Primary Means Of Diagnosis Research Articles

Quantitative multiplexed strategies for human Lyme disease serological testing.

Lyme disease, which is primarily caused by infection with the bacterium Borrelia burgdorferi in the United States or other Borrelia species internationally, presents an ongoing challenge for diagnostics. Serological testing is the primary means of diagnosis but testing approaches differ widely, with varying degrees of sensitivity and specificity. Moreover, there is currently no reliable test to determine disease resolution following treatment. A distinct challenge in Lyme disease diagnostics is the variable patterns of human immune response to a plurality of antigens presented by Borrelia spp. during the infection. Thus, multiplexed testing approaches that capture these patterns and detect serological response against multiple antigens may be the key to prompt, accurate Lyme disease diagnosis. In this review, current state-of-the-art multiplexed diagnostic approaches are presented and compared with respect to their diagnostic accuracy and their potential for monitoring response to treatment.

Neoplastic embolization to systemic and pulmonary arteries

ObjectiveArterial neoplastic emboli are uncommon, accounting for <1% of thromboemboli in the current literature. Nonetheless, this event may be associated with significant morbidity and mortality. Herein, we report a series of 11 cases of arterial neoplastic emboli from a single tertiary care center along with a comprehensive review of the literature to date. The aim of this study was to document the incidence, clinical presentations, and complications of arterial neoplastic emboli as well as to highlight the importance of routine histologic examination of thrombectomy specimens. MethodsPathology archives from a single tertiary care institution were queried to identify cases of surgically resected arterial emboli containing neoplasm (1998-2014). Histopathology was reviewed for confirmation of diagnosis. Patient demographics and oncologic history were abstracted from the medical record. Comprehensive literature review documented 332 patients in 275 reports (1930-2016). ResultsEleven patients (six men) with a median age of 63 years (interquartile range, 42-71 years) were identified through institutional archives. Embolism was the primary form of diagnosis in seven (64%) cases. Cardiac involvement (primary or metastasis) was present in more than half of the cohort. Comprehensive literature review revealed that pulmonary primaries were the most common anatomic origin of arterial neoplastic emboli, followed by gastrointestinal neoplasia. Cardiac involvement was present in 18% of patients, and sentinel identification of neoplasia occurred in 30% of cases. Postmortem evaluation was the primary means of diagnosis in 27%. ConclusionsThis study highlights the importance of routine histopathologic evaluation of embolectomy specimens in patients with and without documented neoplasia.

Clinical and genetic study of a family affected with spinocerebellar ataxia 3 and polycystic kidney disease

To investigate clinical features and genetic mutations of a family affected with spinocerebellar ataxia 3 and polycystic kidney disease. Polymerase chain reaction and DNA sequencing were employed to analyze exon 10 of the SCA3 gene, in addition with all exons and flanking sequences of PKD1 and PKD2 genes. The clinical features were also carefully analyzed. The numbers of CAG repeat in the proband's SCA3 gene were 28/76, with the number of repeats in the mutant allele being in the full range. The sequence of exon 23 of the PKD1 gene was also found to be abnormal. Clinical symptoms of the proband were very serious, which were characterized by obvious ataxia, pyramidal signs, Meige syndrome, depression and high blood pressure. Hereditary spinocerebellar ataxia 3 and autonomic dominant polycystic kidney disease may co-occur, and genetic testing is the primary means of diagnosis.

Colostrum replacer and bovine leukaemia virus sero-positivity

Bovine Leukemia Virus (BLV), a Deltaretrovirus in the Retroviridae family, is the causative agent of Enzootic Bovine Leucosis (EBL). Whilst EBL is still endemic in the Americas and Eastern Europe, most Western European countries are disease free in accordance with European Union legislation e.g. Great Britain has held EBL-free status since 1999. BLV infection is life-long and the presence of antibody and integrated proviral DNA are indicators of exposure to the virus.Screening for antibodies is the primary means of diagnosis. Here we present three case reports of animals which tested BLV antibody positive. As there was no evidence that the animals or their in-contacts were infected with BLV the result was somewhat confusing. Investigation revealed that the animals had been fed a colostrum replacer that was produced outside of Great Britain. As BLV is endemic in some countries, it was considered that BLV antibodies may have been present in the colostrum replacer and thus passively acquired resulting in BLV sero-positivity. The hypothesis was supported by the declining serological antibody titre seen on serial blood sampling. We present data on the serological and molecular testing conducted on the animals and product in support of the hypothesis. The above mentioned cases were all linked by the same brand of colostrum replacer; in addition we provide data derived from the investigation of colostrum replacers from other manufacturers. The policy and International Trade implications will also be discussed.

Ultrasound as the first choice for peripheral nerve imaging?

Advances in imaging have made dramatic differences in the diagnosis, understanding, and treatment of CNS disease, but peripheral nerve imaging remains uncommon. Electrodiagnostic tests, such as nerve conduction studies and EMG, are the primary means of diagnosis, providing functional but not structural information. Imaging has been limited by the small cross-sectional size of peripheral nerves (e.g., <10 mm2 for the normal median nerve), and their often-tortuous anatomical paths. Over the last decade, technological developments in high-resolution ultrasound (US) and MRI have helped to overcome these obstacles, but which method is superior?

The Bedside Evaluation: Ritual and Reason

The bedside evaluation, consisting of the history and physical examination, was once the primary means of diagnosis and clinical monitoring. The recent explosion of imaging and laboratory testing has inverted the diagnostic paradigm. Physicians often bypass the bedside evaluation for immediate testing and therefore encounter an image of the patient before seeing the patient in the flesh. In addition to risking delayed or missed diagnosis of readily recognizable disease, physicians who forgo or circumvent the bedside evaluation risk the loss of an important ritual that can enhance the physician-patient relationship. Patients expect that some form of bedside evaluation will take place when they visit a physician. When physicians complete this evaluation in an expert manner, it can have a salutary effect. If done poorly or not at all, in contrast, it can undermine the physician-patient relationship. Studies suggest that the context, locale, and quality of the bedside evaluation are associated with neurobiological changes in the patient. Recognizing the importance of the bedside evaluation as a healing ritual and a powerful diagnostic tool when paired with judicious use of technology could be a stimulus for the recovery of an ebbing skill set among physicians.

Syphilis in Children: Congenital and Acquired

Syphilis rates in women and congenital syphilis rates have declined steadily in the United States in recent years. However, syphilis remains a worldwide public health problem, with more than 12 million cases in adults and more than half a million pregnancies affected yearly. Prenatal screening and treatment programs are limited or nonexistent in many developing countries. The genome of Treponema pallidum, one of the smallest among prokaryotes, has been sequenced, but methods for continuous in vitro cultivation of the microbe remain elusive. There are no promising candidates for future vaccines at this time. Serologic testing, for both specific treponemal and nontreponemal antibodies, continues to be a primary means of diagnosis. Penicillin remains the drug of choice for congenital and acquired syphilis in childhood. The diagnosis of syphilis beyond early infancy raises concerns for possible child sexual abuse, although progression of congenital syphilis may account for some cases. Syphilis is a potentially eradicable disease, but this can be achieved only with sustained international will and cooperation to fund the necessary screening and treatment programs.

Trends in vascular ring surgery

We sought to review our experience with infants and children with anatomically complete vascular rings (ie, double aortic arch and right aortic arch with left ligamentum) and define perioperative trends in diagnostic imaging, operative techniques, and clinical outcomes. From 1946 through 2003, 209 patients (113 with double aortic arch and 96 with right aortic arch) underwent surgical repair. Mean and median ages at the time of the operation were as follows: double aortic arch, 1.4 +/- 2.4 years and 0.75 years, respectively; right aortic arch, 2.7 +/- 3.9 years and 0.9 years, respectively. Fourteen (14.6%) patients with right aortic arch had an associated Kommerell diverticulum. Cardiac diagnoses were present in 26 (12.4%) of 209 patients. There has been no operative mortality since 1959. In the past 30 years, mean hospital stay decreased from 8 to 3 days. Primary means of diagnosis has shifted from barium swallow and angiography to computed tomographic scanning or magnetic resonance imaging. In the past 10 years, 73% of patients had preoperative or intraoperative bronchoscopy. The technique of operation has shifted to a muscle-sparing left thoracotomy without routine chest drainage. In 7 recent patients with right aortic arch and a Kommerell diverticulum, the diverticulum was resected, and the left subclavian artery was transferred to the left carotid artery as a primary procedure. At our institution, computed tomographic scanning has replaced barium swallow as the diagnostic procedure of choice for vascular ring evaluation. We recommend both preoperative bronchoscopy and echocardiography. Use of a muscle-sparing thoracotomy without routine chest drainage has decreased mean hospital stay. For patients with a right aortic arch and associated Kommerell diverticulum, we recommend diverticulum resection with left subclavian artery transfer to the left carotid artery.

Neuronal Ceroid Lipofuscinosis: What Are the Roles of Electron Microscopy, DNA, and Enzyme Analysis in Diagnosis?

The neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal-storage disorders that occur primarily in chiIdren and rarely in adults. The childhood forms (infantile, late infantile, and juvenile NCLs) are inherited in an autosomalrecessive manner whereas adult NCL is reported to have an autosomal-dominant as well as an autosomal-recessive form. Clinical manifestations include progressive mental and motor degeneration, visual loss (childhood forms), seizures, and early death. The various forms of NCL are distinguished by age of onset, electron microscopy (EM), enzyme analysis, and gene involvement. Before the discovery of gene and protein defects responsible for NCL, identification of the pattern of characteristic inclusions by EM was the primary means of diagnosis before autopsy. Because NCL is a genetically and biochemically diverse disease, EM is still a valuable screening tool. Nevertheless, EM may not be the best first approach due to the invasive nature and cost. Current testing for enzyme deficiencies of palmitoylprotein thioesterase 1 (PPTI) and tripeptidyl-peptidase 1 (TPPl) can be an effective and less invasive approach for some forms of NCL. This paper offers a review of the four forms of NCL, as well as a discussion of the role of EM and enzyme analysis in the diagnosis of NCL. (The J Histotechnol 27:237, 2004)

Pectus excavatum. More than meets the eye.

Pectus excavatum is an anterior chest deformity that is characterized by a depressed sternum. Physical examination is the primary means of diagnosis. Common surgical operations to correct this malformation include the Ravitch and Nuss procedures, both of which have favorable postoperative outcomes. This deformity affects physical, emotional and psychological well-being. In addition, there are several important nursing interventions that need to be considered when caring for patients who have undergone surgical repair for pectus excavatum.

Rapid and simple assay for the determination of tripeptidyl peptidase and palmitoyl protein thioesterase activities in dried blood spots.

Neuronal ceroid lipofuscinoses constitute a group of at least eight inherited, progressive encephalopathies that are characterized by lipofuscin-like inclusions in various tissues and that have recently been classified as CLN1 to CLN8 according to their genetic defects (1). A form with mostly infantile manifestation (CLN1) and the classical late infantile form (CLN2) are caused by deficiencies of the lysosomal enzymes palmitoyl protein thioesterase 1 (PPT1) and tripeptidyl peptidase 1 (TPP1), respectively. The basic defects underlying the other forms are still ill-defined or unknown. To date, more than 30 mutations have been reported in the PPT1 and TPP1 genes, rendering molecular genetic analysis impractical as a primary means of diagnosis. Electron microscopy of characteristic cellular inclusions remains an important diagnostic method, but it is also tedious and not readily available. Enzymatic assays based on fluorescent substrates have recently been reported for PPT1 (2) and TPP1(3). These assays can also be used with isolated leukocytes. However, because few laboratories are experienced in diagnosing these rare disorders, blood samples must be sent to specialized centers by expensive express mail services to avoid loss of enzymatic activity. In our experience, samples for this kind of study frequently arrive in poor condition. As an alternative to the use of leukocytes, methods for determining several lysosomal enzymes from dried blood spots (DBS) have recently been described (4). DBS are also used routinely for enzyme measurements within newborn-screening programs for the detection of biotinidase and galactose-uridyltransferase deficiencies in neonates. DBS require only minute amounts of blood, are easy to …

Decubitus stereotactic core biopsy of the breast: technique and experience.

T he use of dedicated prone tables for stereotactic core biopsy of the breast has been well described I 1, 2J. Because budgetary and space constraints prevented our purchasing such a table, we developed a technique using an add-on stereotactic unit with the patient in the decubitus position, avoiding the problems of movement and syncope sometimes encountered in the upright position. We describe the technique and report on 3 years 6 months’ experience using this technique as the primary means of diagnosis for all mammographic lesions not seen on sonography. Besides the stereotactic unit, no special equipment is needed. This technique provides an optimum approach to all parts of the breast, gives reliable results, and should be widely applicable. especially when funding or space constraints have impeded the implementation of prone stereotactic breast biopsy.

Color Doppler controlled needle biopsy in diagnosis of soft tissue and bone tumors

In a prospective study we investigated 168 patients with musculoskeletal tumors, including 71 sarcomas, by core needle biopsy using the high-speed device Autovac. Monitoring with colour-coded duplex sonography allowed a well-aimed puncture of smaller or deeply localized lesions and also permitted the discrimination of necrotic and viable parts of the tumor. Adequate material for histologic diagnosis including grading and determination of tumor subtype was obtained from soft tissue sarcomas, soft tissue metastases, malignant lymphomas, plasmacytomas, and osteolytic skeletal secondaries. In contrast, in benign soft tissue and bone tumors the diagnosis could be established in only 66% of cases. Although skeletal sarcomas were identified as malignant mesenchymal lesions, a complete histologic classification of tumor subtype frequently was not possible due to an insufficient tissue specimen. With an accuracy of 97% for the diagnosis of malignancy and of 94% for the diagnosis of soft tissue sarcoma the results of core needle biopsies were comparable to those of incisional biopsies, the reference standard in the diagnosis of musculoskeletal tumors. Regarding the known disadvantages and the oncological risks of incisional biopsies, needle biopsy should replace the open procedure as the primary means of diagnosis in soft tissue and osteolytic bone tumors.

Mammographic Screening: A Surgeon's Perspective

Abstract: Prospective randomized trials demonstrate breast cancer mortality reduction in patients offered mammographic screening, conclusively for ages 50–69 and (with longer follow-up) likely for ages 40–49. The 25–30% degree of mortality reduction observed is particularly striking in view of the number of confounding variables in each trial, most of which would act to diminish the observed benefit. Few studies have examined the impact over time of more frequent mammography usage on women found to have breast cancer. During the period in which mammography came into general usage, how did means of cancer diagnosis change, and what was the impact of mammography on stage of disease? 1096 patients were treated in the author's practice for intraductal (DCIS) and invasive breast cancer between 1979 and 1993. Grouped into 5-year treatment intervals, and stratified by age and primary means of diagnosis, trends in tumor size, axillary node status, and tumor histopathology were compared. Over time, patients were increasingly likely 1) to have had mammography previously, 2) to have had their cancers diagnosed mammographically, 3) to have T1a/b (0.1–1.0 cm) tumors, 4) to be axillary node negative, and 5) to have DCIS pathologically. These trends were observed for patients both younger and older than age 50. There was no trend toward earlier-stage disease among patients either self- or physician-diagnosed, supporting the impression that the 15-year trend in this practice toward earlier diagnosis is entirely due to an increased usage of mammography. Mammography every 1–2 years is indicated in all women 40 and older, and every effort should be made to promote mammography among the substantial number of women who have still never had one.

The impact of mammography in 1096 consecutive patients with breast cancer, 1979-1993. Equal value for patients younger and older than age 50 years

Although the benefit of screening mammography in healthy women younger than age 50 remains controversial, few studies have addressed the impact of mammography over time and by patient age, on means of diagnosis and stage of disease among women with breast cancer. One thousand ninety-six consecutive patients with operable breast cancer (both invasive and noninvasive intraductal) treated in this practice between 1979 and 1993 were stratified by primary means of diagnosis (patient, physician, or mammography), age < 50 years, 50 years and older), and time period (1979-83, 1984-88, and 1989-93). Tumor size, lymph node status, and tumor type were compared among these groups. (1) Mammography was the primary means of diagnosis in 28.8% of younger and 42.4% of older patients treated most recently (1989-1993), significantly more often than in the past (P < 0.0005). (2) For cancers diagnosed primarily by either patients or physicians, there was not significant change over time (for either younger or older patients) in clinical presentation, tumor size, lymph node status, or histology. (3) For cancers diagnosed primarily by mammogram, i) 95% of patient self-exams and 56% of physician exams were negative, ii) tumor size was significantly smaller (P < 0.00005), iii) lymph nodes more often were negative (P = 0.0002), and d) histology was more likely to be either in-situ or microinvasive (P < 0.00005). These findings were equally true for younger and older patients. Increased use of mammography, rather than improvement in patient or physician breast examination, explains the progressively earlier stage of breast cancers found in recent years, a benefit equally apparent in patients younger and older than age 50.

Toxoplasma encephalitis in patients with the acquired immunodeficiency syndrome.

Among 504 cases of AIDS diagnosed between 1983 and 1990, there were 86 patients (17%) with toxoplasma encephalitis (TE). All were symptomatic at the time of diagnosis. General signs such as fever, neck stiffness, or headache were present in 87.2%, and 75.6% had focal signs. The primary means of diagnosis was computerized tomographic scanning, revealing 169 lesions of which 80% were immediately contrast-enhancing. All patients had IgG antibodies against Toxoplasma gondii either before (74 of 75 evaluable patients) or at the time of diagnosis of TE (73 of 75). Elevated antibody titers were present in 44% of evaluable patients, compared to 11% of patients with AIDS and other opportunistic infections. Initial treatment was pyrimethamine plus sulfonamides in 65 patients, and pyrimethamine plus clindamycin in 12 patients, with other combinations or no treatment accounting for the remainder. Life-table analysis of the time to discontinuation of treatment because of suspected side effects suggested that sulfadiazine was significantly more toxic, with 48% of patients experiencing an interruption in treatment after 30 days, than pyrimethamine (12%) or clindamycin (24%). The 30-day mortality rate was 12%, and median survival was 310 days after diagnosis, 530 in patients treated with zidovudine and 190 days in those not so treated. Of 82 evaluable patients, 16 relapsed once and 4 of these more than once. The risk of relapse was 27% 1 year after diagnosis of a first episode of TE.

Book reviewRadiology of the Skull and Brain. Vol. III. Anatomy and Pathology. Edited by NewtonT. H. and PottsD. G., pp. lx + 2787–3221, 1977 C. V. Mosby Co., St. Louis; distributed in U.K. Henry Kimpton), £37·45.

Several times in the last few decades neurological advances have changed our primary means of diagnosis. Smaller focal spots, complex movement tomography and safer contrast media used in higher concentration allow increased magnification and show greater detail and progressive refinements in computed tomography show intracranial structures with increased clarity, but the images achieved by any procedure must be resolved in terms of anatomy, physiology and pathology.