Barley diets with different fat sources have hypocholesterolemic effects in chicks.

Saturated fat is known to elevate serum cholesterol, whereas soluble dietary fiber has a hypocholesterolemic effect. The objective of this study was to compare the effects of barley and wheat diets supplemented with five fat sources on lipid metabolism in chicks. In two separate experiments, broiler chicks were fed isonitrogenous diets containing 23% protein, 11.4% dietary fiber and 10% dietary fat for 17 d. Diets contained 60% either hull-less barley or red spring wheat, with either palm oil, dehydrated egg yolk, butter, tallow or corn oil. Growth, feed efficiency, plasma lipids, liver cholesterol, and fecal fat and dry matter were measured. All chicks fed wheat grew faster and had greater food efficiency than those fed barley. All barley-fed chicks had lower (P less than 0.0001) total plasma cholesterol concentration (3.1 to 4.0 mmol/L) than those fed wheat (6.0 to 11.3 mmol/L). Chicks fed palm oil with wheat had the highest total cholesterol, 11.3 mmol/L. Liver cholesterol concentration was higher (P less than 0.0001) for all wheat-fed chicks (22.8-86.4 mmol/g) compared with those fed barley (6.7 to 12.2 mmol/g). Fecal crude fat was higher (P less than 0.05) for chicks fed barley, and excreta dry matter was lower for barley-fed chicks. Results indicate that the high soluble fiber content of this barley exerts a hypocholesterolemic effect in chicks regardless of dietary fat source, possibly mediated through lowered fat absorption.     

Sediment preference in the asiatic clam (Corbicula fluminea) and viviparid snail (Campeloma decisum) as a response to low-level metal and metalloid contamination

Sediment preference experiments were performed with the asiatic clam (Corbicula fluminea) and viviparid snail (Campeloma decisum) to determine the potential use of clam and snail behavior as a response to low-level metal and metalloid contamination. Three sediment types with varying levels of metal contamination were paired in various combinations. Clams and snails were placed in aquaria along the interface between the sediment types. Daily location and burial status were noted for two weeks. Clams spent significantly more days in the uncontaminated sediment when paired with one of the contaminated sediments. Snails spent more days in contaminated sediments when paired with the uncontaminated sediment, but none of these differences was statistically significant. Clams moved fewer days in tanks with the two most contaminated sediment types. Burrowing of snails was relatively unaffected by sediment treatments. The behavior of clams was more sensitive than the behavior of snails to sediment metal contamination. Consequently, clam behavior appears to be a better behavioral indicator of metal contamination.This work was performed under the auspices of the U.S. Department of Energy.     

Pathologic features of cytomegalovirus retinopathy after treatment with the antiviral agent ganciclovir

Ganciclovir is a new antiviral compound (also called BW B759U, DHPG, BIOLF-62, and 2'NDG) that has been used for the treatment of cytomegalovirus (CMV) retinopathy in immunocompromised patients (bone marrow recipients or acquired immune deficiency syndrome [AIDS] victims). The authors studied the eyes of three AIDS patients with CMV retinopathy who died while receiving ganciclovir chemotherapy. Gross, microscopic, and ultrastructural studies of these cases showed varying degrees of retinal scarring and active CMV lesions at the margins of the scars. CMV antigens were localized in cells at all layers of retina at the border of the lesions and in isolated cells in a perivascular location within histologically normal appearing retina. These areas probably represent sites of recrudescence when the drug is discontinued. In situ hybridization using a cloned complementary DNA (cDNA) probe of human CMV corroborated the immunocytologic localization of the virus. Ultrastructural studies showed megalic syncytial cells containing mostly capsids exclusively in the cell nucleus. The cytoplasmic electron-dense membrane-bound bodies that have characterized untreated cases of CMV retinopathy were absent in the treated cases. An attempt to isolate CMV in tissue culture from the vitreous and retina of one of the cases yielded a negative result. Our results indicate that ganciclovir does not effectively eliminate CMV from the retina nor does it suppress expression of all viral genes. Ganciclovir appears to function by limiting viral DNA synthesis and subsequent packaging of viral DNA into infectious units, thereby acting as a virostatic chemotherapeutic agent.     

Detection of the Glanzmann's thrombasthenia mutations in Arab and Iraqi-Jewish patients by polymerase chain reaction and restriction analysis of blood or urine samples.

Severe Glanzmann's thrombasthenia is relatively frequent in Iraqi-Jews and Arabs residing in Israel. We have recently described the mutations responsible for the disease in Iraqi-Jews--an 11 base pair deletion in exon 12 of the glycoprotein IIIa gene, and in Arabs--a 13 base pair deletion at the AG acceptor splice site of exon 4 on the glycoprotein IIb gene. In this communication we show that the Iraqi-Jewish mutation can be identified directly by polymerase chain reaction and gel electrophoresis. With specially designed oligonucleotide primers encompassing the mutation site, an 80 base pair segment amplified in healthy controls was clearly distinguished from the 69 base pair segment produced in patients. Patients from 11 unrelated Iraqi-Jewish families had the same mutation. The Arab mutation was identified by first amplifying a DNA segment consisting of 312 base pairs in controls and of 299 base pairs in patients, and then digestion by a restriction enzyme Stu-1, which recognizes a site that is absent in the mutant gene. In controls the 312 bp segment was digested into 235 and 77 bp fragments, while in patients there was no change in the size of the amplified 299 bp segment. The mutation was found in patients from 3 out of 5 unrelated Arab families. Both Iraqi-Jewish and Arab mutations were detectable in DNA extracted from blood and urine samples. The described simple methods of identifying the mutations should be useful for detection of the numerous potential carriers among the affected kindreds and for prenatal diagnosis using DNA extracted from chorionic villi samples.     

Preliminary analysis of a randomized comparison of 5-fluorouracil versus 5-fluorouracil and high-dose continuous-infusion folinic acid in disseminated colorectal cancer

In this study, 50 patients were randomly assigned to treatment with 5-fluorouracil (FUra) or FUra plus high-dose continuous-infusion folinic acid. Five of 27 evaluable patients in the FUra group versus 10 of 21 patients in the FUra plus folinic acid arm of the study had objective partial remissions, P = 0.02. Time to progression was 3.9 months for FUra and 8.0 months for FUra and folinic acid, P = 0.006; however, median survivals (11.9 versus 14.5 months) were not different in this crossover study. Toxicity in both treatment arms was mild, although patients receiving FUra plus folinic acid experienced significantly more stomatitis than patients treated with FUra alone. This study suggests that high-dose, continuous-infusion folinic acid, which produces a steady-state level of biologically active folates of 10 microM, significantly increases the therapeutic activity of FUra.     

Inhibition of intracellular growth of Histoplasma capsulatum yeast cells by cytokine-activated human monocytes and macrophages.

Human monocytes/macrophages (M psi) were infected with Histoplasma capsulatum yeast cells, and intracellular growth was quantified after 24 h of incubation in medium alone or in medium containing cytokines. Yeast cells multiplied within freshly isolated monocytes, cultured M psi, and alveolar M psi with intracellular generation times of 14.2 +/- 1.4, 18.5 +/- 2.1, and 19.9 +/- 1.9 h (mean +/- standard error of the mean), respectively. Monocytes and M psi inhibited the intracellular growth of yeast cells in response to cytokine supernatant; maximum inhibition was obtained when cytokines were added to cell monolayers immediately after infection. Opsonization of yeast cells in normal serum or in H. capsulatum-immune serum did not affect the intracellular generation time of yeast cells in either control M psi or cytokine-activated M psi.     

Phase I trial and clinical pharmacology of elsamitrucin.

Elsamitrucin (BMY-28090) is an antitumor antibiotic first described in 1985 that has significant oncolytic activity against a number of murine tumors including P388, L1210, B16 and M5076, as well as against MX1 and HCT116 xenografts. Preclinical toxicology studies of elsamitrucin revealed edema of multiple organs associated with hypoproteinemia and, at lethal doses, severe multiorgan toxicity. We conducted a phase I clinical trial (31 patients) of elsamitrucin administered as a 10-min i.v. infusion every 3 weeks. The starting dose (0.6 mg/m2) was 1/3 of the dog low toxic dose. The maximum tolerated dose was 30 mg/m2. Dose-limiting toxicity was reversible hepatic dysfunction manifested by elevated transaminase levels not associated with bilirubin, alkaline phosphatase, or lactate dehydrogenase elevations. Other toxicities included nausea, vomiting, malaise, and phlebitis. Because the hepatic toxicity was brief and reversible, a subsequent study (18 patients) was conducted with elsamitrucin administered every 2 weeks. Reversible grade 3 hepatotoxicity was again observed at 30 mg/m2. Plasma and urine samples from patients receiving doses of 0.6-36 mg/m2 were analyzed for drug content. The maximum plasma concentration and area under the plasma concentration versus time curve values increased linearly with doses up to 25 mg/m2 but not at higher doses. The terminal half-lives, total body clearances, and volume of distribution were 36-60 h, 10-19 liters/h/m2, and 400-1100 liters/m2, respectively. Less than 5% was excreted in the urine in 24 h as parent compound. Bile was collected from one patient with an indwelling biliary catheter. Approximately 22% of the dose was excreted in 48 h, suggesting that biliary excretion of elsamitrucin may be an important route of drug elimination. Based on reversible hepatic toxicity, the phase II recommended dose of elsamitrucin is 25 mg/m2 every 2 weeks.     

Sensory innervation of human thoracolumbar fascia. An immunohistochemical study.

We have studied the human thoracolumbar fascia by using antiserum against neurofilament protein (NFP) and S-100 protein to identify sensory nerve fibers and their endings. Seven surgical specimens from 7 patients were studied with light microscopy. In addition to free nerve endings, two types of encapsulated mechanoreceptors (Ruffini's and Vater-Pacini corpuscles) were identified. These findings support the hypothesis that the thoracolumbar fascia may play a neurosensory role in the lumbar spine mechanism.