Genetic testing for cancer predisposition--an ongoing debate.
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Biomedical subjects
Publications and source records attributed to S Friedman.
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UNLABELLED: Currently recommended antibiotic treatment of suspected neonatal sepsis is ampicillin and an aminoglycoside. Recently, we observed increasing ampicillin and gentamicin resistance in strains of Escherichia coli isolated from neonates at our institution. We therefore reviewed clinical and laboratory records of all neonates with systemic infection, hospitalized from 1994 through 1998, from whom E. coli was isolated from blood and/or cerebrospinal fluid. The influence of perinatal variables (e.g. rupture of foetal membranes > 24h, group B Streptococcus (GBS) colonization, urinary tract infection during pregnancy and the use of antepartum and/or intrapartum antibiotics), and neonatal variables (e.g. gestational age, age at onset of sepsis (early: < or = 72 h, late: >72 h), number of E. coli septic recurrences, and associated underlying medical and/or surgical conditions) on antimicrobial susceptibilities of invasive E. coli isolates was studied. Twenty-three neonates with invasive E. coli infection were identified; most [19 (83%)] presented as late-onset sepsis (LOS). Ampicillin-resistant E. coli were isolated in 75% and 53% of neonates in the early- and late-onset groups, respectively. Gentamicin resistance was found in 50% of early-onset sepsis (EOS) isolates compared with 16% in the late-onset group. Isolates from two neonates with EOS were resistant to both ampicillin and gentamicin. One neonate with EOS and three with LOS had recurrent E. coli sepsis; all isolates were ampicillin-resistant and one was gentamicin-resistant. All these neonates were initially treated with ampicillin and gentamicin. Both groups had associated underlying medical and/or surgical conditions (50% early-onset, 47% late-onset). Maternal GBS colonization occurred in 2 (50%) versus 3 (16%) of EOS and LOS cases, respectively. All GBS colonized women received intrapartum ampicillin prior to delivery. CONCLUSIONS: Ampicillin and gentamicin resistance is emerging in neonatal E. coli isolates from invasive infection. Current- empiric management of neonatal sepsis requires re-evaluation given changing antimicrobial susceptibilities.
The resistance of an experimental sealer (KT-308) to bacterial ingress was assessed in six beagle dogs. In four mandibular premolars per dog, canals were prepared, filled with condensed gutta-percha and either KT-308 or Roth 801 cement (n = 24 roots), and the pulp chambers inoculated with plaque. Two additional premolars per dog were similarly root-filled, but not inoculated (n = 12 and 11, respectively). One incisor per dog was inoculated, but not root-filled (n = 6). Dogs were terminated after 6 months, and jaw blocks were retrieved and processed for light microscopic examination of the periapical tissues. Inflammation about the inoculated roots was significantly lower (p < 0.03) for KT-308 (17%) than Roth 801 cement (46%). Inflammation about the noninoculated roots did not differ significantly between KT-308 (8%) and Roth 801 cement (36%). This study demonstrated a better functional efficacy of KT-308 than of Roth 801 cement, and validated this in vivo model for assessment of root filling materials.
To prevent reinfection after root canal treatment, root filling materials should be antimicrobial. This study assessed the antimicrobial efficacy of KT-308, a modified glass ionomer cement sealer, and three formulations of ZUT, a combination of KT-308 and three different concentrations of a silver-containing zeolite. Discs prepared from the test materials and paper controls were incubated in Brain Heart Infusion broth for 12 wk. At 2-wk intervals, 18 discs from each group were inoculated with Enterococcus faecalis and incubated for periods of 1 to 30 h. After further processing, a 200 microliters aliquot of the broth immersing each disc was plated on agar and assessed for bacterial growth. The remaining broth was measured for optical density. All ZUT discs demonstrated no bacterial growth after 15 h of interaction, in contrast to abundant growth with the KT-308 and paper discs. Thus ZUT effectively suppressed adherent E. faecalis after 15 h, irrespective of its concentration and age.
Previous studies have demonstrated antimicrobial substantivity in root canal dentin up to 7 days after treatment with chlorhexidine. This in vitro study assessed the antimicrobial substantivity of chlorhexidine-treated bovine root dentin over a period of 21 days. Sixty standardized bovine root sections were randomly divided into three equal groups, and their canals immersed in one of the following solutions: (i) sterile saline; (ii) 2.5% NaOCl; or (iii) 0.2% chlorhexidine (CHX). Half the specimens in each group were treated with the solution for 5 min and the other half for 7 days. After solutions were removed, the specimens were incubated at 37 degrees C in Brain Heart Infusion broth containing Enterococcus faecalis (ATCC 29212). A fresh inoculum was added to the broth every other day over a 21-day period. The canals were then enlarged with sterile burs, and the dentin shavings collected and cultured for the presence of cultivable bacteria in the dentinal tubules. Specimens treated with CHX for 7 days demonstrated significantly less dentin colonization by E. faecalis than the other specimens. CHX has potential as an intracanal medicament, if it can be applied for a period of at least 7 days.
Root canal dentin acquires antimicrobial substantivity after exposure to chlorhexidine gluconate (CHX) for 1 wk. Therefore development of a vehicle for delivery of CHX as an intracanal medication is desirable. This in vitro study assessed the efficacy of two CHX delivery vehicles, a controlled-release device and a gel, to affect antimicrobial substantivity of bovine root dentin. Sixty bovine incisor root specimens were prepared with standardized length (10 mm) and canal diameter (3.3 mm), and coated externally with nail polish. Specimens were divided into four equal groups and their canals medicated for 7 days with either: (i) an experimental controlled-release device containing 25% CHX that was immersed in sterile saline; (ii) 2% CHX gel; or (iii) Ca(OH)2 paste. Sterile saline was used as the positive control. After medication, the canals of the specimens were inoculated with Enterococcus faecalis for 21 days. Root canal dentin samples ranging in depth from 0.1 to 0.45 mm were then obtained using sterile round burs of ascending diameter. Each dentin sample was placed in a separate test tube containing Brain Heart Infusion broth and incubated for 24 h. The optical density (OD) of the broth was then measured spectrophotometrically at 540 nm. The positive control showed significantly higher mean OD values (one-way ANOVA and Tukey's Studentized Range Test; p < 0.001) than the three test groups. The CHX controlled-release device group showed significantly lower OD values than the Ca(OH)2 group; however only at dentin depths up to 0.2 mm. In contrast, the CHX gel group consistently showed significantly lower OD values than both the CHX controlled-release device and Ca(OH)2 groups. These results suggest that bovine root canals medicated with 2% CHX gel for 7 days acquire antimicrobial properties for at least 21 days.
A dentin-bonding root canal sealer (ZUT) has been developed, consisting of an experimental glass ionomer cement (KT-308) and an antimicrobial silver-containing zeolite (0.2% by weight). This in vitro study evaluated the ability of ZUT used with or without gutta-percha, to resist bacterial ingress of Enterococcus faecalis over a period of 90 days. Canals of 80 single-rooted teeth were prepared with apical patency and filled as follows (n = 10): KT-308 alone; KT-308 with a single gutta-percha cone (SCGP); ZUT alone; ZUT with SCGP; AH26 alone; AH26 with SCGP; positive control-no root canal filling; and negative control-no root canal filling, with the apices of this group sealed with C&B Metabond cement. Teeth were coated with nail polish except for the apical 2 mm, and each tooth was sealed in a 4-ml glass vial, with an 18-gauge needle inserted through the vial cover and bonded into the pulp chamber with C&B Metabond cement. After sterilization with 2.5 Mrad gamma-radiation, Brain Heart Infusion broth with phenol red was injected into each vial. An inoculum of E. faecalis was pipetted through the needle into the pulp chamber every 5 days, and the broth was monitored daily for color change and turbidity. When change occurred, the broth was cultured for growth of E. faecalis. Kaplan-Meier survival analysis and the log-rank test revealed no significant differences among the three sealers used. The presence of gutta-percha, however, significantly improved resistance to bacterial ingress through obturated root canals (X, p < 0.05). Under the conditions of this study, the hypothesized advantage of ZUT (0.2% zeolite) was not demonstrated.
OBJECTIVE: To describe mortality, morbidity at discharge and neurodevelopmental outcome at 2 years corrected age in extremely low birth weight infants with systemic Candida infection during intensive care stay. METHOD: We identified all extremely low birth weight (birth weight <1000 g) infants diagnosed with Candida sepsis and/or meningoencephalitis between 1988 and mid-1996 in the tertiary neonatal intensive care centers of Toronto. The outcome of the infected infants at discharge and at 2 years corrected age was compared with a cohort of 470 extremely low birth weight infants born between 1990 and 1994. RESULTS: Forty-six extremely low birth weight infants with systemic Candida infection, mean (+/-SD) gestational age of 24.7 +/- 1.6 weeks and birth weight 699 +/- 135 g, were identified. Case fatality rate was 37% (17 of 46), not significantly different from the control group (35%). Data on 27 infected survivors were available at discharge. All had chronic lung disease compared with 33% in the control cases (P = 0.0001), a high incidence of periventricular leukomalacia (26% vs. 12%, P = 0.06) and an increase in severe retinopathy of prematurity (22% vs. 9%, P = 0.04); 60% had adverse neurologic outcomes at 2 years corrected age compared with 35% in the control group, and 41% vs. 12% had severe disabilities (P = 0.005). Cranial ultrasound examination was the only diagnostic modality in 5 of 13 (38%) cases with central nervous system Candida involvement. All infants with brain parenchymal lesions detected by cranial ultrasound had poor outcome. Early diagnosis and commencement of antifungal treatment favorably affected the outcome. CONCLUSIONS: Systemic Candida infection is associated with increased short and long term morbidity in extremely low birth weight infants. Candida infection of the central nervous system has a significant impact on long term neurodevelopmental outcome. Performance of cranial ultrasound examination is recommended as a part of the diagnostic investigation in these infants. Detection of brain parenchymal involvement might provide further information to predict outcome.
BACKGROUND: The Program of All-Inclusive Care for the Elderly (PACE) replicates the model of comprehensive, community-based geriatric care pioneered by On Lok, that enrolls frail older adults who meet states' criteria for nursing home care, and that uses interdisciplinary teams to assess the participants and to deliver care in appropriate settings. As managed care, PACE receives capitated payment from Medicare and Medicaid. Thus, PACE's fiscal incentives are thought to be aligned with the goals of optimizing health, function, and quality of life through the delivery of effective primary, preventive, restorative, supportive, and palliative care and through the avoidance of inappropriate and expensive hospital and nursing home utilization. OBJECTIVES: To describe short-term hospital utilization, hospital discharge diagnoses, time from enrollment to first hospitalization and its clinical predictors, and hospitalization in relation to mortality among PACE participants. METHODS: Data on short-term hospitalization and participants were recovered from PACE's minimum data set. Bed use was evaluated in annual cross-sections of current participants. Primary hospital discharge diagnoses were available for discharges from September 1, 1993 through March 31, 1997. The time from enrollment to hospitalization was calculated for the participants (n = 5478) who were admitted between January 1, 1990 and March 31, 1997. The characteristics of this inception cohort were used to develop a Cox regression model of hospitalization. All PACE deaths were identified and the place of death was recovered, together with the medical records used in the hospital during PACE enrollment or 6 months before death. RESULTS: Bed-days per 1,000 PACE participants per year were comparable with the general Medicare (fee-for-service) population, at 2,046 (in 1998) versus 2014 (in 1997) despite the greater morbidity and disability for PACE participants, as reflected in their enrollment characteristics and primary hospital discharge diagnoses. The time to hospitalization was 773 days (median); 95% confidence interval, 725, 814, and was predicted by disease, treatment, social and demographic factors. Whereas 8% of PACE deaths occurred in acute hospitals, less than one-third of the decedents spent any time in the hospital in the 6-month interval before death. CONCLUSIONS: Overall, short-term hospital utilization among PACE participants is low in contrast with that for other older and disabled populations. Participant predictors of hospitalization in PACE are generally consistent with other studies in older clinical and community populations. Both utilization and risk vary considerably across PACE sites, independent of participant-level risk factors, hence suggesting that further investigation is required to study PACE's management of acute illness and hospitalization decisions. Critical to maintaining PACE's success is an understanding of the independent impact of the organization and the environment of health care on this management.
Over 30% of root filled teeth in the population present with endodontic infective disease, which has either persisted or emerged after treatment. Management of these "failed" cases is a challenge to the clinician, at the levels of diagnosis, case selection, communication and decision, and that is even before techniques are considered. Diagnosis should differentiate between endodontic and other aetiologies, and focus on the site of infection. Case selection should be based on how best to control the infection, but also on the benefit-risk balance of the alternative treatment modalities, the attitudes of the patient and the capability of the clinician. All of the above must be communicated to the patient, who then should make the informed decision regarding the selected treatment. This article discusses the treatment rationale, diagnosis, case selection and communication related to post-treatment endodontic disease.
OBJECTIVE: To determine the correlations between three bacterial dermatoses in cattle, milk production and bulk-milk somatic cell count (BMSCC). DESIGN: Field observations in three dairy cattle herds. METHODS: Milk production, BMSCC, fertility and all herd diseases were recorded by computerised dairy management systems. Each herd was visited twice weekly and the clinical signs, course of diseases and morbidity and culling rates were noted. Bulk-tank milk was sampled twice monthly and analysed for somatic cell count. Bacteriological and histological examinations were carried out from samples collected from affected animals in the respective herds. RESULTS: The acute exudative form of dermatophilosis was diagnosed only in first-calving cows. The morbidity rate was 53% and the culling rate was 16% of the affected animals. The BMSCC increased by a factor of 2.4 times, and there was an average loss of milk production of 30%/cow/day in affected animals. Ulcerative lymphangitis was diagnosed in first-calving cows (22%) and older cows (15%). The culling rate was 28%. The BMSCC increased by a factor of 17.3 times, and the average loss of milk production was 5.5%/affected animal/day. Papillomatous digital dermatitis (PDD) was diagnosed in first-calving cows (25%) and in older cows (18%). The culling rate was 8%. The BMSCC increased by a factor of two times, and the average loss of milk production was 1.7%/affected animal/day. CONCLUSIONS: The correlations between three skin diseases (ulcerative lymphangitis, dermatophilosis, papillomatous digital dermatitis), milk production and BMSCC have been found to be unfavourable.
The monoclonal immunoglobulin products of plasma cell neoplasm can give rise to a variety of manifestations including hyperviscosity, amyloidosis, cryoglobulinemia, neuropathy, and renal failure. A 50-year-old woman with monoclonal cryoglobulinemia developed extensive gangrene and ulceration of both hands and feet over several weeks requiring bilateral below-elbow and below-knee amputations. This case illustrates the importance of qualitative properties of paraprotein.
BACKGROUND: Beta-Carotene has been reported to produce regressions in patients with oral leukoplakia, a premalignant lesion. However, previous studies have all been of short duration, with clinical response as the end point. OBJECTIVE: To evaluate the duration of response and the need for maintenance therapy in subjects who respond to beta-carotene. METHODS: In this multicenter, double-blind, placebo-controlled trial, subjects were given beta-carotene, 60 mg/d, for 6 months. At 6 months, responders were randomized to continue beta-carotene or placebo therapy for 12 additional months. RESULTS: Fifty-four subjects were enrolled in the trial, with 50 being evaluable. At 6 months, 26 subjects (52%) had a clinical response. Twenty-three of the 26 responders completed the second, randomized phase. Only 2 (18%) of 11 in the beta-carotene arm and 2 (17%) of 12 in the placebo arm relapsed. Baseline biopsies were performed in all patients, with dysplasia being present in 19 (38%) of the 50 evaluable patients. A second biopsy was obtained at 6 months in 23 subjects who consented to this procedure. There was improvement of at least 1 grade of dysplasia in 9 (39%), with no change in 14 (61%). Nutritional intake was assessed using food frequency questionnaires. There was no change in carotenoid intake during the trial. Responders had a lower intake of dietary fiber, fruits, folate, and vitamin E supplements than did nonresponders. Beta-carotene levels were measured in plasma and oral cavity cells. Marked increases occurred during the 6-month induction. However, baseline levels were not restored in subjects taking placebo for 6 to 9 months after discontinuation of beta-carotene therapy. CONCLUSIONS: The activity of beta-carotene in patients with oral leukoplakia was confirmed. The responses produced were durable for 1 year.
We report a female patient with congenital toxoplasmosis who presented with hydrops fetalis and cerebral abnormalities, detected on fetal ultrasound. Following prenatal treatment, the hydrops fetalis resolved and at four months of age she has normal growth and development. This case emphasizes the potential good prognosis in cases with congenital toxoplasmosis detected and treated prenatally.
BACKGROUND & AIMS: Adenomatous polyps are by definition dysplastic and pathologically indistinguishable from the dysplasia-associated lesion or mass (DALM) described in 1981. Yet, adenomatous polyps in noncolitic colons are usually removed definitively endoscopically, whereas DALMs are regarded as harbingers of colon cancer, mandating colectomy. METHODS: Since 1988, all of our patients with chronic ulcerative or Crohn's colitis and dysplastic polyps and no coexistent dysplasia in flat mucosa underwent colonoscopic polypectomy. Biopsy specimens were obtained also adjacent to polypectomy sites, from strictures, and throughout the colon at 10-cm intervals. Follow-up colonoscopies and biopsies were performed within 6 months after polypectomy and yearly thereafter. RESULTS: Colonoscopy in 48 patients with chronic colitis (mean duration, 25.4 years) resected 70 polyps (60 in colitic and 10 in noncolitic mucosa). Polyps were detected on screening colonoscopies (29%) and on surveillance (71%). Pathology was tubular adenoma in all polyps from noncolitic mucosa and low-grade dysplasia (57), high-grade dysplasia (2), or carcinoma (1) in polyps from colitic mucosa. Subsequent colonoscopies (mean follow-up, 4.1 years) revealed additional polyps in 48% but no carcinomas. Surgical resection (6 patients) for recurrent polyps confirmed colonoscopic findings. No dysplasia or cancers in flat mucosa were found at surgery or on follow-up colonoscopies. CONCLUSIONS: In patients with chronic colitis who have no dysplasia in flat mucosa, colonoscopic resection of dysplastic polyps can be performed effectively, just as in noncolitic colons.
This study evaluated penetration of Enterococcus faecalis in canals filled with glass ionomer cement sealers. Canals of 40 extracted teeth in four equal experimental groups were prepared and filled with KT-308 (experimental sealer) and a single gutta-percha cone (SC), ZUT (KT-308 with an antibacterial agent) and SC, Kerr sealer and vertically compacted gutta-percha (VC), or Kerr sealer with the antibacterial agent and VC. Eight additional teeth served as positive controls and four as negative controls. Pulp chambers were inoculated with E. faecalis, and bacterial penetration through the filled canals was assessed over a period of 90 days. Incidence of bacterial penetration was significantly higher for ZUT/SC than for Kerr sealer/VC (p < 0.05). KT-308/SC did not differ significantly from any other material. The positive controls showed significantly faster penetration than all the other groups (p < 0.05). It was concluded that KT-308 effectively prevented penetration of E. faecalis, whereas ZUT required further development.
This in vitro study characterized the interface of glass ionomer cement root canal sealers and dentin conditioned by common endodontic irrigants. The interface of Ketac-Endo and two experimental glass ionomer cement sealers (KT-308 and ZUT) with bovine dentin--conditioned with either distilled water, 2.6% NaOCl, or 17% EDTA, followed by 2.6% NaOCl--was investigated. Cylinders of each of the sealers were formed on the conditioned dentin surface and allowed to set for 90 min. They were first shear tested to failure to determine their adhesive bond strength. Then three dentin specimens from each group were processed for scanning electron microscopic study. The test-failed surface of the strongest and weakest bonded specimens was examined. A third specimen, of intermediate bond strength, was cross-sectioned and the interface was also examined. Failures in all of the specimens were found to be mainly cohesive in nature. Specimens conditioned with 2.6% NaOCl only revealed the presence of a hybrid layer at the interface composed of dentin and whichever of the sealers were tested.
This study was designed to determine if digital images stored on the hard drive of a Schick computer dental radiography system could be exported, altered, and then restored to the drive without any visible signs of alteration. Digital images were downloaded from the computer dental radiography system using an I-Omega Zip Drive, 100-MB capacity, and then opened in Corel Photo Paint where images were altered and manufacturer export symbols were edited. The resulting images were printed to a default printer (Fargo Foto Fun). The ease of manipulation of the exported digital images reflects the need for the manufacturer to implement safeguards so that the integrity of digital imaging cannot be compromised. Computer dental radiography has many advantages: conservation of time (instant radiographs), less radiation (50 to 60%), no chemical waste, and many viewing options. However, questions that might be raised regarding the ability of persons with minimal computer expertise, using a commercially available program to alter images should be addressed.