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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

[Drug fever].

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Body Temperature Regulation↗

Orthodenticle regulation during embryonic head development in Drosophila.

The homeobox gene orthodenticle (otd) specifies anterior head development in the Drosophila embryo, otd-related genes are also found in vertebrates, with expression patterns suggesting that they are important for the development of anterior regions of the head and brain. Here, we analyze the molecular mechanisms by which otd expression is activated within its normal domain in the head and repressed outside this region. We demonstrate that, contrary to early models of embryonic pattern formation, high levels of the bicoid morphogen are not required for otd activation or for the establishment of anterior head structures. We also show that the terminal system contributes to otd activation in the head primordium. Finally, we identify a novel pathway mediated by the gap gene huckebein through which three maternal systems cooperate to repress otd expression at the anterior terminus of the embryo.

Animals↗

Sarcoidosis mimicking toxoplasmosis with severe hypercalcaemia and normal 1,25-dihydroxy vitamin D.

We report a case of a female patient with sarcoidosis who presented with a generalized lymphadenopathy and a strong IgG serological test of toxoplasmosis. Progressive lymphadenopathy with a rising plasma calcium (up to 15 mg dL-1) with a normal plasma 1,25-dihydroxy vitamin D concentration occurred later. Corticosteroid therapy resulted in prompt clinical and biochemical responses with normalization of plasma calcium and a significant reduction in 1,25-dihydroxy vitamin D concentration. This is an exceptional presentation of sarcoidosis with severe hypercalcaemia and normal vitamin D metabolites.

Adult↗

Brain abscesses: the lung connection.

Pulmonary arteriovenous fistulas are uncommon abnormalities of capillary development which cause right to left shunting and, if not treated, may lead to severe neurological complications, including meningitis and brain abscess. Pulmonary arteriovenous fistulas are commonly a result of hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber disease) and both conditions may be readily diagnosed by careful history taking and physical examination. Two cases of brain abscess associated with hereditary haemorrhagic telangiectasia, which remained unrecognized for many years, are reported. These cases emphasize the importance of early diagnosis and treatment of pulmonary arteriovenous fistula in preventing central nervous system infections.

Adult↗

Failure of cefonicid prophylaxis for infectious complications related to endoscopic retrograde cholangiopancreatography.

We performed a controlled study to evaluate the role of cefonicid in preventing infectious complications related to retrograde cholangiopancreatography (ERCP). Consecutive patients were randomized to receive prophylaxis with cefonicid (1 g intravenously) 1 hour before the procedure or to be untreated controls. During a 26-month period, 179 ERCPs, including 93 therapeutic procedures, were performed on 164 patients. Prophylaxis was administered before 88 procedures (49%). The rate of bacteremia among treated patients was similar to that among controls (3% vs. 2%, respectively; P = .4). The rate of cholangitis was also similar among both groups (8% vs. 2%, respectively; P = .07). There were no episodes of sepsis, and none of the patients died. The rate of bacteremia was also similar among patients undergoing diagnostic procedures and patients undergoing therapeutic procedures, but all cases of cholangitis occurred in the latter group (0 vs. 10%, respectively; P = .002). Nevertheless, the rate of cholangitis was not significantly changed by the use of prophylaxis (14% among treated patients vs. 5% among controls, P = .12). Therefore, infectious complications could not be prevented by cefonicid prophylaxis.

Bacteremia↗

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↗