Isaac Srugo

Serum levels of tumor necrosis factor-alpha correlate with severity of hepatic encephalopathy due to chronic liver failure.

Background: Several studies have shown that serum levels of tumor necrosis factor‐α (TNF) are significantly elevated in patients with acute and chronic liver diseases, where these elevations are independent of the etiology of the underlying disease. Serum levels of TNF are significantly higher in patients with cirrhosis than in those without cirrhosis, reaching the highest levels in decompensated cirrhosis. It has also been shown that plasma levels of TNF correlate with the severity of hepatic encephalopathy (HE) in fulminant hepatic failure. However, still there are no published data regarding the relationship between blood levels of TNF and the presence or severity of HE in patients with chronic liver failure.

Dengue seroconversion among Israeli travelers to tropical countries.

We tested for dengue seroconversion among 104 Israeli young adults who traveled to tropical countries for at least 3 months. Seven (6.7%) seroconverted during travel; four (3.8%) had immunoglobulin (Ig) M antibodies; one was symptomatic with borderline IgM and a rise in IgG; two others (1.9%) had a rise in IgG titers, without detectable IgM. All four IgM-positive patients had traveled to Southeast Asia.

Use of cellular telephones and transmission of pathogens by medical staff in New York and Israel.

Hands and instruments used by healthcare workers may serve as vectors for the nosocomial transmission of microorganisms. The use of cellular telephones by medical personnel and the associated nosocomial transmission of pathogens have not been thoroughly examined. Findings from our study show that cellular telephones are commonly used by hospital personnel, even during patient contact. One-fifth of the cellular telephones examined in this study were found to harbor pathogenic microorganisms, showing that these devices may serve as vectors for transmission to patients.

Sole pathogen in acute bronchiolitis: is there a role for other organisms apart from respiratory syncytial virus?

Background: Acute bronchiolitis (AB) is a common disease of young children with peak incidence during the winter season. Respiratory syncytial virus (RSV) is a major causative organism, yet recent relatively small sized studies have suggested an increased role of other organisms as sole or codetected organisms. The aim of this study was to assess the prevalence of sole- and mixed-organisms infections in hospitalized children with AB, using combined antigen-based and polymerase chain reaction assays (PCR). Methods: Sputum or nasal wash specimens obtained from 490 previously healthy children ≤2 years of age hospitalized with AB between December 1, 2005 and March 31, 2006 were tested: (1) For RSV, by rapid antigen detection test; (2) For RSV, influenza A, B, Parainfluenza 1 to 3, and adenovirus antigens by direct fluorescent assay; (3) For influenza A and B, RSV, Parainfluenza 1 to 3 viruses RNA by reverse transcription (RT) PCR assay; (4) For human metapneumovirus and rhinovirus RNA by RT real-time PCR assay; (5) For adenovirus, and Bordetella pertussis DNA by conventional PCR assays; (6) For human bocavirus DNA by real-tine PCR assays. Results: At least 1 organism was detected in 465 (91%) children. In 283 (61%), 117 (25%), and 23 (5%) children, 1, 2, and 3/4 organisms were detected, respectively. The most commonly detected organism was RSV, detected in 76%, and as a sole organism in 49%. Rhinovirus, human metapneumovirus, influenza virus A, bocavirus, Bordetella pertussis, and adenovirus were detected as a sole organism in 7%, 2.1%, 1%, 0.6%, 0.6%, and 0.2% of the children, respectively. Conclusions: Respiratory organisms were detected in the majority of the children, of whom about one third suffered from mixed organism infection. RSV was the most prevalent sole detected organism. The relevance of all other organisms may be much less than previously suggested.

Relationship between tumor necrosis factor-alpha and ammonia in patients with hepatic encephalopathy due to chronic liver failure

BACKGROUND. We have recently demonstrated that in humans, circulating levels of tumor necrosis factor‐α (TNF) correlate positively with severity of hepatic encephalopathy (HE) due to chronic liver failure. AIM. The main aim of this larger population study is to determine the relationship between TNF and ammonia in patients with HE and chronic liver failure due to liver cirrhosis. METHODS. Circulating levels of TNF and ammonia were measured in 108 patients with liver cirrhosis due to various etiologies in various clinical grades of HE (grades 0–4). TNF concentrations were measured in venous serum using commercially available solid‐phase high sensitivity enzyme‐linked immunosorbent assay. Ammonia levels were determined in venous plasma by the enzymatic method, using the glutamate dehydrogenase reaction. RESULTS. The mean±SEM values of circulating levels of TNF and ammonia at presentation in patients with grade 0 of HE (n = 30) were 3.89±0.2 pg/mL and 49.8±2.8 µg/mL respectively, in patients with grade 1 of HE (n = 26) were 8.56±0.34 pg/mL and 101.6±6.5 µg/mL respectively, in patients with grade 2 of HE (n = 22) were 11.59±0.48 pg/mL and 160.3±10.7 µg/mL respectively, in patients with grade 3 of HE (n = 20) were 19.98±0.94 pg/mL and 228.8±16.1 µg/mL respectively, and in patients with grade 4 of HE (n = 10) were 51.53±8.59 pg/mL and 284.2±20.3 µg/mL respectively. A significant positive correlation was found between circulating levels of TNF and those of ammonia (r = 0.62, P<0.0001), and also between circulating levels of both substances and severity of HE in these patients (r = 0.95, P<0.0001, and r = 0.9, P<0.0001 respectively). TNF and ammonia were both significant independent predictors of severity of HE (P<0.0001 for both variables). CONCLUSION. The results of this study demonstrate a significant relationship between TNF and ammonia in patients with chronic liver failure and HE, and so strengthen the suggestion that TNF could be strongly involved in the pathogenesis of HE in these patients. Hence, we suggest a new theory in the pathogenesis of HE, the ‘TNF theory’.

A novel host-proteome signature for distinguishing between acute bacterial and viral infections.

Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.

Immunization of pregnant women against pertussis: the effect of timing on antibody avidity.

BACKGROUND The Centers for Disease Control and Prevention recommend tetanus-diphteria-acellular pertussis (Tdap) immunization during pregnancy, preferably at 27-36 weeks gestation. AIMS First, to assess the relative avidity index (RAI) of umbilical cord immunoglobulin G (IgG) to pertussis toxin (PT) for newborns of women immunized with Tdap during late pregnancy as compared to unimmunized women. Second, to assess whether there is a preferential period of gestational Tdap immunization that provides the highest RAI of umbilical cord IgG to PT. METHODS RAI of IgG to PT was assessed via an adapted ELISA using NH4SCN as a dissociating agent. RESULTS We found that newborns of women immunized with Tdap during late pregnancy (n=52) had higher mean RAI of umbilical cord IgG to PT than those of unimmunized women (n=8), 73.77%±12.08 (95% CI, 70.41-77.13) vs. 50.23%±21.32 (95% CI, 32.41-68.06), p<0.001. Further, the RAI of umbilical cord IgG to PT was significantly higher in newborns of women immunized at 27-30(+6) weeks gestation (n=20) when compared with newborns of women immunized at 31-36 weeks (n=22) and >36 weeks (n=7), 79.53%±5.61 (95% CI, 76.91-82.16) vs. 71.56%±12.58 (95% CI, 65.98-77.14) vs. 63.93%±17.98 (95% CI, 47.31-80.56), p<0.03. CONCLUSION Gestational Tdap immunization between 27 and 30(+6) weeks resulted in the highest avidity of IgG to PT conveyed at delivery as compared with immunization beyond 31 weeks gestation. Future studies should be conducted to confirm our findings to optimize pertussis-controlling strategies.

An outbreak of pertussis among young Israeli soldiers

In winter 2001, an outbreak of pertussis involving an estimated 75 people occurred among soldiers serving in an infantry regiment of the Israeli Defense Forces (IDF). Nasopharyngeal swabs were obtained from patients and contacts for culture and PCR. Serum samples were obtained and assayed by ELISA for the presence of IgA, IgM and IgG antibodies to a lysate antigen of Bordetella pertussis. The calculated attack rate was 21% based on clinical signs alone (cough lasting 30 days or longer) and 9.5% based on clinical signs with laboratory confirmation (by PCR, IgA or IgM). A high carriage rate was observed; 20% of the asymptomatic and previously symptomatic subjects were PCR-positive for B. pertussis. These findings emphasize the importance of B. pertussis as a causative agent of epidemic respiratory infections in young adults and reveal the occurrence of a significant proportion of pertussis transient carriers during an outbreak of the disease.

Primary headaches, attention deficit disorder and learning disabilities in children and adolescents

BackgroundPrimary headaches and Learning difficulties are both common in the pediatric population. The goal of our study was to assess the prevalence of learning disabilities and attention deficit disorder in children and adolescents with migraine and tension type headaches.MethodsRetrospective review of medical records of children and adolescents who presented with headache to the outpatient pediatric neurology clinics of Bnai-Zion Medical Center and Meyer Children’s Hospital, Haifa, during the years 2009–2010. Demographics, Headache type, attention deficit disorder (ADHD), learning disabilities and academic achievements were assessed.Results243 patients met the inclusion criteria and were assessed: 135 (55.6%) females and 108 (44.4%) males. 44% were diagnosed with migraine (35.8% of the males, 64.2% of the females, p = 0.04), 47.7% were diagnosed with tension type headache (50.4% of the males, 49.6% of the females). Among patients presenting with headache for the first time, 24% were formerly diagnosed with learning disabilities and 28% were diagnosed with attention deficit disorder (ADHD). ADHD was more prevalent among patients with tension type headache when compared with patients with migraine (36.5% vs. 19.8%, p = 0.006). Poor to average school academic performance was more prevalent among children with tension type headache, whereas good to excellent academic performance was more prevalent among those with migraine.ConclusionsLearning disabilities and ADHD are more common in children and adolescents who are referred for neurological assessment due to primary headaches than is described in the general pediatric population. There is an association between headache diagnosis and school achievements.

Sexually transmitted infections among brothel-based sex workers in Tel-Aviv area, Israel: high prevalence of pharyngeal gonorrhoea

Sex workers play a major role in spreading sexually transmitted infections (STIs). We studied the prevalence rates and risk factors for STIs among 300 brothel-based sex workers in Tel-Aviv. Throat swabs were cultured for Neisseria gonorrhoeae, urine samples were tested by polymerase chain reaction (PCR) for Chlamydia trachomatis and N. gonorrhoeae, and sera were tested for syphilis, human immunodeficiency virus (HIV) and type 2 herpes simplex virus (HSV) antibodies. N. gonorrhoeae was cultured from throat samples of 9.0% of participants; PCR testing of urine was positive for C. trachomatis in 6.3% and for N. gonorrhoeae in 5.0%. Syphilis serology was positive (Venereal Disease Research Laboratory [VDRL] titres >1:8) in 1.3% of women, HSV-2-specific immunoglobulin G was detected in 60% and HIV serology was positive in a single case (0.3%). Having STI was significantly associated with age, number of years in Israel, number of clients a week and condom use for vaginal sex. In a multivariate analysis, having STI was significantly associated with number of clients per week and condom use for vaginal sex. The high prevalence of pharyngeal gonorrhoea reflects most probably the expanding demand of clients for oral sex and the insufficient condom use in this form of sex.