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Biomedical subjects

Nathan Keller

Publications and source records attributed to Nathan Keller.

15 recordsLinked to original sources
PubMed2006

Postexposure treatment with doxycycline for the prevention of tick-borne relapsing fever.

BACKGROUND: Tick-borne relapsing fever (TBRF) is an acute febrile illness. In Israel, TBRF is caused by Borrelia persica and is transmitted by Ornithodoros tholozani ticks. We examined the safety and efficacy of postexposure treatment to prevent TBRF. METHODS: In a double-blind, placebo-controlled trial, 93 healthy subjects with suspected tick exposure (52 with signs of tick bites and 41 close contacts--those without signs but with a similar risk of contact with ticks) were randomly assigned to receive either doxycycline (Dexxon, in a dose of 200 mg the first day and then 100 mg per day for four days) or placebo after presumed exposure to TBRF. Cases of TBRF were defined by fever and a positive blood smear. Serologic analysis for cross-reactivity to Borrelia burgdorferi and polymerase chain reaction (PCR) for the borrelia glpQ gene were also performed. RESULTS: After randomization, 47 subjects (26 with signs of tick bites and 21 close contacts) received doxycycline. Forty-six other subjects (26 with signs of tick bites and 20 close contacts) received placebo. All 10 cases of TBRF identified by a positive blood smear were in the placebo group of subjects with signs of a tick bite (P<0.001). These findings suggested a 100 percent efficacy of preemptive treatment (95 percent confidence interval, 46 to 100 percent). PCR for the borrelia glpQ gene was negative at baseline for all subjects and subsequently positive in all subjects with fever and a positive blood smear. Seroconversion was detected in eight of nine cases of TBRF. PCR and serum samples were negative for all of the other subjects tested. No major treatment-associated adverse effects were identified. CONCLUSIONS: Treatment with doxycycline is safe and efficacious in preventing TBRF after suspected exposure to ticks in a high-risk environment. (ClinicalTrials.gov number, NCT00237016 [ClinicalTrials.gov].).

Adult↗
PubMed2006

MCP-1 in the cerebrospinal fluid of children with acute lymphoblastic leukemia.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC chemokines. MCP-1 has been previously shown to have a major role in the migration of monocytes towards human leukemic cells, yet it cannot increase cytotoxic effects of monocytes on human leukemic cells. AIM: To determine levels of MCP-1 in the CSF of children during various stages of acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: A 19 children with ALL and without known CNS involvement were enrolled in the study. CSF samples were aliquoted at different stages of therapy (diagnosis, induction, and maintenance) and were frozen at -70 degrees C until use. MCP-1 was measured with a sandwich enzyme-linked immunoabsorbent assay. RESULTS: Mean MCP-1 levels in the CSF were 1762.38 pg/ml (range 522-5000 pg/ml). In children without CNS involvement at diagnosis, CSF MCP1 levels did not change over time and remained within this range throughout the diagnosis and treatment stages. CNS involvement was associated with an increased MCP-1 level following chemotherapy, in patients with CNS involvement from 840 to 3990 pg/ml (P<0.0001), and in patients without CNS involvement from 1134 to 1943 pg/ml (P-value of 0.0322). White blood cells found in the CSF at diagnosis have vanished after induction. CONCLUSIONS: CNS involvement in ALL is associated with significantly higher levels of MCP1 during therapy. This significant rise in MCP-1 levels might be one of the mechanisms involved in the regulation of CNS leukemia. Since chemokines target specific leukocyte subsets, inhibition of a single Chemokine ligand or receptor may have a circumscribed effect, endowing the inhibitor with a limited side effect profile. Chemokines should be considered as possible targets for therapeutic intervention.

Adolescent↗
PubMed2005

An outbreak of Phialemonium infective endocarditis linked to intracavernous penile injections for the treatment of impotence.

BACKGROUND: In March 2002, a patient in Tel Aviv, Israel, died of endocarditis caused by Phialemonium curvatum. As part of his therapy for erectile dysfunction, the patient had been trained to self-inject a compound of vasoactive drugs provided by an impotence clinic into his penile corpus cavernosous. METHODS: We identified the used prefilled syringes as the source of his infection. Similar cases were investigated as a putative outbreak of P. curvatum invasive disease among customers of this impotence clinic. P. curvatum isolates, cultured from samples obtained from the patients and from prefilled syringes, were compared by DNA sequencing of the nuclear ribosomal internal transcribed spacer. RESULTS: We identified 2 additional customers at the impotence clinic who had P. curvatum endocarditis. In addition, cultures of unused, prefilled syringes and bottles provided by the same clinic to 5 asymptomatic customers tested positive for pathogenic molds (P. curvatum in 4 cases and Paecilomyces lilacinus in 1). All P. curvatum isolates were of a single genetic type that is known only from this outbreak but is closely related to 3 other P. curvatum genotypes associated with pathogenicity in humans. CONCLUSIONS: P. curvatum is an emerging pathogen that can be readily isolated from blood. We identified an outbreak of P. curvatum endocarditis among men who had erectile dysfunction treated by intracavernous penile injections from contaminated prefilled syringes.

Aged↗
PubMed2005

Recent trends in the epidemiology of non-typhoid Salmonella and antimicrobial resistance: the Israeli experience and worldwide review.

PURPOSE OF REVIEW: The epidemiology of non-typhoid Salmonella has changed significantly since the turn of the century. Interestingly, non-typhoid Salmonella epidemiology in Israel mirrors some important global trends, and these new trends are reviewed. Recent research that has shed more light on the true toll of non-typhoid Salmonella epidemic and resistance is also summarized. RECENT FINDINGS: After more than three decades of a persistent rise, reports from Israel, the US, and the UK indicate that the trend may be reversed and the incidence of NTS illnesses is starting to decline. In contrast, the rates of resistance and multidrug resistance are increasing and expanding worldwide. Of major concern are the increasing rates of multidrug resistance in Salmonella typhimurium, particularly definitive phage-type 104, the alarming increase in low-level ciprofloxacin resistance among several non-typhoid Salmonella serotypes, and the upsurge of high-level ciprofloxacin resistance, mainly in Taiwan. In Israel, high rates of resistance were reported for Salmonella virchow, which accounts for 16% of non-typhoid Salmonella illnesses, and is highly invasive in children. The true burden of Salmonella illnesses in the US was calculated as 520 cases per 100 000, compared with an annual incidence of 13.4 per 100 000 of laboratory confirmed cases. Hospitalization and death rates were 20% and 0.6%, respectively. Infection with resistant non-typhoid Salmonella isolates, and particularly S. typhimurium, increases the likelihood of hospitalization and death. SUMMARY: Many important trends of non-typhoid Salmonella epidemiology are not restricted to a single geographic location, but spread worldwide, reflecting the global nature of the epidemic. This epidemic imposes a heavy burden worldwide.

Adolescent↗
PubMed2005

Seasonal variations in rhino-cerebral Mucor infection.

OBJECTIVES: Rhino-orbito-cerebral mucormycosis (ROCM) is an uncommon, potentially lethal infection that occurs mostly in immunocompromised hosts. The seasonal occurrence of ROCM was studied in two of Israel's largest medical centers. METHODS: A total of 36 patients were seen during a 25-year period in this retrospective bi-institutional cohort study. Meteorologic data were obtained and analyzed for a possible linkage of infection with precipitation and temperature. RESULTS: Twenty-one of the 36 patients (58%) presented between the months of August and October, and 27 patients (75%) presented between the months of August and December. A peak incidence of ROCM was noted in the month of September (13/36 patients; 36%). No association was noted between meteorologic conditions and the incidence of ROCM infection. CONCLUSIONS: A consistent seasonal peak was observed in ROCM. Heightened awareness is important for early recognition and treatment of this disease.

Brain Diseases↗
PubMed2005

Methicillin-resistant Staphylococcus aureus in neonatal intensive care unit.

A neonatal intensive care unit outbreak was caused by a strain of methicillin-resistant Staphylococcus aureus previously found in the community (ST45-MRSA-IV). Fifteen infected neonates were identified, 2 of whom died. This outbreak illustrates how a rare community pathogen can rapidly spread through nosocomial transmission.

Anti-Bacterial Agents↗
PubMed2004

Rapid flow-cytometric susceptibility testing of Candida species.

OBJECTIVES: To develop a rapid flow-cytometric antifungal susceptibility test and to compare results with the standard methods. METHODS: Reference and laboratory strains of Candida were tested for susceptibility to fluconazole and echinocandin by fluorescent flow cytometry using Acridine Orange as indicator of viability. Flow cytometry results were compared with MICs as determined by macrodilution and/or Etest. RESULTS: Seventy Candida strains were tested for susceptibility to fluconazole, and 74 strains for susceptibility to echinocandin. Minimal concentration of fluconazole causing 40% cell damage, as determined by flow cytometry, showed excellent association with MIC, as determined by other methods. The flow method, completed within 5 h, had excellent sensitivity and specificity to distinguish between sensitive, susceptible dose-dependent and resistant strains. The flow cytometry method for echinocandin was completed within 3 h, and minimal concentration causing 50% cell damage was associated with MIC as determined by macrodilution. CONCLUSIONS: Antifungal susceptibility testing by FACS is a reliable, rapid method for determining susceptibility of Candida to fluconazole and echinocandin. The method allows same-day results, assisting in the selection of appropriate antifungal therapy.

Antifungal Agents↗
PubMed2004

Nasopharyngeal carriage of Streptococcus pneumoniae by adults and children in community and family settings.

The rate of Streptococcus pneumoniae carriage among adults was compared with that among children (age, < or =6 years) in the same population. Nasopharyngeal culture results for 1300 adults and 404 children were analyzed. S. pneumoniae was carried by only 4% of the adults, compared with 53% of children in the same community. Young age, day care center attendance, having young siblings, and no antibiotic use during the month before screening were associated with the high carriage rate among children, whereas the only risk factor associated with carriage among adults was the presence of a respiratory infection on the screening day. S. pneumoniae serotype distribution and antibiotic resistance patterns differed between adults and children. Isolates of the same serotype--even of the same clone--differed in their antibiotic susceptibility patterns between children and adults. In a subanalysis of 151 pairs of children and their parents and of 32 pairs of siblings, intrafamilial transmission of S. pneumoniae could not be demonstrated.

Adolescent↗
PubMed2004

Clinical and epidemiological aspects of infections caused by fusarium species: a collaborative study from Israel.

Fusarium infections are an important problem worldwide, commonly affecting immunocompromised individuals. We conducted a retrospective study in two Israeli tertiary medical centers of factors predisposing to infection by Fusarium spp. and their influence on the epidemiology and clinical outcome of this infection. Fusarium spp. were isolated from 89 patients with a median age of 57 years. Sixty-eight patients were considered immunocompetent. Seven patients had disseminated disease, 34 had locally invasive disease, and 48 had superficial infection. Most infections were limited and occurred mainly in lower limbs. Factors associated with in-hospital mortality were chronic renal failure, hematological malignancy, immunosuppression, disseminated infection, and positive blood culture. Multivariate analysis showed that chronic renal failure, hematological malignancy, burns, and disseminated infection were independently associated with mortality. A surge in the frequency of infections was noticed during the summer for patients from rural areas, involving mainly the eyes and lungs. At one of the hospitals (in a mountainous area), there was an increase in the isolation rate over time.

Adolescent↗
PubMed2002

A defined human gastrin sequence stimulates the growth of Helicobacter pylori.

This study describes the interaction between gastrin and Helicobacter pylori. Human gastrin amino acids 4-17 were found to be the minimal growth-stimulating sequence. Gastrin from other mammals did not stimulate bacterial growth. When human serum was used to stimulate bacterial growth in brucella broth, gastrin was shown to be a necessary and sufficient growth-stimulating factor. Competition for the gastrin effect by pentagastrin and cholecystokinin (CCK-8) resulted in inhibition of bacterial growth. This effect was mediated by the four C-terminal amino acids which are shared by gastrin, CCK-8 and pentagastrin. In conclusion, the interaction between gastrin and H. pylori was shown to be specific, essential, and dependent on a defined gastrin sequence.

Amino Acid Sequence↗
PubMed2002

Rhino-orbital and rhino-orbito-cerebral mucormycosis.

BACKGROUND: Rhino-orbito-cerebral mucormycosis (ROCM) is a devastating infection of immunocompromised hosts. We present our experience with 19 ROCM cases and attempt to define preferred diagnostic and treatment protocols. METHODS: All had tissue biopsies obtained studied by direct smear, histologic studies, and cultures. Imaging was obtained in 14 cases. RESULTS: Sixteen patients presented between August and November. Six had mixed fungal infections. Seven patients had end-stage underlying disease or infection and did not undergo surgery and 4 had an indolent form of disease. Patients were treated by surgery and by amphotericin B. The overall survival was 47%. CONCLUSIONS: ROCM may have seasonal incidence peaking in the fall and early winter. The therapeutic approach should be unchanged in cases of mixed fungal infections. Amphotericin B with aggressive debridement remains the mainstay of treatment. Early recognition and treatment are essential. A presentation and survival-dependent classification of ROCM are offered.

Adult↗
PubMed2002

Bacterial induction of autoantibodies to beta2-glycoprotein-I accounts for the infectious etiology of antiphospholipid syndrome.

The antiphospholipid syndrome (APS) is characterized by the presence of pathogenic autoantibodies against beta2-glycoprotein-I (beta2GPI). The factors causing production of anti-beta2GPI remain unidentified, but an association with infectious agents has been reported. Recently, we identified a hexapeptide (TLRVYK) that is recognized specifically by a pathogenic anti-beta2GPI mAb. In the present study we evaluated the APS-related pathogenic potential of microbial pathogens carrying sequences related to this hexapeptide. Mice immunized with a panel of microbial preparations were studied for the development of anti-beta2GPI autoantibodies. IgG specific to the TLRVYK peptide were affinity purified from the immunized mice and passively infused intravenously into naive mice at day 0 of pregnancy. APS parameters were evaluated in the infused mice on day 15 of pregnancy. Following immunization, high titers of antipeptide [TLRVYK] anti-beta2GPI Ab's were observed in mice immunized with Haemophilus influenzae, Neisseria gonorrhoeae, or tetanus toxoid. The specificity of binding to the corresponding target molecules was confirmed by competition and immunoblot assays. Naive mice infused with the affinity-purified antipeptide Ab's had significant thrombocytopenia, prolonged activated partial thromboplastin time and elevated percentage of fetal loss, similar to a control group of mice immunized with a pathogenic anti-beta2GPI mAb. Our study establishes a mechanism of molecular mimicry in experimental APS, demonstrating that bacterial peptides homologous with beta2GPI induce pathogenic anti-beta2GPI Ab's along with APS manifestations.

Animals↗
PubMed2002

Listeria monocytogenes infection in Israel and review of cases worldwide.

Listeria monocytogenes, an uncommon foodborne pathogen, is increasingly recognized as a cause of life-threatening disease. A marked increase in reported cases of listeriosis during 1998 motivated a retrospective nationwide survey of the infection in Israel. From 1995 to 1999, 161 cases were identified; 70 (43%) were perinatal infections, with a fetal mortality rate of 45%. Most (74%) of the 91 nonperinatal infections involved immunocompromised patients with malignancies, chronic liver disease, chronic renal failure, or diabetes mellitus. The common clinical syndromes in these patients were primary bacteremia (47%) and meningitis (28%). The crude case-fatality rate in this group was 38%, with a higher death rate in immunocompromised patients.

Adolescent↗
PubMedDate not supplied

Risk factors for development of nontyphoid Salmonella bacteremia.

The objective of this paper was to identify risk factors for nontyphoid Salmonella bacteremia by making a retrospective chart review of 39 patients with nontyphoid Salmonella bacteremia. The control group included 30 patients with positive Salmonella stool culture (gastroenteritis group). Demographic factors, presenting signs and symptoms, antimicrobial treatment before admission, and microbiologic results were recorded. Nine patients (23%) were excluded owing to recognized risk factors for development of extraintestinal disease. Seventeen cases (57%) occurred during summer time, whereas the gastroenteritis group had a less seasonal tendency. Eighty percent of the patients with Salmonella bacteremia had a previous history of diarrhea. At admission more patients in the bacteremia group were febrile and had leukocytosis (73% vs 33% and 37% vs 20%, respectively). More patients in the bacteremia group had previous antibiotic treatment (57% vs 20%, p<0.01). The Salmonella types were mainly C and D in the bacteremia group (40% each), and B and C in the gastroenteritis group (26% and 52%, respectively). The risk factors for Salmonella bacteremia in previously healthy children include warm season, previous gastrointestinal illness, and preexposure to antibiotics.

Bacteremia↗