Multiparametric Ultrasound Evaluation of the Thyroid: Elastography as a Key Tool in the Risk Prediction of Undetermined Nodules (Bethesda III and IV)—Histopathological Correlation

The purpose of this study was to select thyroid nodules most at risk for malignancy among those cytologically undetermined by fine-needle aspiration biopsy (FNAB), using B-mode, color duplex Doppler and 2-D shear wave shear wave elastography (2-D-SWE). This was a prospective diagnostic accuracy study with 62 Bethesda III/IV nodules according to FNAB (atypia/follicular lesion of undetermined significance or follicular neoplasia/Hürthle cell neoplasm). Ultrasonography (US) data were compared with resection histologic results, revealing 35 of 62 benign nodules (56.4%) and 27 of 62 carcinomas (43.6%). Conventional US was uses to evaluate nodule echogenicity, dimensions, contours, presence of halo and microcalcifications. Doppler US was used to assess the vascularization (exclusively or predominantly peripheral or central) and mean resistance index of three nodule arteries. Elastography was used to evaluate the nodule elastographic pattern; mean nodule deformation index; deformation ratio between nodule and adjacent thyroid parenchyma; and mean deformation ratio between nodule and pre-thyroid musculature (MDR). Statistical analysis included χ², Fisher's exact, Student's t, Mann–Whitney tests and multivariable analysis by multiple logistic regression. Areas under the receiver operating characteristic curves (AUC-ROCs) were used for accuracy analysis. Fifty-eight participants (54.7 ± 14.0 y, 51 women) were studied. The parameters that were statistically significant to the univariate analysis were hypo-echogenicity, nodule diameter greater than width and all parameters analyzed from Doppler and elastography. Multivariate analysis revealed that the MDR (in kPa) was the best parameter for risk analysis of indeterminate nodules. Nodules with MDRs >1.53 exhibited a greater chance of malignancy (AUC-ROC = 0.98). We conclude that 2-D-SWE is able to select malignant nodules among those cytologically indeterminate, thus avoiding unnecessary surgery in these cytologic groups.     

Extraction and immunochemical characterization of cholecystokinin-like peptides from pig and rat brain

Two major classes of immunoreactive cholecystokinin peptides (iCCK) have been identified in rat and pig brains: (i) large basic peptides (big iCCK) resembling the 33-amino acid porcine cholecystokinin (pCCK33) in size and charge; (ii) small acidic peptides (small iCCK) resembling the COOH-terminal fragments of CCK. Boiling 0.1 M HCl maximally extracts big iCCK; boiling 0.1 M NaOH maximally extracts small iCCK. The differences in hormonal forms removed by these extractants are not likely to be due to enzymatic conversion during the extraction procedures. Fractionation on Sephadex G-50 and starch gel electrophoresis combined with radioimmunoassay using three antisera of different specificities--(i) directed towards the NH2 terminus of pCCK33, (ii) produced by immunization with COOH-terminal fragment CCK8, (iii) produced by immunization with COOH-terminal fragment CCK4--are consistent with the hypothesis that a major fraction of big iCCK may represent intact cholecystokinin with a COOH-terminal extension, as has recently been suggested for gastrin, a molecule having a COOH-terminal pentapeptide identical with that of cholecystokinin.     

Low acid output in Pima Indians

Duodenal ulcer has not been observed in full-heritage Pima Indians, while gastric cancer is relatively frequent. To investigate possible underlying factors for this phenomenon, we determined gastric acid output, gastric emptying rate, and plasma levels of gastrin, pepsinogen I, and pepsinogen II in apparently healthy Pima Indian and in Caucasian controls. The Pimas had significantly lower basal and stimulated outputs of gastric acid and higher fasting and postprandial plasma gastrin concentrations than the caucasians. Plasma pepsinogen I levels were similar in the two groups, but plasma pepsinogen II was significantly higher and the ratio of pepsinogen I to pepsinogen II was significantly lower in the Pima Indians. In addition, gastric emptying of an acaloric liqid meal was significantly delayed in the Pimas. The results suggest that the absence of duodenal ulcer in Pima Indians may be related to low gastric acid production and aslow rate of gastric emptying in this population. The associated findings of hypergastrinemia, hyperpepsinogenemia II, and a low ratio of pepsinogen I to pepsinogen II suggest that the hypochlorhydria may reflect an increased pervalence of chronic gastritis in full-heritage Pima Indians. This, in turn, could represent a risk factor for the development of gastric cancer in this population.Supported in part by research Contract 1-Am-6-2219 and grant AM 13233 from the National Institutes of Health, Bethesda, Maryland     

Inhibitory effect of intragastric glucose on gastric acid secretion and gastric emptying of liquids in man

Intragastric glucose inhibits gastric acid secretion and gastric emptying in man. To determine if these effects are mediated by somatostatin—a known inhibitor of gastric acid production, gastrin secretion, and gastric motility—the plasma somatostatin-like immunoreactivity (SLI) levels were determined in healthy human subjects after an intragastric load of 30% glucose solution. These findings were compared with results after an instillation of distilled water. Following the glucose load, the intragastric acid concentration, the acid output, and the fractional gastric emptying rate declined significantly (P<0.01) before either the plasma glucose or plasma insulin levels had increased. Neither the gastrin nor SLI plasma concentrations changed after the water or glucose load. These findings suggest that the suppression of gastric acid secretion and inhibition of the rate of gastric emptying that occur with intragastric glucose are mediated by factors other than changes in the peripheral circulating levels of SLI, gastrin, insulin, or glucose.     

NIH Conference. Herpes simplex virus infection: biology, treatment, and prevention

Herpes simplex viruses cause common mucocutaneous infections, but many aspects of their epidemiology and transmission are incompletely defined. Although the incidence of oral herpes remains relatively unchanged, the incidence of genital herpes is increasing significantly. Definitive diagnosis of herpes remains dependent on virus isolation, but techniques involving direct examination of clinical specimens are increasingly sensitive and may simplify and speed diagnosis. With the advent of acyclovir, effective therapy and suppression of infection are feasible for immunodeficient and selected normal patients. Unanswered questions remain regarding the long-term safety of acyclovir and the potential for emergence of clinically significant drug resistance. No effective vaccines are yet available for herpes virus infections. Promising strategies for vaccine development include preparation of immunogenic proteins, engineering of specially attenuated live virus strains, and incorporation of selected herpes genes into live vaccinia virus vectors.     

Oral acyclovir to suppress recurring herpes simplex virus infections in immunodeficient patients

Thirty-two episodes of herpes simplex virus infection in four immunodeficient patients with frequent recurrences were successfully treated with oral acyclovir, one capsule five times a day for 5 days. In 23 of these episodes, the treatments were extended for 1 to 6 months using two to five capsules a day with the aim of suppressing expected recurrences. In these patients, who routinely had more than one recurrence per month before treatment, there were only six outbreaks during more than 60 patient-months of suppressive therapy. Infection always recurred after treatments were completed, but the time to recurrence was shorter after treatments with two acyclovir capsules per day than after treatments with five capsules per day (p less than 0.001).     

Peptide radioimmunoassays in clinical medicine

The radioimmunoassay technique, first developed for the determination of hormones, has been applied to many substances of biologic interest by clinical and research laboratories around the world. It has had an enormous effect in medicine and biology as a diagnostic tool, a guide to therapy, and a probe for the fine structure of biologic systems. For instance, the assays of insulin, gastrin, secretin, prolactin, and certain tissue-specific enzymes have been invaluable in patient care. Further refinements of current methods, as well as the emergence of new immunoassay techniques, are expected to enhance precision, specificity, reliability, and convenience of the radioimmunoassay in both clinical and research laboratories.