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Biomedical subjects

R Russell

Publications and source records attributed to R Russell.

At least 73 records · Page 4Linked to original sources

Bipolar and antisocial disorders among relatives of ADHD children: parsing familial subtypes of illness.

Attention deficit hyperactivity disorder (ADHD) is a familial disorder that is highly comorbid with conduct disorder and sometimes co-occurs with bipolar disorder. This pattern of comorbidity is also seen among relatives of ADHD probands. A growing literature suggests that ADHD with antisocial comorbidity may be nosologically distinct from other forms of ADHD. A similar pattern has been observed for ADHD and bipolar disorder. Given these results, along with the observed comorbidity between conduct and bipolar disorders, we used data from our study of 140 ADHD and 120 control families to determine if conduct and bipolar disorders in ADHD boys should be considered alternative manifestations of the same familial disorder. The probands and their relatives were examined with DSM-III-R structured diagnostic interviews and were assessed for cognitive, achievement, social, school, and family functioning. Our results provide fairly consistent support for the hypothesis that antisocial- and bipolar-ADHD subtypes are different manifestations of the same familial condition. As predicted by this hypothesis, there was a significant three-way association between variables assessing the family history of each disorder. Moreover, when families were stratified into bipolar, antisocial, and other types, few differences emerged between the bipolar and antisocial families.

Adolescent↗

Kinetic characterization of the ATPase cycle of the DnaK molecular chaperone.

DnaK, the prototype Hsp70 protein of Escherichia coli, functions as a molecular chaperone in protein folding and protein disassembly reactions through cycles of polypeptide binding and release that are coupled to its intrinsic ATPase activity. To further our understanding of these processes, we sought to obtain a quantitative description of the basic ATPase cycle of DnaK. To this end, we have performed steady-state and pre-steady-state kinetics experiments and have determined rate constants corresponding to individual steps in the DnaK ATPase cycle at 25 degrees C. Hydrolysis of ATP proceeds very slowly with a rate constant (khyd approximately 0.02 min-1) at least 10-fold smaller than the rate constant for any other first-order step in the forward reaction pathway. The ATP hydrolysis step has an activation energy of 26.2 +/- 0.4 kcal/mol and is rate limiting in the steady-state under typical in vitro conditions. ATP binds with unusual strength to DnaK, with a measured KD approximately 1 nM. ADP binds considerably less tightly than ATP and dissociates from DnaK with a koff of approximately 0.4 min-1 (compared with a koff of approximately 0.008 min-1 for ATP). However, in the presence of physiologically relevant concentrations of inorganic phosphate (Pi), the release of ADP from DnaK is greatly slowed, approximately to the rate of ATP hydrolysis. Under these conditions, the ADP-bound form of DnaK, the form that binds substrate polypeptides most tightly, was found to represent a significant fraction of the DnaK population. The slowing of ADP release by exogenous Pi is due to thermodynamic coupling of the binding of the two ligands, which produces a coupling energy of approximately 1.6 kcal/mol. This result implies that product release is not strictly ordered. In the absence of exogenous inorganic phosphate, Pi product, by virtue of its higher koff, is released prior to ADP. However, at physiological concentrations of inorganic phosphate, the alternate product release pathway, whereby ADP dissociates from a ternary DnaK.ADP.Pi complex, becomes more prominent.

Adenosine Diphosphate↗

Clinical features of children with both ADHD and mania: does ascertainment source make a difference?

OBJECTIVE: We evaluated the structural diagnostic results of children ascertained through an ADHD diagnosis with comorbid mania to determine if they have the same phenotype as children ascertained through a mania diagnosis with comorbid ADHD. METHOD: We compared a sample of children participating in a family genetic study of ADHD to a sample of children ascertained through a study of childhood mania. RESULTS: Similar correlates of ADHD and mania were observed in children satisfying criteria for both disorders irrespective of ascertainment source. CONCLUSIONS: Findings suggest that children with mania and ADHD have two disorders, their features not varying with the primary diagnostic focus. LIMITATIONS: The results may have been limited by small sample size. CLINICAL RELEVANCE: Because the coexistence of ADHD and mania seriously complicates the course and treatment of children, understanding the compatibility of these disorders has important clinical implications in the management of this population.

Adolescent↗

The effects of age on postprandial thermogenesis at four graded energetic challenges: findings in young and older women.

There remains controversy over the effect of age on postprandial thermogenesis, with some studies observing decreased postprandial thermogenesis in older subjects and other studies finding no effect of age. We investigated this issue in 8 young (25.2+/-1.8 years) and 8 older (72.2+/-2.1 years) healthy glucose-tolerant women with normal thyroid hormone status. Repeated measures of the thermic effect of feeding (TEF) were obtained following consumption of test meals containing 0, 1046, 2092, and 4184 kilojoules (kJ) by using indirect calorimetry. TEF at each meal size was determined once in the older subjects and twice in the younger subjects (during follicular and luteal phases of the menstrual cycle) for a total of 96 measurements. There was a positive dose-response between meal size and TEF (p < .001) that was not significantly affected by age group. The best single predictor of TEF expressed as a percentage of meal energy content was waist-to-hip ratio (R2=67.416, p < .02). These results indicate that aging is not associated with decreased TEF in the absence of factors such as a hypothyroid state or glucose intolerance.

Adult↗

Microcirculatory studies of frostbite injury.

Frostbite represents a spectrum of injury ranging from irreversible cellular destruction to reversible changes seen after rewarming. These changes include increases in tissue edema, circulatory stasis, and progressive thrombosis leading to further tissue necrosis. For this reason, it is often difficult at the time of surgical debridement to determine the extent of frostbite injury. This delayed tissue injury is similar to that seen in muscle during ischemia/reperfusion injury. Muscle that initially appears viable on reperfusion may subsequently necrose due to collapse of the microcirculation. Adherent neutrophils have been specifically cited as important components in ischemia/reperfusion injury and have also been suggested to play a role in frostbite injury. We have used an intravital microscopic muscle preparation to study microcirculatory changes carefully in frostbite injury during rewarming. The right gracilis muscle of male Wistar rats is dissected free from its primary vascular pedicle and the rat is positioned on a specially constructed microsurgical stage. Temperature changes of the muscle are recorded. The prepared axial pattern flap is transilluminated with a microscope and projected on a video screen, allowing measurement of arteriolar diameters and changes in the numbers of stuck and rolling neutrophils before frostbite, during rewarming, and for several hours later. Cold silicone oil is used to freeze the muscle to -5+/-2 degrees C in 2 to 3 minutes and to hold this temperature for 5 minutes. The muscle is rewarmed with 42 degrees C normal saline placed directly on the muscle surface. Baseline vessel diameter and leukocyte counts in 100-mm segments of the microvasculature are recorded as well as at 5, 15, and 30 minutes, and at 1, 2, and 3 hours postrewarming of frozen muscle. Observations from our initial 11 animals show that reperfusion of the muscle following freezing is varied temporally and spatially, with circulation to most vascular segments restored 5 to 10 minutes after rewarming. In 9 of 11 animals we observed the shedding of "white clots" in small arterioles and venules occurring as soon as 5 minutes after thawing. In some instances shedding continued for as long as 1 hour after rewarming. Microvascular hemorrhage was widespread 1 hour following the thaw, but there was no significant increase in neutrophil adherence observed until 3 hours following rewarming. The exact nature of the vascular injury and the composition of the "white clots" are now being determined from ultrastructural studies. Blood flow in microcirculation stops during freezing, but small-vessel perfusion returns immediately on thawing. This suggests that the vascular architecture is maintained during the freezing and thawing. Unlike ischemia/reperfusion injury, neutrophil adhesion plays a smaller role in the early response to frostbite injury. The early microcirculatory observations seen after rewarming suggest progressive and severe perturbations in platelet function and fibrin formation that are significantly different from ischemia/reperfusion injury.

Animals↗

The naturalistic course of pharmacologic treatment of children with maniclike symptoms: a systematic chart review.

OBJECTIVE: To assess the effectiveness of mood stabilizers in treating maniclike symptoms in children. METHOD: Subjects were consecutively referred pediatric patients who, at initial intake, satisfied DSM-III-R criteria for mania on a structured diagnostic interview. We systematically reviewed their clinical records to assess (1) the course of maniclike symptoms and (2) all medications prescribed at each follow-up visit. Survival analysis was used to determine the effect of mood stabilizers and other medications on the course of maniclike symptoms. RESULTS: Of the 59 subjects meeting criteria for mania, 44 (75%) exhibited evidence of maniclike symptoms during follow-up. The occurrence of manic symptoms significantly predicted the subsequent prescription of mood stabilizers (rate ratio = 2.9, 95% confidence interval [CI] = 1.6 to 5.5), and use of mood stabilizers predicted decreases in manic symptoms (rate ratio = 4.9, 95% CI = 1.2 to 20.8). However, improvement was slow and associated with a substantial risk for relapse. CONCLUSION: Mood stabilizers were frequently used in children with maniclike symptoms, and their use was associated with significant improvement of maniclike symptoms, whereas use of antidepressant, antipsychotic, and stimulant medications was not.

Adolescent↗

Familial subtypes of attention deficit hyperactivity disorder: a 4-year follow-up study of children from antisocial-ADHD families.

ADHD is a familial disorder with high rates of comorbidity with conduct disorder in childhood and antisocial personality and substance use disorders in adulthood. A growing literature suggests that ADHD with antisocial comorbidity may be nosologically distinct from other forms of ADHD. Previously, we proposed a family-based stratification that defined Antisocial families as those with either conduct disorder or antisocial personality disorder in the probands or relatives. To provide predictive validity for that stratification, we assessed psychopathology in these families 4 years after their initial assessment. Results show that the probands and siblings from Antisocial families had higher rates of psychopathology during the 4-year follow-up period compared with siblings from Non-antisocial and control families. They also had more deviant ratings on the Child Behavior Checklist (especially for anxious/depressed, delinquent, and aggressive behavior). We found fewer group differences in the academic, psychosocial, and intellectual correlates of ADHD. These results confirm and extend previous work indicating that Antisocial ADHD may be a nosologically and clinically meaningful subform of ADHD.

Adolescent↗

"HPV effect" in the female lower genital tract. A community study.

OBJECTIVE: To determine the distribution of "human papillomavirus (HPV) effect" and intraepithelial neoplasia in the lower female genital tract in one community with a prospective study. STUDY DESIGN: In a family practice setting, colposcopy was offered to all women presenting for a routine cervical cytologic smear. Directed biopsies were taken from areas staining abnormally with acetic acid or iodine. RESULTS: This study of 224 women showed a high incidence of HPV effect in the lower genital tract (68%), including 18% on the vulva. The age distribution suggests a coital influence. A five-year review showed persistence of HPV effect on the vulva or vagina in only one patient. One other woman developed cervical intraepithelial neoplasia (CIN) 1. CONCLUSION: HPV effect is common in the lower genital tract of women under the age of 30 years. Colposcopic study suggested that HPV effect on the vulva and vagina is transient. The relatively high incidence of HPV effect on the vulva may explain why cervical HPV and CIN generally appear only after coitarche, as a consequence of physical transfer. This may help explain why women with a single lifetime sexual partner are not exempt from the risk of cervical cancer or its precursors.

Adolescent↗

Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo.

BACKGROUND: Myocardial ischemia increases heart glucose utilization in vivo. However, whether low-flow ischemia leads to the translocation of glucose transporter (GLUT)-4 and/or GLUT-1 to the sarcolemma in vivo is unknown. METHODS AND RESULTS: In a canine model, we evaluated myocardial glucose metabolism in vivo and the distribution of GLUT-4 and GLUT-1 by use of immunoblotting of sarcolemma and intracellular membranes and immunofluorescence localization with confocal microscopy. In vivo glucose extraction increased fivefold (P < .001) and was associated with net lactate release in the ischemic region. Ischemia led to an increase in the sarcolemma content of both GLUT-4 (15 +/- 2% to 30 +/- 3%, P < .02) and GLUT-1 (41 +/- 4% to 58 +/- 3%, P < .03) compared with the nonischemic region and to a parallel decrease in their intracellular contents. Immunofluorescence demonstrated the presence of both GLUT-4 and GLUT-1 on cardiac myocytes. GLUT-1 had a more prominent cell surface pattern than GLUT-4, which was primarily intracellular in the nonischemic region. However, significant GLUT-4 surface labeling was found in the ischemic region. CONCLUSIONS: Translocation of the insulin-responsive GLUT-4 transporter from an intracellular storage pool to the sarcolemma occurs in vivo during acute low-flow ischemia. GLUT-1 is also present in an intracellular storage pool from which it undergoes translocation to the sarcolemma in response to ischemia. These results indicate that both GLUT-1 and GLUT-4 are important in ischemia-mediated myocardial glucose uptake in vivo.

Animals↗

Clinical and neurophysiological features of tick paralysis.

The clinical and neurophysiological findings in six Australian children with generalized tick paralysis are described. Paralysis is usually caused by the mature female of the species Ixodes holocyclus. It most frequently occurs in the spring and summer months but can be seen at any time of year. Children aged 1-5 years are most commonly affected. The tick is usually found in the scalp, often behind the ear. The typical presentation is a prodrome followed by the development of an unsteady gait, and then ascending, symmetrical, flaccid paralysis. Early cranial nerve involvement is a feature, particularly the presence of both internal and external ophthalmoplegia. In contrast to the experience with North American ticks, worsening of paralysis in the 24-48 h following tick removal is common and the child must be carefully observed over this period. Death from respiratory failure was relatively common in the first half of the century and tick paralysis remains a potentially fatal condition. Respiratory support may be required for > 1 week but full recovery occurs. This is slow with several weeks passing before the child can walk unaided. Anti-toxin has a role in the treatment of seriously ill children but there is a high incidence of acute allergy and serum sickness. Neurophysiological studies reveal low-amplitude compound muscle action potentials with normal motor conduction velocities, normal sensory studies and normal response to repetitive stimulation. The biochemical structure of the toxin of I. holocyclus has not been fully characterized but there are many clinical, neurophysiological and experimental similarities to botulinum toxin.

Acetylcholine↗

Injury consequences from participation in professional rugby league: a preliminary investigation.

OBJECTIVE: To conduct a preliminary investigation to determine if injuries sustained while playing professional rugby league have long term consequences for players after retirement from their playing careers. METHOD: Twenty eight retired players, who had competed in the professional Australian Rugby League competition, responded to a 23 item survey. Respondents were asked to recall all injuries that resulted in them being unable to play for five or more consecutive games. The survey asked players to provide information about age, playing weight, number of games played, position played, number and type of major injuries sustained during their career, and the effects of these injuries both during their career and after retirement. RESULTS: Within the limitations of this study's small sample, it is suggested that players with long term consequences of injury may experience a variety of detrimental effects into retirement, including job limitations, reduced income earning potential, and increased personal medical costs. CONCLUSION: Although research relating to the type and severity of injuries sustained while playing rugby league has been previously undertaken, investigation into the effect injuries sustained during a professional career have on players after retirement has been neglected. This preliminary investigation suggests that retired professional rugby league players may have at least one long term consequence of injuries sustained during their playing career.

Absenteeism↗