The pathogenesis of ataxia-telangiectasia. Learning from a Rosetta Stone.
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Ataxia Telangiectasia↗
Biomedical subjects
C Clark
Publications and source records attributed to C Clark.
Solid phase assay of urine cystine supersaturation in the presence of cystine binding drugs.
PURPOSE: We report a new kind of assay system for urine cystine supersaturation that is accurate in the presence of cystine binding thiol drugs. We measured the molar ratio of cystine dissolved per mole of drug. MATERIALS AND METHODS: Measured amounts of cystine crystals were incubated in buffer or urine for 48 hours with stirring. The solid phase remaining was pelleted by centrifugation, extracted into a high pH buffer and measured. D-penicillamine, tiopronin and captopril were added to determine their effect on solid phase dissolution. RESULTS: Total cystine calculated from urine and solid measurements closely matched the amounts of cystine weighed in, meaning that the assay system successfully recovered the total cystine from the 2 phases. Each drug dissolved solid cystine in a specific and fixed proportion to its molar concentration in the range of 0.2 to 0.4 mM. dissolution per mM. of drug. Solution measurements were not a reliable gauge to the actual amounts of cystine dissolved. CONCLUSIONS: Changes in solid phase cystine accurately reflect buffer or urine supersaturation when thiol drugs are present. The solid phase assay is a technically straightforward and reliable way of assessing cystine movement into and out of urine that avoids complexity of measurement and distortions of assay systems by drugs. This assay enables one to assess the level of drug effect and the need for a change in dosing.
Buffers↗
Toxic effects in dairy cattle following the ingestion of a large volume of canola oil.
The clinical and laboratory findings of a group of 9 dairy cattle that accidentally ingested large volumes of canola oil are described. Four of the animals died, and 3 were necropsied. No specific cause of death was found, although a number of theories are advanced. This is the first report of such an occurrence.
Animal Feed↗
AIDS--the way forward.
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AIDS-Related Opportunistic Infections↗
Genomic instability at the BUB1 locus in colorectal cancer, but not in non-small cell lung cancer.
Genomic instability is observed in the majority of human tumors. Dysregulation of the mitotic spindle checkpoint is thought to be one of the mechanisms that facilitate aneuploidy in tumor cells. Mutations in the mitotic spindle checkpoint kinase BLUB1 cause a dominant negative disruption of the spindle, leading to chromosome instability in cancer cell lines. However, little is known about chromosome 2q14, the genomic region containing BUB1, in human tumors. The BUB1 locus was evaluated in 32 colorectal cancer (CRC) and 20 non-small cell lung cancer (NSCLC) primary tumors using a panel of seven microsatellite repeats for 2q, two CA repeats in BUB1, and gene mutation analysis. The 2q locus was allelically stable in NSCLC but relatively unstable in colorectal primary tumors (20 of 32 tumors, 62.5%). In addition, 14.5% of CRC patients displayed instability within BUB1. Previously described BUB1 mutations and polymorphisms were rare (< 1%) in the CRC or NSCLC tumors. Our data demonstrate 2q and BUB1 allelic instability in CRC and indicate that mutations in BUB1 are rare causes of chromosome instability in CRC or NSCLC. Additional investigations may shed light on the mechanistic impact of the mitotic spindle checkpoint pathway in colorectal tumor initiation and progression.
Adenocarcinoma↗
Outbreak of Escherichia coli O157:H7 leading to the recall of retail ground beef--Winnipeg, Manitoba, May 1999.
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Adolescent↗
Nonoperative management of dens fracture nonunion in elderly patients without myelopathy.
STUDY DESIGN: A retrospective review of elderly patients treated without surgery for chronic mobile nonunions of the odontoid process. Patients were observed on an annual basis with clinical examinations and flexion/extensions plain film radiographs. OBJECTIVES: To evaluate the clinical and radiographic results of elderly patients without myelopathy treated without surgery for dens fracture nonunion. SUMMARY OF BACKGROUND DATA: Because of the risk of progressive myelopathy or sudden neurologic injury, many surgeons recommend operative stabilization for patients with mobile dens nonunions who are able to withstand an operation. There is, however, a lack of information about the radiographic and neurologic progression of dens nonunions. Although a less aggressive surgical approach has been recommended by some authors for elderly or medically compromised patients with acute fractures, long-term follow-up evaluation of patients with resulting nonunions has not been reported. METHODS: A series of elderly patients with chronic, unstable, dens nonunions without myelopathy were treated with a nonoperative treatment protocol. Patients were informed of the nature of their lesion, including the risk of acute or chronic spinal cord injury and the options for operative treatment. Patients were evaluated yearly for clinical and radiographic progression. No intervention to slow progression of atlantoaxial instability was undertaken. RESULTS: None of the patients developed myelopathic symptoms during the follow-up period, and no patient experienced more than a 1 mm radiographic increase in atlantoaxial excursion. None of the reported patients had less than 14 mm available for the spinal cord in either flexion or extension at the start of clinical monitoring. CONCLUSIONS: Although further follow-up evaluation is needed, the authors believe on the basis of this review that this treatment protocol may be considered for patients who are poor candidates for surgical fusion.
Aged↗
Bronchopulmonary and mediastinal leishmaniasis: an unusual clinical presentation of Leishmania donovani infection.
We describe a case of unusual leishmaniasis in a Sudanese man with a history of progressively enlarging granulomatous mediastinal lymphadenopathy, worsening hemoptysis, and an intense mucosal granulomatous inflammatory response in the large bronchi. Leishmania donovani DNA was detected in bronchial biopsies by polymerase chain reaction. This is a novel description of human leishmanial infection in an immunocompetent patient involving this anatomical site. The patient's condition improved clinically, spirometrically, and radiologically after a course of treatment with amphotericin B. The cell-mediated immune response was analyzed before, during, and after successful antileishmanial chemotherapy.
Adult↗
Narrowband TL-01 phototherapy for patch-stage mycosis fungoides.
BACKGROUND: Although patch-stage mycosis fungoides (MF) has a generally good prognosis, and long-term survival rates with current therapies (UV-B, photochemotherapy, topical nitrogen mustards, electron-beam therapy) are similar, there is concern regarding their potential adverse effects. Narrowband or TL-01 UV-B phototherapy (311 nm), in use for more than 10 years, is more effective than broadband UV-B for the treatment of psoriasis, with an efficacy approaching that of psoralen UV-A. This open study assesses TL-01 as an alternative therapy for patch-stage MF. OBSERVATIONS: Eight white patients (4 men, 4 women; age range, 66-83 years) with histologically proven patch-stage MF received TL-01 phototherapy 3 times weekly using a standard protocol. Complete clearance of MF was achieved in 6 cases in a mean of 9 weeks or 26 treatments (range, 20-37 weeks) and 4 patients have had prolonged remissions. Mean duration of clinical improvement has been 20 months (range, 11-40 months). Partial response to TL-01 or poor histologic improvement was associated with rapid relapse. CONCLUSIONS: TL-01 is an effective, convenient therapy that may have less risk of long-term adverse effects than current alternatives. Although larger prospective studies are necessary, for some patients intermittent courses of TL-01 may offer effective long-term therapy.
Aged↗
Preliminary evidence of an association between increased REM density and poor antidepressant response to partial sleep deprivation.
BACKGROUND: One night of total sleep deprivation or of late-night partial sleep deprivation (PSD) produces a temporary remission in approximately 40-60% of patients with major depressive disorder; however, little is known about polysomnography (PSG) characteristics of responders to these types of sleep deprivation (SD). METHODS: Twenty-three unmedicated unipolar patients (17-item Hamilton Depression Rating Scale (HDRS17) >16) and 14 normal controls underwent 1 night of late-night PSD (awake after 3 a.m.) Subjects underwent baseline PSG and received the HDRS17 at standard times before and after PSD. Clinical response was defined as a reduction of >30% in the modified HDRS17 (omitting sleep and weight loss items) following PSD. RESULTS: The 12 responders and 11 nonresponders did not differ from each other significantly on baseline HDRS17 or PSG variables. The only PSG variable correlating with percent decrease in modified HDRS17 was baseline REM density (Pearson's r=-0.52, n=23, P=0.01.) In other words, the lower the baseline REM density, the more robust the antidepressant response was. LIMITATIONS: Subject numbers are relatively small. CONCLUSIONS: Increased REM density, which reflects the number of rapid eye movements per epoch of REM sleep, may be a physiological marker for severity or poor prognosis in a variety of psychiatric disorders, including relapse in recovering alcoholics, suicidality in schizophrenia, and poor response to PSD or interpersonal psychotherapy in depression.
Adult↗
Partner violence and medical encounters: African-American women's perspectives.
OBJECTIVE: To examine the relationship between intimate partner violence (IPV) victimization and patient satisfaction with medical encounters among an African-American population. DESIGN: Cross-sectional, self-administered, anonymous survey. SETTING: Community-based, primary care center. PATIENTS: Consecutive African-American women recruited from an urban health center. A total of 102 women provided sufficient information to reveal whether they were currently experiencing IPV and to allow us to assess their experiences in their most recent primary care encounter. MEASUREMENTS: Patients' perceptions of their most recent encounter using questions adopted from the Medical Interview Satisfaction Scale and Consultation Satisfaction Questionnaire. We used the Conflicts Tactics Scale, supplemented with questions measuring sexual violence and emotional abuse, to assess IPV "in the past year." RESULTS: Women who reported current IPV rated several aspects of the encounter more negatively than did women who did not report current abuse. The IPV victims were less likely to report that they felt respected and accepted during the encounter, and they provided lower ratings of the quality of communication with their providers. CONCLUSIONS: It is unclear why victims of partner violence experience medical encounters as less satisfactory. Researchers need to expand studies of medical encounters as experienced by abused women to determine whether IPV status adversely affects general medical care.
Adolescent↗
Clinical and physiological consequences of rapid tryptophan depletion.
We review here the rapid tryptophan depletion (RTD) methodology and its controversial association with depressive relapse. RTD has been used over the past decade to deplete serotonin (5-hydroxy-tryptamine, or 5-HT) in humans and to probe the role of the central serotonin system in a variety of psychiatric conditions. Its current popularity was stimulated by reports that RTD reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) in remitted patients with a history of depression but not in patients treated with antidepressants which promote catecholaminergic rather than serotonergic neurotransmission (such as tricyclic antidepressants or buproprion). However, RTD has inconsistent effects in terms of full clinical relapse in depressed patients. Pooling the data from all published reports, patients who are either unmedicated and/or fully remitted are much less likely to experience relapse (7 of 61, or approximately 9%) than patients who are recently medicated and partially remitted (63 of 133, or approximately 47%; although, the numbers here may reflect patient overlap between reports). Recently remitted patients who have been treated with non-pharmacological therapies such as total sleep deprivation, electroconvulsive therapy, or bright light therapy also do not commonly show full clinical relapse with RTD. We briefly review RTD effects in other psychiatric disorders, many of which are treated with SSRIs. There is accumulating evidence to suggest that RTD affects central serotonergic neurotransmission. Nevertheless, many questions remain about the ability of RTD to reverse the beneficial effects of SSRIs or MAOIs, or to induce symptoms in unmedicated symptomatic or asymptomatic patients.
Antidepressive Agents↗
Neighborhood poverty as a predictor of intimate partner violence among White, Black, and Hispanic couples in the United States: a multilevel analysis.
PURPOSE: This study assessed the contribution of neighborhood poverty, measured at the census tract level, to the risk of male-to-female and female-to-male partner violence (MFPV, FMPV) among white, black, and Hispanic couples in the United States. METHODS: As part of the 1995 National Alcohol Survey, a representative sample of married/cohabiting couples was obtained through a multistage, multicluster household probability sampling frame. The outcome variables, MFPV and FMPV, were measured through the Conflict Tactics Scale, Form R. Sociodemographic, psychosocial, and alcohol consumption covariates that were statistically significant through bivariate analysis were retained as individual-level predictors. Neighborhood poverty, indicating residence in a census tract where greater than 20% of the population lived below the Federal poverty line, was assessed by appending 1990 Census data to the primary data set. Multilevel logistic regression models were constructed, with separate analyses performed for each outcome (MFPV, FMPV) among the white, black, and Hispanic couples. RESULTS: Couples residing in impoverished neighborhoods are at increased risk for both MFPV and FMPV. The association between residence in an impoverished neighborhood and MFPV was statistically significant for black couples (Odds Ratio [OR] 2.87; 95% Confidence Interval [CI] 1.36, 6.07). The association between residence in an impoverished neighborhood and FMPV was statistically significant for black couples and white couples. CONCLUSIONS: Characteristics of the socioenvironment, such as neighborhood poverty, are associated with the risk of partner violence, particularly among black couples. Policies aimed at reducing community poverty may contribute to effective partner violence prevention strategies.
Black or African American↗
Do executive function deficits differentiate between adolescents with ADHD and oppositional defiant/conduct disorder? A neuropsychological study using the Six Elements Test and Hayling Sentence Completion Test.
Two neuropsychological measures of executive functions--Six Elements Tests (SET) and Hayling Sentence Completion Test (HSCT)--were administered to 110 adolescents, aged 12-15 years. Participants comprised four groups: Attention Deficit Hyperactivity Disorder (ADHD) only (n = 35). ADHD and Oppositional Defiant Disorder/Conduct Disorder (ODD/CD) (n = 38), ODD/CD only (n = 11), and a normal community control group (n = 26). Results indicated that adolescents with ADHD performed significantly worse on both the SET and HSCT than those without ADHD, whether or not they also had ODD/CD. The adolescents with ADHD and with comorbid ADHD and ODD/CD were significantly more impaired in their ability to generate strategies and to monitor their ongoing behavior compared with age-matched controls and adolescents with ODD/CD only. It is argued that among adolescents with clinically significant levels of externalizing behavior problems, executive function deficits are specific to those with ADHD. The findings support the sensitivity of these two relatively new tests of executive functions and their ecological validity in tapping into everyday situations, which are potentially problematic for individuals with ADHD.
Adolescent↗
Computerized left ventricular pressure-volume relationships (pV-loops) using disposable angiographic tip transducer pigtail catheters.
Left ventricular pressure-volume relationships expressed as pV loops could yield important hemodynamic information in the cardiac catheterization laboratory. Many clinical situations might benefit from a quantitative assessment of left ventricular function. Potential applications of pV loops include the assessment of vasoactive and inotropic drugs, balloon valvuloplasty, coronary angioplasty, and surgical treatment of valvular heart disease. For many years the clinical use of pV loops has been hindered by logistical difficulties. The ability to merge on-line concurrent digital imaging data for computation of left ventricular volume and digital left ventricular pressure wave forms obtained from high fidelity tip-transducer angiocatheters has allowed us to develop a technique which can generate pV loops during cardiac catheterization procedures. The method offers an automated measurement of left ventricular volume independent of edge detection or an interactive technique for tracing endocardial borders by a trained operator. Illustrative case studies are included to demonstrate the potential of the method during ventricular angiographic procedures. Implementation and computational time requirements of the method are discussed. The concept and the value of pV loop generation to study left ventricular performance has been known for many years. Combining digital imaging and digital physiologic data obtained with disposable tip-transducer angiocatheters with modern networking technology, the technique can more easily be applied to catheterization procedures and could enhance invasive hemodynamic assessment of left ventricular function.
Angiography↗
Gender affects report of pain and function after arthroscopic anterior cruciate ligament reconstruction.
BACKGROUND: Gender-related differences in pain have been clearly shown in experimental settings. Clinical studies of such differences have produced conflicting findings. No studies have shown a significant difference in pain experience associated with differences in functional outcomes. Arthroscopic anterior cruciate ligament reconstruction (AACLR) produces pain of moderate intensity and provides a useful setting for examining gender-related differences in pain and function. METHODS: This study was a retrospective review of prospectively gathered data collected for a continuous quality improvement program and involved all patients who underwent AACLR at a single outpatient facility since June 1992. Anesthetic, surgical, and perioperative management techniques were standardized. Using a questionnaire, all patients were routinely asked to record pain scores, narcotic consumption, and whether they were able to perform a standardized straight leg-raising maneuver on each of the first 5 postoperative days. RESULTS: A total of 736 patients were enrolled for surgery, 58% of whom completed the entire 5-day questionnaire. Women reported higher pain scores at rest as well as with activity on postoperative day 1 compared with men (P < 0.005). In addition, fewer women were able to perform the straight leg-raising maneuver on postoperative day 1 (P = 0.002) and postoperative day 2 (P = 0.004). There was no difference in the amount of narcotics consumed at any time during the study period. CONCLUSIONS: Women seem to experience greater intensity of pain after AACLR that is associated with a decrease in an intermediate measure of functional outcome. These differences may result from differences in either response to analgesics or neuroprocessing.
Adult↗
Accuracy of base excess--an in vitro evaluation of the Van Slyke equation.
OBJECTIVES: To evaluate the precision, bias and CO2 invariance of base excess as determined by the Van Slyke equation over a wide P(CO2) range at normal and low hemoglobin concentrations. DESIGN: Prospective in vitro study. SETTING: University research laboratory. SUBJECTS: Normal human blood, both undiluted and diluted with plasma. INTERVENTIONS: Two experiments were conducted. In the first, blood unmodified or after adding HCl or sodium bicarbonate was rendered hypercarbic (P(CO2) >70 torr) by gas equilibration. Rapid Pco2 reduction in > or =10 steps to a final P(CO2) < or =20 torr was then performed. In the second experiment, blood unmodified or diluted to a hemoglobin concentration of approximately 4 G% was mixed anaerobically (9:1, vol:vol) with varying concentrations of lactic acid in saline (0-250 mmol/L). MEASUREMENTS AND MAIN RESULTS: In the first experiment, blood gas analysis at each step during the progressive P(CO2) reduction revealed that base excess remained nearly constant (SD all specimens < or =0.6 mmol/L) whereas P(CO2) changed by >80 torr. In the second experiment, simultaneous blood gas and plasma lactate analyses showed that changes in base excess correlated closely with changes in both plasma and whole blood lactate concentrations (r2 > or = 0.91) despite concurrent P(CO2) elevations as great as 200 torr. Quantification by base excess of change in whole blood lactate concentration was precise with slight negative bias (mean negative bias, 1.1+/-1.9 mmol/L) in both diluted and undiluted blood. There was significant underestimation of change in plasma lactate concentration in undiluted blood, presumably because base excess is a whole blood variable. CONCLUSIONS: Base excess calculated using the Van Slyke equation accurately quantifies metabolic (nonrespiratory) acid-base status in blood in vitro. This accuracy is little affected by large simultaneous alterations in P(CO2), or by very low hemoglobin concentrations similar to that used to calculate standard base excess.
Acid-Base Equilibrium↗
CYP3A4 promoter variant in Saudi, Ghanaian and Scottish Caucasian populations.
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Alleles↗