bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune responses in patients with HIV infection after vaccination with recombinant Hepatitis B virus vaccine
Authors: Pasricha Neelam , Datta Usha , Chawla Yogesh , Singh Surjit , Arora Sunil K , Sud Archana , Minz Ranjana W , Saikia Biman , Singh Haqeeqat , James Isaac , Sehgal Shobha
Published: April 2006

Background

Patients with HIV infection are at risk of co-infection with HBV, as the routes of transmission are shared and thus immunization with HBV vaccine could be protective in them. The aim of the present study was to assess the efficacy of recombinant vaccine in treatment-naive HIV positive patients and healthy controls, and to dissect out differences if any, in different limbs of immune response.

Methods

Forty HIV positive patients and 20 HIV negative controls, negative for HBsAg, HBsAbs and HBcAbs were vaccinated with three doses of 40μg and 20μg of vaccine respectively. Patients were divided into high CD4 and low CD4 group based on CD4+ lymphocytes of 200 and < 200/mm3 respectively. Group II consisted of healthy controls. Detection of phenotypic markers was done by flowcytometry. Cytokine estimation was done by sandwich ELISA. HBsAbs were estimated in serum by ELISA.

Results

After vaccination, CD4+, CD8+ and CD3+ cells increased significantly in all the groups. There was no increase in NK cell activity in patients with high CD4+ lymphocytes and only a marginal increase in patients with low CD4+ lymphocytes (170 to 293/mm3) whereas a marked increase was observed in controls (252 to 490/mm3). After vaccination, although an increase in memory cells was observed in HIV positive patients, yet HBsAb levels were significantly lower than controls (P < 0.05) indicating a functional defect of memory cells in HIV/AIDS patients. Basal IFN-γ levels were also significantly lower in HIV/AIDS patients (P < 0.01). Although the levels increased after vaccination, the peak level remained lower than in controls. HBsAb titers were much lower in HIV positive patients compared to controls. (High CD4+ group: 8834 mIU/ml, low CD4+ group: 462 mIU/ml Vs. Controls: 16,906 mIU/ml). IL-4 and IL-10 were low in patients.

Conclusion

Despite a double dose in patients, IL-4 and IL-10, which regulate antibody response, were also lower in patients, and this together with low CD4+ counts and lack of T help, accounted for low HBsAb levels. Vaccination in patients with CD4+ lymphocytes < 50/mm3 was ineffective. Thus early immunization is advocated in all HIV positive patients at a stage when they are still capable of mounting an adequate immune response
N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease
Authors: Borlak Juergen , Reamon-Buettner Stella Marie
Published: April 2006

Background

Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this neural death is unknown, but genetic predisposition and environmental factors may cause the disease. Sequence variations in N-acetyltransferase 2 (NAT2) gene leading to slow acetylation process have been associated with PD, but results are contradictory.

Methods

We analyzed three NAT2 genetic variations, c.481C>T, c.590G>A (p.R197Q) and c.857G>A (p.G286E), which are known to result in a slow acetylator phenotype. Using validated PCR-RFLP assays, we genotyped 243 healthy unrelated Caucasian control subjects and 124 PD patients for these genetic variations. Further, we have undertaken a systematic review of NAT2 studies on PD and we incorporated our results in a meta-analysis consisting of 10 studies, 1,206 PD patients and 1,619 control subjects.

Results

Overall, we did not find significant differences in polymorphic acetylation genotypes in PD and control subjects. In the meta-analysis of slow acetylators from 10 studies and representing 604/1206 PD vs. 732/1619 control subjects, a marginally significant odds ratio (OR) of 1.32 (95% CI 1.12–1.54, p < 0.05) was obtained. Re-analysis of the data to exclude the only two studies showing positive association of slow acetylators to PD, resulted in a non-significant OR (1.07, 95% CI 0.9–1.28). Furthermore, meta-analysis of studies for c.590G>A, where both allele and genotype frequencies in PD vs. control subjects were analyzed, did not give significant summary odds ratios as well.

Conclusion

We found little evidence for differences in polymorphic acetylation genotypes in PD and control subjects. Results of the meta-analyses did not also provide conclusive evidence for an overall association of NAT2 slow acetylator genotypes to PD.
Protective effect of EDTA preadministration on renal ischemia
Authors: Foglieni Chiara , Fulgenzi Alessandro , Ticozzi Paolo , Pellegatta Fabio , Sciorati Clara , Belloni Daniela , Ferrero Elisabetta , Ferrero Maria Elena
Published: April 2006

Background

Chelation therapy with sodium edetate (EDTA) improved renal function and slowed the progression of renal insufficiency in patients subjected to lead intoxication. This study was performed to identify the underlying mechanism of the ability of EDTA treatment to protect kidneys from damage.

Methods

The effects of EDTA administration were studied in a rat model of acute renal failure induced by 60 minutes ischemia followed or not by 60 minutes reperfusion. Renal ischemic damage was evaluated by histological studies and by functional studies, namely serum creatinine and blood urea nitrogen levels. Treatment with EDTA was performed 30 minutes before the induction of ischemia. Polymorphonuclear cell (PMN) adhesion capability, plasmatic nitric oxide (NO) levels and endothelial NO synthase (eNOS) renal expression were studied as well as the EDTA protection from the TNFα-induced vascular leakage in the kidneys. Data was compared by two-way analysis of variance followed by a post hoc test.

Results

EDTA administration resulted in the preservation of both functional and histological parameters of rat kidneys. PMN obtained from peripheral blood of EDTA-treated ischemized rats, displayed a significant reduction in the expression of the adhesion molecule Mac-1 with respect to controls. NO was significantly increased by EDTA administration and eNOS expression was higher and more diffuse in kidneys of rats treated with EDTA than in the controls. Finally, EDTA administration was able to prevent in vivo the TNFα-induced vascular leakage in the kidneys.

Conclusion

This data provides evidence that EDTA treatment is able to protect rat kidneys from ischemic damage possibly through the stimulation of NO production.
Circle of Willis variation in a complex stroke presentation: a case report
Authors: Emsley Hedley CA , Young Carolyn A , White Richard P
Published: April 2006

Background

The impact of circle of Willis anatomical variation upon the presentation of stroke is probably underrecognised.

Case presentation

A 63-year-old right-handed woman developed a left hemiparesis and right leg weakness sequentially following a road traffic accident (RTA). Despite initial concern about the possibility of cervical spinal cord injury, the final diagnosis was bilateral artery-to-artery embolic cerebral infarction with dominant right internal carotid artery.

Conclusion

The case illustrates the complex presentation of stroke as a pseudo-cervical cord lesion and the impact of circle of Willis anatomical variation upon the expression of large vessel cerebrovascular disease.
Corticosteroid co-treatment induces resistance to chemotherapy in surgical resections, xenografts and established cell lines of pancreatic cancer
Authors: Zhang Chengwen , Kolb Armin , Büchler Peter , Cato Andrew CB , Mattern Jürgen , Rittgen Werner , Edler Lutz , Debatin Klaus-Michael , Büchler Markus W , Friess Helmut , Herr Ingrid
Published: April 2006

Background

Chemotherapy for pancreatic carcinoma often has severe side effects that limit its efficacy. The glucocorticoid (GC) dexamethasone (DEX) is frequently used as co-treatment to prevent side effects of chemotherapy such as nausea, for palliative purposes and to treat allergic reactions. While the potent pro-apoptotic properties and the supportive effects of GCs to tumour therapy in lymphoid cells are well studied, the impact of GCs to cytotoxic treatment of pancreatic carcinoma is unknown.

Methods

A prospective study of DEX-mediated resistance was performed using a pancreatic carcinoma xenografted to nude mice, 20 surgical resections and 10 established pancreatic carcinoma cell lines. Anti-apoptotic signaling in response to DEX was examined by Western blot analysis.

Results

In vitro, DEX inhibited drug-induced apoptosis and promoted the growth in all of 10 examined malignant cells. Ex vivo, DEX used in physiological concentrations significantly prevented the cytotoxic effect of gemcitabine and cisplatin in 18 of 20 freshly isolated cell lines from resected pancreatic tumours. No correlation with age, gender, histology, TNM and induction of therapy resistance by DEX co-treatment could be detected. In vivo, DEX totally prevented cytotoxicity of chemotherapy to pancreatic carcinoma cells xenografted to nude mice. Mechanistically, DEX upregulated pro-survival factors and anti-apoptotic genes in established pancreatic carcinoma cells.

Conclusion

These data show that DEX induces therapy resistance in pancreatic carcinoma cells and raise the question whether GC-mediated protection of tumour cells from cancer therapy may be dangerous for patients.
Different regression equations relate age to the incidence of Lauren types 1 and 2 stomach cancer in the SEER database: these equations are unaffected by sex or race
Authors: Wachtel Mitchell S , Zhang Yan , Chiriva-Internati Maurizio , Frezza Eldo E
Published: April 2006

Background

Although impacts upon gastric cancer incidence of race, age, sex, and Lauren type have been individually explored, neither their importance when evaluated together nor the presence or absence of interactions among them have not been fully described.

Methods

This study, derived from SEER (Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute) data, analyzed the incidences of gastric cancer between the years 1992–2001. There were 7882 patients who had developed gastric cancer. The total denominator population was 145,155, 669 persons (68,395,787 for 1992–1996, 78,759,882 for 1997–2001). Patients with multiple tumors were evaluated as per the default of the SEER*Stat program. 160 age-, five year period (1992–1996 vs 1997–2001)-, sex-, race (Asian vs non-Asian)-, Lauren type- specific incidences were derived to form the stratified sample evaluated by linear regression. (160 groups = 2 five year periods × 2 race groups × 2 sexes × 2 Lauren types × 10 age groups.) Linear regression was used to analyze the importance of each of these explanatory variables and to see if there were interactions among the explanatory variables.

Results

Race, sex, age group, and Lauren type were found to be important explanatory variables, as were interactions between Lauren type and each of the other important explanatory variables. In the final model, the contribution of each explanatory variable was highly statistically significant (t > 5, d.f. 151, P < 0.00001). The regression equation for Lauren type 1 had different coefficients for the explanatory variables Race, Sex, and Age, than did the regression equation for Lauren type 2.

Conclusion

The change of the incidence of stomach cancer with respect to age for Lauren type 1 stomach cancer differs from that for Lauren type 2 stomach cancers. The relationships between age and Lauren type do not differ across gender or race. The results support the notion that Lauren type 1 and Lauren type 2 gastric cancers have different etiologies and different patterns of progression from pre-cancer to cancer. The results should be validated by evaluation of other databases.
Recombinant AAV-mediated HSVtk gene transfer with direct intratumoral injections and Tet-On regulation for implanted human breast cancer
Authors: Zi-Bo LI , Zhao-Jun ZENG , Qian CHEN , Sai-Qun LUO , Wei-Xin HU
Published: April 2006

Background

HSVtk/ganciclovir (GCV) gene therapy has been extensively studied in tumors and relies largely on the gene expression of HSVtk. Most studies, however, have failed to demonstrate any significant benefit of a controlled gene expression strategy in cancer treatment. The Tet-On system is commonly used to regulate gene expression following Dox induction. We have evaluated the antitumor effect of HSVtk/ganciclovir gene therapy under Tet-On regulation by means of adeno-associated virus-2 (AAV-2)-mediated HSVtk gene transfer with direct intratumoral injections in mice bearing breast cancer tumors.

Methods

Recombinant adeno-associated virus-2 (rAAV) was constructed and transduced into MCF-7 cell line. GCV treatment to the rAAV infected MCF-7 cells was performed by MTT assay under the doxycycline (Dox) induction or without Dox induction at a vp (viral particle) number of ≥104 /cell. The virus was administered intratumorally to nude mice that had also received GCV intraperitoneally. The antitumor effects were evaluated by measuring tumor regression and histological analysis.

Results

We have demonstrated that GCV treatment to the infected MCF-7 cells under the Dox induction was of more inhibited effects than those without Dox induction at ≥104 vp/cell. In ex vivo experiments, tumor growth of BALB/C nude mice breast cancer was retarded after rAAV-2/HSVtk/Tet-On was injected into the tumors under the Dox induction. Infiltrating cells were also observed in tumors after Dox induction followed by GCV treatment and cells were profoundly damaged. The expression of HSVtk gene in MCF-7 cells and BALB/C nude mice tumors was up-regulated by Tet-On under Dox induction with reverse transcription-PCR (RT-PCR) analysis.

Conclusion

The antitumor effect of rAAV-mediated HSVtk/GCV gene therapy under the Dox induction with direct intratumoral injections may be a useful treatment for breast cancer and other solid tumors.
Polymorphisms of the XRCC1, XRCC3 and XPDgenes and risk of colorectal adenoma and carcinoma, in a Norwegian cohort: a case control study
Authors: Skjelbred Camilla Furu , Sæbø Mona , Wallin Håkan , Nexø Bjørn Andersen , Hagen Per Christian , Lothe Inger Marie Bowitz , Aase Steinar , Johnson Egil , Hansteen Inger-Lise , Vogel Ulla , Kure Elin H
Published: April 2006

Background

Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. Less is known about other DNA repair pathways in colorectal carcinogenesis. In this study we have focused on theXRCC1,XRCC3andXPDgenes, involved in base excision repair, homologous recombinational repair and nucleotide excision repair, respectively.

Methods

We used a case-control study design (157 carcinomas, 983 adenomas and 399 controls) to test the association between five polymorphisms in these DNA repair genes (XRCC1Arg194Trp, Arg280His, Arg399Gln,XRCC3Thr241Met andXPDLys751Gln), and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression model adjusting for age, gender, cigarette smoking and alcohol consumption.

Results

TheXRCC1280His allele was associated with an increased risk of adenomas (OR 2.30, 95% CI 1.19–4.46). TheXRCC1399Gln allele was associated with a reduction of risk of high-risk adenomas (OR 0.62, 95% CI 0.41–0.96). Carriers of the variantXPD751Gln allele had an increased risk of low-risk adenomas (OR 1.40, 95% CI 1.03–1.89), while no association was found with risk of carcinomas.

Conclusion

Our results suggest an increased risk for advanced colorectal neoplasia in individuals with theXRCC1Arg280His polymorphism and a reduced risk associated with theXRCC1Arg399Gln polymorphism. Interestingly, individuals with theXPDLys751Gln polymorphism had an increased risk of low-risk adenomas. This may suggest a role in regression of adenomas.
CD40L induces multidrug resistance to apoptosis in breast carcinoma and lymphoma cells through caspase independent and dependent pathways
Authors: Voorzanger-Rousselot Nathalie , Alberti Laurent , Blay Jean-Yves
Published: April 2006

Background

CD40L was found to reduce doxorubicin-induced apoptosis in non Hodgkin's lymphoma cell lines through caspase-3 dependent mechanism. Whether this represents a general mechanism for other tumor types is unknown.

Methods

The resistance induced by CD40L against apoptosis induced by a panel of cytotoxic chemotherapeutic drugs in non Hodgkin's lymphoma and breast carcinoma cell lines was investigated.

Results

Doxorubicin, cisplatyl, etoposide, vinblastin and paclitaxel increased apoptosis in a dose-dependent manner in breast carcinoma as well as in non Hodgkin's lymphoma cell lines. Co-culture with irradiated L cells expressing CD40L significantly reduced the percentage of apoptotic cells in breast carcinoma and non Hodgkin's lymphoma cell lines treated with these drugs. In breast carcinoma cell lines, these 5 drugs induced an inconsistent increase of caspase-3/7 activity, while in non Hodgkin's lymphoma cell lines all 5 drugs increased caspase-3/7 activity up to 28-fold above baseline. Co-culture with CD40L L cells reduced (-39% to -89%) the activation of caspase-3/7 induced by these agents in all 5 non Hodgkin's lymphoma cell lines, but in none of the 2 breast carcinoma cell lines. Co culture with CD40L L cells also blocked the apoptosis induced by exogenous ceramides in breast carcinoma and non Hodgkin's lymphoma cell lines through a caspase-3-like, 8-like and 9-like dependent pathways.

Conclusion

These results indicate that CD40L expressed on adjacent non tumoral cells induces multidrug resistance to cytotoxic agents and ceramides in both breast carcinoma and non Hodgkin's lymphoma cell lines, albeit through a caspase independent and dependent pathway respectively.
Prognostic value of monitoring tumour markers CA 15-3 and CEA during fulvestrant treatment
Authors: Bartsch Rupert , Wenzel Catharina , Pluschnig Ursula , Hussian Dagmar , Sevelda Ursula , Altorjai Gabriela , Locker Gottfried J , Mader Robert , Zielinski Christoph C , Steger Guenther G
Published: April 2006

Background

At many centres tumour markers are used to detect disease recurrence and to monitor response to therapy in patients with advanced disease, although the real value of serial observation of marker levels remains disputed. In this study, we evaluated the prognostic value of tumour markers for predicting response (partial response [PR], stable disease [SD] ≥ 6 months), de novo disease progression (PD) and secondary PD in patients receiving fulvestrant ('Faslodex') 250 mg/month for the treatment of metastatic breast cancer (MBC).

Methods

Changes in cancer antigen 15–3 (CA 15-3) and carcinoembryonic antigen (CEA) were prospectively monitored (monthly) and were also evaluated for the 3 months preceding secondary PD. Data from 67 patients with previously treated MBC participating in a Compassionate Use Programme were analysed.

Results

In patients with a PR (n = 7 [10.4%]), a non-significant increase in CA 15-3 occurred during the first 6 months of treatment; CEA was significantly reduced (P = 0.0165). In patients with SD ≥ 6 months (n = 28 [41.8%]), both CA 15-3 (P < 0.0001) and CEA (P = 0.0399) levels increased significantly after 6 months treatment. In those experiencing de novo PD (n = 32 [47.8%]), CA 15-3 increased significantly (P < 0.0001) after 4 months; CEA also increased significantly (P = 0.0002) during the same time period. Both CA 15-3 (P < 0.0001) and CEA (P < 0.0001) increased significantly in the 3 months preceding secondary PD.

Conclusion

CA 15-3 increases in patients progressing on fulvestrant but may also increase in those experiencing clinical benefit; this should not be taken as a sign of PD without verification. Overall, both CA 15-3 and CEA appear to be poor prognostic markers for determining progression in patients receiving fulvestrant.
Single nucleotide polymorphisms of the APC gene and colorectal cancer risk: a case-control study in Taiwan
Authors: Chen Shee-Ping , Tsai Shih-Tzu , Jao Shu-Wen , Huang Yen-Lun , Chao Yu-Chen , Chen Yi-Lin , Wu Chang-Chieh , Lin Shinn-Zong , Harn Horng-Jyh
Published: April 2006

Background

Colorectal cancer (CRC), which has become especially prevalent in developed countries, is currently the third highest cause of cancer mortality in Taiwan. Mutation of the adenomatous polyposis coli (APC) gene, a tumour suppressor, is thought to be an early event in colorectal tumourigenesis. To date, however, no large-scale screening for APC gene variants in Chinese subjects has been performed. The present study was undertaken to identify APC gene variants that are significantly associated with the occurrence of CRC in Taiwanese subjects.

Methods

In order to compare the genotype distribution of variant sites, the full-length APC genes of 74 healthy individuals and 80 CRC patients were sequenced.

Results

Among the 154 Taiwanese subjects examined in this study, three new mutations, but no previously reported mutations, were found. One deletion at codon 460 leading to a frameshift and two missense mutations resulting in p.V1125A and p.S1126R substitutions were identified. Additionally, three high risk genotypes associated with three single nucleotide polymorphisms and one low risk genotype at codon 1822 were identified.

Conclusion

The findings of this case-control study are consistent with the proposal that Taiwanese subjects differ from other subjects with respect to phenotypic presentation of APC and CRC risk.
A pilot, prospective evaluation of a novel alternative for maintenance therapy of breast cancer-associated lymphedema [ISRCTN76522412]
Authors: Wilburn Olivia , Wilburn Paul , Rockson Stanley G
Published: April 2006

Background

Prospective investigations of complete decongestive lymphatic physiotherapy (CDPT), including manual lymphatic drainage (MLD), have validated the efficacy of these interventions for the initial reduction of edema and long-term maintenance of limb volume in lymphedema. However, CDPT demands substantial time and effort from patients to maintain these benefits; the treatments are not always well-accepted, and patients may suffer from a deterioration in quality-of-life or a time-dependent loss of initial treatment benefits. A new device designed for home use by the patient, the Flexitouch™, has been developed to mechanically simulate MLD. We have undertaken a prospective, randomized, crossover study of the efficacy of the Flexitouch™, when compared to massage, in the self-administered maintenance therapy of lymphedema.

Methods

A prospective, randomized, crossover study of maintenance therapy was performed in 10 patients with unilateral breast cancer-associated lymphedema of the arm. Each observation phase included self-administered treatment with the Flexitouch™ or massage, 1 hour daily for 14 days, respectively, followed by crossover to the alternate treatment phase. Each treatment phase was preceded by a 1 week treatment washout, with use of garment only. The sequence of treatment was randomly assigned. The potential impact of treatment modality on quality of life was assessed with serial administration of the SF-36.

Results

Statistical analysis disclosed that the order of treatment had no outcome influence, permitting 10 comparisons within each treatment group. Post-treatment arm volume reduced significantly after the Flexitouch™, but not after self-administered massage. The patients' mean weight decreased significantly with Flexitouch™ use, but not with massage. The Flexitouch™ device was apparently well-tolerated and accepted by patients. Serial SF-36 administration showed no deterioration in physical or psychosocial scores compared to baseline measurements; there were no statistical differences in scores when the two treatment modalities were compared.

Conclusion

This short-term prospective evaluation of the Flexitouch™ suggests that the device may provide better maintenance edema control than self-adiminstered massage in breast cancer-associated lymphedema. The apparent ease of use and reliability of response to the device suggest that further broad-scale testing is warranted.
Efficacy of trypan blue in posterior capsulorhexis with optic capture in pediatric cataracts [ISRCTN48221688]
Authors: Sharma Namrata , Balasubramanya Ramamurthy , Dada Vijay K , Vajpayee Rasik B
Published: April 2006

Background

To evaluate the efficacy of trypan blue (0.06%) in posterior capsulorhexis with optic capture in pediatric cataracts.

Methods

In this prospective randomized controlled study, trypan blue dye assisted posterior capsulorhexis with optic capture was performed in 18 eyes (group 1) and no dye was used for posterior capsulorhexis (group 2) in 17 eyes.

Results

The mean size of the posterior capsulorhexis was 4.6 +/-1.77 mm and 4.0 +/- 0.93 mm in the group 1 and 2 respectively. Optic capture was possible in 17 eyes in the group 1 and 11 eyes in the group 2.

Conclusion

Trypan blue facilitates posterior capsulorhexis with optic capture of AcrySof IOL in cases of pediatric cataracts.
Do variations in the theatre team have an impact on the incidence of complications?
Authors: Baylis Oliver J , Adams Wendy E , Allen David , Fraser Scott G
Published: April 2006

Background

To examine whether variations in non-medical personnel influence the incidence of complications in a cataract theatre.

Methods

A retrospective Case-Control study was undertaken in a single-site, designated cataract theatre. Staffing variations within theatre were examined and the incidence of cataract complications was assessed.

Results

100 complicated lists and 200 uncomplicated control lists were chosen. At least 7 nurses were present for every list. Mean experience of the nurses was 6.4 years for case lists and 6.5 years for control lists. Average scrub nurse experience in years was 7.6 years for complicated lists and 8.0 years for controls. 26% of complicated case lists were affected by unplanned leave and 17% in control lists. Odds ratio 1.7 (1.0 to 3.1) 95% CI.

Conclusion

Unplanned leave can have a detrimental effect on the operating list. The impact of this may be modifiable with careful planning.
Insertion of a foldable hydrophobic IOL through the trabeculectomy fistula in cases with Microincision cataract surgery combined with trabeculectomy
Authors: Dada Tanuj , Muralidhar Rajamani , Sethi Harinder S
Published: April 2006

Background

The use of conventional foldable hydrophobic intraocular lenses (IOLs) in microincision cataract surgery (MICS) currently requires wound enlargement. We describe a combined surgical technique of MICS and trabeculectomy with insertion of a foldable IOL through the trabeculectomy fistula.

Methods

After completion of MICS through two side port incisions, a 3.2 mm keratome is used to enter the anterior chamber under the previously outlined scleral flap. An Acrysof multi piece IOL (Alcon labs, Fort Worth, Tx) is inserted into the capsular bag through this incision. The scleral flap is then elevated and a 2 × 2 mm fistula made with a Kelly's punch. The scleral flap and conjunctival closure is performed as usual.

Results

Five patients with primary open angle glaucoma with a visually significant cataract underwent the above mentioned procedure. An IOL was implated in the capsular bag in all cases with no intraperative complications. After surgery, all patients obtained a best corrected visual acuity of 20/20, IOL was well centered at 4 weeks follow up. The mean IOP (without any antiglaucoma medication) was 13.2 + 2.4 mm Hg at 12 weeks with a well formed diffuse filtering bleb in all the cases.

Conclusion

The technique of combining MICS with trabeculectomy and insertion of a foldable IOL through the trabeculectomy fistula is a feasible and valuable technique for cases which require combined cataract and glaucoma surgery.
Risk factors in hospital deaths in severely malnourished children in Kampala, Uganda
Authors: Bachou Hanifa , Tumwine James K , Mwadime Robert KN , Tylleskär Thorkild
Published: April 2006

Background

Although the risk factors for increased fatality among severely malnourished children have been reported, recent information from Africa, during a period of HIV pandemic and constrained health services, remains sketchy. The aim of this study has been to establish the risk factors for excess deaths among hospitalized severely malnourished children of below five years of age.

Method

In 2003, two hundred and twenty consecutively admitted, severely malnourished children were followed in the paediatric wards of Mulago, Uganda's national referral and teaching hospital. The children's baseline health conditions were established by physical examination, along with haematological, biochemical, microbiological and immunological indices.

Results

Of the 220 children, 52 (24%) died, with over 70% of the deaths occurring in the first week of admission. There was no significant difference by sex or age group. The presence of oedema increased the adjusted odds-ratio, but did not reach significance (OR = 2.0; 95% CI = 0.8 – 4.7), similarly for a positive HIV status (OR = 2.6, 95% CI = 0.8 – 8.6). Twenty four out of 52 children who received blood transfusion died (OR = 5.0, 95% CI = 2 – 12); while, 26 out of 62 children who received intravenous infusion died (OR = 4.8, 95% CI = 2 – 12). The outcome of children who received blood or intravenous fluids was less favourable than of children who did not receive them. Adjustment for severity of disease did not change this.

Conclusion

The main risk factors for excess hospital deaths among severely malnourished children in Mulago hospital include blood transfusion and intravenous infusion. An intervention to reduce deaths needs to focus on guideline compliance with respect to blood transfusions/infusions.
"Random" gentamicin concentrations do not predict trough levels in neonates receiving once daily fixed dose regimens
Authors: Boyle Elaine M , Brookes Isobel , Nye Kathy , Watkinson Mike , Riordan F Andrew I
Published: April 2006

Background

Monitoring plasma gentamicin concentrations in neonates 24 hours after a once daily dose (4 mg/kg) often necessitates additional blood sampling. In adults a nomogram has been developed enabling evaluation of gentamicin doses by sampling concentrations with other blood tests, 4 – 16 hours after administration. We attempted to develop a similar nomogram for neonates.

Methods

In addition to standard 24 hour sampling to monitor trough concentrations, one additional "random" gentamicin concentration was measured in each of 50 neonates <4 days of age (median gestation 33 weeks [28–41]), when other blood samples were clinically necessary, 4 – 20 hours after gentamicin administration. 24 hour concentrations of >1 mg/L were considered high, and an indication to extend the dosing interval.

Results

Highest correlation (r2 = 0.51) of plasma gentamicin concentration against time (4 to 20 hours) was with logarithmic regression. A line drawn 0.5 mg/L below the true regression line resulted in all babies with 24 hr gentamicin concentrations >1 mg/L having the additional "random" test result above that line, i.e. 100% sensitivity for 24 hour concentrations>1 mg/L, though only 58% specificity. Having created the nomogram, 39 further babies (median gestation 34 weeks [28–41]), were studied and results tested against the nomogram. In this validation group, sensitivity of the nomogram for 24 hr concentrations >1 mg/L was 92%; specificity 14%, positive predictive value 66%, and negative predictive value 50%.

Prematurity (≤ 37 weeks) was a more sensitive (94%) and specific (61%) indicator of high 24-hour concentrations. 62 (87%) of 71 preterm babies had high 24-hour concentrations.

Conclusion

It was not possible to construct a nomogram to predict gentamicin concentrations at 24 hours in neonates with a variety of gestational ages. Dosage tailored to gestation with monitoring of trough concentrations remains management of choice.
Description of the methodology used in an ongoing pediatric care interventional study of children born with cleft lip and palate in South America [NCT00097149]
Authors: Wehby George L , Castilla Eduardo E , Goco Norman , Rittler Monica , Cosentino Viviana , Javois Lorette , McCarthy Ann Marie , Bobashev Georgiy , Litavecz Stephen , Mariona Alejandra , Dutra Graca , López-Camelo Jorge S , Orioli Iêda M , Murray Jeffrey C
Published: April 2006

Background

The contribution of birth defects, including cleft lip and palate, to neonatal and infant mortality and morbidity is substantial. As other mortality and morbidity causes including infections, hygiene, prematurity, and nutrition are eradicated in less developed countries, the burden of birth defects will increase proportionally.

Methods/Design

We are using cleft lip and palate as a sentinel birth defect to evaluate its burden on neonatal and infant health and to assess the effectiveness of systematic pediatric care during the first month and first two years of life in decreasing this burden. The neonatal intervention, consisting of weekly pediatric evaluation and referral to appropriate care, is delivered to about 696 infants born with cleft lip and/or palate in 47 hospitals in South America. Neonatal mortality in this group will be compared to that in a retrospective control group of about 464 infants born with cleft lip and/or palate in the same hospitals. The subgroup of infants with isolated clefts of both the lip and palate (about 264) is also randomized into two groups, intervened and non-intervened, and further followed up over 2 years. Intervened cases are evaluated by pediatricians every three months and referred for appropriate care. The intervened and non-intervened cases will be compared over study outcomes to evaluate the intervention effectiveness. Non-intervened cases are matched and compared to healthy controls to assess the burden of cleft lip and palate. Outcomes include child's neurological and physical development and family social and economic conditions.

Discussion

Large-scale clinical trials to improve infant health in developing countries are commonly suggested, making it important to share the methods used in ongoing studies with other investigators implementing similar research. We describe here the content of our ongoing pediatric care study in South America. We hope that this may help researchers targeting this area to plan their studies more effectively and encourage the development of similar research efforts to target other birth defects or infant outcomes such as prematurity and low birth weight.
Psychometric properties of the Farsi translation of the kiddie schedule for affective disorders and schizophrenia-present and lifetime version
Authors: Ghanizadeh Ahmad , Mohammadi Mohammad Reza , Yazdanshenas Arash
Published: April 2006

Background

Semi-structural clinical interviews are very important in the area of mental health research and services. There were no studies of the reliability and validity of the Farsi (Persian) version of Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL) in Iran. This study compares the results of face-to-face, semi-structural interview and clinical interview by a child and adolescent psychiatrist.

Method

Subjects were 109 children and adolescents recruited to the child and adolescent psychiatry outpatient clinic of Hafez Hospital. Order of interview (in-psychiatrist or the semi-structural interview) was determined using random assignment within a counterbalanced framework. After, translation and back translation of K-SADS-PL, the Farsi version of K-SADS-PL was provided and used in the study. The interviewer was unaware of the child and adolescent psychiatrist diagnosis at the time of making the interview. Consensual validity, test-retest and inter-rater reliability, sensitivity, specifity, positive and negative predictive validity for the disorders were studied.

Results

Consensual validity of all of the psychiatric disorders was good to excellent. It was highest for panic disorder, conduct disorder, and simple phobia. Consensual validity of anorexia nervosa was 0.49. There was sufficient validity and test-retest and inter-rater reliability and good to excellent sensitivity and specifity and positive and negative predictive validity for nearly all of the disorders. Test-retest reliabilities of attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and tic disorder were 0.81, 0.67, and 0.56; respectively. Inter-rater reliabilities of ADHD, and ODD were 0.69 and 0.69. Tic disorder, post traumatic disorder, panic disorder, and ADHD had the highest positive predictive validities.

Conclusion

The Farsi version of K-SADS-PL is a valid and reliable interview instrument for use in assessing and diagnosising child and adolescent psychiatric disorders.
The development of a multidisciplinary fall risk evaluation tool for demented nursing home patients in the Netherlands
Authors: Neyens Jacques CL , Dijcks Béatrice PJ , van Haastregt Jolanda CM , de Witte Luc P , van den Heuvel Wim JA , Crebolder Harry FJM , Schols Jos MGA
Published: April 2006

Background

Demented nursing home patients are at high risk for falls. Falls and associated injuries can have a considerable influence on the autonomy and quality of life of patients. The prevention of falls among demented patients is therefore an important issue. In order to intervene in an efficient way in this group of patients, it is important to systematically evaluate the fall risk profile of each individual patient so that for each patient tailor-made preventive measures can be taken. Therefore, the objective of the present study is to develop a feasible and evidence based multidisciplinary fall risk evaluation tool to be used for tailoring preventive interventions to the needs of individual demented patients.

Methods

To develop this multidisciplinary fall risk evaluation tool we have chosen to combine scientific evidence on the one hand and experts' opinions on the other hand. Firstly, relevant risk factors for falling in elderly persons were gathered from the literature. Secondly, a group of Dutch experts in the field of falls and fall prevention in the elderly were consulted to judge the suitability of these risk factors for use in a multidisciplinary fall risk evaluation tool for demented nursing home patients. Thirdly, in order to generate a compact list of the most relevant risk factors for falling in demented elderly, all risk factors had to fulfill a set of criteria indicating their relevance for this specific target population. Lastly the final list of risk factors resulting from the above mentioned procedure was presented to the expert group. The members were also asked to give their opinion about the practical use of the tool.

Results

The multidisciplinary fall risk evaluation tool we developed includes the following items: previous falls, use of medication, locomotor functions, and (correct) choice and use of assistive and protective devices. The tool is developed for the multidisciplinary teams of the nursing homes.

Conclusion

This evidence and practice based multidisciplinary fall risk evaluation tool targets the preventive interventions aimed to prevent falls and their negative consequences in demented nursing home patients.
Differences in avoidable mortality between migrants and the native Dutch in the Netherlands
Authors: Stirbu I , Kunst AE , Bos V , Mackenbach JP
Published: April 2006

Background

The quality of the healthcare system and its role in influencing mortality of migrant groups can be explored by examining ethnic variations in 'avoidable' mortality. This study investigates the association between the level of mortality from 'avoidable' causes and ethnic origin in the Netherlands and identifies social factors that contribute to this association.

Methods

Data were obtained from cause of death and population registries in the period 1995–2000. We compared mortality rates for selected 'avoidable' conditions for Turkish, Moroccan, Surinamese and Antillean/Aruban groups to native Dutch.

Results

We found slightly elevated risk in total 'avoidable' mortality for migrant populations (RR = 1.13). Higher risks of death among migrants were observed from almost all infectious diseases (most RR > 3.00) and several chronic conditions including asthma, diabetes and cerebro-vascular disorders (most RR > 1.70). Migrant women experienced a higher risk of death from maternity-related conditions (RR = 3.37). Surinamese and Antillean/Aruban population had a higher mortality risk (RR = 1.65 and 1.31 respectively), while Turkish and Moroccans experienced a lower risk of death (RR = 0.93 and 0.77 respectively) from all 'avoidable' conditions compared to native Dutch. Control for demographic and socioeconomic factors explained a substantial part of ethnic differences in 'avoidable' mortality.

Conclusion

Compared to the native Dutch population, total 'avoidable' mortality was slightly elevated for all migrants combined. Mortality risks varied greatly by cause of death and ethnic origin. The substantial differences in mortality for a few 'avoidable' conditions suggest opportunities for quality improvement within specific areas of the healthcare system targeted to disadvantaged groups.
Smoking particles enhance endothelin A and endothelin B receptor-mediated contractions by enhancing translation in rat bronchi
Authors: Granström Bengt W , Xu Cang-Bao , Nilsson Elisabeth , Vikman Petter , Edvinsson Lars
Published: April 2006

Background

Smoking is known to cause chronic inflammatory changes in the bronchi and to contribute to airway hyper-reactivity, such as in bronchial asthma. To study the effect of smoking on the endothelin system in rat airways, bronchial segments were exposed to DMSO-soluble smoking particles (DSP) from cigarette smoke, to nicotine and to DMSO, respectively.

Methods

Isolated rat bronchial segments were cultured for 24 hours in the presence or absence of DSP, nicotine or DMSO alone. Contractile responses to sarafotoxin 6c (a selective agonist for ETB receptors) and endothelin-1 (an ETA and ETB receptor agonist) were studied by use of a sensitive myograph. Before ET-1 was introduced, the ETB receptors were desensitized by use of S6c. The remaining contractility observed was considered to be the result of selective activation of the ETA receptors. ETA and ETB receptor mRNA expression was analyzed using real-time quantitative PCR. The location and concentration of ETA and ETB receptors were studied by means of immunohistochemistry together with confocal microscopy after overnight incubation with selective antibodies.

Results

After being cultured together with DSP for 24 hours the bronchial segments showed an increased contractility mediated by ETA and ETB receptors, whereas culturing them together with nicotine did not affect their contractility. The up-regulation of their contractility was blunted by cycloheximide treatment, a translational inhibitor. No significant change in the expression of ETA and ETB receptor mRNA through exposure to DMSO or to nicotine exposure alone occurred, although immunohistochemistry revealed a clear increase in ETA and ETB receptors in the smooth muscle after incubation in the presence of DSP. Taken as a whole, this is seen as the presence of a translation mechanism.

Conclusion

The increased contractility of rat bronchi when exposed to DSP appears to be due to a translation mechanism.
The Knee Clinical Assessment Study – CAS(K). A prospective study of knee pain and knee osteoarthritis in the general population: baseline recruitment and retention at 18 months
Authors: Peat George , Thomas Elaine , Handy June , Wood Laurence , Dziedzic Krysia , Myers Helen , Wilkie Ross , Duncan Rachel , Hay Elaine , Hill Jonathan , Lacey Rosie , Croft Peter
Published: April 2006

Background

Selective non-participation at baseline (due to non-response and non-consent) and loss to follow-up are important concerns for longitudinal observational research. We investigated these matters in the context of baseline recruitment and retention at 18 months of participants for a prospective observational cohort study of knee pain and knee osteoarthritis in the general population.

Methods

Participants were recruited to the Knee Clinical Assessment Study – CAS(K) – by a multi-stage process involving response to two postal questionnaires, consent to further contact and medical record review (optional), and attendance at a research clinic. Follow-up at 18-months was by postal questionnaire. The characteristics of responders/consenters were described for each stage in the recruitment process to identify patterns of selective non-participation and loss to follow-up. The external validity of findings from the clinic attenders was tested by comparing the distribution of WOMAC scores and the association between physical function and obesity with the same parameters measured directly in the target population as whole.

Results

3106 adults aged 50 years and over reporting knee pain in the previous 12 months were identified from the first baseline questionnaire. Of these, 819 consented to further contact, responded to the second questionnaire, and attended the research clinics. 776 were successfully followed up at 18 months. There was evidence of selective non-participation during recruitment (aged 80 years and over, lower socioeconomic group, currently in employment, experiencing anxiety or depression, brief episode of knee pain within the previous year). This did not cause significant bias in either the distribution of WOMAC scores or the association between physical function and obesity.

Conclusion

Despite recruiting a minority of the target population to the research clinics and some evidence of selective non-participation, this appears not to have resulted in significant bias of cross-sectional estimates. The main effect of non-participation in the current cohort is likely to be a loss of precision in stratum-specific estimates e.g. in those aged 80 years and over. The subgroup of individuals who attended the research clinics and who make up the CAS(K) cohort can be used to accurately estimate parameters in the reference population as a whole. The potential for selection bias, however, remains an important consideration in each subsequent analysis.