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Biomedical subjects

D Greenberg

Publications and source records attributed to D Greenberg.

At least 55 records · Page 3Linked to original sources

NAGLU mutations underlying Sanfilippo syndrome type B.

Sanfilippo syndrome type B (mucopolysaccharidosis III B) is a rare autosomal recessive disease caused by deficiency of alpha-N-acetylglucosaminidase, one of the enzymes required for the lysosomal degradation of heparan sulfate. The gene for this enzyme, NAGLU, recently was isolated, and several mutations were characterized. We have identified, in amplified exons from nine fibroblast cell lines derived from Sanfilippo syndrome type B patients, 10 additional mutations: Y92H, P115S, Y140C, E153K, R203X, 650insC, 901delAA, P358L, A664V, and L682R. Four of these mutations were found in homozygosity, and only two were seen in more than one cell line. Thus, Sanfilippo syndrome type B shows extensive molecular heterogeneity. Stable transfection of Chinese hamster ovary cells, by cDNA mutagenized to correspond to the NAGLU missense mutations, did not yield active enzyme, demonstrating the deleterious nature of the mutations. Nine of the 10 amino acid substitutions identified to date are clustered near the amino or the carboxyl end of alpha-N-acetylglucosaminidase, suggesting a role for these regions in the transport or function of the enzyme.

Acetylglucosaminidase↗

High prevalence of "Simkania Z," a novel Chlamydia-like bacterium, in infants with acute bronchiolitis.

The newly described microorganism "Simkania Z" ("Z"), an obligate intracellular, penicillin-resistant microorganism most closely related to the chlamydiae, has been associated with adult community-acquired pneumonia. The possible involvement of "Z" in bronchiolitis in infants was examined in a prospective study of 239 infants with bronchiolitis and 78 controls. Other potential etiologic agents sought were respiratory syncytial virus (RSV), adenovirus, and cytomegalovirus. Evidence for the presence of "Z" in nasopharyngeal wash specimens (polymerase chain reaction and/or culture) was found in 25% of infants with bronchiolitis, while controls were all negative (P < .001). A serum IgA response to "Z" infection was detected by immunoperoxidase assay in 15% of infants with bronchiolitis versus 1.3% of controls (P < .001). Clinical findings were not different for infants with bronchiolitis associated with RSV alone, "Z" alone, or RSV and "Z" together. The high prevalence of "Z" in infants with bronchiolitis, often accompanied by an immune response, suggests a possible etiologic role of this agent in the disease.

Adenoviruses, Human↗

Resistance pattern of middle ear fluid isolates in acute otitis media recently treated with antibiotics.

BACKGROUND: Little information is available about the effect of antibiotic treatment on the prevalence and MIC of the subsequently isolated pathogens in cases of acute otitis media (AOM) failing a course of antibiotic therapy. This information is important, particularly regarding the effectiveness of the oral antibiotics used in children failing initial therapy. PATIENTS AND METHODS: One hundred eighty-one children with culture-positive AOM were prospectively studied between October, 1995, and July, 1996. Sixty-three (35%) patients received various antibiotics for variable periods during the 14 days preceding enrollment. RESULTS: A total of 94 Streptococcus pneumoniae (Pnc) and 113 Haemophilus influenzae (Hi) were isolated. Thirty-eight Pnc and 35 Hi were isolated in the 63 patients with recently treated AOM. Pnc as a single isolate was more prevalent in patients recently treated with antibiotics (27 of 63, 43%) than among those not recently treated (32 of 118, 27%, P = 0.047). The MIC50 values of penicillin, cefaclor and cefuroxime axetil for Pnc were significantly higher in the pneumococci isolated from patients recently treated than among those isolated from patients not recently treated with antibiotics (0.38, 3 and 0.75 microg/ml vs. 0.094, 0.38 and 0.12 microg/ml, respectively). Seventy-nine percent of Pnc isolates in the recently treated group had MIC for penicillin of >0.1 microg/ml vs. only 47% in those not recently treated (P < 0.05). The respective figures for MIC >0.5 microg/ml of cefaclor were 79% vs. 41% for the recently treated and not recently treated groups (P < 0.001); cefuroxime MIC >0.5 microg/ml was found in 61 and 25%, respectively (P = 0.001). CONCLUSIONS: Pneumococcus is more prevalent in AOM after a recent antibiotic treatment, and the MIC of the commonly used beta-lactam drugs for Pnc is considerably higher in this setting. In view of our data, the use of oral cephalosporins like cefaclor or cefuroxime as second line drugs in the treatment of unresponsive AOM, particularly in regions where resistant PNC is prevalent, should be reconsidered.

Acute Disease↗

Early eradication of pathogens from middle ear fluid during antibiotic treatment of acute otitis media is associated with improved clinical outcome.

OBJECTIVE: To determine the relation between early bacteriologic eradication and clinical outcome of acute otitis media (AOM) in infants and young children treated with various antibiotics. STUDY DESIGN: The study group consisted of patients ages 3 to 24 months seen at the Pediatric Emergency Room with: (1) symptoms and physical findings consistent with AOM of < or = 7 days duration; (2) no spontaneous perforation or tympanostomy tubes; (3) positive initial middle ear fluid culture; and (4) a follow-up to at least Day 10+/-2 of the study with a second culture performed 72 to 96 h after initiation of antibiotic treatment. Any patient with a positive middle ear fluid culture 72 to 96 h after initiation of antibiotic treatment was considered to have bacteriologic failure. Otologic evaluation was done by an otolaryngologist unaware of the culture results and of the study drug allocation. A clinical score based on body temperature, report of irritability and ear tugging observed by the parents and the appearance and redness of the ear drum as observed by the otolaryngologist was also used for clinical evaluation. RESULTS: The study group consisted of 123 patients, of whom 57 (46%) had positive middle ear fluid 72 to 96 h after initiation of antibiotic treatment. Clinical failure was observed in 21 of 57 (37%) patients in whom bacteriologic eradication did not occur vs. only 2 of 66 (3%) patients with bacteriologic eradication after 3 to 4 days of treatment (P < 0.001). Clinical score for both moderate and severe disease decreased significantly faster in those with bacteriologic eradication than in those in whom middle ear fluid was still culture-positive 72 to 96 h after initiation of treatment. CONCLUSION: Clinical failures in our population were associated with inability to eradicate the causative organisms of AOM from the middle ear fluid within 3 to 4 days after initiation of antibiotic therapy. Most patients (including those without bacteriologic eradication) improved after 3 to 4 days of treatment, but patients with sterile middle ear fluid felt better after 3 to 4 days of treatment than patients in whom middle ear fluid was still culture-positive.

Acute Disease↗

Dynamics of pneumococcal nasopharyngeal colonization during the first days of antibiotic treatment in pediatric patients.

BACKGROUND: Nasopharyngeal (NP) carriage of antibiotic-resistant Streptococcus pneumoniae was shown to be associated with recent antibiotic treatment. To date no studies have evaluated early dynamics of pneumococcal NP carriage during antibiotic treatment. OBJECTIVES: To observe changes in NP pneumococcal carriage within 3 to 4 days after initiation of antibiotic treatment in acute otitis media (AOM). METHODS: Patients ages 3 to 36 months with AOM treated with various antibiotics were prospectively followed. Nasopharyngeal culture for S. pneumoniae was obtained before (Day 1) and 72 to 96 h after initiation of treatment (Days 4 to 5). Antibiogram and serotyping were performed in all isolates as was also the MIC of penicillin. The disappearance and persistence of the initial isolates as well as the appearance of isolates with new serotype or with new antibiotic susceptibility patterns were investigated. RESULTS: A total of 120 patients were studied: 106 received beta-lactam antibiotics and 14 received azithromycin. Among the initial 76 pneumococcal isolates 63, 37 and 13% were resistant to > or =1, > or =2 and > or =3 antibiotic drugs. After 3 to 4 days of treatment with various beta-lactam drugs, 45, 63 and 100% of isolates with MIC values of <0.1 microg/ml, 0.125 to 0.25 microg/ml and 0.38 to 1.0 microg/ml, respectively, persisted in the NP (P = 0.038). There was a difference between the various beta-lactam drugs in their effect on NP colonization: a drug with lower MIC values (cefuroxime-axetil) had a better eradication rate of penicillin-susceptible organisms than a less active one (cefaclor), but neither significantly reduced carriage of penicillin nonsusceptible isolates. Azithromycin eliminated carriage of macrolide-susceptible organisms but increased the carriage of macrolide-resistant ones. In 19 of 120 (16%) patients a new S. pneumoniae isolate was recovered 3 to 4 days after initiation of treatment. Of those 16 (84%) were resistant to the drug the patient was receiving. CONCLUSION: A rapid selection of nonsusceptible NP pneumococcal isolates during antibiotic treatment for AOM is common. This phenomenon may contribute to the spread of resistant pneumococci.

Acute Disease↗

Bacteriologic efficacy of a three-day intramuscular ceftriaxone regimen in nonresponsive acute otitis media.

OBJECTIVE: To determine the bacteriologic efficacy of ceftriaxone in nonresponsive acute otitis media in children. METHODS: In a prospective study 92 patients ages 3 to 36 months (median, 11 months) with culture-proved nonresponsive acute otitis media were studied from January, 1995, through August, 1997. The patients were treated with intramuscular ceftriaxone (50 mg/kg/l/day) for 3 days. Middle ear fluid was aspirated for culture by tympanocentesis on day of enrollment (Day 1); a second tap was performed on Days 4 to 10. Additional middle ear fluid cultures were obtained if clinical relapse occurred. Bacteriologic failure was defined by positive culture on Days 4 to 10. Patients were followed until Day 17+/-2. Susceptibility was measured by E test. RESULTS: The main drugs administered before enrollment were amoxicillin (38%), amoxicillinclavulanate (25%) and cefaclor (20%). Organisms recovered (n=105) were: Haemophilus influenzae, 54; Streptococcus pneumoniae, 47; Moraxella catarrhalis, 2; and Streptococcus pyogenes, 2. Thirty-four (72%) of the 47 S. pneumoniae isolates were intermediately resistant to penicillin (MIC 0.1 to 1.0 microg/ml), but all were susceptible to ceftriaxone (MIC < 0.5 microg/ml). Bacteriologic eradication was achieved in 100 of 105 (95%) cases: 54 of 54 (10O%) H. influenzae, 43 of 47 (92%) S. pneumoniae, 1 of 2 (50%) M. catarrhalis and 2 of 2 (100%) S. pyogenes. Bacteriologic success (with no relapse) occurred in 13 of 13 (100%) penicillin-susceptible S. pneumoniae vs. 28 of 34 (82%) S. pneumoniae intermediately resistant to penicillin (4 cases of bacteriologic failure and 2 cases of relapse). CONCLUSION: A 3-day intramuscular ceftriaxone regimen is efficacious for the treatment of nonresponsive acute otitis media. The optimal duration of treatment in cases of nonresponsive acute otitis media and whether ceftriaxone is efficacious for the treatment of nonresponsive otitis media caused by S. pneumoniae highly resistant to penicillin is yet to be determined.

Acute Disease↗

The treatment of social phobia: a critical assessment.

This article critically reviews the effects of psychological treatment (exposure, cognitive restructuring, social skills training) and pharmacological treatment (MAOIs, reversible MAOIs, anxiolytics and SSRIs) of social phobia. Only controlled studies have been included, and their outcomes were assessed for improvement in anxiety and avoidance, social functioning and clinical status. Both psychological and pharmacological treatments resulted in a significant and meaningful reduction in anxiety and, in most cases, a weakening of the tendency to avoid. Although useful, the effects were not of such a magnitude as to result in remission. Reduction in anxiety was long-lasting in patients treated by psychological methods. The lessening of anxiety did not necessarily lead to meaningfully improved social functioning. The combination of psychological and pharmacological treatments was disappointing, and did not exceed the effects of psychological treatments alone. However, the most promising medications were not tested. Subtype of social phobia and additional diagnoses did not determine the response to treatment.

Behavior Therapy↗

Prospective study to determine clinical relevance of detection of pneumococcal DNA in sera of children by PCR.

We undertook a prospective study to evaluate the accuracy of PCR of serum (aimed at the pneumococcal pneumolysin gene) at detecting pneumococcal infections in infants and children. The assay was positive for all blood and cerebrospinal fluid culture-positive samples and for 38 and 44% of patients with lobar pneumonia and acute otitis media, respectively. It was positive for 17% of healthy controls. There was a marked effect of age on the rate of positivity among healthy controls, with the highest rate (33%) being in 2-year-old children, the age group with the highest rate of nasopharyngeal (NP) carriage; the lowest rate was found among infants <2 months of age (13%) and adults ages 18 to 50 years (0%), age groups with the lowest NP pneumococcal carriage rates. Carriers of pneumococci in the nasopharynges had a higher rate of positivity than noncarriers of pneumococci in the nasopharynges for all groups. Our results suggest that although PCR of serum is a sensitive test for the detection of Streptococcus pneumoniae in sterile fluids, its high rate of positivity for healthy controls, related to NP pneumococcal carriage, might exclude it from being useful in detecting deep-seated pneumococcal infections.

Adolescent↗

Quality management for health care in the Middle East and north Africa: professional cooperation as part of the peace process.

BACKGROUND: In 1993, as the peace process opened up new possibilities for professional cooperation, the Quality Management (QM) Program for Health Care Organizations in the Middle East and North Africa was born of a shared perception that there is a high-priority need to improve the quality of health care and to cope with increasing costs and financial pressures. To date 22 health care organizations--including hospitals, primary care centers, health maintenance organizations, and ministries of health--are members of the QM Program and are actively implementing QM projects. DEVELOPMENT OF THE PROGRAM: The QM Program began with an introductory conference, followed by an intensive training course. During the current phase of the program (1996-1999), a variety of facilitation activities--including training visits to the region by international experts, consultation support to member organizations by volunteer mentors in the United States, professional-exchange seminars, and site visits--are being conducted at the regional and national levels. Since the training course, the QM Program member organizations have implemented more than 40 model QM projects to improve both clinical and nonclinical processes. Projects consistent with national and organizational priorities were selected, with an emphasis on fast-paced improvements that reduce costs and enhance patient satisfaction. FUTURE PLANS: The regional QM Program is envisioned to grow in size and strength through a four-year building process. By the year 2000, a cadre of local leaders should be prepared to carry the program forward into the new millennium.

Africa, Northern↗

Bacteriologic response to oral cephalosporins: are established susceptibility breakpoints appropriate in the case of acute otitis media?

Bacteriologic response to cefuroxime axetil and cefaclor administered for 10 days was evaluated in acute otitis media (AOM) in patients aged 6-36 months. Middle ear fluid culture was obtained by tympanocentesis before treatment, on day 4 or 5 after initiation of treatment, and if clinical relapse occurred before day 17. Bacteriologic failure was observed in 32% of patients receiving cefaclor versus 15% of patients receiving cefuroxime axetil (P = .009). Failure rates increased with increasing MIC: For Streptococcus pneumoniae, 0.5 microg/mL (established as cutoff value for cefuroxime by the National Committee for Clinical Laboratory Standards [NCCLS]) discriminated between success and failure. For Haemophilus influenzae, high failure rates were observed for cefaclor, even with low MICs (< or = 1.0 microg/mL), and with both drugs they tended to increase with increasing MIC, even for values below the cutoff suggested by the NCCLS (8.0 and 4.0 microg/mL for cefaclor and cefuroxime, respectively). Thus, for AOM caused by H. influenzae, lower susceptibility cutoff levels for MICs should be established.

Acute Disease↗

Single-and dual-energy CT with monochromatic synchrotron x-rays.

We explored the potential for clinical research of computed tomography (CT) with monochromatic x-rays using the preclinical multiple energy computed tomography (MECT) system at the National Synchrotron Light Source. MECT has a fixed, horizontal fan beam with a subject apparatus rotating about a vertical axis; it will be used for imaging the human head and neck. Two CdWO4-photodiode array detectors with different spatial resolutions were used. A 10.5 cm diameter acrylic phantom was imaged with MECT at 43 keV and with a conventional CT (CCT) at 80 kVp: spatial resolution approximately equal to 6.5 line pairs (lp)/cm for both; slice height, 2.6 mm for MECT against 3.0 mm for CCT; surface dose, 3.1 cGy for MECT against 2.0 cGy for CCT. The resultant image noise was 1.5 HU for MECT against 3 HU for CCT. Computer simulations of the same images with more precisely matched spatial resolution, slice height and dose indicated an image-noise ratio of 1.4:1.0 for CCT against MECT. A 13.5 cm diameter acrylic phantom imaged with MECT at approximately 0.1 keV above the iodine K edge and with CCT showed, for a 240 micrograms I ml-1 solution, an image contrast of 26 HU for MECT and 13 and 9 HU for the 80 and 100 kVp CCT, respectively. The corresponding numbers from computer simulation of the same images were 26, 12, and 9 HU, respectively. MECT's potential for use in clinical research is discussed.

Acrylates↗

A prospective study of neonatal sepsis and meningitis in southern Israel.

OBJECTIVE: To study the epidemiology of neonatal sepsis and meningitis in the Negev area of southern Israel. DESIGN: A prospective 8-year study conducted at the neonatal intensive care unit and pediatric wards of the Soroka University Medical Center. RESULTS: Two hundred twenty-nine cases of hospital and community-acquired neonatal sepsis occurred during the study period. Thirty-two patients (14%) were meningitis. During this period 70,709 births (59% Jews and 41% Bedouins) were recorded; thus the rates of neonatal sepsis and meningitis were 3.2 and 0.5/1000 live births, respectively. One hundred seventeen (4/1000 live births) cases were recorded in Bedouins and 112 (2.6/1000 live births) in Jewish neonates (P < 0.001). Twenty-six percent of all sepsis cases occurred within < 24 h from birth, 25% from Days 2 to 7 of life and 49% between Days 8 and 28. A total of 251 organisms that were considered true pathogens were isolated. Fifty-seven of all isolates were Gram-negative organisms (mainly Klebsiella pneumoniae (20%) and Escherichia coli (16%)). Gram-positive organisms were isolated in 41% of cases. Although E. coli was the most frequently recovered Gram-negative pathogen in community-acquired late onset sepsis, Klebsiella and Enterobacter spp. represented the most commonly isolated Gram-negative organisms in nosocomial late onset sepsis. All Staphylococcus aureus isolates recovered in late onset sepsis were nosocomial. The incidence of Streptococcus agalactiae was 3 times higher in early onset sepsis than in late onset sepsis. All cases of Streptococcus pneumoniae sepsis occurred in Bedouins. CONCLUSIONS: Neonatal sepsis and meningitis rates in southern Israel are similar to those reported in Western Europe and the United States. The incidence of neonatal sepsis is significantly higher for Bedouins than for Jewish neonates. The distribution of the main pathogens is different in southern Israel and although Gram-negative enteric organisms are predominant, S. agalactiae plays a relatively minor role in the etiology of sepsis during the first month of life. In southern Israel the etiology of community-acquired late onset sepsis is different from that of nosocomial late onset sepsis.

Female↗

Psychogenic cough tic: a case report.

A case of psychogenic cough tic is presented to demonstrate the problems and complications that can arise from misdiagnosis of this dramatic and disabling disorder. It can be confused with TS and may be treated more aggressively than is beneficial. A single case with a recurrent course is described with the hypothesis of a possible autoimmune contribution. The combination of organic precipitants and emotional maintaining factors suggests that psychogenic cough tic is a condition that lies between somatization and transient tic disorder.

Adolescent↗

Serum neuroleptic levels during reduced dose fluphenazine decanoate maintenance therapy.

Forty-one remitted and chronically psychotic schizophrenic out-patients completed a two-year clinical trial during which they were assigned, on the basis of their clinically determined maintenance dosages, to one of two reduced, fixed-dose fluphenazine decanoate (FD) regimens: 35 mg/4 wks (19 patients) or 10 mg/4 wks (22 patients). Eighty-one percent of chronically psychotic patients, who represented 74% of the high dose group, relapsed, in comparison with only 38% of remitted patients (p < .001), who represented 86% of the low dose group. During this study serum neuroleptic levels were assessed, using the radioreceptor assay, before the administration of each FD injection and whenever a patient relapsed. Overall, 334 serum neuroleptic activity measurements were performed. Serum neuroleptic levels were detectable in all patients and were higher, although not significantly, in the 35 mg/4 wks group. The dichotomous clinical outcome of chronically psychotic and remitted patients occurred within the framework of essentially similar serum neuroleptic levels. These findings suggest that: 1) serum neuroleptic levels can be monitored during low dose FD treatment, 2) the poor maintenance therapy outcome of chronically psychotic patients cannot be accounted for by inadequate neuroleptic bioavailability, 3) a majority of remitted FD maintained patients retain their clinical response at serum neuroleptic levels lower than those initially attained at steady state.

Adult↗

Peripheral atropinization does not change meal size controlled by prepyloric mechanisms.

To investigate the role of gastric contractility in the prepyloric control of meal size, we administered atropine methyl nitrate (3 mg/kg,ip) or saline prior to 30-min tests on 3 separate days in which 0.8 M sucrose was ingested by rats after 1 h of food deprivation. Ingested 0.8 M sucrose accumulated in the stomach and did not empty into the small intestine during the test because the pylorus of each rat was closed by inflation of a chronic pyloric cuff. Atropine methyl nitrate had no significant effect on 30-min intake or on the pattern of intake observed at 3-min intervals during the test on any of the three test days. Thus, neither acute nor repetitive experience with atropine methyl nitrate changed the pattern or volume of intake. These results suggest that gastric contractile responses elicited by the intragastric accumulation of 0.8M sucrose during ingestion are not necessary for the control of meal size by prepyloric mechanisms.

Animals↗

Devazepide increases food intake in male but not female Zucker rats.

The genetically obese Zucker rat (fa/fa) is hyperphagic compared to lean controls (Fa/?). This hyperphagia is characterized by increased meal size. Cholecystokinin (CCK) has been shown to decrease meal size in many species including humans. In the present study we investigated the role of endogenous CCK in mediating the hyperphagia of male and female obese Zucker rats. CCKA-type receptors were blocked with the specific antagonist, devazepide, and test meal size was measured. Male obese and lean rats significantly increased food intake following devazepide. Neither obese nor lean female rats significantly increased food intake following devazepide. This is the first demonstration of a gender difference in endogenous CCK-mediated satiety. These results have implications for the higher incidence of eating disorders in females.

Animals↗

Naloxone decreases intake of 10% sucrose in preweanling rats.

To investigate the role of opioids in the mediation of sucrose intake in the preweanling rat pup, we measured the effect of naloxone on intake of pups licking 10% sucrose from the floor of a beaker (independent ingestion test) and of pups ingesting 10% sucrose that was continuously infused through an anterior, sublingual oral catheter (oral catheter test). Pups were tested only once to eliminate the possible effect of test experience. Pups were tested in the second postnatal week (PN7, 9, 10, 11, and 14 days) with naloxone (1 mg/kg) or vehicle controls. Fourteen-day-old pups were also tested with 0.1 and 0.5 mg/kg. Naloxone began to be efficacious for inhibiting intake on PN10 in the oral catheter test and on PN11 in the independent ingestion test. On PN14, the inhibition of intake was dose related and naloxone was more potent for inhibiting intake in independent ingestion tests than in oral catheter tests. Naloxone not only decreased intake, it also decreased the incidence of licking, increased mouthing and resting, and had no significant effect on locomotion. The site of the inhibitory effect of naloxone on intake was in the central nervous system, presumably in the brain, because naloxonemethiodide, an analogue of naloxone that does not cross the blood-brain barrier, did not inhibit sucrose in either test. These results demonstrate that the intake of 10% sucrose depends on endogenous opioids as early as PN10 and that this opioid mechanism operates when pups have not had prior test experience and in a test (oral catheter test) where intake is not dependent on appetitive behaviors.

Animals↗