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Biomedical subjects

J A Gilbert

Publications and source records attributed to J A Gilbert.

At least 55 records · Page 3Linked to original sources
PubMed1994

Plantar flexion injuries of the ankle. An experimental study.

A biomechanical study was designed to test the hypothesis that isolated plantar flexion of the ankle can produce avulsion fractures of the medial and lateral malleoli without fracture of the posterior articular surface of the tibia. Cadaver specimens were subjected to a standard plantar flexion force in the Burstein torsion testing machine. They showed the following typical patterns of injury in 26 of 32 ankles: (1) avulsion of the anterior ankle capsule; (2) a short oblique distal fibular fracture or fibular avulsion of the anterior talofibular ligament; and (3) an oblique medial malleolar fracture or a tear of the deep fibers of the deltoid ligament. Of particular interest was the direction and location of the medial malleolar fracture. This pattern, previously identified with supination-external rotation injuries, was also produced by isolated plantar flexion, which may be attributed to the anatomical attachments of the deltoid ligament on the medial malleolus, as well as the position of the foot and direction of the injuring force.

Adult↗
PubMed1993

Enantiospecific syntheses of alpha-(fluoromethyl)tryptophan analogues: interactions with tryptophan hydroxylase and aromatic L-amino acid decarboxylase.

alpha-Fluoromethyl amino acids are enzyme-activated irreversible inhibitors of amino acid decarboxylases. Aromatic L-amino acid decarboxylase (AADC) is the enzyme responsible for the final step in the biosynthesis of both dopamine and serotonin via decarboxylation of L-dopa and 5-hydroxy-L-tryptophan, respectively. Our goal is to utilize antagonists of the serotonin-producing enzymes (tryptophan hydroxylase and AADC) as the basis for a chemotherapeutic approach to the treatment of carcinoid tumors, a rare tumor type characterized by the overproduction of serotonin. We report here an enantiospecific synthesis of alpha(S)-(fluoromethyl)tryptophan [(S)-11a] and alpha(S)-(fluoromethyl)-5-hydroxytryptophan [(S)-11b], as well as the (R)-enantiomers, based upon recent methodology involving the face-selective alkylation of cyclic tryptophan tautomers. Our synthetic route provided both enantiomers of 11a and 11b with greater than 97% enantiomeric purity based upon evaluation of the NMR spectra of their Mosher's acid derivatives. (S)-11a was evaluated as a substrate for P815 tryptophan hydroxylase and determined to have an apparent Km of 4.31 +/- 1.07 mM, essentially half the value previously reported for the racemic mixture of 11a with rat brain stem tryptophan hydroxylase. (R)-11a was not a substrate for P815 tryptophan hydroxylase. (S)-11b was evaluated as an enzyme-activated irreversible inhibitor of murine liver AADC and determined to have a KI of 24.3 +/- 3.01 microM and a k2 of 2.26 +/- 0.44 min-1. (R)-11b was not an inhibitor of murine liver AADC.

5-Hydroxytryptophan↗
PubMed1993

Failure to find increased TEM at rest and during exercise in aerobically trained and resistance trained subjects.

This study examined the metabolic response to a 763-kcal mixed meal at rest and during 30 min of exercise at 50% maximal oxygen consumption (VO2max) in 8 aerobically trained (AT), 8 resistance trained (RT), and 8 untrained (UT) subjects. Oxygen consumption (VO2) was measured minute by minute during 30 min of exercise by indirect calorimetry on 2 nonconsecutive days (postabsorptive exercise, PA; and postprandial exercise, PP). Total VO2 consumed and total caloric expenditure during the PA and PP conditions were similar for the three groups, indicating that prior food intake did not affect energy expenditure during exercise. Consequently, TEM during exercise did not differ significantly among the groups. Respiratory exchange ratio (R) differed significantly only during the PA condition, with the AT group exhibiting significantly lower R values compared to the RT group, and significantly lower R values compared to the UT group. These data suggest that the consumption of a meal 30 min prior to exercise does not increase TEM during exercise in AT, RT, and UT subjects.

Adolescent↗
PubMed1993

Disseminated intravascular coagulation.

DIC is a consumptive thrombohemorrhagic life-threatening disorder resulting in multiple coagulation, platelet, and fibrinolytic abnormalities. The causes are legion. Diagnosis is both clinical and laboratory based. Therapy remains controversial and should be based on clinical presentation, although some clinical syndromes may allow for specific treatment. Despite aggressive therapy and research, mortality remains high. Recognition of the patient at risk as well as treatment of the underlying disorder is the critical role for the emergency physician.

Disseminated Intravascular Coagulation↗
PubMed1992

Pyridoxine-5'-beta-D-glucoside affects the metabolic utilization of pyridoxine in rats.

A major form of vitamin B-6 in plant-derived foods is pyridoxine-5'-beta-D-glucoside. Previous studies have shown that pyridoxine-5'-beta-D-glucoside is poorly available as a source of vitamin B-6 in rats and is partially utilized in humans. This research was conducted to determine whether unlabeled pyridoxine-5'-beta-D-glucoside affects the metabolic utilization of simultaneously administered isotopically labeled pyridoxine in rats. Three groups of rats (n = 6) were administered a single oral dose of 0, 36 or 72 nmol of unlabeled pyridoxine-5'-beta-D-glucoside along with 166.5 MBq (240 nmol) of [14C]pyridoxine. Twenty-four hours after administration of the dose the rats were killed, and the isotopic distribution of vitamin B-6 metabolites in liver and urine was determined. Urinary 14C and hepatic 14C-labeled pyridoxine phosphate and pyridoxal phosphate were directly related to pyridoxine-5'-beta-D-glucoside dose. Hepatic 14C, 14C-labeled pyridoxal, pyridoxine and pyridoxamine, and the concentration of urinary [14C]4-pyridoxic acid, relative total urinary 14C, were inversely proportional to the dose of pyridoxine-5'-beta-D-glucoside. These results provide evidence that pyridoxine-5'-beta-D-glucoside quantitatively alters the metabolism and in vivo retention of [14C]pyridoxine and that pyridoxine-5'-beta-D-glucoside may retard the utilization of nonglycosylated forms of vitamin B-6.

Administration, Oral↗
PubMed1991

Structure-antinociceptive activity of neurotensin and some novel analogues in the periaqueductal gray region of the brainstem.

Neurotensin, an endogenous tridecapeptide, produces a potent, naloxone-insensitive antinociceptive response when it is microinjected into the periaqueductal gray region of the rat brainstem. In the present study, the ED50 for neurotensin in inducing antinociception was 1.5 nmol, two times more potent than morphine. We sought to find whether neurotensin's antinociceptive effects were mediated by the same receptor that mediates its other functions. We found that the structure-activity relationship of neurotensin-induced antinociception was different from that required for the stimulation of intracellular cyclic GMP production in neuroblastoma clone N1E-115 and the binding to N1E-115 cells, human brain tissue, or rat periaqueductal gray. These data suggest there exists a subtype of neurotensin receptors in neural tissue that mediates its antinociceptive actions.

Analgesics↗
PubMed1991

Patient use of removable partial dentures: two- and four-year telephone interviews.

Two telephone surveys requested patients to report on their use of removable partial dentures that were constructed by undergraduate dental students. In the first survey, of the 431 patients called, 290 were contacted and interviewed 24 to 33 months after their removable partial denture(s) had been inserted. Of these, 258 patients reported using their prostheses and 238 had no apparent problems. In the second survey, the 238 trouble-free removable partial denture wearers from the first survey were called and 169 were contacted and interviewed 48 to 57 months after the removable partial dentures had been inserted. Of these, 156 reported still using their prosthesis and 152 had no apparent problems. These data are provided, along with some interpretive caveats, for dentists to use in discussing treatment options with patients.

Consumer Behavior↗
PubMed1991

Lower thermic effect of a meal post-exercise in aerobically trained and resistance-trained subjects.

Despite the abundance of literature concerning the thermic effect of a test meal (TEM) at rest in trained and untrained subjects, there is little information available concerning the TEM post-exercise. Therefore, it was the purpose of this study to examine the metabolic response to a 763-kcal meal prior to 30 min of exercise at 50% VO2max, in aerobically trained (AT, N = 8), resistance-trained (RT, N = 8), and untrained (UT, N = 8) subjects. Mean (+/- SEM) VO2max was 60.7 +/- 2.3 ml.kg-1.min-1, 52.9 +/- 2.2 ml.kg-1.min-1 and 51.1 +/- 2.2 ml.kg-1.min-1, for the AT, RT, and UT groups, respectively. Mean (+/- SEM) percent fat was 13.7 +/- 1.2, 12.7 +/- 1.9, and 16.9 +/- 1.4 for the AT, RT, and UT groups, respectively. Post-exercise VO2 was measured by indirect calorimetry every half hour, on two nonconsecutive days (post-absorptive (PA) post-exercise and post-prandial (PP) post-exercise) for 3 h. The total TEM (post-exercise PP VO2 minus post-exercise PA VO2) was 4.86 +/- 1.62, 5.22 +/- 1.80, and 9.36 +/- 5.08 I for the AT, RT, and UT groups, respectively. The TEM post-exercise was significantly lower (P less than 0.05) for the AT and RT groups compared with the UT group. Respiratory exchange ratio (R) differed significantly only during the PA post-exercise condition, with the AT group exhibiting significantly lower (P less than 0.01) values compared with the RT and UT groups. PA post-exercise R for the RT group was not significantly different (P = 0.09) from the UT group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Internal fixation of femoral neck fractures. A comparative biomechanical study of Knowles pins and 6.5-mm cancellous screws.

In a comparative biomechanical study of the stability of experimentally produced femoral neck fractures fixed with Knowles pins or with 6.5-mm cancellous screws, 12 matched pairs of anatomic specimen femurs were divided into four groups of standardized osteotomies. One member of each matched pair was fixed with three or four 6.5-mm cancellous screws, whereas the other member was fixed with the same number of Knowles pins. Mechanical testing was performed on an Instron testing machine. There was no statistically significant difference in maximum load to failure or in fixed stiffness between the two methods of fixation. When examining maximum load to failure, three of either device provided fixation equivalent to four. Although there was a difference in absolute fixed stiffness between specimens fixed with three Knowles pins compared to four, when stiffness was expressed as a percentage of intact stiffness, there was no difference between any fixation group. From an analysis of the observed modes of failure and from calculations of the flexural rigidity provided by the devices, it is proposed that the quality of the trabecular bone of the femoral neck is a major factor in the experimental fixation of femoral neck fractures.

Biomechanical Phenomena↗
PubMed1990

Biomechanics of Ender rods, compression screw, and Zickel nail in the fixation of stable subtrochanteric femur osteotomies.

Compression screws, Ender rods, and Zickel nails were evaluated mechanically to determine their resulting stability in the fixation of experimental subtrochanteric femur osteotomies. Twenty-five pairs of human cadaver femurs were used. Experimental osteotomies were created and a random member of each pair was fixed with a compression screw (AMBI system, Richards Mfg. Co). The other member was fixed with either Ender rods or a Zickel nail. The specimens were oriented in a direction to approximate the in vivo position of maximum resultant force on the femur and then subjected to a single progressive load to failure on a materials testing machine. The ultimate strength of fixation with the compression screw was approximately 4.6 times greater than with the Ender rods and 1.8 times greater than that with the Zickel nail. Ender rods and Zickel nails failed primarily in external rotation, whereas the compression screw failed by bone fracturing and varus bending.

Adult↗
PubMed1989

Neurotensin(8-13): comparison of novel analogs for stimulation of cyclic GMP formation in neuroblastoma clone N1E-115 and receptor binding to human brain and intact N1E-115 cells.

Neurotensin(8-13), the carboxyl-terminal portion of neurotensin, is 4-50 times more potent than native neurotensin in binding to intact neuroblastoma N1E-115 cells and human brain tissue and in stimulation of intracellular cyclic GMP production and inositol phospholipid hydrolysis in clone N1E-115 (Gilbert JA and Richelson E, Eur J Pharmacol 99: 245-246, 1984; Gilbert JA et al., Biochem Pharmacol 35: 391-397, 1986; Kanba KS et al., J Neurochem 46: 946-952, 1986; and Kanba KS and Richelson E, Biochem Pharmacol 36: 869-874, 1987). A series of novel analogs of neurotensin (8-13) was synthesized, and a structure-activity study was done comparing the abilities of these peptides to stimulate intracellular cyclic GMP production in intact neuroblastoma clone N1E-115 and to inhibit the binding of [3H]neurotensin to these cells and to membranal preparations from human brain. A direct correlation was found for each analog between its EC50 for biochemical activity and its KD for binding ability in studies with clone N1E-115. Furthermore, a strong correlation existed for each peptide between its KD for binding to neurotensin receptors on these cells and its KD for binding to neurotensin receptors in human brain tissue. In this study, the residues that were important to the biochemical and binding activities of neurotensin (8-13) proved to be identical to the amino acids that are necessary for the functional integrity of native neurotensin (Gilbert JA et al., Biochem Pharmacol 35: 391-397, 1986.

Brain↗
PubMed1989

The effect of external fixation stiffness on early healing of transverse osteotomies.

The effect of bending stiffness of external fixators on the early healing of transverse tibial osteotomies was studied in a canine model to determine whether there is a particular range of fixation stiffness where healing is poor. Five unilateral fixators with different stiffnesses were developed and employed along with a dynamic compression plate to fix experimental osteotomies of dog tibias and the contralateral intact tibias served as controls. The six experimental fixation devices were: plate (P), stainless steel sidebar fixator (SS), stiff aluminum sidebar fixator (SA), intermediate aluminum sidebar fixator (IA), flexible aluminum sidebar fixator (FA), and Delrin sidebar fixator (D). Compared with human tibial fixation methods, the fixators ranged from a rigidity greater than a plate on a human tibia to a flexibility similar to a plaster cast on a human lower leg. Sixty-four adult male mongrel dogs (29 +/- 3 kg) underwent surgery and 52 completed the 9-week study, leaving 7 to 10 dogs in each experimental group (P = 8, SS = 7, SA = 9, IA = 9, FA = 10, D = 9). After the 9-week survival period the experimental tibias were radiographed and callus area was digitized. Both the experimental and control tibias were then tested to failure in four-point bending, and failure moment, stiffness, and energy to failure were determined. Of the 52 osteotomies, only four developed nonunions: 3 of 10 in the FA group and 1 of 7 in the SS group. Using analysis of variance, no statistical differences were detected in failure force, stiffness, or energy to failure as a function of fixator groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

A study of the mechanical strength of long bone defects treated with various bone autograft substitutes: an experimental investigation in the rabbit.

This study was designed to determine which of several bone grafting materials would be the most efficacious substitute for autogenous bone graft in the treatment of segmental long bone defects. The experimental model was a 1-cm defect in the rabbit ulna. The control group had nothing implanted in the defect. The six grafts tested were: (a) autogenous iliac crest bone, (b) autogenous cortical bone (ulna), (c) hydroxylapatite, (d) hydroxylapatite-demineralized bone matrix (allograft) composite graft, (e) freeze-dried bone (allograft), and (f) demineralized bone matrix (allograft). At 6 weeks postoperatively, the ulnas were harvested, examined radiographically, and tested mechanically in torsion. The radiographic examination proved to be of little value because some materials were radiodense at the time of implantation. The rates (percentage) of union, torques at failure, and energy to failure values were statistically significantly higher than control for all groups except hydroxylapatite. We concluded that demineralized bone matrix and hydroxylapatite-demineralized bone matrix composite graft compare favorably with cortical replacement (autograft) in mechanical strength and rate of union and therefore may be satisfactory substitutes for bone grafting. Freeze-dried bone did not appear to be as satisfactory because of its low mean energy to failure, but statistical analysis failed to confirm this opinion. Hydroxylapatite graft, when used alone, does not appear to be a suitable material for grafting segmental bone defects.

Animals↗
PubMed1989

In vitro initial fixation of porous-coated acetabular total hip components. A biomechanical comparative study.

Two-phase in vitro testing was performed to determine the initial mechanical stability of uncemented but fixed porous coated acetabular components. Six each of three-screw fixation, two-peg fixation, and three-spike fixation porous acetabular components were implanted into fresh and embalmed human cadaver acetabula. Measurement of prosthesis-bone displacement at a load of 100 kg did not show a significant difference among the three methods of fixation. However, torque testing showed that three-screw fixation failed at significantly higher loads (46 N-m) than two-peg fixation (32 N-m) or three-spike fixation (32 N-m).

Acetabulum↗
PubMed1989

Experimental spiral fractures. An in vitro biomechanical comparison of lag-screw fixation to plate fixation.

The rigidity and strength of fixation of experimental spiral fractures in canine tibias with triple lag-screw osteosynthesis were compared with fixation by six-hole dynamic compression plating (DCP). Lag-screw fixation was 71% to 77% as stiff in bending and 69% as stiff in torsion as plate fixation. When evaluated by torsion to failure, lag-screw specimens were 68% as strong as plate specimens. Although the difference in energy to failure in torsion was not statistically significant between the two methods, both fell considerably short of control values. The lag preparation was 9% as strong as intact controls, and the plate preparation was 21% as strong as intact controls. Long spiral fractures without comminution are amenable to triple lag-screw osteosynthesis with some loss of rigidity and strength when compared to single-plate fixation. This decrease in rigidity and strength may be outweighed by the avoidance of the stress protection phenomenon noted under rigid plates.

Animals↗
PubMed1989

Reduction of stress shielding beneath a bone plate by use of a polymeric underplate. An experimental study in dogs.

Plating of fractures results in osteopenia beneath the plate because of the stress-shielding effect. This study was performed to determine if a dynamic compression plate fixed to a bone with a low-density polyethylene underplate would loosen over time and with cyclic loading (due to creep and/or accumulated plastic deformation of the underplate) and thus decrease its stress shielding of the bone. Three groups of ten canine femora each were plated and tested in vitro. A nonosteotomized control group (without an underplate) and an experimental group (with an underplate) were cyclically loaded 10(6) times in compression under identical conditions. The third group of bones was osteotomized and plated with underplates and cyclically loaded 10(5) times to ensure that the construct would not fail before early fracture union could occur. The plate screws of the experimental group were significantly looser than those in the control group. This corresponded to a decrease in the underplate thickness that was more than sufficient to account for the looseness of the screws. Strain readings from the plate and bone were highly variable and not conclusive. Therefore, a transfer of load, reflected in the strain magnitude, from the plate to the bone during loosening of the screws could not be documented. None of the osteotomized bones in the third group had fixation failure. This experiment demonstrated that this plate-underplate construct provided strong initial fixation of an osteotomized bone in the laboratory setting without failure of fixation. This construct gradually loosened with time and cyclic loading in vitro and therefore should decrease the stress-shielding effect when applied in vivo.

Animals↗