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Biomedical subjects

R Finkelstein

Publications and source records attributed to R Finkelstein.

At least 55 records · Page 3Linked to original sources

hedgehog, wingless and orthodenticle specify adult head development in Drosophila.

The adult head capsule of Drosophila forms primarily from the eye-antennal imaginal discs. Here, we demonstrate that the head primordium is patterned differently from the discs which give rise to the appendages. We show that the segment polarity genes hedgehog and wingless specify the identities of specific regions of the head capsule. During eye-antennal disc development, hedgehog and wingless expression initially overlap, but subsequently segregate. This regional segregation is critical to head specification and is regulated by the orthodenticle homeobox gene. We also show that orthodenticle is a candidate hedgehog target gene during early eye-antennal disc development.

Animals↗

Surveillance of the use of antibiotic prophylaxis in surgery.

In 1991, updated recommendations for the administration of antimicrobial prophylaxis in surgery were made extensively available to all surgical wards of our hospital. Two years later we surveyed the implementation of these recommendations in our institution. Inpatients undergoing surgical procedures during a 6 month period were prospectively evaluated for the indication, type, timing and duration of antibiotic prophylaxis. On each day of the study, data of patients who underwent surgery in the previous 24-48 h were obtained and monitoring was continued for up to 5 days. Of the 215 evaluated patients 193 (90%) received prophylaxis. This rate was similar for elective and emergency surgeries. The rate of prophylaxis in surgeries for which its use is recommended was significantly higher than in surgeries where compelling data for its use are not available (96 vs. 74%, P = 0.000006). However, many and important deviations of basic principles of antimicrobial prophylaxis in surgery were found. Prophylaxis was administered systematically in some types of surgery lacking compelling data for its use. In almost 50% of the surgical procedures the first dose of antimicrobial prophylaxis was not administered at the optimal timing; prophylaxis was continued for more than 24 h in 21% of the cases, and the use of unstandardized regimens was common. Despite the availability of local guidelines, the implementation of a hospital program with regard to antibiotic prophylaxis in surgery may be difficult. Further measures should be applied to achieve this goal.

Antibiotic Prophylaxis↗

Epidemiology and clinical spectrum of pneumococcal infections: an Israeli viewpoint.

We performed a prospective study of consecutive pneumococcal infections documented during a six-month period in our clinical microbiology laboratory. A total of 59 cultures obtained from clinically significant specimens of 58 patients were positive for Streptococcus pneumoniae. Relative penicillin resistance occurred in 14 strains (24%) and only one (1.7%) was highly resistant to penicillin (minimum inhibitory concentration = 2.0 micrograms ml-1). Resistance to common alternative drugs was not found. Serotypes were of a wide variety, however types 1, 7 and 14 predominated (60% of all blood culture isolates). Twenty-three patients with community-acquired infection required hospitalization. Nosocomial pneumonia developed in three additional cases (14%). Invasive disease was diagnosed in 24 patients with pneumonia representing the most common infection (22 patients). Pneumonia was characterized by a high incidence of serious underlying diseases (82%) and associated bacteraemia (68%). Compared with controls, patients with penicillin-resistant pneumococcal pneumonia had a significantly higher incidence of previous hospitalizations and use of antibiotics (57 vs. 7%, P = 0.02). The overall case fatality rate was high (36%) and did not differ significantly between patients with pneumonia due to resistant and susceptible strains. The epidemiology and clinical spectrum of serious pneumococcal infections in Israel is similar to those described in many parts of the world, but high level resistance to penicillin and to other alternative drugs is still rare.

Aged↗

Morphometry of small airways in smokers and its relationship to emphysema type and hyperresponsiveness.

Based on our previous finding, of increased small airways disease in centrilobular emphysema (CLE) when compared with panlobular emphysema (PLE), we hypothesized that smokers who develop CLE would have increased airway responsiveness associated with airway inflammation and exaggerated airway narrowing, but not smokers with PLE. We compared preoperative methacholine challenge with the morphologic and cellular inflammatory characteristics of the airways in the lungs of six nonsmokers, 10 smokers with CLE, and five smokers with PLE. The airways of the CLE group were narrower than those of the nonsmokers (KS < 0.05) and the PLE group (KS < 0.05), but perimeters were not different. A greater percentage of airways in the CLE group showed infolding of the epithelium and lumen deformity than in the PLE group and nonsmokers (p < 0.05). Airway inner wall thickening (WI) was increased in the CLE group when compared with the PLE group and nonsmokers (p < 0.05), and WI correlated significantly with PC20 in the CLE group (r = -0.64, p < 0.01) but not in the PLE group and nonsmokers. The number of T lymphocytes in the airway walls correlated with PC20 in the CLE group (r = -0.50, p < 0.05) but not in the PLE group. In conclusion, despite similar age, smoking history, and range of airflow limitation, there was a clear difference in the methacholine responsiveness between the emphysema groups, suggesting that responsiveness is not just a reaction to smoking but either a reaction developing in some smokers or an abnormality initially present in some smokers which, in combination with exposure to cigarettes, determines the development of a type of lung disease: CLE.

Aged↗

Alveolar inflammation and its relation to emphysema in smokers.

The prevalent theory in the pathogenesis of emphysema proposes that increased numbers of activated neutrophils and/or alveolar macrophages produce large amounts of proteases, an activity that cannot be regulated by alpha 1-antiproteases, resulting in lung destruction. However, the cells in the lung parenchyma of smokers have not been properly identified. We characterized and quantitated the inflammatory cell load in the lungs of smokers and correlated these findings with the degree of lung destruction. Twenty-one patients, six nonsmokers and 15 smokers, undergoing lung resection were studied. Lungs or lobes were fixed and stained for light microscopy and neutrophil identification and immunohistochemically stained for identification of lymphocytes and macrophages. By point counting, we determined the extent of emphysema by the volume density of the lung parenchyma (Vvalv), and the different cell numbers per cubic millimeter in all lungs. In nonsmokers Vvalv was greater than in smokers. The number of neutrophils/mm3 of lung correlated directly with the Vvalv, (r = 0.71, p < 0.01), whereas the number of alveolar macrophages (r = -0.70) and T-lymphocytes (r = -0.78) correlated negatively with the Vvalv. The number of T-lymphocytes correlated negatively with the number of neutrophils (r = -0.58) and positively with the numbers of alveolar macrophages (r = 0.77). Our data suggest that as long as the inflammatory reaction is predominantly of neutrophils there is no destruction of the lung. However, the extent of lung destruction becomes evident, and its extent is directly related to the number of alveolar macrophages and T-lymphocytes/mm3. We conclude that the T-lymphocyte might be importantly implicated in the pathogenesis of emphysema in smokers.

Adult↗

Pattern formation in Drosophila head development: the role of the orthodenticle homeobox gene.

Significant progress has been made towards understanding how pattern formation occurs in the imaginal discs that give rise to the limbs of Drosophila melanogaster. Here, we examine the process of regional specification that occurs in the eye-antennal discs, which form the head of the adult fruitfly. We demonstrate genetically that there is a graded requirement for the activity of the orthodenticle homeobox gene in forming specific structures of the developing head. Consistent with this result, we show that OTD protein is expressed in a graded fashion across the disc primordia of these structures and that different threshold levels of OTD are required for the formation of specific subdomains of the head. Finally, we provide evidence suggesting that otd acts through the segment polarity gene engrailed to specify medial head development.

Animals↗

[Left-sided group A streptococcal endocarditis and mitral valve prolapse].

Group A beta-hemolytic streptococcus is an infrequent cause of endocarditis. Left-sided endocarditis in intravenous drug abuse is likewise uncommon; it carries a poor prognosis. A case of left-sided group A beta-hemolytic streptococcal endocarditis in a 20-year-old male drug addict with mitral valve prolapse is presented. This association has not been reported previously.

Adult↗

From fly head to mammalian forebrain: the story of otd and Otx.

Many of the genes responsible for axial patterning have been conserved throughout evolution. Recent studies of invertebrates and vertebrates are extending our understanding of this molecular conservation into the anterior region of the animal embryo, including the developing brain. These studies suggest that this domain is specified according to a genetic paradigm that is different from that governing trunk development, and are also beginning to provide insights into the structures that underlie the rostral brain.

Animals↗

Expression of two zebrafish orthodenticle-related genes in the embryonic brain.

To analyze the molecular mechanism of pattern formation in the anteriormost regions of the zebrafish embryo, we isolated two zebrafish sequences, zOtx1 and zOtx2, related to the Drosophila orthodenticle (otd) and two murine Otx genes. zOtx1 and zOtx2 encode predicted gene products which are 82% and 94% identical to the corresponding mouse proteins. Transcripts of both zebrafish genes appear abruptly at high levels in a triangular patch at the animal pole of the mid-gastrula, a region which contains cells fated to become midbrain and forebrain. Between 9 and 14 h of development, zOtx transcripts disappear from forebrain regions in a manner characteristic for each gene, and from 14 to 24 h, particular regions of the forebrain and midbrain express one or both genes. The posterior limit of expression of both genes in 10-30-h embryos forms a sharp boundary at the posterior border of the midbrain. As in the mouse, the early expression patterns of the zOtx genes are consistent with a role in defining midbrain and forebrain territories. However, there are a number of interesting differences between the forebrain and midbrain regions which express the genes in the two species.

Amino Acid Sequence↗

Jejunobronchial fistula: case report and brief discussion of the literature.

Enterobronchial fistulas are extremely rare. Herein we describe a 69-year-old man who had previously undergone resection of a gastric adenocarcinoma. He was hospitalized because of a fever, cough that produced brown sputum, dyspnea at rest, and an 18-kg weight loss during the previous year. A jejunobronchial fistula was diagnosed when methylene blue, which had been added to an enteric feeding, was detected in a bronchus during bronchoscopy. In addition to the current case, we include a brief review of the literature.

Aged↗

Morphological and cellular basis for airflow limitation in smokers.

Airflow limitation has two well-defined components, increased resistance, which is found predominantly in the small airways, and loss of elastic recoil. Small airways contribute to the increased resistance to flow by the narrowing of the airway lumen. Morphometric studies have shown that smokers have increased epithelial abnormalities, cellular inflammatory infiltrates in the airway wall, increased muscle and fibrosis, when compared with nonsmokers. Along with these anatomical changes, an increased percentage of airways < 400 microns in diameter is found. In addition to the measured changes, other nonmeasurable, dynamic events occur in the airways of smokers, which further decrease lumen diameter. There is ample evidence to show that the airways of smokers react to nonspecific stimuli by constricting, which results in increased resistance and decreased forced expiratory volume in one second (FEV1). The pathological changes found in smokers, that could be responsible for active muscle constriction and airway narrowing include: 1) airway epithelial damage, resulting in increased permeability and impairment of other epithelial function; 2) chronic airway inflammation; 3) structural changes in the airway wall; and 4) loss of alveolar attachments. However, not all smokers develop the abovementioned airway abnormalities. We describe how smokers could develop either centrilobular emphysema (CLE), or panlobular emphysema (PLE). We have found that smokers with CLE have more abnormal and narrower small airways, and flow limitation is correlated with the small airway abnormalities and not with loss of recoil. In contrast, smokers with PLE have much less severe airway abnormalities, diffuse emphysema that can be detected microscopically at a stage when FEV1 might be only mildly abnormal, and early changes in elastic recoil as evidenced by the changes in the pressure-volume curve of the lung. Furthermore, in PLE, airflow limitation is correlated with loss of recoil but not with abnormalities in the small airways. We believe that the mechanisms involved in the pathogenesis of the two types of emphysema in smokers are different; an airborne mechanism for CLE, possibly related to airway hyperresponsiveness, and a bloodborne mechanism for PLE, which may be related to dysfunction of alpha 1-antiproteases. We conclude that the separation of smokers based on their emphysema type is essential if we are to understand the pathogenesis of chronic obstructive pulmonary disease (COPD) in these subjects.

Bronchi↗

Fibromyalgia in familial Mediterranean fever.

OBJECTIVE: To determine whether chronic lower body pain in a subpopulation of patients with familial Mediterranean fever (FMF) is due directly to the musculoskeletal manifestations of FMF or whether they are connected to mechanical problems in the low back and leg/foot or to other factors operative in fibromyalgia (FM). METHODS: In 93 consecutive patients with FMF a point count of 14 tender points (TP) was conducted by thumb palpation. Tenderness thresholds were assessed in some of the TP and of control point sites by Chatillon dolorimeter. RESULTS: In female patients with FMF dolorimeter thresholds of fibrositic and control point sites were significantly lower than in male patients with FMF (p < 0.004). Also patients with FMF with back pain and foot/leg pain are more tender than patients with FMF without this characteristic (p < 0.001). CONCLUSION: The detection of FM and definition of tenderness thresholds is relevant to this disease, since musculoskeletal complaints are common in this group of patients but not always explained by objective findings.

Adolescent↗

Outbreak of Candida tropicalis fungemia in a neonatal intensive care unit.

OBJECTIVE: To describe an outbreak of Candida tropicalis fungemia in a neonatal intensive care unit (NICU), to evaluate the risk factors associated with this infection and the possible mode of nosocomial transmission. DESIGN: Descriptive and case-control study. PATIENTS AND METHODS: Surveillance cultures were taken from hospitalized patients, personnel, and inanimate objects in the NICU. Six patients with C tropicalis fungemia (cases) were compared with C tropicalis culture-negative patients matched for duration of exposure to the NICU (controls). RESULTS: During a five-month period, C tropicalis was isolated from 29 blood cultures of six premature infants. The same organism also was isolated from fingernail samples taken from the ward housekeeper, who had a mild onychomycosis, and an asymptomatic nurse. Other potential reservoirs of C tropicalis were not identified among all the other infants or in the hospital environment. The six patients with C tropicalis fungemia were more likely to have received a larger number of antibiotics (4.0 versus 1.8, P < 0.001) and to have been subjected to a longer duration of total parenteral nutrition (TPN) therapy (8.5 versus 2.67 days, P = 0.004) than the controls. CONCLUSIONS: The risk of fungemia in this outbreak can be attributed to a larger number of antibiotics and a longer period of TPN administered to the patients. Analysis of events suggests that the outbreak may have been the result of cross-infection between staff and patients.

Candidiasis↗

Diagnostic efficacy of a DNA probe in pneumonia caused by Legionella species.

A commercial DNA probe kit (Gen-probe) for the detection of rRNA from legionellae was evaluated for its accuracy in diagnosing Legionnaires' disease in 167 patients with pneumonia. The test was performed on freshly obtained clinical respiratory tract samples. Cultures and direct immunofluorescence antibody (DFA) staining of the samples and serological tests were performed simultaneously for all patients. The probe assay result was positive in six patients; five of them had other laboratory evidence of disease (positive cultures or positive serological results or both). Depending on the diagnostic criteria, the probe test had a sensitivity of 31-67%, a specificity of 99% and positive predictive values of 67-83%. The diagnostic performance of the DNA probe assay in this study was superior to that of the DFA test. The results indicate that the examination of respiratory tract secretions by the Gen-probe kit is a suitable screening test for the diagnosis of Legionnaires' disease.

DNA Probes↗

Colonization of the respiratory tract with Legionella species.

Pneumonia is the most important manifestation of disease caused by Legionella species. However, it is still not known for certain how these organisms actually enter the lungs. During a 5-month period 318 hospitalized patients without clinical or radiologic features of pneumonia were enrolled in a survey of sputum colonization with Legionella. Diagnostic tests included cultures, direct fluorescent antibody test (DFA) and DNA probe assay of sputum. Colonization was considered to occur when at least one of these tests was positive. According to our definitions, 1.2-10% of of these patients could have been colonized by Legionella spp. However, all cultures were negative and in all but one of these patients the DFA was the only positive test. A case-control study comparing test-positive and test-negative patients failed to identify any different features of disease or epidemiologic characteristics. These findings suggest that a high rate of false-positive DFA results occurred in our study rather than any new evidence of colonization of the respiratory tract with Legionella.

Case-Control Studies↗

Anaerobic osteomyelitis in patients with Gaucher's disease.

Bone involvement in patients with Gaucher's disease is common, and some of its clinical manifestations may resemble acute osteomyelitis. In addition, many studies have emphasized the high risk of secondary infection when surgical procedures are performed at the site of the involved bone. Nevertheless, these infections have never been well documented in the literature. Presentation of a patient with Gaucher's disease and osteomyelitis due to Prevotella (Bacteroides) melaninogenica provided us the opportunity to review 10 other similar case reports documented in the literature since 1966. This review suggests that acute hematogenic osteomyelitis is an uncommon complication of Gaucher's disease, but it is of interest that in most cases it is due to unusual organisms, particularly anaerobes.

Adult↗

orthodenticle activity is required for the development of medial structures in the larval and adult epidermis of Drosophila.

Lethal alleles of orthodenticle (= otd) cause abnormalities in the embryonic head that reflect an early role in anterior pattern formation. In addition, otd activity is required for the development of the larval and adult epidermis. Clonal analysis of both viable and lethal alleles shows that the adult requirement for otd is restricted to medial regions of certain discs. When otd activity is reduced or removed, some medial precursor cells produce bristles and cuticle characteristic of more lateral structures. Similar medial defects are observed in the larval epidermis of embryos homozygous for lethal otd alleles. Antibodies to otd recognize a nuclear protein found at high levels in the medial region of the eye antennal discs, the leg discs, the genital discs and along the ventral midline of the ventral epidermis of the embryo. These results suggest that the otd gene product is required to specify medial cell fates in both the larval and adult epidermis.

Animals↗