The diagnostic utility of bone marrow aspiration and biopsy in patients with acquired immunodeficiency syndrome

Diagnostic bone marrow aspiration, biopsy, and culture are useful procedures in the evaluation of patients with suspected or proven acquired immunodeficiency syndrome (AIDS) who are febrile. In as many as one fourth of these patients, the information provided by the bone marrow examination may establish a diagnosis of a disseminated opportunistic infection when other studies are not informative. We have also discovered a previously unreported association between thrombocytopenia and the presence of bone marrow granulomas in our patients with AIDS and suggest that thrombocytopenia may be a clue to enable the clinician to predict a positive bone marrow result more accurately. The explanation for this apparent association remains to be elucidated.     

Pneumococcal sepsis and meningitis in vaccinated subjects: a review of 55 reported cases

Fifty-five cases of the occurrence of serious pneumococcal infections in both splenectomized and nonsplenectomized individuals who received pneumococcal vaccine were reviewed from the literature. Reasons for vaccine failure included the occurrence of non-vaccine-type pneumococcal infections (18 cases), possible poor antibody response to the vaccine, especially if it is given postsplenectomy and/or following intensive steroid or other immunosuppressive therapy, and decline in antibody titer over time. Although the total number of vaccinated individuals is unknown, the overwhelming majority of the many thousands of vaccinees have been successfully protected with pneumococcal vaccine. In spite of very rare vaccine failures, pneumococcal vaccination (and perhaps penicillin prophylaxis) is strongly recommended for patients at high risk of developing serious pneumococcal infections, including all individuals undergoing splenectomy for any reason, or for those who have had a splenectomy or have functional asplenia.     

More than economism: the politics of workers' safety and health, 1932-1947

Even within the context of the New Deal, an agency of the Department of Labor was unusual for its innovations and activism. The Division of Labor Standards went beyond the economism of hours and wages to the advocacy of a safe and healthy work place. Unlike the Public Health Service, the division eschewed the "neutrality" of research and information gathering; it sought to intervene, directly and through the states, in the work place. The end of World War II unleashed a conservative reaction that restrained government's responsibility for several decades.     

Predicting recurrence in axillary-node negative breast cancer patients

Summary This study attempted to identify the risk groups in axillary node negative breast cancer patients using validated first-generation prognostic clinical and pathologic factors. An updated 10-year follow-up in 407 such patients treated by surgery alone at Roswell Park between 1976–1987 showed a 10-year recurrence rate (RR) of 19% (95% confidence interval ±5%). Predictors of outcome were, in order of strength: (1) Tumor size (p= 0.0006); RR at 10 years was 2% ± 4 for tumors 0.5cm, 6% ± 7 for tumors 0.6-1.0cm, 16% ± 9 for 1.1–2cm, 29% ± 12 for 2.1–5cm, and 40% ± 31 over 5cm; (2) Histologic differentiation (p = 0.017); poorly differentiated/anaplastic (P/A) tumors had a greater RR (24% ± 8) than well or moderately differentiated (W/M) tumors (13% ± 8); (3) Age (p = 0.046); patients < 35 showed a RR of 28% ± 20, pts 35–50, 22% ± 10, and pts > 50, 17% ± 7 (p = 0.046). Cox Model analysis showed tumor size (4 groups) significant at < 0.0001, histologic differentiation (2 groups) significant at < 0.0005 after allowing for size, and age (±50) significant at <0.05 after allowing for size and differentiation.Combining these variables into subgroups enables selecting groups at various risks of recurrence. Groups with low risk are: (1) patients with tumor1cm, W/M (0% RR), (2) patients with ductal carcinomain situ with microinvasion (0% RR), and (3) patients with tumors 1cm, P/A (8% RR). In a suggestive finding in this last group, those over age 50 achieved a RR of 3% ± 6, while those age 50 or less had RR 14% ± 15. With the exception of this last group, all should be considered highly curable using loco-regional therapy alone, and might be spared the risks and costs of routine systemic adjuvant therapy. Groups with high risk are: (1) patients with tumors > 2cm (RR 32% ± 12), and (2) patients with tumors 1.1–2cm, P/A (RR 21% ± 14). These should receive adjuvant therapy. Groups with intermediate risk are patients with tumor 1.1-2cm, W/M (RR 12% ± 12). In a suggestive finding, those in this group over age 50 had a RR of 11% ± 12, while those up to 50 had a RR of 17% ± 30. These patients should be considered to be prime candidates for clinical trials.Adding second generation factors such as DNA ploidy or S-phase fraction to first generation factors should provide additional information on which to base therapy decisions, particularly in the gray area of intermediate risk. Our study indicates that node-negative breast cancer patients represent a heterogeneous population in terms of risk and prognosis, and that an individualized approach to adjuvant therapy should be taken.Presented in part at the 14th annual San Antonio Breast Cancer Symposium, December 6-7, 1991, and the American Association for Cancer Research, San Diego, CA, May 20-23, 1992     

Efficacy of topical gentamicin treatment after 193-nm photorefractive keratectomy in an experimental Pseudomonas keratitis model

Background: The treatment of Pseudomonas keratitis has many limitations, and further investigation to identify more effective approaches is required. We therefore studied the possible contribution of the debridement effect of 193-nm excimer laser on Pseudomonas keratitis in rabbit eyes. Methods: Pseudomonas keratitis was induced in 30 rabbit eyes by inflicting controlled central corneal scratches and applying a drop of Pseudomonas aeruginosa suspension. After 24 h, one cornea of each animal was photo-ablated (excimer laser: fluency 90 mJ/cm², 10 Hz, 213 pulses), yielding 50 m of tissue ablation, while the follow cornea served as control. Five groups of six animals each were formed and received: a subconjunctival injection of gentamicin 20, mg (group 1), topical 14 mg/ml gentamicin hourly (group 2) or every 2.5 h (group 3), or NaCl 0.9% hourly (group 4) for 8 h. In group 5, animals were sacrificed without additional treatment. After 9 h corneas were excised, homogenized, serially diluted, and plated on agar blood plates. The numbers of colony-forming units (CFU) per cornea were statistically evaluated (Mann-Whitney test). Results: In control eyes, a greater decrease of CFU was observed in group 2 than in group 3 (P = 0.03). In laser-ablated eyes, there was no difference in CFU between groups 2 and 3. Comparison of the excimer-treated and control eyes revealed a greater number of bacteria (CFU) in controls only in group 3 (P=0.02). Conclusion: Our study suggests that controlled debridement of cornea with excimer laser may improve the effect of topical antibiotics.Presented at ECORA First Annual Meeting, 5 October 1993, Bonn, Germany     

The limits of thresholds: silica and the politics of science, 1935 to 1990.

Since the 1930s threshold limit values have been presented as an objectively established measure of US industrial safety. However, there have been important questions raised regarding the adequacy of these thresholds for protecting workers from silicosis. This paper explores the historical debates over silica threshold limit values and the intense political negotiation that accompanied their establishment. In the 1930s and early 1940s, a coalition of business, public health, insurance, and political interests formed in response to a widely perceived "silicosis crisis." Part of the resulting program aimed at containing the crisis was the establishment of threshold limit values. Yet silicosis cases continued to be documented. By the 1960s these cases had become the basis for a number of revisions to the thresholds. In the 1970s, following a National Institute for Occupational Safety and Health recommendation to lower the threshold limit value for silica and to eliminate sand as an abrasive in blasting, industry fought attempts to make the existing values more stringent. This paper traces the process by which threshold limit values became part of a compromise between the health of workers and the economic interests of industry.     

Safety of <7500 RE (<25000 IU) vitamin A daily in adults with retinitis pigmentosa

BACKGROUND: Vitamin A supplementation is being used successfully to treat some forms of cancer and the degenerative eye disease retinitis pigmentosa. The daily biological need for vitamin A is estimated to be 800 retinol equivalents (RE)/d (2667 IU/d) for adult women and 1000 RE/d (3300 IU/d) for adult men; doses > or = 7500 RE (> or = 25000 IU)/d are considered potentially toxic over the long term. OBJECTIVE: We assessed the safety in adults of long-term vitamin A supplementation with doses above the daily biological need but <7500 RE (<25000 IU)/d. DESIGN: Adults aged 18-54 y with retinitis pigmentosa but in generally good health (n = 146) were supplemented with 4500 RE (15000 IU) vitamin A/d for < or = 12 y (group A) and compared with a similar group (n = 149) that received 23 RE (75 IU)/d (trace group). Mean total consumption of vitamin A in group A was 5583 RE (18609 IU)/d (range: 4911-7296 RE/d, or 16369-24318 IU/d) and that in the trace group was 1053 RE (3511 IU)/d (range: 401-3192 RE/d, or 1338-10638 IU/d). RESULTS: Patients in group A showed an 8% increase in mean serum retinol concentration at 5 y and an 18% increase at 12 y (P < 0.001); no retinol value exceeded the upper normal limit (3.49 micromol/L, or 100 microg/dL). Mean serum retinyl esters were elevated approximately 1.7-fold at 5 y and remained relatively stable thereafter. No clinical symptoms or signs of liver toxicity attributable to vitamin A excess were detected. CONCLUSIONS: Prolonged daily consumption of <7500 RE (<25000 IU) vitamin A/d can be considered safe in this age group.     

Obsessive-compulsive symptoms in Prader-Willi and "Prader-Willi-Like" patients

OBJECTIVE: To compare obsessive-compulsive (OC) symptoms in patients with Prader-Willi syndrome (PWS) and symptoms in a group of patients presenting with "Prader-Willi-like" features but without the genetic abnormalities associated with PWS. METHOD: 16 patients aged 4 through 20 years were evaluated in a clinic specializing in the assessment and management of behavioral and food-related problems in PWS. Eight patients were found to have key features of the syndrome but did not have a PWS genotype. These PWS-like subjects were matched to 8 clinic patients with a confirmed deletion of the PWS critical region of the paternally derived chromosome 15. All subjects were evaluated for obesity, IQ, food-related problems, maladaptive behaviors, and non-food-related OC symptoms. RESULTS: There were no differences between the 2 groups with respect to measures of obesity, IQ, food-related difficulties, or overall maladaptive behaviors. The PWS group showed significantly greater numbers of OC symptoms and greater symptom severity. CONCLUSIONS: Patients with PWS have elevated numbers of OC symptoms and significant symptom-related impairment which are not explained by developmental delay, food-related difficulties, or obesity. OC symptoms are part of a behavioral phenotype that accompanies deletions on the proximal long arm of chromosome 15 in PWS.