Immunohistochemical and ultrastructural analysis of dysplastic epithelium of human ocular surface: basement membrane and intermediate filament.

PURPOSE: The dysplastic corneal epithelium is characterized by the abnormal proliferation of epithelial cells. The phenotypes of these cells have not been elucidated. We investigated whether such epithelium expresses the phenotypes of corneal or conjunctival epithelial cells. METHODS: The corneas and conjunctivae from four normal subjects and from one patient with epithelial dysplasia of the central cornea were immunostained for IV and VII collagens and for cytokeratins. Monoclonal antibodies against collagen IV reacted to the [alpha1(IV)]2alpha2(IV) or alpha5(IV) molecule. Anti-cytokeratin antibodies were used to define epithelial cell types. The ultrastructure of the basement membrane (BM) of each specimen also was examined. RESULTS: Type VII collagen immunoreactivity was detected in all the specimens of epithelial BM. The anti-collagen IV [alpha1(IV)]2alpha2(IV) antibody labeled the conjunctival BMs, not the BMs of the corneal epithelia, of each subject. The normal corneal epithelial BM, not the BM of the conjunctival or dysplastic corneal epithelium, was immunolabeled with anti-alpha5(IV) antibody. The pattern of cytokeratin expression in the corneal epithelial dysplasia resembled that seen in the normal conjunctivae. Small breaks in the BM of dysplastic corneal epithelium were ultrastructurally revealed. The number of hemidesmosomes in the dysplastic corneal epithelium was decreased as compared with that in the normal BM. CONCLUSION: The composition of collagen types within the BM and the cellular phenotype of the dysplastic epithelium in the cornea resembled those of conjunctival epithelium, not of the cornea.     

Accuracy of a rapid 10-minute carbon-14 urea breath test for the diagnosis of Helicobacter pylori-associated peptic ulcer disease

Urease in the human gastric mucosa is a marker for infection with Helicobacter pylori (HP), an organism which is associated with peptic ulcer disease. To detect gastric urease, we examined 184 patients (144 males, 40 females; mean age: 49.8±15.6 years) with suspected peptic ulcer disease. Fasting patients were given orally 5 Ci of carbon-14 labelled urea. From each patient only one breath sample was collected in hyamine at 10 min. The amount of ¹⁴C collected at 10 min was expressed as follows: [(DPM/mmol CO₂ collected)/(DPM administered)] × 100 × body weight (kg). The presence of HP colonization was determined by examination of multiple endoscopic prepyloric antral biopsy specimens subjected to culture or a rapid urease test. For the purpose of this study, HP-positive patients were defined as those with characteristic bacteria as indicated by a positive result of either the culture or the rapid urease test; HP-negative patients were defined as those with negative findings on both the culture and the rapid urease test. Of the 184 cases, 99 (53.8%) were positive for HP infection, and 85 (46.2%), negative. The sensitivity and specificity of the rapid 10 min ¹⁴C-urea breath test for the diagnosis of HP-associated peptic ulcer disease were evaluated by a receiver operating characteristic (ROC) curve with a variable cut-off value from 1.5 to 4.5. When a cut-off value of 1.5 was selected, the sensitivity was 100% and the specificity, 83.5%; when a cut-off value of 4.5 was selected, the sensitivity was 54.5% and the specificity, 97.6%. Correspondence to: Chia-Hung Kao     

Time course of satisfaction of search

"Satisfaction of search" (SOS) refers to the effect in which a second lesion remains undetected after detection of another lesion on the same radiograph. The objective of this study was to clarify our understanding of SOS by relating it to total time of inspection and time intervals before, between, and after discovery of lesions. Detection accuracy of native lesions in chest radiographs, before and after the addition of a simulated nodular lesion, was measured for ten observers. Analysis of data from this and a previous experiment showed that average perceptual accuracy of individual receiver operating characteristic curves was significantly reduced with the addition of the nodules. Plots and analyses of search time revealed that, on average, during a typical 46-second inspection of a case, simulated nodules were found at 18 seconds, native abnormalities at 25 seconds, and false positives occurred at 33 seconds. Time needed to find nodules did not depend on whether native lesions were present; time to find native lesions did not change with addition of nodules; and total search time was the same for images with one, two, or no lesions. The detection results show that the SOS effect was obtained, but that interrupting search in order to measure it also diminishes accuracy. Analysis of the time course data relates SOS to perceptual capture and strategic halting of search.     

Dopamine distribution and behavioral alterations resulting from dopamine infusion into the brain of the lesioned rat

In an effort to verify the "dopamine secretion hypothesis" as the mechanism responsible for the antiparkinsonian efficacy of adrenal medullary transplants into the brain, the effects of dopamine infusion into the brains of rats with unilateral substantia nigra lesions were examined. The apomorphine-induced rotation, characteristic of this animal model, was diminished after 7 days of continuous dopamine infusion (10 micrograms/hr) into the ipsilateral striatum, whereas intraventricular infusion was without effect. Chromatographic analysis of the dopamine distribution after 10 days of infusion into either region revealed that ipsilateral delivery of dopamine did not result in contralateral increases in dopamine content. Examination of the adjacent striatum following ipsilateral intraventricular delivery indicated that dopamine had only penetrated 1 mm. Even with intrastriatal delivery, there were still parts of the infused striatum which had below-normal levels of dopamine. The fact that striatal tissue presents a significant barrier to the penetration of dopamine is discussed in relation to adrenal medullary and fetal nigral transplants.     

The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective.

Current regulatory guidances do not address specific study designs for in vitro and in vivo drug-drug interaction studies. There is a common desire by regulatory authorities and by industry sponsors to harmonize approaches, to allow for a better assessment of the significance of findings across different studies and drugs. There is also a growing consensus for the standardization of cytochrome P450 (P450) probe substrates, inhibitors and inducers and for the development of classification systems to improve the communication of risk to health care providers and to patients. While existing guidances cover mainly P450-mediated drug interactions, the importance of other mechanisms, such as transporters, has been recognized more recently, and should also be addressed. This article was prepared by the Pharmaceutical Research and Manufacturers of America (PhRMA) Drug Metabolism and Clinical Pharmacology Technical Working Groups and represents the current industry position. The intent is to define a minimal best practice for in vitro and in vivo pharmacokinetic drug-drug interaction studies targeted to development (not discovery support) and to define a data package that can be expected by regulatory agencies in compound registration dossiers.     

Postero-medio-anterior approach of the ankle for the pilon fracture

A good view of the operative field is important for better reduction and fixation in surgical treatment of fractures. The exposure of the ankle joint for the pilon fracture is commonly through the anterior approach, or combined with the medical approach. But sometimes it is still difficult to have complete viewing of the articular surface and to apply internal fixation by that approach. In recent years, we developed a "postero-medio-anterior" approach of the ankle joint by one incision. This approach provides an excellent exposure of the anterior, medial and posterior aspects of the ankle joint with a clear view of the articular surface. In our 45 cases of pilon fracture during 1991 to 1995, there was no incisional injury to the neurovascular bundle. Superficial wound edge necrosis was noted in two cases which healed later without further procedure. Therefore, we recommend this approach as a simple and reliable incision for open reduction of pilon fractures.     

Blunt hepatic injury: minimal intervention is the policy of treatment

BACKGROUND: Many publications recommend nonoperative treatment for stable blunt hepatic injury patients. Unstable hemodynamic status is the only indication for surgery. When operation is indicated, controversies exist regarding which operative procedure will be more beneficial to the patients. The purposes of this study are to compare the results of operative and nonoperative management of patients with blunt hepatic injuries and to identify the optimal surgical approach when surgery is indicated. METHODS: Different prospective protocols of treating adult blunt hepatic injuries were conducted. From 1992 to 1993 (group I), urgent surgery would be performed in the presence of hemoperitoneum. The policy shifted to aggressive nonoperative approach between 1996 and 1997 (group II). The patients from each period were divided into three subgroups. Group A included the patients who received nonoperative treatment in either period. Group B consisted of the patients who received surgery in the first period and nonoperative management in the second period. Group C included the patients who were operated on in either group. Comparisons were made between matched groups. RESULTS: Groups IA and IIA patients had minor injuries and could be successfully treated nonoperatively. The results of groups IB and IIB were similar concerning hospital stay, morbidity, and mortality. Transfusion requirements of group IIB patients were significantly higher (2.2 vs. 1.1 units,p = 0.01) than those of group IB. However, 25 (58%) celiotomies of group IB patients were nontherapeutic. When surgery was indicated, group IC patients had significantly higher liver-related mortality (14 of 49 vs. 3 of 55, p = 0.002). Anatomic resection was performed more frequently in that period. CONCLUSION: Nonoperative treatment significantly decreased the rate of nontherapeutic laparotomy but carried the risks of higher transfusion requirements and delaying operation. When surgery was indicated, the policy of minimal intervention positively affected the patients' outcomes. The goal of surgery should be hemorrhage control rather than resection of the injured liver tissues.