Ocular Manifestations of Hemoglobin S-C Disease

Three patients with hemoglobin S-C disease, all with ocular lesions, were studied and contrasted with four other patients who had predominantly either hemoglobin S or C but no ocular lesions. Attention is drawn to the diagnostic value of hemoglobin electrophoresis in such cases. With this technique a diagnosis of hemoglobin S-C disease was made in a patient previously thought to the “Eales'' disease”; one sister was found to have asymptomatic hemoglobin S-C disease and unsuspected early ocular lesions. The number of persons in Canada with hemoglobinopathies is increasing. Awareness of an association between abnormal hemoglobins and ocular disease may lead to the recognition of an unsuspected blood disorder or of an unsuspected retinopathy.     

Retroperitoneal Free Air

In the examination of 500 “well” executives, the number of unknown diseases found averaged 5.4 per person. Almost half of these executives had newly detected disease that was potentially significant to their health.Treatment was necessary in more than 47.7 per cent of them.One out of five of the total significant unknown defects found was either a peptic ulcer or gallstones; one out of five was a rectal adenoma; and one out of five was either hypertension or cardiac disease.One-third of the executives were overweight. Diabetes was found in every 20th person; and malignant disease was detected in one of every 41 people.For an examination to be “adequate” for the detection of unknown disease, the general physical examination must be complete and thorough. A proctoscopic is necessary, and certain basic laboratory screening procedures should be completed in each individual.Complete and routine x-ray studies of the gallbladder and gastrointestinal tract should be done, since they are the most important single diagnostic procedure, in detecting early, major, unsuspected, and often asymptomatic diseases.Routine consultations with specialists are a valuable asset in disease detection.Repeated periodic examinations help in detection of new unknown disease that was not present or not noted in earlier examinations.     

A collaborative study of a test for carcinoembryonic antigen (CEA) in the sera of patients with carcinoma of the colon and rectum

Five university centres in Canada and the United States have collaborated in a study of a test for carcinoembryonic antigen, with the Montreal General Hospital laboratory acting as the reference laboratory, examining duplicate halves of specimens from patients examined in local laboratories.Between June 1971 and April 1972, 503 patients were admitted to the study, 146 with cancer of the colon or rectum. Discrimination between colo-rectal cancer and “other” diagnoses was good at 2.5 ng./ml. or more, such a result being obtained in 66% of the patients with colo-rectal cancer in the local laboratories and 62% in the reference laboratory compared with 39% and 33% respectively of patients with “other” diagnoses. Patients with Duke''s C lesions of the colon or rectum were more likely to have raised CEA levels than patients with more localized lesions. CEA was also more commonly found in patients with other cancers and in patients with liver disease than in patients with other (benign) diagnoses.It is concluded that the test can be reproduced in other laboratories and that it or another simplified technique could become an important diagnostic aid for colo-rectal cancer.     

Blood Pressure: A Consideration of Terminology

Concepts of hypertension have changed and changes in terminology to reflect this state of affairs are suggested. Statistically, the best mortality experience is associated with blood pressure commonly regarded as subnormal, and increments of blood pressure above this level are associated with progressive increases in mortality. The terms “normal”, “benign” and “essential” in relation to blood pressure should be abandoned. “Optimal”, “acceptable” and “hypertensive” ranges of blood pressure are suggested. Hypertension is regarded as a symptom of disease, rather than as a disease in itself, and “hypertension”, when used as a diagnostic label, should be qualified always by the primary disease, if known, or by the modifying phrase, “of unknown cause”, if not known.     

Diagnostic Value of Run Chart Analysis: Using Likelihood Ratios to Compare Run Chart Rules on Simulated Data Series

Run charts are widely used in healthcare improvement, but there is little consensus on how to interpret them. The primary aim of this study was to evaluate and compare the diagnostic properties of different sets of run chart rules. A run chart is a line graph of a quality measure over time. The main purpose of the run chart is to detect process improvement or process degradation, which will turn up as non-random patterns in the distribution of data points around the median. Non-random variation may be identified by simple statistical tests including the presence of unusually long runs of data points on one side of the median or if the graph crosses the median unusually few times. However, there is no general agreement on what defines “unusually long” or “unusually few”. Other tests of questionable value are frequently used as well. Three sets of run chart rules (Anhoej, Perla, and Carey rules) have been published in peer reviewed healthcare journals, but these sets differ significantly in their sensitivity and specificity to non-random variation. In this study I investigate the diagnostic values expressed by likelihood ratios of three sets of run chart rules for detection of shifts in process performance using random data series. The study concludes that the Anhoej rules have good diagnostic properties and are superior to the Perla and the Carey rules.     

The Fluorescent Antibody Method in the Study of Immunopathologic Conditions

Histochemical studies of immunopathologic conditions were carried out, using Coons'' fluorescent antibody technique. Experimental conditions studied were: serum sickness, generalized anaphylaxis, the Arthus reaction and experimental glomerulonephritis. Human diseases studied were those referred to as “collagen diseases”. Specific immunologic reactants were localized in the lesions of all experimental conditions studied, thus offering objective evidence of a possible immunologic pathogenesis of the lesions. In human diseases, gamma globulin was localized in the lesions of rheumatic fever, rheumatoid arthritis, systemic lupus erythematosus and amyloidosis. Although the finding of gamma globulin in human lesions might suggest that it is an antibody, such an interpretation should be made with care since the gamma globulin could be deposited on a non-immunologic basis.The tissue-localizing properties of sera from different disease states showed appreciable variability within a given disease, as well as similar localizing properties among sera of different diseases. It is suggested that these serum factors (“autoantibodies”) might result as a host response and are not primarily involved in the pathogenesis of the disease.     

A Cervical Cytology Program in General Practice

In a six-year period 723 women were examined using cervical cytology smears. Fifteen cancers of the cervix were discovered, including two invasive growths and 13 carcinoma in situ. A careful follow-up was carried out, and the later appearance of cancer was noted in 12 of 41 patients who initially showed only atypical cells. It is recommended that all patients showing “positive” cells (atypical, suspicious, or cancer morphology cells) undergo cone biopsy for definitive histological diagnosis. Target lesions should have punch biopsy. Four cancers were found in 170 obstetrical patients, and it is recommended that this proved high-risk group be screened both prenatally and postnatally. The importance of annual screening of all women over 20 years of age for cancer of the cervix by cytological methods is emphasized.     

Fabry Disease – Underestimated in the Differential Diagnosis of Multiple Sclerosis?

Objective

Fabry disease is a rare X-linked inherited lysosomal storage disorder affecting multiple organ systems. It includes central nervous system involvement via micro- and macroangiopathic cerebral changes. Due to its clinical symptoms and frequent MRI lesions, Fabry disease is commonly misdiagnosed as multiple sclerosis. We present an overview of cases from Fabry centres in Germany initially misdiagnosed with multiple sclerosis and report the clinical, MR-tomographical, and laboratory findings.

Methods

Eleven Fabry patients (one male, ten females) initially diagnosed with multiple sclerosis were identified from 187 patient records (5.9%) and analyzed for presenting symptoms, results of the initial diagnostic workup, and the clinical course of the disease.

Results

Four patients were identified as having a “possible” history of MS, and 7 patients as “definite” cases of multiple sclerosis (revised McDonald criteria). On average, Fabry disease was diagnosed 8.2 years (±9.8 years) after the MS diagnosis, and 12.8 years after onset of first symptoms (±10.3 years). All patients revealed white matter lesions on MRI. The lesion pattern and results of cerebrospinal fluid examination were inconsistent and non-specific. White matter lesion volumes ranged from 8.9 mL to 34.8 mL (mean 17.8 mL±11.4 mL). There was no association between extra-neurological manifestations or enzyme activity and lesion load.

Conclusion

There are several anamnestic and clinical hints indicating when Fabry disease should be considered a relevant differential diagnosis of multiple sclerosis, e.g. female patients with asymmetric, confluent white matter lesions on MRI, normal spinal MR imaging, ectatic vertebrobasilar arteries, proteinuria, or lack of intrathecally derived immunoglobulin synthesis.     

Medical Aspects of Violence

Physicians see violence in beaten wives, battered children, rage reactions, murder, and suicide. They should recognize that it may be a symptom of disease if it is unprovoked or bizarre, or is associated with impaired consciousness, confusion or irrationality. Violence in episodic trance-like states suggests limbic disease (temporal lobe lesions, psychomotor epilepsy, or “dyscontrol syndrome”); in association with personality change, dementia, or psychosis, it indicates cortical disease (structural, toxic, or idiopathic).     

Q-Elastography in the Presurgical Diagnosis of Thyroid Nodules with Indeterminate Cytology

Quantitative ultrasound (US) elastography (Q-USE), able to evaluate tissue stiffness has been indicated as a new diagnostic tool to differentiate benign from malignant thyroid lesions. Aim of this prospective study, conducted at the Department of Surgical Sciences, of the “Sapienza” University of Rome, was to evaluate the diagnostic accuracy of Q-USE, compared with US parameters, in thyroid nodules with indeterminate cytology (Thy3).The case study included 140 nodules from 140 consecutive patients. Patient’s thyroid nodules were evaluated by Q-USE, measuring the strain ratio (SR) of stiffness between nodular and surrounding normal thyroid tissue, and conventional US parameters prior fine-needle aspiration cytology. Those with Thy3 diagnosis were included in the study. Forty of the nodules analyzed harbored a malignant lesion. Q-USE demonstrated that malignant nodules have a significant higher stiffness with respect to benign one and an optimun SR cut-off value of 2.05 was individuated following ROC analysis. Univariate analysis showed that hypoechogenicity, irregular margins and SR >2.05 associated with malignancy, with an accuracy of 67.2%, 81,0% and 89.8%, respectively. Data were unaffected by nodule size or thyroiditis. These findings were confirmed in multivariate analysis demonstrating a significant association of the SR and the irregular margins with thyroid nodule’s malignancy. In conclusion, we demonstrated the diagnostic utility of Q-USE in the differential diagnosis of thyroid nodules with indeterminate cytology that, if confirmed, could be of major clinical utility in patients’ presurgical selection.     

Added Value of Antigen ELISA in the Diagnosis of Neurocysticercosis in Resource Poor Settings

Background

Neurocysticercosis (NCC) is the most common cause of acquired epilepsy in Taenia solium endemic areas, primarily situated in low-income countries. Diagnosis is largely based upon the “Del Brutto diagnostic criteria” using the definitive/probable/no NCC diagnosis approach. Neuroimaging and specific T. solium cysticercosis antibody detection results are at the mainstay of this diagnosis, while antigen detection in serum has never been included. This study aimed at evaluating the addition of antigen detection as a major diagnostic criterion, especially in areas where neuroimaging is absent.

Methods

The B158/B60 monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) for the detection of circulating cysticercus antigen was carried out retrospectively on serum samples collected during a hospital-based study from 83 people with epilepsy (PWE) in an endemic area.

Results

The addition of antigen results as a major criterion allowed the correct diagnosis of definitive NCC in 10 out of 17 patients as opposed to 0/17 without antigen results in the absence of neuroimaging. A sensitivity of 100% and a specificity of 84% were determined for the diagnosis of active NCC using antigen ELISA. While the use of a higher cutoff improves the specificity of the test to 96%, it decreases its sensitivity to 83%.

Conclusions

In areas where neuroimaging is absent, NCC diagnosis according to the existing criteria is problematic. Taking into account its limitations for diagnosis of inactive NCC, antigen detection can be of added value for diagnosing NCC in PWE by supporting diagnostic and treatment decisions. Therefore, we recommend a revision of the “Del Brutto diagnostic criteria” for use in resource poor areas and suggest the inclusion of serum antigen detection as a major criterion.     

CYTOLOGIC DETECTION OF CERVICAL CANCER—Four Years' Experience with Routine Smear Examination in Private Practice

Simplified Papanicolaou smear techniques appear to be adaptable to private clinical practice when experienced cytodetection laboratory facilities are available. A private physician''s office seems potentially an efficient, economical and practical place for detection of cervical cancer by use of the smear technique as a routine part of examination of patients.In a series here reported upon, examination of 11,207 cervical smears taken at the first examination of patients of all ages led to diagnosis of unsuspected malignant disease in 80 cases—in all instances at a stage when it should be easily curable. Cancer was not detected in examination of 6,060 smears taken later from women who had had a “negative” smear at the time of first examination, which seems to indicate that the first screening was reasonably accurate.In a few cases, early cancer was detected when smears were reported as “atypical” or “suspicious.” Such reports demand as careful follow-up as do “positive” reports.There are dangers and limitations in wide-spread clinical application of screening by this method. Care must be observed in the development of programs for its use lest the potential benefits in early detection be outweighed by the dangers from misuse.     

Gene-Gene and Gene-Environment Interactions in Meta-Analysis of Genetic Association Studies

Extensive genetic studies have identified a large number of causal genetic variations in many human phenotypes; however, these could not completely explain heritability in complex diseases. Some researchers have proposed that the “missing heritability” may be attributable to gene–gene and gene–environment interactions. Because there are billions of potential interaction combinations, the statistical power of a single study is often ineffective in detecting these interactions. Meta-analysis is a common method of increasing detection power; however, accessing individual data could be difficult. This study presents a simple method that employs aggregated summary values from a “case” group to detect these specific interactions that based on rare disease and independence assumptions. However, these assumptions, particularly the rare disease assumption, may be violated in real situations; therefore, this study further investigated the robustness of our proposed method when it violates the assumptions. In conclusion, we observed that the rare disease assumption is relatively nonessential, whereas the independence assumption is an essential component. Because single nucleotide polymorphisms (SNPs) are often unrelated to environmental factors and SNPs on other chromosomes, researchers should use this method to investigate gene–gene and gene–environment interactions when they are unable to obtain detailed individual patient data.     

Evaluation of the Diagnostic Accuracy of Prototype Rapid Tests for Human African Trypanosomiasis

BackgroundDiagnosis of human African trypanosomiasis (HAT) remains a challenge both for active screening, which is critical in control of the disease, and in the point-of-care scenario where early and accurate diagnosis is essential. Recently, the first field deployment of a lateral flow rapid diagnostic test (RDT) for HAT, “SD BIOLINE HAT” has taken place. In this study, we evaluated the performance of “SD BIOLINE HAT” and two new prototype RDTs.Conclusions/SignificanceBoth “SD BIOLINE HAT” and the prototype devices performed comparably well to one another and also to the published performance range of the card agglutination test for trypanosomiasis in sensitivity and specificity. The performance of individual antigens enabled us to predict that an all-recombinant antigen RDT can be developed with an accuracy equivalent to “ SD BIOLINE HAT.” Such an RDT would have advantages in simplified manufacture, lower unit cost and assured reproducibility.     

Selecting Essential Information for Biosurveillance—A Multi-Criteria Decision Analysis

The National Strategy for Biosurveillancedefines biosurveillance as “the process of gathering, integrating, interpreting, and communicating essential information related to all-hazards threats or disease activity affecting human, animal, or plant health to achieve early detection and warning, contribute to overall situational awareness of the health aspects of an incident, and to enable better decision-making at all levels.” However, the strategy does not specify how “essential information” is to be identified and integrated into the current biosurveillance enterprise, or what the metrics qualify information as being “essential”. Thequestion of data stream identification and selection requires a structured methodology that can systematically evaluate the tradeoffs between the many criteria that need to be taken in account. Multi-Attribute Utility Theory, a type of multi-criteria decision analysis, can provide a well-defined, structured approach that can offer solutions to this problem. While the use of Multi-Attribute Utility Theoryas a practical method to apply formal scientific decision theoretical approaches to complex, multi-criteria problems has been demonstrated in a variety of fields, this method has never been applied to decision support in biosurveillance.We have developed a formalized decision support analytic framework that can facilitate identification of “essential information” for use in biosurveillance systems or processes and we offer this framework to the global BSV community as a tool for optimizing the BSV enterprise. To demonstrate utility, we applied the framework to the problem of evaluating data streams for use in an integrated global infectious disease surveillance system.     

Growth Hormone Release Inhibiting Hormone in Acromegaly

Growth hormone release inhibiting hormone (GHRIH) was administered by constant infusion over 75 minutes to eight acromegalic patients at different doses. 100 to 1,000 μg were equally effective in reducing circulating growth hormone (GH) levels; 25 μg lowered GH levels in only five patients, and at this dose the extent of the fall was smaller than from doses of 100 μg or more. 10 μg was ineffective. Injection of single doses of 500 μg by intravenous, subcutaneous, and intramuscular routes caused only small and transient reductions in GH levels, though the effect was improved by injecting the hormone intramuscularly in 2 ml of 16% gelatin. Injection of a suspension of 4 mg GHRIH in 1 ml of arachis oil lowered growth hormone levels for between three and four hours.In four acromegalic patients an oral 50-g glucose tolerance test was performed during a continuous infusion of either saline or 1,000 μg GHRIH. The “paradoxical” rise in growth hormone seen in these patients during the saline infusion was suppressed by GHRIH. The blood glucose responses were, moreover, modified by GHRIH in that the peak was delayed and occurred at the end of the infusion in each case. A “normal” glucose tolerance curve was converted to a “diabetic” type of response in two patients. This effect could be accounted for by the inhibition of insulin secretion known to occur with large doses of GHRIH.We speculate that acromegaly may be primarily a hypothalmic disease due to deficiency of GHRIH resulting in excessive secretion of growth hormone from the pituitary and adenoma formation due to inappropriate and prolonged stimulation of the pituitary.     

Diagnostic value of nucleolar organizer regions (AgNORs) in brush biopsies of suspicious lesions of the oral cavity.

OBJECTIVE: The aim of this retrospective study was to report on the diagnostic accuracy of AgNOR-analysis as an adjunctive diagnostic tool of conventional oral exfoliative cytology taken from suspicious lesions in our clinic. STUDY DESIGN: Cytological diagnoses obtained from brush biopsies of macroscopically suspicious lesions of the oral mucosa from 75 patients (final diagnoses: 53 histologically proven squamous cell carcinomas, 11 leukoplakias and other inflammatory oral lesions) and from 11 patients with normal mucosa as a negative control group were compared with histological and/or clinical follow-ups. Five smears were doubtful and seven suspicious for tumor cells in the cytologic report. Number of AgNOR's were counted in 100 squamous epithelial cell-nuclei per slide after silver-restaining. RESULTS: Sensitivity of our cytological diagnosis alone on oral smears for the detection of squamous carcinomas was 92.5%, specificity 100%, positive predictive value was 100% and negative 84.6%. The best cut-off value of the mean number of AgNOR dots per nucleus distinguishing benign from malignant cells was 4.8. The percentage of nuclei with more than three AgNORs had a cut-off level of 70%. Applying these methods to twelve doubtful or suspicious cytological diagnoses we were able to correctly establish the diagnosis of malignancy in ten cases of histologically proven cancers and to reveal benignity in two histologically proven cases. Thus we achieved a positive and negative predictive value of 100% each. CONCLUSIONS: Smears from brushings of visible oral lesions, if clinically considered as suspicious for cancer, are an easily practicable, non-invasive, painless, safe and accurate screening method for detection of oral cancerous lesions. We conclude that AgNOR-analysis may be a useful adjunct to other methods in routine cytological diagnosis of oral cancer that can help to solve cytologically suspicious or doubtful cases.     

Cytology of benign multicystic peritoneal mesothelioma in peritoneal washings

Objective:  To describe the cytological aspect of peritoneal washings in benign multicystic peritoneal mesothelioma (BMPM).
Methods:  Three peritoneal washing specimens stained by standard cytological and histological procedures and analysed by light microscopy.
Results:  The specimens showed an abundance of monomorphous mesothelial cells devoid of atypia or mitoses. The mesothelial cells were calretinin positive. They also showed numerous squamous metaplastic cells arranged in flat sheets or isolated cells. The background contained some inflammatory cells.
Conclusion:  The combination of cytology of the peritoneal washing, histology (cell block and surgical specimen) and clinical history allow differentiation of BMPM from other cystic lesions (cystic lymphangioma and malignant mesothelioma).