Considerations of carrier (continued)
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Biomedical subjects
Publications and source records attributed to D A Miller.
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The relationships between job content and hospital pharmacists' work attitudes are examined. A 152-item questionnaire was mailed to 507 hospital pharmacists in southeastern Michigan. The questionnaire included measures of job dimensions, psychological states, and personal and work outcomes. Mean scores for 34 subscales consisting of 2-5 related items were computed. Background characteristics were also assessed. Using factor analysis, the respondents were categorized as clinical, inpatient, outpatient, or generalists depending on their reported relative time spent performing 23 nonadministrative job functions. Analysis of variance was performed across the four groups for each subscale; the level of significance was set at 0.001. The response rate was 56%, representing 283 completed questionnaires. The clinical, outpatient, inpatient, and generalist pharmacist groups consisted of 43, 36, 70, and 134 respondents, respectively. There was a prevalent trend in the rank order in which pharmacists in the four groups responded to various subscales. The clinical group had the highest scores for 13 of the 14 subscales that were significantly different across pharmacist groups. Alternatively, in all but one of the significantly different subscales the inpatient group ranked lowest. Because pharmacists in the clinical group consistently scored higher than the other groups on scales measuring components of job enrichment, the authors concluded that the challenge of hospital pharmacy managers is to adapt the positive features of clinical practice to other areas of the profession.
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The acrocentric chromosomes of 18 unrelated individuals were analyzed by sequential staining by the chromomycin A3/methyl green R-banding technique to identify the chromosomes, followed by an indirect immunoperoxidase technique to detect 5-methylcytosine (5MeC)-rich DNA. The short arms of both chromosomes 15 usually (92% of the chromosomes) had a large collection of 5MeC-rich DNA, which was always rich in AT base pairs. Much less commonly (11% of the possible occasions), a collection of 5MeC-rich DNA was seen on the short arm of a chromosome 13, 14, 21 or 22, and this DNA was always rich in GC base pairs. Sequential distamycin A/DAPI (DA/DAPI) and R-banding studies were carried out in 13 of these 18 individuals. There was bright DA/DAPI fluorescence of the 5MeC-rich region on the short arm of chromosome 15 but not on that of any other acrocentric chromosome. One implication of these findings is that bisatellited or other abnormal chromosomes that are DA/DAPI negative and 5MeC positive cannot be derived from number 15. In the case of a de novo chromosome of this type, the specific origin from any other acrocentric chromosome could be demonstrated by examining 5MeC-binding of the parental chromosomes.
A chemically synthesized form of leukotriene E4 (LTE4) has been studied for its ability to induce contractions in isolated guinea pig ilea, to induce vascular permeability changes in rat skin when injected intradermally, and to induce bronchoconstriction in guinea pigs after intravenous injection. The synthetic compound induced a contraction in the guinea pig ileum which was slower in developing than that induced by histamine but faster in developing than that induced by a crude preparation of SRS-A isolated from guinea pig lung. The compound was 70-fold more active than histamine on the guinea pig ileum (EC50 of 5 x 10(-9) and 3.5 x 10(-7) M, respectively). FPL 55712, a known SRS-A antagonist, exhibited the same potency in blocking the contractions elicited by the synthetic material as it did in blocking contractions produced by guinea pig SRS-A generated biologically (IC50 of 3.5 x 10(-8) M). The synthetic LTE4 induced a dose dependent increase in vascular permeability in the rat skin which was antagonized by the intravenous injection of FPL 55712 (ID50 of 1.2 mg/kg). The synthetic material was also a potent bronchoconstrictor in the guinea pig when injected intravenously. The bronchoconstriction, too, was antagonized by FPL 55712 when injected intravenously (ID50 of 0.2 mg/kg). In both the rat and guinea pig, FPL 55712 exhibited a short duration of action in vivo. The in vivo model systems discussed in this study, utilizing the synthetic form of LTE4 should be useful in the future evaluation of other SRS-A antagonists.
Primary hyperparathyroidism includes a spectrum of abnormalities relative to the size and histologic characteristics of the diseased glands. The lack of uniform agreement upon pathological interpretation and discrepancies between gross and histologic findings perpetuate the controversy regarding the mass of parathyroid tissue necessary to be resected. From 1960 to 1978, 193 primary hyperparathyroid patients (aged 20-80 years; mean: 55 years) were operated on by the senior author with a mean follow-up of 41.5 months. An approach evolved that included gross identification of all parathyroid tissue with frozen section confirmation and assessment of cellularity-the latter modifying the extent of parathyroid resection in 11 patients (11%) of 100 patients who had biopsies of at least four parathyroids. Overall persistence and recurrence rates of hypercalcemia were 6.2% (12 patients) and 1% (two patients), respectively, despite routine biopsy in 100 patients. No permanent hypocalcemia developed, but five patients (2.6%) were hypocalcemia one to 16 weeks postoperatively. No operative deaths occurred. Submission of additional parathyroid tissue by routine biopsy disclosed a higher prevalence of nodular hyperplasia than usually found, and the clinical significance of this finding is discussed. With findings based on gross and microscopic intraoperative study, the authors believe, the surgeon is better able to categorize pathologic variants of hyperparathyroidism and better equipped to deal with recurrent disease.
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In an attempt to determine if pharmacists could make significant contributions to SNF patient care in the area of disease management, the drug therapy of the residents of two SNFs was reviewed once monthly for six months by two clinical pharmacist consultants. Pharmacist-identified problems and recommendations were communicated in writing to the medical staff by means of a communication form attached to the patient's chart. Nearly 72 percent of the recommendations made were accepted by the SNF physicians. Descriptions of the cases and corresponding recommendations were distributed to review-panel physicians. These physicians were asked to agree or disagree with the pharmacists' suggestions, and to rate the clinical significance of each recommendation using a modified Likert scale. The clinical pharmacist-consultants were perceived to have had a significant input into disease management in SNF patients.
Desmethylimipramine (DMI) and atropine were compared in a variety of organ system tests in rats and mice involving muscarinic receptor function in order to assess the anticholinergic-like activity of this tricyclic antidepressant drug. DMI was similar to atropine in maximally inhibiting basal gastric acid secretion and markedly protecting against restraint-induced stomach ulceration. It did not, however, substantially increase pupil size, reduce fecal pellet output, inhibit cholinergically induced salivation or specifically antagonize the CNS effects of carbachol and oxotremorine as did atropine. From these data and previous work indicating that DMI acts at a site in the central nervous system to inhibit gastric acid secretion, it is concluded that the biological effects of this drug are not mediated through an atropine-like mechanism.
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The tumor dormant state established in L5178Y immunized and challenged mice is characterized by a prolonged period of clinical normalcy followed by rapid tumor outgrowth. The tumor cells which emerged after termination of the tumor dormant state had abnormal marker chromosomes identical to those in the L5178Y cells used in the original challenge inoculum, indicating that the emergent tumor cells were progeny of the challenge inoculum. Original and emergent L5178Y cells had equivalent in vivo growth rates, when inoculated into normal DBA/2 mice. The emergent L5178Y cells were less susceptible than original cells to in vitro lysis by tumor dormant PC. Original and emergent L5178Y cells expressed common tumor-associated target antigens for cytolytic effector cells. Both modulation and masking of these target antigens were ruled out as mechanisms for decreased susceptibility to cell-mediated cytolysis. Immunofluorescence revealed heterogeneity in tumor-associated antigen expression within both original and emergent cell populations, with a decreased intensity of staining in the emergent population. Both populations were equally susceptible to lysis by alloimmune cells, alloantiserum, and anti-Thy 1.2 serum, but emergent cells were less susceptible to lysis by serum directed against L5178Y TAA. Quantitative absorption revealed that the emergent L5178Y cells expressed eightfold less serologically detectable TAA than the original cells. These findings indicate that the host immune response developing during establishment of the tumor dormant state selects a stable tumor cell subpopulation which expresses decreased amounts of surface tumor-associated target antigens.
An H4-IIE-C3 hepatoma cell line derived from an ACI rat has been shown to have differentially stained regions attached to the short arms of chromosomes 3, 11 and 13 and the long arm of an unidentified small chromosome. There is cell to cell variability in the number and size of the differentially stained regions, which contain, on the average, about 5% of the total DNA. A series of secondary constrictions occur at intervals along the length of each differentially stained region. These stain with silver by the Ag-AS method, indicating that the differentially stained regions contain sites of active 45S ribosomal precursor RNA transcription. In situ hybridization to metaphase chromosomes shows that the hepatoma cells have a 10 fold increase in DNA coding for 18S and 28S ribosomal RNA, 90% of it located in the differentially stained regions, and no change in the number of genes coding for 5S RNA. These results have been confirmed by filter disc hybridization.
These experiments were conducted to see if the pacing phenomenon found by Kunz and Miller (Respir. Physiol., 22: 167--177, 1974) in the open-loop, unidirectionally ventilated chicken is important in normally breathing birds. In this study, chickens breathed spontaneously through a tracheostomy from a gas source in which the fraction of CO2 (FICO2) could be rapidly changed. A feedback algorithm kept the FICO2 at 0.05 except for a constant duration pulse (approx 0.6 s) of low FICO2 given tau seconds after the beginning of each inspiration. In all birds tested an increase in tau resulted in a proportional increase of both inspiratory period (TI), expiratory period (TE), and the total period (Ttot). Increases in TI were from 0.5 to 1.0 times the increase in tau. Dynamic expeiments showed TI usually changed on the next breath after a step change in tau, and sinusoidal modulation of tau caused concurrent sinusoidal changes in TI, TE, and Ttot. These findings indicate that the phenomenon that produced pacing in the unidirectionally ventilated birds is important to the ventilatory pattern of normal breathing.
The avian respiratory oscillator has been investigated in a unidirectionally ventilated chicken by changing the dynamic pattern of inflow CO2 concentration (FCO2). Stimulation with periodic FCO2 results in a one-to-one synchronization of the respiratory movements that we have called pacing (Respir. Physiol. 22: 167--177, 1974). A two-parameter CO2 threshold model is proposed to explain this behavior. The model states that when FCO2 reaches a threshold level (L), it initiates the beginning of inspiration a constant time interval (LB) later. According to this model, when a triangular FCO2 concentration is used to synchronize the breathing pattern, the time from the minimum of the wave form to the beginning of inspiration (C-B interval) is dependent on the mean value and the rate of rise of FCO2 as determined by period and amplitude of the triangle. Particularly interesting is the prediction that the direction of the relationship (increasing or decreasing) between FCO2 amplitude and the C-B interval is dependent on whether the mean value of FCO2 is above or below the threshold level. Experimental data obtained during amplitude changes support the above prediction.
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Secretion of alpha-amylase by the human parotid gland increased significantly during eight days of hyperbaric exposure. This hyperactivity of the parotid gland presumably resulted from increased autonomic nervous system (ANS) activity attributable to (1)psychological stress in the form of anticipation; (2) dive-related factors, i.e., hyperoxia, PN2, physical stress; or (3) a combination of both. The etiology of the effect must await additional studies, but a consistent and significant elevation in alpha-amylas secretion was found. This previously undescribed effect of hyperbaric exposure indicates that parotid alpha-amylase sampling holds promise as a noninvasive means of monitoring physical and psychological stress, and as an indirect measure of ANS tone.