False Negative Report Research Articles

A clinical test for pregnancy

This paper describes a clinical test that has been found effective in diagnosing pregnancy in the first 10 days after a missed period. The patient is given 125 mg of progesterone im in 2.5 ml of oil, then 4 tablets of 2.5 mg each of conjugated equine estrogens (Premarin, Amnestrogen, or Conestion) are given at bedtime with the same dose repeated the next morning. If no bleeding occurs by Day 8 of treatment, pregnancy is diagnosed. The test was used in 168 women with previously normal menstrual cycles. In 52 pregnancy was present and diagnosed. In the only other false negative report an abortion occurred 2 days after the injection. The test did not affect the course of established intrauterine pregnancies. No severe reactions were seen. A total of 5 false positive reports were given. Of these 2 were taking large doses of phenothiazine tranquilizers, 2 had enlarged ovaries, and 1 had pelvic inflammatory disease. Progesterone alone will not always produce withdrawal bleeding. The combination with estrogen may be needed. This test is considered accurate within the first 10 days of pregnancy in 96% of cases. It has several advantages over other methods.

Lymphography in melanoma. Correlation of radiology with pathology.

Radiological diagnoses after contrast lymphography were compared with histological diagnoses on excised specimens of nodes of 17 melanoma patients. False positive and false negative diagnoses were so common that the value of lymphography in guiding clinical decisions on patient management was nullified. Of 228 nodes examined 63 had filling defects and 9 of these were due to tumor; however, 14 of these 63 nodes initially were diagnosed radiologically as containing tumor. A false negative report on an outlined node was given 9 times, either because the metastasis was small or because a discernible filling defect was misinterpreted. Of 10 nodes which were not outlined with dye, one contained tumor. Useful information for the designing and execution of lymph node excision operations was derived from lymphography.

Exfoliative Cytology in Nose, Throat and Ear malignancy

Cytology is only of value where definite malignant cells are seen. Absence or such cells in no way means that lesion is not of neoplastic nature. False negative report is better than a false positive report as former can be explained by the fact the malignant cells might not have come in swabs and repeat swabs will further reduce the possibility of error. Almost invariably cytology reveals the histomorphological nature of tumour earlier and even gives definite ground for suspicion of benign looking lesions in middle aged persons with no relevant complaints. Cytology studies in Otolaryngology are of definite value in early and rapid diagnosis and effort is being made in this Institute to carry it out as a routine Laboratory investigation.

A routine method for the preparation of the cells of urine.

The value of urinary cytology in the screening of a large industrial population at risk to bladder carcinogens has been amply demonstrated by Crabbe, Cresdee, Scott, and Williams (1956). The standard method of Papanicolaou and Marshall (1945) by which the exfoliated cells are prepared for examination consists simply of smearing the deposit of fixed centrifuged urine on to albuminized slides and staining. Unfortunately, this technique limits the diagnostic value of exfoliative cytology because only a small and possibly unrepresentative propor tion of the cells in a given urine sample are prepared for examination, and these are so widely dispersed in the smear that the labour of finding them further reduces the numbers actually seen. Determinations of the rates of exfoliation of transitional and squamous epithelial cells from the urinary tract in 12 normal males (Rofe, 1955) showed characteris tic rates for individuals, the lowest of which was 6-2 thousands/hour and the highest 148 thousands/ hour. An hour's urine sample, say 60 ml., might thus be expected to contain at least 6,000 cells, yet smears of urine sediment, which usually cover the whole area of a slide, are sometimes found to contain no cells or too few cells on which to report (Chute and Williams, 1948; Vincent Memorial Hospital, 1950; Deden, 1954). Presti and Weyrauch (1955) found as many as 22% of samples (100 ml.) pro duced smears containing less than six cells, but were prepared to interpret smears containing more than this number of cells : this might well account for the unsatisfactory results referred to by them. Schmid lapp and Marshall (1948) refer to instances of finding malignant cells only after several specimens had been examined, and Crabbe (1956) feels that a single smear could quite possibly show no malignant cells although these are present in the sample as a whole : in this way a false negative report could arise. It is evident that the reliability of cytological diagnosis is increased if ample numbers of cells are obtained from every urine sample. If in addition the cells are concentrated within relatively few fields of the microscope, the labour of surveying the whole area of one or more smeared slides is avoided. The present paper describes a procedure by which virtually all the cells in a sample of urine may be mounted within a small area. The method is suitable for routine use and has been found satisfactory over a trial period of several months. Most of the sam ples received for screening are, of course, normal: Fig. 1 demonstrates the kind of preparation obtained from normal male urine. It will be appreciated that if, for example, the only abnormal cells in a urine sample were one or two small clumps, their detection would be relatively easy compared with the likelihood of observing them in one of several possible smears occupying a total area perhaps fifty times greater. The working time required per sample is wholly comparable to the smear technique when account is taken of the elimination of the tedious scanning of each smear. A technician, working alone and using a six-place centrifuge, mounts and stains the whole cell content of 12 urine samples in about o e and a half hours ; examination takes only a few minutes. Thus the whole procedure, including examination, takes no longer than the smear tech nique, and the much larger number of cells examined per patient seems likely to improve diagnostic accuracy, particularly in cases where only a very few suspicious or malignant cells are being exfoliated. The time taken to carry out the test for microscopic haematuria (Oppenheimer, 1920; Crabbe, et al., 1956) could be saved, as erythrocytes also appear in the preparation.