Is patients' perception of time spent with the physician a determinant of ambulatory patient satisfaction?

BACKGROUND: Time management in ambulatory patient visits is increasingly critical. Do patients who perceive a longer visit with internists report increased satisfaction? METHODS: Prospective survey of 1486 consecutively encountered ambulatory visits to 16 primary care physicians (PCPs) in an academic primary care clinic. Patients were queried regarding demographics, health status, perception of time spent before and after ambulatory visits, whether the physician appeared rushed, and visit satisfaction. Physicians were queried regarding time spent, estimated patient satisfaction, and whether they felt rushed. RESULTS: In 69% of 1486 consecutive visits, patient previsit expectation of visit duration was 20 minutes or less. Patient and PCP postvisit estimates of time spent significantly exceeded patient previsit time expectation. Patients who estimated that they spent more time than expected with the PCP were significantly more satisfied with the visit. When patient postvisit estimate of time spent was less than the previsit expectation, visit satisfaction was significantly lower independent of time spent. Patient worry about health and lower self-perceived health status were significantly associated with patient expectation for longer visits. Primary care physicians felt rushed in 10% of encounters. Although PCPs estimated patient satisfaction was significantly lower when they felt rushed, patient satisfaction was identical when PCPs did and did not feel rushed. Patients indicated that PCPs appeared rushed in 3% of encounters, but this perception did not affect patient satisfaction. CONCLUSION: Perceived ambulatory visit duration and meeting or exceeding patient expectation of time needed to be spent with the physician are determinants of patient satisfaction in an ambulatory internal medicine practice.

Simulated car crashes at intersections in drivers with Alzheimer disease.

Current evidence suggests that car crashes in cognitively impaired older drivers often occur because of failure to notice other drivers at intersections. We tested whether licensed drivers with mild to moderate cognitive impairment due to Alzheimer disease (AD) are at greater risk for intersection crashes. In this experiment, 30 participants drove on a virtual highway in a simulator scenario where the approach to within 3.6 seconds of an intersection triggered an illegal incursion by another vehicle. To avoid collision with the incurring vehicle, the driver had to perceive, attend to, and interpret the roadway situation; formulate an evasive plan; and then exert appropriate action on the accelerator, brake, or steering controls, all under pressure of time. The results showed that 6 of 18 drivers with AD (33%) experienced crashes versus none of 12 nondemented drivers of similar age. Use of a visual tool that plots control over steering wheel position, brake and accelerator pedals, vehicle speed, and vehicle position during the 5 seconds preceding a crash event showed inattention and control responses that were either inappropriate or too slow. The findings were combined with those in another recent study of collision avoidance in drivers with AD that focused on potential rear end collisions. Predictors of crashes in the combined studies included visuospatial impairment, disordered attention, reduced processing of visual motion cues, and overall cognitive decline. The results help to specify the linkage between decline in certain cognitive domains and increased crash risk in AD and also support the use of high-fidelity simulation and neuropsychologic assessment in an effort to standardize the assessment of fitness to drive in persons with medical impairments.

Recognition of patient referral desires in an academic managed care plan frequency, determinants, and outcomes.

OBJECTIVE: To determine the frequency and determinants of provider nonrecognition of patients' desires for specialist referral. DESIGN: Prospective study. SETTING: Internal medicine clinic in an academic medical center providing primary care to patients enrolled in a managed care plan. PARTICIPANTS: Twelve faculty internists serving as primary care providers (PCPs) for 856 patient visits. MEASUREMENTS AND MAIN RESULTS: Patients were given previsit and postvisit questionnaires asking about referral desire and visit satisfaction. Providers, blinded to patients' referral desire, were asked after the visit whether a referral was discussed, who initiated the referral discussion, and whether the referral was indicated. Providers failed to discuss referral with 27% of patients who indicated a definite desire for referral and with 56% of patients, who indicated a possible desire for referral. There was significant variability in provider recognition of patient referral desire. Recognition is defined as the provider indicating that a referral was discussed when the patient marked a definite or possible desire for referral. Provider recognition improved significantly (P <.05), when the patient had more than one referral desire, if the patient or a family member was a health care worker and when the patient noted a definite desire versus a possible desire for referral. Patients were more likely (P <.05) to initiate a referral discussion when they had seen the PCP previously and had more than one referral desire. Of patient-initiated referral requests, 14% were considered "not indicated" by PCPs. Satisfaction with care did not differ in patients with a referral desire that were referred and those that were nor referred. CONCLUSIONS: These PCPs frequently failed to explicitly recognize patients' referral desires. Patients were more likely to initiate discussions of a referral desire when they saw their usual PCP and had more than a single referral desire.

Modulation of cholesterol concentration in Caco-2 cells by incubation with different n-6 fatty acids.

Incorporation of exogenous cholesterol was compared in human adenocarcinoma colon cells (Caco-2) after incubation with 100 microM of either linoleic acid (LA, 18:2n-6), gamma-linolenic acid (GLA, 18:3n-6), arachidonic acid (AA, 20:4n-6) or adrenic acid (or n-6 docosatetraenoic acid, DTA, 22:4n-6). In both cells 7 days after seeding and 14 days after confluency, incubation with LA significantly raised the proportion of 18:2n-6 but not its long-chain metabolites in cellular phospholipid. Incubation with GLA increased the levels of 18:3n-6, 20:3n-6, and 20:4n-6. Incubation with AA increased the levels of 20:4n-6 and 22:4n-6, and incubation with DTA increased the levels of 22:4n-6 as well as its retro-conversion metabolite, 20:4n-6. A subsequent addition of cholesterol (180 microM) to the medium significantly raised the cellular cholesterol level but less so in the cells 7 days after seeding incubated with GLA. The increase in cellular cholesterol level was generally greater in the cells of 7 days after seeding, particularly those incubated with long-chain highly unsaturated n-6 fatty acids, than in those of 14 days after confluency. These findings suggest that the cell growth and the extent of unsaturation in cell membrane phospholipid fatty acids modulate the incorporation of the exogenous cholesterol into the Caco-2 cells.

N-3 and n-6 fatty acid metabolism in undifferentiated and differentiated human intestine cell line (Caco-2).

Metabolism of n-6 and n-3 fatty acids in the undifferentiated and differentiated human adenocarcinoma colon cell line (Caco-2) was studied. In cells incubated with either 18:2n-6 or 18:3n-3, no significant amounts of long chain n-6 and n-3 metabolites were found. Incubation with either 18:3n-6 or 18:4n-3 raised significantly the levels of 20:3n-6 and 20:4n-3, respectively. In the undifferentiated cells, significant proportions of 20:3n-6 and 20:4n-3 were further delta 5-desaturated to form 20:4n-6 and 20:5n-3, respectively. Incubation with either 20:4n-6 or 20:5n-3 raised the levels of their direct elongation products, 22:4n-6 and 22:5n-3, respectively. Incubation with 22:4n-6 or 22:5n-3 increased the levels of 20:4n-6 and 20:5n-6. These results suggest that delta 6-desaturation in the Caco-2 cells is less active in comparison with elongation, delta 5-desaturation and retro-conversion. These enzymes were modulated by the state of differentiation, and appeared to be non-specific to n-3 and n-6 fatty acids. When cells were incubated with 18:3n-6 and 18:4n-3 concomitantly, the levels of incorporation of total n-6 fatty acids into cellular lipids were greater than those of the n-3 fatty acids, whereas the ratios of 20+22 carbon metabolites to 18-carbon precursor favored n-3 over n-6 fatty acids. These results suggest that n-3 and n-6 fatty acids were not metabolized identically in Caco-2 cells.

Virucidal effect of murine duodenal extracts: studies with lactate dehydrogenase-elevating virus.

Mucosal resistance to infection with lactate dehydrogenase-elevating virus (LDV) has been previously demonstrated, and the LDV system presents an important murine model for the study of mucosal barriers to viral infection. In the present study, duodenal molecules were isolated from normal mice which had potent virucidal activity, when tested against LDV as well as canine herpes, canine hepatitis, Semliki forest, and visna viruses. The virucidal activity was demonstrated to be non-immune in nature, and was present in apparently non-enzymatic protein molecules, having a molecular mass of between 10-100 kDa by membrane filtration and 10-17 kDa by gel filtration. The anti-LDV activity of these molecules was suppressed by anti-duodenum antibodies in vitro, and in vivo studies suggested a possible protective role for the anti-viral molecules. We conclude that the normal mouse duodenum contains potent virucidal molecules, which are of interest to the study of biological and molecular mechanisms of viral resistance.

Changes in saccharide and phospholipid content associated with drug storage in cultured rabbit aorta muscle cells.

In the investigation of cellular changes associated with intracellular drug storage, we incubated cultured rabbit aorta muscle cells with various amphiphilic agents. Disobutamide, chloroquine, and desipramine each increased cellular content of rhamnose, arabinose, mannose, glucose, and total saccharides; these agents also elevated total and individual phospholipid of all classes. Amiodarone did not alter total saccharide content, but increased total phospholipid. Tilorone, in contrast, decreased total saccharides, but phospholipid content was unchanged. All test agents decreased xylose content. By light microscopy, disobutamide, chloroquine, and tilorone induced clear cytoplasmic vacuoles; desipramine induced dense cytoplasmic granules; and amiodarone induced both cytoplasmic changes. By electron microscopy, the content of the cellular alterations induced by disobutamide was primarily electron lucent; that of the alterations induced by desipramine was primarily concentric lamellar bodies/flocculent electron-dense structures; and that of the alterations induced by amiodarone was a mixture of both. There was no correlation, therefore, between the induced cellular chemical contents and morphologic changes. Despite the physicochemical similarity of the amphiphilic drugs (all have cationic and lipophilic moieties), the chemical responses they induced were different. The results suggest that amphiphilic drugs alter processes involving saccharides as well as those of phospholipid metabolism. The origin of the saccharide moieties associated with the induced changes in monosaccharide contents is not known. Increased content of phosphatidylinositol, mannose, and glycosyl residues is consistent with the suggestion that amphiphilic drugs may cause an increase in membrane anchor synthesis. The inhibition of lysosomal enzyme activities responsible for the degradation of phospholipid and other anchors may also account for the observed increase in monosaccharides and phosphatidylinositol content.

Cell-mediated contraction of collagen lattices in serum-free medium: effect of serum and nonserum factors.

This study was conducted to identify a defined, serum-free culture medium that supports cell dependent contraction of a collagen lattice. Collagen lattices were found to contract in cultures containing human foreskin fibroblasts (HFF) or rabbit aortic smooth muscle (RASM) cells incubated in serum-free medium. HFF and RASM cells required different supplements to contract the collagen gels. HFF cultured in Dulbecco's modified Eagle's (DME) medium supplemented with bovine serum albumin (BSA) and either endothelial cell growth supplement (EnGS), insulin (In), or platelet derived growth factor (PDGF) supported collagen lattice contraction. Replacement of BSA with casein without the addition of other supplements improved contraction. In contrast, RASM cells supplemented with BSA, EnGS, In, and PDGF were able to contract collagen gels only minimally. Similar to HFF, RASM cells cultured in DME medium supplemented with casein, but without the addition of other supplements, contracted collagen lattices. HFF-mediated collagen contraction was inhibited by prostaglandins E1 or E2, fibronectin, or ascorbic acid. The reported serum-free model provides a useful in vitro method to investigate the role of serum and nonserum factors regulating cell mediated-contraction of insoluble collagen fibrils.

The susceptibility of various cultured cells to induction of clear cytoplasmic vacuoles by disobutamide.

Cultured cells were found to be highly useful for investigating intracellular storage of amphiphilic compounds using disobutamide as a model agent. To select types of cultured cells most suitable for investigations, cells of dog coronary artery muscle, rabbit aorta muscle, rat urinary bladder carcinoma, rat basophilic leukaemia, human skin fibroblasts, bovine aorta endothelium, Chinese hamster ovary tumour and mouse fibroblasts were incubated with 0, 1, 2, 4, 6, 8 and 10 x 10(-4)m-disobutamide for 24 hr. Cultures were examined in situ by phase light microscopy for the presence of clear cytoplasmic vacuoles, cell death (cell detachment), and for drug effect on confluency/cell count. Disobutamide induced vacuoles in all cell types except rat leukaemia. The drug induced cell death and reduction in confluency or cell count in cultures of all cell types except rat carcinoma and rabbit aorta muscle. Release of lactic dehydrogenase from cells confirmed the relative resistance of the rat carcinoma and rabbit cells, and susceptibility of rat leukaemia, to drug-induced cell death. By means of electron microscopy of rat carcinoma and rabbit cells, it was established that vacuoles were membrane-bound and their content was predominantly electron-lucent.

Disobutamide: a model agent for investigating intracellular drug storage.

Disobutamide, a bis tertiary amine (pKa1 = 8.6; pKa2 = 10.2) cationic amphiphilic compound, and a putative cardiac antiarrhythmic drug induced clear cytoplasmic vacuoles in dogs and rats. Ultrastructurally, the vacuoles were membrane-bound vesicles containing primarily electron-lucent material. Some concentric lamellar bodies indicative of phospholipidosis were also present. Although numerous vacuoles were seen in one-year toxicity studies in dogs and rats, there was no apparent evidence of necrosis, inflammation, atrophy, hypoplasia, hyperplasia, or metaplasia. Clinical signs or laboratory findings indicative of functional impairment were also not apparent. The picture of the vacuolation in vivo was one of storage. In cultured cells vacuoles were shown to be storage sites for disobutamide and specifically in distended vesicles of the cytoplasmic acidic compartments, such as lysosomes, endocytic, and probably transport vesicles. Storage of the drug in acidic vesicles is compatible with the dibasic nature of the cationic moiety of disobutamide. The intrinsic cell chemicals which accumulate in the vacuoles along with disobutamide remain unknown. Disobutamide may be a useful agent for defining experimentally the borderline between physiologic limits (normal function) and toxicity (functional impairment) in the condition of intracellular drug storage abnormalities and for advancing knowledge of storage mechanisms.

Structural determinants of cationic amphiphilic amines which induce clear cytoplasmic vacuoles in cultured cells.

Disobutamide (D), an antiarrhythmic cationic amphiphilic amine (CAA), was withdrawn from clinical testing when clear cytoplasmic vacuoles (CCV) were found in the rat and dog during toxicity studies. To delineate the structural determinants of amines that induce CCV, we exposed cultured rat urinary bladder carcinoma and rabbit aorta muscle cells to numerous cationic drugs and chemicals and examined cells by phase light microscopy. The cationic moiety of these CAA was responsible for the induction of CCV. The very potent inducers were compounds that had two strongly basic amine (cationic) centers. The bis tertiary amines were particularly potent inducers. Aliphatic diamines of minimal lipophilicity-induced CCV, thus showing that an "amphiphilic" structural feature, though present in many CAA drugs, is not necessary for CCV induction. The distance between the two cationic centers was irrelevant to the induction of CCV. These results support the concept that CCV are a manifestation of intracellular (e.g., intralysosomal) drug storage. These structural delineations will be useful in future drug design and for further understanding of drug-cell interactions. Based on these findings, we were able to synthesize an antiarrhythmic CAA which did not induce CCV.

The pH dependence of disobutamide-induced clear cytoplasmic vacuoles in cultured cells.

Cellular uptake of disobutamide (D), and clear cytoplasmic vacuoles (CCV) induction by D in cultured rat urinary bladder carcinoma cells were dependent on the culture medium pH. At pH 6.0-6.7, drug uptake was slow and no CCV formed in 24 hr. At pH 7.0-8.0, the rate of D uptake and early appearance of CCV were directly proportional to increased basicity. This was explained by the increasing fraction of un-ionized D molecules at increasing basicity of the culture medium. It is only these electrically neutral D molecules which can penetrate the lipoidal cell membrane to induce formation of CCV. Intracellular presence of D was demonstrated by mass spectrometry methods. The results indicate that D is incorporated intracellularly, that D and not its metabolite(s) is in cells, and suggest that CCV are a result of drug sequesteration.

Development of an in vitro and in vivo epithelial tumor model for the study of invasion.

Three continuous cell lines were isolated from N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT)-induced carcinoma of the Fischer rat urinary bladder by standard explant techniques. RBTCC-2 carcinoma cells were derived from a noninvasive FANFT tumor of Stage 0, RBTCC-5 carcinoma cells were from an invasive FANFT tumor of Stage B2, and RBTCC-8 carcinoma cells were from a s.c. metastasis of a FANFT tumor of Stage D2. Invasive and metastatic carcinoma cells were differentiated from their noninvasive counterparts by cellular and nuclear pleomorphism, cell size, nuclear:cytoplasmic ratio, number of nucleoli, and abnormalities of occludens junctions. Using low (less than 10) and high (greater than 80) passages of these cell strains, tumorigenicity experiments in syngeneic rats showed that the normal in vivo progression of FANFT tumors was interrupted by the isolation of carcinoma cells to cell culture. Histological appearance and biological behavior of tumor isografts closely resembled those of the original FANFT tumors. This was best demonstrated when tumor cells were inoculated adjacent to rat femurs. The destruction of bone, monitored radiographically and histologically, served as a measure of the invasive potential of the tumor cells. Destruction and deep invasion were observed only with isografts of invasive and metastatic carcinoma cells, presumably due to collagenolytic activity. Despite rapid degradation of bone by these isografts, the natural resistance of cartilage to tumor invasion could not be overcome. These carcinoma cell lines, together with their normal epithelial counterparts and the major supporting cells of connective tissue characterized previously by our laboratory, provide a unique system to study tumor invasion.

The isolation and characterization in vitro of normal epithelial cells, endothelial cells and fibroblasts from rat urinary bladder.

Epithelial cells, microvascular endothelial cells, and fibroblasts have been isolated in culture from normal urinary bladders of Fischer rats. Normal epithelial cells were cultured most efficiently when transitional epithelial sheets were plated on to collagen-coated roller flasks. The epithelial sheets were obtained by two micro-dissection techniques. In the first method, the epithelium was peeled as a large coherent sheet from the submucosal connective tissue following subepithelial injection of a collagenase solution, and after incubation of the bladders in the same enzyme solution. Epithelial sheets with intact basal cell layers were essential for culture success. On collagenous matrices, epithelial differentiation was similar to that in vivo. The in vitro transitional epithelium was composed of three cell layers, namely superficial, intermediate, and basal cells. Basal cells were attached to newly synthesized basal lamina by means of hemidesmosomes. Superficial cells were sealed at their apical lateral membranes by a junctional complex, i.e. a terminal bar. Asymmetric luminal membrane plaques were not apparent. In the second method, the epithelium was separated from the underlying connective tissue after collagenase--trypsin digestion of everted urinary bladders. Although the digest consisted mainly of epithelial cells, these rarely survived the first passage when plated on conventional plastic growth surfaces. After the third culture week, epithelial cells usually died and slowly growing colonies of fibroblasts or large flattened epitheloid cells became apparent. Epitheloid cells were identified by their typical ultrastructure as endothelial cells, showing Weibel--Palade bodies and pinocytotic caveolae. These cells were reactive with antiserum against factor VIII. The free surface of monolayer cultures was non-thrombogenic when incubated in the presence of platelets. Fibroblasts were isolated from heavily contaminated epithelial cell cultures after differential trypsinization. These three cells types represent the normal control cells of an in vitro tumor model for the study of invasiveness. All three cell types are involved in the formation and functional maintenance of the epithelial--stromal junction. The study of cell--cell and cell--matrix interactions may provide important clues for the understanding of tumor invasiveness, a process that starts at the epithelial--stromal junction and proceeds with its destruction.