Hodgkin's disease type Richter's syndrome in chronic lymphocytic leukemia.
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Aged↗
Biomedical subjects
D Ellis
Publications and source records attributed to D Ellis.
Modeling computer interest in older adults: the role of age, education, computer knowledge, and computer anxiety.
We proposed a mediation model to examine the effects of age, education, computer knowledge, and computer anxiety on computer interest in older adults. We hypothesized that computer knowledge and computer anxiety would fully mediate the effects of age and education on computer interest. A sample of 330 older adults from local senior-citizen apartment buildings completed a survey that included an assessment of the constructs included in the model. Using structural equation modeling, we found that the results supported the hypothesized mediation model. In particular, the effect of computer knowledge operated on computer interest through computer anxiety. The effect of age was not fully mitigated by the other model variables, indicating the need for future research that identifies and models other correlates of age and computer interest. The most immediate application of this research is the finding that a simple 3-item instrument can be used to assess computer interest in older populations. This will help professionals plan and implement computer services in public-access settings for older adults. An additional application of this research is the information it provides for training program designers.
Age Factors↗
Risk factors for detecting germline BRCA1 and BRCA2 founder mutations in Ashkenazi Jewish women with breast or ovarian cancer.
We ascertained 184 Ashkenazi Jewish women with breast/ovarian cancer (171 breast and 13 ovarian cancers, two of the former also had ovarian cancer) in a self-referral study. They were tested for germline founder mutations in BRCA1 (185delAG, 5382insC, 188del11) and BRCA2 (6174delT). Personal/family histories were correlated with mutation status. Logistic regression was used to develop a model to predict those breast cancer cases likely to be germline BRCA1/BRCA2 mutation carriers in this population. The most important factors were age at diagnosis, personal/family history of ovarian cancer, or breast cancer diagnosed before 60 years in a first degree relative. A total of 15.8% of breast cancer cases, one of 13 ovarian cancer cases (7.7%), and both cases with ovarian and breast cancer carried one of the founder mutations. Age at diagnosis in carriers (44.6 years) was significantly lower than in non-carriers (52.1 years) (p<0.001), and was slightly lower in BRCA1 than BRCA2 carriers. Thirty three percent of carriers had no family history of breast or ovarian cancer in first or second degree relatives. Conversely, 12% of non-mutation carriers had strong family histories, with both a first and a second degree relative diagnosed with breast or ovarian cancer. The predicted values from the logistic model can be used to define criteria for identifying Ashkenazi Jewish women with breast cancer who are at high risk of carrying BRCA1 and BRCA2 mutations. The following criteria would identify those at approximately 10% risk: (1) breast cancer <50 years, (2) breast cancer <60 years with a first degree relative with breast cancer <60 years, or (3) breast cancer <70 years and a first or second degree relative with ovarian cancer.
Adult↗
Identification of germline missense mutations and rare allelic variants in the ATM gene in early-onset breast cancer.
Epidemiological studies have shown an increased risk of breast cancer in obligate ataxia telangiectasia (A-T) heterozygotes. We analyzed 100 samples from young breast cancer patients for mutations in ataxia-telangiectasia mutated (ATM), the gene responsible for the autosomal recessive condition, A-T, to determine whether A-T heterozygosity predisposes such individuals to develop breast cancer. These patients were selected from families with a moderate or absent family history of breast cancer and included a subset of 16 radiosensitive patients. Forty-four germline sequence variants were detected by fluorescent chemical cleavage of mismatch of RT-PCR products. These included seven rare variants found in nine patients (three described for the first time), but no truncating mutations. Although three variants were detected in the radiosensitive subset, this was not statistically significant compared to the nonradiosensitive group. One variant, G2765S, is likely to be a missense mutation, but the other six variants probably represent rare polymorphisms. However, five of the seven rare germline variants detected showed loss of heterozygosity of the wild-type ATM allele for one or more markers close to the ATM locus in matched tumor DNA. This high rate of somatic inactivation of ATM may indicate either that these rare variants play a role in breast cancer development or alternatively that a neighboring tumor suppressor gene is important for tumorigenesis. We found germline truncating ATM mutations to be rare in these young breast cancer patients and therefore they are unlikely to play a role in the etiology of their disease. Genes Chromosomes Cancer 26:286-294, 1999.
Adult↗
Image is all but interpretation is the key.
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Animals↗
Comparison of one week of oral terbinafine (250 mg/day) with four weeks of treatment with clotrimazole 1% cream in interdigital tinea pedis.
Treatment of interdigital tinea pedis often involves long-term therapy with topically applied preparations. Effective oral preparations, such as the allylamine terbinafine (Lamisil), taken over a shorter period, could provide a useful therapeutic alternative. A total of 269 patients from five centres with clinically diagnosed interdigital tinea pedis were entered into this double-blind, randomized, double-dummy, parallel-group study comparing oral terbinafine 250 mg once daily for 1 week with 1% clotrimazole (Canesten) cream applied twice daily for 4 weeks. Of these, 137 patients were evaluable for efficacy (confirmed dermatophyte infection by microscopy and culture): 63 terbinafine and 74 clotrimazole. At week 4, the mycological cure rates (negative culture at week 1 and negative results on microscopy and culture at week 4 onwards) were very similar (71% for clotrimazole and 72% for terbinafine). There was a faster response rate in the terbinafine group with respect to signs and symptoms at week 1. Both treatments were equally well tolerated; adverse events occurred equally in the two groups. In conclusion, oral terbinafine in a single daily dose of 250 mg for 1 week is as effective and as well tolerated as 1% clotrimazole cream applied twice daily for 4 weeks in the treatment of interdigital tinea pedis.
Adolescent↗
Identification of missense and truncating mutations in the BRCA1 gene in sporadic and familial breast and ovarian cancer.
The cloning of the breast and ovarian cancer susceptibility gene, BRCA1, allows direct estimation of the proportion of these cancers in the general population which can be attributed to germline mutations in this gene. We have used a combination of SSCP, heteroduplex analysis, and chemical cleavage of mismatch to screen the BRCA1 gene for mutations in the germline of 42 patients with breast or ovarian cancer who either have a moderate family history of these cancers, or have no family history of malignancy but a very early onset of the disease. A total of 30 sequence variants were observed, eight of which have not been described previously. Three sequence changes detected by chemical cleavage or heteroduplex analysis were missed by SSCP. The variants included 13 missense mutations, which were assessed for their pathogenic implications. Two of these (M18T and A1708E) are nonconservative substitutions which are located in evolutionarily conserved regions of the gene: M18T lies just upstream of the RING finger motif, and A1708E abolishes the transcriptional transactivation activity of the carboxy-terminal region of BRCA1. Mutations were observed in eight patients overall (19.0%), and protein-truncating mutations occurred in five of 27 (18.5%) families with 1-3 cases of breast or ovarian cancer. The data suggest that a significant proportion of patients with a modest or no family history of these cancers may carry germline mutations in BRCA1.
Adult↗
Urinary measurement of transforming growth factor-beta and type IV collagen as new markers of renal injury: application in diabetic nephropathy.
Urinary samples were concentrated rapidly and efficiently and were used to develop several protein assays that may be of value in monitoring individuals with progressive renal disorders. Transforming growth factor-beta1 (TGF-11) and retinol binding protein (RBP) were measured with modification of commercially available methods used to assay serum specimens; type 3 collagen (T3C) was measured with a new immunonephelometric assay. The precision characteristics of these assays are comparable with those reported for microalbuminuria. The clinical utility of measuring a panel of these markers was demonstrated in urine samples from 16 control subjects and from 46 individuals with insulin-dependent diabetes mellitus (IDDM) with various albumin excretion rates (AERs). TGF-beta1 and T3C were used as markers of cytokine expression and of the renal fibrogenic process, whereas RBP excretion served as a marker of tubular injury or dysfunction. Compared with controls, T3C excretion was significantly increased in 18 normoalbuminuric and further increased in 13 microalbuminuric (AER 20 < or = 200 microg/min) IDDM subjects. RBP excretion was increased in macroalbuminuric IDDM subjects (AER >200 microg/min, overt nephropathy). Significant correlations were also found between AER and RBP in all but macroalbuminuric individuals, whereas TGF-beta1 correlated with T3C excretion in controls and in normoalbuminuric diabetic subjects. Urinary RBP but not AER was an excellent predictor of diabetic nephropathy as defined by serum creatinine (P = 0.0001). This underscores the importance of an early tubulopathy in the subsequent development of glomerulopathy and overt nephropathy. The data suggest that longitudinal monitoring of a panel of urinary markers such as that used in the current study may better define their relevance in progressive glomerulosclerosis and may also provide greater insight into the mechanisms underlying such process.
Adult↗
Teaching medical mycology in the year 2000.
Medical mycology is of increasing interest to the basic scientist, pathologist, microbiologist and clinician. This interest has been prompted by the rising number of immunosuppressed patients with opportunistic fungal infections, the expanding boundaries of the so-called endemic mycoses, the recognition of several major new endemic mycoses and a variety of other emerging fungal infections, and the development of potent, non-toxic antifungal drugs to treat these infections. The world of mycology is changing dramatically, especially in developing countries which have only limited resources to cope with the impact of the compromised host and the introduction of costly new antifungal drugs. Consequently, there is an urgent need to increase our effectiveness as teachers of medical mycology at all levels and in all regions of the world.
Education, Graduate↗
Cumulative glycemic exposure and microvascular complications in insulin-dependent diabetes mellitus. The glycemic threshold revisited.
BACKGROUND: The development of microvascular insulin-dependent diabetes mellitus (IDDM) complications has been shown to be related to both duration of diabetes and the degree of glycemic exposure. However, controversy exists as to whether there is a threshold of glycemic exposure, below which there is minimal risk. Furthermore, there are few data describing the relationship of total glycemic exposure (duration x degree) to complications rates-a potentially useful research and clinical tool. OBJECTIVES: To determine a cumulative glycemic exposure variable that combines the effect of both degree and duration of hyperglycemia and to evaluate this variable in terms of its relation to microvascular complications. The association between cumulative glycemic exposure and complication risk was also examined to evaluate whether there was a threshold effect. METHODS: A total of 353 patients with IDDM who had completed the first 6 years of follow-up in the Pittsburgh Epidemiology of Diabetes Complications Study were included in this analysis. These subjects had a mean age of 27.9 years, and the mean duration of the disease was 19.4 years. Subjects were examined at baseline (cycle 1) and then biennially (cycle 2, cycle 3, and cycle 4) for diabetes complications. Total glycosylated hemoglobin (HbA1) was measured at each cycle. A cumulative glycemic exposure variable, named A1months, was calculated by multiplying the number of HbA1 units above normal at each cycle by the number of months between the midpoints of the preceding and succeeding cycle intervals. RESULTS: The mean number of A1months experienced at the time of diagnosis of proliferative retinopathy (914), microalbuminuria (952), overt nephropathy (1043), and distal symmetrical polyneuropathy (1043) did not vary by duration of diabetes. Thus, approximately 1000 A1months were needed (on average) for the advanced complications to develop. Although the risk for developing proliferative retinopathy rose gradually as A1months increased, a more abrupt increase in the risk was seen (again at approximately 1000 A1months) for microalbuminuria (odds ratio, 6.9; 95% confidence interval, 2.5-19.1), overt nephropathy (odds ratio, 6.5; 95% confidence interval, 2.0-21.7), and distal symmetrical polyneuropathy (odds ratio, 6.5; 95% confidence interval, 2.4-17.8). Nonetheless, complications developed in the majority of cases at glycemic exposures below 1000 A1months. The cumulative glycemic exposure variable A1months does not predict complications any better than its component variables (duration and HbA1). Furthermore, formal statistical testing failed to show a definitive threshold for any complication. CONCLUSIONS: Although A1months does not enhance prediction of complications, it may be a useful summary measure of glycemic exposure for both patients and physicians. However, although subjects with 1000 A1months or more appear to be at increased risk of developing most microvascular complications, because the majority of complications arise in subjects with less than this exposure, this threshold value should only be considered a minimal goal. For example, our data suggest that for most microvascular complications to develop, it would take, on average, 83 years with an HbA1 unit at 1% above normal, 42 years at 2% above normal, 28 years at 3% above normal. 21 years at 4% above normal, and 18 years at 5% above normal.
Adolescent↗
Aortic and renal artery thrombosis in a neonate: recovery with thrombolytic therapy.
This report describes a neonate with acute renal failure associated with extensive aortic and bilateral renal artery thrombosis attributed to inadequate breastfeeding and severe dehydration. Dialytic and general supportive care, together with concurrent anticoagulation, and continuous aggressive intrathrombic instillation of urokinase for 5 days resulted in near-complete thrombolysis. Renal functional recovery began 11 days after the onset of anuria. Despite ischemic atrophy of the left kidney, renal function and blood pressure were normal on follow-up. Thus, in neonates thrombolytic therapy may positively impact survival and recovery of renal function even in the setting of prolonged ischemic renal injury.
Aortic Diseases↗
Blunt abdominal trauma secondary to misuse of standard cleaning equipment: a preventable occupational hazard.
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Abdominal Injuries↗
Thalidomide: a novel therapy for microsporidiosis.
BACKGROUND & AIMS: Microsporidiosis is a common cause of chronic diarrhea in human immunodeficiency virus (HIV)-seropositive individuals and often does not respond to treatment. Fecal tumor necrosis factor alpha (TNF-alpha) is elevated in microsporidiosis; therefore, thalidomide, an anti-TNF-alpha agent, was used as therapy. METHODS: Eighteen subjects with chronic diarrhea caused by Enterocytozoon bieneusi that had not responded symptomatically to albendazole and 1 untreated subject with Encephalitozoon intestinalis received 1 month of thalidomide, 100 mg nocte. Clinical response was assessed by stool frequency and body weight, histological response by light microscopy with villus height/crypt depth ratios and electron microscopy, and immunologic response by fecal TNF-alpha level. RESULTS: Seven subjects with chronic diarrhea due to E. bieneusi had a complete clinical response, and 3 had a partial response to thalidomide. There was a significant decrease in stool frequency from 5.3 to 3.1 per day (P = 0.001), and weight increased significantly by 1.2 kg (P < 0.02). Thalidomide significantly increased the villus height/crypt depth ratio (1.95 to 2.07; P = 0.045) and number of abnormal forms of microsporidia (P < 0.01). Fecal TNF-alpha level nonsignificantly decreased from 17.9 to 8.9 U/mL. There was apparent disruption of all stages of the life cycle of E. intestinalis. CONCLUSIONS: Thalidomide may be an effective therapy for diarrhea and weight loss from E. bieneusi.
Acquired Immunodeficiency Syndrome↗
Hereditary demyelinating neuropathy of infancy. A genetically complex syndrome.
Nine cases are described of a demyelinating peripheral neuropathy that had an onset in infancy. The clinical features conformed to those of type III hereditary motor and sensory neuropathy or Dejerine-Sottas disease. All showed a severe neurological deficit and had profoundly reduced nerve conduction velocities. Amongst these cases we identified four novel point mutations in the peripheral myelin protein 22 (PMP22) gene. These were Ser72Trp, Ser76lle and Leu80Pro. The Ser72Trp mutation was dominantly inherited by a mother and son, both severely affected. Two novel mutations in the gene for P0 myelin protein were also detected. These were Ile134Thr in exon 3, and a complex rearrangement in exon 4. The remaining three patients had presumed autosomal recessive inheritance. In these, no abnormality for the PMP22 and P0 genes was detected and a mutation at another locus or loci seems probable. On nerve biopsy the final two cases were shown to be examples of hereditary neuropathy with focally folded myelin sheaths. One showed both bulbar and diaphragmatic involvement. It is concluded that hereditary demyelinating neuropathy of infancy is genetically heterogeneous. Mutational screening for the PMP22 and P0 genes and nerve biopsy are therefore merited in patients with a childhood demyelinating neuropathy that is more severe than usual and in whom a chromosome 17 duplication is not present.
Adolescent↗
The Arabidopsis NIM1 protein shows homology to the mammalian transcription factor inhibitor I kappa B.
The NIM1 (for noninducible immunity) gene product is involved in the signal transduction cascade leading to both systemic acquired resistance (SAR) and gene-for-gene disease resistance in Arabidopsis. We have isolated and characterized five new alleles of nim1 that show a range of phenotypes from weakly impaired in chemically induced pathogenesis-related protein-1 gene expression and fungal resistance to very strongly blocked. We have isolated the NIM1 gene by using a map-based cloning procedure. Interestingly, the NIM1 protein shows sequence homology to the mammalian signal transduction factor I kappa B subclass alpha. NF-kappa B/I kappa B signaling pathways are implicated in disease resistance responses in a range of organisms from Drosophila to mammals, suggesting that the SAR signaling pathway in plants is representative of an ancient and ubiquitous defense mechanism in higher organisms.
Amino Acid Sequence↗
Confirmed histoplasmosis in an Australian dog.
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Animals↗
Rethinking estrangement, interventions, and intimate femicide.
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Americas↗
Estrangement, interventions, and male violence toward female partners.
The primary objective of this paper is to integrate three relatively distinct lines of research on male violence towards intimate female partners. First, the relation between conjugal violence and estrangement is examined. We found them to be positively associated, but they can vary independently. Second, we examined the association between estrangement and interventions. Estrangement was found to be associated with private, private/public and mainly public interventions depending upon the level of estrangement. High levels of estrangement are strongly but not invariably associated with ending the relationship. Third, we reviewed the link between interventions and violence. Interventions which empower battered female partners are most effective in ending male partner violence. Taken together, the findings tend not to support hypotheses derived from the theory of male proprietariness. Implications for social policy are discussed in the final segment.
Battered Women↗