A retrospective six-year national survey of P. multocida infections in Israel.

Pasteurella multocida is the commonest organism infecting pet bites. Anecdotal reports tend to overemphasize dramatic outcomes. We aimed to study a large database of P. multocida infections. This retrospective survey of P. multocida infections in Israeli hospitals refers to the y 2000-2005. Clinical microbiologists were contacted by email and asked to perform a back-search of their hospital's records for isolates of P. multocida. The charts of patients growing P. multocida were abstracted into a structured questionnaire. 77 cases were identified in 12 hospitals, yielding an annual incidence of 0.19/100,000. The mean age was 49.2+/-26.5 y and the mortality rate was 2.6%. Those who died were >65 y of age, had diabetes mellitus or cirrhosis and were bacteraemic. One-third of the cases occurred in people aged > or =65 y. Cats caused most of these infections (54%). Surgery for debridement was common (53.7%), but no-one required amputation; a second- and third-look operation was necessary for these patients. Bacteraemia was found in 32.5% of patients and was significantly more common among those aged >60 y (p =0.044). Hospitalized patients with P. multocida have a favourable prognosis, apart from elderly and bacteraemic patients with comorbidities. Surgery and reoperations may be required in about half of the patients.

Influx of extended-spectrum beta-lactamase-producing enterobacteriaceae into the hospital.

BACKGROUND: The prevalence of infections caused by extended-spectrum beta -lactamase (ESBL)-producing Enterobacteriaceae is increasing worldwide. The influx of these bacteria into hospitals has major implications for infection-control and empirical treatment strategies. METHODS: Isolates from 2 patient cohorts--patients with gram-negative bacteremia within 2 days after admission and patients screened for fecal colonization at admission--were assessed for ESBL production. ESBL phenotype was confirmed according to Clinical and Laboratory Standards Institute guidelines. Predictors of ESBL phenotype were examined by univariate and multivariate analyses. RESULTS: Of 80 Enterobacteriaceae isolates from blood samples obtained at admission to the hospital, 13.7% produced ESBL. Thirty-eight patients with ESBL-positive isolates and 72 with ESBL-negative isolates were included in a case-control study. Predictors of ESBL production were male sex and nursing home residence (area under receiver operator characteristic curve, 0.7). Of 241 persons screened at admission, 26 (10.8%) had fecal carriage of ESBL-producing Enterobacteriaceae. Predictors of fecal carriage were poor functional status, antibiotic use, chronic renal insufficiency, liver disease, and use of histamine2 blockers (area under receiver operator characteristic curve, 0.8). Four (15.4%) of the 26 individuals with fecal carriage had subsequent bacteremia with ceftazidime-resistant Enterobacteriaceae, compared with 1 (0.5%) noncarrier (odds ratio, 38.9; P<.001). Of 80 ESBL-producing Enterobacteriaceae isolates obtained at admission, 65 were health care associated, and 15 were community acquired. The 15 community-acquired ESBL-producing Enterobacteriaceae belonged to diverse clones. The most prevalent ESBL gene among these isolates was CTX-M-2 (found in 53.3% of the isolates). CONCLUSIONS: We report high rates of bacteremia and colonization with ESBL-producing Enterobacteriaceae at admission to our institution, which may undermine infection-control measures and complicate the selection of empirical treatment.

Estradiol binding in ovariectomy-responsive and -nonresponsive rat mammary carcinoma.

MTW9, a transplantable mammary tumor in Wistar-Furth rats, is dependent upon high levels of serum prolactin for growth. The mammary tumor can be maintained by coimplantation with a pituitary mammosomatotropic tumor (MTW9-MtT) or by chronic perphenazine administration (MTW9-P). MTW9-MtT does not regress after ovariectomy (OVEX) alone, while, MTW9-P regresses rapidly whether or not rats are maintained on perphenazine. Cytosol estradiol binding was determined in MTW9-MtT, 47.6 +/- 3.6 (N = 9), Kd 9.9 +/- 2.0 X 10(-11) M; MTW9-P, 195.5 +/- 9.1 (n = 16), Kd 27.6 +/- 4.7 X 10(-11) M; MTW9-P after perphenazine was withdrawn, 86.0 +/- 6.0 (n = 6), Kd 9.9 +/- 1.5 X 10(-11) M. Eight S and 4 S peaks were found in cytosols from both tumors by sucrose gradient centrifugation; the peaks differ qualitatively and quantitatively. The possibility that differences in binding levels result from sites filled with endogenous estradiol was critically examined and rejected. Withdrawal of perphenazine results in reduction of estradiol binding but retention of response to OVEX. Hence, response of MTW9-P to OVEX cannot be explained by the 3- to 4-fold increase in estradiol binding over MTW9-MtT. The relationship between estradiol binding and response to OVEX is under study using both mammary tumor models.

Modelling Tumor Treating Fields for the treatment of lung-based tumors.

Tumor Treating Fields (TTFields), low-intensity electric fields in the frequency range of 100-500 kHz, exhibit antimitotic activity in cancer cells. TTFields were approved by the U. S. Food and Drug Administration for the treatment of recurrent glioblastoma in 2011. Preclinical evidence and pilot studies suggest that TTFields could be effective for treating certain types of lung cancer, and that treatment efficacy depends on the electric field intensity. To optimize TTFields delivery to the lungs, it is important to understand how TTFields distribute within the chest. Here we present simulations showing how TTFields are distributed in the thorax and torso, and demonstrate how the electric field distribution within the body can be controlled by personalizing the layout of the arrays used to deliver the field.

Enzyme immunoassay for the diagnosis of cat-scratch disease defined by polymerase chain reaction.

Whole-cell immunofluorescent antibody (IFA) tests for detection of anti-Bartonella henselae immunoglobulin (Ig) G are commonly used to diagnose cat-scratch disease (CSD). The need to cultivate B. henselae in Vero cells for antigen preparation and the absence of routinely applied IFA assays for IgM constitute the major disadvantages of this form of test. We describe the results of an enzyme immunoassay (EIA) for IgM and IgG that used N-lauroyl-sarcosine-insoluble outer membrane antigens from agar-grown B. henselae performed in 84 patients with definite CSD (regional lymphadenitis, cat contact, and > or =1 confirmatory test: polymerase chain reaction, skin test, or B. henselae culture). Although this method has been used as a diagnostic tool in several case reports, it has not previously been evaluated in a large study of definitively proven CSD cases. Results of this study indicate that the EIA described herein can play an important role in the serodiagnosis of CSD, although improvement of the sensitivity, particularly that of the IgM, would be desirable.

Shigellosis in adults: epidemiologic, clinical, and laboratory features.

One hundred and sixteen cases of adult patients hospitalized for shigellosis have been reviewed. The most common presentation included diarrhea (most frequently watery), fever, and abdominal pain, while dysentery has been less frequent. S. flexneri infection, as compared to S. sonnei, was more common in elderly patients and in males, and was characterized by a more prolonged clinical course. Abnormalities of serum electrolytes and hepatic enzymes were the most common laboratory complications, most often seen in elderly patients. Most isolates exhibited susceptibility to the common antimicrobial agents used in shigellosis therapy.

High anti-cytomegalovirus (CMV) IgG antibody titer is associated with coronary artery disease and may predict post-coronary balloon angioplasty restenosis.

Recent studies have demonstrated that cytomegalovirus (CMV) DNA was found in atherosclerotic coronary arteries in restenotic lesions, and prior infection with CMV could be a strong independent risk factor for restenosis after coronary atherectomy. We studied the correlation between anti-CMV antibody titer and coronary artery disease. Sixty-five patients (50 men and 15 women) with coronary artery disease were enrolled prospectively. All had symptomatic coronary artery disease with an angiographic documentation of a de novo single coronary lesion. All underwent balloon coronary angioplasty and were followed for 12 months with a thallium perfusion scan 3 months after angioplasty. Patients who had recurrent chest pain and/or a positive thallium scan had another coronary angiography. Blood samples were taken before angiography and 1 and 3 months later. Patients with high anti-CMV titer > or = 1:800 had a higher prevalence of coronary artery disease (p <0.001) than seropositive patients with a lower antibody titer (< or = 1:400); patients with high antibody titer (> or = 1:800) had a higher restenosis rate than seropositive patients with a low antibody titer (< or = 1:400) (p <0.05). High antibody titers against CMV (IgG) may be a strong marker for coronary artery disease, and might predict post-coronary angioplasty restenosis. These findings support the infectious theory of atherosclerosis (especially with prior CMV infection), and also suggest that a chronic immunologic response has a role in atherosclerosis and restenosis.

DNA amplification for the diagnosis of cat-scratch disease in small-quantity clinical specimens.

Diagnosis of cat-scratch disease (CSD) by polymerase chain reaction (PCR) of lymph node fineneedle aspiration (FNA) and primary lesion specimens can be difficult owing to the minute amount of available material. A PCR assay specifically suited to test these specimens was developed. First, small-quantity (10 microL) samples were prepared from 17 CSD-positive and 16 CSD-negative specimens, and DNA extraction and amplification from these samples were compared using 3 methods. Sensitivity and specificity of PCR were 100% using material collected on glass microscope slides and by using Qiagen (Hilden, Germany) columns for DNA extraction. Then, this method was used to test 11 archival glass microscope slides of FNA (7 malignant neoplasms, 4 undiagnosed lymphadenitis) and 2 primary lesion specimens. Two of the 4 lymphadenitis samples and the 2 primary lesion specimens were PCR positive. The technique presented could facilitate CSD diagnosis from a wider range of clinical samples.

Gain in mass density of bone following strenuous physical activity.

A group of 223 military recruits aged 18-21 years underwent strenuous physical training for a period of 14 weeks. The absolute bone density of the distal tibia in both lower limbs was measured before the training period and at its end. The density was determined by the Compton scattering technique, which has been developed in our laboratory; this method provides the bone mass of all bone constituents per unit volume. The distribution curve of the bone density in both tibiae shifted to higher values at the end of the training period. The mean bone density in the right and left tibia increased significantly by 7.5%. This study indicates that following an intensive physical exercise regime, a significant increase in the mass density of bone can be obtained in young adults within a short period.

Effect of intense physical activity on the bone-mineral content in the lower limbs of young adults.

The effect of intense physical training on the bone-mineral content of young adults who are unaccustomed to physical activity has not yet been established. In this study, 268 male recruits, eighteen to twenty-one years old, were evaluated before and after fourteen weeks of strenuous physical training. The bone-mineral content of both legs at the level of the distal third of the tibia in each individual was measured using single-beam photon absorptiometry. The subjects started their training with equal values for bone-mineral content in both legs. During the training period, the average bone-mineral content of the left leg increased by 11.1 per cent and that of the right leg, by 5.2 per cent. In the group of subjects who did not complete the training course, mainly because they incurred stress fractures, the increase in bone-mineral content was significantly less than the increase in those who completed the program. This study indicated that in young adults a high level of loading of bone results in either a stress fracture or a rapid increase in bone-mineral content.

Is idiopathic atrial fibrillation caused by occult thyrotoxicosis? A study of one hundred consecutive patients with atrial fibrillation.

In this study we evaluated the possible relationship between idiopathic atrial fibrillation and occult thyrotoxicosis, diagnosed by lack of response of thyroid stimulating hormone to administration of thyrotropin releasing hormone. Three groups were compared: 25 patients with idiopathic atrial fibrillation; 52 with cardiovascular atrial fibrillation; and 27 with sinus rhythm. Patients were excluded with any clinical evidence of thyrotoxicosis or with elevated serum FT4 level, as well as those with diseases or on medications known to be associated with a diminished response to administration of the releasing hormone. A flat test (lack of response) was found in only 4% of the patients. There was no significant difference among the 3 groups. Based on these data we believe that there is no relationship between idiopathic atrial fibrillation or any other type of atrial fibrillation and occult thyrotoxicosis.

The area moment of inertia of the tibia: a risk factor for stress fractures.

In a prospective study of stress fractures among Israeli infantry recruits, the area moment of inertia of the tibia was found to have a statistically significant correlation with the incidence of tibial, femoral and total stress fractures. Recruits with "low" area moments of inertia of the tibia were found to have higher stress fracture morbidity than those with "high" area moments of inertia. The best correlation was obtained when the area moment of inertia was calculated about the AP axis of bending at a cross-sectional level corresponding to the narrowest tibial width on lateral X-rays, a point which is at the distal quarter of the tibia. This finding indicates that bending forces about the approximate AP axis are an important causal factor for tibial and many other stress fractures. The bone's bending strength, or ability to resist bending moments, as measured by the area moment of inertia, helps determine risk to stress fracture.

Pseudomonas aeruginosa bacteremia: an analysis of 123 episodes, with particular emphasis on the effect of antibiotic therapy.

OBJECTIVES: To review current experience with Pseudomonas aeruginosa bacteremia and compare outcome of patients treated with single-drug, versus combination therapy. METHODS: The charts of all patients with P. aeruginosa bacteremia between 1990 and 1992 were reviewed, and pertinent demographic, clinical, and bacteriologic data were retrieved. In addition, similar data were collected from a series of patients with P. aeruginosa bacteremia from the literature of the past 20 years. RESULTS: One hundred and twenty-three episodes of P. aeruginosa bacteremia in 121 patients were identified. Most patients were older than 70 years, had at least one underlying condition, and had acquired the infection in the hospital. Attributable mortality was 34%. After exclusion for early mortality and inappropriate therapy, 57 patients remained eligible for comparison of outcome according to therapy protocol. Mortality from infection was equal between the group of 42 patients who received monotherapy and the 15 patients who received combination therapy (14% and 13%, respectively). The literature review revealed eight articles describing 21 to 410 episodes of Pseudomonas bacteremia. The clinical characteristics of these series did not differ significantly from those of the present series. CONCLUSIONS: Incidence, epidemiology, clinical characteristics, and outcome of pseudomonas sepsis did not change significantly over the past 2 decades. Appropriate monotherapy was as effective as combination drug therapy for individuals with pseudomonas bacteremia surviving the first 2 days of infection.

The long-term followup of soldiers with stress fractures.

A group of 295 Israeli infantry recruits was evaluated in a prospective study of stress fractures which began in basic training. On the basis of scintigraphy, 91 of the recruits (31%) were found to have sustained stress fractures during basic training. Sixty-six of the 91 recruits with stress fractures (72%) were followed for a minimum of 1 year after basic training to determine the natural history of a soldier who sustains a stress fracture and resumes training after a period of rest. Five clinical patterns were observed: (1) uneventful recovery (47%); (2) protracted recovery (13.6%); (3) symptoms consistent with recurrent stress fractures in new sites (19.6%); (4) intermittent nonstress fracture bone pain (16.7%); and (5) chronic stress fractures (3%). The incidence of recurrent stress fractures was 10.6%. A control group of 60 recruits who sustained no stress fractures in basic training had a 1.7% incidence of stress fractures after basic training. Recruits who sustained stress fractures in basic training continued to be a higher risk for stress fractures during subsequent training.

Stress fractures. Identifiable risk factors.

To answer the question why such large differences in stress fracture morbidity rates (2% to 64%) exist in different countries, we prospectively evaluated 312 recruits for possible risk factors for stress fractures. Prior to training, each recruit underwent an evaluation including the following: orthopaedic examination, foot and tibial radiographs, measurements of tibial bone width, bone mineral content, bone density, aerobic physical fitness and leg power, assessments of somatotype and smoking habits, and evaluation of sociological and psychological factors. Using a multivariate analysis, two risk factors were identified: recruits with stress fractures had significantly narrower tibiae (P less than 0.001), and a higher degree of external rotation of the hip (P = 0.016). These two variables were independent and cumulative. Stress fracture morbidity was 17%, 29%, and 45% when neither, one, or both risk factors were present, respectively (P less than 0.001). Identification of these risk factors might explain the susceptibility of some people to stress fractures.

Negative bone scans in impending tibial stress fractures. A report of three cases.

Three highly motivated military recruits who presented with tibial pain on exertion are reported. Their initial bone scan assessments to rule out stress fracture were normal, and the recruits were returned to demanding training. One month later, because of persistent and increasing tibial pain, they were rescanned and focal activity representative of tibial stress fractures was found in each case. Until now it has been assumed that a negative bone scan ruled out a stress fracture unequivocally. Our reported cases show that bone pain may in fact precede scintigraphic evidence of a stress fracture. Persistent and increasing bone pain during demanding physical activity, even in the presence of a prior normal bone scan, may represent stress fracture and repeat bone scan may be indicated.

Cat-scratch disease osteomyelitis from a dog scratch.

Osteomyelitis is a rare manifestation of cat-scratch disease in patients who do not have AIDS. The clinical presentation and non-specific subacute course of the disease make diagnosis difficult. We present a child with osteomyelitis of a metacarpal following a dog scratch. Bartonella henselae was found to be the aetiological agent. The bone healed after treatment with antibiotics. Increased awareness and a comprehensive medical history are needed to identify patients with suspected Bartonella henselae osteomyelitis.

Recurrent stress fractures in military recruits. One-year follow-up of 66 recruits.

Of 66 recruits who sustained stress fractures during basic training and returned to training after a period of rest, seven (10.6%) suffered recurrent fractures within one year. None of the recurrences was at the original anatomical site. All of the recruits with recurrent stress fractures had had at least one of their initial stress fractures in the femur. This suggests that a femoral stress fracture carries a high risk of recurrence at other sites.

Stress fractures in military recruits. A prospective study showing an unusually high incidence.

In a prospective study of 295 male Israeli military recruits a 31% incidence of stress fractures was found. Eighty per cent of the fractures were in the tibial or femoral shaft, while only 8% occurred in the tarsus and metatarsus. Sixty-nine per cent of the femoral stress fractures were asymptomatic, but only 8% of those in the tibia. Even asymptomatic stress fractures do, however, need to be treated. Possible explanations for the unusually high incidence of stress fractures in this study are discussed.