Israel Medical Association Journal

Background: The evaluation of influenza vaccine activity and potency are based on the immune response to hemagglutinin, and protection is indicated when a ≥ 1:40 titer of hemagglutination inhibition serum antibody is present. Neuraminidase, the second surface glycoprotein, may also have a role in protection, but little information on the immunologic response to this component is available.

Objectives: To determine whether any response to neuraminidase is evoked by intranasal immunization with a novel, whole, inactivated anti-influenza vaccine.

Methods: This study was part of a more comprehensive study of mucosal and serum immune response to this vaccine. Fifty-four young adults were immunized intranasally, 9 intramuscularly and 18 received a placebo. Twenty-three elderly people were immunized intramuscularly, and 21 elderly and 17 children were immunized intranasally. Serum and nasal antibodies to antigens N1 and N2 were determined by the lectin neuraminidase test.

Results: Serum response following intranasal vaccination was lower than after intramuscular vaccination, and ranged from 21.4 to 35.3% and 33.3 to 64.7% following intranasal vaccination and 52.2 to 77.8% and 47.8 to 88.9% after intramuscular vaccination, to N1 and N2 respectively. Nasal antibody response was low and was found only after intranasal vaccination, and response to N2 was better than to the N1 antigen.

Conclusions: It may be beneficial if future vaccines would include competent hemagglutinin and neuraminidase, which would afford a higher level of protection.
 

Background: We recently published preliminary evidence on the effectiveness of hypertonic saline in infants with viral bronchiolitis.

Objective: To further establish the efficacy of nebulized hypertonic saline in these infants

Methods: In a continuing, second-year randomized, double-blind controlled trial, an additional 41 infants (age 2.6 ± 1 months) hospitalized with viral bronchiolitis were recruited during the winter of 2001–2002. The infants received inhalation of 1.5 mg epinephrine dissolved either in 4 ml normal (0.9%) saline (Group I, n=20) or 4 ml hypertonic (3%) saline (Group II, n=22). The therapy was repeated three times daily until discharge. Pooling our 2 years of experience (2000–2002), a total of 93 hospitalized infants with viral bronchiolitis were recruited; 45 were assigned to Group I and 48 to Group II.

Results: The clinical scores at baseline were 7.6 ± 0.7 for Group I vs. 7.4 ± 1.3 for Group II (P = NS). However, the clinical scores at days 1 and 2 after inhalation differed significantly between the two groups, invariably favoring Group II: 7 ± 1 vs. 6.25 ± 1.1 (P < 0.05), 6.45 ± 1 vs. 5.35 ± 1.35 (P < 0.05), respectively. Adding aerosolized 3% saline to 1.5 mg epinephrine reduced the hospitalization stay from 3.5 ± 1.7 days in Group I to 2.6 ± 1.4 in Group II (P < 0.05). The pooled data of both years revealed that adding 3% saline to the inhalation mixture decreased hospitalization stay from 3.6 ± 1.6 to 2.8 ± 1.3 days (P < 0.05).
Conclusions: This second-year experience and our 2 year pooled data analysis strengthen the evidence that the combination of 3% saline/1.5 mg epinephrine benefits hospitalized infants with viral bronchiolitis

Objectives: To compare the seasonality of children with T1DM in different populations around the world for which data were available.

Methods: We analyzed large cohorts of T1DM patients with a clinical disease onset before age 14 or 18 years.

Results: We found a seasonality pattern only in ethnically homogenous populations (such as Ashkenazi Jews, Israeli Arabs, individuals in Sardinia and Canterbury, New Zealand, and Afro-Americans) but not in heterogeneous populations (such as in Sydney, Pittsburgh and Denver).

Conclusions: Our findings attempt to explain the controversial data in the literature by showing that ethnically heterogeneous populations with a mixture of patients with various genetic backgrounds and environmental exposures mask the different seasonality pattern of month of birth that many children with diabetes present when compared to the general population.

Objectives: To determine the prevalence of different pathogens in patients presenting to our sexually transmitted disease clinic with hematospermia.

Methods: Between January 1999 and January 2000, 16 patients presented to our STD[1] clinic with hematospermia after other non-infectious pathologies had been excluded by a referring physician. After obtaining informed consent, subjects completed a questionnaire addressing symptoms and sexual behavior. First void urine samples, as well as genitourinary and serum specimens were tested for Chlamydia trachomatis, Ureaplasma urealyticum and Herpes simplex virus. Standard bacterial cultures were also performed.

Results: Laboratory testing detected a pathogen in 12 of the 16 males presenting with hematospermia. The sexually transmitted pathogens detected were Herpes simplex virus in 5 patients (42%), Chlamydia trachomatis in 4 (33%), Enterococcus fecalis in 2 (17%), and Ureaplasma urealyticum in 1 (8%). In all cases in which a pathogen was identified, the appropriate antimicrobial agent was administered. Symptoms resolved for each patient following antimicrobial therapy. During a 1 year follow-up, all 12 patients remained free of disease.

Conclusions: Recent advances in microbiologic diagnostic techniques have facilitated the detection of pathogens in patients with hematospermia, thereby enhancing the efficacy of treatment.

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[1] STD = sexually transmitted disease

Objectives: To define the incidence of congenital CMV infection in two different subpopulations, as a model for the entire population of Israel.

Methods: Urine specimens were randomly collected from 2,000 newborns in Shaare Zedek Medical Center, Jerusalem, and HaEmek Medical Center, Afula (1,000 specimens each). These hospitals have many characteristic differences, presumably representing the diverse population of Israel. Urine specimens were subjected to a CMV PCR[2] reaction and positive specimens were validated by urine viral culture. Maternal seroprevalence was determined in a representative sample of the mothers in each hospital. Epidemiologic characteristics of the mothers were extracted from hospital records and compared.

Results: The population in Shaare Zedek Medical Center was mostly Jewish (95.8%) and urban (87.0%), as compared to that of HaEmek Medical Center (49.2% and 61.0%, respectively, P < 0.01). Nevertheless, CMV seroprevalence was similar: 81.5% and 85%, respectively. Ten (1.0%) and 4 (0.4%) newborns, respectively, were found to have congenital CMV infection (not significant).

Conclusions: The combined incidence of congenital CMV infection in the study population was 0.7% (95% confidence interval 0.3–1.0%). If this rate is extrapolated to the entire population of Israel, then a total of 945 cases of congenital CMV can be expected among the 135,000 annual deliveries. A nationwide screening program for congenital CMV should be considered.

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[1] CMV = cytomegalovirus

[2] PCR = polymerase chain reaction

The ubiquitin-proteasome pathway has a central role in selective degradation of intracellular proteins. Among the key proteins degraded by the system are those involved in the control of inflammation, cell cycle regulation and gene expression. With numerous important cellular pathways affected, derangements in the ubiquitin system were shown to result in a variety of human diseases including malignancies, neurodegenerative diseases and hereditary syndromes, and proteasome inhibition was implicated as a potential treatment for cancer and inflammatory conditions. Two proteasome inhibitors are currently under clinical evaluation for multiple myeloma and acute ischemic stroke. The ubiquitin system also has an important function in the immune and inflammatory response. It is involved in antigen processing and presentation to cytotoxic T cells, and the activation of nuclear factor-kappa B – the central transcription factor of the immune system. Since the proteasome is the central source of antigenic peptides that are presented to the immune system, some viruses, such as the Epstein-Barr virus, developed escape mechanisms that manipulate the ubiquitin-proteasome system in order to persist in the infected host. Understanding the mechanisms underlying the production of viral antigens by the ubiquitin-proteasome system may have therapeutic applications such as future development of vaccines.