In vitro and in vivo properties of a fully human IgG1 monoclonal antibody that combats multidrug resistant Pseudomonas aeruginosa.

The development of an anti-bacterial drug in the form of a monoclonal antibody (mAb) targeting an exposed virulence factor, represents an innovative therapeutic strategy. Consequently, a fully human IgG1 mAb (LST-007) targeting Pseudomonas aeruginosa (PA) flagellin type b was recombinantly expressed and characterized in vitro and in an infection model driven by a multidrug resistant (MDR) PA strain. LST-007 demonstrated a highly specific binding towards whole PA bacteria harboring flagellin type b and its recombinant counterpart, with a K(D) of 7.4x10(-10) M. In bioactivity assays, LST-007 or titers of Cmax sera derived from pharmacokinetic studies, markedly attenuated PA motility in an equipotent manner. In vivo, parenteral LST-007 (20 mg/kg) given as a single or double-dosing paradigm post-infection, afforded survival (up to 75% at Day 7) in a lethal model of pneumonia driven by the intratracheal (i.t.) instillation of an LD(80) of the MDR PA isolate. This protective effect was markedly superior to that of imipenem (30% survival at Day 7) and totally devoid with an irrelevant, human isotype mAb. These data lay credence that LST-007 may be a valuable adjunct to the limited list of anti-bacterials that can tackle MDR PA strains, thereby warranting its continued development for eventual clinical evaluation.

Acute low back pain: is gatekeeping second best?

BACKGROUND: Low back pain is a common problem managed by primary care physicians and orthopedic specialists. OBJECTIVES: To evaluate the outcome of new LBP episodes in patients who chose to visit either an orthopedist or their general practitioner. METHODS: All patients visiting the orthopedist or physician during the study period were screened for a new complaint of LBP. After the initial visit the patients were interviewed by phone using a structured questionnaire, with a follow-up interview one month later. The study was performed at Clalit Health Services primary care and consultation clinics. A random sample of 125 GPs and 17 orthopedists were chosen. Consecutively recruited were 166 patients who visited the GP and 75 the orthopedist. The main outcome measures evaluated were perceived complaint severity and degree of disturbance to everyday functioning, problem resolution, and health services utilization. RESULTS: Patients who decided to first visit the orthopedist indicated a higher disturbance to everyday functioning (75% vs. 70%, P < 0.01), were invited for further follow-up visits (6% vs. 51%, P < 0.05) and had more computed tomography and bone scans (20 vs. 3%, P < 0.001 and 9 vs. 2%, P < 0.05, respectively). Health status after one month showed that patients who chose the GP were more likely to have their problem solved (36 vs. 17%, P < 0.05). CONCLUSIONS: Symptom resolution for a new LBP complaint was significantly higher in patients who decided on the GP, even when controlling for severity of illness and degree of disturbance to everyday functioning.

Chronic pain: a population-based study.

BACKGROUND: The prevalence of chronic pain in the general population ranges from 10% to over 40%, depending on the definition and the population studied. No large study has been conducted in Israel. OBJECTIVES: To evaluate the prevalence of patients with chronic pain, and characterize them in a large community random sample. METHODS: We conducted a survey of Clalit Health Services members, interviewing them by phone. A random sample of 4063 Clalit members, 25 years or older and Hebrew speakers, were screened for chronic pain, defined as: any pain or discomfort that in the last 6 months has persisted continuously or intermittently for more than 3 months. RESULTS: Eight percent (n=325) refused to participate. Of the 3738 included in the study, 1722 (46%) reported chronic pain in at least one site. Most of the patients were over 50-years-old (62%) (mean age 56 +/- 16, range 27-97 years). Women suffered significantly more than men, as did those who were older, less educated and born in Israel and Eastern Europe. Prevalent painful sites were the back (32%), limbs (17%) and head (13%). More than a third reported severe pain and impaired life activities. Only 4.8% of the patients suffering from chronic pain were referred to pain specialists and 11% used complementary medicine. A logistic regression model showed that women and patients with a low education level were the only significant variables predicting higher life impact index and higher pain severity. CONCLUSIONS: We found a high prevalence of chronic pain in the study population. Chronic pain causes severe disturbance to quality of life. A low rate of referral to pain specialists and complementary medicine was observed.

Development of abdominal pain and IBS following gynecological surgery: a prospective, controlled study.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) develops after bacterial enteritis that causes injury to the bowel mucosa. It's unclear whether abdominal pain or IBS results from gynecological surgery that could injure abdominopelvic nerves. The aim of this prospective, controlled study was to assess the incidence of pain or IBS in women undergoing elective gynecological surgery compared to non-surgical controls and to identify factors associated with their development. METHODS: One hundred thirty-two women without GI symptoms undergoing elective gynecological surgery for non-painful conditions were compared with 123 non-surgery controls without GI symptoms. Socio-demographic, psychosocial, and surgery-related variables were potential predictor variables of pain at 3 and/or 12 months. RESULTS: Three surgical patients (2.7%), but no controls, developed IBS at 12 months. Significantly more surgical patients had abdominal pain at 3 or 12 months (15.3% vs 3.6%, P=.003). No socio-demographic or surgery-related variables predicted pain development, but it was predicted by psychosocial factors including anticipation of difficult recovery from surgery (P=.01), perception of severity/constancy of illness (P=.04), and reduced sense of coherence (P=.01). CONCLUSIONS: Among women undergoing gynecological for non-pain indications the development of IBS was not significantly greater than controls. However, abdominal pain did develop in 17% of women in the surgical group, suggesting that surgery facilitated its development. Notably, only psychosocial variables predicted pain development, implying that pain development associated with central registration and amplification of the afferent signal (via cognitive and emotional input) must be considered along with the peripheral injury itself. These findings contribute to understanding the pathophysiology of functional GI pain.

Prevalence of GERD symptoms in a representative Israeli adult population.

The prevalence of gastroesophageal reflux disease (GERD) symptoms in the general population is lower in Asian than Western countries. Data are lacking for countries in the Middle East. The aim of the study was to determine the prevalence and severity of GERD symptoms among Israeli Jews. A questionnaire including 8 specific questions for GERD symptoms was administered by telephone interview to a representative sample of the population. One thousand two hundred twenty-one of 1839 individuals were successfully contacted and 981 had valid, complete data. The mean age was 45.0 years and 55% were females. Over the previous year 34.8% of the respondents reported suffering any GERD symptom. Of these 11.6% reported retrosternal burning, 11.7% retrosternal pain, 19.0% an acid taste in the mouth, and 17.5% reflux of gastric content. In all, 6.5%, 5.2%, 10.4%, and 7.9%, respectively, suffered these symptoms at least once a week, and 2.0%, 1.8%, 2.4%, and 2.3%, respectively, defined their symptoms as frequent and severe. Male sex (P=0.01) and a functional lower gastrointestinal (GI) disorder (P<0.0001) contributed significantly to the severity of upper GI reflux-like symptoms. In conclusion, GERD symptoms are common among Israeli Jews. The symptoms are generally of mild-to-moderate severity and are significantly associated with lower functional GI disorders.

[Mothers know best].

BACKGROUND: Nutrition has a critical effect on the infant's brain development during pregnancy and the first 18 months of life. Inappropriate diet can cause infant mortality. Research has shown that medical professionals lack the required knowledge regarding nutrition and that there are no suitable instructional programs on this subject for them. OBJECTIVES: To examine the knowledge and attitudes of gynecologists, pediatricians and nurses who work in mother and child health clinics of "Maccabi" Healthcare Services in Israel concerning infants' and pregnant women's nutrition and to compare these findings to the public's general knowledge. METHODS: The study population consisted of gynecologists and pediatricians who work in "Maccabi" Healthcare Services throughout the country and all the nurses at the family healthy clinics. In addition, a sample of mothers attending six different family health clinics was recruited. Four structured questionnaires were created for each group in the study population (gynecologist, pediatricians, nurses and mothers). The questionnaires included questions that evaluated the knowledge and attitudes toward infants' nutrition. RESULTS: The mothers showed high level of knowledge (67% correctly answered 3 or more of the 4 questions, compared to 51% of nurses, 27% or pediatricians, 38% of gynecologists, p < 0.01). The physicians showed a higher level of knowledge in the questions related to their specialty. When asked about the effect of nutritional instruction on the infants' health, the pediatricians answered correctly at a higher rate than the other study groups (74% of pediatricians answered correctly 3 out of 3 questions, compared to 60% of gynecologists, 47% nurses, p < 0.01). Professionals believe that they can train mothers on nutritional issues. CONCLUSIONS: Appointing a nutritionist to the mother and child clinics should be considered, as the professional caregivers of pregnant women and infants were found to be lacking in sufficient knowledge in certain aspects of nutrition for these populations.