Ultrasonically activated shears in thyroid surgery

BACKGROUND: Ultrasonically activated shears (UAS) have been documented to be both safe and fast devices in laparoscopic surgery. We studied whether the use of UAS would have some advantage in thyroid surgery. METHODS: Thyroidectomies, performed by one senior endocrine surgeon between December 1996 and February 1997, were retrospectively matched, with patients operated on by the same surgeon using the conventional method. RESULTS: Six pairs of total thyroidectomies and one pair of lobectomies could be matched. Mean operating time was 100 minutes for the patients operated on with the UAS and 154 minutes for the patients operated on with the conventional method. The mean operating time with the UAS was thus on average 64.6% of the operation time with the conventional method, with a 95% confidence interval from 50.1% to 83.5% (t = 4.00, 6 df, P = 0.007). CONCLUSIONS: In this material the use of UAS reduced significantly operating time in thyroidectomies.     

Effects of cellular pharmacology on drug distribution in tissues

The efficacy of targeted therapeutics such as immunotoxins is directly related to both the extent of distribution achievable and the degree of drug internalization by individual cells in the tissue of interest. The factors that influence the tissue distribution of such drugs include drug transport; receptor/drug binding; and cellular pharmacology, the processing and routing of the drug within cells. To examine the importance of cellular pharmacology, previously treated only superficially, we have developed a mathematical model for drug transport in tissues that includes drug and receptor internalization, recycling, and degradation, as well as drug diffusion in the extracellular space and binding to cell surface receptors. We have applied this "cellular pharmacology model" to a model drug/cell system, specifically, transferrin and the well-defined transferrin cycle in CHO cells. We compare simulation results to models with extracellular diffusion only or diffusion with binding to cell surface receptors and present a parameter sensitivity analysis. The comparison of models illustrates that inclusion of intracellular trafficking significantly increases the total transferrin concentration throughout much of the tissue while decreasing the penetration depth. Increasing receptor affinity or tissue receptor density reduces permeation of extracellular drug while increasing the peak value of the intracellular drug concentration, resulting in "internal trapping" of transferrin near the source; this could account for heterogeneity of drug distributions observed in experimental systems. Other results indicate that the degree of drug internalization is not predicted by the total drug profile. Hence, when intracellular drug is required for a therapeutic effect, the optimal treatment may not result from conditions that produce the maximal total drug distribution. Examination of models that include cellular pharmacology may help guide rational drug design and provide useful information for whole body pharmacokinetic studies.     

Transvaginal power Doppler angiography of the fetal brain

BACKGROUND AND OBJECTIVES: The stratum corneum of some of the scaly (parakeratotic) diseases was examined with light and scanning electron microscopy (SEM) with the purpose to reveal the importance of this layer in the diagnosis of some of the diseases associated with the formation of scales. MATERIALS AND METHODS: Two biopsies of the skin surface were taken: one, obtained from 80 patients with various parakeratotic scaly diseases and from 25 control subjects, was processed for light microscopy; the other biopsy for SEM was taken from 10 control subjects and 25 patients. The diagnoses of these patients were: psoriasis (5 patients), erythrodermic psoriasis (2 subjects), parapsoriasis (5 patients), pityriasis rubra pilaris (5 subjects), pityriasis rosea (3 subjects), and seborrheic dermatitis (5 subjects). RESULTS: The light microscopic studies showed that normal corneocytes are of polygonal shape with their largest diameter measuring 42 microns; these cells lacked nuclei. All parakeratotic cells appeared bizarre in shape, smaller than normal, and the cells contained a nucleus. With SEM, normal cells appeared relatively regular in size and shape, trabeculated, and had a flat surface. Cells examined in all the diseases revealed various sizes, outlines, and trabeculae. Specific surface patterns (print) of diseased cells were: "fish-scale" in psoriasis; "marbled" in parapsoriasis, "rocky stone" in pityriasis rubra pilaris; "heart-shaped" in seborrheic dermatitis, and semicrystalloid in pityriasis rosea. CONCLUSIONS: Parakeratosis is characterized not only by the retention of the nucleus in keratinocytes, but is also characterized by a cell of smaller size. The specific print of a disease helps in the diagnosis. The print will change with different stages of a disease.     

Susceptibility to tropical theileriosis of calves born to dams immunized with Theileria annulata (Hisar) cell culture vaccine

Epidemiological evidence suggests that millet might play a role in the etiology of endemic goiter. Recently, we showed that a traditional fermentation procedure of two pearl millet (Pennisetum americanum L. Lecke) cultivars grown in Sudan modified their effects on the weight of the thyroid gland and thyroid hormone profile in rats. In the present study, we report that this fermentation procedure reduced the ash contents of millet by about 40% and removed considerable amounts of Mg (>50%), Zn (27-39%) and K (45%). Other minerals (Ca, Fe, Cu) were not affected. Feeding of one fermented cultivar resulted in significant reduction in bone Mg and Zn contents, whereas feeding of the other fermented cultivar resulted in reduction of bone Mg only. Dietary Mg intake and bone Mg contents correlated negatively with serum T3. Groups fed the millet diets had higher serum Se level compared to those fed wheat or casein diets and feeding of fermented millet resulted in a further increase in serum Se level. Thus our data indicate that in rats the enhanced effects of millet on the thyroid induced by fermentation is likely related to removal of minerals from millet and/or chemical transformation of the goitrogens contained in millet.     

Performance of Holstein and Swedish-Red × Jersey/Holstein crossbred dairy cows within low- and medium-concentrate grassland-based systems

This 2 × 2 factorial design experiment was conducted to compare the performance of spring-calving Holstein dairy cows (HOL, n = 34) with Swedish Red × Jersey/Holstein crossbred (SR × J/HOL, n = 34) dairy cows within low and medium concentrate input grassland-based dairy systems. The experiment commenced when cows calved and encompassed 1 full lactation. Cows were offered diets containing grass silage and concentrates [70:30 dry matter (DM) ratio, and 40:60 DM ratio, for low and medium, respectively] until turnout, grazed grass plus either 1.0 or 4.0 kg of concentrate/d during the grazing period (low and medium, respectively), and grass silage and concentrates (85:15 DM ratio, and 70:30 DM ratio, for low and medium, respectively) from rehousing and until drying off. No significant genotype × system interactions were present for any of the feed intake or full-lactation milk production data examined. Full-lactation concentrate DM intakes were 769 and 1,902 kg/cow for the low and medium systems, respectively, whereas HOL cows had a higher total DM intake than SR × J/HOL cows in early lactation, but not in late lactation. Although HOL cows had a higher lactation milk yield than SR × J/HOL cows, the latter produced milk with a higher fat and protein content, and thus fat plus protein yield was unaffected by genotype. Milk produced by the SR × J/HOL cows had a higher degree of saturation of fatty acids than milk produced by the HOL cows, and the somatic cell score of milk produced by the former was also higher. Throughout the lactation, HOL cows were on average 30 kg heavier than SR × J/HOL cows, whereas the SR × J/HOL cows had a higher body condition score than the HOL cows. Holstein cows had a higher incidence of mastitis and ovarian dysfunction that SR × J/HOL cows.     

Effect of milk allowance on concentrate intake, ruminal environment, and ruminal development in milk-fed Holstein calves

The aim of the present experiment was to test the hypothesis that a barley-based concentrate would induce an acidic ruminal environment in young calves and that increased milk allowance would alleviate this condition. Eight Holstein calves ruminally cannulated at d 7 ± 1 of age were used to study the effect of variation in barley-based starter concentrate intake induced by 4 different milk allowances (3.10, 4.84, 6.60, and 8.34 kg of milk replacer/d; 123 g of dry matter/kg of milk) on the ruminal environment, blood variables, and fore-stomach development from wk 2 to 5 of age. Twelve ruminal fluid samples were collected during a weekly 24-h sampling in 4 consecutive weeks. Blood samples were collected by venipuncture between 1200 and 1300 h on ruminal sampling days. Rumen papillae development and visceral organ mass were recorded at slaughter. A linear treatment × week effect was observed for concentrate intake, with the calves fed the lowest milk allowance having the fastest increase in concentrate intake whereby these calves reached the same ME intake in wk 5 compared with calves with the highest milk allowance. Effects on ruminal variables were dominated by week of sampling, with minor differences among treatments. Ruminal pH was below 5.5 for 5 to 13 h/d and all calves with concentrate intake above 20 g of dry matter/d were observed to have a daily ruminal pH minimum at pH 5.5 or lower. The ruminal concentration of total volatile fatty acids (VFA) increased from 71 to 133 ± 9 mmol/L in wk 2 to 5 and was characterized by a relatively high molar proportion of propionate, increasing from 34 to 40 mol/100 mol of VFA in wk 2 to 5. In addition, the presence of ethanol and propanol as well as numerous VFA esters points to a ruminal environment with a relatively high hydrogen pressure. Plasma glucose and insulin responded to the highest milk allowance in wk 2 to 4. Plasma VFA and ketone bodies increased with the lowest milk allowance in wk 4 to 5. At slaughter, empty wet weights of the rumen + reticulum and omasum as well as mass of digesta in these compartments were found to decrease linearly and perirenal fat was found to increase linearly with milk allowance, indicating that the milk allowance changed the body composition of the calves. Lengths of ruminal papillae in the atrium and ventral ruminal sac were not affected by treatment. We concluded that the ruminal environment of young calves fed a barley-based starter concentrate was characterized by a low ruminal pH and high VFA concentration regardless of the milk allowance.     

Ribonuclease P (RNase P) RNA is converted to a Cd(2+)-ribozyme by a single Rp-phosphorothioate modification in the precursor tRNA at the RNase P cleavage site

To study the cleavage mechanism of bacterial Nase P RNA, we have synthesized precursor tRNA substrates carrying a single Rp- or Sp-phosphorothioate modification at the RNase P cleavage site. Both the Sp- and the Rp-diastereomer reduced the rate of processing by Escherichia coli RNase P RNA at least 1000-fold under conditions where the chemical step is rate-limiting. The Rp-modification had no effect and the Sp-modification had a moderate effect on precursor tRNA ground state binding to RNase P RNA. Processing of the Rp-diastereomeric substrate was largely restored in the presence of the "thiophilic" Cd2+ as the only divalent metal ion, demonstrating direct metal ion coordination to the (pro)-Rp substituent at the cleavage site and arguing against a specific role for Mg(2+)-ions at the pro-Sp oxygen. For the Rp-diastereomeric substrate, Hill plot analysis revealed a cooperative dependence upon [Cd2+] of nH = 1.8, consistent with a two-metal ion mechanism. In the presence of the Sp-modification, neither Mn2+ nor Cd2+ was able to restore detectable cleavage at the canonical site. Instead, the ribozyme promotes cleavage at the neighboring unmodified phosphodiester with low efficiency. Dramatic inhibition of the chemical step by both the Rp- and Sp-phosphorothioate modification is unprecedented among known ribozymes and points to unique features of transition state geometry in the RNase P RNA-catalyzed reaction.     

Retinoic acid metabolism in cultured retinal pigment epithelial cells

PURPOSE: To examine the stability of retinoic acid administered to cultured bovine retinal pigment epithelial (RPE) cells and to determine if RPE cells metabolize retinoic acid by a cytochrome P-450 mechanism. METHODS: Retinoic acid metabolism was examined in cultured RPE cells and subcellular fractions quantitatively by a thin-layer chromatography procedure and qualitatively by normal and reverse phase high-performance liquid chromatography. RESULTS: Cultured bovine RPE cells were found to have an activity that converts retinoic acid into more polar metabolites rapidly released from the cell. The highest specific activity for this process is found in the post-mitochondrial pellet (100,000g), is induced by retinoic acid, and is inhibited by ketoconazole. The major product of the RPE cell-mediated metabolism of retinoic acid is 4-oxo-retinoic acid, a known P-450 monooxygenase product of retinoic acid. The retinoic acid metabolizing activity is greatest in primary RPE cultures and decreases with aging in culture. CONCLUSIONS: These data suggest that a cytochrome P-450 monooxygenase is involved in the metabolism of retinoic acid in RPE cells, and this is similar to the findings of other investigators using other cells and tissues. The authors' findings suggest that the RPE may be important in the deactivation of this biologically potent retinoid in the retina.