High-resolution immunophenotyping of subcellular compartments in tissue microarrays by enzyme metallography.

Ultrasensitive bright field in situ hybridization assays using enzyme metallography (EnzMet) have been developed and validated, but little is known regarding the applicability of EnzMet for immunophenotypic detection of protein via IHC. Superior resolution via discrete metallographic deposits offers the potential for enhancing high-resolution immunophenotyping. Using high-complexity tissue microarrays (TMAs), 88 common solid tumors were evaluated by automated EnzMet (Nanoprobes and Ventana). Targets were chosen to assess the ability of EnzMet to specifically localize encoded antigens in the nucleus (estrogen receptor), cytoplasm (cytokeratins), and cytoplasmic membrane (HER2) in TMAs. Results were compared with conventional IHC diaminobenzidine (DAB) immunostaining. There was full concordance between the EnzMet and conventional IHC results. Furthermore, the EnzMet reaction products did not appreciably diffuse, were dense and sharply defined, and provided excellent high-resolution differentiation of cellular compartments in paraffin sections for the nuclear, cytoplasmic, and cell membrane-localized antigens evaluated. The higher density of elemental silver deposited during enzyme metallography permitted evaluation of core immunophenotypes at a relatively low magnification, allowing more tissue to be screened in an efficient manner. This preliminary study shows the utility of using enzyme metallography for high-resolution immunophenotyping in TMAs.     

Marked hypodiploidy in blast phase chronic myelogenous leukemia: report of a case and review of the literature

The emergence of a near-haploid clone of cells in blast phase chronic myelogenous leukemia is an unusual event. We report such a case and review eight other cases described in the English literature. The significance of the substantial loss of genetic material is discussed as is the phenotypic and genotypic heterogeneity observed in this group of patients.     

Cavernous sinus involvement in recurrent Nelson's syndrome

Summary Two cases of meningiomas, which are considered to have been caused by the preceding irradiation, are reported. In both cases, the cytokinetic study of the tumour using bromodeoxyuridine (BrdU) was performed. The percent of the tumour cells in the S phase of the cell cycle was less than 1% in both cases. The low labelling indices might suggest a relatively slow growing potential of these tumours, though the radiation-induced meningiomas were reported as being rapidly growing and malignant.     

Management of catheter-related infections in pediatric patients

Broviac catheters are commonly used to provide parenteral nutrition and access for infusion of blood products and drugs to pediatric patients. Sepsis is the most common serious complication of continued catheter use. Although removal of the catheter is generally recommended when it becomes contaminated, it may not be feasible to do so without compromising patient care. We evaluated the management of catheter-related infections in pediatric patients with and without removal of catheter. Seventy-seven episodes of catheter sepsis were evaluated in 61 pediatric patients; 24 were neonates and 37 were older children. The catheters were used for multiple purposes in 75% of cases. The most common microorganisms isolated were Staphylococcus epidermidis in 26%, Klebsiella pneumoniae in 9%, and Streptococcus viridans in 8% of cases; other pathogens included group D Enterococcus, Staphylococcus aureus, and Escherichia coli. Pseudomonas aeruginosa was isolated in four older children. Thirty-five patients were treated with antibiotics without catheter removal. Thirty patients received appropriate antibiotic therapy based on the susceptibility data. Twenty-six of these 30 patients responded within 5 days of therapy whereas the others required 15-39 days of treatment. Lack of response was mainly associated with the presence of abscess, immunocompromised status, and organisms P. aeruginosa and Candida albicans. Based on the sensitivity and minimum inhibitory concentration data, a combined regimen of gentamicin and vancomycin would be an effective initial therapy. These findings suggest that (1) catheter sepsis can be managed with appropriate antibiotics, and (2) when continued use of Broviac catheter is desired, a trial of antibiotic therapy should be attempted before catheter removal.     

Venous Irritation Related to Intravenous Administration of Phenytoin versus Fosphenytoin

Study Objective . To compare the frequency, severity, and time course of venous irritation after administration of a single intravenous dose of phenytoin with an equimolar dose of fosphenytoin, a water-soluble phenytoin prodrug. Design . Randomized, double-blind, two-period, crossover study. Setting . University hospital clinical research unit. Patients . Twelve healthy volunteers within 15% of ideal body weight and with no clinically significant abnormalities on physical examination, medical history, or laboratory assessment. Interventions . Volunteers randomly received a 30-minute infusion of phenytoin sodium 250 mg (250 mg/5 ml) or an equimolar dose of fosphenytoin 375 mg (375 mg/5 ml). Subjects returned for the crossover treatment 14–21 days later. Measurements and Main Results . Subjects assessed venous irritation (pain, burning, itching), and investigators evaluated phlebitis (erythema, swelling, tenderness), induration, exudation, and cording. Phenytoin was associated with a significantly higher degree of pain at the infusion site in all subjects and a significant degree of phlebitis in eight subjects (p<0.05); cording occurred in six subjects. The time course of phenytoin-induced phlebitis was bimodal. Erythema and tenderness were prominent at the end of the infusion and again at 24 hours. Cording was first noted between 24 hours and 1 week after infusion. In contrast, fosphenytoin was associated with mild pain in two subjects, one incident of phlebitis, and no erythema or cording. Conclusions . Fosphenytoin administration resulted in significantly less venous irritation and phlebitis compared with an equimolar dose of phenytoin. The clinical use of this water-soluble phenytoin prodrug should minimize the frequency and severity of infusion-site reactions and should allow convenient, rapid, intravenous administration of drug, undiluted or admixed with intravenous solutions.     

Infantile depression,nonorganic failure to thrive,and DSM-III-R: A different perspective

A controversy exists regarding the classification of nonorganic failure to thrive within the psychiatric nomenclature. There are a number of DSM-III-R diagnoses that may be applied to NOFTT, including Reactive Attachment Disorder of Infancy (RADI) and Major Depressive Disorder (MDD). The behaviors characteristic of NOFTT are symptomatic of depression, and are similar to those exhibited by infants with anaclitic depression as well as those of the adult with depression. The correspondence of the behaviours of NOFTT and the DSM-III-R criteria for Major Depression are reviewed, as are the conceptual and therapeutic reasons to view NOFTT infants as suffering from Depression.     

Mineral balance in adult men: effect of four refined fibers

Eleven men consumed a basal diet alone and with cellulose (Na-carboxymethylcellulose, locust bean gum, or karaya gum) added at 7.5 g fiber per 1000 calories for 4 wk each. Food, urine, and fecal composites were collected during the last 8 d of each feeding period. Bowel transit time was not significantly affected; however, total dry fecal weight was significantly increased after the refined fibers compared with that after the basal diet. Adding refined fibers to the basal diet did not significantly affect apparent mineral balance of calcium, magnesium, manganese, iron, copper, or zinc, with the exception of a negative mineral balance for manganese with carboxymethylcellulose. Karaya gum had a mean positive balance for all minerals tested. These results indicate that the hypocholesterolemic effect of the fibers that form gels occurs without compromising mineral balance in those subjects consuming Recommended Dietary Allowance levels of the minerals studied.