Prevalence of anti-hepatitis B surface antibodies among children and adolescents vaccinated in infancy and effect of booster dose administered within a pilot study.

We determined the prevalence of anti-hepatitis B surface antibodies (anti-HBs) among children and adolescents vaccinated for hepatitis B virus in infancy as part of the routine vaccination programme. A representative serum sample of the Israeli population age 0-19 was tested. In a separate pilot study, a booster dose of hepatitis B vaccine was administered to 31 candidates for national service, who were fully vaccinated in infancy and tested negative for hepatitis B surface antibodies at age 17-19 years and anti-HBs antibodies were assessed 8 weeks later. Of the 1273 samples tested, 631 (49·6%) were positive to anti-HBs antibodies. Seropositivity rates were 89·5% among infants aged 6-12 months and declined significantly with age to 20·7% at age 19 years. No differences in seropositivity rates were observed between Jews and Arabs, males and females and those born in Israel and in other countries. Seroconversion rate among the 31 individuals who received a booster dose was 90·3% (95% CI: 75·1-96·6%). We recommend a booster dose for healthcare personnel before starting to work at the health care facility.

Development and validation of a real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay for investigation of wild poliovirus type 1-South Asian (SOAS) strain reintroduced into Israel, 2013 to 2014.

In February 2013, wild poliovirus type 1 (WPV1) was reintroduced into southern Israel and resulted in continuous silent circulation in the highly immune population. As a part of the public health emergency response, a novel real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was developed, to allow for the sensitive and specific detection of the circulatingWPV1-South Asian (SOAS) strain. Specific primers and probes derived from the VP-1 region were designed, based on sequenced sewage isolates, and used to simultaneously amplify this WPV1-SOAS sequence together with bacteriophage MS-2 as internal control. High titre WPV1-SOAS stock virus was used for assay optimisation and 50 processed sewage samples collected from southern Israel and tested by reference culture based methods were used for analytical validation of the assay's performance. The limit of detection of the multiplex qRT-PCR (SOAS/MS-2) assay was 0.1 plaque-forming unit (pfu)/reaction (20 pfu/mL) for WPV1-SOAS RNA with 100% sensitivity, specificity, positive and negative predictive values when compared to the culture based method. The turnaround time was rapid, providing results for environmental samples within 24 to 48 hours from completion of sewage processing, instead of five to seven days by culture-based analysis. Direct sewage testing by qRT-PCR assay proved to be a useful tool for rapid detection and environmental surveillance of WPV1-SOAS circulating strain during emergency response. Application of the approach for detection of WPV1-SOAS in stool samples obtained during acute flaccid paralysis (AFP) surveillance or field surveys should be further evaluated.

Molecular epidemiology of silent introduction and sustained transmission of wild poliovirus type 1, Israel, 2013.

Poliovirus vaccine coverage in Israel is over 90%. The last nine birth cohorts have been vaccinated exclusively with inactivated polio vaccine (IPV). However, between February and July 2013 type 1 wild poliovirus (WPV1) was detected persistently in 10 and intermittently in 8 of 47 environmental surveillance sites in southern and central Israel and in 30 stool samples collected during July from healthy individuals in southern Israel. We report results of sequence and phylogenetic analyses of genes encoding capsid proteins to determine the source and transmission mode of the virus. WPV1 capsid protein 1 nucleotide sequences were most closely related to South Asia (SOAS) cluster R3A polioviruses circulating in Pakistan in 2012 and isolated from Egyptian sewage in December 2012. There was no noticeable geographical clustering within WPV1-positive sites. Uniform codon usage among isolates from Pakistan, Egypt and Israel showed no signs of optimisation or deoptimisation. Bayesian phylogenetic time clock analysis of the entire capsid coding region (2,643 nt) with a 1.1% evolutionary rate indicated that Israeli and Egyptian WPV1-SOAS lineages diverged in September 2012, while Israeli isolates split into two sub-branches after January 2013. This suggests one or more introduction events into Israel with subsequent silent circulation despite high population immunity.

Intensified environmental surveillance supporting the response to wild poliovirus type 1 silent circulation in Israel, 2013.

An emergency response was triggered by recovery of wild poliovirus type 1 (WPV1) of the South Asia (SOAS) lineage from sewage in southern Israel in April 2013 during routine environmental surveillance. Public health risk assessment necessitated intensification of environmental surveillance in order to facilitate countrywide monitoring of WPV1-SOAS circulation. This involved increasing sampling frequency and broadening the geographical area, for better coverage of the population at risk, as well as modifying sewage testing algorithms to accommodate a newly developed WPV1-SOAS-specific quantitative real-time RT-PCR assay for screening of RNA extracted directly from sewage concentrates, in addition to standard virus isolation. Intensified surveillance in 74 sites across Israel between 1 February and 31 August 2013 documented a sustained high viral load of WPV1-SOAS in sewage samples from six Bedouin settlements and two cities with Jewish and Arab populations in the South district. Lower viral loads and intermittent detection were documented in sampling sites representing 14 mixed communities in three of the five health districts in central and northern Israel. Environmental surveillance plays a fundamental role in routine monitoring of WPV circulation in polio-free countries. The rapid assay specific for the circulating strain facilitated implementation of intensified surveillance and informed the public health response and decision-making.

Insidious reintroduction of wild poliovirus into Israel, 2013.

Israel was certified as polio-free country in June 2002, along with the rest of the World Health Organization European Region. Some 11 years later, wild-type polio virus 1 (WPV1) was isolated initially from routine sewage samples collected between 7 and 13 April 2013 in two cities in the Southern district. WPV1-specific analysis of samples indicated WPV1 introduction into that area in early February 2013. National supplementary immunisation with oral polio vaccine has been ongoing since August 2013.

Intestinal immunity following a combined enhanced inactivated polio vaccine/oral polio vaccine programme in Israel.

Intestinal immunity was studied in a polio-free community immunised with a combined enhanced inactivated/oral polio vaccine (EIPV/OPV) vaccination programme. Poliovirus excretion was evaluated in three groups of infants primed with a partial (2 EIPV+2 OPV) or complete (3 EIPV+3 OPV) dose schedule. Poliovirus replicated in the gut of 59.8-55.8% of infants in the three groups 7 days after administration of an additional OPV dose. Significant decreases in the percent of type-specific-virus excreters appeared after 14 and 21 days for serotypes 1 and 2, and after 21 and 28 days for serotype 3. The percent of excreters was inversely correlated with pre-challenge neutralising antibody (NA) titers (p<0.05). Intrafamilial virus transmission to mothers and siblings was minimal. The principal factor for interruption of disease and virus transmission in the community was a strong and persistent humoral immunity with immunological memory. A satisfactory level of family hygiene contributed towards breaking the chain of transmission of poliovirus to contacts.

Advanced environmental surveillance and molecular analyses indicate separate importations rather than endemic circulation of wild type 1 poliovirus in Gaza district in 2002.

An improved sewage surveillance algorithm (sample acquisition, processing, and molecular analysis) for wild and vaccine-derived polioviruses was developed and validated. It was based on plaque isolation with sensitive and high-throughput methods. The molecular analysis included sequencing; a comparison of the type, rate, and distribution of nucleotide substitutions with a profile for outbreaks evolving from a single progenitor; and phylogenetic analysis for relative similarity. The analyses revealed that two environmental wild type 1 isolates from the Gaza district in 2002 were imported separately, most likely from Egyptian southern governorates, and were not linked by endemic circulation. These findings illustrate the continuous spreading potential of wild-type poliovirus and underscore the value of extensive environmental surveillance employing advanced molecular analysis to monitor wild poliovirus in poliomyelitis-free regions.

[Early results of one-stage septic revision arthroplasties with antibiotic-laden cement. A clinical and statistical analysis]. / Frühergebnisse des einzeitigen septischen TEP-Wechsel mit antibiotikahaltigem Knochenzement. Klinische und statistische Analyse.

BACKGROUND: Periprosthetic infections will generally require revision arthroplasty. The one-stage revision arthroplasty with antibiotic-laden cement is hence an attractive therapeutic option, since it only requires one operation, has a low morbidity and, if successful, is cost-efficient. MATERIALS AND METHODS: We performed one-stage revision arthroplasties. The exchanged prostheses were fixed with antibiotic-laden cement after biotic resistance was determined. All patients were treated with postoperative systemic antibiotics. RESULTS: After a mean postoperative examination period of 18.4 months, we confirmed eradication of infection in 14 of 15 knee joints and in 15 of 16 hip joints. The mean duration of hospital stay was 23 days. Patients' satisfaction was high (93.55%) and the clinical results were satisfactory. CONCLUSION: Our analysis shows that our low early reinfection rate (6.45%) is within statistical expectation. Furthermore, we have showed that there is evidence to suggest that the rate of successful outcomes in one-stage revision arthroplasties, at least at the hip, is not different from the rate of two-stage revision arthroplasties and that the difference may be interpreted as stochastic deviation (p=0.264494). According to existing studies, an analogy to knee arthroplasties can be assumed. We demonstrated that one-stage revision is an adequate therapeutic option if patients are carefully selected and under the supervision of an experienced surgeon.

The role of tamoxifen in the treatment of symptomatic uterine leiomyomata -- a pilot study.

OBJECTIVES: To determine the efficacy of tamoxifen in patients with leiomyomata complaining of abdominal pains and vaginal bleeding. STUDY DESIGN: Prospective, randomized, double blind study. A total of 10 patients received for 6 months 20 mg tamoxifen daily, and 10 women received placebo. All patients underwent serial pelvic and ultrasound exams and endometrial sampling was performed prior to initiation of treatment. After 5 years, the patients were interviewed again. RESULTS: Uterine size was not affected by the use of tamoxifen. Patients reported a blood loss decrease of 40--50% at the end of the study (P=0.0001). In the control group a slight increase in blood loss was reported. Hemoglobin levels remained unchanged in both groups. In the study group patients reported after 4 months of treatment a substantial decrease in the intensity of pain (P=0.018). Seven patients in the study group and one patient in the control group developed ovarian cysts. CONCLUSIONS: Treatment with tamoxifen added only marginal benefit while causing unacceptable side effects. Tamoxifen does not seem to be a useful adjunct in the treatment of symptomatic uterine leiomyomata and its use for this indication should be discouraged.

Fibrous connective tissue lesion mimicking a vestibular schwannoma: case report.

OBJECTIVE AND IMPORTANCE: Cerebellopontine angle fibromas are rare pathological entities that can mimic the presentation of vestibular schwannomas (VSs). Diagnosis of these benign lesions, however, is important, because treatment options may be different. The clinical, radiological, and intraoperative features of these unusual lesions of the cerebellopontine angle are discussed, with review of the relevant literature. CLINICAL PRESENTATION: A 41-year-old man presented with recurrent episodes of diminished hearing on the left side, accompanied by facial ticks and pain on the same side. Magnetic resonance imaging and computed tomographic scans revealed a 1.5-cm, primarily intracanalicular lesion, suggesting a left VS. INTERVENTION: The lesion was partially removed through a retrosigmoid suboccipital craniotomy. Its intraoperative appearance and hard fibrotic consistency differed from the classic features of VSs. The pathological findings indicated nontumoral fibrous connective tissue. The lesion exhibited no features of inflammation or fat and was also negative for S-100 staining. Follow-up magnetic resonance imaging scans demonstrated a small residual lesion, which exhibited shrinkage in subsequent magnetic resonance imaging studies. The painful ticks disappeared and facial nerve weakness improved postoperatively. CONCLUSION: Although cerebellopontine angle fibromas may present similar radiological features, their clinical presentation may be somewhat different from that of typical VSs. If a fibroma is suspected, radiosurgery should be avoided; limited surgery may be considered as an option for patients experiencing symptoms. Because fibromas may be intraoperatively noted to be fibrotic and vascular, radical removal may not be easy or justified. After the final diagnosis has been reached, conservative treatment of the residual lesion may be the best option.

'Subinhibitory' erythromycin represses production of Pseudomonas aeruginosa lectins, autoinducer and virulence factors.

Pseudomonas aeruginosa infection is preceded by selective adhesion of the bacteria to the host target cells via diverse adhesins, including lectins. This step enables maximal damage to the target host cells by the bacterially secreted injurious toxins and enzymes. The production of both lectins and many of the virulence factors is positively controlled by transcription activators including signaling autoinducers (N-acyl-L-homoserine lactones). We show in this communication that erythromycin at subminimal growth inhibitory concentrations simultaneously suppresses the production of P. aeruginosa hemagglutinins (including lectins), protease, hemolysin and homoserine lactone autoinducers. The antibiotic-treated bacteria also show reduced virulence to mice, endorsing clinical observations that indicate the efficiency of low-dose erythromycin treatment of persistent drug-resistant P. aeruginosa infections.

Sternal wound infections in patients after coronary artery bypass grafting using bilateral skeletonized internal mammary arteries.

OBJECTIVES: This study evaluated the risks of sternal wound infections in patients undergoing myocardial revascularization using bilateral skeletonized internal mammary arteries (IMAs). BACKGROUND: The skeletonized IMA is longer than the pedicled one, thus providing the cardiac surgeon with increased versatility for arterial myocardial revascularization without the use of vein grafts. It is isolated from the chest wall gently with scissors and silver clips, and no cauterization is employed. Preservation of collateral blood supply to the sternum and avoidance of thermal injury enable more rapid healing and decrease the risk of sternal wound infection. METHODS: From April 1996 to August 1997, 545 patients underwent arterial myocardial revascularization using bilateral skeletonized IMAs. The right gastroepiploic artery was used in 100 patients (18%). The average age of the patients was 65 years; 431 (79%) were men and 114 (21%) were women; 179 (33%) were older than 70 years of age; 166 (30%) were diabetics. The average number of grafts was 3.2 per patient. RESULTS: The 30-day operative mortality rate was 2% (n = 11). There were six perioperative infarcts (1.1%) and six strokes (1.1%); 9 patients had sternal infection (1.7%) and 15 (2.8%) had superficial infection. Risk factors for sternal infection were chronic obstructive pulmonary disease and emergency operation. Superficial sternal wound infections were more common in women and in patients with chronic obstructive pulmonary disease, renal failure, or peripheral vascular disease. The 1-year actuarial survival rate was 97%. Two of the six late deaths were not cardiac-related. Late dehiscence occurred in three patients (0.6%). The death rate (early and late) of patients with any sternal complication was higher than that of patients without those complications (33% vs. 2.7%). CONCLUSIONS: Routine arterial myocardial revascularization using bilateral skeletonized IMAs is safe, and postoperative morbidity and mortality rates are low, even in elderly patients and those with diabetes. Chronic obstructive pulmonary disease and emergency operations were found to be associated with an increased risk of sternal infections, and the authors recommend avoiding the use of bilateral skeletonized IMAs in patients with these preoperative risk factors.

Planter foot pressures in pregnant women.

UNLABELLED: The physiological changes occurring during pregnancy may be responsible for the faulty foot position leading to backache and lower limb pain. We evaluated the changes in the plantar foot pressures during pregnancy. Twenty-eight, full-term, healthy, pregnant women, average age 28 years, were examined and evaluated clinically, and the plantar foot pressure distribution was measured statically and dynamically using the EMED system. Twenty-eight, non-pregnant women, average age 25 years, served as the control group. In the static measurements, the pregnant women had significantly lower maximal forefoot pressures and higher hindfoot pressures than the non-pregnant women. The area of the foot in contact with the measuring pressure plate was greater in the pregnant women than in the non-pregnant women. In the dynamic measurements, the maximal force in almost every area of interest was significantly higher. The total force exerted on the pressure plate at the instant of maximal force of every area of interest during the whole step was higher in the pregnant group. On the medial side of the forefoot there was a slight decrease in the contact time of the maximal force. The peak pressures were higher in the midfoot of both feet and on the lateral side of the right forefoot in the pregnant women. In the medial side of the forefoot, the peak pressures were lower in pregnant women. CONCLUSIONS: The pregnant woman has a different pattern of gait. There is an increase of load on the lateral side of the foot and the hindfoot. These changes may be responsible for the musculoskeletal complaints of lower limb pain in pregnant women.

Synergism of tumor necrosis factor-alpha and melphalan in systemic and regional administration: animal study.

Tumor necrosis factor (TNF) is a highly cytotoxic cytokine. However, due to its severe side effects, the only clinical situation allowing its administration in humans is isolated limb perfusion (ILP). Early studies have shown that TNF alone is of limited efficacy even at high doses via ILP, and that a chemotherapeutic agent needs to be added. The most commonly used drug in this setting is melphalan which is considered to be synergistic with TNF. However, since melphalan has not been commonly used in sarcoma, we believed that confirmation of its synergistic effect with TNF in an experimental sarcoma model could prove valuable for future drug choice. B16F10 melanoma and CT26 colon carcinoma cells were injected subcutaneously (s.c.) into mice, while GF fibrosarcoma cells were injected s.c. into the hindleg of Wistar rats. The animals were then divided into four treatment groups: TNF alone, melphalan alone, TNF and melphalan, and 0.9% NaCl controls. Mice were treated with intraperitoneal injections and rats by ILP. TNF dosage was 20 microgram for mice and 200 microgram for rats. Melphalan was given at 5-10 mg/kg for both mice and rats. Results showed synergism of TNF and melphalan in both modes of therapy. In the systemic administration groups (mice carrying B16F10 and CT26 tumors), tumors increased in size in all but the combined TNF-melphalan group. In the regional delivery groups (rats carrying GF sarcoma cells treated via ILP), there was a 16% decrease in tumor volume in rats treated with TNF alone, a 29% decrease in rats treated with melphalan, and a 75% decrease in the combined TNF-melphalan group. In conclusion, TNF and melphalan proved to be highly synergistic in both systemic and regional delivery. This fact makes melphalan an adequate choice for TNF perfusion in advanced limb malignancies.

[Central neurocytoma].

4 cases of central neurocytoma are reported. Sex distribution was symmetrical, average age at presentation was 29.7 years, and duration of symptoms varied from 1 day to 5 years. Headache and nausea were the most frequent symptoms; 1 patient was asymptomatic, 3 tumors were located in the left lateral ventricle and 1 in the third ventricle. 3 were operated on via an interhemispheric transcallosal route and 1 transcortically. Morbidity included symptomatic subdural effusions (2 cases), short term memory deficit (1) and transient hemiparesis with aphasia (1). There was no mortality.

[Restorative proctocolectomy for ulcerative colitis and familial polyposis].

From 1987-1994 we performed 35 proctocolectomies with ileal pouch anal anastomosis. The indication for operation was ulcerative colitis in 29 and familial polyposis in 6. The mean ages at operation were 35 and 25 years, respectively. The most common postoperative complication was small bowel obstruction in 25% of the patients, requiring re-operation in half of them. The incidence of this complication may be reduced by operating in only 1 stage when possible, without creating a protective ileostomy. The second serious complication was pouchitis, in 17%, which was controlled by antibiotics. There has been no mortality. All patients, except for 2 with an S-shaped pouch, evacuate spontaneously a mean of 5 bowel movements a day. Continence was mildly impaired (usually night-staining of a pad) in 30% of patients in whom the pouch-anal anastomosis was performed after stripping the mucosa of the rectal remnant. In those in whom the pouch-anal anastomosis was performed by means of the double stapling technique, continence was almost completely preserved. We therefore recommend that proctocolectomy with ileal pouch-anal anastomosis be performed in 1 stage when possible, using the double stapling technique. Staged operation should be reserved for severely ill patients, or when stripping of the rectal mucosa is performed for familial polyposis and ulcerative colitis with severe dysplasia.

[Stereotactic brain biopsy].

During a 3-year period starting in 1991, 49 patients with brain lesions underwent 50 stereotactic brain biopsy procedures. The average age was 46 years (range 4-74). Specimens were taken from various brain regions, particularly from the deep aspect of the cerebral hemispheres and midline structures. The pathologic entities included 27 gliomas (13 glioblastomas, 6 astrocytomas, 3 anaplastic astrocytomas, 1 pilocytic astrocytoma and 4 oligodendrogliomas), 5 lymphomas, 2 germinomas, 1 primitive neuroectodermal tumor, 2 metastatic tumors and 11 non-neoplastic lesions (4 demyelination, 2 infarcts, 1 hematoma, 1 brain abscess, 1 radiation necrosis, 1 Alzheimer's disease and in 1 case no diagnosis). The diagnostic success of the stereotactic brain biopsies in this series was 96% (in 98% of the patients). The mean hospital stay was 3 days. 1 patient with a multifocal bilateral glioblastoma died due to early postoperative hematoma of the basal ganglia (2%). Another 2 patients underwent craniotomy due to post-biopsy hematoma. They continued to suffer from hemiparesis after discharge. Transient Horner's syndrome was noted in 1 patient. Thus the permanent morbidity rate was 4%. We conclude that stereotactic brain biopsy can be performed relatively safely, has a high diagnostic yield, and facilitates planning of treatment.

Embryonic cultures but not embryos transplanted to the mouse's brain grow rapidly without immunosuppression.

Embryos and embryocultures can be successfully transplanted into various bodily organs. However immunosuppression or homogenicity are required for the success of such experimental manipulation. Since the brain is considered immunologically privileged, we transplanted 2-4 cell embryos of C57BL x BALB/c, embryonic stem cells (ES) or embryoid bodies (EB) cultures into the hippocampus of the heterogeneous mouse stock HS/IBg. Both ES and EB cultures developed into an extensive growth, eventually larger than the brain itself, causing the death of the host in less than 29 days. The growth was identified as teratoma, mostly made of immature cells and tissues of diverse origin. Thus, the overall histological picture was that of a malignant teratoma. On the other hand, no embryos were found at any time after the transplantation; apparently, they could not survive in the host brain. The growth rate and the relative lack of rejection suggest that the brain offers a unique medium for ES and EB cultures but, not to embryos.

Morphometric and freeze-fracture studies on peripheral nerve in shiverer mice.

Observations have been made on the peripheral nerves of shiverer (shi/shi) mice in comparison with control animals. Although this mutant lacks P1 myelin basic protein in peripheral and central myelin, myelin is defective only in the central nervous system. No ultrastructural abnormalities were observed in the shiverer nerves. Myelin spacing was normal. The density and distribution of intramembranous particles on the E and P faces of myelin and in the axolemma of myelinated and unmyelinated axons did not differ between the shiverer and control mice. Morphometric studies showed that external myelinated fiber diameter was significantly less and that myelin thickness was slightly but significantly greater in relation to axon diameter in the shiverer mice, suggesting a minor degree of axonal atrophy. It is concluded that P1 protein is not necessary for the formation and maintenance of the normal structure of peripheral myelin. The failure to detect differences in intramembranous particle density in myelin between shiverer and control mice indicates that P1 protein is not detected in freeze-fracture preparations.