Effects of acetylcholine, carbachol, and mannitol on rabbit corneal endothelial function as assessed by corneal deturgescence

Background: Anterior chamber miotic solutions are widely used in ophthalmic surgery to induce pupillary contraction. We investigated whether the acetylcholine, carbachol, or mannitol present in perfusing solutions can affect corneal endothelial function. Methods: Freshly dissected deepithelized rabbit corneas were mounted in a Dikstein-Maurice chamber at 36 °C. The endothelial sides were perfused with six solutions: (A) 55 mM (1%) acetylcholine Cl plus modified balanced salts; (B) control for A, with acetylcholine Cl replaced by sucrose; (C) 0.55 mM (0.01%) carbachol Cl plus balanced salts; (D) balanced salts solution (BS; control for C); (E) 3% mannitol plus modified balanced salts; and (F) modified balanced salts (control for E, with mannitol replaced by sucrose). Corneal thickness was followed for 3 h in each experiment. The effect of solution E did not differ from that of solution F. Results: The carbachol-containing solution produced a small increase in corneal thickness compared to the control solution, while the acetylcholine-containing solution resulted in corneal thickness lower than that in control preparations. Conclusion: From these data, acetylcholine is harmless to the endothelium, and may actually stimulate its fluid pump mechanism. Carbachol, on the other hand, appears to have a detrimental effect.     

Vertical Banded Gastroplasty-Gastric Bypass with and without the Interposition of Jejunum: Preliminary Report

Background: The complications of the gastric pouch in gastric bypass surgery are well known. Since the first report of this surgery 30 years ago, new technical aspects that make it safer and more effective have been implemented. Methods: As a modification of gastric bypass, the authors have performed 305 vertical banded gastroplasty-gastric bypass procedures. Two groups of patients underwent the procedure: Group I (n = 206) without a limb of jejunum interposed between the gastric pouch and the excluded stomach, and Group II (n = 99) with a limb of jejunum interposed between the pouch and the stomach. The results regarding excess weight loss and complications of the gastric pouch during the first year after surgery were compared. Results: Age, sex, initial weight, body mass index, and percentage of ideal weight were similar in both groups. Excess weight loss was also similar. The complications in Group I were 1 leak, 3 left subphrenic abscesses, 2 erosive gastritis with bleeding, 1 stenosis of the gastrojejunostomy, 1 perforated ulcer, and 4 marginal ulcers with bleeding. Two patients in Group II developed bleeding from the staple-line. Conclusions: These preliminary data suggest that complications of the gastric pouch can be reduced by interposing a limb of jejunum between the pouch and the excluded stomach. This is an early experience; long-term results are pending.     

Semiconductor diode laser transscleral cyclophotocoagulation versus filtering surgery with Mitomycin-C

Both filtering surgery with Mitomycin-C and diode laser cyclophotocoagulation have proved to be effective alternatives in cases of glaucoma with poor surgical prognosis. The right eyes of 40 pigmented rabbits were randomly divided into 2 groups: Mitomycin-C group underwent filtering surgery with application of 0.4 mg/ml of Mitomycin-C whereas the diode laser (DL) group received 15 applications of 1.8 J (1800 mW. 1000 ms) distributed in 270°. Mean IOP showed statistical differences in two periods between days 3–13 and 45–60 — Mann-Whitney U test — with a higher IOP lowering in the DL group. The comparison of IOP survival curves (Log-Rank test) was not significant p = 0.070809. Ocular hypertension, hyphema and inflammatory signs were higher in the DL group, both in short and long term, but in terms of statistical significance only ocular hypertension showed differences p = 0.00011717 - Fisher exact test. Microscopic examination revealed patent sclerostomies in 60% of the MMC group eyes with different grades of fibroblastic proliferation. In the DL group we observed necrosis of the sclieral stroma and of the pigmented and unpigmented ciliary epithelium, with signs of thermal coagulation of the ciliary stroma and of the stromal vasculature. We must point out that the treatment with laser has proved to be more effective although both treatments showed very acceptable IOP lowering until 2 months after the surgery.     

Identification and characterization of a T-helper peptide from carcinoembryonic antigen.

PURPOSE: The purpose of this research was to identify promiscuous T-helper cell determinants (THd) from carcinoembryonic antigen (CEA) to be used to prime T-cell help for cancer therapy. CEA was selected because this antigen is expressed in an important variety of carcinomas. EXPERIMENTAL DESIGN: Potential promiscuous THd from CEA were predicted using available computer algorithms. Predicted peptides were synthesized and tested in binding experiments to different HLA-DR molecules. Binder peptides were then used to prime T-cell responses both in vitro and in vivo. RESULTS: Twenty 15-mer peptides from CEA were predicted to bind to different HLA-DR molecules. The promiscuous character of these peptides was demonstrated in binding experiments. Fifteen of 20 peptides tested were able to bind to HLA-DR4, but only CEA (625-639) was shown to be presented after processing of recombinant CEA. CEA (625-639) was also found to be presented by HLA-DR53. Moreover, immunization of HLA-DR4 transgenic mice with CEA (625-639) in conjunction with class I epitope OVA (257-264), induced a CTL response specific of OVA (257-264). CONCLUSIONS: CEA (625-639) might be a relevant promiscuous THd peptide for cancer therapy.     

Circulating growth factor levels are associated with tumorigenesis in neurofibromatosis type 1.

PURPOSE: Neurofibromatosis type 1 (NF1) is characterized by systemic development of neurofibromas. Early clinical diagnosis can be ambiguous, and genetic diagnosis can be prohibitively difficult. Dysregulation of a number of growth factors has been suggested to be a mechanism of pathogenesis. This study was performed to assess the contribution of circulating growth factors for diffuse tumorigenesis and the diagnostic value of circulating growth factor identification in serum. EXPERIMENTAL DESIGN: The growth stimulation of neurofibroma-derived cells by serum from NF1 patients was tested, and serum growth factor levels in a cohort of NF1 patients (n = 39) between the ages of 7 and 70 years were analyzed. RESULTS: Concentrations of midkine (MK) and stem cell factor, but not epidermal growth factor, were substantially increased in serum of NF1 patients when compared with healthy controls. Within the NF1 group, MK levels increased dramatically at puberty from an average of 0.79 ng/mL in patients <18 years to 1.18 ng/mL in patients >18 years old. Stem cell factor and MK concentrations above a defined threshold in serum of NF1 patients are of diagnostic benefit for 96% of patients in the cohort tested. Furthermore, serum from NF1 patients enhanced proliferation of human neurofibroma-derived primary Schwann cells and endothelial cells substantially better than normal serum. CONCLUSIONS: Enhanced circulating growth factor levels contribute to diffuse tumorigenesis in NF1 and may provide the basis for molecular diagnosis.     

ZD1839, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, induces the formation of inactive EGFR/HER2 and EGFR/HER3 heterodimers and prevents heregulin signaling in HER2-overexpressing breast cancer cells.

PURPOSE: ZD1839 is a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) that has shown clinical activity against EGFR-expressing tumors. Our aim was to explore the effects of ZD1839 in breast cancer cell lines expressing different levels of EGFR and the closely related HER2 receptor. EXPERIMENTAL DESIGN: We studied the growth-inhibitory effects of ZD1839 in a series of breast carcinoma cell lines. In HER2-overexpressing BT-474 breast cancer cells, we studied the effects of ZD1839 on cell growth and heterodimerization of receptors under basal and ligand-stimulated conditions. RESULTS: ZD1839 was an equally potent inhibitor of growth in breast cancer cells expressing high levels of EGFR and HER2. In BT-474 breast cancer cells, ZD1839 abolished EGF- and heregulin-induced activation of ErbB receptors and downstream signaling molecules. Because ZD1839 does not inhibit the HER2 tyrosine kinase in vitro, and because heregulin is a ligand that activates HER2 by binding to HER3 and HER4 but does not bind to the EGFR, our findings suggested that ZD1839 interfered with HER2 function in intact cells. Searching for mechanisms, we report that ZD1839 induces the formation of inactive unphosphorylated EGFR/HER2 and EGFR/HER3 heterodimers. Furthermore, ZD1839 completely abolishes basal and heregulin-induced formation of active phosphorylated HER2/HER3 heterodimers. CONCLUSIONS: ZD1839 inhibits the growth of HER2-overexpressing breast cancer cells, possibly by sequestration of HER2 and HER3 receptors in an inactive heterodimer configuration with the EGFR. Our findings suggest that there is a strong rationale to conduct clinical trials of ZD1839 in patients with HER2-overexpressing breast tumors.     

Prevention of central venous catheter-related bloodstream infections using non-technologic strategies.

OBJECTIVE: To evaluate the incidence of nosocomial bacteremias related to the use of non-impregnated central venous catheters (CVCs) when only non-technologic strategies were used to prevent them. DESIGN: This was a prospective study of infectious complications of CVCs placed in intensive care unit (ICU) patients from April 1997 to December 2001. SETTING: The medical-surgical ICU of a tertiary-care, university-affiliated hospital in Argentina. METHODS: We studied all patients admitted to the ICU using non-impregnated CVCs. Maximal sterile barrier precautions (ie, use of cap, mask, sterile gown, sterile gloves, and large sterile drape), strict handwashing, preparation of the patients' skin with antiseptic solutions, insertion and management of catheters by trained personnel, and continuing quality improvement programs aimed at appropriate insertion and maintenance of catheters were employed. RESULTS: During the study period, 2,525 patients were admitted to the ICU. Eight hundred sixty-eight patients had 1,037 CVCs inserted. The number of CVC-related bloodstream infections (BSIs), acquired in the ICU, was 2.7 per 1,000 CVC-days (13 nosocomial CVC-related BSIs during 4,770 days of CVC use). Microorganisms isolated included methicillin-susceptible Staphylococcus aureus (n = 6), methicillin-resistant S. aureus (n = 2), coagulase-negative methicillin-resistant Staphylococcus (n = 2), Escherichia coli (n = 1), Klebsiella pneumoniae (n = 1), and Enterobacter cloacae (n = 1). CONCLUSIONS: A low rate of catheter-related BSI was achieved without antimicrobial-impregnated catheters. The incidence of CVC-associated bacteremias corresponded to the 10th to 20th percentile range of the National Nosocomial Infections Surveillance System hospitals for the same type of ICU.