Human herpesvirus-8 is not associated with angiolymphoid hyperplasia with eosinophilia

BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is an angioproliferative lesion, typically consisting of single or multiple red papules or nodules in the head and neck region. The etiology of ALHE, whether reactive or neoplastic, is unclear. It has been well documented in the literature that human herpesvirus-8 (HHV-8) DNA is present in the majority of cases of Kaposi's sarcoma; however, there is contradictory data regarding the association of this virus with ALHE. METHODS: We performed immunohistochemical studies for HHV-8 on paraffin-embedded tissue from 23 cases of histologically confirmed ALHE. Polymerase chain reaction (PCR) analysis for HHV-8 DNA was performed on 14 of the 23 cases that had adequate remaining tissue for the procedure. The results of the immunohistochemical studies and PCR analysis were compared. RESULTS: HHV-8 immunohistochemical studies were negative in all 23 cases of ALHE. PCR-based analysis on 14 cases failed to identify HHV-8 DNA. CONCLUSIONS: Combined data from several, small published studies are equivocal for an association between HHV-8 and ALHE. The results of our large study show no association between HHV-8 and ALHE.     

Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts

Diabetes alters cardiac substrate metabolism. The cardiac phenotype in insulin-resistant states has not been comprehensively characterized. The goal of these studies was to determine whether the hearts of leptin-deficient 8-week-old ob/ob mice were able to modulate cardiac substrate utilization in response to insulin or to changes in fatty acid delivery. Ob/ob mice were insulin resistant and glucose intolerant. Insulin signal transduction and insulin-stimulated glucose uptake were markedly impaired in ob/ob cardiomyocytes. Insulin-stimulated rates of glycolysis and glucose oxidation were 1.5- and 1.8-fold higher in wild-type hearts, respectively, versus ob/ob, and glucose metabolism in ob/ob hearts was unresponsive to insulin. Increasing concentrations of palmitate from 0.4 mmol/l (low) to 1.2 mmol/l (high) led to a decline in glucose oxidation in wild-type hearts, whereas glucose oxidation remained depressed and did not change in ob/ob mouse hearts. In contrast, fatty acid utilization in ob/ob hearts was 1.5- to 2-fold greater in the absence or presence of 1 nmol/l insulin and rose with increasing palmitate concentrations. Moreover, the ability of insulin to reduce palmitate oxidation rates was blunted in the hearts of ob/ob mice. Under low-palmitate and insulin-free conditions, cardiac performance was significantly greater in wild-type hearts. However, in the presence of high palmitate and 1 nmol/l insulin, cardiac performance in ob/ob mouse hearts was relatively preserved, whereas function in wild-type mouse hearts declined substantially. Under all perfusion conditions, myocardial oxygen consumption was higher in ob/ob hearts, ranging from 30% higher in low-palmitate conditions to greater than twofold higher under high-palmitate conditions. These data indicate that although the hearts of glucose-intolerant ob/ob mice are capable of maintaining their function under conditions of increased fatty acid supply and hyperinsulinemia, they are insulin-resistant, metabolically inefficient, and unable to modulate substrate utilization in response to changes in insulin and fatty acid supply.     

Late results of primary esophageal repair for spontaneous rupture of the esophagus (Boerhaave's syndrome)

Surgical management of Boerhaave's syndrome remains controversial. If left untreated, this is often a fatal condition. This was a retrospective review of cases operated on by one surgeon between 1981 and 1997. Eleven patients (8 males and 3 females), mean age of 63 years (range, 49-74 years), with Boerhaave's syndrome were treated surgically. A history of vomiting (10/11) and/or chest pain (11/11) was elicited in most cases, but only 3 of 11 cases were diagnosed correctly at presentation. From the onset of symptoms to diagnosis, the median delay was 30 hours (range, 6-1440 hours), and in 8 of 11 cases, the diagnosis was made >24 hours after the onset of symptoms. In all 11 cases, site of rupture was the lower one-third of the esophagus (9 to the left pleural cavity and 2 to the right pleural cavity). All cases were treated surgically after active initial resuscitation. The repair was further augmented by either a diaphragmatic flap (n = 1), bovine pericardial patch (n = 2), or Grillo pleural wrap (n = 8). A feeding jejunostomy was used in every case. Although the mean postoperative intensive care unit stay was only 1.8 days, the mean hospital stay was 37.5 days (range, 15-70 days). There were two hospital deaths (18%). After a mean follow-up of 12.5 years (range, 5-20 years), 7 of 11 patients (63%) are alive and asymptomatic. There was one death that was unrelated to the esophageal surgery. Only one patient reported dysphagia to solid food 5 years following primary esophageal repair. Prompt diagnosis and aggressive surgical management has acceptable in-hospital mortality. This condition is associated with significant morbidity, but the long-term outlook for the survivors is very favorable.     

Preparation and biological evaluation of 153Sm-DOTMP as a potential agent for bone pain palliation

BACKGROUND: Designing ideal radiopharmaceuticals for use as bone pain palliative agents requires the use of a moderate energy beta emitter as the radionuclide and a polyaminophosphonic acid as the carrier molecule. Cyclic polyaminophosphonic acid ligands are known for endowing higher thermodynamic stability and kinetic inertness of the radiolabelled agent when complexed with radiolanthanides. AIM: To use Sm (T1/2=46.27 h, Ebeta,max=0.81 MeV, Egamma=103 keV) as the radioisotope, obtainable at an adequate specific activity and high radionuclidic purity by irradiation of a natural Sm2O3 target, and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid (DOTMP) as the carrier ligand. RESULTS: The radiolabelling yields under optimized conditions were near quantitative with the additional merit of using a relatively low ligand:metal ratio of 2:1 unlike the 250-fold excess of ligands used in the case of the established agent, Sm-EDTMP. Radiochemical purity was retained with insignificant dissociation on storage up to 10 d at room temperature. Biodistribution studies in Wistar rats demonstrated selective skeletal uptake (4.52%+/-0.49% of injected activity per gram in tibia at 30 min post-injection) with rapid blood clearance and minimal uptake in any of the major organs. No leaching of skeletal activity was observed up to 48 h post-injection. Scintigraphic studies carried out in rabbits also showed significant skeletal accumulation and almost no retention of activity in other vital organs/tissues.     

Effect of endosulfan on male reproductive development

There is experimental evidence of adverse effects of endosulfan on the male reproductive system, but there are no human data. Therefore, we undertook a study to examine the relationship between environmental endosulfan exposure and reproductive development in male children and adolescents. The study population was composed of 117 male schoolchildren (10-19 years of age) of a village situated at the foothills of cashew plantations, where endosulfan had been aerially sprayed for more than 20 years, and 90 comparable controls with no such exposure history. The study parameters included recording of clinical history, physical examination, sexual maturity rating (SMR) according to Tanner stages, and estimation of serum levels of testosterone, luteinizing hormone (LH), follicle-stimulating hormone, and endosulfan residues (70 study and 47 control subjects). Mean +/- SE serum endosulfan levels in the study group (7.47 +/- 1.19 ppb) were significantly higher (p < 0.001) than in controls (1.37 +/- 0.40 ppb). Multiple regression analysis showed that SMR scoring for development of pubic hair, testes, penis, and serum testosterone level was positively related to age and negatively related to aerial exposure to endosulfan (AEE; p < 0.01). Serum LH levels were significantly positively related to AEE after controlling for age (p < 0.01). The prevalence of congenital abnormalities related to testicular descent (congenital hydrocele, undescended testis, and congenital inguinal hernia) among study and controls subjects was 5.1% and 1.1%, respectively, but the differences were statistically nonsignificant. Our study results suggest that endosulfan exposure in male children may delay sexual maturity and interfere with sex hormone synthesis. Our study is limited by small sample size and nonparticipation.     

New method of electrode placement for determination of cardiac output using impedance cardiography

In thirty eight young healthy adult subjects, cardiac output was determined non-invasively by using two methods of electrode placement viz. vertical (uses silver braided wires in a band shape) and horizontal (conventional stick-on type surface ECG electrodes), using the technique of Impedance Cardiography. The recordings were taken in supine position on the same day in two separate sets with 30.0 min interval between two sets. In each set of recording, five successive recordings, each at an interval of five minutes were taken. The mean values of cardiac out put by two methods were compared. For the set I, the respective values (Mean +/- SD) of cardiac output by horizontal and vertical methods for the each of the five recordings were 4.87 +/- 0.77 and 5.03 +/- 0.64 for the first, 4.87 +/- 0.71 and 4.91 +/- 0.66 for the second, 4.99 +/- 0.67 and 5.00 +/- 0.70 for the third, 4.78 +/- 0.69 and 4.98 +/- 0.61 for the fourth, 4.84 +/- 0.69 and 4.98 +/- 0.62 for the fifth recording in supine position. The respective P values for these pairs for between the group comparisons were 0.33, 0.50, 0.96, 0.17, and 0.36. In addition, to see the repeatability for each method, within the group comparison was done, the P values were 0.71 and 0.91 for the horizontal and vertical methods, respectively. The mean value of cardiac output did not differ significantly between two methods for recordings of set II in supine position. The cardiac output measurement by placing four spot electrodes horizontally, gave consistent result on repeated measurements and their values showed concordance with the cardiac output values obtained by conventional four band electrodes tied around the chest.     

The new enzyme-linked immunosorbent digoxin assay on the ADVIA Integrated Modular System is virtually free from oleander interference

Despite known toxicity of oleander, this product is used in herbal preparations. Oleander interferes with various digoxin immunoassays. It is possible that a person taking digoxin also may take oleander-containing herbal products, and digoxin immunoassays interfering with oleander cannot be used for therapeutic monitoring of digoxin. Recently, Bayer Diagnostics introduced a new enzyme-linked chemiluminescent immunosorbent digoxin assay for application on the ADVIA IMS System (ECLIA-digoxin). We studied potential interference of oleander with this new digoxin assay and found that this assay is virtually free from oleander interference. When aliquots of drug-free serum pools were supplemented with ethyl alcohol extract of oleander leaf or pure oleandrin standard, we observed significant apparent digoxin concentration when measured by the fluorescence polarization immunoassay (FPIA) but minimal digoxin-like immunoreactivity using the ECLIA digoxin assay. Because cross-reactivity should be studied in the presence of primary analyte, we prepared 2 serum pools using sera from patients receiving digoxin. Then aliquots of first digoxin pool were supplemented with oleandrin standard and aliquots of second digoxin pool with oleander extract. We observed significant increases in apparent digoxin concentration in the presence of both oleandrin and oleander extract using the FPIA. However, we observed no statistically significant change in digoxin concentration when ECLIA digoxin assay was used, indicating that this assay is virtually free from oleander interference.     

EphB4 expression and biological significance in prostate cancer

Prostate cancer is the most common cancer in men. Advanced prostate cancer spreading beyond the gland is incurable. Identifying factors that regulate the spread of tumor into the regional nodes and distant sites would guide the development of novel diagnostic, prognostic, and therapeutic targets. The aim of our study was to examine the expression and biological role of EphB4 in prostate cancer. EphB4 mRNA is expressed in 64 of 72 (89%) prostate tumor tissues assessed. EphB4 protein expression is found in the majority (41 of 62, 66%) of tumors, and 3 of 20 (15%) normal prostate tissues. Little or no expression was observed in benign prostate epithelial cell line, but EphB4 was expressed in all prostate cancer cell lines to varying degrees. EphB4 protein levels are high in the PC3 prostate cancer cell line and several folds higher in a metastatic clone of PC3 (PC3M) where overexpression was accompanied by EphB4 gene amplification. EphB4 expression is induced by loss of PTEN, p53, and induced by epidermal growth factor/epidermal growth factor receptor and insulin-like growth factor-I/insulin-like growth factor-IR. Knockdown of the EphB4 protein using EphB4 short interfering RNA or antisense oligodeoxynucleotide significantly inhibits cell growth/viability, migration, and invasion, and induces apoptosis in prostate cancer cell lines. Antisense oligodeoxynucleotide targeting EphB4 in vivo showed antitumor activity in murine human tumor xenograft model. These data show a role for EphB4 in prostate cancer and provide a rationale to study EphB4 for diagnostic, prognostic, and therapeutic applications.     

Comparison between pre-prandial and post-prandial heart rate variability (HRV)

After food ingestion, peptides are released in GIT, which cause local vasodilatation. Therefore, after meals, redistribution of blood occurs because of shifting of large amounts of blood into GIT. In normal individuals, this is well compensated and does not lead to post-prandial hypotension. The mechanism of post-prandial hypotension is well known. We hypothesized that there may be a decrease in parasympathetic activity (tone) after meals to compensate for the change in blood distribution. We carried out the study to find out the changes in the autonomic tone before and after meals (lunch) in normal individuals, using Heart Rate Variability (HRV). From the series of RR intervals marked, the time domain and frequency domain measures of HRV were obtained using Nevrokard software (version 6.4). Continuous ECG was recorded in 15 healthy adult subjects (mean age 29.06 +/- 6.2; 13 males and 2 females). The ECG was recorded in pre-prandial and post-prandial state for a period of five minutes each as follows: (1) just before the subjects had lunch, (2) 15 minutes after lunch, (3) 1 hour after lunch, and (4) 2 hours after lunch. Time domain and frequency domain measures of HRV were compared between pre-prandial state and rest of post-prandial states. The autonomic tone parameters did not show a significant change between the pre-prandial state and the immediate post-prandial state. [Range, i.e., the difference between the maximum and minimum RR intervals (406 +/- 161.14 vs. 416.66 +/- 125), standard-deviation of normal to normal RR interval (56.33 +/- 22.72 vs. 67.63 +/- 26.50), RMSSD (55.02 +/- 35.85 vs. 63.87 +/- 32.60), NN50 (42.13 +/- 29.43 vs. 51.86 +/- 29.83), PNN50 (12.67 +/- 10.29 vs. 15.27 +/- 9.71), HF (49.53 +/- 15.10 vs. 47.07 +/- 16.88), LF (41.41 +/- 13.18 vs. 46.49 +/- 15.99), LF/HF (0.98 +/- 0.53 vs. 1.26 +/- 0.90), total power (148.27 +/- 37.78 vs. 137.61 +/- 37.10)]. No significant change was seen in the above parameters between the pre-prandial state and the later phases of post-prandial state. Since there is no significant decrease in the time domain measures and the HF value between the pre-prandial and the post-prandial states, we conclude that the parasympathetic tone is not altered. The parameters denoting sympathetic tone, ie, LF and LF/HF, also do not show a significant change. This indicates that the cardiovascular autonomic tone is not affected by ingestion of meals in normal individuals. Thus we refute our hypothesis. In conclusion, the HRV parameters do not alter significantly after meals in normal individuals.     

Anticipation in Crohn's disease may be influenced by gender and ethnicity of the transmitting parent

Objective: We sought to examine whether anticipation (an earlier age of onset in succeeding generations) is observed in Crohn's disease (CD) patients within the New York metropolitan area, and whether there are differences in the degree of anticipation with respect to gender and ethnicity of the affected parent.
Methods: Sixty-one parent-child pairs both affected by CD were identified; about half of the pairs were of Ashkenazi Jewish descent. An additional 17 pairs of second-degree relatives with CD were also identified. The intergenerational difference in age at diagnosis (AAD) was used to perform regression analysis and the degree of anticipation among subsets of patients separated on the basis of gender and ethnicity of the transmitting parent was determined.
Results: The AAD was consistently (90% of the time) lower in the younger member of the 61 parent-child pairs (35.3 ± 1.6 yr vs 20.8 ± 1.1 yr,   p = 0.0001  ). Furthermore, the degree of anticipation was significantly greater for father-child pairs (20.6 ± 3.2 yr) than for mother-child pairs (11.7 ± 2.1 yr). However, when the patient population where the parent had an AAD of < 28 was analyzed separately, there was a lack of clear-cut evidence of anticipation in the population as a whole. Only when the population was subdivided by ethnicity was there convincing evidence of anticipation in the Jewish population.
Conclusions: Ascertainment bias may be responsible for the apparent anticipation observed in the CD population as a whole or in the nonJewish CD subgroup. However, the Jewish CD population displays strong evidence of anticipation even after correction for ascertainment bias.