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Study of the performance of 5 French and 7 French catheters in coronary angiography: a functional comparison.

The functional efficacy of a conventional 7F (high flow) coronary catheter (hand injection) was compared with a 5F (high flow) catheter using hand and powered injection in 29 patients with ischemic heart disease. Patients were randomized to 5F or 7F catheters as the initial catheter. Consecutive comparative coronary angiograms were performed in the 15 degrees right anterior oblique (RAO) view using Judkin's technique. Visual diagnostic grade (Grade 1 = Diagnostic, Grade 2 = Equivocal, Grade 3 = Nondiagnostic), vessel filling, vessel density (using a densitometer and corrected for background), streaming, and dislodgement were all evaluated independently by two experienced angiographers with correlation of results. Mean diagnostic grade (1.31 +/- 0.48) was significantly better with the 7F compared to 5F (hand) 1.72 +/- 0.81 and 5F (power) 2.00 +/- 0.71 (P less than or equal to 0.05) for each. Streaming was seen in 55% of injections with 5F (hand) versus 88.5% with 5F (power) and 20.7% with 7F. Measured vessel density was not different for the two catheters. Coronary injection dislodgement occurred significantly more often with 5F power injections than with hand injection of either catheter. Finally, in 6 (30%) of 20 patients in which the 5F was randomly the second catheter used, the operator had to revert to the 7F catheter in order to obtain adequate images. In conclusion, angiographic quality is reduced with 5F catheters compared to 7F high flow in certain patients. Thus, to achieve optimal diagnostic angiograms, larger lumen catheters may be required during certain procedures initially begun with 5F catheters.

Blood Flow Velocity↗

Diagnostic efficacy of MnDPDP in MR imaging of the liver. A phase III multicentre study.

PURPOSE: To assess the diagnostic efficacy, safety and tolerability of mangafodipir trisodium (MnDPDP, Teslascan) in MR imaging of the liver. MATERIAL AND METHODS: Eighty-two patients from 4 centres underwent MR imaging with pre-contrast sequences including T1-weighted SE and GRE, and T2-weighted turbo SE sequences. MnDPDP at a dose of 5 mumol/kg b.w. was administered by slow i.v. infusion, and 20-60 min after infusion the T1-weighted SE and GRE sequences were repeated. Diagnostic efficacy was evaluated by counting the number of lesions and by evaluating whether more information for lesion characterisation was available in post-contrast images. Safety and tolerability were assessed by recording adverse events and infusion-related discomfort. RESULTS: Significantly more lesions were found in MnDPDP-enhanced T1-weighted SE and GRE images than in unenhanced images of the same sequences. More lesions were also found in these images compared with T2-weighted images at a level of marginal significance. More information was obtained from MnDPDP-enhanced images in 40 cases. Mild to moderate adverse events were experienced by 17% of the patients. CONCLUSION: MnDPDP-enhanced images can improve lesion detection in the liver and are helpful for lesion characterisation. To obtain optimal diagnostic information of liver lesions T2-weighted images are also valuable. MnDPDP is a safe contrast agent for MR imaging of liver lesions.

Adult↗

Laboratory diagnosis of immune heparin-induced thrombocytopenia.

Immune heparin-induced thrombocytopenia (HIT) is a distinct immunohematologic syndrome in which laboratory detection of the pathogenic HIT antibodies is diagnostically useful. Assays can be broadly classified as platelet activation assays (which detect HIT antibodies based on their characteristic platelet-activating properties) and antigen assays (which measure antibodies reactive against platelet factor 4 complexed with heparin or other polyanions). Available tests vary considerably in their sensitivity-specificity profiles for detecting the antibodies and in their predictive values. The high sensitivity of certain assays means that HIT can be readily ruled out (high negative predictive value). However, because heparin-treated patients often generate nonpathogenic antibodies, a positive test does not necessarily indicate clinical HIT. Laboratory methods for detecting HIT antibodies have undergone an evolution similar to that of red blood cell serology and which parallels the Goldilocks tale, that is, progression from too insensitive (too hard) to too sensitive (too soft) to "just right." However, optimal diagnostic information requires that laboratory test results be interpreted in the appropriate clinical context.

Clinical Laboratory Techniques↗

Overcoming the errors of in-house PCR used in the clinical laboratory for the diagnosis of extrapulmonary tuberculosis.

Our experiences from 1993 to 1997 in the development and use of IS6110 base PCR for the diagnosis of extrapulmonary tuberculosis in a routine clinical setting revealed that error-correcting processes can improve existing diagnostic methodology. The reamplification method initially used had a sensitivity of 90.91% and a specificity of 93.75%. The concern was focused on the false positive results of this method caused by product-carryover contamination. This method was changed to single round PCR with carryover prevention by uracil DNA glycosylase (UDG), resulting in a 100% specificity but only 63% sensitivity. Dot blot hybridization was added after the single round PCR, increasing the sensitivity to 87.50%. However, false positivity resulted from the nonspecific dot blot hybridization signal, reducing the specificity to 89.47%. The hybridization of PCR was changed to a Southern blot with a new oligonucleotide probe giving the sensitivity of 85.71% and raising the specificity to 99.52%. We conclude that the PCR protocol for routine clinical use should include UDG for carryover prevention and hybridization with specific probes to optimize diagnostic sensitivity and specificity in extrapulmonary tuberculosis testing.

Bias↗

External validation of IASP diagnostic criteria for Complex Regional Pain Syndrome and proposed research diagnostic criteria. International Association for the Study of Pain.

Recent work in our research consortium has raised internal validity concerns regarding the current IASP criteria for Complex Regional Pain Syndrome (CRPS), suggesting problems with inadequate sensitivity and specificity. The current study explored the external validity of these IASP criteria for CRPS. A standardized evaluation of signs and symptoms of CRPS was conducted by study physicians in 117 patients meeting IASP criteria for CRPS, and 43 patients experiencing neuropathic pain with established non-CRPS etiology (e.g. diabetic neuropathy, post-herpetic neuralgia). Multiple discriminant function analyses were used to test the ability of the IASP diagnostic criteria and decision rules, as well as proposed research modifications of these criteria, to discriminate between CRPS patients and those experiencing non-CRPS neuropathic pain. Current IASP criteria and decision rules (e.g. signs or symptoms of edema, or color changes or sweating changes satisfy criterion 3) discriminated significantly between groups (P < 0.001). However, although sensitivity was quite high (0.98), specificity was poor (0.36), and a positive diagnosis of CRPS was likely to be correct in as few as 40% of cases. Empirically-based research modifications to the criteria, which are more comprehensive and require presence of signs and symptoms, were also tested. These modified criteria were also able to discriminate significantly, between the CRPS and non-CRPS groups (P < 0.001). A decision rule, requiring at least two sign categories and four symptom categories to be positive optimized diagnostic efficiency, with a diagnosis of CRPS likely to be accurate in up to 84% of cases, and a diagnosis of non-CRPS neuropathic pain likely to be accurate in up to 88% of cases. These results indicate that the current IASP criteria for CRPS have inadequate specificity and are likely to lead to overdiagnosis. Proposed modifications to these criteria substantially improve their external validity and merit further evaluation.

Adult↗

Clinical effectiveness and cost-effectiveness of tests for the diagnosis and investigation of urinary tract infection in children: a systematic review and economic model.

OBJECTIVES: To determine the diagnostic accuracy of tests for detecting urinary tract infection (UTI) in children under 5 years of age and to evaluate the effectiveness of tests used to investigate further children with confirmed UTI. Also, to evaluate the effectiveness of following up children with UTI and the cost-effectiveness of diagnostic and imaging tests for the diagnosis and follow-up of UTI in children under 5. An additional objective was to develop a preliminary diagnostic algorithm for healthcare professionals. DATA SOURCES: Electronic databases were searched up to the end of 2002/early 2003. Consultation with experts in the field. REVIEW METHODS: A systematic review was undertaken using published guidelines and results were analysed according to test grouping: diagnosis of UTI and further investigation of UTI. The cost-effectiveness results from existing evaluations were synthesised. A separate cost-effectiveness model was developed using the best available evidence, in part derived from the results of the systematic review, to illustrate the potential cost-effectiveness of some alternative management strategies in a UK setting. The results of the systematic review were used to propose diagnostic algorithms for the diagnosis and further investigation of UTI in children. Economic analyses did not contribute directly to the development of these algorithms. RESULTS: The studies included in the review provided very little data on the accuracy of clinical investigations for the diagnosis of UTI, and criteria for clinical suspicion of UTI were not further defined. The majority of studies included in the review found that clean voided midstream urine (CVU) samples had similar accuracy to suprapubic aspiration (SPA) samples when cultured with the advantage of being a non-invasive collection method that can be used in the GP's surgery. Pad, nappy or bag specimens may be appropriate methods for obtaining a urine sample in non-toilet-trained children, although only limited data were available. Although the glucose test was reported to have the highest accuracy in terms of both ruling in and ruling out disease, only a limited number of studies of this test were included and these were conducted over 30 years ago. Dipstick tests are easy to perform in the GP's surgery, give an immediate result and are relatively cheap. The results of the systematic review showed that a dipstick for leucocyte esterase (LE) and nitrite, where both test results are interpreted in combination, was a good test both for ruling in (both positive) and ruling out (both negative) a UTI. A dipstick positive for either LE or nitrite and negative for the other provides inconclusive diagnostic information and further testing is therefore required in these patients. Microscopy is more time consuming and expensive to perform than a dipstick test, but potentially quicker and cheaper than culture. As with dipstick tests, a combination of microscopy for pyuria and bacteriuria can be used accurately to rule in and rule out a UTI. An indeterminate test result is again obtained if microscopy is positive for either pyuria or bacteriuria, and negative for the other. Confirmatory culture is required in these patients. In patients considered to have a UTI, further culture to determine antibiotic sensitivities may be an option to inform treatment decisions. Only one study satisfied the inclusion criteria of the economic review and the review highlighted a number of potential limitations of this study for NHS decision-making. A separate decision-analytic model was therefore developed to provide a more reliable estimate of the optimal strategy regarding the diagnosis and further investigation of children under 5 with suspected UTI from the perspective of the NHS. The economic model found that the optimal diagnostic strategy for children presenting with symptoms suggestive of UTI depends on a number of key factors. These included the relevant subgroup of children concerned, in terms of gender and age, and the health service's maximum willingness to pay for an additional quality-adjusted life-year. CONCLUSIONS: The results of the systematic review were used to derive an algorithm for the diagnosis of UTI in children under 5. This algorithm represents the conclusions of the review in terms of effective practice. There were insufficient data to propose an algorithm for the further investigation of UTI in children under 5. The quality assessment highlighted several areas that could be improved upon in future diagnostic accuracy studies.

Algorithms↗

[Prognostic value of noninvasive coronary plaque burden quantification in patients with risk factors].

Non-invasive quantitative indices of atherosclerosis are promising new parameters for an improved prognostic stratification of patients with risk factors that aim at individualized risk factor assessment and modification. In a recently published ACC/AHA consensus document, further data on the diagnostic and prognostic value of coronary calcified plaque quantification were strongly encouraged prior to its use in the general population. In this present work we summarize data published since, which contribute significantly to the prognostic value of fast CT-based noninvasive coronary calcified plaque quantification. It is a measure of atherosclerostic disease activity and is hence an index for the likelihood of future cardiovascular events. Current data indicate that noninvasive quantification of coronary atherosclerosis has incremental prognostic value beyond conventional single risk factor assessment. However, it is not clear yet whether it has a significant value beyond quantitative combined risk assessment using complex risk prediction models such as Framingham charts. Results from ongoing prospective trials such as the MESA study in the US and the Heinz Nixdorf Recall study in Germany will clarify some of the pending issues. In addition, it is still unclear, at what stage of the disease process, which of the available imaging tools will provide optimal diagnostic and prognostic value for the individual patient.

Adult↗

Low-dose multidetector-row CT angiography of the infra-renal aorta and lower extremity vessels: image quality and diagnostic accuracy in comparison with standard DSA.

To investigate the possibility of reducing X-ray exposure during multidetector-row spiral computed tomographic (MDCT) angiography and to compare the image quality and diagnostic accuracy of different dosages with digital subtraction angiography (DSA) in the evaluation of the infra-renal aorta and lower extremities vessels. Seventy-five patients, randomly divided into three groups of 25 patients each, were evaluated for atherosclerotic disease with four-row spiral CT angiography (4x2.5 mm) and DSA. MDCT scanning parameters were kept constant, except for milliamperage (mAs): group A: 50 mAs; group B: 100 mAs; group C: 130 mAs. Images were analysed by two vascular radiologists in consensus. DSA represented the standard of reference. The diagnostic value of MDCT and total radiation exposure were evaluated for each data set. The simulated effective dose was 3.7 mSv for 50 mAs, 8.2 mSv for 100 mAs and 13.7 mSv for 130 mAs for men, and 4 mSv for 50 mAs, 8.9 mSv for 100 mAs and 14.8 mSv for 130 mAs for women. The dose reduction was 74% for group A and 40% for group B. The evaluation of the presence and degree of stenoses revealed a sensitivity, specificity, accuracy, PPV and NPV of 96%, 94%, 95%, 83% and 99% for Group A (50 mAs), 96%, 96%, 96%, 89% and 99% for Group B (100 mAs) and 98%, 96%, 97%, 91% and 100% for the standard dose protocol, Group C (130 mAs). Low-dose scanning is thus a feasible and accurate option for four-row CT angiography of the peripheral vessels. This technique provides substantial reduction of the radiation dose delivered to the patient while maintaining optimal diagnostic accuracy.

Adult↗

Comparison of three assays for total serum prostate-specific antigen and percentage of free prostate-specific antigen in predicting prostate histology.

OBJECTIVES: To determine the statistical performance of three different assays for prostate specific antigen (PSA) and the percentage of free PSA with respect to the differentiation of histologic benign prostatic hyperplasia (BPH) and prostate cancer in men who underwent surgical removal of prostate tissue. METHODS: Serum of 86 men scheduled for prostate surgery (transurethral resection of the prostate [TURP], simple open prostatectomy, radical prostatectomy, cystoprostatectomy) was frozen and subjected to measurement in batches using three different assays for total PSA (Hybritech Tandem-E, Abbott IMx, Tosoh AIA-600) and free PSA by the Hybritech method after a single freeze-thaw cycle. The histologic diagnosis of the removed tissue (35 BPH and 51 cancer) was used as a "gold standard" for classification of disease status. Sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency were calculated for the three total PSA assays and the free/total PSA ratios for the entire cohort and subsets. Receiver-operating characteristic (ROC) curve analysis was used to compare the performance of the assays and ratios. RESULTS: Mean and median total PSA values differed slightly between the three assays for all patients, and for those with BPH and cancer, but this difference was not significant. Because of a considerable overlap, the differences between the mean PSA values for men with BPH and prostate cancer were not significant. At a cutpoint of 4.0 ng/mL, sensitivity with respect to the differentiation between BPH and prostate cancer was 68.6% for all three total PSA assays; the respective AUCs (0.613-0.625) were not significantly different. While the performance of the free/total PSA ratios was superior, the differences were only significant when subsets of patients were considered with a total PSA between 4 and 10 ng/mL or 4 and 15 ng/mL (AUCs 0.789-0.816). Likewise, sensitivity, specificity, and diagnostic efficiency was better in these subsets of patients. CONCLUSIONS: In this study in which a "gold standard" based on histologic analysis of the entire (or large part of) the prostate gland was used to classify disease status, the three assays for total serum PSA (Hybritech Tandem-E, Abbott IMx, and Tosoh AIA-600) performed very similarly with identical sensitivities (at a cutpoint of 4.0 ng/mL) and comparable AUCs with respect to the differentiation of men with histologic BPH and prostate cancer. The ratios of free/total PSA calculated as free PSA by the Hybritech manual immunoradiometric assay (IRMA) method over all three total PSA assays, performed marginally better in the entire patient population. However, in the subsets of patients with a PSA of 4-10 ng/mL and 4-15 ng/mL, all three ratios performed significantly better than the three total PSA assays. The proper choice of a cutpoint for the ratio (15%, 17%, 19%, or 21%) depends on the desirability of maximizing either sensitivity or specificity while optimizing diagnostic efficiency.

Adult↗

Diagnostic power of the vaginal washing-fluid prolactin assay as an alternative method for the diagnosis of premature rupture of membranes.

OBJECTIVE: The purpose of this study was to determine the reliability of the vaginal washing-fluid prolactin assay for the diagnosis of premature rupture of membranes (PROM) and to determine a diagnostic cut-off value. STUDY DESIGN: Seventy pregnant women between 11 and 40 weeks of gestation who were admitted with vaginal fluid leakage were included in the study group, and were then further subdivided into two subgroups according to amniotic fluid pooling and nitrazine paper test results. Group 1 was the 'confirmed PROM group', positive for both pooling and nitrazine (38 patients). Group 2 was the 'suspected but unconfirmed PROM group' which had possible pooling and/or nitrazine (32 patients). Seventy pregnant women between 11 and 40 weeks of gestation without any complaint and complication were included in the control group (group 3). All patients underwent vaginal washing-fluid sampling and prolactin level determination. For the statistical analysis one-way analysis of variance, Tukey multiple comparison test, chi2 test and receiver operating characteristic (ROC) curve analysis were used. RESULTS: Geometric mean values of vaginal washing-fluid prolactin levels were 616.59 microIU/ml for group 1, 23.98 microIU/ml for group 2 and 10 microIU/ml for group 3 (p < 0.0001). The optimal diagnostic cut-off value was found to be 30 microIU/ml with 95% sensitivity, 78% specificity, 84% positive predictive value, 93% negative predictive value, 87% accuracy and 11.30 relative risk. CONCLUSIONS: We recommend vaginal washing-fluid prolactin level determination as an alternative diagnostic method for PROM.

Adult↗

Genomic approach to identification of Mycobacterium bovis diagnostic antigens in cattle.

Differential delayed-type hypersensitivity skin testing with tuberculin purified protein derivatives from Mycobacterium bovis and M. avium is the standard for diagnosing bovine tuberculosis. However, improved tests based on defined, specific antigens are urgently needed. In the present study, a combination of bioinformatics, molecular biology, and bovine models of infection were used to screen mycobacterial proteins for their potential as diagnostic reagents which could be used in a whole-blood assay for diagnosis of tuberculosis. Initial screening of 28 proteins selected in silico and expressed as recombinants in Escherichia coli indicated that CFP-10, ESAT-6, TB27.4, TB16.2, TB15.8, and TB10.4 induced strong gamma interferon responses in experimentally infected cattle. A more thorough investigation over time in two groups of animals infected with a high (10(6) CFU) and a low (10(4) CFU) dose of M. bovis revealed that, for both groups, the strength of the in vitro response to individual antigens varied greatly over time. However, combining the results for ESAT-6, CFP-10, and TB27.4, possibly supplemented with TB10.4, gave sensitivities at different infection stages close to those obtained with M. bovis purified protein derivative. Importantly, while responsiveness to ESAT-6 and CFP-10 correlated strongly for individual samples, the same was not the case for ESAT-6 and TB27.4 responsiveness. The results suggest that combinations of specific antigens such as these have great potential in development of optimized diagnostic systems for bovine tuberculosis.

Animals↗

A logistic regression analysis of multiple noninvasive tests for the prediction of the presence and extent of coronary artery disease in men.

The incremental diagnostic yield of clinical data, exercise ECG, stress thallium scintigraphy, and cardiac fluoroscopy to predict coronary and multivessel disease was assessed in 171 symptomatic men by means of multiple logistic regression analyses. When clinical variables alone were analyzed, chest pain type and age were predictive of coronary disease, whereas chest pain type, age, a family history of premature coronary disease before age 55 years, and abnormal ST-T wave changes on the rest ECG were predictive of multivessel disease. The percentage of patients correctly classified by cardiac fluoroscopy (presence or absence of coronary artery calcification), exercise ECG, and thallium scintigraphy was 9%, 25%, and 50%, respectively, greater than for clinical variables, when the presence or absence of coronary disease was the outcome, and 13%, 25%, and 29%, respectively, when multivessel disease was studied; 5% of patients were misclassified. When the 37 clinical and noninvasive test variables were analyzed jointly, the most significant variable predictive of coronary disease was an abnormal thallium scan and for multivessel disease, the amount of exercise performed. The data from this study provide a quantitative model and confirm previous reports that optimal diagnostic efficacy is obtained when noninvasive tests are ordered sequentially. In symptomatic men, cardiac fluoroscopy is a relatively ineffective test when compared to exercise ECG and thallium scintigraphy.

Adult↗

Diagnostic value of cytology of voided urine.

Cytologic examination of the sediment of voided urine is the only noninvasive method of detection, diagnosis and follow-up of tumors of the bladder and other anatomic components of the lower urinary tract. In order to assess the value of cytology of voided urine, we analyzed the diagnostic yield in 203 episodes, each composed of three sediments of voided urine obtained on consecutive days. For each one of these episodes, histologic material was available and was reviewed. Of special interest were 181 instances of primary or recurrent bladder tumors; in 37 of these patients, random biopsies of the bladder were also available for review. The concept of intraurothelial neoplasia (IUN), graded I, II or III, was introduced to describe degrees of atypia in flat urothelium, with IUN grade III corresponding to nonpapillary carcinoma in situ. The results documented that cytology of voided urine is highly reliable in the diagnosis of high-grade tumors, with a sensitivity of 94.2%. In primary flat carcinoma in situ (IUN III), the sensitivity was 100%. The method failed in the recognition of grade I papillary tumors and in about one-third of grade II tumors. There were no false-positive results in this study. In the 151 positive cases, the cytologic diagnosis was established on the first specimen in 79%, on the second specimen in an additional 14% and on the third specimen in 7% of cases. These results justify the use of three consecutive daily urine specimens for optimal diagnostic results. There is a remarkable similarity between the presence of cancer cells in voided urine and the DNA ploidy of bladder tumors, as established by Tribukait. The observations reported herein suggest that positive urine cytologies may correspond to aneuploid tumors and hence be not only of diagnostic but also of prognostic value. A direct proof of this hypothesis is under investigation; the results of this study justify the need for a field trial of an automated image analysis diagnostic system that was developed in this department.

Carcinoma↗

Change in anatomic distribution and incidence of colorectal carcinoma over a period of 15 years: clinical considerations.

PURPOSE: Colorectal cancer is the second most common cancer in the Netherlands. Its incidence rates are among the highest in Europe. In the past decades, a right-sided shift of the subsite location of colorectal cancer has been reported. These changes in anatomic distribution might have clinical implications for the use of diagnostic or screening tools for colorectal cancer. This study was designed to investigate the change in incidence and anatomic distribution of colorectal cancer in a population over a period of 15 years. METHODS: The incidence of colorectal cancer in an eastern part of the Netherlands (700,000 inhabitants) was determined for two years, 1981 and 1996. From the regional laboratory of pathology, data including age, gender, subsite location, and Dukes classification were collected. The subsite location of colorectal cancer was divided into two groups: proximal and distal (the latter being within sigmoidoscopy reach). RESULTS: No differences in age and gender distribution were found. In 1981, the diagnosis of colorectal cancer was made in 232 patients in this region, and in 1996, it was made in 410 patients. The population remained almost stable during this time. Therefore, the incidence rose from 33 to 55 per 100,000 inhabitants from 1981 to 1996, respectively. In 1981, 25 percent of the carcinomas were proximal (to the sigmoid colon); this increased to 37 percent in 1996 ( P< 0.05). CONCLUSIONS: The incidence of colorectal cancer has almost doubled from 1981 to 1996 in this Dutch region. The proportion of proximal colorectal cancer has increased from 25 to 37 percent. These findings add to the notion that sigmoidoscopy is not the optimal diagnostic or screening tool for colorectal cancer.

Aged↗

[Diagnosis of middle cerebral artery spasm by determination of flow velocity and the Lindegaard index with transcranial color Doppler sonography].

BACKGROUND AND PURPOSE: Recent reports have demonstrated the high utility of transcranial color-coded duplex sonography (TCCS) in the diagnosis of advanced spasm of the middle cerebral artery, whereas its accuracy in the diagnosis of mild vasospasm is reported to be lower. Relation of blood flow velocity in the middle cerebral artery (MCA) to that in the extracranial internal carotid artery (VMCA/VICA index) is recommended as being helpful in the diagnosis of vasospasm (the so called Lindegaard Index). Nevertheless, the exact diagnostic value of this index using the TCCS method remains to be established. The purpose of this study is to estimate the accuracy of TCCS in the diagnosis of MCA vasospasm, as based on the VMCA/VICA index. MATERIAL AND METHODS: The VMCA/VICA index was calculated in 195 patients (285 middle cerebral arteries) who were scheduled for cerebral arteriography. The TCCS study and color-coded duplex sonography of the internal carotid arteries were performed immediately before arteriography. RESULTS: A mild grade of MCA spasm was diagnosed angiographically in 21, and moderate-to-severe spasm in 29 MCAs out of 285 successfully insonated arteries. Peak-systolic, mean and end-diastolic blood velocities were measured using transcranial color sonography in the MCA and related to the respective velocities in the ipsilateral extracranial internal carotid artery. Receiver-operating characteristic curves (ROC) were calculated for particular velocities and for the related VMCA/VICA indices. By comparison of the areas under the ROC curves it was shown that the use of the VMCA/VICA index does not improve the accuracy of TCCS in the diagnosis of advanced MCA spasm, whereas it improves accuracy in the diagnosis of mild vasospasm. In particular, accuracy can be improved by the use of the VMCA/VICA index based on the end-diastolic velocity. The optimal diagnostic threshold of the VMCA/VICA index was determined at 3.9. CONCLUSIONS: The use of VMCA/VICA index improves the accuracy of TCCS in the diagnosis of mild vasospasm of the middle cerebral artery.

Adult↗

Diagnostic evaluation of grass- and birch-allergic patients with oral allergy syndrome.

BACKGROUND: Patients with birch and grass allergy often suffer from oral allergy symptoms when ingesting cross-reacting fresh fruits and vegetables. However, fruit and vegetable allergen extracts are often readily degradable or contain clinically irrelevant cross-reacting epitopes, resulting in diagnostic discrepancies when fruit and vegetable allergic reactions are evaluated. The risk of using nonstandardized fresh food extracts for skin testing may also be of concern. The objective was to compare and evaluate the clinical utility of selected recombinant grass and birch cross-reacting food allergens with fresh and commercial melon, hazelnut, and apple extracts. METHODS: Thirty-six grass- and or birch-allergic patients and 17 control subjects consented to participate in the study. All subjects were skin prick tested and had basophil histamine-release tests done with fresh fruits and various extracts of hazelnut, apple, and melon. The diagnosis of oral allergy syndrome was confirmed by oral challenges. In addition, histamine release to recombinant Bet v 1 and Bet v 2, and recombinant Phl p 1 and Phl p 2, Phl p 5 was performed. RESULTS: The skin prick test with fresh hazelnut, apple, and melon showed sensitivities of 0.97, 0.92, and 0.89, respectively. The corresponding specificities were 0.78, 0.72, and 0.82, respectively. In contrast, the histamine-release test with hazelnut, apple, and melon gave sensitivities of 0.87, 0.71, and 1.00, respectively. The corresponding specificities were 0.65, 0.93, and 0.43. The skin prick test showed excellent negative predictive value (> 90%). No added value of recombinant allergen testing was noted. Oral challenge did not result in severe systemic reactions, and no systemic reactions were observed with skin prick tests with fresh fruits. CONCLUSION: The skin prick test showed an almost optimal diagnostic value with a satisfactory sensitivity (> 89%) and excellent negative predictive value with fresh fruits. When the skin prick test with fresh nut and apple cannot be performed, histamine release is a diagnostic alternative. Histamine release with melon showed lack of specificity. This was probably due to extensive IgE cross-reactivity with pollen, since these patients also responded to recombinant Phl p 1 and Bet v 1. Skin testing and challenges with fresh fruits were safe.

Adult↗

A comparative analysis of FISH, RT-PCR, and cytogenetics for the diagnosis of bcr-abl-positive leukemias.

Philadelphia (Ph) chromosome-positive leukemias, with the bcr-abl gene translocation, have a dismal prognosis. The identification of Ph-positive patients is vitally important because only aggressive therapeutic approaches, such as allogeneic bone marrow transplantation, may result in long-term disease-free survival. Routine diagnostic methods, such as Southern blot analysis and cytogenetics, may lead to false-negative results. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis is considered the most sensitive tool for the detection of the bcr-abl translocation, and it is widely used alone or in combination with karyotyping or Southern blot analysis to identify Ph-positive cases. In this study, we used fluorescence in situ hybridization (FISH) with BCR and ABL double-color probes for detecting Ph-positive leukemias. The FISH results were compared with the results of cytogenetic and RT-PCR analyses in 75 patients with leukemia or other myeloproliferative syndromes (chronic myeloid leukemia, 30; acute lymphoblastic leukemia, 24; acute myelogenous leukemia, 6; essential (hemorrhagic) thrombocythemia, 12; chronic myelomonocytic leukemia, 2; and polycythemia vera, 1). FISH analysis proved to be simple, extremely reliable and sensitive; bcr-abl fusion detection was successful in the presence of all types of molecular junctions i.e., (b2a2, b3a2, and e1a2). Furthermore, a Ph-positive case that proved fusion negative by RT-PCR was identified as positive by FISH. The sensitivity of RT-PCR and FISH related to Ph-positive cases were 97% and 100%, respectively. Regarding specificity, in 4 (5%) of 75 patients, RT-PCR provided false-positive results. Cross-contamination was identified because a new specimen was harvested and reanalyzed when FISH, cytogenetics, and RT-PCR results were contradictory. We believe FISH is an optimal diagnostic method to detect bcr-abl translocation that can be used alone or to validate the results of RT-PCR analysis.

Bone Marrow↗

Evaluation and management of the man who has failed primary curative therapy for prostate cancer.

The recurrence of prostate cancer after potentially curative local therapy is becoming a significant urologic problem. There are few prospective randomized trials, and the optimal diagnostic and treatment strategies for men who fail potentially curative therapy are not known. The experience to date seems to suggest the following as a reasonable approach. A detectable serum PSA level (> or = 0.4 ng/mL) after radical prostatectomy is evidence of residual or recurrent prostate cancer. Men with low- or moderate-grade cancers (Gleason score < 7), with capsular penetration, or with positive surgical margins in whom disease recurs more than 2 years after radical prostatectomy with a PSA doubling time greater than 12 months seem likely to harbor a local recurrence and are the only good candidates for salvage therapy. Unless there is a palpable recurrence, transrectal ultrasound and biopsy are generally not recommended, and CT scanning and bone scintigraphy usually do not provide helpful information. The role of monoclonal antibody scanning is currently investigational. Men with high-grade tumors (Gleason score > or = 7) or with seminal vesicle or lymph node involvement in whom disease recurs within 2 years of radical prostatectomy are most appropriately observed or treated with early hormonal therapy. Men who do not achieve a PSA nadir of 0.5 ng/mL or less within 2 years of radiotherapy are very likely to harbor residual disease. For young healthy men who are willing to accept a substantial risk of impotency, urinary incontinence, and bladder neck contractures, salvage radical prostatectomy is a reasonable option if the preradiation tumor characteristics are acceptable (PSA < 10 ng/mL, Gleason score < or = 6) and if the current PSA is less than 10 ng/mL. Salvage cryotherapy may result in substantial morbidity and should only be offered on an investigational basis. Other men failing radiation may be observed or treated with hormonal therapy. There is seldom a role for repeat biopsy. Because the optimal time to begin hormone therapy is still not known, early or delayed treatment are both reasonable options. Testicular androgen ablation by orchiectomy or LHRH agonists is considered standard therapy. Combined therapy with an antiandrogen does not seem to be beneficial for all patients and should not be routinely used. Sexually active men in whom preservation of potency is important can be offered an investigational regimen such as a 5-alpha-reductase inhibitor combined with an oral antiandrogen or intermittent LHRH agonist therapy. It is hoped that the results of ongoing randomized trials and future research will establish efficient and effective practice guidelines to evaluate and treat men who have failed potentially curative therapy for localized prostate cancer. This remains a very important and controversial topic that will challenge many practicing urologists.

Cryotherapy↗