Trophic effects of unsulfated cholecystokinin on mouse pancreas and human pancreatic cancer.

The effect of unsulfated cholecystokinin on pancreatic growth was evaluated in two experimental models in vivo and in vitro. Mice were injected with sulfated cholecystokinin (CCKs) or unsulfated cholecystokinin (CCKu) (10 or 20 micrograms/kg) or vehicle twice daily for 15 days. Animals were then killed and pancreatic weights, protein, amylase, and DNA content were evaluated. In vitro, growth was evaluated by DNA synthesis and viable cell counts. MIA PaCa-2 and BxPC-3 human pancreatic cancer cells were treated with CCKs or CCKu (10(-12) to 10(-9) M) for 48 or 72 h in the presence of [3H]thymidine to evaluate DNA synthesis. Viable cell counts were performed on both cell lines grown in the presence or absence of unsulfated CCK (10(-12) to 10(-9) M) for 96 h. Pancreatic weight, protein, amylase, and DNA were significantly increased in animals treated with either CCKs or CCKu. However, pancreatic weight, protein, and amylase were significantly higher in mice treated with CCKs compared to CCKu (p less than 0.005). DNA content and index of hyperplasia were the same whether mice were treated with CCKs or CCKu. CCKu was as potent a stimulus for DNA synthesis as CCKs in MIA PaCa-2 and BxPC-3 cells. Finally, CCKu increased cell counts in both pancreatic cancer cell lines. These data suggest that the mechanisms responsible for CCK-induced growth of normal pancreas and pancreatic cancer may differ from those that regulate secretion.     

Steady-state dose proportionality of a once-a-day sustained-release diltiazem hydrochloride formulation in healthy subjects.

In this open-label, randomized, cross-over study, 12 healthy subjects received four doses of a new sustained-release formulation of diltiazem hydrochloride for six consecutive days. Blood samples were drawn on days 5 and 6 for determination of plasma diltiazem and desacetyldiltiazem levels. The peak concentrations after 120, 240, 360, and 480 mg of diltiazem were 48.1, 112.6, 180.9, and 276.8 ng/ml, respectively, while the mean minimum concentrations were 6.3, 14.6, 24.9, and 44.6 ng/ml. The areas under the concentration-time curves were 702, 1,642, 2,622, and 4,004 ng.hr/ml. Prolonged, continuous absorption of diltiazem was noted over the 24-hour dosing period. The dose-adjusted mean steady-state plasma diltiazem levels after the four doses were significantly different, consistent with diltiazem's nonlinear absorption, but the plasma profiles were similar, indicating that the diltiazem release rate was not dose-dependent. Therapeutic plasma diltiazem levels (greater than or equal to 40 ng/ml) were maintained for 24 hours after the three larger doses. The changes in the pharmacokinetics of desacetyldiltiazem over the four diltiazem doses were similar to those of diltiazem. The number of adverse treatment experiences tended to increase with the higher doses, but none were severe. The results indicate that, according to their pharmacokinetic profiles, doses of 240 mg to 480 mg of diltiazem are suitable for once-daily administration.     

Comparative evaluation of the API 20S system and the automicrobic system gram-positive identification card for species identification of streptococci.

Two commercial methods, the API 20S system (API; Analytab Products, Inc., Plainview, N.Y.) and the Gram-Positive Identification Card (GPI; Vitek Systems, Inc., Hazelwood, Mo.), were evaluated without additional tests for the identification of 241 streptococcus strains. Organisms included 60 beta-hemolytic strains, 36 group D strains, 26 Streptococcus pneumoniae strains, and 119 viridans streptococcus strains. API correctly identified to species 68.3% of beta-hemolytic strains, 86.1% of group D strains, 53.9% of S. pneumoniae strains, and 12.6% of viridans streptococci. This method provided excellent identification of group A and B and S. faecalis strains. Overall, API correctly identified 41.9% of strains to species, with 41.1% good likelihood but low selectivity, 15.8% incorrect, and 1.2% not identified. GPI correctly identified to species 58.3% of beta-hemolytic strains, 97.2% of group D strains, 80.8% of S. pneumoniae strains, and 57.2% of viridans streptococci. Group A, B, and D strains were all accurately identified by this system. Overall, GPI correctly identified to species 66.0% of strains, with 8.7% correct preliminary identification, 20.8% incorrect, and 4.6% not identified. Both methods represent a worthwhile advance in streptococcal identification. Neither system, however, can be recommended for species identification of the viridans group at this time.     

The vasa vasorum and angioplasty

Interruption of flow in the vasa vasorum may lead to medial necrosis and aneurysm formation. The purpose of this study was to determine whether angioplasty produces significant alterations in the morphology or blood flow of the vasa vasorum of the dilated artery. The morphology of the canine vasa vasorum was studied before and after angioplasty; in a separate experiment vessel wall blood flow (VWBF) in canine carotid arteries was measured after angioplasty to determine whether physiologic regulation of the blood flow was disrupted by arterial dilation. No morphologic changes could be demonstrated in the vasa vasorum of the dilated artery; however, VWBF was increased by 1194 +/- 215% (mean +/- standard error, p less than 0.01) between 90 and 120 minutes after angioplasty. VWBF in the adjacent nondilated arterial segment was also increased (720 +/- 177% between 10-30 minutes, p less than 0.01) but returned toward normal after 60 minutes. Adenosine caused a "paradoxical" decrease in VWBF (p less than 0.05) of the dilated arterial segment while causing increased VWBF (p less than 0.05) in the thoracic aorta. Angioplasty appears to produce persistent hyperemia in the dilated arterial wall. A paradoxical response to adenosine suggests that vasa vasorum in the dilated arterial segment are maximally vasodilated. This may be due to mechanical disruption of vasomotor tone or to release of vasoactive substances.     

Longitudinal neurological follow-up of a group of HIV-seropositive and HIV-seronegative hemophiliacs: results from the hemophilia growth and development study

BACKGROUND: Boys and young men with hemophilia treated with factor infusions before 1985 had a substantial risk of acquiring the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome. This study was designed to assess the effects of HIV and hemophilia per se on neurological function in a large cohort of subjects with hemophilia, and to investigate the relationships between neurological disease and death during follow-up. METHODS: Three hundred thirty-three boys and young men (207 HIV seropositive and 126 HIV seronegative) were evaluated longitudinally in a multicenter, multidisciplinary study. Neurological history and examination were conducted at baseline and annually for 4 years. The relationship between neurological variables, HIV serostatus, CD4+ cell counts, and vital status at the conclusion of the study was examined using logistic regression models. RESULTS: The risks of nonhemophilia-associated muscle atrophy, behavior change, and gait disturbance increased with time in immune compromised HIV-seropositive subjects compared with HIV seronegative or immunologically stable HIV-seropositive subjects. The risk of behavior change in immune compromised HIV-seropositive hemophiliacs, for example, rose to 60% by year 4 versus 10% to 17% for the other study groups. Forty-five subjects (13.5%), all of whom were HIV seropositive, died by year 4. Subjects who died had had increased risks of hyperreflexia, nonhemophilia-associated muscle atrophy, and behavior change. CONCLUSIONS: These results indicate that immune compromised, HIV-seropositive hemophiliacs have high rates of neurological abnormalities over time and that neurological abnormalities were common among subjects who later died. By contrast, immunologically stable HIV-seropositive subjects did not differ from the HIV-seronegative participants. Hemophilia per se was associated with progressive abnormalities of gait, coordination, and motor function.     

氯地滴眼液的含量测定

目的：采用ＨＰＬＣ法测定氯地滴眼液中氯霉素和地塞米松磷酸钠的含量。方法：色谱分析条件：ＯＤＳ柱作分析柱,流动相为甲醇／水体系,０￣８ｍｉｎ使用４０％甲醇,８￣１６ｍｉｎ使用６０％甲醇,流速１ｍｌ／ｍｉｎ,０￣９ｍｉｎ２４０ｎｍ紫外检测,：二组分分离良好。各组各组性关系良好,平均回收率氯霉素９９．８％（ＲＳＤ＝１．２％,ｎ＝５）,地塞米松磷酸钠９９．４％（ＲＳＤ＝０．７％,ｎ＝５）,结论：该法用于氯