105Changes in Nitric Oxide Levels After Deep Dermal injury in the Female,Red Duroc Pig (FRDP)

Introduction : Hypertrophic scar is a devastating sequel to burns and other tangential skin injuries. It follows deep dermal injuries and does not occur after superficial injuries. Nitric oxide (NO) plays many important roles in wound healing from inflammation to scar remodeling. Studies have shown that expression of nitric oxide synthase and nitric oxide production are decreased in human hypertrophic scar. However little is known about NO involvement in the early stages of hypertrophic scarring, because of the lack of an animal model. It was recently reported that the female red Duroc pig (FRDP) makes thick scar, which is similar to human hypertrophic scar. We hypothesized that NO production in wounds on the female, red Duroc pig is similar to that of human hypertrophic scar and that NO involvement in deep wounds is different from that in superficial wounds. Methods : Superficial (0.015” to 0.030”) and deep (0.045” to 0.060”) wounds were created on the backs of four FRDPs. Biopsies were collected at weeks 1.5, 4, 8 and 21 post wounding including samples of uninjured skin. Nitric oxide levels were measured with the Griess reaction assay and normalized with tissue protein level. Results : Superficial wounds healed with an invisible scar whereas the deep wounds healed with scar resembling mild hypertrophic scar. The thickness of the scars from the deep wounds was significantly greater than uninjured skin and healed superficial wounds (p < 0.01). NO levels were increased at 1.5 weeks in deep wounds compared to superficial wounds and uninjured skin (p < 0.05). At 8 weeks, NO levels in deep wounds had returned to the level of uninjured tissue and superficial wounds. By 21 weeks, NO levels had decreased significantly when compared to superficial wounds (p < 0.01). There were no differences in NO levels between uninjured skin and superficial wounds at any time point (p > 0.05). Conclusions : NO production is similar in late, deep wounds on the female, red Duroc pig to that reported in the literature for human hypertrophic scar further validating this animal model. NO production is quite different after deep wounds as compared to superficial wounds in the FRDP. Early elevation in nitric oxide production might account for excessive inflammation in deep wounds that become thick scars in the FRDP. Nitric oxide regulators and effects at early stages of scar formation should be elucidated further and the FRDP appears to be a useful model.     

Dr. William O. Coffee and his absorption cure for cataract

Dr. William O. Coffee was an ophthalmologist who conducted an office and mail-order practice in the Midwest from the 1880s until 1927. His main stock in trade was a self-discovered absorption cure for a variety of ocular diseases, with particular emphasis on the medical cure of cataracts. Dr. Coffee's career was a checkered one, marked by dubious credentials, exuberant self-promotion, unlikely and exaggerated claims of medical successes, plagiarism, and rejection by the medical "establishment." Certain parallels may be drawn between his activities and some currently observed practices in ophthalmology.     

Effect of previous supramaximal work on lacticaemia during supra-anaerobic threshold exercise

Summary Twelve male and female subjects (eight trained, four untrained) exercised for 30 min on a treadmill at an intensity of maximal O₂ consumption (% O_2max) 90.0%, SD 4.7 greater than the anaerobic threshold of 4 mmol ·1^–1 (Th_an =83.6% O_2max, SD 8.9). Time-dependent changes in blood lactate concentration ([la_b]) during exercise occurred in two phases: the oxygen uptake ( O₂) transient phase (from 0 to 4 min) and the O₂ steady-state phase (4–30 min). During the transient phase, [la_b] increased markedly (l.30 mmol · l ^–1 · min ^–1, SD 0.13). During the steady-state phase, [la_b] increased slightly (0.02 mmol · 1^–1 · min^–1, SD 0.06) and when individual values were considered, it was seen that there were no time-dependent increases in [la_b] in half of the subjects. Following hyperlacticaemia (8.8 mmol -l^–1, SD 2.0) induced by a previous 2 min of supramaximal exercise (120% O_2max), [la_b] decreased during the O₂ transient (–0.118 mmol · 1^–1 · min^–1, SD 0.209) and steady-state (–0.088 mmol · 1^–1 · min ^–1, SD 0.103) phases of 30 min exercise (91.4% O_2max, SD 4.8). In conclusion, it was not possible from the Th_an to determine the maximal [la_b] steady state for each subject. In addition, lactate accumulated during previous supramaximal exercise was eliminated during the O₂ transient phase of exercise performed at an intensity above the Th_an. This effect is probably largely explained by the reduction in oxygen deficit during the transient phase. Under these conditions, the time-course of changes in [la_b] during the O₂ steady state was also affected.     

乳腺管状小叶癌

乳腺管状小叶癌（Tubulolobular carcinoma，TLC）最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征，并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁（中位年龄60岁）。1例双侧乳腺受累，5例病变为多灶性。肿瘤直径0．5-2．5cm，色灰褐，质硬。组织学观察：TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂，且两者比例相当（统称为管状小叶模式）。     

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.     

Does the addition of recombinant LH in WHO group II anovulatory women over-responding to FSH treatment reduce the number of developing follicles? A dose-finding study

BACKGROUND: In anovulatory women undergoing ovulation induction, addition of recombinant human LH (rLH) to FSH treatment may promote the dominance of a leading follicle when administered in the late follicular phase. The objective of this study was to find the optimal dose of rLH that can maintain the growth of a dominant follicle, whilst causing atresia of secondary follicles. METHODS: Women with infertility due to anovulation and over-responding to FSH treatment were randomized to receive, in addition to 37.5 IU recombinant human FSH (rFSH), either placebo or different doses of rLH (6.8, 13.6, 30 or 60 microg) daily for a maximum of 7 days. The primary efficacy endpoint was the proportion of patients who had exactly one follicle > or = 16 mm on hCG day. RESULTS: Among 153 enrolled patients, the five treatment groups were similar in terms of baseline characteristics. The proportion of patients with exactly one follicle > or = 16 mm ranged from 13.3% in the placebo group to 32.1% in the 30 microg rLH group (P = 0.048). The pregnancy rate ranged from 10.3% in the 60 microg group to 28.6% in the 30 microg rLH group. Adverse events were similar between groups. CONCLUSIONS: In patients over-responding to FSH during ovulation induction, doses of up to 30 microg rLH/day appear to increase the proportion of patients developing a single dominant follicle (> or = 16 mm). Our data support the 'LH ceiling' concept whereby addition of rLH is able to control development of the follicular cohort.