The clinical laboratory diagnosis of chronic granulomatous disease of childhood.
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Previously, it has been observed that methionine enkephalin and leucine enkephalin contribute to hypoxia-induced pial artery dilation in the newborn pig. It has also been observed that the cyclooxygenase inhibitor indomethacin attenuates hypoxic hyperemia in piglets. The present study was designed to determine the relationship between opioids and prostaglandins in hypoxia-induced pial artery dilation. Newborn pigs equipped with closed cranial windows were used to measure pial artery diameter and collect cortical periarachnoid cerebrospinal fluid (CSF) for assay of opioids and prostaglandins. Hypoxia-induced artery vasodilation was mildly attenuated during moderate hypoxia (PaCO2 approximately 35 mm Hg), while this response was blunted during severe hypoxia (PaO2 approximately 25 mm Hg) by indomethacin, 5 mg/kg iv (23% +/- 1 % vs 18% +/- 1% and 33% +/- 2% vs 21% +/- 2% for moderate and severe hypoxia in the absence and presence of indomethacin, respectively). Hypoxic dilation was accompanied by increased CSF prostaglandin E2 (PGE2) concentration (1260 +/- 37 vs 1734 +/- 67 and 1256 +/- 33 vs 2859 +/- 189 pg/ml for moderate and severe hypoxia, respectively). Similar changes in CSF 6 keto PGF1alpha concentration during hypoxia were also observed. Topical PGE2 (10,100 ng/ml) increased CSF methionine enkephalin (874 +/- 35, 1290 +/- 44, and 1791 +/- 143 pg/ml for control, 10 and 100 ng/ml PGE2 respectively). Similar increases in CSF methionine enkephalin concentration were observed for topical PGI2. Additionally, these two prostaglandins also increased CSF leucine enkephalin concentration. Furthermore, while indomethacin had no effect on the release of CSF methionine enkephalin during moderate hypoxia, it attenuated the release of this opioid during severe hypoxia (786 +/- 27 and 2633 +/- 74 vs 781 +/- 51 and 2467 +/- 52; 926 +/- 15 and 3489 +/- 156 vs 898 +/- 11 and 2314 +/- 124 pg/ml for control and moderate/severe hypoxia before and after indomethacin, respectively). Similar effects of indomethacin on hypoxic release of leucine enkephalin were also observed. These data indicate that prostaglandins contribute to hypoxic pial dilation. Additionally, these data show that prostaglandins release the opioids methionine enkephalin and leucine enkephalin. Finally, these data suggest that elevated prostaglandin concentrations during severe hypoxia release opioids which in turn contribute to hypoxic pial dilation.
A modified skin window system was developed and utilized for examination of the local inflammatory response in the chicken. Data were collected at 2, 4, 6, 8, 12, 24, 28, 32 and 48 hours following wing-web scarification. The first cells observed were heterophils and they remained the predominant type through 32 hours. Mononuclears began infiltrating at a rapid rate of 8 to 12 hours, and by 48 hours they represented slightly more than one-half of the total cells observed. The total number of cells present increased rapidly to a peak at 24 hours, and then declined during the 24 to 48 hour period. The percentage of heterophils and mononuclears showed an inverse relationship throughout the 48 hour period, as appreciable numbers of eosinophils and basophils were not observed. Macrophages were the predominant mononuclear cells. Degranulation of heterophils was extensive in the 2 to 4 hour periods, but was much less common thereafter. As the time after scarification increased, macrophages exhibited; (1) increased cytoplasm to nucleus ratio, (2) increased numbers of phagocytic vacuoles, and (3) a marked tendency to form giant cells. The results obtained in this study were similar to those recorded for mammals, except that the percentage shift toward mononuclears occurred at a faster rate in mammals.
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OBJECTIVE: Stereotactic radiotherapy (ablative radiation) is a modality that holds considerable promise for effective treatment of intracranial and extracranial malignancies. Although tumor vasculature is relatively resistant to small fractionated doses of ionizing radiation, large ablative doses of ionizing radiation lead to effective demise of the tumor vasculature. The purpose of this study was (1) to noninvasively monitor and compare tumor physiologic parameters in response to ablative radiation treatments and (2) to use these noninvasive parameters to optimize the schedule of administration of radiation therapy. METHODS: Lewis lung carcinoma tumors were implanted into C57BL/6 mice and treated with ablative radiation. The kinetics of change in physiologic parameters of a response to single-dose 20-Gy treatments was measured. Parameters studied included tumor blood flow, apoptosis, and proliferation rates. Serial tumor sections were stained to correlate noninvasive Doppler assessment of tumor blood flow with microvasculature histologic findings. RESULTS: A single administration of 20 Gy led to an incomplete tumor vascular response, with subsequent recovery of tumor blood flow within 4 days after treatment. Sustained reduction of tumor blood flow by administering the successive ablative radiation treatment before tumor blood flow recovery led to a 3-fold tumor growth delay. The difference in tumor volumes at each measurement time point (every 2 days) was statistically significant (P=.016). CONCLUSIONS: This study suggests a rational design of schedule optimization for radiation-mediated, vasculature-directed treatments guided by noninvasive assessment of tumor blood flow levels to ultimately improve the tumor response.
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In 7 patients with less than 4 months of regular hemodialysis treatment (RDT), in 28 patients with more than 4 months RDT and in 9 normal subjects, the skin window technic of Rebuck and Crowley was used to study the cellular response and the phagocytic activity of macrophages. Phagocytosis of carbon particles is decreased in the patients with less than 4 months dialysis, whereas it is not significantly different from the normals in those being dialyzed for longer periods.
Following non-specific inflammation, greater numbers of mononuclears than polymorphonuclear leukocytes were found to migrate into a 'skin-window' in patients with late syphilis. This mononuclear preponderance was statistically significant, the normal control subjects showing a preponderance of polymorphonuclears.
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