Blastocystis hominis: a new pathogen in day-care centres?
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Biomedical subjects
Publications and source records attributed to L Valiquette.
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Vitamin D3 (D3) is not active but must be hydroxylated at C-25 in liver before acquiring its hormonal potential in the kidney. The sterol-27 hydroxylase (gene symbol: CYP27A) catalyses the oxidation of sterol side chain in bile acid synthesis but the enzyme is also known as a D3-25 hydroxylase. The study examined the expression of the gene encoding CYP27A in adult and fetal human livers and kidneys. Thirty-nine adults (18 men and 21 women; mean age 58 years in men and 57 years in women) and three normal fetuses gestational age 17-19 weeks were studied. Tissue CYP27A mRNA and serum 25OHD concentrations were measured. Normal specimens: CYP27A transcript was found to be higher in adult than in fetal livers but its expression was similar in adult and fetal kidneys. In fetuses, no difference was observed between CYP27A levels in livers and kidneys. In adult livers CYP27A levels were higher in women than in men. Hepatic CYP27A mRNA and serum 25OHD concentrations were both found to be higher in summer than in winter. Multiple linear regression analyses indicate that the season of the year and the serum 25OHD concentrations (but not 1,25(OH)2D concentrations) are the best predictors of CYP27A mRNA abundance in normal adult livers. In situ hybridization illustrates a clear label in hepatocytes which increases in intensity in the perivenous region of the hepatic acinus. Pathological specimens: In one man with an hepatic carcinoma there was a very large increase in CYP27A (> 1000 fold) compared to the level found in the normal liver. In that patient, serum 25OHD concentrations were found to be high considering the level of CYP27A mRNA in the normal hepatic area suggesting that the neoplastic tissue contributed to the C-25 hydroxylation of vitamin D. Specimens obtained from two patients suffering from focal hepatic hyperplasia indicate that in one case the level of CYP27A mRNA was twice as high in the pathological than in the normal area while in the other its levels were similar in both areas. No difference in the CYP27A transcript was observed between specimens obtained from normal areas and those obtained form either an hepatic adenoma or from two intrahepatic colonic metastases. CYP27A is present not only in the human adult liver but also in the adult kidney, and in the fetal liver and kidney. Our findings illustrate that CYP27A can be significantly upregulated in certain pathological situations such as in hepatic carcinoma and that the neoplastic tissue could contribute to the circulating concentration of 25OHD.
BACKGROUND: A family history increases the risk of kidney stone passage independent of dietary risk factors. However, the metabolic basis for familial aggregation of urolithiasis is unknown. METHODS: We evaluated metabolic risk factors in families with at least two sibs with a history of calcium stones. Sibs underwent outpatient evaluations simultaneously, including 24-hour urine collection and oral calcium loading. Phenotypes were compared between affected and unaffected sibs from the same sibship. RESULTS: Eighty-three sibships comprising 388 sibs (212 affected sibs, 114 males and 98 females, and 176 unaffected sibs, 68 males and 108 females) from 71 families were analyzed. Daily urine calcium excretion was higher in affected compared with unaffected sibs (0.64 +/- 0.33 vs. 0.50 +/- 0.22 mmol Ca(2+)/mmol creatinine, respectively, P < 10(-5)). This corresponded to absolute values of 7.4 +/- 3.9 and 5.1 +/- 2.3 mmol Ca(2+)/day, respectively, for affected and unaffected males, and 5.4 +/- 2.6 and 4.2 +/- 1.9 mmol Ca(2+)/day, respectively, for affected and unaffected female sibs. When analyzed by tertile of onset age of stone passage, the differences in urine calcium were only significant in the first two tertiles (with onset age of stone passage <35 years). The fasting urine Ca(2+)/creatinine ratio was significantly higher in stone formers compared with control sibs (0.46 +/- 0.27 vs. 0.40 +/- 0.27, P = 0.04), as was the postcalcium load Ca(2+)/creatinine ratio (0.57 +/- 0.46 vs. 0.43 +/- 0.41, respectively, P = 0.02). Body mass index was marginally significantly higher in stone forming sibs (P = 0.04). Other urine phenotypes, including oxalate, phosphate, magnesium, citrate, urate, sodium, ammonium, and volume, were not associated with stone passage. CONCLUSION: Increased urine calcium excretion is the only phenotype associated with a kidney stone formation in these French-Canadian families.
Urinary tract infections (UTIs) are the most common infections seen in the hospital setting, and the second most common infections seen in the general population. Due to women's anatomy, UTIs are especially problematic for them, and up to one-third of all women will experience a UTI at some point during their lifetimes. Appropriate treatment of a UTI requires accurate classification that includes infection site, complexity of the infection, and the likelihood of recurrence. The predominant pathogen in both complicated and uncomplicated UTI remains pathogenic Escherichia coli, although Klebsiella sp. and Proteus appear with increased frequency in complicated UTI. Most often, bacteria cause UTIs by ascending means through the urethra into the bladder. Bacteria must possess virulence factors to cause UTI. Host defense factors that predispose patients to UTI include urinary stasis, abnormal urinary tract anatomy, diabetes mellitus, debility, and aging. Estrogen-related issues and short urethras predispose women to UTI. Although urine culture, with >105 colony-forming units/mL (CFU/mL) in symptomatic patients, remains the diagnostic "gold standard," correlation of the patient's history and physical examination with urinalysis (including nitrite dipstick and leukocyte esterase test) results usually suffices to diagnose UTI. Three-day of antimicrobial treatment is recommended for simple cystitis. Acute pyelonephritis, an infection of the kidney parenchyma tissue, is treated with antibiotics for 7 to 14 days depending on the antimicrobial agent used and the severity of infection. In addition, patient classification determines the need for hospitalization or for urological imaging studies. Women with recurrent UTIs merit consideration for antimicrobial prophylaxis. Self-administered topical vaginal estradiol cream is an important adjunct in UTI prevention for postmenopausal women. Asymptomatic bacteruria only merits antimicrobial therapy in high-risk patients or those colonized with Proteus species.
PURPOSE: We determined whether genetic variation at 3 loci coding for putative crystallization inhibitors is linked to calcium urolithiasis. MATERIALS AND METHODS: We studied a cohort of 64 French-Canadian sibships including multiple recurrent calcium stone formers, comprising 154 independent pairs of siblings with at least 1 stone episode. Physical and meiotic mapping of the genes coding for osteopontin and uromodulin (Tamm-Horsfall protein) as well as the osteocalcin related gene (ORG or putative nephrocalcin) was performed and microsatellite markers were identified. We used nonparametric linkage analysis in the whole affected sib pair cohort as well as in affected pairs without hypercalciuria, that is concordant for 24-hour urine calcium excretion in the first quartile (mean plus or minus standard deviation 0.053 +/- 0.020 mmol./kg. or 3.4 +/- 1.3 mmol. daily), and in the first and second quartiles (mean 0.064 +/- 0.027 mmol./kg. or 4.9 +/- 2.1 mmol. daily, respectively). RESULTS: Lod scores were less than 0.3 for all 3 loci using these affection statuses. Further analysis enabled the exclusion of uromodulin at (relative risk or lambda = 3.9 and 2.5), osteopontin (lambda = 2.7 and 1.6) and ORG (lambda = 5.5 and 3.7) for affected sib pairs concordant for urine calcium excretion in the lowest and 2 lowest quartiles, respectively. CONCLUSIONS: Loci encoding 3 crystallization inhibitors are unlikely to be major genes involved in calcium stone formation in our population.
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BACKGROUND: Calcium urolithiasis is in part genetically determined and associated with idiopathic hypercalciuria. METHODS: We have used a candidate gene approach to determine whether the calcium-sensing receptor (CaR) gene is linked to idiopathic hypercalciuria and calcium urolithiasis in a cohort of French Canadian sibships with multiple affected members (64 sibships from 55 pedigrees yielding 359 affected sibling pairs with > or =1 stone episode). RESULTS: Using nonparametric linkage analysis with various intragenic and flanking markers, we showed that the CaR gene could be excluded as a major gene for hypercalciuric stone formation. We excluded the CaR (lod score <-2) at lambdas values of 1.5, 1.68, and 2.6 for sib pairs concordant for at least one stone passage, at least two stone passages, and at least one stone passage and calciuria above the 75th percentile, respectively. Quantitative trait linkage analyses did not suggest that the CaR gene was linked to biochemical markers of idiopathic hypercalciuria. CONCLUSIONS: This study shows that genetic variants of the CaR gene are not associated with idiopathic hypercalciuria and calcium nephrolithiasis in this population of French Canadians.
A spreadsheet-based model for economically characterizing the operation of a radiation treatment program has been used to perform a quantitative financial analysis of scheduled and unscheduled downtime. The incremental cost of downtime is broken down into three categories: remuneration of in-house or third party service technologists, decreased patient capacity, and local operating procedures for dealing with downtime. Different service arrangements and operating procedures are simulated to demonstrate the financial cost of treatment machine unavailability due to either preventative maintenance or unexpected breakdown. Depending on the service arrangement and operating policies for accommodating downtime, the combined cost of scheduled and unscheduled downtime (at 5%) can exceed 10% of the total cost of the radiation treatment program. It has also been demonstrated that the greatest cost component of downtime is decreased patient capacity, which can exceed $400,000 (CAN) when unscheduled downtime reaches 5%. The interpretation of this cost depends on the funding environment. Although the emphasis of this study has been the financial consequences of downtime, there are other factors which must be considered when developing policies and procedures for accommodating downtime such as effects on treatment, patient convenience and quality of life for staff. Even though the numerical results are strictly valid only within the context of the simulations performed, they do provide a broad framework within which medical physicists can make recommendations regarding service support and downtime.
BACKGROUND: One of the more prevalent conditions associated with aging is urinary incontinence (UI), which may affect up to 55% of women and 34% of men older than 65 years. As a result of increasing longevity in developed nations, the proportion of UI-susceptible individuals continues to grow, presenting clinical and economic challenges to healthcare providers. OBJECTIVE: To assist the clinician in making informed decisions regarding UI, provide information on the wider ramifications of the disease, and provide a comprehensive overview of the condition. DATA SOURCES: MEDLINE (1966-December 1998) was searched for relevant publications using the following search terms: UI, UI in the elderly, treatment of UI, oxybutynin, flavoxate, vasopressin, quality of life in UI, and economic impact of UI. DATA SYNTHESIS: Key articles relating to the etiology, diagnosis, classification, economic burden, quality of life, and treatment of UI were retrieved, and this information formed the basis of the review. CONCLUSIONS: Although UI can be controlled relatively well with existing therapies, only about 50% of affected patients may actually seek care. There are a variety of therapeutic options available for the treatment of UI, although pharmacologic intervention is presently a relatively minor component of overall care; this suggests that effective drug therapy might play a more significant role in the future. The economic burden associated with the care of the incontinent patient is substantial, and in the US the direct medical cost of the disease was estimated at $25.5 billion in 1995. The disease also has a large impact on the individual UI patient, negatively affecting many parameters normally associated with a tolerable health-related quality of life.
Urinary incontinence is a frequent condition that is usually clinically classified into three main subgroups: urge, stress and mixed. The latter, which can account for up to 50% of the patients, is notoriously heterogeneous. It is one of the reasons why the reports of therapeutic approaches to treat incontinence vary in the medical literature and it also explains the difficulty to compare results between studies. In an attempt to address this problem and to clarify the field of urinary incontinence, we have developed new clinical classification of urinary incontinence (FPSUND) where each symptom related to incontinence is rated from 0 (no symptoms) to 3 (severe symptoms). In this acronym, "F" stands for frequency of micturition, "P" for the use of protection, "S" for the stress component of incontinence, "U" for urgency, "N" for the number of nocturnal micturition and "D" for the number of diurnal micturition. Urologists from nine different centers across Canada were asked to evaluate female patients suffering from urinary incontinence using the FPSUND classification. A total of 148 women, aged 18 to 70, suffering from urinary incontinence were thus enrolled in the study. A second, independent evaluation of the same patients was performed by registered nurses or by urodynamic technicians. The reproducibility of the classification between two observers, as measured by the Weighted Kappa score was excellent, with kappa scores between 0.47 and 0.74 (p<0.05). Overall, the users of the classification found it very easy to use in a clinical setting. We would like to propose the FPSUND classification of urinary incontinence as a useful mean to evaluate patients suffering from incontinence and as a way to assess treatment outcome.
The purpose of this study was to evaluate, from the perspective of the Quebec health system, the cost and cost-efficacy of using NMP22 compared with the currently recommended monitoring procedure following a transurethral resection of a bladder tumor (TURBT). This evaluation was based on results from the study by Soloway, et al. It was performed using a decision analysis technique which compared a follow-up modality using NMP22 with the conventional follow-up monitoring procedure for the first 6 months after an initial transurethral resection of a bladder tumor. Each routine cystoscopy and cytology costs a total of $155. For the 6 months following initial TURBT, the cost for standard follow-up monitoring totaled $311, while the cost for the NMP22 monitoring modality was $257. On average, using NMP22 would have saved $55 per patient during the first 6 months of follow-up, resulting in a cost saving of approximately 18%. As well, 64.3% of patients would have undergone only one cystoscopy during the 6 month period, instead of the two done using the conventional modality. The trade-off for using NMP22 is that some patients would have a 3 month delay before diagnosis of a recurrence. This would occur in 8.9% of patients. NMP22 is less expensive than conventional monitoring follow-up of bladder cancer, and it can decrease patient discomfort by reducing the need for cystoscopy. Implementing it as routine follow-up monitoring should be considered, particularly for patients with low-grade tumors.
OBJECTIVE: To review the long-term follow-up, in terms of recurrence and progression, of transitional cell carcinoma of the bladder treated with intravesical BCG with the following indications: CIS, Ta and T1. MATERIALS AND METHODS: Ninety-two patients who had received complete course of BCG between 1987 and 1993 were included in the study and followed for an average of 59 months (range 12 to 102). RESULTS: The recurrence and progression were looked at. Patients treated with BCG for Carcinoma in situ, 11 of 19 (53%) remained tumor-free after 1 or 2 courses of BCG for the duration of the follow-up (mean 4.9 years, range 1.5 to 8.5 years). For patients treated for recurring tumors, 17 of 50 (34%) had no recurrences after 1 or 2 courses of BCG with the same follow-up. When facing multiple tumors, 10 of 23 (43%) patients did not experience recurrences. Therefore, in the 92 patients treated, 38 presented no recurrences after 1 or 2 courses of BCG, for a success rate of 41%. In terms of progression, of the 19 patients treated with BCG for CIS, 4 (21%) went on to develop muscle invasive disease. Of the 50 patients treated for recurrent tumors, 2 (4%) eventually developed lamina propria invasion (initial lesion was a Ta tumor), 4 (8%) carcinoma in situ and 7 (14%) muscle invasive disease, for an overall progression rate of 26% in this group. Of the 25 patients treated for multiple tumors, 1 (4%) developed CIS and 3 (12%) presented with muscle invasive disease, for an overall progression rate of 16% for the duration of the follow-up. Therefore, 21 of 92 (23%) patients had progression of their disease following BCG therapy. No prognostic factors for recurrence or progression could be identified in these tumors. CONCLUSION: When indications warrant its use, BCG is effective in reducing recurrences and limiting progression in TCC of the bladder. Recurrence within 2 years of treatment is, however, a sign of poor prognosis and other therapeutic options should be sought.
PURPOSE: We evaluate the long-term outcome of initial Ta grade 1 transitional cell carcinoma. MATERIALS AND METHODS: A total of 152 patients with initial Ta grade 1 bladder tumor were followed for a mean of 76 months (range 6 to 241). Recurrence was defined as positive findings on cystoscopy or biopsy. Progression was defined as an increase in tumor grade or stage. RESULTS: Tumor recurrence in 83 of 152 patients (55%) was noted within 12 months of followup in 38 patients (46%), between 12 and 24 in 11 (13%), and between 24 and 60 in 22 (27%). A significant number of recurrences (12, 14%) were diagnosed more than 60 months after the first tumor. Of 83 patients with recurrence 31 (37%) had progression, including 21 to grade 2 and 2 to grade 3 disease. Carcinoma in situ was diagnosed in 3 patients and 5 had muscle invasive disease. Progression occurred more than 24 months after initial diagnosis in 20 patients and more than 60 months after first tumor event (2 had carcinoma in situ and 2 had muscle invasive disease) in 12. CONCLUSIONS: Ta grade 1 bladder transitional cell carcinomas have a high recurrence rate and progression is not uncommon. These findings warrant close long-term followup, even when in some settings the trend is to discontinue followup after 5 years without any abnormal findings.
Calcium is the principal crystalline constituent in up to 80% of kidney stones. Epidemiologic studies have suggested that genetic predisposition plays a major role in the etiology of this condition. This study evaluates by a candidate-gene approach whether the vitamin D receptor (VDR) locus on chromosome 12q12-14 is implicated in idiopathic hypercalciuria and calcium nephrolithiasis in a cohort of 47 French Canadian pedigrees. These comprised 54 sibships with a total of 303 pairs of siblings concordant for > or =1 stone episode. Evidence is provided for linkage to nephrolithiasis with microsatellite marker D12S339 (near the VDR locus, P = 0.01), as well as with flanking markers (D12S1663: P = 0.03 and D12S368: P = 0.01). Inclusion of unaffected sibs in the analyses also supported evidence for linkage. Quantitative trait linkage analysis of urinary calcium excretion yielded linkage to some, but not all, markers. This appears to be the first study to suggest linkage for idiopathic calcium stone formation.
PURPOSE: A multicenter study was undertaken to evaluate the safety, efficacy and cost of electromotive drug administration of intravesical lidocaine to produce bladder local anesthesia as an alternative to traditional methods of spinal or general anesthesia. MATERIALS AND METHODS: A total of 94 patients were enrolled in the study who had either a history of bladder tumor that required cold cup bladder biopsy with fulguration for possible recurrence as a comparison trial, a bladder tumor treated with transurethral resection/fulguration or benign prostatic hyperplasia/carcinoma treated with transurethral resection. Pain scores using a Verbal Rating Scale were recorded for each individual biopsy, fulguration and resection event. Data for direct and indirect costs were collected using a standardized form for each patient to capture the details of the procedure, including times, drugs and disposables for each patient. RESULTS: There was a significant reduction in pain for patients who received electromotive intravesical lidocaine compared to no anesthesia for biopsy (p<0.03). Similarly, electromotive intravesical lidocaine for bladder biopsy and transurethral bladder tumor resection/fulguration was associated with higher patient satisfaction compared to previous treatments (p<0.00002). In contrast, electromotive intravesical lidocaine was insufficient for 3 of 6 transurethral prostatic resections. The cost per patient was about $146 Cdn less with electromotive intravesical lidocaine than with conventional general/spinal anesthesia. CONCLUSIONS: Electromotive intravesical lidocaine may be a safe, effective and affordable form of anesthesia for the ambulatory care of patients requiring transurethral bladder biopsy, resection or fulguration with a potential for cost savings.
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