Time and money: effects of no-shows at a family practice residency clinic.

BACKGROUND: When patients fail to appear for scheduled appointments, the flow of patient care is interrupted, and clinic productivity declines. This study investigated the impact of failed appointments on a clinic by measuring time and money lost after taking into account same-day treatment patients (walk-ins). METHODS: Schedule information was retrieved for 4,055 visits over 20 business days. Data were collected on appointment status (show, no-show, cancel, walk-in), time allocated for the appointment, charges for visit, date and time of the visit, and other appointment information. RESULTS: No-shows and cancellations represented 31.1% of scheduled appointments and 32.2% of scheduled time. Rates of failed appointments varied by type of provider, patient demographics, and patient status (new versus established). Walk-in patients replaced 61.0% of failed appointments but only 42.4% of the time blocked for those appointments. Walk-in visits generated 89.5% of the charges associated with scheduled visits. Over the course of a year, total revenue shortfalls could range from 3% to 14% of total clinic income. CONCLUSIONS: Failed appointments pose financial as well as administrative problems for residency practices. Proactive reminder systems are needed to promote patient attendance.

Antisense oligodeoxynucleotide and ribozyme design.

The overwhelming advances of the last few years in the field of nucleic acid-based technologies laid the basis for the development of this new technology as a frontier method not only to combat diseases and infections but also to study gene function. The development of antisense strategies has generated considerable expectations in the neurosciences and, in particular, behavioral neurobiology. Antisense application in the brain has become a technology with tremendous impact, especially for determining the molecular pathways and substrates of behavior of an organism controlled by independent stimuli. The antisense agents, either oligodeoxynucleotides or ribozymes, interfere in the genetic flow of information from DNA via RNA to protein. According to the literature it seems clear that appropriately modified antisense compounds successfully and stably bind to their target ribonucleic acid molecules. This antisense binding leads to a decrease in the corresponding protein levels. If the targeted protein exerts detrimental effects on the cell or tissue, its reduction should be beneficial from a therapeutic point of view. If the investigator wants to study the function of a specific gene product the selective and transient downregulation of the corresponding target protein will help in functional analysis. In the following article I describe the chemical nature of the antisense oligodeoxynucleotides and some of the most commonly used derivatives and give some guidelines on antisense construction and application. The possible mode of action is discussed, as is expansion of the oligonucleotide-based application to ribozyme-mediated gene inhibition. Finally, problems that may be encountered during antisense application are discussed.

Population-based survey of complementary and alternative medicine usage, patient satisfaction, and physician involvement. South Carolina Complementary Medicine Program Baseline Research Team.

BACKGROUND: With an increasing proportion of Americans using complementary or alternative medicine (CAM), physicians need to know which patients are using CAM to effectively manage care. METHODS: In this cross-sectional study, telephone interviews were conducted with 1,584 South Carolina adults (ages 18 and older); 66% responded to the survey of demographics, general health, frequency of CAM use, perceived CAM effectiveness, and physician knowledge of CAM use. RESULTS: A total of 44% had used a CAM during the past year. Increasing age and higher education were significantly associated with CAM use. More than 60% perceived CAM therapy as very effective, and 89% said they would recommend CAM to others. Physicians were unaware of CAM use in 57% of their patients using CAM. CONCLUSION: Complementary or alternative medicine use in this rural Southern state is similar to national usage. Users view CAM as effective. Physicians are frequently unaware of patients' CAM use. More research is needed to establish CAM effectiveness and how CAM affects medical care, training, and public health.

Suppression of nidogen-1 translation by antisense targeting affects the adhesive properties of cultured astrocytes.

The multidomain glycoprotein nidogen-1 is a common component of basal membranes. Nidogen-1 is produced by the endothelial cells and the mesenchymal cells of the developing central nervous system. Recent results give evidence that nidogen-1 may also be secreted by cultured Schwann cells to basement membranes of peripheral nerves. We were interested in ascertaining whether astrocytes, which have the capacity to produce laminin and fibronectin and are an important source of extracellular matrix (ECM) molecule secretion in the brain, might also produce nidogen-1. Immunocytochemistry, in combination with polymerase chain reaction and in situ hybridization techniques, revealed that astrocytes in culture synthesize nidogen-1. To show the functional significance of the nidogen-1 secretion by astrocytes, antisense targeting techniques were applied. These experiments showed that nidogen-1 may be an essential modulator of astrocytic adhesion to the substrate. The suppression of nidogen-1 synthesis by the application of antisense oligonucleotides induced a morphological transition from a flat, polygonal to a round cell and was accompanied by the detachment of the astrocytes from the substrate. Hence, nidogen-1 might be an important component of the ECM secreted by astrocytes. The suppression of nidogen-1 synthesis may disturb the aggregation of ECM molecules to a functional basement membrane and thus reduce the astrocytic adhesion to the substrate. Nidogen-1 secretion to basement membranes by astrocytes may have important functional implications during blood-brain barrier and scar formation.

Residency training in mental health: a South Carolina family practice research consortium study.

BACKGROUND: This study explored attitudinal, demographic, and residency training factors that affect the use of mental health (MH) interventions by family physicians. METHODS: All 872 alumni from seven family practice residency programs in South Carolina were sent a mail-back survey about MH issues. Alumni returned 400 surveys (46%). RESULTS: An estimated 25% of routine patient care visits required some MH counseling. Interventions categorized by respondents as "often used" included counseling plus medication (58%), referral plus medication (39%), and counseling alone (30%). When respondents assessed their residency training, only psychopharmacology received high ratings from a majority of physicians (65%). Lectures, hospital rounds, and one-on-one supervision were the most common teaching methods. The use of multiple teaching methods was associated with higher perceived training quality. Nearly two thirds (62%) of physicians were interested in continuing education in MH counseling. CONCLUSIONS: Family physicians have positive attitudes toward MH counseling and often provide MH interventions. Physicians' satisfaction with residency training in MH topics, however, could be improved. More MH teaching in ambulatory settings may be appropriate.

Integrin family of cell adhesion molecules in the injured brain: regulation and cellular localization in the normal and regenerating mouse facial motor nucleus.

Integrins are a large family of heterodimeric glycoproteins that play a crucial role in cell adhesion during development, inflammation, and tissue repair. In the current study, we investigated the localization of different integrin subunits in the mouse facial motor nucleus and their regulation after transection of the facial nerve. In the normal mouse brain, there was clear immunoreactivity for alpha5-, alpha6-, and beta1-integrin subunits on blood vessel endothelia and for alphaM- and beta2-subunits on resting parenchymal microglia. Facial nerve transection led to an up-regulation of the beta1-subunit on the axotomized neurons and an increase in the alpha4-, alpha5-, alpha6-, beta1-, alphaM-, alphaX-, and beta2-subunits on the adjacent, activated microglia. Quantification of the microglial integrins revealed two different expression patterns. The subunits alpha5 and alpha6 showed a monophasic increase with a maximum at day 4, the alphaM-subunit a biphasic regulation, with an early peak at day 1 and an elevated plateau between day 14 and 42. At day 14, there was also an influx of lymphocytes immunoreactive for the alpha4beta1- and alphaLbeta2-integrins, which aggregated at sites of neural debris and phagocytotic microglia. This finding was accompanied by a significant increase of the alpha5beta1-integrin on blood vessel endothelia. In summary, facial axotomy is followed by a strong and cell-type-specific expression of integrins on the affected neurons and on surrounding microglia, lymphocytes, and vascular endothelia. The presence of several, strikingly different temporal patterns suggests a selective involvement of these molecules in the different adhesive events during regeneration in the central nervous system.

Economic impact of hospital closure on small rural counties, 1984 to 1988: demonstration of a comparative analysis approach.

Hospital closure in a rural community may affect the locale's economic prospects as well as the health of its residents. Studies of economic effects have primarily relied on modeling techniques rather than observation of actual change. This study demonstrates the use of a comparative analysis approach for estimating the economic effects of hospital closure on small rural counties. The experiences of 103 small rural counties at which a hospital closed between 1984 and 1988 was compared with a matched group of counties at which no closure took place. "Comparable" counties were selected based on seven scales measuring the similarity between a closure county and potential comparisons. Three scales examined population and economic characteristics in the year before closure; two scales measured change throughout a three-year period preceding closure; and two scales measured change throughout a five-year period preceding closure. Closure effects were measured through a multivariate analysis of the post-closure economic history of closure and comparison counties. The key assumption is that similar counties should have similar experiences over time. If an event occurs within some of these counties but not others, this event should have visible effects. Comparative analysis suggested that earned income in closure counties (excluding farming and mining income) was lower than in comparison counties subsequent to closure and that labor force growth was similarly affected. A comparative analysis approach produces results that parallel those obtained from economic modeling and should be considered for further research.

Downregulation of brain mineralocorticoid and glucocorticoid receptor by antisense oligodeoxynucleotide treatment fails to alter spatial navigation in rats.

Adult male Brown Norway rats were long-term intracerebroventricularly (i.c.v.) infused with antisense oligodeoxynucleotides (18-mer, double endcapped phosphorothioate protected) targeting either mineralocorticoid or glucocorticoid receptor mRNA, or received the respective mixed bases sequence or vehicle. Mineralocorticoid receptor-mixed bases and glucocorticoid receptor-mixed bases oligodeoxynucleotide infusion (1 microg/0.5 microl/h) over a time period of seven days did not alter hippocampal mineralocorticoid receptor and glucocorticoid receptor binding when compared to vehicle treatment. In contrast, i.c.v. administration of mineralocorticoid receptor, as well as glucocorticoid receptor-antisense over the same time period resulted in a significantly reduced binding of mineralocorticoid receptor and glucocorticoid receptor in the hippocampus [mineralocorticoid receptor-antisense group approx. 72% of mineralocorticoid receptor-mixed bases and vehicle groups (100%); glucocorticoid receptor antisense group approx. 77% of glucocorticoid receptor-mixed bases and vehicle]. The specificity of these antisense effects is indicated by the finding that rats treated with mineralocorticoid receptor-antisense did not show any changes in glucocorticoid receptor and vice versa. Animals treated according to this infusion protocol and tested in the Morris water maze for their spatial navigation abilities failed to show significant differences among the groups. These data indicate that a reduction of hippocampal mineralocorticoid receptor or glucocorticoid receptor binding capacity by 20-30% does not interfere with spatial navigation.

Organizational environment and perceptions of teaching quality in seven South Carolina family medicine residency programs.

PURPOSE: To explore the relationship between organizational environment and teaching quality in seven family medicine residency programs. METHOD: In 1995, a questionnaire on organizational environment was administered to the faculties at all seven family medicine residency programs in South Carolina. Eighty-seven percent of the faculty members participated, as did convenience samples of residents, nurses, and administrative staff. The questionnaire measured seven variables: teaching quality, job satisfaction, organizational climate, employees' autonomy, goal attainment, organizational commitment, and job-related stress. RESULTS: Residents, nurses, and administrative staff who were connected to programs at which faculty expressed high levels of job satisfaction assessed teaching quality as higher than did those at other programs. The residents' perceptions of teaching quality were positively correlated with high ratings of organizational climate and job-related stress. The staffs' ratings of goal attainment were also associated with teaching quality. Faculty satisfaction was associated with their reported employee autonomy and goal attainment. CONCLUSION: The organizational characteristics of family medicine residency programs significantly influence the perceptions of teaching quality: specifically, there perceptions are correlated with the degree to which faculty are satisfied with their work environments. In addition, residents' and staffs' perceptions of teaching quality are associated with their attitudes toward their organizations' environments.

Corticotropin-releasing hormone receptor (type I) antisense targeting reduces anxiety.

Two brain-derived corticotropin-releasing hormone receptors have been cloned, termed corticotropin-releasing hormone receptors type I and type 2. Antisense oligodeoxynucleotides targeted to the cloned rat and mouse corticotropin-releasing hormone receptors type I messenger RNA reduced the binding of the natural ligand of the corticotropin-releasing hormone receptors type I and also the release of adenocorticotrophic hormone in primary rat anterior pituitary cells and in clonal mouse pituitary cells (AtT-20) by up to 60% in an application time-dependent manner. Studies on intracellular uptake of fluorescence-labelled oligodeoxynucleotides indicated a cytoplasmic accumulation starting within two to four hours after application of oligodeoxynucleotides in vitro. In vivo, antisense oligodeoxynucleotides infused intra-cerebroventricularly reduced binding of radiolabelled corticotropin-releasing hormone receptors in central sites of the rat brain. Anxiety induced by i.c.v. administration of corticotropin-releasing hormone was attenuated by corticotropin-releasing hormone receptors type I antisense treatment as determined in the elevated plus maze and in the novel open field test. The corticotropin-releasing hormone-induced behavioural changes were absent in corticotropin-releasing hormone receptors type I antisense-pretreated animals. These results show that the selected antisense probes used were able to suppress corticotropin-releasing hormone receptors type I function in vitro as well as in vivo and suggest that the development of drugs blocking this specific receptor might lead to a novel class of anxiolytics.

Clinical feasibility of a free-weight strength-training program for older adults.

BACKGROUND: An emerging trend in the field of gerontology is the recognition that older adults, especially the frail elderly population, can increase their levels of strength and thus improve functional capability. Social acceptance of physical frailty and provision of care and assistance to dependent persons has now turned to helping the frail elderly adults maintain or improve functional independence. METHODS: The purpose of our study was to show the feasibility and effectiveness of a low-cost strength-training program using free weights for increasing strength and functional fitness among older adult volunteers. Participants aged 73 to 94 years were residents of a multilevel care retirement community in Columbia, SC. The strength-training program, led by an instructor, used dumbbells and ankle weights and was conducted in a multipurpose recreation room at the retirement facility. RESULTS: Functional performance measures (timed chair stand, 6-meter walk, stair climb, balance) handgrip strength, and self-assessment of activity level were outcome measures. All 25 participants completed the strength-training program. The average program adherence rate of all participants was 87 percent. No participant injuries or other adverse effects were observed. Functional performance measures improved significantly among program participants, with the greatest improvement in the timed chair stand (33.5 percent improvement) and the stair climb (17.6 percent improvement). CONCLUSION: Free-weight strength-training programs are appropriate for older adults, can be implemented in community settings, and are associated with significant improvement in functional performance.

Patient and physician satisfaction with an outpatient care visit.

BACKGROUND: The purpose of this study was to identify factors contributing to patient and physician satisfaction during outpatient care visits, and to determine the degree to which physician and patient satisfaction are related. METHODS: The sample (N = 250) was drawn from the outpatient practice of the University of South Carolina Department of Family and Preventive Medicine. Opinions were obtained by self-administered written questionnaires for physicians and by interviews with patients conducted by second-year medical students. RESULTS: Most encounters (88%) were satisfying for the physician. Resident physicians reported greater satisfaction than did faculty. Physicians were most satisfied with encounters in which they believed they had adequate time, were competent to address patient problems, and communicated successfully with the patient. Patient satisfaction was high (78% highly satisfied). Patients were more likely to be fully satisfied if they believed themselves to be in good health, did not wait long, and had health insurance. Unperceived patient dissatisfaction was associated with waiting time and a belief that the physician did not pay attention. No relationship was found between patient satisfaction and physician satisfaction. CONCLUSIONS: The majority of patient care encounters were satisfying for both participants. The pervasive effect of waiting time on patient satisfaction emphasizes the need for careful scheduling. Lower satisfaction among faculty physicians should be explored to identify possible interventions to prevent physician burnout. Pressures from managed care organizations may decrease physician satisfaction if these take the form of reducing the time available for each patient or restricting physicians' ability to seek subspecialist consultation.

Centrally administered oligodeoxynucleotides in rats: occurrence of non-specific effects.

We studied the effects of various intracerebroventricularly administered oligodeoxynucleotides on body temperature, locomotor activity, food intake and water consumption in rats during a 24 h period with a radio-telemetric system. Both complete phosphorothioate oligodeoxynucleotides and end-inverted oligodeoxynucleotides dose-dependently elevated body temperature, suppressed food and fluid intake and inhibited nighttime activity. Apparently these effects do not depend on the nucleotide sequence because antisense and sense arginine vasopressin and oxytocin oligodeoxynucleotides, as well as a missense oligodeoxynucleotide produced comparable changes in the autonomous and behavioral parameters. In control experiments neither contaminants from the chemical synthesis nor endotoxins produced such effects, whereas native DNA from salmon sperm did. Fever and sickness-like behavior in response to missense phosphorothioate oligodeoxynucleotides were accompanied by elevated concentrations of circulating corticosterone and by a marked increase in interleukin 6 mRNA in brain and spleen, indicating that centrally administered oligodeoxynucleotides stimulate the production of pyrogenic inflammatory mediators in both central nervous system and peripheral tissues. Our results indicate that centrally administered oligodeoxynucleotides produce beside their intended sequence-specific effects also transient and sequence-independent effects due to their nucleic acid structure.

Rat hypothalamus neuron-like cells in primary culture accumulate and translate mRNA coding for the amphibian P-domain peptide xP1.

1. Neurons seem to possess the intrinsic capability to incorporate and translate exogenous RNA. For further evaluation of this phenomenon, we wanted to study the uptake and processing capacity of rat hypothalamic neurons for species-unspecific heterologous cRNA under in vitro conditions. 2. cRNA coding for the amphibian p-domain peptide xP1 was prepared by in vitro transcription and added to the culture medium of rat hypothalamic cells, derived from E18 fetuses. 3. After 2 hr, a fraction of the hypothalamic neuron-like cells had accumulated the radiolabeled transcripts, as could be demonstrated by autoradiographic assessment. Specific immunostaining for xP1 could be demonstrated 18 hr after incubation with the cRNA. 4. Our findings indicate that hypothalamic neuron-like cells are capable of accumulating and translating nonmammalian transcripts. Since it was only a portion of hypothalamic cells that showed this effect, specific recognition sites for RNA may be presented by certain neurons, further supporting the assumption that binding, uptake, and translation of cRNA transcripts represent a general neural property which is malleable to functional status.

Expression of the trefoil polypeptide ITF in PC12 cells.

Trefoil polypeptides are expressed mainly in the amphibian skin and the gastrointestinal tract of mammals, usually coexpressed with mucin-glycoproteins. Recently, the trefoil polypeptides were shown to be expressed also in different areas of the human and murine brain. To investigate the expression and possible functions of ITF in rat pheochromocytoma (PC12) cells were employed. PC12 cells show a low basal expression of this polypeptide as determined by reverse transcriptase-polymerase chain reaction. After treatment with the synthetic glucocorticoid dexamethasone, the second messenger cyclic adenosine monophosphate and the neurotrophic factor nerve growth factor the expression of the trefoil polypeptide ITF was increased as shown by reverse transcriptase-polymerase chain reaction and by immunocytochemistry. Since these various stimuli can directly can directly alter the expression level of this peptide we conclude that the presented results may from the basis for further investigations of possible functions of this novel gut-brain polypeptide in neurons using PC12 cells.

Increased stress-induced adrenocorticotropin response after long-term intracerebroventricular treatment of rats with antisense mineralocorticoid receptor oligodeoxynucleotides.

Brain corticosteroid receptors, the type 1 mineralocorticoid receptor (MR) and the type 2 glucocorticoid receptor (GR), are involved in the regulation of neuroendocrine and behavioral responses during ongoing and stressful conditions. To further investigate the role of MR in these responses, we treated male Wistar rats intracerebroventricularly (icv) for 1 week with an 18-base end-capped phosphorothioate-protected antisense oligodeoxynucleotide (ODN) directed against MR mRNA (MR-AS). A mixed bases sequence (MR-MB) and vehicle (0.9% saline) served as controls. The ODN solution was administered by continuous infusion (1 microgram/0.5 microliter/h) via an icv cannula connected with polyethylene tubing to a subcutaneously implanted Alzet miniosmotic pump. No nonspecific effects of the ODNs, such as signs of sickness behavior or loss of body weight, were observed at any time during the treatment. The MR-AS treatment produced a 21% decline in hippocampal MR concentrations. Hippocampal GR levels were not affected by the treatment. MR and GR levels after MR-MB treatment were similar to those found after treatment with the vehicle. In situ hybridization experiments using an [35S]-labeled antisense MR probe showed that hippocampal MR mRNA levels were increased in MR-AS-treated rats. No changes were found in basal early morning levels of plasma ACTH and corticosterone which is consistent with the lack of any changes in adrenal and thymus weight. When rats were socially defeated for 10 min by a male and female resident and then placed for 5 min in the elevated plus-maze, no changes in the anxiety-like behavior were observed in MR-AS-treated animals. However, MR-AS-treated rats killed immediately after the behavioral test had markedly higher plasma ACTH, but not corticosterone, levels than the MR-MB and saline controls. In conclusion, down-regulation of the brain MR produces an enhanced responsiveness of ACTH to stressful situations which appears to be accompanied by a reduced sensitivity of the adrenal gland to ACTH.

Infusions of tyrosine hydroxylase antisense oligodeoxynucleotide into substantia nigra of the rat: effects on tyrosine hydroxylase mRNA and protein content, striatal dopamine release and behaviour.

Modulation of the transcriptional message of tyrosine hydroxylase was investigated in vivo in the rat nigrostriatal dopamine system with unmodified antisense oligodeoxynucleotide, mismatch oligodeoxynucleotide or vehicle controls. Oligodeoxynucleotide was infused (0.5 microgram/0.5 microliter/h) unilaterally into the substantia nigra by an osmotic minipump system over 14 days. The presence of oligodeoxynucleotide in the brain was verified by in situ hybridization and fluorescence labelling. Animals treated with unmodified antisense oligodeoxynucleotide showed ipsilateral turning behaviour when challenged systemically with the indirect dopamine agonist amphetamine, whereas mismatch- and vehicle-infused rats showed no such behavioural asymmetries. In the substantia nigra, antisense treatment had no effects on tyrosine hydroxylase mRNA, but it led to a reduction in tyrosine hydroxylase protein content. Tissue levels of dopamine, measured in postmortem tissue punches of the neostriatum and substantia nigra, were reduced in the oligodeoxynucleotide-treated hemisphere. Furthermore, basal extracellular levels of dopamine, monitored by in vivo microdialysis, were also lower in the neostriatum ipsilateral to antisense infusion and showed a weaker response to an amphetamine challenge when compared with the contralateral side. These effects were not observed after infusion of mismatch oligodeoxynucleotide or vehicle into the substantia nigra. Finally, the GABAergic enzyme glutamate decarboxylase was not affected in the antisense-treated substantia nigra, indicating that non-specific damage in this area was not caused by this treatment. Our results indicate that antisense oligodeoxynucleotide treatment against tyrosine hydroxylase in the substantia nigra has behavioural and neurochemical effects that are comparable with known actions of dopamine neurotoxins, which are conventional pharmacological tools for the depletion of dopamine. Furthermore, our data show the potential of antisense targetting to reveal new relationships between neurotransmitter-related enzymes and behavioural parameters, because the possibility of selectively and discretely manipulating tyrosine hydroxylase function is likely to produce new insights into the physiological and behavioural functions of the dopaminergic nigrostriatal system.