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.     

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.     

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.     

The Australian Incident Monitoring Study. Oesophageal intubation: an analysis of 2000 incident reports

There were 35 oesophageal intubations in the first 2000 incidents reported to the Australian Incident Monitoring Study (AIMS). These reports confirm existing impressions that misplacement of the endotracheal tube can occur in trained as well as untrained hands, and that auscultation is an unreliable test. On the other hand, the value of capnography is emphasised, with no false positives in the 16 cases in which the instrument was used. There was one false negative. Over the 4 years of the AIMS study, reports have declined in frequency. It is possible that the early detection of oesophageal intubation by capnography has altered its status to the extent that anaesthetists no longer regard it as a "critical" incident. It is highly recommended that the presence of the expected concentration of carbon dioxide in expired air be confirmed by capnography immediately after any endotracheal intubation.     

Some relationships between skills in word-category recall and factors in adults' aphasia

It has long been recognized that a basic dimension to the lexical organization of the brain is semantic, and some brain mapping studies have indicated that the brain fields are distinctly different from some grammatical classes. Findings from the present investigation showed consistent relationships between 29 aphasic adults' performances on tasks involving graphic and gestural skills and those involving sequential recall of spoken words from different word categories. Each adult received the Porch Index of Communication Abilities which relies upon the physical manipulation of objects to assess verbal, gestural, and graphic abilities. Scores on a test requiring recall of word strings of nouns, verbs, adverbs, adjectives, or prepositions were used to predict the subscale scores from the Graphic and Gestural factors of the index. Recall scores for verb and preposition were predictive of the aphasic subjects' performances on the Graphic subscale, and noun and preposition scores were predictors of subjects' scores on the Gestural subscale. The results are related to other research showing that verb and preposition skills are predictive of fine motor abilities of children with communication disorders and brain-mapping studies. Some discussion centers on possible overlapping functions of brain activity involving word categories, language, and fine motor skills.     

Radiation-induced enhanced proliferation of human squamous cancer cells in vitro: a release from inhibition by epidermal growth factor

Ionizing radiation is believed to stimulate the repopulation of squamous carcinoma cells that survive the early portion of a fractionated course of radiotherapy. To characterize any intrinsic radiation-induced adaptive response and to examine whether epidermal growth factor (EGF) influences this response, A431 and 183A cells were irradiated with repeated daily exposures of 0.5-0.75 Gy and then grown in monolayer culture for 7 days with or without EGF at a 1 ng/ml concentration. Cell numbers were quantified using a microtiter dye-reduction assay. EGF alone caused approximately 70% and 30% growth inhibition of human SC A431 and 183A cells, respectively. Although radiation alone did not affect proliferative rates in these conditions, radiation eliminated the EGF-related growth inhibition in both cell lines. This effect was dose dependent in single radiation exposure experiments. Cell cycle analyses indicated that EGF initially promoted entry into S-phase 3 days after treatment but caused a G1-S block after 7 days. Treatment with radiation recruited cells into S-phase and G2-M, an effect which was sustained 7 days after treatment, overriding the influence of EGF. Radiation-induced modulation of the response of human squamous carcinoma cells to EGF in vitro after single and repeated radiation exposures suggests a proliferation response that may underlie enhanced repopulation of tumor clonogens in vivo.