CANCER DETECTION CENTERS—The Experience to Date in California

Cancer “detection centers” (that is, centers for the examination of presumably well or asymptomatic persons) have been tried out in four different California communities during the last three years. In all instances—as in most other such centers throughout the United States—they have not been successful in restricting examination to well persons.The detection centers in California may therefore be described more accurately as “cancer examination and detection clinics.”Three of the four centers have been closed owing to the small yield of cancer cases discovered, plus the fact that the cost of operation exceeded the total available funds of the local branch of the Cancer Society. In addition, it was extremely difficult to obtain and maintain competence on the part of the professional staff in such centers.A more practical approach to the problem of earlier tumor detection would appear to be emphasis on making “every physician''s office a detection center,” and stressing the annual examination of persons over 40 years of age for tumors in the five common accessible sites. These are the tumors most readily curable today.     

Lymphangiography: Its Practical Value in Surgically Staged Patients with Hodgkin's Disease

Since the introduction of “staging laparotomy” (to determine the disease''s stage) in assessing Hodgkin''s disease, some observers have argued that lymphangiography could be safely omitted in the initial diagnostic evaluation.To test these opinions a series of 75 patients with Hodgkin''s disease who had a staging laparotomy and histological correlation with lymphangiograms was reviewed. Of 16 examinations with positive results, one proved to be a false positive. Of the 14 examinations with equivocal results, one proved histologically positive. In the remaining 45 lymphangiograms, five were falsely negative. In all five of these patients abdominal lymph nodes were involved, but in areas that do not routinely opacify on lower extremity lymphangiography. The overall accuracy was 90 percent.Therapeutically, the lymphangiogram permits accurate planning for treatment by radiation therapy so that all known disease is treated and yet bone marrow is not excessively irradiated. Changes in lymph node architecture after therapy provide valuable information as to regression of the disease or signs of its early recurrence.     

BRONCHOGENIC CARCINOMA IN SAN DIEGO COUNTY—Relation of Mortality Rates to Findings in Mass Chest X-Ray Survey

Nearly half the population of San Diego County was examined by chest x-ray for bronchogenic carcinoma. The disease was correctly diagnosed in 20 persons, of whom 17 died. Twenty-four others in whom it was not detected in survey films died of the disease in the following two years.Of the 20 cases found, 16 were in men, all more than 54 years of age, and of the 24 who died after “negative” classification, 20 were men over 40.The death rate for men over 40 years of age from bronchogenic carcinoma is about one in a thousand. Because of the frequently rapid progress of the disease after onset, and the poor prognosis after the appearance of symptoms, x-ray examination every six months for men over 40 should be considered.     

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.     

School Screening for Scoliosis—One Experience in California Using Clinical Examination and Moiré Photography

In 1980 the legislature of the state of California mandated that school screening programs for scoliosis be implemented. This law resulted in variations in methods and efficacy of the programs. One such program using clinical examination and moiré photography was administered to adolescent girls in two secondary schools in Santa Clara County. The findings of 10% of the clinical examinations were ruled to be “positive,” 18% on moiré photography alone and 8% on both examinations. The correlation between the two diagnostic procedures was poor (r = .16). Follow-up was done to determine the outcome of the “positive” cases. In all, 25% of the children classified as having scoliosis had no medical follow-up one year from the request by the screening program team. The documented false-positive rate was 15% based on the screening examination. Definitive radiographic evaluation was reported in very few of the positive cases.Our experience shows the weakness of local programs that have no subject follow-up. It is suggested that public education may be a more effective solution than mass school screening mandates.     

“Skid Row” Syndrome: A Medical Profile of the Chronic Drunkenness Offender

From skid row, 227 chronic “drunks”, inmates of the Toronto Jail, were studied to determine the physical features and illnesses of this group. Complete physical examinations, liver function tests, routine hematology, urinalysis, chest radiographs were carried out and previous hospital records were obtained for each man. The data were analyzed by IBM computer and reported in terms of body systems. Items that occurred in sufficient frequency were separated out and listed to compile a “skid row” syndrome. The men averaged 45 years of age, had been drinking heavily for 20 years and had four drunken convictions a year. Tuberculosis was found in 8.8%. Epilepsy was confirmed in 8%. Cirrhosis of the liver was definite in 3% of the group; 75% were under the Canadian average weight, and 25% had significant body deformities. It was estimated that, if necessary therapy was carried out, 90% of the men would be able to perform useful labour.     

Cross-Sectional Study on Antibiotic Usage in Pigs in Germany

To be able to analyze the relationship between the level of resistance and the use of antimicrobials, it is necessary to collect detailed data on antimicrobial usage. For this reason, data on antimicrobial use on 495 pig farms from entire Germany were collected and analyzed. In Germany, each application and dispensing of medicines to food-producing animals is documented in detail obligatorily by the veterinarian. This information was collected retrospectively for the year 2011. The analyses undertook separate examinations on the age groups sow, piglet, weaner and fattening pig; both the route of administration and indication per active ingredient, and active ingredient class, were evaluated. In total, 20,374 kg of antimicrobial substances were used in the study population. Tetracyclines were used in highest amounts, followed by beta-lactams, trimethoprim-sulfonamides and macrolides. Concerning the frequency of using an active substance per animal, polypeptides were most commonly administered. In all age groups, respiratory infections were the main indication for using antimicrobials, followed by intestinal diseases in piglets, weaners and fattening pigs and diseases of reproductive organs in sows. Over a period of 100 days, the median number of treatment days with one antimicrobial substance for piglets was 15 days, for weaners about 6 days, for fattening pigs about 4 days and for sows about 1 day. A multifactorial ANOVA was conducted to investigate which factors are associated with the treatment frequency. The factors “veterinarian” and “age group” were related to the treatment frequency, just as the interaction between “veterinarian” and “farm size” as well as the interaction between “veterinarian” and “age group”.     

When is screening effective in reducing the death rate?

Periodic screening programs for the early detection of chronic diseases such as cancer and heart disease may not always lead to a reduction in the number of deaths from the disease. Some improvement is usually possible with the use of a more sensitive detection test, or by lowering the age for the first screening examination, or by decreasing the period between examinations. However, the extent of the reduction in deaths that is attainable with these changes is limited by the underlying biological behavior of the disease as well as by the rate at which the disease is detected without the screening examination, i.e., by the “natural history” of the disease. The effectiveness of a periodic screening program is derived as a function of this natural history, the period between examinations, the sensitivity of the detection test, the age at the first examination, and the age distribution of the rate of the disease initiation in the screened population. A detailed discussion is given of how these results might be used to estimate the effectiveness of any planned periodic screening program. The analysis of a simple example suggests that for some diseases decreasing the interval between screening examinations may not lead to a significant lowering of the death rate, i.e., there may be a natural lower bound on the screening period.     

Lead in Bones and Drinking Water in Towns with Hard and Soft Water

In two comparable series of medicolegal necropsies the lead content of ribs was found to be much higher in three soft water than in three hard water towns in England and Wales. Fourteen out of 96 “overnight” tap water samples from five soft water and five hard water towns in England and Wales and from Glasgow (soft water) had lead concentrations of over 0·1 p.p.m.; values over 0·3 p.p.m. were found only in Glasgow. The possible relevance of the findings to the association of cardiovascular disease and soft drinking water is discussed.     

A Visual Dual-Aptamer Logic Gate for Sensitive Discrimination of Prion Diseases-Associated Isoform with Reusable Magnetic Microparticles and Fluorescence Quantum Dots

Molecular logic gates, which have attracted increasing research interest and are crucial for the development of molecular-scale computers, simplify the results of measurements and detections, leaving the diagnosis of disease either “yes” or “no”. Prion diseases are a group of fatal neurodegenerative disorders that happen in human and animals. The main problem with a diagnosis of prion diseases is how to sensitively and selectively discriminate and detection of the minute amount of PrP^Res in biological samples. Our previous work had demonstrated that dual-aptamer strategy could achieve highly sensitive and selective discrimination and detection of prion protein (cellular prion protein, PrP^C, and the diseases associated isoform, PrP^Res) in serum and brain. Inspired by the advantages of molecular logic gate, we further conceived a new concept for dual-aptamer logic gate that responds to two chemical input signals (PrP^C or PrP^Res and Gdn-HCl) and generates a change in fluorescence intensity as the output signal. It was found that PrP^Res performs the “OR” logic operation while PrP^C performs “XOR” logic operation when they get through the gate consisted of aptamer modified reusable magnetic microparticles (MMPs-Apt1) and quantum dots (QDs-Apt2). The dual-aptamer logic gate simplifies the discrimination results of PrP^Res, leaving the detection of PrP^Res either “yes” or “no”. The development of OR logic gate based on dual-aptamer strategy and two chemical input signals (PrP^Res and Gdn-HCl) is an important step toward the design of prion diseases diagnosis and therapy systems.     

Ocular Findings in Several Metabolic Diseases

Changes in ocular findings have been noted in association with several metabolic diseases.In homocystinuria the crystalline lens in the majority of cases is subluxated inferiorly, while in Marfan''s syndrome the dislocation was upward.In cystinosis, slit-lamp examination reveals numerous gold crystal-like cystine deposits in both the cornea and bulbar conjunctiva.Patients with galactosemia have cataracts of the “oil drop” type, which usually can be seen with an ophthalmoscope even though the opacity is not dense.Eight patients with Lowe''s syndrome who were observed had cataracts, and four of them had severe glaucoma.Three of five patients with glycogen storage disease Type I had yellowish deposits in the macular and paramacular areas, thought to be due to hypercholesterolemia.     

On the Subjective Acceptance during Cardiovascular Magnetic Resonance Imaging at 7.0 Tesla

Purpose

This study examines the subjective acceptance during UHF-CMR in a cohort of healthy volunteers who underwent a cardiac MR examination at 7.0T.

Methods

Within a period of two-and-a-half years (January 2012 to June 2014) a total of 165 healthy volunteers (41 female, 124 male) without any known history of cardiac disease underwent UHF-CMR. For the assessment of the subjective acceptance a questionnaire was used to examine the participants experience prior, during and after the UHF-CMR examination. For this purpose, subjects were asked to respond to the questionnaire in an exit interview held immediately after the completion of the UHF-CMR examination under supervision of a study nurse to ensure accurate understanding of the questions. All questions were answered with “yes” or “no” including space for additional comments.

Results

Transient muscular contraction was documented in 12.7% of the questionnaires. Muscular contraction was reported to occur only during periods of scanning with the magnetic field gradients being rapidly switched. Dizziness during the study was reported by 12.7% of the subjects. Taste of metal was reported by 10.1% of the study population. Light flashes were reported by 3.6% of the entire cohort. 13% of the subjects reported side effects/observations which were not explicitly listed in the questionnaire but covered by the question about other side effects. No severe side effects as vomiting or syncope after scanning occurred. No increase in heart rate was observed during the UHF-CMR exam versus the baseline clinical examination.

Conclusions

This study adds to the literature by detailing the subjective acceptance of cardiovascular magnetic resonance imaging examinations at a magnetic field strength of 7.0T. Cardiac MR examinations at 7.0T are well tolerated by healthy subjects. Broader observational and multi-center studies including patient cohorts with cardiac diseases are required to gain further insights into the subjective acceptance of UHF-CMR examinations.     

The frequency of genetic disease and congenital malformation among patients in a pediatric hospital

A sample of 12,801 admissions to a pediatric hospital was surveyed in 1969-70 to determine the prevalence of disease which could be classified as “genetic” in origin or related to “congenital malformation”.“Genetic” admissions accounted for 11.1% of the total while 18.5% were for congenital malformations; about 2% (unknown group) were probably genetic. Therefore about one third of all admissions represent the effect of abnormal gene-environment interrelations at some point in the development or life of the patient.The “genetic” patient is admitted more often to a medical service while the patient with congenital malformation usually goes to a surgical service; the former stays 7.3 days and the latter 8.6 days. A disproportionate number of patients staying longer than 10 days were found in the group with congenital malformations. Seventy percent of the patients with multiple admissions (3.2% of all admissions) have genetic illness or congenital malformation.     

Using Linkage Analysis to Detect Gene-Gene Interaction by Stratifying Family Data on Known Disease,or Disease-Associated,Alleles

Detecting gene-gene interaction in complex diseases is a major challenge for common disease genetics. Most interaction detection approaches use disease-marker associations and such methods have low power and unknown reliability in real data. We developed and tested a powerful linkage-analysis-based gene-gene interaction detection strategy based on conditioning the family data on a known disease-causing allele or disease-associated marker allele. We computer-generated multipoint linkage data for a disease caused by two epistatically interacting loci (A and B). We examined several two-locus epistatic inheritance models: dominant-dominant, dominant-recessive, recessive-dominant, recessive-recessive. At one of the loci (A), there was a known disease-related allele. We stratified the family data on the presence of this allele, eliminating family members who were without it. This elimination step has the effect of raising the “penetrance” at the second locus (B). We then calculated the lod score at the second locus (B) and compared the pre- and post-stratification lod scores at B. A positive difference indicated interaction. We also examined if it was possible to detect interaction with locus B based on a disease-marker association (instead of an identified disease allele) at locus A. We also tested whether the presence of genetic heterogeneity would generate false positive evidence of interaction. The power to detect interaction for a known disease allele was 60–90%. The probability of false positives, based on heterogeneity, was low. Decreasing linkage disequilibrium between the disease and marker at locus A decreased the likelihood of detecting interaction. The allele frequency of the associated marker made little difference to the power.     

External Quality Assessment of Molecular Detection of Ebola Virus in China

In 2014, Ebola hemorrhagic fever broke out in West Africa. As contact between China and West Africa is frequent, the possibility that Ebola virus would enter China was high. Thus, an external assessment of the quality of Ebola virus detection was organized by the National Center for Clinical Laboratories in China. Virus-like particles encapsulating known sequences of epidemic strains of Ebola virus from 2014 were prepared as positive quality controls. The sample panel, which was composed of seven positive and three negative samples, was dispatched to 19 laboratories participating in this assessment of Ebola virus detection. Accurate detection was reported at 14 of the 19 participating laboratories, with a sensitivity of 91.43% and a specificity of 100%. Four participants (21.05%) reported false-negative results and were classified as “acceptable.” One participant (5.26%) did not detect any positive samples and was thus classified as “improvable.” Based on the results returned, the ability to detect weakly positive Ebola specimens should be improved. Furthermore, commercial assays and the standard primers offered by the Chinese Centers for Disease Control and Prevention were found to be most accurate and dependable for Ebola detection. A two-target detection approach is recommended for Ebola screening; this approach could reduce the probability of false-negative results. Additionally, standardization of operations and punctual adjustment of instruments are necessary for the control and prevention of Ebola virus.     

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.     

AMEBIASIS MASQUERADING AS APPENDICITIS

In fifteen cases of amebiasis masquerading as appendicitis, the important findings were nausea, vomiting, epigastric pain, pain in the right lower quadrant of the abdomen, fever, and leukocytosis.Amebiasis ought to be considered and appropriate studies carried out in differential diagnosis of cases in which symptoms indicate acute, subacute or “chronic” appendicitis. Depending on indications, the studies should include radiography with barium enema, sigmoidoscopy, complement fixation test, a minimum of nine stool examinations, a stool culture, and examination of purged stools unless this is contraindicated.     

INITIAL CARE OF ACUTE BACK INJURIES

The mechanism of injury to the back should be obtained with the utmost accuracy and set down in the history as a separate paragraph under that heading. This is usually best obtained by questioning and requestioning the patient during the course of the examination. A history of any previous back affections should also be obtained at the first visit.The detailed examination of the back is not complete without a general physical examination.X-ray studies should be done immediately in all cases in which the injury has been caused by direct violence or forceful indirect violence (as in “jackknife” injury).Terms such as “disc disease,” “ruptured intervertebral disc” and various others that convey a similar meaning should not be used as the initial diagnosis and should be withheld until such a diagnosis is definitely established.The plan of treatment may include a period in hospital or of rest at home, or it may be carried out with the patient ambulatory. Corsets and braces should be prescribed only when they are to serve a definite function and the same can be said of physiotherapy.     

Thalassaemia in the British

Different forms of thalassaemia or related disorders were found in 116 people of apparently pure British stock. Among them were one family with a child homozygous for β-thalassaemia and eight heterozygous relatives, 16 families with 83 persons heterozygous for β-thalassaemia, two families with three persons with Hb H disease and three heterozygous for α-thalassaemia 1, one family with a child apparently homozygous for the “silent β-thalassaemia gene,” one family with six members heterozygous for a form of β-thalassaemia intermedia, and three families with 11 members heterozygous for different types of hereditary persistence of fetal haemoglobin. The clinical, haematological, and haemoglobin biosynthetic findings in these persons were similar to those of patients with thalassaemia from other racial groups. The heterozygous state for β-thalassaemia is overlooked in British patients, particularly during pregnancy, because it is not considered in the differential diagnosis of refractory anaemia. In many cases this leads to much unnecessary investigation and potentially harmful treatment.There seem to be several varieties of hereditary persistence of fetal haemoglobin production among British people. These conditions, while not causing anaemia, may cause difficulties during examination of maternal blood for fetal cells and may, if inherited with a β-thalassaemia gene, produce an unusually high level of Hb F in a person heterozygous for β-thalassaemia.     

Onset,Early Stages,and Prognosis of Rheumatoid Arthritis: A Clinical Study of 100 Patients with 11-year Follow-up

One hundred patients with “definite” or “classical” rheumatoid arthritis were followed in a hospital clinic from within one year of the onset of the arthritis. The average interval between onset and first attendance was 3·7 months. Onset was commoner in the winter, transient prodromal symptoms being noted in 23, with possible precipitating factors in 14. The serum rheumatoid factor test was positive at some time in 88.The patients were reassessed between eight and 14 years later. Seventeen died during this period, five possibly as a result of the disease or its treatment.The remaining patients had improved as a whole in terms of the blood sedimentation rate, haemoglobin, titre of the rheumatoid factor test, and status of the disease, but there was an overall deterioration in functional capacity. Both the rheumatoid factor titre and the functional capacity at an earlier review could be directly correlated with the outcome, but other factors were not found to influence the ultimate prognosis.