Possible effects of environmentally stimulated endogenous opiates.
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Biomedical subjects
Publications and source records attributed to C W Smith.
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Clinical data were obtained on 33 patients involved in 27 episodes of ciguatera fish poisoning occurring during a 14-week period on St Thomas in the US Virgin Islands. All patients had gastrointestinal tract symptoms, with 30 patients (91%) complaining of diarrhea and 23 patients (70%) complaining of vomiting; these symptoms occurred early in the disease and were of short duration. Twenty-three patients (70%) complained of malaise, and 19 patients (58%) had pain and weakness in the lower extremities. Dysesthesias were noted by 19 patients (58%); the median duration of dysesthesias was two weeks or more, with symptoms present is some cases for more than two months. Cardiovascular signs and symptoms, including both hypotension and bradycardia were noted in some acute cases. Therapy included antidiarrheal and antiemetic agents, intravenous fluids, atropine, and pralidoxime chloride. Efficacy of pralidoxime therapy could not be established on the basis of our data.
Seven cases of congenital cardiac anomalies in calves were reviewed from the files of the Ohio Veterinary Diagnostic Laboratory. The collection of material occurred during a six-month period from June 1977 to January 1978. The major clinical signs were dyspnoea, failure to gain weight and sudden death in young animals. The cardiac defects included two patent ductus arteriosus, two anomalies of the coronary vessels, one persistent truncus arteriosus, one transposition of the aorta and pulmonary artery and one ventricular septal defect.
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A quantitative cineangiographic method is presented for studying neonatal lamb ventricular volumes and pump function without thoracotomy or surgical instrumentation of the heart. When this method was employed in lambs with a mean age of 24.4 hours it was found that the right and left ventricular end-diastolic volumes, ejection fractions and systolic outputs did not differ significantly at this early postnatal time. Restudy of these lambs at a mean age of 15.6 days showed that right and left ventricular end-diastolic volumes, normalized for body weight, and ejection fractions had not changed significantly. Although systolic outputs decreased, the difference was not significant. Thus there is early postnatal equalization of left and right heart volumes, and deviations from this relation should suggest abnormal hemodynamic function.
A large number of cultures of the bacterium E. coli have been grown in weak alternating magnetic fields of square waveform, at frequencies of 50 Hz and 16.66 Hz. Control cultures were simultaneously grown under ambient conditions identical except for the almost complete absence of any magnetic field. The mean generation time (MGT) for a culture subjected to alternating magnetic fields is significantly reduced by comparison with that for the control cultures. Application of the F-ratio test indicates a probability of less than one in two million that the effects observed are due to chance. A marked threshold effect is observed, along with strong indications of periodicity in the graph of MGT against magnetic field strength. Within the limits of experimental error, these effects correspond to integral changes in the number of magnetic flux quanta linking an individual bacterial cell during the process of division.
The described procedure permits assessment of the neutrophil shape change response to formyl-methionyl peptides added directly to EDTA anticoagulated whole blood. Response is monitored by counting the resultant number of "bipolar" neutrophil forms present on stained blood films. The preparation of monolayer blood films with a blood "spinner" facilitates uniform sample analysis. Time- and dose-response relationships for neutrophil bipolar shape formation (BSF) agree with data reported for other neutrophil response measurements. No significant change in leukocyte or platelet counts occurred after the addition of control or stimulatory agents to whole blood, nor did 90 min aging of freshly collected blood samples appear to influence the BSF response. In a study of hospitalized patients, BSF values were generally similar in those patients with normal or elevated leukocyte counts, while significantly decreased BSF was observed in leukopenic patients. A significant rise in BSF was detected as patient absolute neutrophil counts increased from a normal to an elevated range. When compared with a control group, the distribution of BSF response values for patients was significantly different. The simple and rapid measurement of BSF in whole blood might facilitate clinical assessment of neutrophil responsiveness, by eliminating many of the difficulties associated with neutrophil isolation.
Neutrophil function was investigated in a male child with glycogenosis type Ib who demonstrated susceptibility to staphylococcal infections and neutropenia. Random motility and directed migration of the patient's neutrophils in vitro were profoundly diminished. The patient's neutrophils stimulated in suspension with chemotactic factors (CFs) generated chemiluminescence that was comparable to or greater than that generated by neutrophils from controls, but the patient's neutrophils failed to assume a normal bipolar configuration in response to chemotactic stimuli. They also failed to demonstrate enhanced adherence after a single exposure to CFs or decreased adherence after sequential exposures to increasing concentrations of CFs. Unlike neutrophils from controls, the patient's neutrophils failed to redistribute surface adhesion sites from lamellipodia (anterior pole) to uropods (tail) after sequential CF stimuli. These findings indicate a functional link between CF-induced configurational changes and altered adhesiveness of neutrophils under conditions of directed locomotion and suggest that a redistribution of surface adhesion sites is related to the mechanism of neutrophil locomotion.
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At 400 MHz the 1H chemical shifts, peptide NH-C alpha H coupling constants (JN alpha) and peptide hydrogen exchange rates of [Glu4] oxytocin in aqueous solution closely resemble those previously reported for oxytocin under comparable conditions, indicating that both the parent hormone and its analogue have similar conformations in this solvent. The hydrogen exchange data suggest a dynamic equilibrium between conformation(s) in which the peptide NH's of Asn5 and Cys6 are internally hydrogen bonded and conformation(s) in which these hydrogens are bonded to the solvent. [Glu4] oxytocin forms 1:1 complexes with lanthanide metal ions. The diamagnetic La3+ complex exhibits values of JN alpha very similar to those of the metal free hormone analogue, suggesting that coordination of the metal is accompanied by minimal perturbation of the peptide backbone. Specific average proton-metal distances estimated from Gd3+ induced paramagnetic relaxation effects indicate that the metal is probably coordinated to the Glu4 carboxyl group and the sidechain carbonyl of Asn5. Limiting shifts induced by binding of paramagnetic Yb3+ are also reported.
Radionuclide and contrast ventriculography were evaluated for their ability to estimate myocardial ischemia. In 14 closed-chest, sedated dogs, a small and larger region of ischemia were produced by inflating balloon occluders on the left anterior descending coronary artery. The systemic arterial pressure, atrial-paced heart rate, global ejection fraction by radionuclide and contrast ventriculography, regional wall-motion abnormalities (as the percentage of abnormally contracting segments), and regional myocardial blood flow (using the microsphere technique) were measured during an initial control period, two separate ischemic periods, and a final control period. The regional ischemic weights based on myocardial blood flow ranged from 0 to 38.5 g and were grouped as zero, small (range 0 to less than 10 g, mean 3.40 g), and large regions of ischemia (greater than 10 g, mean 24.8 g). Regional wall-motion abnormalities were sensitive qualitative indicators of ischemia. Receiver operating characteristic analysis showed that both ventriculographic methods were highly sensitive, specific, and accurate for detecting regional ischemia. Contrast ventriculography was slightly superior for detecting small regions less than 4 g, but the methods were equal for regions greater than 4 g. The arterial pressure and heart rate were unchanged during ischemia. For small regions of ischemia, the global ejection fraction did not fall using either the contrast or radionuclide technique, but it fell significantly when large regions were produced. There was a quantitative relationship between the percentage of abnormally contracting segments and the grams of myocardial ischemia (for radionuclide ventriculography, r = 0.65, P = 0.003, and for contrast ventriculography, r = 0.75, P less than 0.001), but for many small regions of ischemia, wall-motion changes were greater than anticipated, suggesting hypofunction of the continguous normal tissue. This study demonstrated that both radionuclide and contrast ventriculography were quite sensitive and specific for detecting measured amounts of regional ischemia. The functional changes resulting from ischemia are quantitatively related to the extent of regional ischemia, small areas resulting in regional wall motion abnormalities, and large areas producing both reduced global ejection fraction and wall motion changes.
To determine the mechanism(s) of diminished, stimulated, and directed migration of neonatal (N) polymorphonuclear leukocytes (PMN), chemotactic factor (CF) sensory and PMN effector functions were studied in healthy N and adult or maternal controls (C). N PMN demonstrated high affinity binding for N-formyl-methionyl-leucyl-[3H]phenylalanine (fMLP), which was saturable between 40 and 100 nM as observed with C PMN. The kinetics of binding and the characteristics of dissociation of binding by N PMN were equivalent to control PMN. Both "threshold" and "peak" concentrations (1 and 10 nM, respectively) of fMLP effected comparable PMN chemiluminescence among neonates and controls. An equivalent threshold concentration (0.05 nM) of fMLP effected N and C PMN shape change in suspension, and a maximally effective concentration (5 nM) induced comparable bipolar configuration, although uropod formation was only 38 +/- 8% of N PMN, compared with 73 +/- 11% of C PMN (P less than 0.01). Striking abnormalities of N PMN adherence were identified: mean +/- SD base-line (unstimulated) N adherence values (39 +/- 8%) were equal to C (38 +/- 9%), but diminished increments in response to single CF stimuli were noted among N (fMLP: 42 +/- 7% (N), 70 +/- 11% (C); C5a: 41 +/- 6% (N), 68 +/- 6% (C); BCF: 41 +/- 6% (N), 63 +/- 9% (C), P less than 0.01 for each CF). On sequential exposure to increasing concentrations of CF N PMN failed to demonstrate expected decreased adherence values; sequential stimuli with fMLP (0.1 nM, 10 nM) or C5a (8 microgram protein/ml, 32 microgram protein/ml) effected mean +/- 1 SD values of 51 +/- 9% (N), 30 +/- 9% (C), and 34 +/- 10 (N), 48 +/- 14% (C), respectively. As demonstrated with a latex bead-binding technique, N PMN failed to redistribute adhesion sites to the cell's tail under the same experimental conditions; in 21 N samples studied, restricted unipolar binding occurred in 33 +/- 8% (fMLP) or 37 +/- 7% (C5a) of PMN in contrast to C values of 70% (fMLP), or 71% (C5a), P less than 0.001. Similar findings were observed when PMN were preincubated with colchicine (25 microgram/ml); expected diminished adherence scores (compared with base-line values) were demonstrated with C PMN but not with N cells, P less than 0.01. Additionally colchicine-induced redistribution of adhesion sites as was observed with C samples (72 +/- 14% unipolar binding) was significantly (P less than 0.001) less among N PMN (31 +/- 11% unipolar binding). These investigations indicate that CF sensory mechanisms of N PMN are normal, compared with healthy adult or maternal controls. Diminished stimulated locomotion of the N PMN may be functionally related to reduced modulation of cell adhesiveness by chemotactic stimulation.
A questionnaire administered to 200 patients in a midwestern multispecialty clinic showed patients often have little understanding of the role of physician's assistant in the health care system. They are often equally confused about his or her education and training. Nevertheless, patients are generally receptive to the physician's assistant if they feel he is closely supervised by the physician. Most patients prefer that the physician's assistant perform "routine" functions rather than make independent diagnostic and treatment decisions.
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