Recurrent infectious mononucleosis caused by Epstein-Barr virus with persistent splenomegaly

We present the clinical case of a 20-year-old male soldier who appeared in general good physical condition. He suffered from infectious mononucleosis caused by Epstein-Barr virus that had recurred 2 years after the first serologically documented episode. The detected splenomegaly persisted in the healthy young man, who otherwise showed no apparent immune deficiency. To our knowledge, this is an extremely rare condition.     

Cardiovascular effects of verapamil and quinidine at normal and elevated ambient pressure

Cardiovascular parameters were measured in rats before and after administration of verapamil and quinidine, a slow Ca2+ and fast Na+ channel blocker, respectively, at normal and elevated ambient pressure [5 bar (500 kPa)]. Left ventricular pressure (Pivt), maximal velocity of Plvt rise (+dP/dt) and fall (-dP/dt), and heart rate (HR), arterial systolic pressure (Pasys), and mean arterial pressure (MAP) were measured in all animals using catheters connected to pressure transducers. Cardiac output (Q), and myocardial blood flow (MBF) were detected by the microsphere technique. Total peripheral vascular resistance (TPVR), myocardial vascular resistance (MVR) and oxygen consumption of the heart (VO2) was calculated. In Groups 1a (control group; 1 bar) and 1b (test group; 1-5 bar), verapamil (1.5 mg x kg(-1)) caused a reduction in Plvt, +dP/dt, -dP/dt, Pasys, MAP, VO2, TPVR, and MVR in both groups at 1 bar (100 kPa), and these parameters remained depressed for at least 50 min in Group 1a. However, MBF increased after verapamil injection. After compression to 5 bar (500 kPa), Plvt, dP/dt, Pasys, VO2, and MBF were markedly elevated (Group 1b). No change in HR, SV, or Q was found in either of the groups. In Groups 2a (control group; 1 bar) and 2b (test group; 1-5 bar), quinidine (5 mg x kg(-1)), infused over a period of 10 min, reduced Plvt, +dP/dt, -dP/dt, MAP, Pasys, VO2, Q, stroke volume (SV), TPVR and MBF at 1 bar (100 kPa). These parameters remained depressed for almost the whole experimental period in Group 2a, while Plvt, +/-dP/dt, Pasys, MAP and VO2 were enhanced during exposure to 5 bar (500 kPa) in Group 2b. The HR was unchanged by quinidine in Group 2a, but was increased at elevated ambient pressure in Group 2b, whereas the MBF was unchanged in both groups. The present results show that verapamil and quinidine have a depressant effect on cardiac function, arterial pressure and VO2 at normal atmospheric pressure, whereas MBF was enhanced only in the verapamil group. During exposure to elevated ambient pressure, cardiac function, arterial pressure and VO2 increased despite adequate inhibition of slow Ca2+ and fast Na+ channels.     

New York State universal newborn hearing screening demonstration project: effects of screening protocol on inpatient outcome measures

OBJECTIVE: To examine differences among various test protocols on the fail rate at hospital discharge for infants in the well-baby nursery (WBN) and neonatal intensive care unit (NICU) who received hearing screening through a universal newborn hearing screening demonstration project. DESIGN: The outcomes of several screening protocols were examined. Two technologies were used: transient evoked otoacoustic emissions (TEOAEs) alone or in combination with the auditory brain stem response (ABR). The performance of test protocols in both nurseries within eight hospitals was examined over a 2- to 3-yr period. In the WBN, six hospitals used a screening protocol of TEOAE technology first followed by an ABR (automated or conventional) technology screening for newborns who referred on TEOAE screening. Two hospitals used TEOAE only in the WBN. Seven hospitals used screening protocols in the NICU that used a combination of TEOAE and ABR technologies (TEOAE technology administered first or second, before or after TEOAE, or TEOAE and ABR tests on all infants). Only one hospital used TEOAE technology exclusively for hearing screening. RESULTS: Significant differences among screening protocols were found across hospitals in the first, second, and third years of the program. The combination of TEOAE technology and ABR technology (a two-technology screening protocol) resulted in a significantly lower fail rate at hospital discharge than the use of a single-technology (TEOAE). Fail rates at discharge were twice as high using the one-technology protocol versus two-technology protocol, even when the best outcomes from program year 3 were considered exclusively. Results of two-technology versus one-technology protocols were similar in the NICU. Use of a second technology for screening TEOAE fails significantly reduced every hospital that used the protocol's fail rate at discharge. CONCLUSIONS: A two-technology screening protocol resulted in significantly lower fail rates at hospital discharge in both the WBN and NICU nurseries than use of a single-technology (TEOAE) hearing screening protocol.     

Effects of ATP infusion on glucose turnover and gluconeogenesis in patients with advanced non-small-cell lung cancer

Cancer cachexia is associated with elevated lipolysis, proteolysis and gluconeogenesis. ATP infusion has been found to significantly inhibit loss of body weight, fat mass and fat-free mass in patients with advanced lung cancer. The present study was aimed at exploring the effects of ATP on whole-body glucose turnover, alanine turnover and gluconeogenesis from alanine. Twelve patients with advanced non-small-cell lung cancer (NSCLC) were studied 1 week before and during 22-24 h of continuous ATP infusion. After an overnight fast, turnover rates of glucose and alanine, and gluconeogenesis from alanine, were determined using primed constant infusions of ?6, 6-(2)H(2)?lucose and ?3-(13)C?lanine. Thirteen NSCLC patients and eleven healthy subjects were studied as control groups without ATP infusion. During high-dose ATP infusion (75 microg.min(-1).kg(-1)), glucose turnover was 0.62+/-0.07 mmol.h(-1).kg(-1), compared with 0. 44+/-0.13 mmol.h(-1).kg(-1) at baseline (P=0.04). For gluconeogenesis a similar, but non-significant, trend was observed ?baseline, 0.30+/-0.16 mmol.h(-1).kg(-1); during ATP, 0.37+/-0.13 mmol.h(-1).kg(-1) (P=0.08). At lower ATP doses (37-50 microg. min(-1).kg(-1)) these effects were not detected. The relative increase in glucose turnover during ATP infusion compared with baseline showed a significant correlation with the ATP dose (r=0.58, P=0.02). No change in alanine turnover was observed at any ATP dose. The results of this study indicate an increase in glucose turnover during high-dose ATP infusion compared with baseline levels. During high-dose ATP infusion, glucose turnover was similar to that during low-dose ATP infusion and to that in control NSCLC patients. Between ATP infusions, however, glucose turnover in patients treated with high-dose ATP was significantly lower than that in the low-dose and control NSCLC patients (P=0.04 and P=0.03 respectively), and similar to that in healthy subjects. This would suggest that repeated high-dose ATP infusions may inhibit glucose turnover between infusion periods.     

Dietary prevention of allergic diseases in infants and small children.

Because of scientific fraud four trials have been excluded from the original Cochrane meta-analysis on formulas containing hydrolyzed protein for prevention of allergy and food intolerance in infants. Unlike the conclusions of the revised Cochrane review the export group set up by the Section on Paediatrics, European Academy of Allergology and Clinical Immunology (SP-EAACI) do not find that the exclusion of the four trials demands a change of the previous recommendations regarding primary dietary prevention of allergic diseases. Ideally, recommendations on primary dietary prevention should be based only on the results of randomized and quasi-randomized trials (selection criteria in the Cochrane review). However, regarding breastfeeding randomization is unethical, Therefore, in the development of recommendations on dietary primary prevention, high-quality systematic reviews of high-quality cohort studies should be included in the evidence base. The study type combined with assessment of the methodological quality determines the level of evidence. In view of some methodological concerns in the Cochrane meta-analysis, particularly regarding definitions and diagnostic criteria for outcome measures and inclusion of non peer-reviewed studies/reports, a revision of the Cochrane analysis may seem warranted. Based on analysis of published peer-reviewed observational and interventional studies the results still indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is effective in the prevention of allergic diseases in high-risk infants, particularly in early infancy regarding food allergy and eczema. The most effective dietary regimen is exclusively breastfeeding for at least 4-6 months or, in absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months, combined with avoidance of solid food and cow's milk for the first 4 months.     

Pharmacokinetics and cerebrospinal fluid penetration of phenylacetate and phenylbutyrate in the nonhuman primate

INTRODUCTION: Phenylbutyrate (PB) and its metabolite phenylacetate (PA) demonstrate anticancer activity in vitro through promotion of cell differentiation, induction of apoptosis through the p21 pathway, inhibition of histone deacetylase, and in the case of PB, direct cytotoxicity. We studied the pharmacokinetics, metabolism, and cerebrospinal fluid (CSF) penetration of PA and PB after intravenous (i.v.) administration in the nonhuman primate. METHODS: Three animals received 85 mg/kg PA and 130 mg/kg PB as a 30-min infusion. Blood and CSF samples were obtained at 15, 30, 35, 45, 60 or 75 min, and at 1.5, 2.5, 3.5, 5.5, 6.5, 8.5, 10.5 and 24.5 h after the start of the infusion. Plasma was separated immediately, and plasma and CSF were frozen until HPLC analysis was performed. RESULTS: After i.v. PA administration, the plasma area under the concentration-time curve (AUC) of PA (median +/- SD) was 82 +/- 16 mg/ml.min, the CSF AUC was 24 +/- 7 mg/ml.min, clearance (Cl) was 1 +/- 0.3 ml/min per kg, and the AUCCSF:AUCplasma ratio was 28 +/- 19%. After i.v. PB administration, the plasma PB AUC was 19 +/- 3 mg/ml.min, the CSF PB AUC was 8 +/- 11 mg/ml.min, the PB Cl was 7 +/- 1 ml/min per kg, and the AUCCSF:AUCplasma ratio was 41 +/- 47%. The PA plasma AUC after i.v. PB administration was 50 +/- 9 mg/ml.min, the CSF AUC was 31 +/- 24 mg/ml.min, and the AUCCSF:AUCplasma ratio was 53 +/- 46%. CONCLUSIONS: These data indicate that PA and PB penetrate well into the CSF after i.v. administration. There may be an advantage to administration of PB over PA, since the administration of PB results in significant exposure to both active compounds. Clinical trials to evaluate the activity of PA and PB in pediatric central nervous system tumors are in progress.     

Unmyelinated nerve fiber degeneration in chronic inflammatory demyelinating polyneuropathy

To determine whether unmyelinated nerve fibers escape degeneration as one might expect in an immune response exclusively directed at myelin, we performed a morphometric examination of unmyelinated axons and myelinated nerve fibers in sural nerve biopsy specimens of 14 patients with a chronic inflammatory demyelinating polyneuropathy (CIDP) and of 12 age-matched normal controls. The numbers of unmyelinated axons, myelinated nerve fibers, denervated Schwann cell units and collagen pockets were quantified and related to the clinical and electrophysiological data of the patients with CIDP. In 4 patients with a rapid onset of the neuropathy and a highly elevated CSF protein, the numbers of both unmyelinated axons and myelinated nerve fibers were decreased equally. In 8 patients we found that the unmyelinated axons were relatively spared compared with the loss of myelinated nerve fibers. In these patients, however, the presence of denervated Schwann cell units and of collagen pockets was increased. We conclude that unmyelinated nerve fibers are affected in patients with CIDP.     

Acceptance and long-term compliance of nCPAP in obstructive sleep apnea

In a retrospective cohort study, we evaluated whether improvements in nasal continuous positive airway pressure (nCPAP) technology, particularly the introduction of automatic adjustment of the nCPAP pressure (auto-CPAP), have led to better acceptance and (long-term) compliance in patients with obstructive sleep apnea syndrome (OSAS) as compared to earlier reported data. Questionnaires were sent to 256 patients, who were referred to our clinic for an overnight polysomnography from January 1997 to July 2005 and received nCPAP therapy for OSAS. Of the 256 patients, 24 patients were unavailable for follow-up. Of the remaining 232 patients, 58 patients (25%) had discontinued therapy, while 174 patients (75%) were still using nCPAP after 2 months to 8 years of follow-up. One Hundred and thirty eight (79%) of these 174 patients used nCPAP for at least 4 h/night during ≥ 5 nights/week, 82,1% of the conventional nCPAP (fixed pressure CPAP) group (n = 78) and 77,1% of the auto-CPAP group (n = 96). Therefore, including the 58 failures, only 59.5% of patients can be seen as compliant. There were no statistical differences between the fixed pressure CPAP and auto-CPAP users, and between the compliant and non-compliant users according to age, BMI, AHI and Epworth sleepiness scale (ESS). Auto-CPAP patients used significantly more cm H2O. The long-term compliance of nCPAP therapy has have increased only slightly since the introduction of the fixed pressure CPAP 25 years ago, in spite of many efforts to improve it. It seems that a plateau has been reached and that it is unrealistic to aim at a substantially higher compliance rate.     

The electrocardiogram in traumatic right atrial rupture

We report the case of a previously healthy 20-year-old man who had a traumatic rupture of the right atrium. On admission an electrocardiogram (ECG) was recorded which is highly remarkable and, retrospectively, suggestive for the diagnosis. The patient died soon after the ECG, and the diagnosis was made at autopsy.