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Biomedical subjects

D S Smith

Publications and source records attributed to D S Smith.

At least 163 records · Page 9Linked to original sources

The attachment of collagenous ligament to stereom in primary spines of the sea-urchin, Eucidaris tribuloides.

The similar proximal and distal attachments to the stereom of primary spine ligament in the echinoid Eucidaris tribuloides are described, from thin sections and SEM studies on frozen and fractured spine articulations and ligaments from decalcified material. The orthogonal structure of the general stereom is modified on the attachment zones where bundles of collagen cylinders enter approximately hexagonally arranged channels. Straps of collagen extend in parallel series between adjacent bundles via regularly placed ports and collagen loops rather than non-striated 'tendons' pass over skeletal trabeculae. The regular pattern of collagen straps is most evident on the proximal and distal attachment zones. Mechanical features of the non-adhesive mode of attachment are considered, together with similarities and differences between insertion of muscle cells and mutable collagenous tissue (ligament) in echinoderms.

Animals↗

The effect of oral midazolam on anxiety of preschool children during laceration repair.

Preschool age children often experience marked anxiety and physical pain during laceration repair. Locally infiltrated anesthetics or topical tetracaine, adrenaline, and cocaine (TAC) usually control the physical pain but have little or no effect on anxiety. Midazolam is a short-acting benzodiazepine with anxiolytic, hypnotic, and antegrade amnestic effects. In a double-blind, randomized clinical trial, we evaluated the efficacy of midazolam in alleviating anxiety during laceration repair in children less than 6 years old. On admission to the emergency department, anxiety level was determined on a scale of 1 to 4 based on a predetermined behavior criteria. Patients with high anxiety level (3 or 4) received a single oral dose of either midazolam (0.2 mg/kg) or placebo. The anxiolytic effect of midazolam was considered adequate if the anxiety level decreased two or more points (from 4 to less than or equal to 2 or from 3 to 1) during laceration repair. In the midazolam group (30), 70% of the children had a two-point or more decrease in anxiety level compared with 12% in the placebo group (25) (P less than .0001). No respiratory depression or other complications were noted in the midazolam group. We conclude that a single oral dose of midazolam (0.2 mg/kg) is a safe and effective treatment for alleviating anxiety in children less than 6 years old during laceration repair in the ED.

Administration, Oral↗

Experimental brain ischaemia: assessment of injury by magnetic resonance spectroscopy and histology.

Phosphorus magnetic resonance spectroscopy (31P-MRS) was made to measure changes in brain high energy phosphate compounds, adenosine triphosphate (ATP) and phosphocreatine (PCr), inorganic phosphorus (Pi) and intracellular pH (pHi) during a prolonged period of incomplete brain ischaemia produced, in anaesthetized dogs, by bilateral carotid occlusion together with haemorrhagic hypotension for intervals of up to 300 min. Mean arterial blood pressure (MABP) was lowered in a stepwise fashion, until signs of metabolic decompensation (as estimated by MRS) occurred. At that point MABP was varied against further evidence of metabolic decompensation in an attempt to maintain a more constant degree of insult. At the end of the ischaemic period MABP was restored and the animals observed during a 3 h recovery period. At the end of the recovery period the brains were perfusion-fixed for histological examination. A semi-quantitative method of histological evaluation was used to determine the degree of histological damage. This permitted assignment of an 'ischaemic score' to the tissue sampled from each animal. Comparisons were then made between the magnitude of this 'ischaemic score' and the changes in metabolic and physiological variables (ATP, PCr, pHi and MABP) as well as an estimator of phosphorylation potential (PCr/Pi), which were all measured during the ischaemic insult. Histological examination showed a wide variety of neuronal alterations, including dark and pale type injury, which correlated directly with the metabolic derangements brought about by ischaemia. The degree of damage determined from this histological assessment correlated best with the duration and degree of change in PCr/Pi, supporting the use of this ratio as a critical index of cellular energy state. In particular there was a strong linear relationship between the degree of leucocyte recruitment and changes in PCr/Pi. To summarize, metabolic changes, determined by MRS, correlate with the degree of histological damage, and in turn, the classical descriptions of acute ischaemic neuronal injury appear to be validated by MRS determinations of metabolic changes during ischaemia.

Adenosine Triphosphate↗

Distinguishing cerebrospinal fluid abnormalities in children with bacterial meningitis and traumatic lumbar puncture.

The characteristics of cerebrospinal fluid (CSF) associated with traumatic lumbar puncture, defined as CSF red blood cell (RBC) count greater than 1000/mm3, were reviewed in 92 previously healthy children greater than 1 month of age; 30 had bacterial meningitis and 62 had negative CSF cultures. The purpose was to distinguish CSF profiles of the two groups despite contamination with peripheral blood elements. In each case, white blood cell (WBC) counts were observed (O) and compared with those predicted (P), calculated as P = CSF RBC X (blood WBC/blood RBC). Comparison of O:P ratios revealed that all 30 patients with bacterial meningitis had ratios greater than or equal to 1, 28 (93%) had ratios greater than 10, and 24 (80%) had ratios greater than 100; by contrast, only 2 patients (3%) with culture-negative CSF had ratios greater than 10, 21 (34%) had ratios of 1-10, and 39 (63%) had ratios less than 1. Significant differences were observed in the rate of O:P ratio greater than or equal to 1 (100% vs. 32%), CSF differential cell count predominance of polymorphonuclear leukocytes (97% vs. 11%), hypoglycorrhachia (73% vs. 3%), and positive Gram's-stained smear for pathologic organisms (80% vs. 0) in those with and without bacterial meningitis, respectively (P less than .0001). Thus, in children greater than 1 month of age, CSF abnormalities associated with bacterial meningitis are rarely obscured by blood contamination from traumatic lumbar puncture.

Cerebrospinal Fluid↗

Reperfusion hyperoxia in brain after circulatory arrest in humans.

Changes in the electroencephalogram (EEG), mean arterial blood pressure (MABP), and hemoglobin saturation in brain vasculature of lightly anesthetized normothermic humans undergoing induced circulatory arrest for implantation of an automatic internal cardioverting defibrillator were studied. EEG was measured using a four-channel bipolar montage and hemoglobin saturation was measured transcranially using reflectance spectroscopy at 760 nm with an isosbestic reference at 800 nm. Hemoglobin saturation of blood in the quadriceps muscle was also measured. Thirty-two episodes of hypotension due to ventricular fibrillation were studied along with 31 episodes of hypotension related to ventricular tachycardia and rapid ventricular pacing. In a typical fibrillatory event there was a decrease in MABP followed almost immediately by changes in hemoglobin saturation of blood in the brain vasculature. The first changes in EEG were detected an average of 6.5 s (P less than 0.001, paired t test) after the beginning of change of brain vascular hemoglobin. In some cases changes in hemoglobin saturation could be detected without changes in EEG. Desaturation curves from muscle and brain were significantly different, suggesting that the brain probe was measuring hemoglobin change in a rapidly metabolizing volume of tissue that was dissimilar to the skin, muscle, and bone monitored by the probe over the quadriceps muscle. Examination of the 32 episodes of circulatory arrest revealed a marked response that began immediately with recirculation characterized by an increase of the hemoglobin saturation signal from brain vasculature to above baseline as the duration of circulatory arrest exceeded 37 s, this response is termed reperfusion hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Reflections on the anesthesia-neurosurgical alliance.

This is an uncommon article for a modern scientific journal in that it contains no data, it is written in the first person, and it recounts only the personal experiences of a clinical neurosurgeon about the evolution of neurosurgery, anesthesiology, and neuroanesthesiology in Philadelphia from 1939 to 1988, when the surgeon retired from the operating room. The surgeon, Fred Murtagh, practiced neurosurgery during an extraordinarily formative time for American medicine and neurosurgery. He was on the faculty of Temple University for many years and currently is Emeritus Professor of Neurosurgery at the University of Pennsylvania. His observations are from the point of view of a man who has been in the operating room continuously since the early 1940s grappling with the practical problems confronting the neurosurgeon. In addition, he is a highly observant individual and considered by many to be an extraordinary teacher. With respect to the genesis of this article, the neuroanesthesia group at the University of Pennsylvania invited Dr. Murtagh to one of their monthly meetings. A tape recorder was placed in front of him and we were privileged to listen to 2 h of reminiscence about his career and relationships between anesthesiologists and neurosurgeons. Over a several year period, Fred Murtagh and D. S. Smith extracted that tape and wrote the following article. It is my belief that this article, despite its unorthodox format, contains observations of import to clinicians in general and to those who practice the subspecialty of neurosurgical anesthesia.

Journal Article↗

Characterization of a nerve growth factor-stimulated protein kinase in PC12 cells which phosphorylates microtubule-associated protein 2 and pp250.

Treatment of PC12 cells with nerve growth factor (NGF) resulted in the rapid, but transient, activation of a protein kinase which specifically phosphorylated an endogenous 250-kDa cytoskeletal protein (pp250). We report that the microtubule-associated protein, MAP2, is an alternative substrate for the NGF-activated kinase. NGF treatment maximally activated the kinase within 5 min; however, the activity declined with longer exposure to NGF. The enzyme was localized predominantly in microsomal and soluble fractions and phosphorylated MAP2 on serine and threonine residues. The soluble enzyme was fractionated by DEAE chromatography and gel filtration and had an apparent Mr of 45,000. The enzyme was purified to near homogeneity by chromatofocussing and had a pI of 4.9. Kinetic analysis revealed that NGF treatment caused a sevenfold increase in Vmax for MAP2. The Km with respect to the MAP2 substrate was approximately 50 nM and was not altered by NGF treatment. A novel feature of the NGF-stimulated enzyme was its sharp dependence on Mn2+ concentration. The active enzyme is likely to be phosphorylated, because inclusion of phosphatase inhibitors was required for recovery of optimal activity and the activity was lost on treatment of the enzyme with alkaline phosphatase. Histones, tubulin, casein, bovine serum albumin, and the ribosomal subunit protein S-6 were not phosphorylated by this enzyme. The NGF-stimulated kinase was distinct from A kinase, C kinase, or other NGF-stimulated kinases. The rapid and transient activation of the protein kinase upon NGF treatment suggests that the enzyme may play a role in signal transduction in PC12 cells.

Adrenal Gland Neoplasms↗

Oxidative phosphorylation system during steady-state hypoxia in the dog brain.

The relationship between biochemical and physiological responses and tissue O2 during hypoxia was investigated in vivo in the dog brain by 31P nuclear magnetic resonance (NMR) spectroscopy. Our findings demonstrate how ATP synthesis in the brain can be maintained during hypoxia because of compensatory changes in NADH, ADP, and Pi. Eleven beagle dogs were anesthetized and mechanically ventilated, and a steady-state graded hypoxia was induced by decreasing the fraction of inspired O2 (FIO2) stepwise at 20-min intervals. Biochemical metabolites were measured using 31P-NMR and fluorescence spectroscopy. When sagittal sinus O2 partial pressure (PVO2) had decreased to 15 Torr, NADH increased by 30%, Pi increased by 50%, and phosphocreatine (PCr) decreased by 20%. In contrast, ATP remained constant. There was a 10% increase in ADP in dogs that maintained a steady temperature, but ADP decreased by as much as 30% in dogs in which body temperature decreased with the falling PVO2. PCr/Pi was logarithmically related to the phosphorylation potential during steady-state hypoxia. Compensation for the O2 lack is attributed to increases in ADP, Pi, and NADH as a result of the reciprocal relationship of the Michaelis-Menten equation. If the Michaelis-Menten constants (Km) of ADP, Pi, and O2 are the same as determined in vitro in mitochondria, the minimum brain cytosolic O2 capable of maintaining a steady-state ATP is near its Km (0.1 Torr) at a PVO2 of 7.5 Torr. At this critical O2 level, PCr/Pi is 0.9, intracellular pH is 6.75, phosphorylation potential is 38.5 mM-1, and the calculated maximum velocity of ATP formation by oxidative phosphorylation is 55% of normal.

Adenosine Diphosphate↗

Cerebral energy metabolism and oxygen state during hypoxia in neonate and adult dogs.

The relationship between a noninvasive determination of relative oxygen saturation of Hb circulating in brain tissue (StO2) and energy metabolism was investigated with respect to age [dogs in three age groups (0 to 6-d-old, 7- to 21-d-old, and adults)] and to severity of brain hypoxia using double beam spectroscopy of Hb deoxygenation and nuclear magnetic resonance spectroscopy of energy metabolism. The in vivo oxy-Hb dissociation was determined from the relationship between StO2 curve in the adult dog brain and sagittal sinus oxygen partial pressure during graded hypoxemia and found to be sigmoidal with an oxygen dissociation constant of 26.6 mm Hg. This agreed with an in vitro determination for oxygen dissociation constant of 28.2 mm Hg in adult dog red cells. The arterial oxygen pressure at which brain StO2 was reduced by 50% was shifted toward the right with increasing age (22.2, 33.8, and 40.8 mm Hg, respectively). This correlated with an in vitro oxygen dissociation constant of red cell Hb of 17.0, 22.3, and 28.2 mm Hg in the three age groups, respectively. The phosphocreatine-inorganic phosphate ratio (PCr/Pi) was used to relate changes in cellular energy metabolism during hypoxia with changes in StO2. There was no change in PCr/Pi when StO2 had decreased to 50% of the control value. However, when the brain StO2 had decreased to between 7 and 15%, a reduction of PCr/Pi to 50% of the normoxic value occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Elevated liver transaminase levels in children with blunt abdominal trauma: a predictor of liver injury.

The medical records of 43 hemodynamically stable children with elevated serum transaminase levels (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) who underwent abdominal computed tomographic (CT) scan for blunt abdominal trauma were reviewed. Nineteen patients (44.2%) had AST levels greater than 450 IU/L and ALT levels greater than 250 IU/L, and 17 of these 19 patients had hepatic injury identified on abdominal CT scan. Of the 43 patients, 25 (58.1%) had AST and ALT levels of less than 450 IU/L and 250 IU/L, respectively, and none of these patients had evidence of hepatic injury on CT scan. Elevated serum transaminase levels (AST greater than 450 IU/L and ALT greater than 250 IU/L) identified all of the patients with hepatic injury visible on abdominal CT scan. The sensitivity and specificity of elevated serum transaminase levels were 100% and 92.3%, respectively, for predicting hepatic injury. It is recommended that hemodynamically stable pediatric patients with blunt abdominal trauma and AST levels greater than 450 IU/L and/or ALT levels greater than 250 IU/L undergo abdominal CT scan to determine the presence and extent of hepatic injury. Children with serum transaminase levels below these values are at decreased risk of liver injury.

Abdominal Injuries↗

Outcome studies in stroke rehabilitation. The South Australian Stroke Study.

Like most longitudinal studies, this review has posed more questions than answers. It has, however, enabled us to make the following important statements about stroke rehabilitation outcome: 1. The determinants of outcome depend to a great extent on factors other than the nature and extent of the impairment. It seems that the patient's subjective perception of himself as either well or ill may be a major determinant of subsequent behavior in terms of functional dependence (disability). 2. What people are able to do at 6 months or more after the completion of formal rehabilitation is the real measure of its effectiveness. 3. An index of "quality of life" based on, for example, the concepts of the Frenchay index is needed to evaluate the role and function of people in community living.

Activities of Daily Living↗

Comparison of three different activation methods for coupling antibodies to magnetisable cellulose particles.

The periodate and 1,1'-carbonyldiimidazole activation methods were compared with the cyanogen bromide procedure for coupling antibodies to magnetisable cellulose/iron oxide solid-phase particles. Fluoroimmunoassays for quinine, primaquine, normetanephrine and cannabinoids were employed to assess the binding properties of such coupled solid phases. The cyanogen bromide and 1,1'-carbonyldiimidazole methods gave similar products in most cases, while the specific binding capacity of periodate coupled particles was between two and five times lower. Nevertheless, comparable standard curves could be obtained with solid phase coupled by each method. The periodate and 1,1'-carbonyldiimidazole methods are acceptable alternatives, notably for laboratories lacking the facility to handle the toxic cyanogen bromide.

Animals↗

Clinical indicators of intracranial lesion on computed tomographic scan in children with parietal skull fracture.

We conducted a review of 98 cases of pediatric traumatic parietal skull fracture in which computed tomographic (CT) scans of the head were obtained during a seven-year period. There were 69 instances of an associated intracranial lesion identified in 47 children, including parenchymal injury (23), epidural hematoma (17), subdural hematoma (11), cerebral edema (ten), and subarachnoid hemorrhage (eight). Compared with 51 other children with parietal skull fracture and normal CT scans, the clinical characteristics significantly associated with the presence of an intracranial lesion were symptoms of neurologic dysfunction (loss or altered level of consciousness and/or seizure activity), neurologic compromise on examination (altered level of consciousness and/or focal deficit), or complicated skull fracture (bilateral, diastatic, and/or depressed). Of the 47 children with an intracranial lesion on CT scan, 44 had at least one of these significant clinical characteristics (sensitivity, 93%; specificity, 50%; positive-predictive value, 62%; and negative-predictive value, 96%). Children who sustain traumatic parietal skull fracture commonly experience associated intracranial injury. Those with evidence of neurologic deficit or complicated skull fracture are at particularly high risk, and should receive cranial CT scan evaluation.

Brain Injuries↗

Augmentation of acetaminophen analgesia by the antihistamine phenyltoloxamine.

A double-blind, placebo-controlled, parallel-group study was performed to compare the analgesic activity of the combination of 650 mg acetaminophen plus 60 mg phenyltoloxamine citrate with that of 650 mg acetaminophen alone. Two hundred female inpatients who had severe pain associated with a recent episiotomy procedure were randomly assigned to receive a single dose of one of the two active treatments or a placebo. Analgesia was assessed over a 6-hour period. Treatments were compared on the basis of standard subjective scales for pain intensity and relief, a number of derived variables based on these data and two global measures. For essentially all measures, the two active treatments were significantly superior to the placebo control. The combination was significantly superior to acetaminophen alone for all analgesic measures including SPID, TOTAL, and global ratings. The results of this study demonstrate that 60 mg phenyltoloxamine produces significant augmentation of the analgesic activity of 650 mg acetaminophen in postepisiotomy pain.

Acetaminophen↗

Serological cross-reactions between crab saxitoxin-induced protein and paralytic shellfish poison-contaminated shellfish.

A polyclonal antiserum generated against crab saxitoxin-induced protein was tested against paralytic shellfish poison (PSP)-contaminated crabs and shellfish. Antibody-reactive proteins in PSP-contaminated bivalve mollusc extracts were localized using SDS-PAGE and immunoblotting. PSP-contaminated clams and oysters possessed a higher degree of immunoreactivity to the saxitoxin-induced protein found in PSP-resistant crabs than their respective non-contaminated controls.

Animals↗

Stress reaction of the pars interarticularis leading to spondylolysis. A cause of adolescent low back pain.

We report an adolescent with progression from a stress reaction of the pars interarticularis without radiographic findings, to radiographic fracture and spondylolysis, illustrating the evolution of spondylolysis in an athletically active early adolescent. Gymnastics, diving, pole vaulting, or collision/contact sports such as football, soccer, hockey, and la crosse are common sports with a disproportional frequency of spondylolysis. Rotational forces around the long axis of the spine with load bearing hyperextension are important in etiology. Low back pain in the active adolescent or preadolescent, even with normal oblique lumbar radiographs, may have a treatable origin--stress reaction or fracture of a lumbar pars interarticularis. Screening evaluation is the standing one-leg extension maneuver. Liberal use of nuclear studies for minimal back symptoms in athletic adolescents may help exclude this relatively common, potentially treatable condition, spondylolysis of the pars interarticularis.

Athletic Injuries↗