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Approaches towards the development of a vaccine against tuberculosis: recombinant BCG and DNA vaccine.

The last few years have witnessed intense research on vaccine development against tuberculosis. This has been driven by the upsurge of tuberculosis cases globally, especially those caused by multi-drug-resistant Mycobacterium tuberculosis strains. Various vaccine strategies are currently being developed which can be broadly divided into the so-called living and non-living vaccines. Examples are attenuated members of the M. tuberculosis complex, recombinant mycobacteria, subunit proteins and DNA vaccines. Given current developments, we anticipate that recombinant BCG and DNA vaccines are the most promising. Multiple epitopes of M. tuberculosis may need to be cloned in a vaccine construct for the desired efficacy to be achieved. The technique of assembly polymerase chain reaction could facilitate such a cloning procedure.

BCG Vaccine↗

Risk factors of tuberculosis among health care workers in Sabah, Malaysia.

Tuberculosis (TB) is one of the main public health problems in Sabah; 30% of the total number of TB cases reported in Malaysia every year occur in Sabah. The average incidence of TB among health care workers over the past 5 years is 280.4 per 100,000 population (1, Annual Report of Sabah State TB Control Programme, 1998). At present, there are no specific measures for the prevention of TB transmission in health care facilities. A case-control study was conducted among health care workers in Sabah in 2000-2001. Cases were health care workers with TB diagnosed between January 1990 and June 2000. Controls were health care workers without TB and working in the same facility as cases during the disease episode. The study attempted to identify risk factors for TB among the study population. Data were collected through structured interviews and review of patients' records. The notification rate of TB among health care workers was significantly higher than that to the general population (Z=4.893, p<0.01). The average notification rate of TB among health care workers over the last 5 years was two times higher than in the general population (280.4/100,000 compared to 153.9/100,000). Regression results showed that ethnicity, designation, family contact and TB related knowledge did not significantly contribute to the risk of contracting TB in this study. However, after controlling for the above factors, age, gender, history of TB contact outside the workplace (other than family contact), duration of service and failure to use respiratory protection when performing high-risk procedures, were the main risk factors of TB among health care workers. This study succeeded in identifying some of the risk factors of TB among health care workers. We managed to include the large ratio of controls to case (3:1) and those cases spanned over a period of 10 years. However, the findings from the study have to be applied with caution due to the limitations of this study, which include recall bias, dropouts, and small sample size. Based on the study findings, we recommend that health care workers in the first 10 years of service should take extra precautions, such as using respiratory protection when performing procedures that are considered to be of high risk with respect to TB infection. They should also undergo TB screening at least once every 2 years and, if symptomatic, offered prophylactic treatment. The Respiratory Protection Programme should be fully implemented to help reduce the risk of TB among health care workers in Sabah.

Case-Control Studies↗

Genetic variants of Banana streak virus in Mauritius.

Genetic variations among isolates of Banana streak virus (BSV) were assessed using two sets of primers. The virus, found in banana accessions in Mauritius, was compared to a Nigerian isolate from cultivar Obino l'Ewai (BSOEV). On the basis of the observed size of amplicons, some Mauritius strains were different from l'Ewai BSOEV. Both Southern blot hybridization and the nucleotide sequences of the PCR products confirmed that they were of episomal BSV origin. An isolate of sugarcane bacilliform virus (SCBV) was found to be also very similar to the BSV isolated from banana samples. Nucleotide sequence analysis showed that even the same size PCR products had differing sequences. The dendrogram placed the isolates from Mauritius in a cluster separate from BSV and SCBV from other geographical locations.

Badnavirus↗

Sorption of Zn(II), Pb(II), and Co(II) using natural sorbents: equilibrium and kinetic studies.

Natural Jordanian sorbent (consisting of primary minerals, i.e., quartz and aluminosilicates and secondary minerals, i.e., calcite and dolomite) was shown to be effective for removing Zn(II), Pb(II) and Co(II) from aqueous solution. The major mineral constitutions of the sorbent are calcite and quartz. Dolomite was present as minor mineral and palygorskite was present as trace mineral. The sorbent has microporous structure with a modest surface area of 14.4 m(2)g(-1). pH(zpc) (pH of zero point charge) of the sorbent was estimated by alkaline-titration methods and a value of 9.5 was obtained. The sorption capacities of the metals were: 2.860, 0.320, 0.076 mmol cation g(-1) for Zn(II), Pb(II) and Co(II) at pH 6.5, 4.5 and 7.0, respectively. The shape of the experimental isotherm of Zn(II) was of a "L2" type, while that of Pb(II) and Co(II) was of a "L1" type according to Giles classification for isotherms. Sorption data of metals were described by Langmuir and Freundlich models over the entire concentration range. It was found that the mechanism of metal sorption was mainly due to precipitation of metal carbonate complexes. The overall sorption capacity decreased after acid treatment, as this decreased the extent of precipitation on calcite and dolomite. The effect of Zn(II) ions concentration on sorption kinetics was investigated. Kinetic data were accurately fitted to pseudo-first order and external diffusion models which indicated that sorption of Zn(II) occurred on the exterior surface of the sorbent and the contribution of internal diffusion mechanism was insignificant. Furthermore, the sorption rate of Zn(II) was found to be slow, where only 10-20% of the maximum capacity was utilized in the first 30 min of interaction.

Adsorption↗

Immunocompetence may be important in the effectiveness of Mectizan (ivermectin) in the treatment of human onchocerciasis.

Mectizan (Ivermectin) has been proved to be central to the control of onchoceriasis through self-sustainable community-based treatment. The possibility of parasitological unresponsiveness to this treatment or selection for drug resistance has emerged recently in many occasions. The reason for the reduced ability of Mectizan to maintain low levels of dermal microfilariae and early recurrent pruritus can only be speculated upon. Here, we report our own findings to address this particular issue.

Animals↗

Distribution of hydatid cysts into the liver with reference to cystobiliary communications and cavity-related complications.

BACKGROUND: This study was designed to test a hypothesis that intrahepatic hydatid cyst location can effect the incidence of cystobiliary communications and the cavity-related complications. METHODS: A total of 121 cysts treated by conservative surgical methods in 113 patients were evaluated prospectively. Cysts were grouped as near to the liver hilum (segment I, III, IVb, V, and VI) and far from the hilum (segment II, IVa, VII, and VIII). RESULTS: There were 58 (48%) hilar and 63 (52%) peripheral cysts. We found more cystobiliary communications (48% versus 27%, P = 0.015), more biliary leakage (36% versus 10%, P <0.001), and more biliary fistula (12% versus 3%, P = 0.080) in the cysts near to the hilum than far from the hilum. Postoperative hospital stay was longer in the cysts near to the hilum (12.3 +/- 3.1 days) than the cysts far from the hilum (7.7 +/- 2.7 days, P = 0.022). CONCLUSIONS: The location of the hydatid cyst near to the liver hilum is a risk factor for the cystobiliary communications and the cavity related complications.

Adolescent↗

Elimination of mucosectomy during restorative proctocolectomy in patients with ulcerative colitis may provide better results in low-volume centers.

BACKGROUND: To compare the outcomes of hand-sewn and double-stapling techniques among ulcerative colitis patients undergoing restorative proctocolectomy at a center that has limited experience with restorative proctocolectomy. METHODS: Forty-four patients with ulcerative colitis were divided into two groups according to the anastomosis techniques: hand sewing and double stapling. Postoperative early and late complications, postoperative hospital stay, and long-term functional results were compared. RESULTS: Pelvic sepsis (9% versus 36%, P = 0.03), operation time (median 240 minutes versus 270 minutes, P = 0.01), postoperative hospital stay (median 9 days versus 12 days, P = 0.04), and night incontinence (42% versus 80%, P = 0.07) were less common in the double-stapling group. CONCLUSIONS: We recommend the double-stapling technique to centers that do not have extensive experience with restorative proctocolectomy for ulcerative colitis. This technique provides a good postoperative course in most patients and provides satisfactory long-term results. The results of the double-stapling group were similar to the results of the high-volume centers.

Adolescent↗

Selective attention in social phobia and the moderating effect of a concurrent depressive disorder.

Studies using the modified Stroop colour naming task have provided results consistent with the hypothesis that social phobia is associated with an attentional bias towards negative social-evaluative words. However, these results could also have arisen as a consequence of non-attentional processes. For this reason, the present study uses a modified version of MacLeod et al.'s (J. Abnorm. Psychol. 95 (1986) 15) dot-probe task, which provides a more direct measure of attention. Patients with social phobia (n=28), patients with social phobia and a concurrent depressive disorder (n=33), and non-patients (n=40) were presented with word pairs each consisting of a neutral word and a threat word. The results indicated that patients with social phobia show an attentional bias towards social-threat words while non-patients tend to avoid social-threat words. Patients with social phobia and a concurrent depressive disorder behaved like non-patients, indicating that concurrent depression abolishes the attentional bias. Physical threat words were also included in the study. The main analysis indicated that social phobia is also associated with an attentional bias to physical threat. However, a post hoc analysis (which requires replication) suggested that the physical threat bias might have arisen because some social phobia patients also had another anxiety disorder in which physical concerns are likely to have been prominent. Overall, the results emphasise the importance of assessing comorbidity when investigating attentional biases.

Adult↗

Ionic blockade of the rat connexin40 gap junction channel by large tetraalkylammonium ions.

The rat connexin40 gap junction channel is permeable to monovalent cations including tetramethylammonium and tetraethylammonium ions. Larger tetraalkyammonium (TAA(+)) ions beginning with tetrabutylammonium (TBA(+)) reduced KCl junctional currents disproportionately. Ionic blockade by tetrapentylammonium (TPeA(+)) and tetrahexylammonium (THxA(+)) ions were concentration- and voltage-dependent and occurred only when TAA(+) ions were on the same side as net K(+) efflux across the junction, indicative of block of the ionic permeation pathway. The voltage-dependent dissociation constants (K(m)(V(j))) were lower for THxA(+) than TPeA(+), consistent with steric effects within the pore. The K(m)-V(j) relationships for TPeA(+) and THxA(+) were fit with different reaction rate models for a symmetrical (homotypic) connexin gap junction channel and were described by either a one- or two-site model that assumed each ion traversed the entire V(j) field. Bilateral addition of TPeA(+) ions confirmed a common site of interaction within the pore that possessed identical K(m)(V(j)) values for cis-trans concentrations of TPeA(+) ions as indicated by the modeled I-V relations and rapid channel block that precluded unitary current measurements. The TAA(+) block of K(+) currents and bilateral TPeA(+) interactions did not alter V(j)-gating of Cx40 gap junctions. N-octyl-tributylammonium and -triethylammonium also blocked rCx40 channels with higher affinity and faster kinetics than TBA(+) or TPeA(+), indicative of a hydrophobic site within the pore near the site of block.

Animals↗

Voltage-dependent blockade of connexin40 gap junctions by spermine.

The effects of spermine and spermidine, endogenous polyamines that block many forms of ion channels, were investigated in homotypic connexin (Cx)-40 gap junctions expressed in N2A cells. Spermine blocked up to 95% of I(j) through homotypic Cx40 gap junctions in a concentration- and transjunctional voltage (V(j))-dependent manner. V(j) was varied from 5 to 50 mV in 5-mV steps and the dissociation constants (K(m)) were determined from spermine concentrations ranging from 10 micro M to 2 mM. The K(m) values ranged from 4.9 mM to 107 micro M for 8.6 < or = V(j) < or = 37.7 mV, within the physiological range of intracellular spermine for V(j) > or = 20 mV. The K(m) values for spermidine were > or = 5 mM. Estimates of the electrical distance (delta) for spermine (z = +4) and spermidine (z = +3) were 0.96 and 0.76 respectively. Cx40 single channel conductance was 129 pS in the presence of 2-mM spermine and channel open probability was significantly reduced in a V(j)-dependent manner. Similar concentrations of spermine did not block I(j) through homotypic Cx43 gap junctions, indicating that spermine selectively blocks Cx40 gap junctions. This is contrary to our previous findings that large tetraalkylammonium ions, also known to block several forms of ion channels, block junctional currents (I(j)) through homotypic connexin Cx40 and Cx43 gap junctions.

Animals↗

Increased plasma nitrate levels in patients with crush syndrome in the Marmara earthquake.

BACKGROUND: Crush syndrome has been described as extensive muscle damage, leading to acute renal failure. The aim of this study was to evaluate the possible role of nitric oxide, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in crush syndrome. PATIENTS AND METHODS: A total of 17 patients suffering from crush syndrome, 7 patients without crush syndrome and 10 healthy controls were enrolled in the study. Plasma nitrate, TNF-alpha, IL-1 beta levels and biochemical parameters were measured. RESULTS: All patients with crush syndrome demonstrated acute renal failure. Plasma nitrate levels were elevated significantly in the crush syndrome patients compared with patients without crush syndrome (33.5 +/- 20.1 vs. 15.3 +/- 5 micromol/l, p=0.014). There was no significant difference in TNF-alpha and IL-1 beta levels between control and patient groups. CONCLUSION: Increased plasma nitrate levels in the crush syndrome may be related either to the elevated production of NO or the diminished excretion of nitrate or both.

Adolescent↗

[The Fear of Negative Evaluation scale (FNE): psychometric properties of the French version].

BACKGROUND: The Fear of Negative Evaluation scale (FNE: Watson and Friend, 1969) is the measure most commonly used to determine the degree to which people experience apprehension at the prospect of being negatively evaluated. Although the development of the FNE preceded the inclusion of social anxiety disorder (or social phobia) in the diagnostic classification system, it is widely used as a measure of cognitive symptoms because the feature tapped by this measure is at the core of recent cognitive models of social-anxiety. According to these models, socially anxious individuals divide their attention between the internal representations of their social self (negative images and "felt sense") and external cues that could be taken as a sign of negative evaluation by others. The FNE was validated in a student and patient population in English speaking countries. The English version demonstrates adequate empirical validity. It shows excellent internal consistency and one-factor structure. Test retest reliability is satisfying. It is proved to be sensible to change after treatment. It is well correlated with other measures of social anxiety demonstrating good convergent validity. However, divergent and discriminate validity have been a subject of controversy. The aim of the present study was to assess the psychometric properties of the French version of the FNE in order to obtain a valid instrument measuring the cognitive component of social anxiety. METHOD: The social anxiety group consisted of 88 patients referred to our clinic for cognitive-behavioural group therapy. All met ICD-10 criteria for social phobia (generalized subtype) as determined by the Composite International Diagnostic Interview (social phobia section). Additional axis-I diagnostic information was obtained using the Mini International Neuropsychiatric Interview (MINI: Lecrubier et al., 1997) for ICD-10. The non-patient control group consisted of 80 participants who didn't respond to social anxiety CIDI criteria. All participants were rated by the assessor on the Liebowitz Social Anxiety Scale (LSAS) and completed the following self-report questionnaires: the Fear of Negative Evaluation questionnaire (FNE), the State-Trait-Anxiety Inventory (STAI A-B), and the Beck Depression Inventory (BDI 13). RESULTS: The internal consistency is very good with Kuder-Richardson 20 coefficient of 0,94 corresponding to coefficients found in the validity studies of the original version of the FNE. One factor Anova tests showed that our two groups of subjects differed significantly on the FNE [F (1.166)=282.26, p<0.001]. Patients had a mean score of 25.6 with a standard deviation of 4.1 and the non patient control subjects had a mean score of 12.1 with a standard deviation of 6.1. This result confirms the empirical validity of the instrument. In the patient sample, the FNE was significantly correlated with the LSAS total score (r=0.55; p<0.001). This result indicates good convergent validity. However, the FNE was also significantly correlated with the BDI-13 (r=0.48; p<0.001) and the STAI B (r=0.47; p<0.001). However because high levels of general anxiety and depression are common among patients with social anxiety disorder, substantial correlations between measures of social anxiety and measures of general anxiety and depression should be probably expected. A multiple regression analysis shows a significant association of the FNE with the LSAS (Beta=0.39, p<0.001) and the STAIB (Beta=0.28, p<0.01) We explored the unidimensionality of the scale by using a principal component analysis of tetrachoric correlation suitable for dichotomic items. One sole factor with an eigenvalue superior to 1 emerged. We deduce therefore that our results are in favour of the unidimensionality of the French version of the FNE. CONCLUSION: The present study shows that the French version of the FNE has good psychometric properties and differentiates social phobic patients from the non-clinical control subjects. Given the importance that models of social anxiety attribute to cognitive processes and the importance of cognitive techniques in its treatment, we consider that the French version of the FNE is an adequate and valid questionnaire to be used in research and therapy.

Adult↗

The effect of serum obtained before and after treatment for endometriosis on in vitro development of two-cell mouse embryos.

OBJECTIVE: To evaluate the effect of serum obtained before and after treatment for endometriosis on in vitro development of two-cell mouse embryos. DESIGN: Pretreatment and post-treatment comparison of mouse embryo development in serum supplements from patients with endometriosis; results were compared using chi 2 analysis. SETTING: Infertility Clinic, Shimane Medical University, Izumo, Japan. PATIENTS: Ten consecutive women with endometriosis who underwent treatment for the disease. Seven women who were managed expectantly served as controls. INTERVENTIONS: All patients underwent laparoscopic or conservative surgery. This was followed by a 6-month course of either danazol 400 mg/d (6 patients) or buserelin acetate 900 micrograms/d (4 patients). MAIN OUTCOME MEASURE(S): Total number of embryos that reached blastocyst stage after 72 hours of incubation were compared before and after treatment. RESULTS: Before treatment, 23% of the embryos reached blastocyst stage, whereas 8 of the 10 serum samples were embryo toxic. After treatment, significantly more embryos (59%) developed to blastocysts, and only one serum sample remained embryo toxic. In the control group, there was no significant difference in the number of embryos that reached blastocyst stage after expectant treatment. CONCLUSION: The embryo toxicity of serum samples from patients with endometriosis is lost after treatment.

Animals↗

Improving the quality of obstetric care at the teaching hospital, Zaria, Nigeria.

PRELIMINARY STUDIES: Research at Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria, showed delay in treating women with obstetric complications and highlighted multiple contributing factors. INTERVENTIONS: In response, a surgical theater was restored to working order, the maternity ward renovated, resident physicians trained in obstetrics and an emergency drug pack system instituted. A system of blood donation from families of women attending antenatal clinics was introduced. Later, community interventions focused on improving access and reducing delay in seeking care. RESULTS: Mean admission-to-treatment interval was reduced by 57%, from 3.7 h in 1990 to 1.6 h in 1995. The proportion of women treated in less than 30 min increased from 39% in mid-1993 to 87% in late 1995. Case fatality rate (CFR) among women with major obstetric complications fell from 14% in 1990 to 11% in 1995. The annual number of women with complications seen, however, declined from 326 in 1990 to 65 in 1995. COSTS: Cost of material improvements was approximately US$135,000, of which 65% was provided by government. An additional $8000 per year in new staff salaries was paid by the government. CONCLUSIONS: Hospital obstetric services can be improved and government can be mobilized to contribute. Treatment delay and obstetric CFR can be reduced. Deteriorating economic conditions, however, may diminish utilization of services despite improvements.

Community Networks↗

The effect of improving maternity services in a secondary facility, Zaria, Nigeria. The Zaria PMM Team.

PRELIMINARY STUDIES: Facility review at the secondary hospital in Makarfi revealed a lack of drugs and skilled personnel and delays in treating and referring women with obstetric complications. INTERVENTIONS: In 1994, maternity facilities were renovated, a revolving drug fund was introduced, midwives were trained and an ambulance was restored to service. Attempts to secure a physician with skills in treating obstetric emergencies were unsuccessful. Prior to these activities, obstetric services at the referral hospital were improved. Community interventions focused on improving utilization by women with complications. RESULTS: Between 1990 and 1995, substantial increases occurred in antenatal attendance (2517 to 5565 per year) and deliveries (325 to 1952 per year). The number of women with complications seeking care at this facility, however, dropped from 85 in 1990 to 28 in 1995. Referrals to higher level facilities increased from four in 1990 to 17 in 1995. COSTS: The cost of the interventions was approximately US $32,000. Ninety-eight percent was paid by the government and 2% by PMM. CONCLUSIONS: Improving the quality of maternity services can increase utilization by women with uncomplicated pregnancies. However, utilization of emergency services appears to be influenced by other factors, such as the ability to treat obstetric complications and prevailing economic conditions.

Female↗

Community loan funds and transport services for obstetric emergencies in northern Nigeria.

PRELIMINARY STUDIES: Focus group discussions and a community survey indicated that inadequate funds and transport caused delays in deciding to seek emergency obstetric care and in reaching facilities. INTERVENTIONS: Following improvements in the quality of obstetric services, a community loan program was established in early 1995. Community members determined its features: compulsory contributions; community administration; loans for obstetric complications only; no interest; a 6-month grace period; and 24-month repayment. A transport system was also established, in which private vehicle drivers agreed to respond to calls for emergency transport and charge a set fee. RESULTS: The equivalent of US $20,500 was collected from 81 annual and 2273 one-time contributors. Eighteen loans were approved in 9 months. Repayment data are not yet available. For the transport system, 23 drivers pledged permanent participation and 58 pledged to take part in 6-month rotations. They transported 18 women. COSTS: The cost of these interventions was $3409 for the loan fund and $2272 for the transport system. Sixty percent of the cost was paid by the community and the rest by the PMM project. CONCLUSIONS: Community-managed loan and transport systems for women with obstetric emergencies can be established and may contribute to reducing delay in obtaining emergency obstetric care.

Costs and Cost Analysis↗