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PubMed1995

Diagnosis of acute intermittent porphyria in northern Sweden: an evaluation of mutation analysis and biochemical methods.

OBJECTIVE: To validate the use of a recently observed guanine to adenine mutation in exon 10 in the porphobilinogen deaminase (PBGD) gene as a diagnostic marker of acute intermittent porphyria (AIP). To evaluate the efficiency of the traditional biochemical diagnostic methods. DESIGN: Matched and blinded case-control study (1:4). SETTING: A primary health care centre in Arjeplog, the National Porphyria Research Unit and a department of clinical genetics in Stockholm. SUBJECTS: A total of 48/49 (98%) patients over the age of 15 years living in Arjeplog with AIP, diagnosed according to standard clinical and biochemical criteria. For each AIP patient, four controls were matched for age, sex and geographical area and 164/196 (86%) participated. In the validity study, 35 patients were selected as indisputable AIP gene carriers, according to strict biochemical criteria, and 92 matched controls were selected with strict exclusion criteria. MAIN OUTCOME MEASURES: Validity, specificity and sensitivity of DNA diagnosis for this AIP mutation. Specificity and sensitivity of traditional biochemical methods. RESULTS: Validity study: the mutation was found in all 35 individuals classified as carriers of AIP. None of the 92 controls had the mutation. Evaluation study: all 48 AIP gene carriers, diagnosed by traditional methods, had the mutation, as had one of the control persons. In an inconclusive group of five persons with heredity for AIP, two had a positive DNA test. CONCLUSIONS: The PBGD mutation analysis was found to have full specificity and sensitivity and can be used as the sole diagnostic method in the family complex studied, representing the major AIP mutation in Sweden. The traditional diagnostic methods, used in optimal combinations, work in most cases, but they do not show high precision. However, they must be used when the specific mutation in the PBGD gene is not known.

Adolescent↗

PubMed1997

Improved Assessment of Pathological Regurgitation in Patients with Prosthetic Heart Valves by Multiplane Transesophageal Echocardiography.

The aim of this study was to evaluate the diagnostic increment of individually optimized axes in the assessment of pathological prosthetic valve regurgitation. Forty-two patients with pathologically regurgitant prostheses in the aortic (n = 21), mitral (n = 15), and tricuspid (n = 6) positions were examined by multiplane transesophageal echocardiography. The investigation was performed utilizing the transverse axis first, the longitudinal axis second, and the intermediate axes afterwards. The presence of regurgitation, the differentiation between trans- and perivalvular origin, and the localization of perivalvular leakages at the sewing ring were evaluated. Findings in the biplane and intermediate axes were compared to surgery or autopsy in all patients. There was slightly higher detection rate for aortic prosthetic regurgitation using the intermediate axes than the biplane axes. The intermediate axes revealed significantly fewer differences to the morphological control than the biplane axes with regard to the differentiation of peri- and transprosthetic aortic regurgitation and to the localization of a periprosthetic aortic regurgitant origin. The intermediate axes provided significantly better agreement to surgery/autopsy than the biplane axes regarding the localization of the origin of mitral periprosthetic regurgitation. Morphological visualization of the perivalvular gap adds important information on the precise localization of the regurgitant origin. The pathological gap was visualized significantly more often using the intermediate than the biplane axes in all types of prostheses. The data in this study therefore suggest that multiplane transesophageal echocardiography is superior to biplane transesophageal echocardiography in the assessment of pathologic prosthetic regurgitation.

Journal Article↗

PubMedDate not supplied

Parametrized x-ray absorption in diagnostic radiology from Monte Carlo calculations: implications for x-ray detector design.

The integral dose to the patient and image signal to noise ratio (SNR) are inexorably coupled in x-ray-based diagnostic imaging. Advancements and optimal design of imaging devices need to consider the SNR as well as patient dose. The figure of merit, FOM = (SNR)2/(integral dose), is a useful parameter in optimizing detector designs because it is independent of input exposure, and therefore eliminates exposure as a design consideration. Although numerical calculation of the SNR is relatively straightforward in most cases, the integral dose calculation is made complex due to its scatter component's high dependency on both x-ray energy and patient thickness. Monte Carlo calculations over a range of monoenergetic x-ray energies were used to calculate total energy absorption, and the results are parametrized using polynomial expressions. The results are shown to be applicable to any arbitrary polyenergetic spectrum. An example using the above FOM is given to illustrate the utility of the parametrized results. The parametrized results may prove useful in the computer simulations of x-ray detector systems where the above FOM is utilized.

Absorption↗

PubMed2004

Comparison of enzyme-linked immunosorbent assay, Western blotting, microagglutination, indirect immunofluorescence assay, and flow cytometry for serological diagnosis of tularemia.

The serodiagnostic efficiencies of five different approaches to detecting antibodies (immunoglobulins G, A, and M) developed in clinically proven infections with Francisella tularensis have been assessed. Fifty serum samples from patients suffering from tularemia during an outbreak in Sweden were compared with samples from 50 healthy blood donors (controls) by using an enzyme-linked immunosorbent assay (ELISA), microagglutination (MA), Western blotting (WB), an indirect immunofluorescence assay (IIFA), and flow cytometry (FC). ELISA, WB, and FC were based on the use of preparations of lipopolysaccharides (LPS) of the live vaccine strain of Francisella tularensis subsp. holarctica (ATCC 29684) as a capture antigen. Whole methanol-fixed bacteria were used for IIFA and MA. Optimized protocols yielded a diagnostic sensitivity and specificity of 100% for WB, MA, and FC, 98% for ELISA, and 93% for IIFA. A total of 6,632 serum samples from individuals between the ages of 18 and 79 years, representatively recruited from all regions of Germany, were screened to estimate and confirm the positive predictive value (PVpos) of the ELISA. Serum samples from 15 (0.226%) individuals tested positive for F. tularensis-specific antibodies by ELISA and confirmatory WB. The resulting prevalence-dependent PVpos of 10.2% and specificity of 98.1% were consistent with our findings for tularemia patients and controls. We conclude that the combined usage of a screening ELISA and a confirmatory WB based on LPS as a common antigen, as well as the MA, is a suitable serodiagnostic tool, while the quality of the IIFA is hampered by subjective variations of the results. FC is a promising new approach that might be improved further in terms of multiplex analyses or high-throughput applications.

Adolescent↗

PubMed2002

Optimization and evaluation of a PCR assay for detecting toxoplasmic encephalitis in patients with AIDS.

Toxoplasma gondii is a common life-threatening opportunistic infection. We used experimental murine T. gondii infection to optimize the PCR for diagnostic use, define its sensitivity, and characterize the time course and tissue distribution of experimental toxoplasmosis. PCR conditions were adjusted until the assay reliably detected quantities of DNA derived from less than a single parasite. Forty-two mice were inoculated intraperitoneally with T. gondii tachyzoites and sacrificed from 6 to 72 h later. Examination of tissues with PCR and histology revealed progression of infection from blood to lung, heart, liver, and brain, with PCR consistently detecting parasites earlier than microscopy and with no false-positive results. We then evaluated the diagnostic value of this PCR assay in human patients. We studied cerebrospinal fluid and serum samples from 12 patients with AIDS and confirmed toxoplasmic encephalitis (defined as positive mouse inoculation and/or all of the Centers for Disease Control clinical diagnostic criteria), 12 human immunodeficiency virus-infected patients with suspected cerebral toxoplasmosis who had neither CDC diagnostic criteria nor positive mouse inoculation, 26 human immunodeficiency virus-infected patients with other opportunistic infections and no signs of cerebral toxoplasmosis, and 18 immunocompetent patients with neurocysticercosis. Eleven of the 12 patients with confirmed toxoplasmosis had positive PCR results in either blood or cerebrospinal fluid samples (6 of 9 blood samples and 8 of 12 cerebrospinal fluid samples). All samples from control patients were negative. This study demonstrates the high sensitivity, specificity, and clinical utility of PCR in the diagnosis of toxoplasmic encephalitis in a resource-poor setting.

AIDS-Related Opportunistic Infections↗

PubMed2004

Development, implementation, and impact of acceptability criteria for serologic tests for infectious diseases.

Serologic testing is essential for the diagnosis of some infectious diseases and yet is fraught with potential pitfalls. All parts of the diagnostic process must be optimized to ensure that serologic tests perform adequately. Recognizing that a lack of clinical data and correctly timed, paired sera frequently led to uninterpretable serology results at our laboratory, we developed and implemented simple acceptability criteria for serologic tests. We assessed the impact of these criteria by comparing submissions and results for the year before and the year after implementation of the criteria. The number of serologic tests performed declined by 25% after implementation of the acceptability criteria, despite an increase in requests for serologic tests. Inappropriate testing of acute-phase sera alone fell from 49 to 0% (P < 0.001) for the tests monitored. Appropriate submission of paired sera rose from 9 to 19% (P = 0.006). The proportion of results classified as interpretable rose from 52 to 100% (P < 0.001). We recommend that acceptability criteria be developed and applied to samples submitted to clinical microbiology laboratories for serologic testing.

Bacterial Infections↗

PubMed1995

Microbiological investigation of polyarthralgia.

Results of serological investigations on patients with joint pain, arthralgia or polyarthritis were analysed and this information was used to develop a diagnostic algorithm to ensure optimal utilisation of laboratory resources. Accordingly, all cases are now examined for parvovirus IgM, mycoplasma IgM and streptococcal antibodies. Further tests are undertaken by following the algorithm after obtaining supplementary information from a questionnaire. This approach is put forward as a preliminary standard which other laboratories may like to evaluate and develop according to local requirements.

Algorithms↗

PubMedDate not supplied

Solitary pulmonary nodules: Part II. Evaluation of the indeterminate nodule.

Various strategies may be used to evaluate indeterminate solitary pulmonary nodules. Growth rate assessment is an important and cost-effective step in the evaluation of these nodules. Clinical features (eg, patient age, history of prior malignancy, presenting symptoms, smoking history) can be useful in suggesting the diagnosis and aiding in management planning. Bayesian analysis allows more precise determination of the probability of malignancy (pCa). Decision analysis models suggest that the most cost-effective management strategy depends on the pCa for a given nodule. At contrast material-enhanced computed tomography, nodular enhancement of less than 15 HU is strongly predictive of a benign lesion, whereas enhancement of more than 20 HU typically indicates malignancy. At 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography, lesions with low FDG uptake are typically benign, whereas those with increased FDG uptake are typically malignant. Results of transthoracic needle aspiration biopsy influence management in approximately 50% of cases and, in indeterminate lesions with a pCa between 0.05 and 0.6, is the best initial diagnostic procedure. It is optimally used in peripheral nodules and has been reported to establish a benign diagnosis in up to 91% of cases. Although there is no one correct management approach, the ability to distinguish benign from malignant solitary pulmonary lesions has improved with the use of these strategies.

Bayes Theorem↗

PubMed2000

Urinary N-acetyl-beta-D-glucosaminidase and neopterin aid in the diagnosis of rejection and acute tubular necrosis in initially nonfunctioning kidney grafts.

AIM: The study aimed at investigating urinary neopterin, a marker of cellular immune response, and urinary N-acetyl-beta-D-glucosaminidase (NAG), a marker of tubular damage, as noninvasive means to differentiate between acute tubular necrosis (ATN) and rejection in initially nonfunctioning (INF) human renal transplants. METHODS: Seventy-two renal transplant patients were studied. Forty-five of them experienced an uncomplicated early posttransplant course, 27 patients suffered from INF. Twenty-two patients experienced ATN, 5 patients had a total of six biopsy-proven rejections. The NAG activity was measured by a colorimetric assay, neopterin by high-performance liquid chromatography. Receiver operating characteristics (ROC) analysis was applied to compute diagnostic performance and an optimal discriminating threshold. RESULTS: Demographic characteristics (age, gender, cold and warm ischemia periods, HLA mismatches) and posttransplant urinary NAG and neopterin excretions did not differ between ATN and rejection groups. Both urinary NAG and neopterin excretions were lower in the control group (NAG 1.8 +/- 1.0 U/mmol urinary creatinine; neopterin 270 +/- 126 nmol/mmol urinary creatinine; mean +/- SD) as compared with the ATN group (NAG 12 +/- 10 U/mmol, p < 0.001 vs. control group; neopterin 303 +/- 195 nmol/mmol, n.s.) and the rejection group (NAG 7 +/- 8 U/mmol, p < 0. 01; neopterin 508 +/- 419 nmol/mmol, p < 0.01). The ratio of urinary neopterin to NAG excretion (uNNR; dimension nmol neopterin/U NAG activity) increased during rejections as compared with ATN (139 +/- 74 vs. 50 +/- 38 nmol/U, p < 0.01). The area under the ROC curve for uNNR was 0.88 +/- 0.07 (p < 0.001). Applying a ROC-estimated optimal discriminator of uNNR (80 nmol/U), 16 patients with ATN and all six rejection episodes were classified correctly. CONCLUSION: The uNNR provides a noninvasive means to aid in the differential diagnosis of rejection and ATN in INF human renal transplants.

Acetylglucosaminidase↗

PubMed1997

In vitro identification of angioplasty-induced injury by use of vascular acoustic emissions.

BACKGROUND: We have developed a novel method of diagnosing stress-induced vascular injury. This approach uses the sound energy released from atherosclerotic arterial tissue during in vitro balloon angioplasty to characterize type and severity of induced trauma. METHODS AND RESULTS: Thirty-two postmortem human peripheral arterial specimens 1.0 cm long were subjected to in vitro balloon angioplasty with simultaneous acoustic emission monitoring. Specimens were examined before and after angioplasty to ascertain the extent of angioplasty-induced injury. Gross observation was used to identify dissection. A three-dimensional intravascular ultrasound reconstruction technique was used to estimate the luminal surface area of the specimen. Change in luminal surface area (postangioplasty minus preangioplasty) was used to quantify induced injury. The energy content and spectral distribution of the digitally acquired vascular acoustic emission (VAE) signals were computed. Comparisons of angioplasty-induced trauma with VAE signal characteristics were made. Dissection (mural laceration of variable depth) was observed in 15 of 32 specimens. Eleven showed no evidence of induced dissection, and 6 had preexisting intimal disruptions. The energy content of the VAE signals collected from specimens with dissection was greater than that obtained from those in which dissection was absent: 845 +/- 89.4 mJ (mean +/- SEM; n = 15) versus 128 +/- 40.8 mJ (n = 1 l; P < .001). Comparison of induced trauma and VAE signal energy demonstrated a proportional relationship (r = .87, P < .001, n = 32). CONCLUSIONS: VAE signals contain information characterizing type and severity of angioplasty-induced arterial injury. Because vascular injury is related to adverse procedural outcome, development of VAE technology as an adjunct to conventional diagnostic modalities may facilitate optimal balloon angioplasty delivery and postprocedural care.

Analysis of Variance↗

PubMed2005

Utility of prostate-specific antigen kinetics in addition to clinical factors in the selection of patients for salvage local therapy.

A detectable and rising prostate-specific antigen (PSA) level after radical prostatectomy or a rising PSA above the nadir value after radiation therapy may represent a local failure, distant failure, or both. Determining the site or sites of failure is critical for selecting the appropriate salvage therapy. Nevertheless, although PSA failure precedes clinically evident failure by several years, determining the source of the biochemical failure is often not possible using currently available diagnostic studies. Selecting the optimal therapeutic approach may be guided by the initial clinical factors (eg, T-category, PSA, biopsy Gleason score). If the patient has had a radical prostatectomy, then the pathologic outcomes of the surgery (eg, pathologic T-category and prostatectomy Gleason score, nodal and margin status) may provide further information. Beyond pretreatment clinical and post-treatment pathologic factors, PSA kinetics, and specifically a pretreatment PSA velocity > 2 ng/mL/year, an interval to PSA failure < 3 years and a post-treatment PSA doubling time < 3 months place a man at increased risk for metastases and subsequent prostate cancer-specific mortality, making these men poor candidates for local-only salvage therapy. Therefore, the optimal candidate for local-only salvage therapy is a man whose pretreatment PSA velocity was 2 ng/mL/year or less, interval to PSA failure exceeds 3 years, and post-treatment PSA doubling time is at least 12 months, and who did not have biopsy or prostatectomy Gleason score of 8 to 10 or seminal vesicle or lymph node involvement.

Biomarkers, Tumor↗

PubMed2003

Pheochromocytoma: state-of-the-art and future prospects.

This review provides current understanding of the pathophysiology of pheochromocytoma and the wide range of associated clinical manifestations that have led to earlier recognition of the disease. In addition, it reviews optimal screening methods and localization techniques that have enhanced the clinician's ability to make the diagnosis with greater certainty. This article will also discuss alternative antihypertensive regimens and innovative anesthetic and surgical procedures that have made successful management more promising than ever before. Areas requiring further development include additional clinical experience with the measurement of plasma metanephrines that have been shown to have high sensitivity and specificity in the diagnosis of sporadic and familial pheochromocytoma, optimizing cost effectiveness of diagnostic imaging, improving the ability to predict and treat malignant pheochromocytoma, and elucidating not only the surgical approach but, perhaps with rapid advances in molecular genetics, ways of preventing familial pheochromocytoma.

Adrenal Gland Neoplasms↗

PubMed1985

Single versus repeated dose human chorionic gonadotropin stimulation in the differential diagnosis of hypogonadotropic hypogonadism.

The responses of serum testosterone (T), 17 alpha-hydroxyprogesterone, and 17 beta-estradiol (E2) to four im injections of hCG (5000 IU/1.7 m2) given on days 0, 4, 7, and 10 were studied in 10 prepubertal and 10 pubertal boys with hypogonadotropic hypogonadism (groups O and P, respectively). Serum was obtained before each injection and on day 14. The results were compared with those of controls, 16 prepubertal boys with incomplete testicular descent and 6 pubertal boys with constitutional delay of puberty. Serum T levels increased significantly in groups O and P to 2.0 and 4.6 nmol/liter, respectively, after the first injection, then progressively to 5.8 and 11.2 nmol/liter. Basal T levels of group O did not differ from those of the controls, but were subnormal for group P (P less than 0.001). Stimulated T levels were subnormal in both groups (P less than 0.01 and P less than 0.001), but repeated doses increased the difference from the control value only in group P. A difference in E2 response between patients and controls appeared in puberty; only the pubertal control boys had substantial increases in E2 (P less than 0.001). Our results show that the optimal protocol for a diagnostic hCG test in prepubertal boys is a single dose of hCG, with determination of T levels 4 days later. In puberty, if the basal T levels are inconclusive, repeated doses of hCG should be given with determination of both T and E2. These findings also suggest that the full inhibitory effect of E2 on T synthesis results from a pubertal maturation process, possibly induced by endogenous gonadotropins, which cannot be induced by two weeks of hCG stimulation in prepubertal boys or those with hypogonadotropic hypogonadism.

17-alpha-Hydroxyprogesterone↗

PubMed2001

Advances in intravenous thrombolytic therapy for treatment of acute stroke.

Intravenous tissue plasminogen activator (tPA) is an effective therapy for treatment of acute ischemic stroke when administered within 3 hours of symptom onset. Three large randomized clinical trials that have attempted to extend the time window for tPA treatment beyond 3 hours have failed to demonstrate convincing evidence of efficacy. A recently published prospective, monitored, multicenter study of 389 patients, who were treated with tPA for ischemic stroke at 57 medical centers (24 academic, 33 community) across the United States, demonstrated favorable outcomes and low rates of symptomatic intracerebral hemorrhage. Recent advances in neuroimaging, including diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI), have the potential to differentiate salvageable ischemic brain tissue from irreversibly injured tissue. Preliminary data suggest that acute stroke patients who present with a PWI lesion that is considerably larger than the initial DWI lesion may be good candidates for intravenous thrombolysis, even beyond 3 hours after symptom onset. Additional research is required to clarify the optimal use of these diagnostic techniques and their cost-effectiveness.

Acute Disease↗

PubMed1985

Intramuscular hemangioma of the head and neck.

Intramuscular hemangiomas are unusual tumors in the head and neck region that occur most frequently in the masseter muscle and are often confused with parotid neoplasms. Four cases are described and the literature reviewed. The diagnosis and management of these tumors are discussed in view of the fact that accurate preoperative diagnosis is unusual and tumor recurrence rates high. Increased awareness of the clinical presentation of intramuscular hemangiomas should enhance diagnostic accuracy and facilitate optimal treatment planning.

Adult↗

PubMed2000

Pneumonia in the elderly.

Pneumonia is a frequent cause of mortality and morbidity in the elderly. This article discusses pneumonia in the elderly based on causative organisms and sites where the pneumonia was acquired. Community-acquired pneumonia, nursing home-acquired pneumonia and nosocomial pneumonia in the elderly are reviewed from a diagnostic and therapeutic perspective. Optimal antimicrobial therapy is based on knowledge of the pulmonary pathogens associated with community-acquired, nursing home-acquired and nosocomial pneumonias. Antibiotic dosing should take into account the functional action of the liver and kidneys in individuals of advanced age.

Journal Article↗

PubMed2006

Detection of HER2 gene amplification by fluorescence in situ hybridization in breast cancer.

Fluorescence in situ hybridization (FISH) is increasingly recognized as the most accurate and predictive test for both HER2 gene amplification or expression and response to Herceptin therapy in breast cancer. Diagnostic procedures for FISH require rigorous quality control, as with all diagnostic procedures, which rely on standardized methodologies. We describe the use of FISH for HER2 in our own laboratory, based on more than 4000 diagnostic assays, and the optimal approaches to scoring HER2 gene amplification in breast cancer.

Breast Neoplasms↗

PubMed1996

Detection of bleeding in patients with major pelvic fractures: value of contrast-enhanced CT.

OBJECTIVE: We performed a retrospective review of trauma patients who had undergone both pelvic angiography and preangiographic i.v. contrast-enhanced CT to determine whether CT can accurately demonstrate the presence or absence of pelvic bleeding in patients with multisystem trauma and major pelvic fractures. SUBJECTS AND METHODS: We reviewed the medical records and imaging studies of all patients, identified through a trauma radiology database, who had undergone pelvic angiography and preangiographic contrast-enhanced CT during a 48-month period. Results of CT scans were recorded by consensus interpretation of three radiologists without knowledge of angiographic findings. Sites of contrast material extravasation seen on CT scans were noted and compared with sites of bleeding or vascular injury identified by selective pelvic angiography. RESULTS: Thirty patients with blunt trauma and pelvic fractures underwent both pelvic angiography and preangiographic CT studies. Findings on pelvic angiograms were positive at 26 sites in 19 patients and included contrast agent extravasation at 23 sites and vessel abnormalities without extravasation at three sites. Preangiographic pelvic CT scans showed contrast agent extravasation at 20 sites in 16 patients. Three patients had no contrast agent extravasation demonstrated by CT but had bleeding demonstrated by angiography. CT detected bleeding in 16 of 19 patients who had extravasation or vascular injury demonstrated by angiography, for a sensitivity of 84%. Results of pelvic angiography were negative in 11 patients, and none had evidence of bleeding on preangiographic CT scans. Two sites of contrast agent extravasation identified in two patients by CT did not show bleeding at angiography, for a specificity of 85% for the detection of bleeding. The overall accuracy of CT for determining the presence or absence of bleeding was 90%. CONCLUSION: Knowledge of sites of ongoing hemorrhage is crucial for optimizing the sequence of diagnostic and therapeutic studies in patients with blunt trauma. Contrast-enhanced CT of the pelvis, which is often performed for hemodynamically stable trauma patients, is a noninvasive technique that is highly accurate in determining the presence or absence of ongoing pelvic hemorrhage. This information can assist in initial management decisions involving patients with multisystem trauma and major pelvic fractures.

Adolescent↗