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Biomedical subjects

C R Clark

Publications and source records attributed to C R Clark.

At least 73 records · Page 4Linked to original sources

Effects of designer drugs on the chicken embryo and 1-day-old chicken.

The present study was conducted to examine the effects of d-amphetamine and the designer drugs 3,4-methylenedioxymethamphetamine (MDMA), N-methyl-3,4-methylenedioxyphenyl-3-butamine (HMDMA), 3,4-methylenedioxyphenyl-2-butanamine (BDB), 3,4-methylenedioxyphenyl-1-ethanamine (MDM1EA) in the chick embryo and the young chicken. HMDMA and MDM1EA had no effect on motility on day 14 of embryogenesis, while MDMA, BDB, and d-amphetamine decreased embryonic motility at one or more doses. On day 1 posthatch, chickens were challenged with cumulative injections of water or the same drug that they had received in ova. With the exception of MDM1EA, all of the drugs produced effects such as distress vocalization, wing extension, tremor, flat body posture, bursting forward movements, loss of righting reflex, and convulsant-like kicking. Pretreatment with drug in ova resulted in tolerance to certain drug effects and supersensitivity to other drug effects. Furthermore, BDB significantly decreased hatchability, MDM1EA decreased body weight, and HMDMA decreased liver weight. Further studies are needed to determine the mechanism(s) of toxicity in this species.

3,4-Methylenedioxyamphetamine↗

Behavioral and developmental effects of two 3,4-methylenedioxymethamphetamine (MDMA) derivatives.

The effects of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstacy') and two structurally related compounds, N-methyl-1-(3,4-methylenedioxyphenyl)-1-ethanamine (MDM1EA) and N-methyl-1-(3,4-methylenedioxyphenyl)-3-butanamine (HMDMA) were examined in two preparations: (i) a drug discrimination procedure in MDMA-trained rats and (ii) the chicken embryo, for determination of the direct effects of these compounds on the developing organism. The highest doses of MDM1EA and HMDMA partially substituted for MDMA, whereas higher (30-60 mg/kg) doses of HMDMA evoked clonic seizures in a separate group of rats. In chicken embryos MDMA had no effect on body, brain or liver weight, while the highest dose of MDM1EA decreased body weight and the 2 lowest doses of HMDMA increased body weight. All doses of HMDMA decreased liver weight (expressed as % body weight) when compared with contemporaneous water-treated controls. Taken together, the results of these experiments suggest that structurally related compounds share some stimulus properties with MDMA and may therefore share abuse liability. Furthermore, both MDMA-related compounds produced adverse effects on the developing organism, whereas MDMA did not.

3,4-Methylenedioxyamphetamine↗

Abnormal stimulus processing in posttraumatic stress disorder.

This study investigated event-related potential (ERP) indices of information processing in sufferers of posttraumatic stress disorder (PTSD). ERPs were obtained from 18 PTSD patients and 20 controls while they performed a target discrimination task requiring the detection of infrequent target tones from a background sequence of frequent and infrequent distractor tones. A delayed N2 and an attenuated P3 that failed to differentiate target from distractor tones indicated that patients had abnormal difficulty distinguishing task stimuli of differing relevance. It is proposed that this difficulty is reflected behaviorally in the slowed reaction time by patients to target stimuli and may underlie the disturbed concentration and memory impairments found in PTSD. It may also be related to dysfunction in central noradrenaline function, which has been shown to be both crucial in selective attention and abnormal in PTSD.

Adult↗

Pharmacokinetics and dialyzability of sulindac and metabolites in patients with end-stage renal failure.

Sulindac was administered as a single 300-mg oral dose to six patients with end-stage renal failure and six normal subjects. Plasma concentrations of sulindac and its sulfide and sulfone metabolites were examined over a 48-hour period. As determined by ultrafiltration methods at 37 degrees C, the percentage free of sulindac and sulindac sulfide in plasma was greater, respectively, in the patients with renal failure (10.50 +/- 2.42 and 9.96 +/- 1.21) than in the normal subjects (6.78 +/- 0.45 and 6.01 +/- 0.37). Free sulindac plasma concentrations were not different between the two groups. However, sulindac sulfide, total and free, plasma concentrations were substantially decreased in the group with renal failure. Total area under the curve (AUC) of the sulfide metabolite was 18% in the normal subjects and the free AUC was 29%. In patients with renal failure, the apparent half-lives of sulindac (1.98 +/- 0.76 hours) and sulindac sulfide (15.6 +/- 5.8 hours) were not different from those of normal subjects. Sulindac sulfone half-life was highly variable and longer in the patient group. Studies of dialysis clearance showed that sulindac and its metabolites are poorly dialyzed. A 4-hour dialysis period increased the plasma binding of both sulindac and sulindac sulfide in the patient group. Based on the decreased plasma concentration of the active sulindac sulfide metabolite in the patient group, dosage adjustments may be required in patients with end-stage renal failure.

Administration, Oral↗

Efficacy of phemister bone grafting in nontraumatic aseptic necrosis of the femoral head.

The authors retrospectively reviewed 40 patients who underwent 52 Phemister bone grafting procedures for nontraumatic aseptic necrosis of the femoral head to better define indications and to evaluate long-term effectiveness of the procedure. The minimum follow-up period was 2 years, and evaluation included physical examination, Iowa hip rating, and radiographs utilizing Marcus and Enneking's staging system. At 2 years following grafting, 13 (76%) of the 17 hips grafted at stage II progressed at least one stage, as did 7 (64%) of the 11 hips grafted at stage III, and 19 (86%) of the 22 hips grafted at stage IV. At the latest follow-up evaluation, 15 (88%) of the 17 hips grafted at stage II progressed at least one stage (follow-up period, 2-10 years), as did 9 (82%) of 11 hips grafted at stage III (follow-up period, 2-10 years), and 21 (95%) of the 22 hips grafted at stage IV (follow-up period, 2-12 years). Twelve (23%) of the 52 hips underwent femoral head or total hip arthroplasty, and the overall Iowa hip rating was 72. The authors' experience confirms reports of other series that do not recommend Phemister bone grafting once collapse is present. The role of structural bone grafting as a temporizing procedure is uncertain.

Adult↗

Uncemented total hip arthroplasty in patients with aseptic necrosis of the femoral head and previous bone grafting.

Tibial strut bone grafting and more recently fibular strut grating (vascularized) have been used in the treatment of aseptic necrosis of the femoral head. The authors evaluated the technical aspects and results of uncemented total hip arthroplasty after previous tibial bone grafting of the femoral head in patients with aseptic necrosis. Review of postoperative radiographs demonstrated that residual tibial graft prevented optimal femoral canal fit and positioning of the prosthetic stem in 10 of 13 hips (in the coronal plane). In the nine hips with a minimum 2-year follow-up period, two required revision for loosening of the femoral component. The authors recommend that, when performing an uncemented total hip arthroplasty in patients with previous strut grafting, special attention be directed to adequate graft removal, particularly in the lateral greater trochanteric fossa to prevent varus placement of the femoral component. An intraoperative anteroposterior radiograph with the final femoral broach in place may be useful in verifying adequate strut graft removal and optimal canal fill with proper prosthesis positioning.

Adult↗

Low-dose depot medication in schizophrenia.

Depot antipsychotic medication is a major component of the maintenance treatment of schizophrenia, but it is still not clear what constitutes an appropriate dose. A number of studies comparing low with standard doses of depot antipsychotic medication on a variety of outcome measures have been published in the last decade. A review of these studies indicates that, compared to standard-dose treatment, low-dose medication tends to improve psychosocial function and reduce the frequency of side effects but may result in an increase in positive symptoms. In such cases, a temporary increase in dose appears to control symptoms and terminate relapse episodes. An explanation of the relative efficacy of low-dose treatment may be derived from recent work in radioreceptor ligand binding.

Antipsychotic Agents↗

In vivo kinematics of the cervical spine. Part I: Development of a roentgen stereophotogrammetric technique using metallic markers and assessment of its accuracy.

A technique for simultaneous roentgen stereophotogrammetry (RS) was developed, and its accuracy was assessed. In vitro models fabricated from dried cadaveric C4 and C5 vertebrae were used to simulate the motion behavior of the cervical spine. Metallic markers made of Vitallium beads (diameter < 0.3 mm) were implanted into the posterior and anterior surfaces of each vertebra at surgically accessible locations to simulate the bead placement for both posterior and anterior surgical approaches to the cervical spine. A series of roentgen stereo pairs were obtained to systematically assess the accuracy (validity) of displacement measurements in anteroposterior (AP) translation, axial rotation, and flexion/extension. In addition, the effects of soft tissue density on the accuracy of the system were investigated by obtaining a series of roentgen stereo pairs with the experimental model immersed in a water bath. The coordinates of the metallic markers on the radiographs were then digitized by two raters who were not informed of the actual motion (i.e., blind study). The results indicated a high accuracy throughout the study. Overall root mean square errors were 0.07 mm for AP translation, 0.08 degrees for axial rotation, and 0.14 degrees for flexion/extension. The corresponding accuracy estimates (R2 values by linear regression analysis) were very high (0.992, 0.998, and 0.995) when the measurement results were compared with the actual displacements. The water bath did not affect measurement accuracy, indicating that soft tissue density should have little effect on the accuracy of the technique for in vivo applications. This system appears to be an accurate and reliable method for assessment of simulated in vivo cervical spine motion, regardless of the rater. The technique has been further used in in vivo assessment of cervical spine kinematics in one patient to confirm the efficacy of the developed technique.

Atlanto-Axial Joint↗

Effects of capsaicin on the pharmacokinetics of antipyrine, theophylline and quinine in rats.

Capsaicin is the active principal of capsicum fruits, such as hot peppers. The influence of 1-week pretreatment of capsaicin (25 mg kg-1) on the pharmacokinetics of antipyrine, theophylline and quinine was investigated in rats. The drugs were given as an intravenous bolus dose. The control rats received the vehicle solvent (polyethylene glycol) only. Clearance of antipyrine in the capsaicin-pretreated rats was significantly lower than that observed in the control rats (0.241 +/- 0.029 vs 0.344 +/- 0.034 L h-1 kg-1, P < 0.05). This is consistent with a prolongation in the elimination half-life of antipyrine in animals pretreated with capsaicin (2.06 +/- 0.30 vs 1.61 +/- 0.27 h), as the volume of distribution was not significantly changed. In contrast, capsaicin pretreatment had no significant effect on the pharmacokinetics of theophylline and quinine.

Administration, Oral↗

Dynamic response of the occipito-atlanto-axial (C0-C1-C2) complex in right axial rotation.

The torque-angular deformation in right axial rotation until failure of the ligamentous occipito-atlanto-axial complex subjected to variable loading rate (dynamic) axial torque was characterized using a biaxial MTS system. A special fixture and gear box that permitted right axial rotation of the specimen until failure without imposing any additional constraints were used to obtain the data. The specimens were divided into three groups and tested until failure at three different dynamic loading rates: 50, 100, and 400 degrees/s. A previous study by the authors provided data for quasi-static (4 degrees/s) loading conditions. The torque versus rotation curves can be divided into two straight regions and two transition zones. The plots clearly indicated that at loading rates higher than 4 degrees/s, the specimens became stiffer in the region of steadily increasing resistance prior to failure. The increase in stiffness was maximum at 100 degrees/s. The stiffness decreased somewhat at 400 degrees/s in comparison with 100 degrees/s, but this decrease was not significant. The resulting torque-right axial rotation curves were also examined to estimate the magnitude of maximum resistance (torque) and the corresponding angular rotation value. The average maximum resistance torque increased from 13.6 Nm at 4 degrees/s to 27.8 Nm at 100 degrees/s. The corresponding right angular rotation data (65-78 degrees), however, did not show any significant variation with loading rate. Posttest dissection of the specimens indicated that the type of injury observed was related to the rate of axial loading imposed on a specimen during testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Covert orientation of visual attention after closed head injury.

The ability to orient visual attention covertly was studied in 11 patients who had suffered a moderate or severe closed head injury (CHI) at least 1 year previously. Their performance was compared to nine matched controls using a cued reaction time (RT) task which measured the RT benefit of valid directional cueing and the RT cost of miscueing. The CHI and control groups did not differ in overall RT. Relative to controls, the CHI group showed normal cost but hardly any benefit, indicating that the normal capacity to pre-align attention with a cued location was impaired.

Adult↗

Two-generation reproduction study of hydrotreated shale oil vapors.

Two generations of Sprague-Dawley rats were each exposed to vapors generated by countercurrent distillation (50 degrees C) at 0, 0.5, 2.5, and 5.0 mg/liter, for 6 hr/day, 5 days/week, for 124-126 days prior to mating. After mating, exposure was continuous except for the last day of gestation through lactation for F0 dams, and the last day of gestation through Day 6 of lactation for F1 dams. F1 pups were not exposed during lactation; F2 pups were exposed via nursing only. Body weights were recorded weekly before mating; organ and body weights were recorded on Days 1, 13, and 30 of gestation and on Days 1, 4, and 21 of lactation. Histopathology, reproductive performance, and certain sperm parameters were evaluated. The test material significantly (p less than 0.05) depressed body weights of F0 males and brain and lung weights of F1 weanling males at 5.0 mg/liter. Testicular weights of F1 weanling males were depressed at the 0.5 and 5.0 mg/liter concentrations. While a dose-related decrease in sperm count and sperm ATP levels and an increase in ATP/sperm ratios were observed in F0 males at 2.5 and 5.0 mg/liter, there was no adverse effect on overall reproductive performance.

Animals↗

GC-MS identification of amine-solvent condensation products formed during analysis of drugs of abuse.

The use of methanol or ethanol as the injection solvent for the gas chromatographic-mass spectral (GC-MS) analysis of low molecular weight amine drugs of abuse results in the formation of additional components in the sample. Primary amines, such as amphetamine, 3,4-methylenedioxyamphetamine, and phenethylamine, yield imines upon injection as methanol or ethanol solutions. In methanol, the imine formed has a mass that is 12 mass units higher than the parent compound. In ethanol, the products formed have 26 additional mass units. Secondary amines appear to undergo methylation under similar conditions with methanol as the injection solvent. These products are absent from the analysis of equivalent amine samples dissolved in chloroform.

Alcohols↗

Meniscus-like synovial fold in the atlantoaxial (C1-C2) joint.

Some of the synovial joints in the human body have a fibrocartilaginous disc interposed between the joint surfaces to absorb or evenly distribute loads. Examples of fibrocartilagenous discs include the intervertebral disc, knee joint meniscus, and triangular fibrocartilages in the distal radioulnar joint and the acromioclavicular joints. The joint capsule and the surrounding tissue from nine cervical spines (18 C1-C2 joints) were dissected and prepared for gross examination and histology. We found meniscus-like synovial folds in 13 of the 18 atlantoaxial joints. These folds were located at the anteromedial and posteromedial aspect of the joint. Each synovial fold was of semilunar shape, with a thickened outer edge and thin inner edge giving a wedge-shape cross section. In one case, the synovial fold was grossly similar in appearance to a knee joint meniscus, and on histological examination there was evidence of cartilagenous metaplasia in part of the fold. The findings are compared with the limited data reported in the literature.

Aged↗