Effect of copper on the up-regulation/down-regulation of genes, cytotoxicity and ion dissolution for mesoporous bioactive glasses.

In the present study, copper-based (25 - x)CaO - xCuO -10P2O5 - 5B2O3 - 60SiO2 (x = 2.5, 5, 7.5, 10 mol%) mesoporous bioactive glasses (MBGs) were synthesized using the sol-gel technique with cetyltrimethyl ammonium bromide as the structure-directing agent. The live-dead cell count and cytocompatibility of MBGs for J774A.1 murine macrophages have also been investigated for different concentrations of MBGs. The ionic dissolution profile for Ca, P and Si has been evaluated in the simulated body fluid. The effect of copper content as well as the ionic dissolution products on the up-regulation and down-regulation of TGIF-2, HDAC-4, Smurf-1, mir-30c and mir-130a genes for the murine model are investigated using reverse transcription-polymerase chain reaction. Silica and calcium release follows a similar trend as followed by gene up-regulation of TGIF-2, HDAC-4 and mir-30c genes. This indicates that silica and calcium release influence gene expression.

Optimization of Z-axis automatic exposure control for multidetector row CT evaluation of neck and comparison with fixed tube current technique for image quality and radiation dose.

BACKGROUND AND PURPOSE: Z-axis automatic exposure control (AEC) technique automatically adjusts tube current based on size of body region scanned. The purpose of the current study was to compare diagnostic acceptability, noise, and radiation exposure of multidetector row CT (MDCT) of neck performed with z-axis AEC and with fixed current. MATERIALS AND METHODS: Two study groups of 26 patients each underwent MDCT of neck using z-axis AEC with 8 noise index (NI), 150-440 mA, and 10 NI, 75-440 mA, respectively. A control group consisting of another 26 patients underwent MDCT of neck with fixed-current technique (300 mA). Objective noise and mean tube current-time products (mA . s) were recorded. Two radiologists evaluated images for diagnostic acceptability and subjective noise on a 5-point scale. RESULTS: All CT examinations of study and control groups were diagnostically acceptable, though objective noise was significantly more with z-axis AEC (shoulder: NI 8, 20.6 +/- 6.2 HU; NI 10, 22.2 +/- 4.6 HU) than with fixed current (16.2 +/- 6 HU) (P = .01). There was no significant difference between AEC and fixed current in diagnostic acceptability and subjective noise (P = .22-.42). AEC resulted in significant radiation dose reduction (NI 8, 186.3 +/- 20.5 mA . s; NI 10, 158.1 +/- 21.2 mA x s), compared with fixed current (235 +/- 21.8 mA x s). CONCLUSION: Z-axis AEC resulted in similar subjective noise and diagnostic acceptability, with radiation dose reduction of 21% for NI of 8 and 33% for NI of 10, respectively, for MDCT evaluation of neck, compared with those of fixed current technique.

Evaluation of left ventricular endocardial volumes and ejection fractions computed from gated perfusion SPECT with magnetic resonance imaging: comparison of two methods.

BACKGROUND: Two methods of computing left ventricular volumes and ejection fraction (EF) from 8-frame gated perfusion single photon emission computed tomography (SPECT) were compared with each other and with magnetic resonance (MR) imaging. METHODS AND RESULTS: Thirty-five subjects underwent 8-frame gated dual-isotope SPECT imaging and 12- to 16-frame gated MR imaging. Endocardial boundaries on short-axis MR images were hand traced by experts blinded to any SPECT results. Volumes and EF were computed with the use of Simpson's rule. SPECT images were analyzed for the same functional variables with the use of 2 automatic programs, Quantitative Gated SPECT (QGS) and the Emory Cardiac Toolbox (ECTb). The mean difference between MR and SPECT EF was 0.008 for ECTb and 0.08 for QGS. QGS showed a slight trend toward higher correlation for EF (r = 0.72, SE of the estimate = 0.08) than ECTb (r = 0.70, SE of the estimate = 0.09). For both SPECT methods, left ventricular volumes were similarly correlated with MR, although SPECT volumes were higher than MR values by approximately 30%. CONCLUSIONS: QGS and ECTb values of cardiac function computed from 8-frame gated perfusion SPECT correlate very well with each other and correlate well with MR. Averaged over all subjects, ECTb measurements of EF are not significantly different from MR values but QGS significantly underestimates the MR values.

Sentinel node staging of early breast cancer using lymphoscintigraphy and the intraoperative gamma detecting probe.

Lymphoscintigraphy combined with intraoperative gamma-probe detection of sentinel lymph nodes in patients with inoperable early primary breast cancers is effective for staging the disease. The clinical alternative is axillary lymph node dissection, which is a far more invasive procedure and is accompanied by significant morbidity. Accuracy of staging is enhanced by immunohistochemical staining of micrometastases, which pathologists can easily perform for one to three sentinel lymph nodes, but not for 20 to 30 nodes, using axillary dissection procedure. Optimum methodology is presented for performing sentinel lymph node imaging and is important for accurate identification of sentinel node(s).

Clonotypic structure of the human CD4+ memory T cell response to cytomegalovirus.

High steady-state frequencies of CMV-specific CD4(+) memory T cells are maintained in CMV-exposed subjects, and these cells are thought to play a key role in the immunologic control of this permanent infection. However, the essential components of this response are poorly defined. Here, we report the use of a step-wise application of flow cytometric and molecular techniques to determine the number and size of the TCR Vbeta-defined clonotypes within freshly obtained CMV-specific CD4(+) memory T cell populations of four healthy, CMV-exposed human subjects. This analysis revealed a stable clonotypic hierarchy in which 1-3 dominant clonotypes are maintained in concert with more numerous subdominant and minor clonotypes. These dominant clonotypes accounted for 10-50% of the overall CMV response, and comprised from 0.3 to 4.0% of peripheral blood CD4(+) T cells. Two subjects displayed immunodominant responses to single epitopes within the CMV matrix phosphoprotein pp65; these single epitope responses were mediated by a single dominant clonotype in one subject, and by multiple subdominant and minor clonotypes in the other. Thus, the CMV-specific CD4(+) T cell memory repertoire in normal subjects is characterized by striking clonotypic dominance and the potential for epitope focusing, suggesting that primary responsibility for immunosurveillance against CMV reactivation rests with a handful of clones recognizing a limited array of CMV determinants. These data have important implications for the understanding of mechanisms by which a genetically stable chronic viral pathogen such as CMV is controlled, and offer possible insight into the failure of such control for a genetically flexible pathogen like HIV-1.

In vitro effects of transcatheter injection on structure, cell viability, and cell metabolism in fibroblast-impregnated alginate microspheres.

PURPOSE: To determine if microsphere-encapsulated cell preparations can be delivered through a microcatheter without compromising microsphere structure, cell viability, or metabolism. MATERIALS AND METHODS: Fibroblast-impregnated microspheres were fabricated by using 1.0% alginate and rabbit synovial fibroblasts. Fibroblast-impregnated alginate microspheres injected through microcatheters were analyzed in parallel with identical noninjected microspheres. The effects of transcatheter injection on structure and cell viability (percentage of viable cells per microsphere) were correlated with microsphere size. Structural effects were analyzed by using light microscopy, and 7-day percentage (ratio of live cells to dead cells) cell viability was assessed with confocal microscopy and fluorescent staining. In a second series of experiments, the metabolism of small microspheres was studied during a course of 7 days by using a spectrophotometric bioanalyzer. RESULTS: Transcatheter injection caused fracturing and/or fragmentation of large (800-1,000 microm) and medium (500-750 microm) microspheres, while small (250-400 microm) microspheres were structurally unaffected by transcatheter injection. Fracturing and fragmentation were associated with cell release from the alginate matrix. Although transcatheter injection reduced cell viability by 17%-23% in all size categories, it did not cause a detectable alteration in the rate of glucose metabolism. CONCLUSION: Transcatheter injection was physiologically well tolerated by fibroblasts encapsulated in alginate microspheres; however, when microsphere diameter exceeded the catheter diameter, fracturing and fragmentation of microspheres compromised the sequestration function of the microsphere vector.

The cutaneous response in humans to Treponema pallidum lipoprotein analogues involves cellular elements of both innate and adaptive immunity.

To extend prior studies implicating treponemal lipoproteins as major proinflammatory agonists of syphilitic infection, we examined the responses induced by intradermal injection of human subjects with synthetic lipoprotein analogues (lipopeptides) corresponding to the N termini of the 17- and 47-kDa lipoproteins of Treponema pallidum. Responses were assessed visually and by flow cytometric analysis of dermal leukocyte populations within fluids aspirated from suction blisters raised over the injection sites. Lipopeptides elicited dose-dependent increases in erythema/induration and cellular infiltrates. Compared with peripheral blood, blister fluids were highly enriched for monocytes/macrophages, cutaneous lymphocyte Ag-positive memory T cells, and dendritic cells. PB and blister fluids contained highly similar ratios of CD123(-)/CD11c(+) (DC1) and CD123(+)/CD11c(-) (DC2) dendritic cells. Staining for maturation/differentiation markers (CD83, CD1a) and costimulatory molecules (CD80/CD86) revealed that blister fluid DC1, but not DC2, cells were more developmentally advanced than their peripheral blood counterparts. Of particular relevance to the ability of syphilitic lesions to facilitate the transmission of M-tropic strains of HIV-1 was a marked enhancement of CCR5 positivity among mononuclear cells in the blister fluids. Treponemal lipopeptides have the capacity to induce an inflammatory milieu reminiscent of that found in early syphilis lesions. In contrast with in vitro studies, which have focused upon the ability of these agonists to stimulate isolated innate immune effector cells, in this study we show that in a complex tissue environment these molecules have the capacity to recruit cellular elements representing the adaptive as well as the innate arm of the cellular immune response.

Putative immunodominant human immunodeficiency virus-specific CD8(+) T-cell responses cannot be predicted by major histocompatibility complex class I haplotype.

Recent studies of human immunodeficiency virus (HIV)-specific CD8(+) T cells have focused on responses to single, usually HLA-A2-restricted epitopes as surrogate measures of the overall response to HIV. However, the assumption that a response to one epitope is representative of the total response is unconfirmed. Here we assess epitope immunodominance and HIV-specific CD8(+) T-cell response complexity using cytokine flow cytometry to examine CD8(+) T-cell responses in 11 HLA-A2(+) HIV(+) individuals. Initial studies demonstrated that only 4 of 11 patients recognized the putative immunodominant HLA-A2-restricted p17 epitope SLYNTVATL, suggesting that the remaining subjects might lack significant HIV-specific CD8(+) T-cell responses. However, five of six SLYNTVATL nonresponders recognized other HIV epitopes, and two of four SLYNTVATL responders had greater responses to HIV peptides restricted by other class I alleles. In several individuals, no HLA-A2-restricted epitopes were recognized, but CD8(+) T-cell responses were detected to epitopes restricted by other HLA class I alleles. These data indicate that an individual's overall CD8(+) T-cell response to HIV is not adequately represented by the response to a single epitope and that individual major histocompatibility complex class I alleles do not predict an immunodominant response restricted by that allele. Accurate quantification of total HIV-specific CD8(+) T-cell responses will require assessment of the response to all possible epitopes.

Career advancement of men and women in academic radiology: is the playing field level?

RATIONALE AND OBJECTIVES: The authors' purposes were to determine if there are gender differences in the speed of promotion and/or academic productivity in academic radiology and if this situation had changed since a previous study was performed in 1987. MATERIALS AND METHODS: Surveys were distributed to faculty members of academic radiology departments in May 1997. A total of 707 surveys were analyzed according to gender for time at rank for assistant and associate professor levels, in relation to publication rate, grant funding rate, and distribution of professional time. RESULTS: There was no difference between genders in the time at assistant professor rank. Among all current professors, women had been associate professors longer than men, but there was no difference between genders for those who had been in academic radiology for less than 15 years. There was no gender difference at any rank in the rate of publishing original articles. There was no difference in funding rates, although men had more total grant support. Male associate professors reported spending more time in administration and slightly more time in total hours at work than did their female colleagues, and male professors spent slightly more time teaching residents. Otherwise, there is no difference in how men and women at any rank spend their professional time. There are, however, lower percentages of women in tenured positions and in the uppermost levels of departmental administration. CONCLUSION: The time at rank for men and women and their rate of publication appear to have equalized. Women still are underrepresented at the uppermost levels of departmental administration, however, and are less likely than men to hold tenured positions.

Distribution of human CMV-specific memory T cells among the CD8pos. subsets defined by CD57, CD27, and CD45 isoforms.

Chronic antigenic stimulation has been associated with peripheral blood expansions of CD8pos. T cells characterized by CD57 expression, loss of CD27 expression, and reversal of the CD45RO(bright) /RA(dim) phenotype usually associated with immunological memory towards a CD45RO(dim) /RA(bright) phenotype. However, the relationship and functional significance of these subset(s) has remained controversial. Here, this issue was addressed using a novel flow cytometric technique that allows simultaneous detection of human cytomegalovirus (HCMV)-specific CD8pos. memory T cells by rapid (< 6 h) HCMV peptide-specific induction of cytokine synthesis, and their phenotypic characterization, including CD57, CD27 and CD45RA/RO. The vast majority of resting CD8(pos.) T cells capable of rapid induction of IFN-gamma and TNF-alpha synthesis in response to HCMV peptides were found in a subset characterized by intermediate to high expression of CD57, down-regulation/loss of CD27, and varying degrees of reversal of the classical "memory" CD45RO(bright) /RA(dim) phenotype. This subpopulation likely includes the fully differentiated memory cells responsible for the long-term immune defense against HCMV reactivation.

The road to success: factors affecting the speed of promotion of academic radiologists.

RATIONALE AND OBJECTIVES: The authors' purpose was to determine the factors influencing the speed of promotion of academic radiologists. MATERIALS AND METHODS: Three hundred forty-three surveys from faculty members of academic radiology departments with continuous academic careers were analyzed for time in rank at assistant and associate professor levels in relation to publication rate, grant funding rate, and distribution of professional time. Individuals promoted faster than the median time (6 years for assistant professors, 5 years for associate professors) were considered "fast track" and were compared with the remainder of the group. RESULTS: At the assistant professor level, fast track individuals had significantly higher rates of total publications and original articles than did others. At the level of associate professor, fast track individuals had significantly faster rates of publication of original articles, but no significant difference existed in total publication rate. No significant difference was found in the rate of founding of fast track individuals and others. Those with funding were not more likely to be on a fast track than those without funding. Fast track individuals spent significantly more time in administration at the assistant professor level than did other faculty, but no other significant differences were discovered in time distribution at the assistant or associate professor level. CONCLUSIONS: The rate of publishing original articles at the assistant and associate professor levels and the rate of overall publication at the assistant professor level were the most important parameters in predicting speed of promotion.

Normal human CD4+ memory T cells display broad heterogeneity in their activation threshold for cytokine synthesis.

CD4+ memory T cells coordinate immune responses against viruses and other pathogens via the Ag-induced secretion of potent effector cytokines. The efficacy of these responses depends on both the overall number of pathogen-specific memory T cells and the particular array of cytokines that these cells are programmed to secrete. Here, we provide evidence that heterogeneity in Ag triggering thresholds constitutes an additional critical determinant of memory T cell function. Using a novel assay that allows single-cell detection of Ag-specific T cell cytokine production, we demonstrate that CMV-specific CD4+ memory cells from human peripheral blood display pronounced differences in their costimulatory requirements for Ag-induced triggering of IFN-gamma and IL-2 secretion, ranging from cells that trigger with little costimulation (e.g., resting APC alone) to cells requiring potent costimulation through multiple pathways (resting APC plus multiple costimulatory mAbs, or activated APC). These differences in costimulatory requirements are independent of clonal differences in TCR signaling intensity, consistent with an intrinsic activation-threshold heterogeneity that is "downstream" from the TCR. Thus, "effective" frequencies of Ag-specific CD4+ memory T cells appear to depend on the activation status of available APC, a dependence that would allow the immune system to rapidly adjust the number of functional Ag-specific memory T cells in a particular effector site according to local conditions.

Treatment of brain tumors in children is associated with abnormal MR spectroscopic ratios in brain tissue remote from the tumor site.

PURPOSE: Children who have brain tumors are at risk for a variety of treatment-related sequelae, including neuropsychological and cognitive impairment, neurologic deficits, and neuroendocrinologic disturbances. We sought to determine the value of proton MR spectroscopy in assessing brain tissue remote from the tumor site to ascertain the effects of chemotherapy and radiation treatment in these patients. METHODS: Single-voxel proton MR spectra from 70 patients (111 spectra) and 11 healthy volunteers (11 spectra) were analyzed. NAA/Cr, NAA/Cho, and Cho/Cr ratios based on peak areas were obtained from nonneoplastic regions of the frontal lobe. The relationship between MR spectroscopic ratios and treatment was determined. RESULTS: NAA-containing ratios were decreased in patients as compared with control subjects. The presence of gadolinium-based contrast material did not cause significant changes in the ratios as compared with precontrast data. When chemotherapy was a component of a child's treatment protocol, we found a significant decline in NAA/Cr ratios. Patients who underwent both chemotherapy and radiation therapy showed a trend toward lower NAA-containing ratios if the chemotherapy was administered before the radiation therapy. Patients receiving whole-brain radiation had a trend toward lower NAA-containing ratios than did those who had only focal tumor treatment. CONCLUSION: In children with brain tumors, MR spectroscopy of brain tissue remote from the tumor reveals treatment-related biochemical changes.

Determination of antigen-specific memory/effector CD4+ T cell frequencies by flow cytometry: evidence for a novel, antigen-specific homeostatic mechanism in HIV-associated immunodeficiency.

The highly regulated secretion of effector cytokines by CD4+ T cells plays a critical role in immune protection against pathogens such as cytomegalovirus. Here, we directly compare the frequency and functional characteristics of cytomegalovirus-specific CD4+ memory/effector T cells in normal and HIV+ subjects using a novel, highly efficient multiparameter flow cytometric assay that detects the rapid intracellular accumulation of cytokine(s) after short-term (6 h) in vitro antigen stimulation. Responses in this assay correlate precisely with independent measures of sensitization history (e.g., seroreactivity), and allow the simultaneous assessment of multiple cytokines in single effector T cells. Healthy HIV- individuals manifested an average of 0.71, 0.72, 0.38, and 0.06% CD4+ T cells responding to cytomegalovirus with gamma-IFN, TNF-alpha, IL-2, and IL-4 production, respectively, with the simultaneous production of gamma-IFN, TNF-alpha, and IL-2 being the most common effector phenotype. Significantly, overall cytomegalovirus-specific CD4+ effector frequencies were markedly higher among 40% of HIV+ subjects (2.7-8.0%), and demonstrated a predominately polarized gamma-IFN+/TNF-alpha+/IL-2-/IL-4- phenotype. In contrast, CD4+ effector frequencies for heterologous, nonubiquitous viruses such as the mumps virus were low or absent in the HIV+ group. These data suggest the existence of homeostatic mechanisms in HIV disease that selectively preserve memory T cell populations reactive with ubiquitous pathogens such as cytomegalovirus-likely at the expense of T cell memory to more sporadically encountered infectious agents.

Immune reconstitution with donor-derived memory/effector T cells after orthotopic liver transplantation.

Therapeutic hematopoietic stem cell transplantation has made great strides in recent years, providing curative therapy for many previously untreatable diseases. Nevertheless, the applicability and effectiveness of this procedure continues to be restricted by adverse immunoregulatory states, including graft rejection, graft vs. host disease (GvHD), and/or persistent immunodeficiency. Here, we provide evidence that long-term hematopoietic stem cell transplantation across major histocompatibility complex (MHC) barriers is possible in the human with limited adverse sequelae. We observed the rapid, complete, and stable replacement of recipient hematopoiesis and B lymphopoiesis with donor-derived cells approximately 6 weeks following orthotopic liver transplantation for hemochromatosis. Long-term T lineage reconstitution also occurred, but most intriguingly, derived almost exclusively from expansion of mature, memory/effector T cells from the transplanted liver. Although demonstrating both functional and molecular evidence of a simplified T cell receptor (TCR) repertoire and unable to become sensitized to "new" antigens (Ag), this patient demonstrated long-term clinical immunocompetence. Moreover, the transplanted T cells were effectively tolerant to host tissues as the patient did not manifest clinically significant GvHD off immunosuppressive therapy. These observations suggest that isolated memory/effector T cell populations have the potential of promoting stem cell engraftment in an allogeneic host without persistent GvHD, and to provide sufficient immune reconstitution to provide the recipient with long-term immune homeostasis.

MR of the brain in children.

MR imaging has firmly established its place as the cornerstone of pediatric neuroimaging. Recent advances in MR imaging have led to decreased imaging time, high resolution studies, and new methods for obtaining tissue contrast. Magnetic resonance angiography (MRA) now obviates the need for angiography in some children, although its extended role is still to be defined. Normal and abnormal development and myelination patterns have been further defined with MR imaging. The patterns of brain injury resulting from hypoxia and ischemia vary with the degree of the insult as well as the gestational age of the child. These patterns of hypoxic-ischemic encephalopathy can be analyzed to determine when the insult occurred. Neuronal migration disorders and phakomatoses can be diagnosed with confidence at an early age, thus facilitating genetic counseling. MR imaging can detect the most common lesions associated with childhood epilepsy, such as hippocampal sclerosis, focal cortical dysplasias, and low-grade tumors. Other areas, including pediatric AIDS, toxicity-related injury, metabolic/mitochondrial conditions, and disorders associated with iatrogenic injury, can be diagnosed with MR. Spectroscopy provides information that should prove useful in evaluating and monitoring neuronal and other brain tissue disorders in children.

Analysis of allogeneic and syngeneic rat heart transplants using 23Na magnetic resonance spectroscopy.

This study defines the total sodium-23 magnetic resonance spectroscopy (23Na MRS) signal from in vivo heterotopic rat heart transplants in the early post-transplant period and examines the utility of this noninvasive method for monitoring allograft rejection. Measurements were performed at 4.7 T. Syngeneic (n = 6) and allogeneic (n = 6) donor hearts were transplanted into the neck of recipient rats. There were 27 MRS observations between days 0 and 29 post-transplant. Heart grafts were excised at various intervals post-transplant for histologic examination. Allogeneic heart grafts rejected between days 4 and 5 post-transplant while syngeneic grafts continued to beat. All hearts showed ischemic damage. Allogeneic hearts showed cellular rejection by Day 1. 23Na MRS showed a steady elevation in signal in the 3 days prior to rejection and a sharp rise after rejection. 23Na MRS accurately identified full rejection and was also sensitive to the rejection process.

Direct demonstration of cytokine synthesis heterogeneity among human memory/effector T cells by flow cytometry.

The array of cytokines produced by T cells in effector sites is a primary means by which these cells mediate host defense. It is well recognized that cloned T cells are heterogeneous with regard to cytokine synthesis and, thus, in their ability to mediate specific immune responses, but the extent to which the patterns of cytokine secretion observed in cloned cells reflect actual populations of memory/effector T cells existing in vivo is largely unknown. Here, we report our findings using a multiparameter flow cytometric assay that allows simultaneous determination of an individual T-cell's ability to produce multiple cytokines and its phenotype after only short (4 to 8 hours) in vitro incubation with an activating stimulus and the secretion inhibitor Brefeldin A. This assay shows a rapid accumulation of interleukin-2 (IL-2), IL-4, and gamma-interferon (gamma-IFN) in the cytoplasm of CD4+ cells after stimulation with either accessory cell-independent (phorbol 12-myristate 13-acetate [PMA] + ionomycin [I]) or accessory cell-dependent (staphylococcal enterotoxins [SE] A and B) T-cell-activating stimuli. Further analysis showed that production of gamma-IFN and IL-4 is predominantly, if not exclusively, restricted to the CD45ROhigh memory/effector T-cell subset, whereas IL-2 may be produced by both the CD45ROhigh and CD45ROlow subsets. Simultaneous determination of IL-2 and gamma-IFN production among CD45ROhigh/CD4+ T cells showed distinct subsets that produce each of these cytokines alone (an average of 30% for IL-2 alone, 8% for gamma-IFN alone), both (16%), or neither (46%). Similar analyses with the small IL-4-producing memory/effector T-cell subset (only 4.3% of total CD4+/CD45ROhigh T cells) showed that an average of 51% of these IL-4-producing cells also synthesize average of 51% of these IL-4-producing cells also synthesize IL-2, 23% synthesize only IL-4, 16% synthesize all three cytokines, and 9.6% synthesize IL-4 and gamma-IFN. These patterns of cytokine synthesis were found to be similar with both PMA + I and SEA/SEB stimulation and were observed in both peripheral blood memory/effector CD4+ T cells and in T cells of similar phenotype obtained from cutaneous delayed-type hypersensitivity sites. Taken together, these data strongly support the in vivo existence of human memory/effector T-cell subsets with "preprogrammed" cytokine synthesis potential, although they suggest that these subsets may be more complex than originally proposed in the TH1/TH2 hypothesis.

Patients' perceptions of increased pharmacy contact.

This prospective, randomized study was conducted to determine if increased patient contact between pharmacists and patients would result in greater patient awareness and satisfaction with their hospital stay and particularly with pharmacists and pharmacy services. Eligible patients were randomized to receive either the usual pharmacy care with minimum contact with the pharmacist, or expanded services based on increased contact with the pharmacist. A questionnaire was used to determine patient awareness and satisfaction. Statistically significant differences were found between the groups on awareness and satisfaction with pharmacy services scales as well as total scores. Total patient scores were highly reliable, with an alpha coefficient of 0.87. In addition, comments by patients in the group with increased contact were overwhelmingly positive, in contrast to those receiving usual care. Patients desire and appreciate greater contact with pharmacists.