Federal polices affecting vaccine research and production.

The federal government is the single most important determinant of the extent of vaccine research, development, and use in the United States. Federal actions having a positive effect include the finacing of vaccine research and development and of major public immunization programs. Federal policies that may be contributing to a decline in the private sector's commitment to vaccine development include an unwillingness to resolve certain liability issues. The nation depends heavily on vaccines to prevent several childhood diseases. For that and other reasons, decisive government efforts are needed to help stimulate the creation of new vaccines and to ensure the continued supply and use of existing safe and efficacious vaccines.

Comparison of nuclear DNA content in primary and metastatic papillary thyroid carcinoma.

Nuclear DNA values were determined in 40 primary papillary thyroid carcinomas, as well as in 52 corresponding local recurrences and metastases were observed either at the time of diagnosis or up to 20 years later. The patient population consisted of 34 survivors and 6 nonsurvivors. In survivors, both the primary tumors and their recurrences and metastases exhibited a majority of cells with DNA values within the normal diploid region, whereas nonsurvivors showed increased and scattered DNA values. In all cases, the primary tumors and the corresponding recurrences and metastases showed similar DNA distribution patterns even if many years had passed between the detection of the primary tumor and the metastases. The results indicate that in papillary thyroid carcinomas, the DNA distribution patterns in the primary tumor and the corresponding recurrences or metastases are generally similar throughout the entire period of disease.

Identification and characterization of non-dividing cell populations in phase II cultures of human glial cells.

It has been reported that cultures of normal cells in phase II contain a non-multiplying cell population, the size of which increases with passage number. In phase II cultures of normal human glial cells we have found two subpopulations of non-proliferating cells, one of which has a characteristic morphology, and differs from the actively dividing cells in a number of respects: (1) they are larger although of various sizes and are well spread over a very large substratum area: (2) they contain a great number of granules showing acid phosphatase activity, being heavy metal positive and displaying the characteristic natural fluorescence of lipofuscin pigment; and (3) they frequently contained a central somewhat irregular nucleus with various numbers of darkly staining nucleolar-like structures. Cytophotometric nuclear DNA measurements of the described "large" cell population show a decreased proportion of diploid cells as compared to their smaller sister cells. Moreover, with increasing passage number, the DNA values for large cells shift towards higher ploidy levels resulting in a scattered aneuploid pattern in the oldest passage. This "large" cell subpopulation consists of between 2% and 3% of all passages and becomes greatly decreased following subcultivation. The other subpopulation of non-dividing cells is generally morphologically similar to the dividers, increases in size with passage number and is the more important in the phase III phenomenon.

Biologic considerations and operative strategy in papillary thyroid carcinoma: arguments against the routine performance of total thyroidectomy.

Reasons cited for the routine performance of total thyroidectomy in patients with papillary thyroid carcinoma include: fear of multicentric neoplastic foci causing local recurrence and death; risk of anaplastic transformation of unresected multifocal microscopic carcinoma; toxicity of high-dose radioactive iodine to ablate normal thyroid remnants; and lack of reliable criteria for grading malignancy and identifying patients at high risk. However, autopsy studies have detected microscopic foci of papillary thyroid cancer as incidental findings in up to 24% of patients dead of other diseases. The prevalence of anaplastic transformation of papillary thyroid carcinoma as determined from reports in the literature is less than 1%. A retrospective investigation of 90 patients with papillary thyroid carcinoma derived from the Swedish National Cancer Registry showed no complications from radioiodine ablation of postoperative thyroid remnants in 45 patients. Retrospective analysis of the DNA content of tumors at the time of the initial operation showed a significant difference between a group of 10 patients who died of recurrent and metastatic papillary thyroid carcinoma and a group of 16 patients alive at least 10 years after operation despite distant metastases or recurrent cancer in the thyroid bed and/or cervical lymph nodes. The risk of permanent hypoparathyroidism is higher in patients after total thyroidectomy without apparent improvement in survival rates when compared with less extensive resections. Therefore it is proposed that the criteria for total thyroidectomy in patients with papillary thyroid carcinoma be limited to: tumors that clinically involve both lobes of the thyroid gland, extracapsular spread of cancer requiring enbloc resection, and reoperations where scarring prevents accurate delineation of the extent of the tumor. By differentiating patients at high risk for death from papillary thyroid carcinoma from patients at low risk, the measurement of DNA content may decrease the need for routine total thyroidectomy.

Expression of the myc protooncogene in canine rhabdomyosarcoma.

The expression of the protooncogene c-myc in a canine rhabdomyosarcoma was examined. It was found that this highly malignant tumour contained vast quantities of RNA that hybridized with a cDNA probe for c-myc. Restriction fragment length analysis after endonuclease digestion of tumour DNA did not reveal any rearrangements in this gene locus. The potential role of this oncogene in the development of canine rhabdomyosarcoma is discussed.

Reoperation for primary hyperparathyroidism.

The reasons for failure of the initial exploration and the results of reoperation were analyzed in 53 patients with a diagnosis of primary hyperparathyroidism, 29 of whom were referred after initial operations elsewhere. Seventy-nine reoperations were performed. Sternotomy was used in 15 patients, and in retrospect was necessary in only 5. There was no operative mortality. The reasons for initial failure were incorrect diagnosis in 6 patients, true recurrence in 4 and persistent disease in 43. Persistence was caused by surgical failure in two thirds and pathology failure in one third. Of 47 patients reoperated on for hyperparathyroidism, 39 (83 percent) were cured, a rate warranting this type of surgery. Analysis of a long-term series of initial operations demonstrates a persistence rate of 5 percent (24 of 461) and a recurrence rate of 1 percent (4 of 461) in this disease. The need for reoperation was les than 1 percent over the recent 5 year period.

Endometriosis of lung and pleura diagnosed by aspiration biopsy.

A case of intrathoracid endometriosis with pulmonary and pleural localizations is reported. The use of the aspiration biopsy technique for diagnosis is illustrated with cytologic and histologic evidence.

Planimetric studies on fine needle aspirates from follicular adenoma and follicular carcinoma of the thyroid.

A planimetric study was performed on fine needle aspiration biopsy smears from 21 follicular thyroid adenomas, 13 follicular thyroid carcinomas and 7 nontoxic goiters. The nuclear and the cytoplasmic projected areas were measured in each smear on 50 cells with intact nuclei. The nuclear-cytoplasmic area was calculated. Significant differences in mean nuclear area were found between benign and malignant follicular neoplasms and between neoplastic cells and cells from nontoxic goiter. Planimetry of cells aspirated from follicular neoplasms permitted differentiation between carcinomas and adenomas with a high degree of statistical probability.

The cytology of a giant-cell, osteoclastoma-like malignant thyroid neoplasms. A case report.

The cytologic findings on aspirated material in a rare giant-cell, "osteoclastoma-like," malignant neoplasm of the thyroid are reported.

Cost effectiveness and cost benefit of vaccination against pneumococcal pneumonia: implications for clinical practice.

The economic techniques of cost-effectiveness and cost-benefit analysis have provided useful insights into the potential advantages of vaccination against pneumococcal pneumonia. They suggest that the cost of vaccinating persons 65 years and older and perhaps younger persons with high risk conditions would be reasonable when compared with the cost of treatment for pneumococcal pneumonia. These findings, together with other considerations, may guide physicians and health care policymakers in deciding which individuals might be expected to benefit from pneumococcal vaccination.

Fine-needle aspiration cytology in thyroid disease.

Fine-needle aspiration biopsy of palpable lesions of the thyroid is a diagnostic method routinely used in several medical centres, but still relatively new in others. Experience has shown that the technical steps involved in this biopsy procedure, that is, palpation, aspiration, smear making, fixation and staining, are critical for good results, and they are therefore reviewed and illustrated. Another prerequisite for the use of aspiration biopsy cytology is a specially interested cytopathologist who is familiar with the methodological aspects, as well as the interpretation of cells in aspirates. A description is given of the different cytological patterns in smears of fine-needle aspirates for clinical thyroid diseases, such as simple and toxic goitre, different types of thyroiditis (acute, subacute and chronic) as well as the various differentiated thyroid neoplasms (follicular, papillary, medullary), anaplastic carcinomas and lymphomas. The limits of cytological diagnosis are indicated and differential diagnostic aspects are discussed. diagnostic accuracy of aspiration biopsy cytology, with particular reference to tumour diagnosis, is high: no false positive diagnoses are made by experienced cytopathologists, whereas false negative tumour diagnosis can occur in about 10 per cent of cases. Such results are the reason for the special position of fine-needle aspiration biopsy among other methods in the diagnostic work-up of patients with thyroid disease.

Transrectal fine-needle aspiration biopsy for cytologic diagnosis and grading of prostatic carcinoma.

In this article, the Karolinska experience of transrectal fine-needle aspiration biopsy of prostatic carcinoma, which now extends over more than twenty years, is evaluated. The cytologic criteria for diagnosing prostatic carcinoma in aspirates are well defined. While accuracy for cytodiagnosis is similar to that of histopathologic diagnosis, fine-needle aspiration is a less traumatic, cheaper procedure compared with histologic biopsy methods. Accuracy depends very much upon the skill of the examiner taking the cell samples and on the alertness of the cytopathologist for possible diagnostic pitfalls. Cytologic grading of prostatic carcinoma into well, moderately, and poorly differentiated types has been shown to be correlated significantly not only to histopathologic grading, but also to clinical stage, response to hormonal therapy and survival. The degree of tumor differentiation is well reproduced by independent observers. Cytochemical parameters, such as DNA measurement, constitute a potential refinement of cytologic grading, especially in moderately differentiated carcinomas. In medical centers with long experience of fine-needle aspiration biopsy, the method has a central role in diagnosis and management of prostatic carcinoma, including posttherapy follow-up.

Aspiration biopsy cytology of the pancreas.

The cytology of benign and neoplastic conditions of the pancreas in fine needle aspirates is reviewed. A series of 40 fine needle biopsies of the pancreas performed at Karolinkska Hospital, Stockholm, in the period 1969--1978 confirms that the method is virtually free from complications. The diagnostic accuracy of peroperative fine needle aspiration of pancreatic carcinoma was 82% and for transbdominal aspiration 71%. No false positive diagnoses were noted. The most important factors influencing diagnostic accuracy are experience with correct biopsy technique, multiple punctures and tumor size.

The role of fine-needle aspiration cytology in the management of thyroid disease.

Fine-needle aspiration cytology of the thyroid gland is a low-cost office procedure which even in children does not require regional anaesthesia. The method is safe, without appreciable complications or side effects. Since the needling is readily accepted by patients, it can be repeated when necessary. A morphological diagnosis is then rapidly obtainable, and time-consuming and expensive investigations are bypassed. In the hands of experienced cytopathologists, fine-needle biopsy is a reliable means of selecting patients for surgery, thereby reducing the frequency of operations for benign lesions. The cytological report enables the clinician to recognize the conditions which will benefit from non-surgical management, for example colloid goitre, thyroiditis and lymphoma, and also to plan surgical strategy in papillary, medullary and anaplastic giant cell neoplasms. In follicular neoplasms, aspiration biopsy cytology does not permit reliable distinction between adenoma and carcinoma. With combined consideration of aspiration biopsy cytology and scintiscans, however, it is possible to distinguish non-neoplastic from neoplastic follicular proliferation. In cases where cytological study does not give a specific or conclusive diagnosis, broad disease categories such as inflammatory or neoplastic states can be recognized. Even for these patients, therefore, the method can serve as a guide in the further management. In post-therapy follow-up of thyroid neoplasms, aspiration biopsy cytology permits rapid detection of recurrence.