Epithelial tissue formation in matrix culture and in histophysiologic gradient culture

Summary Formation of epithelial tissues in culture so that they become facsimiles in their structure of such tissues in nature requires procedures that comply with several spatial imperatives: a) three-dimensional growth; b) histophysiologic conditions that provide, concurrently, gradients of maturation and of diffusion of metabolites; and c) growth as layers of cells without free edges. Many steps have been required in the evolution of these methods. Two systems are described here in sufficient detail to serve as a manual. Three-dimensional growth of masses of epithelial tissue is accomplished in matrix culture using Gelfoam sponge and collagen-coated cellulose sponge. Radial gradient culture, a recent development, provides conditions that comply with the requirements of histophysiologic gradients and of epithelial tissue growth in layers without interruption in their continuity.     

Neurochemical mechanisms mediating the behavioral and cognitive effects of nicotine

Data are reviewed, largely from experiments in the authors'laboratory, that suggest three modes of action of systemic nicotine in producing three different types of effect upon behavior and cognitive function. (1) Preexposure of a stimulus without consequence makes it harder subsequently to form associations to that stimulus, a form of selective attention known as latent inhibition. Latent inhibition is blocked by nicotine, an effect that is apparently mediated by a nicotine-induced increase in dopamine release in the nucleus accumbens. (2) A single dose of nicotine proactively increases the partial reinforcement extinction effect measured several weeks later: that is, resistance to extinction is decreased by nicotine in animals that have been trained on a continuous reinforcement schedule, and increased in animals trained on a partial reinforcement schedule. This effect appears to be due to increased synthesis of tyrosine hydroxylase in the cell bodies of noradrenergic neurons in the locus coeruleus, followed by axonal transport to the hippocampus and increased synthesis and release of noradrenaline in that structure. (3) Nicotine improves vigilance in animals with cognitive deficits due to destruction of the forebrain cholinergic projection system, either as a consequence of excitotoxic lesions of the nuclei of origin of this system or after prolonged alcohol consumption; and also in human subjects with Alzheimer's disease (in which this system undergoes degeneration). This effect is most likely due to an action at denervated cholinergic synapses in the hippocampus and neocortex. © 1994 Wiley-Liss, Inc.     

Single-Agent versus Combination Antibiotic Therapy in the Management of Intraabdominal Infections

For the treatment of intraabdominal infection, single-agent antimicrobial regimens such as β-lactams with good antianaerobic activity are frequent alternatives to combination regimens such as aminoglycosides or aztreonam plus an antianaerobic agent such as clindamycin or metronidazole. The major issues in selecting a regimen are relative efficacy, potential for adverse drug effects, and cost. Single agents are clearly equivalent to combinations in preventing infectious complications after penetrating abdominal trauma and in treating established intraabdominal infections of mild to moderate severity or in relatively low-risk patients. A few trials demonstrated their equivalency in patients at high risk of mortality, although experience is limited. Single-agent regimens may reduce the risks of adverse drug effects compared with combination regimens, but they are not always less expensive.     

Ampicillin-Sulbactam versus Cefoxitin for Prophylaxis in High-Risk Patients Undergoing Abdominal Surgery

This double-blind study compared ampicillin-sulbactam 3 g versus cefoxitin 2 g in 136 adult patients at risk for developing an infection after abdominal surgery. Separate randomization schedules were used for colorectal, upper gastrointestinal/biliary, and other abdominal procedures. Study antibiotics were administered within 30 minutes before incision and repeated 6 hours later. Patients having colorectal surgery received a third dose of antibiotic 6 hours after the second. Efficacy evaluations were made on 123 patients, 62 in the ampicillin-sulbactam group and 61 in the cefoxitin group. The overall postoperative infection rates were 12.9% for ampicillin-sulbactam and 9.8% for cefoxitin (p>0.05); one wound infection occurred in each group. Adverse events were experienced by 13.2% of the ampicillin-sulbactam and 19.1% of the cefoxitin recipients (p>0.05). Cost-minimization analysis revealed that ampicillin-sulbactam was a cost-effective alternative to cefoxitin for the prevention of infection after abdominal surgery.     

Phase II evaluation of merbarone in renal cell carcinoma

Summary The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m² IV continuous infusion days 1–5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1–15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.     

Induction of collagenase synthesis in chondrocytes by a factor synthesized by inflamed synovial tissue

Rabbit inflamed synovial tissue grown in culture synthesizes a factor that induces collagenase synthesis in chondrocytes and in cartilage. Synthesis of this factor by the synovial tissue is inhibited by cycloheximide but not by indomethacin. The factor has an apparent molecular weight of 30,000, is stable to heat and to trypsin treatment but is inactivated by acid. Induction of collagenase synthesis in chondrocytes occurs after a lag period of 6 hours.     

The Effect of High-Dose Ascorbate Supplementation on Plasma Lipoprotein(a) Levels in Patients With Premature Coronary Heart Disease

Study Objective . To determine the efficacy of high-dose ascorbate supplementation in lowering lipoprotein(a) [Lp(a)] levels in patients with premature coronary heart disease (CHD). Design . Randomized, double-blind, placebo-controlled trial. Setting . Outpatient clinic. Patients . Forty-four patients with documented premature CHD. defined as confirmed myocardial infarction and/or angiographically determined stenosis of 50% or greater in at least one major coronary artery before age 60 years. Interventions . Patients were block randomized on the basis of age, gender, and screening Lp(a) concentrations to receive ascorbate 4.5 g/day or placebo for 12 weeks. Measurements and Main Results . High-dose ascorbate was well tolerated and produced a marked elevation in mean plasma ascorbate levels (+1.2 mg/dl; p<0.001). Multiple linear regression analysis revealed no significant effect of supplementation on postintervention Lp(a) levels (p=0.39) in a model that included treatment group assignment, and baseline Lp(a) levels. Conclusions . Our findings do not support a clinically important lowering effect of high-dose ascorbate on plasma Lp(a) in patients with premature CHD.     

The Influence of Routine Completion Arteriography on Outcome following Carotid Endarterectomy

n = 69) normal; Group B (n= 29), abnormal, severe defects; Group C (n= 56), abnormal, mild–moderate defect. RCA detected 32 defects in Group B: 10 internal carotid (ICA), seven endpoint flaps, two kinks, one dissection; 16 external carotid (ECA), 10 severe endpoint defects and six total occlusion; six common carotid (CCA), five irregular proximal shelfs, one web. Thirty of 32 defects were successfully repaired as confirmed by normal repeat RCA studies; one ECA defect was not repaired and the ICA dissection was irreparable. In Group C, 67 mild–moderate defects were identified, but not corrected. These included <30% stenosis in the ICA (12), ECA (18), CCA (24), and vein patch corrugation or irregularity (13). For the entire series the postoperative ICA occlusion rate was 2% (3/154), stroke rate 2.6% (4/154), and a subsequent >50% restenosis rate of 7% (11/154). The yield from routine carotid completion arteriograms was significant, with 19% of studies identifying a severe defect that required repair. Although the difference in stroke rates and restenosis between the different groups did not reach statistical significance, patients with normal intraoperative arteriograms initially or after correction of a significant RCA defect had no early carotid occlusion (p= 0.05, Fisher's exact test) compared to patients with residual RCA defects. All early carotid occlusions occurred in patients with unrepaired defects. We conclude that RCA is an important method of quality control after CEA and exerts a subtle, but real, reduction in postoperative complications.     

Unusual Delayed Manifestation of a Penetrating Chest Trauma

Abstract Pericardial tamponade remains a diagnostic challenge to the clinician especially when the patient is well compensated hemodynamically. We report an unusual case who sought medical help 1 month after having been stabbed in his chest. An investigation revealed a perforation of the myocardium and a pericardial tamponade. The patient survived thanks to a large organized clot that plugged the perforation. The patient was exposed to increased risk due to delayed onset, recognition, and therapy of the tamponade. Most reports on this subject deal with acute pericardial tamponade. Only few cases of delayed pericardial tamponade have been reported. A review of the relevant literature and the therapeutic approaches are discussed.