Biomedical subjects

M Aronson

Publications and source records attributed to M Aronson.

At least 19 recordsLinked to original sources

PubMed2006

Infectivity of nanovirus DNAs: induction of disease by cloned genome components of Faba bean necrotic yellows virus.

Circumstantial evidence suggests that the genome of Faba bean necrotic yellows virus (FBNYV), a nanovirus, consists of eight distinct, circular, single-stranded DNAs, each of about 1 kb and encoding only one protein. Here, the use of cloned full-length FBNYV DNAs for reproducing FBNYV-like symptoms in Vicia faba, the principal natural host of FBNYV, is reported. Characteristic symptoms of FBNYV infection were obtained in faba bean plants following biolistic DNA delivery or agroinoculation with all eight FBNYV DNAs. Although the eight different DNAs have been invariably detected in field samples infected with the various geographical FBNYV isolates, experimental infection with different combinations of fewer than eight DNAs also led to typical FBNYV symptoms. Even only five genome components, DNA-R, DNA-S, DNA-M, DNA-U1 and DNA-U2, were sufficient for inducing disease symptoms in V. faba upon agroinoculation. Symptomatic plants agroinoculated or bombarded with eight DNAs contained typical FBNYV virions; however, the virus was not transmitted by Aphis craccivora or Acyrthosiphon pisum, two efficient aphid vectors of FBNYV.

Animals↗

PubMed2005

Family history and molecular features of children, adolescents, and young adults with colorectal carcinoma.

BACKGROUND: Colorectal cancer is extremely rare in childhood. Published case series reporting children and adolescents with colorectal cancer have not focused on the underlying genetic aspects of the tumour or genetic susceptibility of the families. AIMS: We examined a cohort of patients with early onset colorectal cancer to determine whether a specific genetic predisposition could be elucidated. In particular, we focused on whether DNA mismatch repair gene deficiency which causes hereditary non-polyposis colorectal cancer (HNPCC) could be elucidated. METHODS: Patients with colorectal cancer </=24 years of age were identified from a database at the Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital, Toronto. Detailed pedigrees were ascertained from the proband or parents. Tumours were tested for microsatellite instability, a hallmark of HNPCC. Germline mismatch repair gene mutations (MSH2 and MLH1) were sought in some cases. Clinical data were obtained by chart audit. RESULTS: Among 1382 probands in our registry, 16 (1%) colorectal cancer patients were 24 years or younger at the time of diagnosis. Microsatellite instability was identified in tumours from eight (73%) of 11 evaluated patients. Germline mutations in mismatch repair genes were identified in six of 12 patients, including MSH2 (n = 3), MLH1 (n = 2), and PMS2 (n = 1). Ten (63%) of 16 families met the Amsterdam criteria for HNPCC. Among these, six were screened for mismatch repair gene mutations and three were found to carry MSH2 or MLH1 germline mutations. Location of the colorectal cancers included rectum/sigmoid (n = 9), splenic flexure (n = 2), hepatic flexure (n = 3), and caecum (n = 2). Forty four per cent (7/16) of these young cases developed additional malignancies (gastrointestinal (n = 8) and extraintestinal (n = 4)) during follow up (mean 12.8 (SD 12.4) years (range 0.08-30)). CONCLUSIONS: Patients with early onset colorectal carcinoma often have an inherited predisposition to the disease. Tumours with high frequency microsatellite instability and germline mutations of mismatch repair genes are sufficiently common in this patient population that they should be considered, even though family histories may not satisfy the stringent Amsterdam criteria for HNPCC. Young colorectal cancer patients are at increased risk of developing second gastrointestinal and extraintestinal malignancies.

Adolescent↗

PubMed2001

Motivations and psychosocial impact of genetic testing for HNPCC.

A type of hereditary colorectal cancer (CRC) known as hereditary nonpolyposis colorectal cancer (HNPCC) is associated with MLHI and MSH2 gene mutations. This study consists of a pilot, cross-sectional study of 50 individuals who were engaged in the genetic testing process for HNPCC. The study investigated the motivations and attitudes around genetic testing and current psychosocial functioning through the use of standardized measures, as well as obtained information on disclosure patterns associated with test results. The mean age of the sample was 44.3 years. (SD = 15.0). Twenty-three individuals were identified as "carriers" (13 had a previous history of CRC), seven were "non-carriers" and 20 individuals were still awaiting test results. The primary motivations for participating in genetic testing were similar to previous reports and included: wanting to know if more screening tests were needed, obtaining information about the risk for offspring and increasing certainty around their own risk. The psychosocial scores demonstrated that a subgroup of individuals exhibited distress, with greater distress for those individuals awaiting results or testing positive. There was a high level of satisfaction associated with the experience of testing. Individuals in this study tended to disclose their test results to a variety of family and non-family members. Disclosure was primarily associated with positive experiences however, some individuals reported regret around disclosure of their results. These preliminary findings should be further explored in a larger prospective study design over multiple time points.

Adult↗

PubMed2001

Inability of an "energy transfer diagnostician" to distinguish between fertile and infertile women.

CONTEXT: Various forms of "energy healing" have become popular in the United States. OBJECTIVE: To test the assertion that an energy healer can, without physical contact, distinguish the presence or absence of internal organ pathology in individuals who lack overt physical findings. DESIGN: Observational randomized study, in which we tested the assertion by a well-recognized alternative healer that he had particular skill in using energy transfer to detect the presence or absence of fertility disorders in women. PATIENTS: Convenience sample of 37 women, 28 of whom had documented pathology resulting in infertility, and 9 of whom were fertile. OUTCOMES: The healer was provided with no medical history and performed diagnostic evaluations without physical contact with the blindfolded, clothed, and silent subjects. We compared to random chance the ability of the healer to establish a diagnosis of fertility or fertility disorder. SETTING: Teaching hospital. MAIN RESULTS: The healer was unable to distinguish the presence or absence of fertility disorders in the study subjects. CONCLUSION: This study points to further need for fair yet rigorous assessment of claims that energy transfer can lead to accurate clinical diagnoses.

Energy Transfer↗

PubMed2000

Leukocyte adhesiveness/aggregation test (LAAT) to discriminate between viral and bacterial infections in children.

OBJECTIVES: We previously noted that white blood cells (WBC) have increased adhesive properties during bacterial infections. Here, we aim to explore the possibility of using the different adhesive properties of WBC as a means of differentiating between viral and bacterial infections, a common problem in paediatrics. METHODS: The adhesive properties of WBC in the peripheral blood of 25 children with documented bacterial infections, 15 with documented viral infections and 36 with probable viral infections, were studied by means of a leukocyte adhesiveness/aggregation slide test (LAAT). The results of the LAAT were compared with those of the other acute phase reactants, namely WBC, differential count and erythrocyte sedimentation rate (ESR), which were taken in the same blood sample in each patient. RESULTS: The sensitivity, specificity and positive predictive value were 92%, 96%, and 92%, respectively for the LAAT; 83%, 87% and 80% for the ESR; 56%, 78% and 56% for the white blood cell count; and 54%, 74% and 50% for the differential count. CONCLUSIONS: The presence of bacterial infections in children can be tested using a simple slide test to reveal the increased state of leukocyte adhesiveness/aggregation in the peripheral blood. The LAAT is a reliable, rapid and inexpensive test, and it can be a useful laboratory tool for the paediatrician treating a child with acute febrile illness.

Bacterial Infections↗

PubMed2000

Ontario familial colon cancer registry: methods and first-year response rates.

The Ontario Familial Colon Cancer Registry (OFCCR) is a novel registry that collects family history information, epidemiologic data, blood samples and tumour specimens from a population-based sample of colorectal cancer patients and their families. Families are classified as either high familial risk, intermediate familial/other risk or low (sporadic) risk for colorectal cancer. Obtaining high response rates in genetic family studies is especially challenging because of both the time commitment required and issues of confidentiality. The first-year response rate was 61%, resulting in 1,395 participating probands. In an attempt to assess potential response bias, we compared participants with non-participants. The age and sex of participants did not differ from non-participating probands; however, cases in rural areas were somewhat more likely to participate. To date, 57% of 1,587 relatives participated; females were more likely to participate, and relatives of low familial risk were least likely to participate. The OFCCR is an excellent resource that will facilitate the study of genetic and environmental factors associated with colorectal cancer.

Adult↗

PubMed1998

Elevated adhesiveness/aggregation of peripheral blood leukocytes in patients with major depression.

A simple slide test was used to determine the effects of major depression (MD) and heterocyclic antidepressants on leukocyte adhesiveness/aggregation (LAA) in the peripheral blood. Eighty subjects were categorized into four equal groups: untreated-MD patients, treated-MD patients, nondepressed patients treated with antidepressants and healthy controls. Significantly higher LAA values were observed both in untreated- and treated-MD patients, 13.8+/-1.7% and 13.5+/-1.9% respectively, compared to nondepressed-treated patients and healthy controls, 5.4+/-0.9% and 6.4+/-0.7% respectively (P < 0.0001). Increased LAA was associated with the depressive episode, was not affected by antidepressants and may potentially serve as a useful laboratory state marker for MD.

Adult↗

PubMed1998

Serum creatinine and blood urea nitrogen over a six-year period in the very old. Creatinine and BUN in the very old.

In a population of 141 very elderly subjects, there was a small but significant decline in BUN and creatinine at 3 years, which persisted at 6 years although partially attenuated. A similar pattern of falling BUN and creatinine was seen in the 31 subjects who began the study with mild azotemia. There was no significant change in the subjects' mean Body Mass Index during the 6-year period of observation. The azotemic subjects had a rate of death or dropout from the study similar to that of the entire cohort. Mean systolic blood pressure fell by 5.4 mm Hg (p < 0.05) and diastolic blood pressure by 2.1 mm Hg (p = NS) by 6 years. Users of diuretics or NSAID had a mean BUN and creatinine comparable to those not taking these medications. We conclude that BUN and serum creatinine do not necessarily increase with time in the old old, even in those with mild azotemia, hence, several determinations of these parameters may be needed to ensure accuracy. While renal function in the elderly probably does not improve with time, it may stabilize due to improvement in blood pressure. Use of diuretics and NSAID by functioning elderly individuals is not necessarily associated with worsening azotemia.

Aged↗

PubMed1998

The leukocyte adhesiveness/aggregation test as an inflammation-related, plasma-dependent agglutination phenomenon.

The leukocyte adhesiveness/aggregation test (LAAT) is a non-specific marker of inflammation. In the present study, we examined the expression of the CD11b/CD18 as well as the CD62L antigens on the surface of peripheral blood leukocytes in 84 patients with various inflammatory conditions and 60 controls by using whole blood flow cytometry. We also conducted several in vitro experiments in order to explain the mechanism of the leukocyte adhesiveness/aggregation. A significant (r= -0.36, p<0.001) negative correlation was found between the expression of CD62L on the surface of peripheral blood polymorphonuclears and the state of LAA. There was no correlation between the availability of the CD11b/CD18 antigen and the adhesive state of these cells. In a series of in vitro experiments, we could show that it is possible to significantly reduce the number of aggregated leukocytes in the peripheral blood by using dilutions with buffer but not with plasma. There is no change in the degree of aggregation following incubation at low temperature in the presence of an aerobic metabolism blocker or following incubation with a divalent ion chelator. Additionally, white blood cells could be seen to adhere to protein-rich areas in the peripheral slides. We assume that the state of LAA in the peripheral blood as revealed by the LAA test is more a plasma factor-dependent agglutination than a firm aggregation phenomenon. Factors other than the leukocyte integrins or selectins should be sought as being responsible for this LAA phenomenon.

Adult↗

PubMed1998

Vancomycin control measures at a tertiary-care hospital: impact of interventions on volume and patterns of use.

OBJECTIVE: Evaluate vancomycin prescribing patterns in a tertiary-care hospital before and after interventions to decrease vancomycin utilization. DESIGN: Before/after analysis of interventions to limit vancomycin use. SETTING: 420-bed academic tertiary-care center. INTERVENTIONS: Educational efforts began August 10, 1994, and involved lectures to medical house staff followed by mailings to all physicians and posting of guidelines for vancomycin use on hospital information systems. Active interventions began November 15, 1994, and included automatic stop orders for vancomycin at 72 hours, alerts attached to the medical record, and, for 2 weeks only, computer alerts to physicians following each vancomycin order. Parenteral vancomycin use was estimated from the hospital pharmacy database of all medication orders. Records of a random sample of 344 patients receiving vancomycin between May 1, 1994, and April 30, 1995, were reviewed for an indication meeting published guidelines. RESULTS: Vancomycin prescribing decreased by 22% following interventions, from 8.5 to 6.8 courses per 100 discharges (P<.05). The estimated proportion of vancomycin ordered for an indication meeting published guidelines was 36.6% overall, with no significant change following interventions. However, during the 2 weeks that computer alerts were in place, 60% of vancomycin use was for an approved indication. CONCLUSIONS: Parenteral vancomycin prescribing decreased significantly following interventions, but the majority of orders still were not for an indication meeting published guidelines. Further improvement in the appropriateness of vancomycin prescribing potentially could be accomplished by more aggressive interventions, such as computer alerts, or by targeting specific aspects of prescribing patterns.

Algorithms↗

PubMed1998

Neuropsychological disorders in children exposed to alcohol during pregnancy: a follow-up study of 24 children to alcoholic mothers in Göteborg, Sweden.

This paper reports on a follow-up study of 24 children to alcoholic mothers at 12 to 14 years of age. The mothers were offered support to help them stop drinking during pregnancy and was grouped to time point of instituted sobriety. Six of the 24 children attended a school for the mentally retarded, and 11 children had some kind of special education. The children have difficulties in mathematics, logical conclusions, visual perception, spatial relations, and short-range memory/attention. Sixteen children were in fostercare. A clear correlation between the occurrence and severity of neuropsychological problems and the degree of alcohol exposure in utero was found.

Adolescent↗

PubMed1997

Anti-neoplastic activity of paclitaxel on experimental superficial bladder cancer: in vivo and in vitro studies.

The effects of intravesical administration of paclitaxel (taxol) in a bladder tumor model in mice, as well as the drug's in vitro activity on the same tumor cells, have been studied. Two cell lines, derived from MBT-2 cells, were employed in these experiments. The T50 line (obtained by many passages in mice) was much more aggressive in vivo than the T5 line. In vivo paclitaxel treatment for 3 days after T5 implantation resulted in a considerable retardation of tumor growth, whereas under the same conditions the T50 line was much less, although still significantly, affected. When treatment was started 1 day after tumor implantation, both tumor variants were affected by paclitaxel to the same extent. The in vitro experiments utilized the MiCK assay, which allows continuous recording of the kinetics of cell growth. These studies revealed a 39.8% inhibition of cell growth by 2.10(-8)M paclitaxel in the T50 line and a 30-fold increase in concentration had only a small additional effect on the degree of inhibition. At 2.10(-8)M paclitaxel, growth of T5 was inhibited by 21.7%, which increased to 35.2% at 6.10(-7)M. The treated cells displayed bundles of microtubuli, as described for other paclitaxel-treated cells.

Administration, Intravesical↗

PubMed1997

Thymic aging in ICR female mice is suspended by prolonged hydrocortisone exposure.

Age-related decline of the thymus in ICR female mice was studied following long-term (three month) weekly exposure to hydrocortisone acetate. When examined one week after cortisone injections, the well-known thymic atrophy was observed. Five weeks after 12 hydrocortisone injections, the cortical volume fraction (Vc), cortical/medullary ratio (C/M), the number of thymocytes and CD4/CD8 profiles were in the range that characterizes younger mice, compared with PBS-injected mice, uninjected controls, or mice given a single hydrocortisone injection 5 weeks earlier. It seems as if thymic involution with age was suspended during the period of glucocorticoid exposure.

Aging↗

PubMed1997

Comparison of nuclear DNA content in locally invasive and noninvasive papillary carcinoma of the thyroid gland.

Extrathyroidal invasion of papillary carcinoma of the thyroid gland has a very bad prognosis. A retrospective study was performed on 40 specimens from patients with papillary carcinoma of the thyroid gland to find out whether DNA ploidy correlated with aggressive tumor behavior. The nuclear DNA content of 20 locally aggressive papillary thyroid carcinomas was studied by flow cytometry. The results were compared with those of a matched control group of 20 patients with noninvasive papillary tumors. Forty percent of the tumors with spread to extrathyroid tissue were aneuploid, whereas all the tumors without such extension were diploid. This difference was statistically significant (p < 0.003). The data suggest that the differentiation of locally noninvasive and invasive papillary thyroid carcinomas may be potentially possible by nuclear DNA determination.

Aneuploidy↗

PubMed1997

The effect of erythromycin on resolution of symptoms among adults with pharyngitis not caused by group A streptococcus.

OBJECTIVE: To determine the effect of treatment with erythromycin on the resolution of symptoms among adults with pharyngitis not caused by group A streptococcus (GAS). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Ambulatory setting (hospital-based general internal medicine practices, walk-in clinic, employee health service, and university health service). PATIENTS: One hundred and eighty-six adults who met eligibility criteria and whose chief complaint included sore throat. Patients with positive cultures for GAS were excluded. INTERVENTION: Ninety-three patients received erythromycin (333 mg three times daily for 10 days) and 93 control patients received placebo. MEASUREMENTS AND MAIN RESULTS: Major outcome measurements included time to improvement in sore throat, time to improvement in cough, time to improvement in activity level, and subjective sense of well-being. The average age of the patients studied was 26.6 years; 35% were men. Patients given erythromycin had more rapid resolution of sore throat symptoms (hazard ratio 1.43: 95% confidence interval [CI] 1.00, 2.03: p = .049). Cough also resolved more rapidly in patients receiving erythromycin (hazard ratio 2.22: 95% CI 1.01, 4.88: p = .05). There were no differences between the two treatment groups in improvement of activity level or how sick patients felt in general. Most of the benefit in resolution of sore throat was conferred on patients who sought medical care within 2 days of onset. CONCLUSIONS: Our results suggest that the benefit of erythromycin treatment for patients with non-GAS pharyngitis is small and of borderline statistical significance. Because of the small size of the effect and because widespread use of erythromycin could promote drug resistance, we do not recommend routine use of erythromycin in adult patients with this type of pharyngitis.

Adult↗

PubMed1997

Attention deficits and autistic spectrum problems in children exposed to alcohol during gestation: a follow-up study.

Children born to mothers who had abused alcohol throughout pregnancy had severe behavioural and intellectual problems which remained at age 11 to 14 years. Of 24 children examined, 10 had attention deficit hyperactivity disorder (ADHD) with or without developmental coordination disorder, two had Asperger syndrome, and one had an autistic-like condition not meeting the criteria for Asperger syndrome. Six of these 24 attended special schools for the mentally retarded and a further 11 were given special education, leaving only seven attending regular schools without any type of support. The children had difficulties in mathematics, logical conclusions, visual perception, spatial relations, short-term memory, and attention. Sixteen children lived in foster homes. There was a clear correlation between the occurrence and severity of the neuropsychiatric disorder and the degree of alcohol exposure in utero.

Adolescent↗

PubMed1996

Increased leukocyte adhesiveness/aggregation in patients with inflammatory bowel disease during remission. Further evidence for subclinical inflammation.

PURPOSE: We have used a novel leukocyte adhesiveness/aggregation test (LAAT) to show that many patients with inflammatory bowel disease (IBD) in clinical remission have a subclinical low grade inflammation. METHODS: Included in the study are 500 controls, 96 patients with IBD in remission, and 106 patients in relapse. RESULTS: The percent of aggregated white blood cells detected in the peripheral blood was 5.9 +/- 3.9, 9.1 +/- 5.9, and 18.8 +/- 9.4, respectively. The difference between each group and any other was significant at P < 0.0001. Similar results were obtained when other acute phase reactants like the erythrocyte sedimentation rate, white blood cell count, differential count, and C-reactive protein level were examined. However, in a linear regression analysis, LAAT was the only significant (P < 0.0006) variable that could classify correctly each subject to the appropriate category of control and IBD in remission or relapse. CONCLUSIONS: Identification of patients with IBD in clinical remission who have ongoing inflammation may be of clinical-therapeutic relevance. The LAAT is a simple, rapid, and convenient test. The present study indicates that it is also very sensitive.

Adolescent↗

PubMed1996

Treatment of experimental mouse bladder tumour by LPS-induced epithelial cell shedding.

The purpose of the present study was to explore the therapeutic potential of serial administration of shedding-inducing endotoxin in a mouse tumour bladder model. The studies were conducted with two variants derived from the MBT-2 tumour namely, T5 and T50, the latter being far more aggressive than the former. It was found that T5 tumours responded to intravesical lipopolysaccharides (LPS) instillation by a considerable reduction in their pace of growth (P < 0.0001) when treatment was initiated 3 days after tumour implantation, but not when started after 7 days. The T50 variant did not respond to LPS when treated 3 days after implantation, but a considerable reduction in rate of growth occurred when treatment was started after 1-2 days. Shedding induced by intravesically instilled LPS was found to retard considerably the progression rate of experimental bladder tumour.

Administration, Intravesical↗