response against C-76 infection was significantly delayed and lower than against GM-1. The two Trichinella isolates were indistinguishable, however, by western blotting analysis, although recognition of larval antigens was quantitatively higher than adult ones. Interestingly, the principle larval antigenic components recognized by pigs were those recognized by the monoclonal anti-sera NIM-M1. Finally, there were no serological patterns indicative of the stage of infection ("antibody windows") discriminating, for example between early versus late infections.

Animals↗

Immunization of mice against Trichinella spiralis and T. britovi using excretory and secretory antigens.

Immune responses to immunization and infection with Trichinella spiralis and T. britovi were studied in NIH high-responder mice. Overall it was shown that T. britovi was the more immunogenic, immunization and challenge with this species giving greater host-protective immunity. This greater immunogenicity was reflected in higher proliferative responses when mesenteric node lymphocytes (MLNC) from immunized mice were restimulated with T. britovi antigens in vitro and in higher levels of T helper 2 (Th2) lymphocyte-dependent specific IgG1 antibody responses against this species. MLNC from mice immunized against T. britovi released more IL-5 when restimulated in vitro, again suggesting a greater T helper 2 subset response, but after infection the highest levels of IL-5 were recorded from MLNC taken from T. spiralis challenged mice. These data are discussed in relation to current understanding of immunological differences between species and isolates of the genus Trichinella.

Animals↗

Infectivity of Trichinella isolates in mice is determined by host immune responsiveness.

A comparison was made of the development, survival and reproduction of 5 isolates of Trichinella spiralis in inbred mice. Low responder C57BL/10 mice allowed worms of all isolates to survive longer and reproduce more successfully than did high responder NIH mice, suggesting that host immunity exerted a dominant influence upon infectivity. One isolate (Is-5 (W) -an arctic isolate) had a markedly lower infectivity than all other isolates, and was selected for more detailed study, together with isolate Is-1 (S) (a temperate isolate) which showed high infectivity. The lower infectivity of Is-5 (W) reflected a more rapid onset of immunity in mice infected with this parasite, immunity reducing the reproductive potential of female worms and causing an early expulsion from the intestine. No evidence of a dose-dependent suppression of immunity was found to explain the higher infectivity of Is-1 (S). Is-5 (W) provided a very rapid mucosal mastocytosis Is-1 (S) elicited higher levels of circulating parasite-specific antibodies than did Is-5 (W). These results are discussed in relation to the interplay of parasite immunogenicity and host immune responsiveness in determining infectivity, and point to the importance of identifying those immunodominant parasite molecules which control the balance of the host-parasite relationship.

Animals↗

Infectivity, antigenicity and host responses to isolates of the genus Trichinella.

Comparisons were made of the infectivity and antigenicity of 4 Trichinella spiralis isolates (S, D, Y, W), of quite different geographical origins, and T. pseudospiralis (P) in rapid- and slow-responder inbred mice. Infectivity was measured by the Index of Reproductive Capacity (ICR) expressed as the ratio between the number of muscle larvae recovered on day 30 post-infection (p.i.) and the numbers of larvae given at infection. Antigen recognition was measured by the degree of proliferation of mesenteric lymph node cells (MLNC) to in vitro stimulation with crude muscle larvae antigen (CMLA) and by the total antibody responses to CMLA at day 25 p.i. as measured by ELISA. Regarding infectivity the isolates fell into two groups, high infectivity (S, D and Y) and low infectivity (W and P). Analysis of CMLA, detergent-stripped (CTAB) and 125I-labelled surface larval proteins was made by SDS-PAGE under reducing conditions. Differences in antigen profiles were seen in all antigen preparations, being most noticeable in CTAB and 125I-labelled proteins from W and P isolates. Antigen recognition by polyclonal infection-derived antisera and by monoclonal antibodies raised against the T. spiralis London strain (L) was studied in the W (Arctic) and S (Spanish) isolates. Polyclonal antisera recognized different antigens in the S and W isolates, as did the monoclonal antibody, although recognition was more restricted. Neither antibody recognized a 64 kDa band in the W isolate which was clearly visible in the others tested.

Animals↗

Predictors of condom use in Mexican migrant laborers.

The purpose of this study was to explore predictors of condom use with occasional sex partners and regular sex partners, as well as carrying condoms in a new high-risk group for HIV infection, Mexican migrant laborers. This study extends previous findings by (1) exploring additional predictors not previously examined, (2) utilizing a large sample of male and female Mexican migrant laborers, (3) carefully controlling for the effects of various demographic and lifestyle variables related to condom use, and (4) assessing the interactive effects of gender on predictors of condom use. Snowball sampling was used to survey 501 adult Mexican migrant laborers. Results revealed that condom use with occasional sex partners was predicted by carrying condoms and condom self-efficacy and that women were more likely to use condoms with occasional partners when both men and women knew someone with HIV/AIDS. Condom use with regular sex partners was predicted by procondom social norms, less negative attitudes toward condoms, not knowing someone with HIV/AIDS, and condom self-efficacy. Carrying condoms was predicted by procondom social norms, less negative attitudes toward condoms, condom self-efficacy, worry about contracting HIV/AIDS, and women were more likely than men to carry condoms when both men and women were married. Understanding these findings, future research directions, and implications for condom promotion strategies with Mexican migrant laborers are discussed.

Adult↗

Evaluation of a hospital-based community liaison pharmacy service in Northern Ireland.

OBJECTIVE: To evaluate the impact of a hospital based community liaison pharmacy service on a range of outcomes in patients aged more than 55 years and taking more than 3 prescribed drugs, who had been admitted to the medical unit of a district general hospital in Northern Ireland. METHODS: Having recruited 243 patients, a total of 162 patients completed the full protocol (81 randomly assigned to intervention and 81 to control; mean age of control patients 75 years; mean age of intervention patients 73 years). The interventions by the community liaison pharmacist included: preparation of an accurate medication record following a full review of current medication use; medication counselling; provision of a medicines record sheet informing the patient how to take their drugs; provision of a pharmaceutical discharge letter detailing changes made to drug therapy (this was faxed to the patient's GP and community pharmacist on the day of discharge); provision of a Medicines Helpline. RESULTS: The key findings were as follows: problems were identified in 80% of the intervention patients' prescription charts, 49% of which related to drug omissions from the patients' domiciliary prescriptions. The GP practice record was the most accurate (mean error rate 12.6%) while the GP referral letter was the least accurate (mean error rate 47.3%) source of medication information. Drugs patients brought to hospital were also an inaccurate source (mean error rate 44.0%). The intervention group patients, when compared with control patients, had a significant reduction (P = 0.005) in drug mismatch between drugs prescribed at discharge and taken at home, and had a greater knowledge of their drug regimen 10-14 days after discharge (P < 0.001). The vast majority of patients (96%) felt that the provision of a medicine helpline was a useful service. CONCLUSIONS: The study indicated clear benefits from the involvement of a hospital based community liaison pharmacist in achieving seamless pharmaceutical care between the primary and secondary healthcare settings.

Aged↗