Biomedical subjects
Publications and source records attributed to J L Boyd.
Most of the previously reported lumbosacral nerve root avulsions presented with pseudomeningoceles at the time of delayed initial imaging. We report a case of traumatic lumbosacral nerve root injury associated with an isolated femur fracture and demonstrate the evolution of pseudomeningoceles following nerve root avulsions and edema in the perineural fat identified on the initial MR imaging.
The interpretation of results measured by quantitative ultrasound (QUS) of the heel depends on the population studied. We measured estimated bone mineral density (BMD) of the heel using the Hologic Sahara sonometer. People were studied at county fairs, health fairs, and churches. Subjects were not on treatments that would affect bone density, other than calcium supplementation. This included 823 Caucasian women, 131 African American women, and 301 Caucasian men. In contrast to women, for Caucasian men the squared term for age was not significant, and a straight line of decline was the best fit for estimated BMD. African American women had a standard deviation larger than that reported by Hologic for Caucasian women. We compared a history of self-reported fractures with a subject's estimated BMD. An estimated BMD of 0.57 gm/cm2 included 75% of all fractures. This cutoff point was associated with increased fracture prevalence in subjects over age 50, relative risk of 1.4. This result corresponds to the Hologic data T-score of -0.2. When used as a screening tool for osteoporosis fracture risk, an estimated BMD of 0.57 gm/cm2 seems reasonable in those subjects over age 50.
AIMS: Local prostaglandin (PG) production contributes to tachyphylaxis to angiotensin II (ANGII) in veins. Our aim was to assess the hypothesis that local nitric oxide (NO) generation is also, in part, responsible for tachyphylaxis to ANGII in veins, using the Aellig dorsal hand vein technique. METHODS: Eight healthy male volunteers received 600 mg of aspirin (orally) to inhibit PG production. The venoconstrictor effects of ANGII and noradrenaline (NA) were then compared in dorsal hand veins during co-infusion of the NO synthase inhibitor L-NMMA or saline, on separate occasions. RESULTS: ANGII and NA produced a similar degree of initial venoconstriction. However, the response to ANGII was significantly attenuated by 12 min compared with NA (AUC 147 +/- 38 vs 196 +/- 40, respectively; [95% confidence interval for difference: 7, 92], P = 0.02). Infusion of L-NMMA did not influence the response to ANGII or NA (P = 0.2 and P = 0.3, respectively). CONCLUSIONS: Tachyphylaxis to ANGII in dorsal hand veins is not dependent on local NO release.
Previously, the estrogen receptor (ER) ligand 4-[1-(p-hydroxyphenyl)-2-phenylethyl]phenoxyacetic acid (5) was found to have differential bone loss suppressive effects in the ovariectomized (OVX) rat approaching those of selective ER modulators (SERMs) such as tamoxifen. In an effort to improve efficacy, analogues of this compound were prepared which incorporated features designed to reduce polarity/ionizability. Thus, the acetic acid side chain of 5 was replaced by n-butanoic acid and 1H-tetrazol-4-ylmethyl moieties, to give 8 and 10, respectively. Also, the phenolic hydroxyl of 5 was replaced, giving deoxy analogue 9. We also developed new methods for the synthesis of triarylethylene variants of 5 and 9, namely 4-([1-(p-hydroxyphenyl)-2-phenyl-1-butenyl]phenoxy)-n-butanoic acid (6) and its des-hydroxy counterpart (7), because the former of these had in vitro antiestrogenic effects characteristic of known SERMs. In the OVX rat, 6 and 7 were as effective as 17 beta-estradiol in suppressing serum markers of bone resorption/turnover, namely osteocalcin and deoxypyridinoline, but had only 30% of the uterotrophic efficacy of 17 beta-estradiol. This study has thus identified two triarylethylene oxybutyric acids, 6 and 7, that have differential bone/uterus effects like those of known SERMs.
Hyperhomocystinemia is a risk factor for cardiovascular disease, and acute elevation of plasma homocysteine after methionine loading impairs endothelial function in healthy subjects. Interestingly, pretreatment with vitamin C can ameliorate this effect. We have already shown that acute oral vitamin C administration reduces arterial stiffness in healthy subjects, and the aim of the present study was to investigate the effect of methionine loading on arterial stiffness with and without concomitant vitamin C using the noninvasive technique of pulse wave analysis. Eight healthy male subjects (mean age, 29 years; range, 20-42 years) were studied on three occasions at weekly intervals. In a double-blind, double-dummy, randomized order they received orally either 100 mg/kg methionine, 100 mg/kg methionine plus 2 g of vitamin C, or matching placebos. Peripheral and central blood pressure, heart rate, cardiac index, arterial stiffness, and plasma homocysteine levels were assessed at baseline and 6 hours after dosing. Compared with placebo, there was no significant change in any of the hemodynamic parameters, including arterial stiffness, after oral methionine, although plasma homocysteine did increase from 11.5 +/- 1.6 to 28.7 +/- 4.4 microM (mean +/- SEM; p < 0.001). Combined methionine and vitamin C led to a similar increase in plasma homocysteine but significantly reduced augmentation index by 10.5 +/- 3.2% (p = 0.02). Acute hyperhomocystinemia does not significantly alter arterial stiffness, as assessed by pulse wave analysis, whereas a combination of methionine and vitamin C leads to a similar reduction in augmentation index to that previously described after vitamin C alone. These data reinforce evidence that vitamin C reduces arterial stiffness but do not indicate any important interaction with oral methionine.
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BACKGROUND: It has been determined that prostate cancer cells overexpress the matrix metalloprotease matrilysin (MMP-7), but the factors regulating this expression have not been identified. Fibroblast growth factors (FGF), which are expressed in the prostate, might participate in paracrine regulation of matrilysin expression by prostate cancer cells. METHODS: We tested the ability of recombinant FGF proteins and prostate fibroblast-conditioned media (PFCM) to induce promatrilysin expression in the prostate carcinoma cell line, LNCaP, and in normal prostate epithelial (PrEC) cells. We also characterized prostate fibroblast FGF expression by reverse transcriptase-polymerase chain reaction (RT-PCR). An inhibitor of FGF receptor activation (SU5402) was used to determine the role of FGF proteins in the induction of promatrilysin expression by PFCM. RESULTS: Recombinant FGF-1, FGF-2, FGF-9, FGF-10, and PFCM significantly induced promatrilysin expression in LNCaP cells but not in PrEC cells. Prostate fibroblasts express mRNAs for these FGF proteins, and inhibition of LNCaP cell FGF receptors with SU5402 substantially reduced the induction of promatrilysin expression by PFCM. CONCLUSIONS: Stromally expressed FGF proteins induce promatrilysin expression in a prostate carcinoma cell, and may provide a mechanism for the overexpression of promatrilysin observed in prostate cancer.
Fifty-four patients who underwent arthroscopically assisted anterior cruciate ligament reconstruction with bone-patellar tendon-bone autograft or allograft were studied prospectively to compare a postoperative home based rehabilitation program with a clinic based program. Fifty-four patients (mean age, 30 years) were assigned randomly to the home based program (27 patients) or the clinic based program (27 patients). The home based schedule featured six physical therapy visits during a 6-month postoperative study period, whereas the clinic based schedule specified 24 physical therapy visits during those 6 months. All patients entered in the study met strict selection criteria: age older than 15 years, no previous ligament repair or reconstruction, no complicating medical conditions, no collegiate or professional athletes, reconstruction at least 6 weeks after injury, and informed consent. At the 6-month followup, no significant statistical differences were found between the two groups in range of motion, thigh atrophy, anterior drawer compliance, hopping tests, Lysholm scores, or subjective health status scores. Thus, the authors conclude that in a selected group of patients who have undergone anterior cruciate ligament reconstruction, a home based postoperative rehabilitation program is feasible, safe, and effective.
A series of 33 patients with combined (injurious) sleepwalking, sleep terrors, and rapid eye movement (REM) sleep behavior disorder (viz. "parasomnia overlap disorder") was gathered over an 8-year period. Patients underwent clinical and polysomnographic evaluations. Mean age was 34 +/- 14 (SD) years; mean age of parasomnia onset was 15 +/- 16 years (range 1-66); 70% (n = 23) were males. An idiopathic subgroup (n = 22) had a significantly earlier mean age of parasomnia onset (9 +/- 7 years) than a symptomatic subgroup (n = 11) (27 +/- 23 years, p = 0.002), whose parasomnia began with either of the following: neurologic disorders, n = 6 [congenital Mobius syndrome, narcolepsy, multiple sclerosis, brain tumor (and treatment), brain trauma, indeterminate disorder (exaggerated startle response/atypical cataplexy)]; nocturnal paroxysmal atrial fibrillation, n = 1; posttraumatic stress disorder/major depression, n = 1; chronic ethanol/amphetamine abuse and withdrawal, n = 1; or mixed disorders (schizophrenia, brain trauma, substance abuse), n = 2. The rate of DSM-III-R (Diagnostic and Statistical Manual, 3rd edition, revised) Axis 1 psychiatric disorders was not elevated; group scores on various psychometric tests were not elevated. Forty-five percent (n = 15) had previously received psychologic or psychiatric therapy for their parasomnia, without benefit. Treatment outcome was available for n = 20 patients; 90% (n = 18) had substantial parasomnia control with bedtime clonazepam (n = 13), alprazolam and/or carbamazepine (n = 4), or self-hypnosis (n = 1). Thus, "parasomnia overlap disorder" is a treatable condition that emerges in various clinical settings and can be understood within the context of current knowledge on parasomnias and motor control/dyscontrol during sleep.
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Serial assessments of cognition, mood, and disability were carried out at nine month intervals over a 54 month period on a cohort of 87 patients with Parkinson's disease (PD) and a matched cohort of 50 control subjects. Dementia was diagnosed from data by rigorously applying DSM-III-R criteria. Initially, 6% (5/87) PD patients were demented, compared with none of the 50 control subjects. A further 10 PD patients met the dementia criteria during the follow up period; this was equivalent, with survival analysis, to a cumulative incidence of 19%. With the number of person years of observation as the denominator, the incidence was 47.6/1000 person years of observation. None of the control subjects fulfilled dementia criteria during the follow up period. The patients with PD who became demented during follow up were older at onset of Parkinson's disease than patients who did not become demented, had a longer duration of Parkinson's disease, and were older at inclusion to the study.
Hypomagnesemia is a common disorder in noncardiac surgical patients in the postoperative period, but the effect of cardiac surgery on serum magnesium concentrations remains unclear. The authors hypothesized that cardiac surgery is associated with hypomagnesemia, and prospectively studied 101 subjects (60 +/- 13.1 years of age) undergoing coronary artery revascularization (n = 70), valve replacement (n = 24), or both simultaneously (n = 7). Blood samples and clinical biochemical data were collected before induction of anesthesia, prior to cardiopulmonary bypass (CPB), immediately after CPB, and on postoperative day 1. Blood samples were analyzed for ultrafilterable magnesium, total magnesium, ionized calcium, parathyroid hormone, and free fatty acid concentrations. Outcome variables were also determined. Eighteen of 99 (18.2%) subjects had hypomagnesemia preinduction and this number increased to 71 of 100 (71.0%) following cessation of CPB (P less than 0.05). Patients with postoperative hypomagnesemia had a higher frequency of atrial dysrhythmias (22 of 71 [31.0%] v 3 of 29 [10.3%], P less than 0.05) and required prolonged mechanical ventilatory support (22 of 63 [34.9%] v 4 of 33 [12.1%], P less than 0.05). Hypomagnesemia is common following cardiac surgical procedures with CPB and is associated with clinically important postoperative morbidity.
The performance of 47 patients with Parkinson's disease on a battery of tests of cognition, motor function, disability and mood was compared with the performance of 47 healthy control subjects who were matched to the patients on the basis of age, sex and pre-morbid IQ. An increased prevalence of impairment over a range of cognitive functions was observed in the Parkinson's disease patients as compared with their matched controls. The differences between the Parkinson's disease patients and controls could not be accounted for by factors such as depressed mood, effects of medication or motor impairment. Our findings are discussed in relation to the methodology of previous studies in this area and to the need for a comprehensive clinico-pathological longitudinal study.
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We evaluated the efficacy of a computer-assisted continuous infusion device (CACI) using a two-drug infusion of midazolam and sufentanil as an anesthetic technique during pediatric cardiac surgery. Seventeen pediatric patients were anesthetized with CACI using age-appropriate pharmacokinetic models for administering sufentanil and midazolam. Predicted CACI plasma concentrations were correlated with assayed plasma drug concentrations at eight predefined intervals. The accuracy was assessed using median absolute prediction error. We found that plasma levels predicted by CACI provided a reasonable approximation of measured plasma concentrations for both drugs. The median absolute prediction error for sufentanil during cardiopulmonary bypass was compared with measurements made off of cardiopulmonary bypass (both pre and post cardiopulmonary bypass) and were 49% and 32%, respectively, and for midazolam 44% and 32%, respectively. We conclude that (a) current kinetic models provide a reasonable estimate of plasma drug concentrations, and (b) the ease of administration and targeted plasma level provided by the CACI system is an alternative to inhalation anesthesia using calibrated vaporizers.
To study the effect of deep hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism and oxygenation, we measured the cerebral metabolic rate for oxygen (CMRO2) and assessed brain oxygenation by near infrared spectroscopy before, during, and after hypothermic bypass in 15 pediatric patients. One group underwent repair during deep hypothermic bypass (18 degrees C) with continuous flow (n = 9); the second group underwent deep hypothermic bypass with total circulatory arrest (n = 6). In the continuous-flow group, CMRO2 returned to control during rewarming and after cardiopulmonary bypass, as did oxyhemoglobin and deoxyhemoglobin in brain tissue. In the total circulatory arrest group, the oxyhemoglobin and the oxidation state of cytochrome aa3 oxidase decreased significantly during circulatory arrest. After cardiopulmonary bypass, the cytochrome oxidation state and the CMRO2 were significantly lower than control measurements, and brain tissue deoxyhemoglobin was elevated. Results of this study indicate that intracellular brain oxygenation decreases significantly during circulatory arrest and remains impaired after rewarming and cardiopulmonary bypass despite normalization of oxygen availability.
Cardiopulmonary bypass management in neonates, infants, and children often requires the use of deep hypothermia at 18 degrees C with occasional periods of circulatory arrest and represents marked physiologic extremes of temperature and perfusion. The safety of these techniques is largely dependent on the reduction of metabolism, particularly cerebral metabolism. We studied the effect of hypothermia on cerebral metabolism during cardiac surgery and quantified the changes. Cerebral metabolism was measured before, during, and after hypothermic cardiopulmonary bypass in 46 pediatric patients, aged 1 day to 14 years. Patients were grouped on the basis of the different bypass techniques commonly used in children: group A--moderate hypothermic bypass at 28 degrees C; group B--deep hypothermic bypass at 18 degrees to 20 degrees C with maintenance of continuous flow; and group C--deep hypothermic circulatory arrest at 18 degrees C. Cerebral metabolism significantly decreased under hypothermic conditions in all groups compared with control levels at normothermia, the data demonstrating an exponential relationship between temperature and cerebral metabolism and an average temperature coefficient of 3.65. There was no significant difference in the rate of metabolism reduction (temperature coefficient) in patients cooled to 28 degrees and 18 degrees C. From these data we were able to derive an equation that numerically expresses a hypothermic metabolic index, which quantitates duration of brain protection provided by reduction of cerebral metabolism owing to hypothermic bypass over any temperature range. Based on this index, patients cooled to 28 degrees C have a predicted ischemic tolerance of 11 to 19 minutes. The predicted duration that the brain can tolerate ischemia ("safe" period of deep hypothermic circulatory arrest) in patients cooled to 18 degrees C, based on our metabolic index, is 39 to 65 minutes, similar to the safe period of deep hypothermic circulatory arrest known to be tolerated clinically. In groups A and B (no circulatory arrest), cerebral metabolism returned to control in the rewarming phase of bypass and after bypass. In group C (circulatory arrest), cerebral metabolism and oxygen extraction remained significantly reduced during rewarming and after bypass, suggesting disordered cerebral metabolism and oxygen utilization after deep hypothermic circulatory arrest. The results of this study suggest that cerebral metabolism is exponentially related to temperature during hypothermic bypass with a temperature coefficient of 3.65 in neonates infants and children. Deep hypothermic circulatory arrest changes cerebral metabolism and blood flow after the arrest period despite adequate hypothermic suppression of metabolism.