Mother-to-child transmission of extended-spectrum-beta-lactamase-producing Enterobacteriaceae.

BACKGROUND: Preterm infants are at high risk for extended-spectrum-beta-lactamase-producing Enterobacteriaceae (ESBL-E) sepsis and neonatal intensive care unit (NICU) outbreaks. Maternal colonization with ESBL-E may be precursory to mother-to-child transmission. However, there is no consensus regarding surveillance of pregnant women for ESBL-E colonization. AIM: To identify pairs of mothers and infants harbouring same-strain ESBL-E colonization and to determine whether maternal transmission may play a role in increasing ESBL-E carriage in preterm infants. METHODS: This was a one-year analysis from an ongoing, prospective ESBL-E surveillance of mothers of premature infants and their offspring. Mother-infant pairs colonized with the same bacteria underwent strain analysis using pulsed-field gel electrophoresis (PFGE). Clinical parameters were collected from the hospital computerized records. FINDINGS: Between January 2015 and January 2016, 313/409 (76.5%) mothers and all 478 (100%) infants were screened for ESBL-E colonization; carriage rates were 21.5% and 14.8%, respectively. Four (5.6%) colonized infants developed late-onset sepsis and two (2.8%) died. Twenty-five mother-infant pairs colonized with the same bacterial strain were identified; a subgroup of 10 pairs of isolates underwent PFGE, and 70% displayed an identical PFGE fingerprint. No similarities were found between isolates recovered from unrelated neonates and mothers. ESBL-E colonization was found significantly earlier in infants of mothers colonized at birth (P<0.001) compared with infants of non-colonized mothers. CONCLUSIONS: ESBL-E carriage rates in mothers and NICU infants with non-negligible maternal-neonatal ESBL-E transmission in the study region indicate that maternal colonization surveillance and/or further infection control interventions should be considered.

Stress impairs the efficacy of immune stimulation by CpG-C: Potential neuroendocrine mediating mechanisms and significance to tumor metastasis and the perioperative period.

We recently reported that immune stimulation can be compromised if animals are simultaneously subjected to stressful conditions. To test the generalizability of these findings, and to elucidate neuroendocrine mediating mechanisms, we herein employed CpG-C, a novel TLR-9 immune-stimulating agent. Animals were subjected to ongoing stress (20-h of wet cage exposure) during CpG-C treatment, and antagonists to glucocorticoids, ß-adrenoceptor, COX2, or opioids were employed (RU486, nadolol, etodolac, naltrexone). In F344 rats, marginating-pulmonary NK cell numbers and cytotoxicity were studied, and the NK-sensitive MADB106 experimental metastasis model was used. In Balb/C mice, experimental hepatic metastases of the CT-26 colon tumor were studied; and in C57BL/6J mice, survival rates following excision of B16 melanoma was assessed - both mouse tumor models involved surgical stress. The findings indicated that simultaneous blockade of glucocorticoid and ß-adrenergic receptors improved CpG-C efficacy against MADB106 metastasis. In mice bearing B16 melanoma, long-term survival rate was improved by CpG-C only when employed simultaneously with blockers of glucocorticoids, catecholamines, and prostaglandins. Prolonged stress impaired CpG-C efficacy in potentiating NK activity, and in resisting MADB106 metastasis in both sexes, as also supported by in vitro studies. This latter effect was not blocked by any of the antagonists or by adrenalectomy. In the CT26 model, prolonged stress only partially reduced the efficacy of CpG-C. Overall, our findings indicate that ongoing behavioral stress and surgery can jeopardize immune-stimulatory interventions and abolish their beneficial metastasis-reducing impacts. These findings have implications for the clinical setting, which often involve psychological and physiological stress responses during immune-stimulation.

GAB2 induces tumor angiogenesis in NRAS-driven melanoma.

GAB2 is a scaffold protein with diverse upstream and downstream effectors. MAPK and PI3K signaling pathways are known effectors of GAB2. It is amplified and overexpressed in a variety of human tumors including melanoma. Here we show a previously undescribed role for GAB2 in NRAS-driven melanoma. Specifically, we found that GAB2 is co-expressed with mutant NRAS in melanoma cell lines and tumor samples and its expression correlated with metastatic potential. Co-expression of GAB2(WT) and NRAS(G12D) in melanocytes and in melanoma cells increased anchorage-independent growth by providing GAB2-expressing cells a survival advantage through upregulation of BCL-2 family of anti-apoptotic factors. Of note, collaboration of GAB2 with mutant NRAS enhanced tumorigenesis in vivo and led to an increased vessel density with strong CD34 and VEGFR2 activity. We found that GAB2 facilitiated an angiogenic switch by upregulating HIF-1α and VEGF levels. This angiogenic response was significantly suppressed with the MEK inhibitor PD325901. These data suggest that GAB2-mediated signaling cascades collaborate with NRAS-driven downstream activation for conferring an aggressive phenotype in melanoma. Second, we show that GAB2/NRAS signaling axis is non-linear and non-redundant in melanocytes and melanoma, and thus are acting independent of each other. Finally, we establish a link between GAB2 and angiogenesis in melanoma for the first time. In conclusion, our findings provide evidence that GAB2 is a novel regulator of tumor angiogenesis in NRAS-driven melanoma through regulation of HIF-1α and VEGF expressions mediated by RAS-RAF-MEK-ERK signaling.

PGE2 suppresses NK activity in vivo directly and through adrenal hormones: effects that cannot be reflected by ex vivo assessment of NK cytotoxicity.

Surgery can suppress in vivo levels of NK cell cytotoxicity (NKCC) through various mechanisms, including catecholamine-, glucocorticoid (CORT)-, and prostaglandin (PG)-mediated responses. However, PGs are synthesized locally following tissue damage, driving proinflammatory and CORT responses, while their systemic levels are often unaffected. Thus, we herein studied the role of adrenal factors in mediating in vivo effects of PGs on NKCC, using adrenalectomized and sham-operated F344 rats subjected to surgery or PGE(2) administration. In vivo and ex vivo approaches were employed, based on intravenous administration of the NK-sensitive MADB106 tumor line, and based on ex vivo assessment of YAC-1 and MADB106 target-line lysis. Additionally, in vitro studies assessed the kinetics of the impact of epinephrine, CORT, and PGE(2) on NKCC. The results indicated that suppression of NKCC by epinephrine and PGE(2) are short lasting, and cannot be evident when these compounds are removed from the in vitro assay milieu, or in the context of ex vivo assessment of NKCC. In contrast, the effects of CORT are long-lasting and are reflected in both conditions even after its removal. Marginating-pulmonary NKCC was less susceptible to suppression than circulating NKCC, when tested against the xenogeneic YAC-1 target line, but not against the syngeneic MADB106 line, which seems to involve different cytotoxicity mechanisms. Overall, these findings indicate that elevated systemic PG levels can directly suppress NKCC in vivo, but following laparotomy adrenal hormones mediate most of the effects of endogenously-released PGs. Additionally, the ex vivo approach seems limited in reflecting the short-lasting NK-suppressive effects of catecholamines and PGs.

Postoperative voiding dysfunction in older male renal transplant recipients.

OBJECTIVE: To evaluate the incidence of voiding dysfunction in older male renal transplant recipients. PATIENTS AND METHODS: Data for 103 patients aged 60 years or older (mean age, 65.7 years; group 1) who underwent transplantation at our center between January 1999 and August 2007 were compared with data for a group of 139 younger patients (mean age, 50.1 years; group 2) treated within the same time frame. RESULTS: Postoperatively, 28 group 1 recipients (27%) and 26 group 2 recipients (19%) experienced voiding dysfunction after removal of the transurethral catheter (P = .12). The most common cause was bladder outlet obstruction due to benign prostatic hyperplasia in 26 patients in group 1 (25%) and 17 patients in group 2 (12%) (P = .009). Bladder neck contracture, urethral stricture, and detrusor underactivity were diagnosed in the other patients. Transurethral resection of the prostate gland was performed in 21 group 1 patients (20%) and 14 group 2 patients (10%) (P = .02) at a mean of 31.1 and 29.5 days, respectively (P = .23) after transplantation. Surgical procedures were performed without complication, and symptoms did not recur postoperatively. CONCLUSIONS: Our data reveal a high incidence of voiding dysfunction in older male renal transplant recipients. High residual urine and urinary retention after renal transplantation may induce recurrent urinary tract infections, cause relevant complications, and seriously affect graft function. Recognizing the substantial effects of postoperative voiding dysfunction will enable optimum management of older kidney transplant recipients.

Assisted reproduction professionals' awareness and attitudes towards their own IVF cycles.

OBJECTIVE: Professionals involved in assisted reproductive technologies (ART) have in-depth awareness and knowledge of the risks of multiple pregnancies at the conclusion of in vitro fertilization (IVF) treatment. The aim of the study was to investigate ART professionals' attitudes towards the awareness of the risk of infertility, as well as the decision-making process in IVF issues. METHODS: Seventy ART professionals answered a questionnaire covering demographic data, infertility awareness and attitudes towards IVF. RESULTS: Approximately half (50.8%) of the participants thought that they were not at risk of infertility. However, if they received a diagnosis of infertility, none would accept childlessness and almost all would undergo IVF. In an IVF cycle, the number of high-quality embryos transferred would be around three, but if treatment was extended to a third cycle, a higher percentage of participants would elect to transfer four or more embryos. All participants would prefer to undergo IVF and accept the risk of multiple pregnancy than remaining childless. It was found that less than a third of ART professionals considered triplets to be an unacceptable complication of IVF. CONCLUSIONS: Diagnosis of infertility affects all participants psychosocially, supporting the idea that the emotional aspects of wanting a biological child, and decision making about whether to undertake ART, outweigh the medical position regarding the risks and benefits of IVF.

Clonal variability of group B Streptococcus among different groups of carriers in southern Israel.

A high prevalence of maternal group B Streptococcus (GBS) carriage and an extremely low incidence of invasive neonatal disease have been reported from southern Israel. In order to obtain insight into this discrepancy, this study was performed to determine the population structure of GBS from asymptomatic pregnant women living in this area. Seventy-two strains from maternal GBS carriers were characterized using multilocus sequence typing (MLST). Epidemiologic characteristics of the carriers and their newborns, including demographic variables, obstetric status, and general health parameters, were collected by means of a postpartum interview and a review of the relevant medical records. The MLST analysis grouped the bacteria into six different lineages (clonal complexes). Lineage ST-2 was prevalent among Bedouin-Arabs (p=0.01) and lineage ST-22 among Jews (p=0.001). Lineage ST-17 was prevalent among carriers who emigrated after 1997 from western nations of the former USSR (p<0.001). Lineage ST-22 was associated with carriage of surface-protein C (p=0.01) and lineage ST-17 with surface-protein R (p<0.01). Lineage ST-2 was prevalent among consumers of antibiotics (p=0.02) and was associated with erythromycin-resistant strains (p<0.001). Each subgroup of the southern Israeli maternal population has a different distribution of GBS clones. The clones prevalent among the Bedouin-Arabs and the Jews are known to be of low virulence. Lineage ST-17, which is associated with invasive disease, is prevalent among women who emigrated from western Soviet nations. Therefore, a different policy of GBS prophylaxis, resembling the one executed in endemic areas, should be considered in this population.

Successful control of an Acinetobacter baumannii outbreak in a neonatal intensive care unit.

We describe an outbreak of Acinetobacter baumannii in a neonatal intensive care unit (NICU), and our investigation to determine the source and mode of transmission and identify the population at risk. A case (infected infant) was defined as a patient hospitalized in the NICU during the outbreak period, with clinical signs of sepsis and isolation of A. baumannii. In colonized infants, A. baumannii was isolated from body surfaces without signs of infection. Infected infants were separated and treated by a different medical team. Cultures were taken from working surfaces and along the infant's admission passage from the delivery room to the NICU. The outbreak strain was identified by pulsed-field gel electrophoresis (PFGE). Nine cases and eight colonized infants met the definition criteria. Cases were younger than colonized infants with regard to gestational age and age of diagnosis and had lower birthweights (P<0.01). The outbreak strain was only isolated from hygroscopic bandages used on skin under the ventilation tube and umbilical catheters. Discontinuing the use of the bandages put an end to the outbreak. We conclude that a rapid and thorough investigation of the environment during an outbreak of A. baumannii is essential to finding the source of the infection, and that hygroscopic bandages may be a source of such outbreaks.

[LaMedica. The medical education academy on the internet]. / LaMedica. Die medizinische Lernakademie im Internet.

At present, "modern media" are still a novelty in medical education. The "LaMedica Project"--a program supported by the Federal Ministry for Education and Research--intends to provide an Internet-based education and training system for the entire field of medicine, using all available media resources. This online educational program will provide subjects for medical laypersons as well as medical experts. Various styles of learning and different learning requests will be promoted. The project presented mirrors the cutting edge of database technology, computer-based training and media didactics, critical content processing as well as supplying individual subjects. This report summarizes our 10 months of experience with this program at the Department for Urology and Pediatric Urology of the Johann Wolfgang Goethe University of Frankfurt Main.

Attenuation of the tumor-promoting effect of surgery by spinal blockade in rats.

BACKGROUND: The perioperative period is characterized by a state of immunosuppression, which was shown in animal studies to underlie the promotion of tumor metastasis by surgery. As this immunosuppression is partly ascribed to the neuroendocrine stress response, the authors hypothesized that spinal blockade, known to attenuate this response, may reduce the tumor-promoting effect of surgery. METHODS: Fischer-344 rats were subjected to a laparotomy during general halothane anesthesia alone or combined with either systemic morphine (10 mg/kg) or spinal block using bupivacaine (50 microg) with morphine (10 microg). Control groups were either anesthetized or undisturbed. Blood was drawn 5 h after surgery to assess number and activity of natural killer cells, or rats were inoculated intravenously with MADB106 adenocarcinoma cells, which metastasize only to the lungs. Metastatic development was assessed by quantifying lung retention of tumor cells 24 h after inoculation or by counting pulmonary metastases 3 weeks later. RESULTS: Laparotomy conducted during general anesthesia alone increased lung tumor retention up to 17-fold. The addition of spinal block reduced this effect by 70%. The number of metastases increased from 16.7 +/- 10.5 (mean +/- SD) in the control group to 37.2 +/- 24.4 after surgery and was reduced to 10.5 +/- 4.7 during spinal block. Systemic morphine also reduced the effects of surgery, but to a lesser degree. Natural killer cell activity was suppressed to a similar extent by surgery and by anesthesia alone. CONCLUSIONS: The addition of spinal blockade to general halothane anesthesia markedly attenuates the promotion of metastasis by surgery.

Timing within the oestrous cycle modulates adrenergic suppression of NK activity and resistance to metastasis: possible clinical implications.

Clinical observations suggest that the rate of metastatic development and long-term mortality following surgery in breast cancer patients is influenced by the menstrual phase during which surgery is conducted. The menstrual cycle is known to modulate various physiological responses and medical conditions that involve adrenergic mechanisms (e.g., asthma). Natural killer activity (NKA), an immune function controlling metastasis, is suppressed following surgery, and in vitro by adrenaline. We therefore hypothesize that the clinical observation may be partly attributable to surgery-induced adrenergic suppression of NK-dependent resistance to metastasis, a suppression that depends on menstrual phase during surgery. To test this hypothesis in rats, 140 F344 females at different phases of their oestrous cycle were injected with a beta-adrenergic agonist, metaproterenol (MP) (0.4 or 0.8 mg kg(-1), s.c.), or with vehicle, before i.v. inoculation with MADB106 tumour cells. This syngeneic mammary adenocarcinoma line metastasizes only to the lungs, and is highly sensitive to NKA. In a second experiment, the suppression of NKA by MP was studied in vitro in blood drawn at different phases of the oestrous cycle (n = 36). Finally, the effects of stress on the number and activity of NK cells were assessed along the oestrous cycle (n = 71). The findings indicate that the suppressive effects of MP on resistance to metastasis and on NKA, are significantly greater during the oestrous phase characterized by high oestradiol levels (D3/proestrus/oestrus). Similarly, NKA per cell was suppressed by stress only during this phase. In untreated animals, in which inadvertent stress was minimized, no effects of the oestrous cycle on NKA or on resistance to metastasis were evident. These findings indicate that the oestrous cycle modulates adrenergic suppression of NKA and of resistance to metastasis. The relevance of these findings to the above clinical observation, as well as that of our related findings in women from a parallel study, is discussed.

Application of physico-chemical amendments for the counteraction of mercury pollution

In order to counteract mercury pollution, due to gold recovery practices, in situ strategies are required. In this study, some physico-chemical additions were tested, in different environmental compartments, to verify their potential to mitigate mercury contamination. Results indicate that the addition of sulfide reduces chemical methylation of Hg(II), but enhances the solubility of Hg0. The use of oxides, phosphate, and organic matter may be effective in the immobilization of Hg(II), depending upon Hg speciation. Calcium was effective in counteracting the solubility enhancement of Hg0 promoted by the presence of Aldrich humic acid.

Successful non-surgical treatment of Candida tropicalis endocarditis with liposomal amphotericin-B (AmBisome).

Fungal endocarditis in children is most commonly a complication of palliative or curative surgery for congenital heart disease, rheumatic valvulitis and prolonged indwelling central venous and umbilical catheters. We describe here the case of a 3-y-old patient with chronic diarrhoea and prolonged total parenteral alimentation who developed severe C. tropicalis endocarditis and was treated successfully using a liposomal preparation of amphotericin-B (AmBisome) without surgical intervention.

Safety and immunogenicity of tetravalent pneumococcal vaccines containing 6B, 14, 19F and 23F polysaccharides conjugated to either tetanus toxoid or diphtheria toxoid in young infants and their boosterability by native polysaccharide antigens.

BACKGROUND: New vaccines against pneumococcal infections in infancy are needed. We assessed in young infants the safety and immunogenicity of two tetravalent vaccines containing pneumococcal 6B, 14, 19F and 23F polysaccharides conjugated to either tetanus toxoid (Pnc-T) or diphtheria toxoid (Pnc-D). METHODS: Pnc-T or Pnc-D containing 3 microg of polysaccharide of each of the four pneumococcal polysaccharides or placebo were given intramuscularly in a double blinded fashion (25 infants per group) at 2, 4 and 6 months of age. At 12 months of age all 75 children were boosted with a 23-valent nonconjugate polysaccharide pneumococcal vaccine. Serum type-specific anticapsular antibody concentrations were measured at 2, 4, 6, 7, 12 and 13 months of age. Adverse events occurring within 72 h after each injection were recorded. RESULTS: Both Pnc-T and Pnc-D were well-tolerated. Pnc-T and Pnc-D had higher antibody concentrations compared with placebo after primary immunity (type 6B, 1.66, 1.40 and 0.60 microg/ml, respectively; type 14, 4.81, 2.65 and 2.22 microg/ml, respectively; type 19F, 2.40, 3.48 and 0.83 microg/ml, respectively; type 23F, 0.96, 0.44 and 0.35 microg/ml, respectively). Proportions of infants with concentrations above 1.0 microg/ml were also higher in the vaccine recipients than in those given placebo. After booster with the nonconjugate polysaccharide vaccine, both geometric antibody concentration and proportion with concentrations > or =1.0 microg/ml were significantly higher among either Pnc-T or Pnc-D recipients than among placebo recipients. CONCLUSIONS: Both Pnc-T and Pnc-D were well-tolerated, induced serotype-specific anticapsular antibodies and induced immunologic memory.

Reduction of pneumococcal nasopharyngeal carriage in early infancy after immunization with tetravalent pneumococcal vaccines conjugated to either tetanus toxoid or diphtheria toxoid.

BACKGROUND: Pneumococcal nasopharyngeal colonization is important for transmission of the organisms. We assessed the ability of two tetravalent conjugate vaccines administered in early infancy to prevent carriage of vaccine-related pneumococci. METHODS: A vaccine containing pneumococcal type 6B, 14, 19F and 23F polysaccharide conjugated to tetanus toxoid (Pnc-T) and a vaccine containing the same four polysaccharides conjugated to diphtheria toxoid (Pnc-D) were compared with placebo, in a double blinded study (25 infants per group). Vaccines (or placebo) were injected at 2, 4 and 6 months of age. At 12 months of age a native (nonconjugate) polysaccharide vaccine was administered as a booster. Serum type-specific anticapsular antibody concentrations were measured and nasopharyngeal cultures were obtained at 2, 4, 6, 7, 12 and 13 months of age. RESULTS: In general carriage of all pneumococci (vaccine- and non-vaccine-related) was low at age 2 months and increased with age. However, for the vaccine-related serotypes (6A, 6B, 14, 19F and 23F) carriage was not increased with age in Pnc-D or Pnc-T recipients. Of all cultures obtained after the full primary series, 7 of 72 (10%), 3 of 62 (5%) and 19 or 70 (27%) were positive for the vaccine-related pneumococcal serotypes among the Pnc-D, Pnc-T and placebo recipients, respectively (P = 0.001 for Pnc-D vs. placebo; P = 0.014 for Pnc-T vs. placebo). Most of the antibiotic-resistant isolates belonged to the vaccine-related serotypes. CONCLUSIONS: A significant reduction in the carriage of vaccine-related strains after administration of conjugate vaccines was observed. These preliminary results suggest that transmission of specific pneumococcal serotypes most often associated with disease and antibiotic resistance may at least partially be controlled by immunization.

Immunogenicity and safety of a liquid combination of DTP-PRP-T [corrected] vs lyophilized PRP-T reconstituted with DTP.

The immunogenicity and safety of a combined diphtheria, tetanus, pertussis and Haemophilus influenzae type b-tetanus conjugate vaccine (DTP-PRP-T) was compared to the same combination obtained by the reconstitution of H. influenzae type b-tetanus conjugate vaccine lyophilized (PRP-T) with liquid diphtheria-tetanus-pertussis vaccine (DTP). Two hundred and sixty-two healthy infants were randomized to receive a intramuscular injection of 0.5 ml of one of the above combination vaccines at 2, 4 and 6 months of age, and a subgroup of 134 infants received a booster dose at 12 months. Serum antibody levels to each vaccine component were measured at ages 2, 6, 7, 12 and 13 months. Systemic and local reactions were assessed during the first 3 days after each injection by diary cards distributed to the parents. After the third dose and booster administered at 12 months of age, significant equivalence between the groups was observed, and the geometric mean titer of anti H. influenzae type b capsular polysaccharide (Hib-CP) antibodies were 5.9 and 32.6 micrograms ml-1 for the liquid combination group and 5.8 and 19.4 for the lyophilized group, respectively. After the third dose, anti-Hib-PC antibody levels of > or = 1.0 microgram ml-1 and 0.15 microgram ml-1 were seen in 94% and 100%, respectively, of the liquid combination group and 90 and 99%, respectively of the lyophilized group. After the booster dose, levels of > or = 1.0 microgram ml-1 were observed in 100% and 93.5% of the liquid combination group and the lyophilized combination group, respectively. Systemic and local reactions to the vaccination were generally mild and did not differ significantly between the groups. We conclude that the liquid combination of DTP-PRP-T is safe and at least as immunogenic as the lyophilized preparation. This liquid preparation, like other combined vaccines may be helpful for planning vaccination programs with a reduced number of injections.

Safety and immunogenicity of a combined pentavalent diphtheria, tetanus, acellular pertussis, inactivated poliovirus and Haemophilus influenzae type b-tetanus conjugate vaccine in infants, compared with a whole cell pertussis pentavalent vaccine.

BACKGROUND: We compared the safety and immunogenicity of two combined diphtheria-tetanus-pertussis-inactivated poliovirus vaccines containing either acellular (Pa, SmithKline Beecham Biologicals) or whole cell (Pw, Pasteur Merieux Connaught) pertussis components, mixed with a Haemophilus influenzae type b polysaccharide polyribosylribitol phosphate-tetanus conjugate vaccine in an open, randomized study in healthy infants. DESIGN: The combined vaccines were given at 2, 4, 6 and 12 months of age, and serum samples were obtained at ages 2, 6, 7, 12 and 13 months. Adverse events were obtained by diary cards. RESULTS: The Pa group (n = 101) had a clearly lower incidence of both local and systemic adverse events than the Pw group (n = 100). Immunogenicity was comparable for the diphtheria and tetanus components, but significantly superior for pertussis toxin, filamentous hemagglutinin, pertactin and polioviruses 1, 2 and 3 in the Pa group. Both groups had an appropriate response with regard to H. influenzae type b polysaccharide polyribosylribitol phosphate, but the dynamics of the response were significantly different: geometric mean concentrations (micrograms per ml) after the second, third and booster doses were 1.27, 5.06 and 23.12 in the Pa group and 2.72, 6.66 and 13.59 in the Pw group, respectively (P = 0.0002 after second dose; P = 0.0005 after booster). CONCLUSION: The presently studied diphtheria, tetanus, acellular pertussis-H. influenzae b vaccine conjugated to tetanus toxoid combination was at least as immunogenic as the diphtheria, tetanus, whole cell pertussis-H. influenzae b vaccine conjugated to tetanus toxoid combination, with a significantly better safety profile. This is of obvious importance in countries where inactivated poliovirus vaccine is part of the routine infant immunization programs.

Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine.

Children 12-18 months old were randomized to receive one dose of a conjugate heptavalent pneumococcal vaccine, two doses of the same vaccine, or one dose of a 23-valent native polysaccharide vaccine. Before immunization, pneumococci included in the conjugate vaccine were isolated from 24% of the children, and an antibiotic-resistant pneumococcus was isolated from 22% of the children. The vaccines had no effect on carriage of non-vaccine-type pneumococci. In contrast, there was a significant reduction in carriage of vaccine-type pneumococci 3 months after one dose and 1 month after a second dose of conjugate vaccine (from 25% to 9% and 7%, respectively; P < .001). No effect was seen after vaccination with the nonconjugate vaccine. One year after immunization, carriage of antibiotic-resistant vaccine-type pneumococci in children receiving conjugate vaccine was lower than that in children receiving the nonconjugate vaccine (4% vs. 14%, P = .042). Conjugate pneumococcal vaccines may reduce spread of pneumococci in the community.

Nasopharyngeal colonization in southern Israel with antibiotic-resistant pneumococci during the first 2 years of life: relation to serotypes likely to be included in pneumococcal conjugate vaccines.

Nasopharyngeal carriage of Streptococcus pneumoniae was studied in 162 healthy infants at ages 2, 4, 6, 7, 12, and 13 months and in an additional 352 healthy children at ages 12, 15, 18, 21, and 24 months. Carriage was 26%, 39%, and 62% at 2, 12, and 24 months, respectively, and the respective resistance to > or = 1 antibiotic was 11%, 19%, and 27%. The presence of an older sibling or antibiotic treatment during the month preceding the culture was associated with carriage of resistant pneumococci in infants, whereas attendance at large day care centers was associated with carriage during the second year of life. Antibiotic resistance was detected in all 7 serotypes included in the candidate pediatric conjugate vaccines and was significantly more prevalent among vaccine-type pneumococci than among non-vaccine-type pneumococci. The use of conjugate vaccines may reduce the spread of resistant pneumococci.

[A national qualifying internal medicine examination for Israeli medical students].

In 1991 the deans of the 4 medical schools in Israel decided to institute a national qualifying examination in internal medicine. This marked the beginning of the process of unifying the qualifying examinations in all major medical fields. We describe the development of the examination, experience with its administration to 720 students in 1992-1994, and the outcome of this initial effort. The examinations were prepared by a committee of senior faculty from the 4 schools, representing all the relevant clinical areas. Professional consultation was provided by the Unit for Medical Education of Tel Aviv University. Each examination consisted of 180 multiple choice items, reflecting an agreed representation of the various medical specialties, and was designed to test both comprehension and problem-solving ability. A syllabus was published by the committee and distributed to students and faculty in preparation for the examination. In composing the examination, the committee took into consideration differences in general policy and varying emphases in the curricula of the 4 schools. Analysis of the results of the 3 annual examinations showed both a high level of reliability and high quality of the majority of the individual test items. There was a trend with time to slightly lower average scores, and fewer passed the exam last year. There was improvement in the results after the first 2 years in the area of problem-solving related to interpretation of imaging, blood smears and clinical photographs, but this trend did not continue into 1994. The introduction of a high level examination based on a common syllabus provided important feedback, improving both student motivation and clinical teaching. For all schools, the outcome of the examination served as an important external indicator of teaching standards. Following this positive experience, uniform examinations in surgical subjects and pediatrics were introduced for the first time in 1993. The committee recommends that Israeli medical schools gradually introduce a comprehensive qualifying examination based on a mutually agreed list of objectives and syllabus.