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Biomedical subjects

R Russell

Publications and source records attributed to R Russell.

At least 19 recordsLinked 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

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

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

Long term backache after childbirth: prospective search for causative factors.

OBJECTIVES: To assess in a prospective randomised study the association between motor block resulting from high and low dose epidural infusions of bupivacaine in labour and the incidence of long term backache after childbirth, and to compare the incidence of backache in women not receiving epidural analgesia. DESIGN: Women requesting epidural analgesia in labour between October 1991 and March 1994 were randomised to receive infusions of either bupivacaine alone or low dose bupivacaine with opioid. Data were collected during labour and the immediate postpartum period from these women and from women recruited at random over the same time from those who had laboured without epidural analgesia. A postal questionnaire about symptoms was sent three months after childbirth to all women. Further data were collected one year after childbirth from those who had reported new backache at three months. SETTING: St Thomas's Hospital, London. SUBJECTS: 599 women were recruited, of whom 450 (75%) replied to a follow up questionnaire. RESULTS: 152 women (33.8% of responders) reported backache lasting three months after delivery and, of these, 33 (7.3%) had not previously suffered with backache. There were no significant differences between the treatment groups in the incidence of postnatal backache overall or of new backache or any symptoms after childbirth. Among all demographic, obstetric, and epidural variables examined the only factors significantly associated with backache after childbirth were backache before and during pregnancy. CONCLUSIONS: The incidence of new long term backache was not significantly increased in women who received epidural analgesia in labour. Motor block resulting from epidural local anaesthetic administration was not a significant factor in the development of backache.

Adult

Folate synthesized by bacteria in the human upper small intestine is assimilated by the host.

BACKGROUND & AIMS: Some intestinal flora are known to synthesize folate. The aim of this study was to determine whether folate synthesized by small intestinal flora is assimilated by the human host. METHODS: Subjects with atrophic gastritis and healthy volunteers were studied before and after omeprazole administration. A double-lumen perfusion tube was placed in the duodenum. 3H-labeled P-aminobenzoic acid, a precursor substrate for bacterial folate synthesis, was perfused. Downstream intestinal aspirates and a 48-hour urine collection were obtained. RESULTS: Atrophic gastritis and omeprazole administration were associated with increases in duodenal pH and in small intestinal flora. Bacterially synthesized folates were isolated from the intestinal aspirates. Tritiated 5-methyltetrahydrofolate, a major metabolite of folate, was isolated from the urine of omeprazole-treated subjects in greater quantities than from drug-free subjects (P<0.01); the quantity of tritiated 5-methyltetrahydrofolate in the urine of the subjects with atrophic gastritis was similarly elevated. CONCLUSIONS: (1) Mild bacterial overgrowth caused by atrophic gastritis and administration of omeprazole are associated with de novo folate synthesis in the lumen of the small intestine; (2) the human host absorbs and uses some of these folates; and (3) the contribution to folate nutriture from this source remains unclear.

4-Aminobenzoic Acid

Postabsorptive and postprandial energy expenditure and substrate oxidation do not change during the menstrual cycle in young women.

There is little information on the effects of the menstrual cycle on the thermic effect of feeding (TEF) and postprandial substrate oxidation. To address these issues, a dose-response study was conducted in eight young women to whom test meals containing 0, 1046, 2092 and 4148 kJ were administered on nonconsecutive days, once each during the follicular phase and once during the luteal phase of the menstrual cycle. Postprandial energy expenditure was measured until it returned to base line (test duration for the 0 kJ meal was matched to duration of 4184 kJ meal). There was no significant difference between menstrual cycle phases in the duration of the thermogenic response to any size meal. TEF, calculated by four different methods, did not differ between follicular and luteal phases, and a comparable dose-response was observed in both phases. Similarly, there was no effect of menstrual cycle phase on postabsorptive or postprandial protein, fat, or carbohydrate oxidation. In conclusion, postabsorptive and postprandial energy expenditure and substrate oxidations did not differ in young women during the follicular and luteal phases of the menstrual cycle.

Adult

Liver function and morphology after resuscitation from severe hemorrhagic shock with hemoglobin solutions or autologous blood.

OBJECTIVE: To test the effects of three hemoglobin solutions on liver function and hepatic morphology after resuscitation from severe hemorrhagic shock. DESIGN: Prospective study. SETTING: Laboratory. SUBJECTS: Thirty-three beagle dogs. INTERVENTION: Hemorrhagic shock was induced in anesthetized dogs by removal of blood at a rate of 2 mL/kg/min until systolic blood pressure (BP) reached 50 mm Hg. BP was maintained at this level 2 hrs by further withdrawing 5 to 10 mL aliquots whenever BP increased > 50 mm Hg. Resuscitation was then initiated with autologous whole blood (n = 7), 4% pyridoxalated-hemoglobin-polyoxyethylene conjugate (4% PHP [n = 6]), 8% pyridoxalated-hemoglobin-polyoxyethylene conjugate (8% PHP [n = 9], or 8% stroma-free hemoglobin (n = 7). Four dogs were managed identically but were not resuscitated. Gross necropsy and histologic examination of the liver were performed on all dogs after 7 days, or earlier if death occurred. MEASUREMENTS AND MAIN RESULTS: In vitro interferences of PHP and stroma-free hemoglobin with liver function tests were determined and recommendations for interpretation of results from blood samples containing PHP and stroma-free hemoglobin were made. Blood was collected before, during, and after resuscitation from hemorrhagic shock. The dogs were then awakened and survivors were monitored daily with blood sampling until they were killed and necropsy was performed. After 7 days, the survival rate following hemorrhagic shock was 100% for whole blood and 4% PHP, 86% for stroma-free hemoglobin, and 33% for 8% PHP. Of the resuscitated dogs not surviving 7 days, all but one died within 27 hrs from coagulopathy. All dogs not resuscitated died within 1.75 hrs after 2 hrs of shock. Bilirubin, alkaline phosphatase, and lactic dehydrogenase concentrations could not be measured due to interferences of stroma-free hemoglobin and PHP. Aspartate (AST) and alanine (ALT) aminotransferase concentrations could be measured after dilution to overcome the interferences. Significant increases in AST and ALT values in all groups 24 hrs after resuscitation were attributed to hypoxic hepatocellular damage associated with the severity of the shock model rather than to the resuscitation fluid. Liver histology showed no changes attributed to toxic damage of hepatocytes in dogs resuscitated with stroma-free hemoglobin or PHP. However, changes, were less severe in dogs resuscitated with 4% PHP than in other groups. CONCLUSION: Morphologic studies at necropsy and liver function tests in dogs receiving hemoglobin solutions, compared with autologous blood, support the conclusion that the PHP and stroma-free hemoglobin solutions tested did not produce hepatic toxicity when used as resuscitation fluids in this model of severe shock.

Acute Disease

Epidural infusion of low-dose bupivacaine and opioid in labour. Does reducing motor block increase the spontaneous delivery rate?

Labouring women were randomly allocated to receive epidural infusions during labour of either 0.125% plain bupivacaine (n = 200) or a combination of 0.0625% bupivacaine with either 2.5 micrograms.ml-1 fentanyl or 0.25 micrograms.ml-1 sufentanil (n = 199) each starting at 12 ml.h-1 and adjusted as necessary to maintain analgesia. The dose of bupivacaine, both hourly (p < 0.001) and total (p < 0.001), was significantly lower in the group receiving the combination. Motor block was significantly less common and less severe in the combination group (p < 0.001). These reductions did not result in a significant increase in spontaneous deliveries. Maternal satisfaction with first (p < 0.001) and second stage analgesia (p < 0.001) was significantly increased in the combination group. The addition of opioid to the epidural infusion did not reduce the incidence of perineal pain. There were no significant differences between the groups in neonatal outcome or the incidence of early postnatal symptoms.

Adult

Colposcopy in general practice.

Primary care physicians are in an excellent position to identify women most at risk for cancer precursors. They can use a variety of modalities, including colposcopy thus reducing patient anxiety and waiting time. This article describes a training program for such a service, which includes at least 100 colposcopy examinations under supervision. It is applicable outside a hospital clinic setting. Subsequent practice must have a referral base sufficient to maintain competence as well as economic viability. All GP colposcopists in the Perth area attend regular quality assurance meetings. An audit has shown that properly trained GPs can achieve a level of competence equivalent to that expected of their specialist colleagues (89% concordance between colposcopic impression and histology). The format of the audit was based on that of the Royal Australian College of Obstetricians and Gynaecologists (RACOG). Treatment must be performed by experts. General practice is the appropriate location for community screening studies using colposcopy.

Clinical Competence