Fungi in megakaryocytes. An unusual manifestation of fungal infection of the bone marrow.

When fungi infect the bone marrow, typically they are associated with granuloma formation and/or necrosis, and the fungi are found within histiocytes or admixed with necrotic debris. Recently two bone marrow biopsy specimens were encountered in which fungi were confined to the cytoplasm of megakaryocytes, a finding not previously reported in the literature. The first case was that of a 46-year-old man with pulmonary histoplasmosis and no known immunodeficiency. The second was that of a 38-year-old man with the acquired immune deficiency syndrome and cryptococcal meningitis. In the first case, many megakaryocytes contained fungal forms consistent with Histoplasma. In the second, one small cluster of megakaryocytes contained several budding yeast consistent with Cryptococcus. Neither marrow biopsy specimen had necrosis, granulomas, or histiocytic infiltration. In both cases, because of the unusual localization of the fungi, they were initially overlooked. The bone marrow may contain fungi even in the absence of abnormalities suggesting fungal infection on routinely stained sections. A silver stain or a periodic acid--Schiff stain should be performed on all marrow biopsy specimens in cases of known or suspected fungal infection outside the marrow. The phenomenon of megakaryocyte emperipolesis is well known, and this process may be responsible for the apparent ability of megakaryocytes to internalize fungi.     

Extensive transmission of Mycobacterium tuberculosis from a child

BACKGROUND AND METHODS: Young children rarely transmit tuberculosis. In July 1998, infectious tuberculosis was identified in a nine-year-old boy in North Dakota who was screened because extrapulmonary tuberculosis had been diagnosed in his female guardian. The child, who had come from the Republic of the Marshall Islands in 1996, had bilateral cavitary tuberculosis. Because he was the only known possible source for his female guardian's tuberculosis, an investigation of the child's contacts was undertaken. We identified family, school, day-care, and other social contacts and notified these people of their exposure. We asked the contacts to complete a questionnaire and performed tuberculin skin tests. RESULTS: Of the 276 contacts of the child whom we tested, 56 (20 percent) had a positive tuberculin skin test (induration of at least 10 mm), including 3 of the child's 4 household members, 16 of his 24 classroom contacts, 10 of 32 school-bus riders, and 9 of 61 day-care contacts. A total of 118 persons received preventive therapy, including 56 young children who were prescribed preventive therapy until skin tests performed at least 12 weeks after exposure were negative. The one additional case identified was in the twin brother of the nine-year-old patient. The twin was not considered infectious on the basis of a sputum smear that was negative on microscopical examination. CONCLUSIONS: This investigation showed that a young child can transmit Mycobacterium tuberculosis to a large number of contacts. Children with tuberculosis, especially cavitary or laryngeal tuberculosis, should be considered potentially infectious, and screening of their contacts for infection with M. tuberculosis or active tuberculosis may be required.     

Effect of physical exercise on adoptive experimental auto-immune encephalomyelitis in rats

The aim of the study was to determine whether different programmes of exercise influence adoptive monophasic experimental auto-immune encephalomyelitis (adoptive EAE), a paralytic disease mediated by T-cells. Adoptive EAE was induced by the transfer of activated encephalitogenic T-lymphocytes into syngeneic recipients (Lewis rats, n = 85) and its development was followed by two independent observers. The results showed that 2 days of severe exercise (250 and 300 min) performed after the adoptive transfer of EAE slightly delayed the onset of the disease (P < 0.008) and the day of its maximal severity (P < 0.016) without affecting the overall severity of the disease. When this programme of exercise was performed before the cell transfer, it had no effect (P > 0.05). Two more moderate exercise programmes (5 × 120 min of running at constant speed or 5 × 60 min of running at variable speed, 5 consecutive days) performed between the adoptive transfer and the onset of the disease did not modify the development of the clinical signs of adoptive EAE (P >0.05). These results showed that severe exercise slightly influenced the effector phase of monophasic EAE and confirmed that physical exercise performed before the onset of experimental auto-immune diseases did not exacerbate the clinical signs.     

Splenic immunomodulation with swimming-induced stress in rats.

In order to determine the effects of swimming-induced stress, young male Wistar rats swam for a single session of 2 h duration, or for one 2-h session a day for five consecutive days. The absolute number of splenic mononuclear cells and the in vitro proliferation of mitogen-stimulated (PHA) T lymphocytes were studied. A single swimming session did not significantly diminish the number of splenic mononuclear cells, but it did significantly reduce splenic T-lymphocyte proliferation. This effect on T-lymphocyte proliferation was significantly blocked, in part, by subcutaneous injection of naltrexone before a swimming session. It was not significantly blocked by pre-exercise oral administration of aminoglutethimide. Repeated swimming sessions induced no significant changes in immune parameters. In conclusion, these data suggest that immunosuppression seen with a single swimming-induced stress period may partly be due to endogenous opioids, and that repetition of the swimming session reduced swimming-induced immunomodulation.     

Increasing access to medical education for students from medically underserved communities: one program's success.

The Premedical Honors College (PHC) is an eight-year, BS-MD program created in 1994 by Baylor College of Medicine (BCM) and The University of Texas-Pan American (UT-PA) to increase the number of physicians addressing the health care needs of underserved populations in Texas. The PHC targets South Texas, a 13-county, medically underserved area with a population that is 82% Hispanic. To date, the PHC has had 159 matriculants and 71 graduates, of whom 60 (84.5%) have matriculated into medical school. These results are significant considering that in 1996, only four students from all five South Texas colleges (combined enrollment of 30000 students) were accepted to medical school. An outcomes study comparing PHC matriculants with students of similar academic ability, ethnicity, and interest in medicine revealed that the odds of medical school matriculation were seven times higher for PHC students than for non-PHC students. The PHC's initial success has been acknowledged by the Texas legislature, which recently passed a bill to promote the PHC's replication. In addition, the number of PHC students-of whom 95% are Mexican American-who matriculate into medical school annually is significant nationally. In 2001, only 386 U.S. medical school matriculants (2.3% of all matriculants) were Mexican American; 17 of these students (4.4%) were PHC graduates. If current trends continue, the PHC could significantly expand the number of physicians serving minority and medically underserved populations in Texas and the nation. Also, the PHC provides an opportunity for research on programs designed to create pathways from high school to medical school.     

Utilization of health statistics in peripheral structures in developing countries]

Health information in developing countries serves mostly to diseases notification and activity registration, but rarely is it used for analyzing the health status of populations or the results of health intervention. Moreover, it is stored at a national level, mainly to fill monthly or yearly reports, and very seldom at a peripheral level where it would be probably more helpful. On the basis of experiences realized in Senegal and Nepal, we try to answer the two following questions: how to make health statistics utilizable, i.e. which criteria of relevance and quality recommend and how to utilize them concretely where they are produced, taking into account their well known limits?     

A comparison of paraganglioma, carcinoid tumor, and small-cell carcinoma of the larynx

Laryngeal paraganglioma, carcinoid tumor, and small-cell carcinoma are rare. Histologically they are similar to analogous tumors in other locations but may be difficult to identify in small biopsy specimens. We compared the light microscopic, histochemical, immunohistochemical, and electron microscopic features of two laryngeal paragangliomas, one carcinoid tumor, and six small-cell carcinomas. The paraganglioma chief cells stained with Grimelius stain and for chromogranin and neuron-specific enolase. The carcinoid tumor cells stained with Grimelius stain and for chromogranin, serotonin, neuron-specific enolase, and keratin. The small-cell carcinoma cells stained for keratin and neuron-specific enolase. The patients with paragangliomas and carcinoid tumor remain healthy through 20 months of follow-up. Four of the patients with small-cell carcinomas have died. Distinction between these tumors is warranted by differing histologic appearances, staining characteristics, and biologic behavior.     

Dual antibiotic loaded bone cement in patients at high infection risks in arthroplasty: Rationale of use for prophylaxis and scientific evidence

In view of the demographic changes and projected increase of arthroplasty procedures worldwide, the number of prosthetic joint infection cases will naturally grow. Therefore, in order to counteract this trend more rigid rules and a stricter implementation of effective preventive strategies is of highest importance. In the absence of a "miracle weapon" priorities should lie in evidence-based measures including preoperative optimization of patients at higher infection risks, the fulfilment of strict hygiene rules in the operating theatre and an effective antibiotic prophylaxis regimen. Instead of a "one size fits all" philosophy, it has been proposed to adjust the antibiotic prophylaxis protocol to major infection risks taking into account important patient-and procedure-related risk factors. A stronger focus on the local application mode via use of high dose dual antibioticloaded bone cement in such risk situations may have its advantages and is easy to apply in the theatre. The more potent antimicrobial growth inhibition in vitro and the strong reduction of the prosthetic joint infection rate in risk for infection patients with aid of dual antibiotic-loaded bone cement in clinical studies align with this hypothesis.     

Functional interaction between entorhinal cortex and basolateral amygdala during trace conditioning of odor aversion in the rat

In rats, conditioned odor aversion (COA) occurs only if the time interval separating the odor from the subsequent intoxication is very short suggesting that the memory trace of the odor is subject to rapid decay. Recent results from our laboratory have found that lesion of the entorhinal cortex (EC), and activation of the basolateral nucleus of the amygdala (BLA) rendered COA tolerant to long interstimulus interval. The present study examined whether the odor memory trace depends on the interaction between the EC and the BLA. Rats lesioned in the EC received infusions of muscimol (a GABA(A) receptor agonist) into the BLA immediately after the odor presentation during acquisition of COA. Injection of muscimol into BLA prevented tolerance of COA to long interstimulus interval induced by EC lesions. This suggests that EC modulates the short-term memory trace of the odor by controlling the GABAergic activity of the BLA during acquisition of COA.