Human brucellosis: do we need to revise our therapeutic policy?

OBJECTIVE: To identify risk factors of relapse among patients with osteoarticular brucellosis. METHODS: In a prospective cohort study, we investigated 90 patients with diagnosis of brucellosis, as established by clinical picture and at least 4-fold rise in antibody titer. Osteoarticular involvement was defined by inflammatory signs and radiographic changes. Thirty-five patients received combination therapy of 2 drugs (rifampicin + cotrimoxazole or doxycycline), while 55 patients received a combination of 3 drugs (streptomycin + rifampicin + doxycycline). Monthly followup comprised clinical and laboratory examinations (seroagglutination, IgG, IgM antibody titers). Recovery of patients was based on clinical improvement and seroagglutination antibody titer < or = 1:80, as well as negative results for IgG and IgM antibody titers. Incidence of relapse was recorded during the 2 year period of followup after finishing the course of treatment. RESULTS: All patients continued treatment beyond the usual 6 week period previously recommended. Relapse occurred in 59.3% in patients who received treatment for 5 months or less, while relapse occurred in 7.9% among those who received treatment for more than 5 months (p < 0.001). Sixty percent of patients who received combination therapy of 2 drugs had relapse, while there was no relapse in patients who received 3 drugs in combination (p < 0.001). Logistic regression analysis identified duration of treatment < 5 months and IgG level (above 50 U/ml) as independent predictors for relapse; the predictivity of the model was 85.6%. CONCLUSION: Extending treatment for longer than previously recommended (6 weeks) resulted in an incidence of relapse significantly lower than for shorter courses of treatment. IgG antibody in addition to seroagglutinating antibody titers are useful for serological followup of patients with brucellosis.     

Localised Ewing sarcoma/PNET of bone--prognostic factors and international data comparison

BACKGROUND: To determine if the distribution of prognostic factors accounted for the differences when the outcome for localised Ewing Sarcoma/PNET bone in Saudi Arabia was compared with results from countries with well developed health care systems. PROCEDURE: Retrospective analysis was undertaken of 163 consecutive patients of all ages, treated with radical intent at KFSHRC from 1975 to 1998. Standard chemotherapy was commenced in all patients. The local treatment modality was resection +/- radiation in 30% and radiation treatment alone in 67%. Size data were available for 51 patients treated from 1994 to 1998, inclusive. One third of these patients had tumors with volume >500 ml. RESULTS: Three year survival significantly increased with the year of diagnosis, 1975-1988 45%; 1989-1993 55%; and 1993-1998 63% (P = 0.006). Favorable prognostic factors were age < or =14 (P = 0.07); site, distal extremity, and skull (P = 0.08); and volume < or = 200 ml (P = 0.06). Secondary prognostic factors were response to induction chemotherapy, both histological, 100% necrosis, (P = 0.04) and clinical CR+PR, (P = 0.02). From 1994 to 1998, 3 year survival for tumors in the distal extremity and skull was 80% and for small tumors, < 200 ml, at any site was 82%. In comparison, the 3 year survival for patients with tumors at any other sites was 60%, and for tumors >200 ml, 55%. CONCLUSIONS: Overall survival progressively improved. From 1994 to 1998 the survival of patients with small tumors and/or favorable sites was similar to the best reported results. It was not possible to compare results by tumor size for large tumors, > 500 ml, due to the absence of data from elsewhere. A better staging system is required for the international comparison of results.     

A novel mutation in the chloride channel gene,CLCNKB, as a cause of Gitelman and Bartter syndromes

BACKGROUND: Gitelman syndrome (GS) and Bartter syndrome (BS) are hereditary hypokalemic tubulopathies with distinct phenotypic features. GS has been considered a genetically homogeneous disorder caused by mutation in the gene encoding the NaCl cotransporter (TSC) of the distal convoluted tubule. In contrast, BS is caused by mutations in the genes encoding either the Na-K-2Cl cotransporter (NKCC2), the K+ channel (ROMK) or the Cl- channel (ClC-Kb) of the thick ascending limb. The purpose of this study was to examine the clinical, biochemical and genetic characteristics of a very large inbred Bedouin kindred in Northern Israel with hereditary hypokalemic tubulopathy. METHODS: Twelve family members affected with hypokalemic tubulopathy, as well as 26 close relatives were clinically and biochemically evaluated. All study participants underwent genetic linkage analysis. Mutation analysis was performed in affected individuals. RESULTS: Evaluation of affected family members (age range 3 to 36 years) revealed phenotypic features of both GS and classic Bartter syndrome (CBS). Features typical of GS included late age of presentation (>15 years) in 7 patients (58%), normal growth in 9 (75%), hypomagnesemia (SMg <0.7mmol/L) in 5 (42%), hypermagnesiuria (FEMg>5%) in 6 (50%) and hypocalciuria (urinary calcium/creatinine mmol/mmol <0.15) in 5 (42%). Features typical of CBS included early age of presentation (<1 year) in 3 (25%), polyuria/dehydration in 4 (33%), growth retardation in 3 (25%), hypercalciuria (urinary calcium/creatinine mmol/mmoverline>0.55) in 4 (33%) and nephrolithiasis in 1 (8%). Linkage analysis in affected patients excluded the TSC gene, SLC12A3, as the mutated gene, but demonstrated linkage to the Cl- channel gene, CLCNKB, on chromosome 1p36. Mutation analysis by direct sequencing revealed a novel homozygous missense mutation, arginine 438 to histidine (R438H), in exon 13 of CLCNKB in all patients. A restriction fragment length polymorphism (RFLP) analysis has been developed to aid in genotyping of family members. CONCLUSIONS: Our findings demonstrate intrafamilial heterogeneity, namely the presence of GS and CBS phenotypes, in a kindred with the CLCNKB R438H mutation. We conclude that GS can be caused by a mutation in a gene other than SLC12A3. The exact role of the CLCNKB R438H mutation in the pathogenesis of the electrolyte and mineral abnormalities in GS and CBS remains to be established.     

Surgically staged focal liver lesions: accuracy and reproducibility of dual-phase helical CT for detection and characterization

PURPOSE: To assess the accuracy and reproducibility of dual-phase helical computed tomography (CT) in enabling preoperative detection and characterization of surgically staged focal liver lesions. MATERIALS AND METHODS: Surgically and histopathologically proven liver lesions were evaluated by three experienced CT readers. These lesions were present in 77 patients who underwent dual-phase helical CT. Images were interpreted separately by the three blinded reviewers. Each lesion was graded on a nine-point scale of confidence, with 1 being definitely benign, 9 being definitely malignant, and 5 being indeterminate. The chi2 test was used to determine if the distribution of lesion classifications was different between readers. RESULTS: There was a total of 237 lesions: 73 were benign and 164 were malignant. Sensitivity for lesion detection was 69%, 70%, and 71% for the three reviewers, respectively. Specificity was 91%, 86%, and 90%, and the area under the curve for the alternative-free response receiver operating characteristic curve was 0.84, 0.83, and 0.85, respectively. The difference in the distributions of lesion classification between the three reviewers was not statistically significant (P =.67) as determined by chi2 analysis. CONCLUSION: Dual-phase CT has sensitivity of 69%-71% and high specificity (86%-91%) in enabling the detection and characterization of focal liver lesions. Interpretation is highly reproducible, as there is minimal variation between experienced reviewers.     

Carcinosarcoma of the urinary bladder: dynamic contrast-enhanced MR imaging with clinical and pathologic correlation

OBJECTIVE: This article describes the MR imaging features of carcinosarcoma of the urinary bladder with clinical presentation and pathologic correlation in three adults. CONCLUSION: Carcinosarcoma of the urinary bladder is a rare and aggressive tumor that has a clinical presentation similar to that of transitional cell carcinoma of the bladder. Dynamic gadolinium-enhanced MR imaging features are discussed.     

Present trends in the treatment of advanced non small-cell lung cancer

Lung cancer is the leading cause of cancer deaths all over the world. As most patients present with advanced disease, major efforts have been made in the treatment of such disease with systemic chemotherapy. Several new agents and new combinations of chemotherapy have been developed recently. This article reviews the randomized clinical trials investigating chemotherapy for advanced non small-cell lung cancer (NSCLC) in relapse or progressive disease while being treated and in elderly patients. Therapies that incorporate new biological agents to target specific defects in lung cancer are also discussed. Several clinical trials have demonstrated improvement in overall survival as well as quality of life with presently available chemotherapy treatment of advanced NSCLC. Better options are available for the elderly as well as those having relapse after first-line chemotherapy. Despite all this progress the 5-year survival rate still remains at a dismal 14%. New therapies with good results are still desired.     

Trends in prevalence,awareness, treatment,and control of hypertension in the United States, 1988-2000

Context  Prior analyses of National Health and Nutrition Examination Survey (NHANES) data through 1991 have suggested that hypertension prevalence is declining, but more recent self-reported rates of hypertension suggest that the rate is increasing. Objective  To describe trends in the prevalence, awareness, treatment, and control of hypertension in the United States using NHANES data. Design, Setting, and Participants  Survey using a stratified multistage probability sample of the civilian noninstitutionalized population. The most recent NHANES survey, conducted in 1999-2000 (n = 5448), was compared with the 2 phases of NHANES III conducted in 1988-1991 (n = 9901) and 1991-1994 (n = 9717). Individuals aged 18 years or older were included in this analysis. Main Outcome Measures  Hypertension, defined as a measured blood pressure of 140/90 mm Hg or greater or reported use of antihypertensive medications. Hypertension awareness and treatment were assessed with standardized questions. Hypertension control was defined as treatment with antihypertensive medication and a measured blood pressure of less than 140/90 mm Hg. Results  In 1999-2000, 28.7% of NHANES participants had hypertension, an increase of 3.7% (95% confidence interval [CI], 0%-8.3%) from 1988-1991. Hypertension prevalence was highest in non-Hispanic blacks (33.5%), increased with age (65.4% among those aged =" BORDER="0">60 years), and tended to be higher in women (30.1%). In a multiple regression analysis, increasing age, increasing body mass index, and non-Hispanic black race/ethnicity were independently associated with increased rates of hypertension. Overall, in 1999-2000, 68.9% were aware of their hypertension (nonsignificant decline of -0.3%; 95% CI, -4.2% to 3.6%), 58.4% were treated (increase of 6.0%; 95% CI, 1.2%-10.8%), and hypertension was controlled in 31.0% (increase of 6.4%; 95% CI, 1.6%-11.2%). Women, Mexican Americans, and those aged 60 years or older had significantly lower rates of control compared with men, younger individuals, and non-Hispanic whites. Conclusions  Contrary to earlier reports, hypertension prevalence is increasing in the United States. Hypertension control rates, although improving, continue to be low. Programs targeting hypertension prevention and treatment are of utmost importance.      

Continuous venovenous hemofiltration with or without extracorporeal membrane oxygenation in children.

OBJECTIVES: We report the frequency of usage, patient demographics, and outcomes in children treated with continuous venovenous hemofiltration (CVVH) in three pediatric intensive care units (PICUs), with one unit providing combined extracorporeal membrane oxygenation (ECMO) and CVVH. DESIGN: Prospective database analysis. SETTING: Three regional PICUs in the Trent Haemofiltration Network with two general PICUs admitting 450-500 patients annually and the other providing regional cardiac support and a supraregional service for ECMO (600-650 admissions annually with 50 ECMO patients). PATIENTS: Children who underwent CVVH alone or in combination with ECMO or other therapies between January 2000 and December 2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 115 children (58 male) treated, with a median age of 18 months (range 1 day to 17 yrs) and median weight of 12 kg (range 1.8-119 kg). In the two PICUs without ECMO, CVVH was undertaken in 2.5% of admissions annually compared with 3% of annual admissions to the PICU with an ECMO service. Fifty-five patients received CVVH alone (group 1), while 53 patients underwent CVVH in conjunction with ECMO (group 2). In addition, five patients received plasmafiltration followed by CVVH, and two patients were treated with combined CVVH and molecular adsorbents recirculating system. Mean duration of therapy in group 1 was 142 hrs (1-840 hrs) and in group 2,231 hrs (3-1104 hrs). Overall patient survival was 43% with 29 of 55 (53%) CVVH patients surviving and 18 of 53 (34%) of those treated with ECMO plus CVVH. CONCLUSIONS: Performing CVVH in a heterogeneous population with large age and weight ranges poses significant clinical and technical challenges. The low frequency of CVVH use, as well as the use of other extracorporeal therapies, also raises problems with maintaining nursing skills. Objective clinical and biochemical markers for commencing CVVH alone or in combination with ECMO remain to be defined.     

Low-grade astrocytoma--a retrospective analysis of 102 patients

One hundred and two patients (57 males, 45 females, median age 17 years) with histologically proven low-grade astrocytoma (grades I, II) treated between 1978 and 1994 were retrospectively analyzed at the King Faisal Specialist Hospital & Research Center. Microscopic investigation showed 50 patients (48%) with grade I tumors as opposed to 52 patients (52%) with grade II tumors. Fifteen patients (15%) had complete surgical excision, 55 (52%) had partial excision and 32 (31%) had biopsy only; 68 patients (66%) received external radiotherapy with a median dose of 54 Gy (range 45-68.5 Gy). With a median follow-up of 3.3 years, the 5 and 10 years, overall actuarial survival rates were 78% and 62%, respectively while the progression-free survival rates at 5 and 10 years were 69%, and 35%, respectively. Age and performance status were significant prognostic factors in terms of overall survival on univariate (p = 0.05 and 0.05, respectively) and multivariate analysis (p = 0.005 and 0.006, respectively).     

A smoking survey of college students in India: implications for designing an antismoking policy

A survey of 599 college students was conducted in Andhra Pradesh, India, to formulate an anti-smoking policy for youth. There were 64.6% boys and 35.4% girls between 15 and 22 years, and 8.2% of students (n = 49, 48M + 1F) were smokers. It is a taboo for girls to smoke. There is no current anti-smoking policy and one is proposed based on the smoking survey results. The policy includes parental pressure to curb smoking, and a ban on (1) advertising of tobacco products, (2) smoking in public places and (3) teachers smoking in school. An increase in the price of cigarettes was approved by a majority of the students. The survey revealed a gap in the knowledge of students about the ill effects of smoking, which can be rectified by health education programs.