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The adaptive branch of the immune system learns pathogenic patterns and remembers them for future encounters. It does so through dynamic and diverse repertoires of T- and B- cell receptors (TCR and BCRs, respectively). These huge immune repertoires in each individual present investigators with the challenge of extracting meaningful biological information from multi-dimensional data. The ability to embed these DNA and amino acid textual sequences in a vector-space is an important step towards developing effective analysis methods. Here we present Immune2vec, an adaptation of a natural language processing (NLP)-based embedding technique for BCR repertoire sequencing data. We validate Immune2vec on amino acid 3-gram sequences, continuing to longer BCR sequences, and finally to entire repertoires. Our work demonstrates Immune2vec to be a reliable low-dimensional representation that preserves relevant information of immune sequencing data, such as n-gram properties and IGHV gene family classification. Applying Immune2vec along with machine learning approaches to patient data exemplifies how distinct clinical conditions can be effectively stratified, indicating that the embedding space can be used for feature extraction and exploratory data analysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ostrovsky-Berman, Frankel, Polak and Yaari.)

Background: The evolution of pituitary surgery has made it a safe and effective form of treatment; however, risks of inadequate tumor resection, cerebrospinal fluid (CSF) leak, pituitary dysfunction, and vascular injury still exist. The use of intraoperative ultrasonography (IOUS) in pituitary surgery has been well described. Recent advancements in ultrasound technology have allowed for expanded utility as described here., Methods: A retrospective review was performed between January 2016 and December 2019. One hundred thirty-eight patients (mean age 53.7 years, 47% females) were identified undergoing transsphenoidal surgery for pituitary tumors. Thirty-four patients had IOUS performed using a side-firing ultrasound probe, while 104 did not. Data was analyzed for preoperative (demographics, clinical, and radiographic features), perioperative (blood loss, operative time), and postoperative (complications, length of stay, hormone remission, and extent of resection) outcomes., Results: There were no significant differences in patient age, gender, tumor volume, Knosp grade, and hormone-secreting status between the two groups. Patients treated using IOUS had significantly higher rates of gross total resection (79% vs. 44%, p = 0.0008), shorter operative times (74 vs. 146 min, p < 0.0001), lower blood loss (119 vs. 284 cc, p < 0.0001), and hospital stays (2.9 vs. 4.2 days, p = 0.001). Overall complication rates were lower in the IOUS group compared to standard pituitary surgery but did not reach significance., Conclusions: Recent improvements in ultrasound technology have allowed for miniaturization of probes capable of delivering high-resolution images. The use of IOUS in transsphenoidal pituitary surgery may significantly increase rates of gross total resection, while decreasing blood loss, hospital LOS, and operative time.

Background: The provision of unnecessary Emergency Medical Services care remains a challenge throughout the US and contributes to Emergency Department overcrowding, delayed services and lower quality of care. New EMS models of care have shown promise in improving access to health services for patients who do not need urgent care. The goals of this study were (1) to identify factors associated with EMS utilization (911) and (2) their effects on total EMS calls and transports in an MIH program., Methods: The study sample included 110 MIH patients referred to the program or considered high-users of EMS services between November 2016 and September 2018. The study employed descriptive statistics and Poisson regressions to estimate the effects of covariates on total EMS calls and transports., Results: The typical enrollee is a 60-year-old single Black male living with two other individuals. He has a PCP, takes 12 medications and is compliant with his treatment. The likelihood of calling and/or being transported by EMS was higher for males, patients at high risk for falls, patients with asthma/COPD, psychiatric or behavioral illnesses, and longer travel times to a PCP. Each prescribed medication increased the risk for EMS calls or transports by 4%. The program achieved clear reductions in 911 calls and transports and savings of more than 140,000 USD in the first month., Conclusions: This study shows that age, marital status, high fall risk scores, the number of medications, psychiatric/behavioral illness, asthma/COPD, CHF, CVA/stroke and medication compliance may be good predictors of EMS use in an MIH setting. MIH programs can help control utilization of EMS care and reduce both EMS calls and transports.

Radiculopathy in patients with metastatic spine disease (MSD) may be palliated with open or microsurgical techniques. However, delay of chemoradiation, infection risk, extended hospitalization periods, and surgical site pain may complicate surgical efforts to improve these patients' lives. Endoscopic approaches, heretofore used almost exclusively in degenerative spine disease, may also palliate debilitating pain while mitigating the drawbacks of surgical intervention in providing focal tumor debulking. Specimen for histopathologic diagnosis, which is of increasing importance in oncology treatments, may also be obtained by the endoscopic approach. The first case is of a 61-year-old woman with right thigh pain and weakness referable to a foraminal component of metastatic disease who underwent transforaminal endoscopic decompression through a single port with resolution of her primary pain complaint. The second case is of a 50-year-old man with history of urothelial cancer who presented with L5 radicular pain referable to foraminal tumor compression who underwent similar procedure with stabilization of his primary pain complaints. Adequate tissue biopsy was obtained in both cases. Endoscopic technique may allow direct visualization with minimal morbidity for effective decompression of symptomatic metastatic disease resulting from compression of the exiting and traversing nerve roots. Patients compromised from systemic disease may benefit from this less invasive approach that requires neither endotracheal intubation nor extended hospital stay., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 AME Case Reports. All rights reserved.)

Background: There are few engaging, patient centered, and reliable e-Health sources, particularly for patients with low health literacy., Objectives: We tested the Patient Activated Learning System (PALS) against WebMD. We hypothesized that participants using PALS would have higher knowledge scores, greater perceived learning, comfort, and trust than participants using WebMD., Methods: Participants with hypertension from an urban Internal Medicine practice were randomized to view 5 web pages in PALS orWebMD containing information about chlorthalidone. We assessed knowledge, learning perceptions, comfort, and trust through surveys immediately and one week following the intervention., Results: 104 participants completed both survey sets (PALS = 51,WebMD = 53). Immediate post intervention mean knowledge scores were higher for the PALS participants [(4.33 vs. 3.62 (P = .003)]. A greater proportion of PALS participants answered ≥4/5 questions correctly (82% vs. 57%; IRR 1.46 [95% CI 1.13-1.89]). A greater proportion of PALS participants agreed they would feel comfortable taking chlorthalidone if prescribed to them (73% vs. 55%; IRR 1.38 [95% CI 1.04-1.84]). One-week recall and trust were similar in the two groups., Conclusions: PALS may have advantages overWebMD for immediate knowledge acquisition, perceived learning, and comfort., Implications: PALS is a promising new approach to eHealth patient education. ClinicalTrials.gov registration identifier: NCT03156634., (Published by Elsevier B.V.)

Study Design: Retrospective analysis of prospectively collected follow-up data for 2.9 years., Objective: To determine the natural history of subsequent morphometric fracture rates at adjacent levels (one level above or below a previous known baseline fracture) in a large patient database., Summary of Background Data: The long-term risk and risk factors for adjacent-level vertebral fractures in patients with osteoporosis are unknown., Methods: The fracture intervention trial is a large randomized, placebo-controlled trial of alendronate treatment for osteoporosis. Data from both bisphosphonate-treated and bisphosphonate-naive patients (N = 1950, vertebral fracture arm) was analyzed to detect incident morphometric fracture rates., Results: During a mean follow-up of 2.9 years, 3.4% of patients in the alendronate group and 7.4% in the placebo group experienced adjacent-level vertebral fractures. The annual rate of adjacent-level vertebral fractures was 1.2% in the alendronate group, and 2.5% in the placebo group (overall, 1.8% per year in both groups combined). As expected, the thoracolumbar region (defined as T11, T12, and L1) seemed to be the most prone to new adjacent-level fractures. Among females with baseline prevalent fractures at the thoracolumbar junction, who subsequently experienced at least one new fracture anywhere along the spine (N = 124), 40.3% had a new adjacent-level fracture in this region. Older age at randomization, lower bone mineral density, inactivity, and placebo therapy were significantly associated with the development of adjacent-level fractures in univariate analysis (P ≤ 0.05). Multivariate analysis indicated decreased odds of adjacent-level fractures with bisphosphonate therapy and higher bone mineral density, and increased odds with older age at randomization (P ≤ 0.05)., Conclusion: New vertebral fractures adjacent to prevalent fractures occurred relatively infrequently in this treatment trial of alendronate in females with osteoporosis, and were more common with older age at randomization, lower bone mineral density and placebo treatment.

Background: Assessment of decision-making capacity is a common and important function of psychiatric consultants. However, the sources of variability in evaluators' judgments have not been well characterized., Objective: To examine the degree and potential sources of variability in the categorical capacity judgments of experienced psychiatrists., Method: The setting was a study comparing the decision-making capacities of 188 persons with Alzheimer's disease to appoint a research proxy and to consent to two hypothetical randomized controlled trials for dementia (a new drug RCT and a neurosurgical RCT). We compared five experienced consultation psychiatrists' capacity judgments for 555 videotaped capacity interviews. Both quantitative and qualitative data were used., Results: Pair wise kappa statistics ranged from slight agreement (0.17) to substantial agreement (0.64) with group kappa statistics ranging from fair to moderate agreement (0.40 to 0.45) for the psychiatrists' judgments regarding the three capacities. The sources of variability included varying "strictness" among judges, moderate test-retest reliability within judges, the relative novelty of assessing decision-making capacity for research participation decisions, as well as the limitations of the methods used to obtain capacity judgments in the study., Discussion: There is considerable variability in capacity judgments of experienced consultation psychiatrists regarding the capacities to appoint a research proxy and to consent to research. The potential sources of variability identified in this study may provide starting points for more effective training in capacity assessment., (Copyright © 2011 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

To investigate adult neural stem cell (NSC) biology in relation to glioma, the C6 glioma cell line was tagged with green fluorescent protein (GFP) and inoculated into the brain of adult rats. The in vivo biological response of the brain to glioma was studied using immunohistochemical analysis of the subventricular zone (SVZ), peritumoral areas, and glioma. Nestin immunoreactive cells were found infiltrating glioma, but the distribution of abnormal immunoreactivity was restricted to the dorsal and medial border of the tumor relative to the ipsilateral ventricle. The SVZ was found to be hypertrophic, hypercellular, and up-regulated nestin expression. Furthermore, a dense contiguous population of nestin immunoreactive cells could be found streaming from ipsilateral dorsal tip of the SVZ, tracking along the ventral margin of the corpus callosum, and fanning out to encompass and infiltrate the proximal tumor border. Although most cells were either nestin or glial fibrillary acidic protein (GFAP) immunoreactive in the SVZ and along the ventral margin of the corpus callosum, the number of cells co-expressing both markers increased proportionally as the tumor was approached so that the predominant cell population along the proximal tumor border was GFAP immunoreactive. Finally, we demonstrated that a significant proportion of cells found in areas of abnormal immunoreactivity were proliferating, especially in peritumoral areas. In summary, there is an induction of neuropoietic activity in a rat intracranial glioma model that results in an infiltration and accumulation of abnormal nestin and GFAP expressing cells with proliferative potential along the dorsal and medial border of intracranial C6 glioma.

Much evidence points to a relationship among kidney disease, lipoprotein metabolism, and the enzyme lipoprotein lipase (LPL), but there is little information on LPL in the kidney. The range of LPL activity in the kidney in five species differed by >500-fold. The highest activity was in mink, followed by mice, Chinese hamsters, and rats, whereas the activity was low in guinea pigs. In contrast, the ranges for LPL activities in heart and adipose tissue were less than six- and fourfold, respectively. The activity in the kidney (in mice) decreased by >50% on food deprivation for 6 h without corresponding changes in mRNA or mass. This decrease in LPL activity did not occur when transcription was blocked with actinomycin D. Immunostaining for kidney LPL in mice and mink indicated that the enzyme is produced in tubular epithelial cells. To explore the previously suggested possibility that the negatively charged glomerular filter picks up LPL from the blood, bovine LPL was injected into rats and mice. This resulted in decoration of the glomerular capillary network with LPL. This study shows that in some species LPL is produced in the kidney and is subject to nutritional regulation by a posttranscriptional mechanism. In addition, LPL can be picked up from blood in the glomerulus.

Although a majority of high-grade gliomas express the apoptosis-inducing receptor Fas, little is known about the extent of apoptosis or prognostic significance of Fas expression in these tumors. In situ labeling of apoptotic cells and Ki-67 immunohistochemistry were performed on 51 high-grade human astrocytomas previously characterized for Fas expression. Survival data was compiled from patient records and correlated with tumor grade, apoptotic index (AI) and Fas expression. A significant correlation was found between tumor grade and the AI and Ki-67 labeling index (LI); however, only the AI increased significantly with Fas expression. The AI increased from 0.39 +/- 0.12% to 0.82 +/- 0.10% in grade III vs. IV astrocytomas (P = 0.003). The Ki-67-LI increased from 3.64 +/- 1.5% to 11.35 +/- 2.1% in grade III vs. IV astrocytomas (P = 0.004). Additionally, tumors expressing higher Fas levels had a greater AI than those expressing lower levels (0.81 +/- 0.11% vs. 0.43 +/- 0.11%) (P = 0.017). Despite longer median survivals for patients with tumors exhibiting high Fas expression, statistical significance was not achieved. Patients with grade III astrocytomas demonstrated a median survival of 20 vs. 18 months for tumors with high vs. low Fas expression (P = 0.51). Patients with grade IV astrocytomas demonstrated a median survival of 9 vs. 7.4 months for tumors with high vs. low Fas expression, respectively (P = 0.77). Although the degree of Fas expression in high-grade astrocytomas appears to correlate with the apoptotic rate, no overall differences in survival could be demonstrated between tumors expressing high vs. low Fas levels.

Existential issues in group psychotherapy derive from existential thought both as a philosophy and as a value system. Its origins derive from the weakening of traditional values and the growing alienation of man from himself. The unique features of existentialism can be applied to all forms of therapy. These features are universal to humankind. They are finiteness, aloneness, guilt, responsibility, and freedom. In including existential concerns as part of group psychotherapy, therapist and patients move more closely to bilateral relationships and subjective interactions.

The authors report 3 patients, 2 children and 1 adult, each of whom presented with an unusual myxoid lesion reminiscent of pilocytic astrocytoma but with other features of myxopapillary ependymoma. The magnetic resonance imaging findings in all cases showed a diffusely contrast-enhancing suprasellar mass focally extending into the third ventricle. Involvement of adjacent structures was more extensive in both infants. By light microscopy, all were composed of a monotonous population of cells with delicate piloid-like processes, loosely arranged within a prominent myxoid background. Focally, the neoplastic cells converged upon small blood vessels in pseudorosette-like formations. These histomorphologic features are identical to those of the recently described astrocytoma with monomorphous pilomyxoid features. In addition, the individual tumor cells showed strong cytoplasmic immunoreactivity with antibodies to glial fibrillary acidic protein (GFAP) and vimentin, as well as nuclear and cytoplasmic staining with S-100. All stained positive for synaptophysin and negative for chromogranin. By electron microscopy, the tumor cells were bipolar with elongated processes and apical surfaces displaying microvilli, cytoplasmic blebs and rare cilia. Vesicles and coated pits were seen, as were occasional synaptoid complexes. The current study serves to expand our clincopathologic experience with this rare and enigmatic lesion, with particular attention given to the ultrastructural characteristics.

Objective: The cellular "death" receptor Fas has been proposed to be a potential specific target for anti-glioma therapy. However, little is known regarding the effects of Fas expression on glioma viability in vivo. The goal of this study was to clarify the relationships among Fas expression, apoptosis, and survival rates for high-grade astrocytomas., Methods: Fas expression was measured in several human glioblastoma multiforme cell lines and a malignant rat glioma cell line (36B10), before and after Fas up-regulation by gene transfer. Expression was correlated with the degree of Fas-mediated cytotoxicity and apoptosis induced after Fas activation. Subsequently, rats underwent intracranial implantation of either wild-type or genetically altered 36B10 cell lines, for study of the effects of Fas up-regulation on survival rates., Results: Low levels of cell surface Fas expression in glioblastomas multiforme were correlated with their limited susceptibility to Fas-mediated cytotoxicity. Through Fas receptor up-regulation, relationships among increased Fas expression, Fas-mediated cytotoxicity, and apoptosis were demonstrated. The percentage of cells undergoing apoptosis after exposure to a Fas ligand-producing cell line increased from 4% in the sham-transfected line (36B10-) to 27% in the Fas-transfected line (36B10-Fas). After intracranial implantation of these tumors into rats, the median survival time increased significantly from 14 days (36B10 and 36B10-) to 24.5 days (36B10-Fas), which represents a 75% increase in the survival time for the greater Fas-expressing group (P = 0.0005)., Conclusion: It seems that the overall low rate of apoptosis in high-grade astrocytomas is related to low levels of cell surface Fas expression. With increases in cellular Fas expression, rates of Fas-mediated apoptosis and survival rates were increased.

Moisture released from rubber stoppers of pharmaceutical products may adversely affect product quality during storage. The objective of the current study was to identify an appropriate method to quantify free moisture in processed stoppers. The moisture content in stoppers is commonly determined by the Karl Fischer (KF) method. However, for the FM257/2 stoppers from Helvoet, our results suggest that the KF assay results are always lower than that from the gravimetric method and increase with the KF oven temperatures used. The systematic study presented in this manuscript shows that, although moisture results vary with respect to KF oven temperatures, reproducible results are obtained at fixed temperatures. Therefore, the observed variation can not be explained by the release of volatile chemicals from this rubber-affecting KF reagents. Furthermore, by extrapolating moisture results obtained with different thicknesses of rubber slabs to zero thickness, it was found that the diffusion barrier is also not a major source for the variation. It is hypothesized that the moisture in rubber stoppers can be free or bound. The KF method measures both free and bound moisture. As higher KF oven temperatures are used, more bound moisture is released and determined by the KF method. By deducting the bound moisture (measured by the KF method for samples dried at 100 degrees C for one week) from the sample moisture, the amount of free moisture (which is releasable) can be estimated. A KF oven temperature at 250 degrees C is recommended based on the accuracy and precision of the results. This method was validated by showing consistency with the gravimetric method for stoppers undergoing desorption at 25 degrees C and 0% relative humidity (equilibrated with P2O5). An example is also presented to show the application of this method.

Object: The management of odontoid fractures remains controversial. Evidence-based methodology was used to review the published data on odontoid fracture management to determine the state of the current practices reported in the literature., Methods: The Medline literature (1966-1999) was searched using the keywords "odontoid," "odontoid fracture," and "cervical fracture" and graded using a four-tiered system. Those articles meeting selection criteria were divided in an attempt to formulate practice guidelines and standards or options for each fracture type. Evidentiary tables were constructed by treatment type. Ninety-five articles were reviewed. Five articles for Type I, 16 for Type II, and 14 for Type III odontoid fractures met selection criteria. All studies reviewed contained Class III data (American Medical Association data classification)., Conclusions: There is insufficient evidence to establish a standard or guideline for odontoid fracture management. Given the extent of Class III evidence and outcomes reported on Type I and Type III fractures, a well-designed casecontrolled study would appear to provide sufficient evidence to establish a practice guideline, suggesting that cervical immobilization for 6 to 8 weeks is appropriate management. In cases of Type II fracture, analysis of the Class III evidence suggests that both operative and nonoperative management remain treatment options. A randomized trial or serial case-controlled studies will be required to establish either a guideline or treatment standard for this fracture type.

Gliomas of all grades have been shown to express FasL, an apoptosis-inducing protein. Because of the ability of FasL to be cleaved from cell surfaces by metalloproteinases, soluble FasL can be released by FasL bearing cells into surrounding tissues. In the present study, we demonstrate the presence of sFasL in the cyst fluids of astrocytomas. Additionally, a human T-cell line, Jurkat, exposed to astrocytoma cyst fluid resulted in significantly increased cytotoxicity as compared to controls, an effect blocked by FasL neutralizing antibodies. This suggests that sFasL, may be utilized as a means of escaping immune surveillance by these tumors.

Object: Available therapies for Cushing's disease are often inadequate or involve the risk of significant morbidity. Accordingly, the need arises for the development of novel treatments, especially for cases caused by corticotroph hyperplasia, a condition difficult to treat using standard therapies. In this study, the authors investigated the use of phosphorothioate antisense oligonucleotides as a potential treatment for Cushing's disease., Methods: Corticotrophs, obtained from a patient with Cushing's disease in whom pathological findings showed multifocal areas of corticotroph adenoma and hyperplasia, were grown in tissue culture. By assessing cell viability and using immunoradiometric assay techniques, it was determined that these cells grew autonomously and secreted adrenocorticotropic hormone (ACTH) in vitro. A fully phosphorothioated antisense oligonucleotide was constructed to be complementary to the first 25 bp of the region coding for ACTH in exon 3 of the proopiomelanocortin precursor. After incubation of the corticotrophs with liposome-coated phosphorothioate antisense oligonucleotides, a greater than 90% decrease in ACTH release was noted on Days 3 and 6, compared with nonsense-treated controls (p < 0.05)., Conclusions: Antisense oligonucleotides may prove to be a useful adjunct in treating Cushing's disease by targeting one of its fundamental problems, ACTH hypersecretion.

Transoral odontoidectomy is often performed in the treatment of cervicomedullary junction disease. The operating microscope is frequently used to improve visualization in this narrow field of view. In the setting of complex anatomy or surgical revision the authors hypothesized that combining frameless stereotactic technique with intraoperative microscopy would improve the ability to visualize and identify intraoperative anatomy. In addition they believed that the ability to visualize the targeted region directly in the operating microscope "image injection" would be of particular interest in this setting, provided that sufficient accuracy for use could be obtained in the registration process. The authors assessed the efficacy of this approach in a cadaveric model and obtained sufficient accuracy to warrant use in the operating room. This technique was applied in the surgical management of a 56-year-old woman with rheumatoid arthritis who had undergone a previous decompressive transoral procedure. Subsequently she suffered progressive deterioration and was found to have residual bony compression of the anterior cervicomedullary junction. The authors performed decompressive surgery and obtained satisfactory results by using the image-injected technique, and the patient experienced subsequent clinical improvement. The authors conclude that the image-injected frameless stereotactic technique is of potential benefit, particularly in the narrow window of approach of the transoral odontoidectomy.

Human astrocytomas frequently co-express Fas (APO-1/CD95) and Fas ligand (FasL), yet do not appear to be overly susceptible to suicidal, fratricidal and immune-mediated elimination. This suggests that these gliomas have acquired mechanisms to prevent Fas-mediated apoptosis from occurring. Candidates for such a role include transforming growth factor-beta2 (TGFbeta2) and B-cell lymphoma/leukemia-2 (Bcl-2). TGFbeta2 effectively functions by hiding tumor cells from the immune system. This may potentially prevent the delivery of FasL from cytolytic T cells to Fas bearing astrocytomas. Bcl-2 works by rendering gliomas resistant to Fas-mediated apoptosis. Using immunohistochemistry, we analyzed seventy-six human astrocytomas (11 World Health Organization (WHO) grade I, 17 grade II, 17 grade III, and 31 grade IV) for the expression of Fas, FasL, TGFbeta2 and Bcl-2 in vivo. Positive immunoreactivity was found to significantly increase with increasing tumor grade for Fas (p < 0.0002), FasL (p < 0.0001), TGFbeta2 (p < 0.001) and Bcl-2 (p < 0.01). In addition, Fas/FasL co-expression, a counter-intuitive combination of factors in regards to glioma survival, also increased with WHO grade. Forty-five of 76 (59%) astrocytomas co-expressed Fas and FasL. Of those co-expressing Fas and FasL, 44 of 45 (98%) produced TGFbeta2, and 26 of 45 (58%) expressed Bcl-2. We found a significant positive correlation between Fas/FasL co-expression and TGFbeta2 (p < 0.002) and Bcl-2 (p < 0.005) production. We conclude that Fas and FasL are frequently co-expressed in human astrocytomas and these tumors are likely to produce other immunosuppressive and antiapoptotic factors such as TGFbeta2 and Bcl-2.

A multisite field trial was conducted at 11 institutions to test the clinical reliability of a 29-item consultation-liaison (C-L) psychiatry assessment instrument. Twenty-five raters viewed videotapes of two "trainees" conducting clinical interviews with a simulated patient. One trainee was a medical student, the other was a fellow in psychiatry. Raters completed the 29-item assessment instrument for each trainee. The mean value scores reflected the skill of each trainee. The medical student had a mean score of 1.93, whereas the C-L fellow had a mean score of 3.13 which parallels the expected level of skill for the two interviewers. Eighty-six percent of the items (25/29) had a standard deviation (SD) of less than 1.0. Each of the remaining four items (14%) had a SD minimally greater than 1.0. These results reflect clear wording of items with measurable parameters defined for assessing trainees' skills. The authors present different uses for the assessment instrument, including giving feedback to trainees regarding interviewing techniques and skills; setting "gold" and "lead" standards for clinical C-L interviewing skills; and training supervisors in evaluation using a standardized assessment instrument.

To investigate the extra susceptibility of diabetics to some nephrotoxic agents, adult normal and diabetic Chinese hamsters (6-7 animals in each group) were injected subcutaneously with different doses of cadmium-metallothionein (Cd-MT) equivalent to 0.0, 0.1 or 0.25 mg Cd/kg body weight and the first 24 hr urinary outputs were collected. Several days prior to exposure to the Cd-MT the diabetic hamsters were hyperglycaemic, and plasma insulin levels and body weights were elevated in some of the diabetics. The higher dose of Cd-MT caused significant spillage of N-acetyl-beta-glucosaminidase (U-NAG) activity and protein into the urine of both normal and diabetic animals. The higher dose of Cd-MT was more toxic to the diabetic kidneys because U-NAG levels were higher in the diabetics (2.5-fold higher than normal). U-Cd levels were proportional to the injected Cd-MT dose. U-Zn levels were not consistently affected by the injected Cd-MT although it had contained small amounts of Zn. Therefore, genetic diabetes in the Chinese hamster appears to increase susceptibility to acute cadmium-MT nephrotoxicity. The mechanisms underlying this need to be further investigated.

To characterize insulin release and cytoplasmic free Ca2+ ([Ca2+]i) levels in the diabetic Chinese hamster islet B cell, islets from genetically normal (subline M) and diabetic (subline L) hamsters were collagenase isolated. Insulin release and glucose utilization (conversion of D-[5-(3H)]glucose to 3H2O) were measured in whole islets; [Ca2+]i levels were measured in single islet cells using fura-2. The Ca2+ channel agonist, 12 mmol/l perchlorate, ClO4-, increased the subnormal insulin response during 20 mmol/l glucose perifusion, but did not normalize it. Glucose utilization measured over a 2-h period was normal. Glucose induced an initial decrease and then a rise in [Ca2+]i in 85% of the normal (presumably B) cells. In diabetic cells, the [Ca2+]i response was delayed, subnormal and only observed in 23% of the cells. When perchlorate or another Ca2+ channel agonist, 10 mumol/l CGP 28392, was added with glucose, a larger proportion of the diabetic cells (61-67%) showed increased [Ca2+]i and the mean [Ca2+]i response was not different from normal. However, neither perchlorate nor CGP 28392 could normalize glucose-stimulated insulin release, and K(+)-induced insulin release was decreased in diabetic islets. The K(+)-induced [Ca2+]i rise was essentially normal in all the diabetic islet cells. Therefore, the diabetic hamster islet appears to metabolize glucose normally, but has a diminished insulin response to glucose and K+. The Ca2+ channel agonists markedly improve the subnormal [Ca2+]i response but not the insulin response. Glucose-induced elevation of [Ca2+]i and exocytosis appear defective in the diabetic Chinese hamster B cell.

Changes in health care funding have greatly enhanced the value of consultation-liaison services to their parent hospitals. This paper reviews representative studies showing that consultation-liaison interventions improve patient care, enhance patients' satisfaction with treatment, and reduce polypharmacy, adverse drug reactions, and subsequent hospitalizations. Reductions in costs of hospitalization realized by consultation-liaison interventions are also described, including average reductions in hospital stays of one to one and a half days, upgrades in diagnosis-related group (DRG) codes, and timely patient transfers to inpatient medical-psychiatric units or inpatient psychiatric facilities. These data suggest that consultation-liaison services will become increasingly important over the next few years.

Insulin release and 45Ca2+ uptake were studied in isolated islets from Chinese hamsters of genetically diabetic and normal sublines. The calcium channel agonist, perchlorate (ClO4-, 12 mmol/L), augmented both 45Ca2+ uptake and insulin release from normal islets in the presence of 20 but not 1 mmol/L glucose. The agonist also amplified the glucose-stimulated 45Ca2+ uptake and insulin release from diabetic islets but did not normalize the insulin release despite normal insulin concentration in the diabetic Chinese hamster islets. The dry weight of the diabetic islets was subnormal (54%, p < 0.005) but the insulin concentration (insulin per dry weight of islet tissue) was not different from normal (122%). It appears that there are defective mechanisms in addition to the glucose-stimulated influx of Ca2+ in diabetic islet B cells.

Group treatment of the chronically mentally ill has often been a fruitless and exasperating experience. The intense emotional responses of group leaders in working with this chronic population reinforces a spiral of repetitive failures. An attempt to intervene in this chronic spiral will be presented by the author's experience in leading a training group of mental health workers who, in turn, lead groups of chronic patients. In particular, the effects of projective identification on various holding environments will be examined by using the methodology of object relations. Understanding and utilizing countertransference responses of the training leader illuminate the unconscious aims of chronic patients to perpetuate their internal and interpersonal lives by their effect on the group leaders who work with them and on each other. This understanding can lead to interventions that have more constructive outcomes.

The diabetic syndrome in Chinese hamsters is progressive and there is a decrease in the size of the pancreatic islets. To what extent this is due to impaired DNA replication in their islet cells is unknown. Therefore 3H-thymidine incorporation into islet cells was studied in genetically diabetic (subline L) male hamsters aged 17-20 days, 6 weeks, 3, 6 and 12 months. Because adrenal weight was decreased at almost all ages, studies of adrenal morphology and function were also performed. Age- and sex-matched normal (subline M) hamsters served as controls. Autoradiography showed progressively falling labeling with increasing age in both normal and diabetic animals in both islets and adrenals. At the earliest age studied, the diabetic subline animals were normoglycemic but showed hyperinsulinemia. DNA replication was reduced both in the islet cells and the adrenal cortex. From 6 weeks of age and onwards, the diabetic hamsters were hyperglycemic and usually hyperinsulinemic but DNA replication in both islets and adrenals was not different from that in normals. Histomorphometry showed reduced volume in both the adrenal medulla and cortex in 3-month-old diabetic hamsters. In 12-month-old male and female diabetic hamsters plasma cortisol and aldosterone and 24-hour urinary epinephrine were normal, but urinary norepinephrine and dopamine levels were excessive. Thus, in contrast to what is found in the obese-hyperglycemic mouse, there was no increased islet cell DNA replication in response to the increased functional demand in the diabetic Chinese hamster.(ABSTRACT TRUNCATED AT 250 WORDS)

To clarify whether elemental changes are present before the onset of diabetes, freeze-dried pancreas sections from young (18-19 days old), genetically prediabetic Chinese hamsters were subjected to proton bombardment and the concentrations of 15 elements (Na, Mg, Al, P, S, Cl, K, Ca, Mn, Fe, Cu, Zn, Rb, Cd, and Pb) in B cells and exocrine pancreas were calculated from the x-rays emitted. We have previously shown that islet B cells and exocrine pancreas from adult, overtly diabetic Chinese hamsters contain subnormal levels of Al (-61%, -88%) and excess levels of Cu (+92%, +59%), Rb (+13%, +13%), and Mg (+6%, +6%) in B cells and exocrine pancreas, respectively (Juntti-Berggren et al., Biosci Rep 1976;7:33-41). In the present study the prediabetic B cells contained normal levels of all 15 elements, whereas the prediabetic exocrine pancreas contained a subnormal level of Fe (-10%; p less than 0.005). Hence, the development of diabetes in the Chinese hamster does not seem to be associated with an early change in the elemental composition of the pancreatic B cells. In fact, the overt diabetic condition may cause changes in the body's handling of some elements.

Some data in the literature suggest that heightened activity of the pineal gland may be diabetogenic. The onset of insulin-dependent diabetes mellitus is highest during the winter months and at puberty when melatonin levels are also greatest. To study the direct effects of pineal hormones on insulin release, hand-dissected ob/ob-mouse islets of Langerhans were incubated in vitro with melatonin (1 nmol/l to 100 mumol/l) or arginine vasotocin (1 pmol/l to 10 mumol/l) and D-glucose (3 or 20 mmol/l for 1 hr. Melatonin did not affect basal or glucose-stimulated insulin release. Arginine vasotocin (AVT) did not affect basal insulin release, but at presumably pharmacological levels (1 and 10 mumol/l) the peptide significantly increased glucose-stimulated insulin release. We conclude that melatonin and AVT at physiological concentrations have no direct effect on islet insulin release, and that any diabetogenic effect of the pineal gland must occur via suppression of insulin action or via production of a metabolite or hormone that suppresses insulin release.

Freeze-dried pancreas sections from 7-, 17- and 27-week-old genetically diabetic (db/db) and normal (+/-/+/-) mice were subjected to proton bombardment and the concentrations of 15 elements in B cells and exocrine pancreas were calculated from the characteristic X-rays emitted. In the 7-week-old diabetic animals, B cells contained significantly above-normal levels of Na and S, while exocrine pancreas contained subnormal levels of Ca, and excess Mn. The B cells from the 17-week-old diabetic animals contained subnormal levels of Cu and the exocrine pancreas of the 27-week-old diabetic animals was deficient in Cd. The 7-, 17- and 27-week-old, genetically diabetic (db/db) mice were hyperglycemic, hyperinsulinemic and heavier than age-matched normal (+/-/+/-) mice. Although significant changes were found in elemental composition when comparing both B cells and exocrine pancreas at different ages, the changes were not consistent. Therefore, it appears as if the measured elemental changes were random and not related to the onset of diabetes.

Islets isolated from ob/ob mice which had been fed a vitamin D-deficient diet released significantly less insulin in response to glucose than did vitamin D-replete islets but showed normal net 45Ca2+ uptake. To determine whether vitamin D3 has a direct effect on the pancreatic B cell, islets from ob/ob mice on a normal diet were exposed to vitamin D3 in vitro for 1 week or only 3 h, and then glucose-stimulated 45Ca2+ uptake and insulin release were measured. Exposure to 1 nM or 1 microM vitamin D3 for 1 week stimulated 45Ca2+ uptake in the presence of 3 mM, but not 20 mM glucose, and did not affect insulin release. Exposure to vitamin D3 for 3 h did not significantly increase net 45Ca2+ uptake although there was a tendency to such an effect (P = 0.10). In conclusion, vitamin D-deficiency in vivo suppressed subsequent glucose-stimulated insulin release in vitro and this effect may be due to a direct effect of the sterol (or one of its metabolites) on calcium handling by the B cell.

Kinetics of (45)Ca efflux and insulin release were studied in collagenase-isolated rat islets during 2-h perifusions with calcium-depleted (0.05 mM) bicarbonate-phosphate buffer containing 2.2 mM glucose. Addition of glucose (16.7 mM) suppressed (45)Ca efflux by 30%. Removal of glucose caused an "off response" of insulin release. The perifusion of a normal concentration of Ca (2.3 mM) greatly stimulated (45)Ca efflux, indicating Ca <--> (45)Ca exchange. When Ca and glucose were superimposed, the effects on (45)Ca efflux and insulin release depended upon the order of presentation of the stimuli: when Ca was added to an ongoing 16.7-mM glucose perifusion, biphasic patterns of (45)Ca and insulin release were seen; when glucose was superimposed on a Ca perifusion, an inhibition of the Ca-stimulated (45)Ca efflux occurred, and a reduced but clearly biphasic insulin response was seen. The subsequent insulin off response after with-drawal of the glucose was also reduced. Mathematical "peeling" of (45)Ca efflux curves from unstimulated islets suggests that there are at least two, and probably three, different intracellular Ca compartments (not including the extracellular sucrose space). At the beginning of perifusion, these three compartments (I, II, III) contain 25, 56, and 19% of the intracellular (45)Ca, and their rates of efflux are 6.7, 1.2, and 0.1%/min, respectively. Glucose appears to suppress efflux from the largest compartment (II); Ca appears to exchange with (45)Ca from a more inert compartment (III). The relationship between insulin and (45)Ca release is not stoichiometric.

Hereditary insulin-deficient diabetes mellitus occurs in certain sublines of nonobese Chinese hamsters. Several characteristics of this syndrome are similar to those seen in insulin-deficient human diabetics. Therefore, to characterize pancreatic islet function, dynamic insulin and glucagon release from normal and nonketotic diabetic hamster pancreases in response to glucose (300 mg/100 ml) and theophylline (10 mM), infused singly and together, was studied in vitro.20-min glucose infusions of normal hamster pancreases caused biphasic insulin release, consisting of a rapid first peak and a gradually rising second phase, similar to that reported for man in vivo. Both phases were significantly reduced in the diabetic pancreases. Theophylline alone stimulated similar nonphasic insulin release in both the normal and the diabetic pancreases. Glucose and theophylline together caused greater insulin release than either stimulant alone in both normals and diabetics; however, the diabetic response was still subnormal. Glucose suppressed glucagon release from normal pancreases; suppression was significantly impaired in diabetics. Theophylline stimulated nonphasic glucagon release in both the normals and diabetics. Glucose partially suppressed the theophylline-stimulated release in both groups.Insulin/glucagon molar ratios of the diabetics were consistently subnormal, although individual hormone levels often overlapped into the normal range. IN SUMMARY, THE PANCREASES OF GENETICALLY DIABETIC CHINESE HAMSTERS PERFUSED IN VITRO SHOWED: (a) decreased first and second phase insulin release in response to glucose-containing stimuli-only partially ameliorated by theophylline-, and (b) impaired suppression of glucagon in response to glucose, resulting in (c) a decreased insulin/glucagon molar ratio. These data support the suggestion that both alpha and beta cells of diabetic pancreases may be insensitive to glucose.

Release of insulin and glucagon from perfused pancreases in vitro of 40 normal male and female Chinese hamsters (from one inbred subline) and 110 male and female diabetic hamsters (from three inbred sublines) was measured in response to glucose plus arginine, theophylline alone, or potassium alone, in order to determine if differences in hormone secretion exist among different diabetic sublines. Glucose plus arginine and potassium produced subnormal insulin responses in all three diabetic sublines, whereas theophylline induced 'normal' or above normal insulin responses. Excessive glucagon release was consistently seen in only one diabetic subline. The female normal animals showed greater insulin release than the male normal hamsters in response to glucose plus arginine. This sex difference was not seen in the diabetic animals.

Described here is a participant-observation strategy employed as one portion of the evaluation research at Family House, a residential treatment program for alcoholic mothers and their children. Major objectives of this leg of a two-legged research design combining this approach with a more standard pre- and post-test strategy were to document and analyze the processes of social development in the new "small society." The ethnographer acted as consultant, with "raw data" generated in the form of daily observations dictated on the rotating basis by staff members over a two-year period. The resulting narrative was coded and analyzed by the anthropologist, utilizing a phenomenological or interpretationist perspective which allowed the "native categories" of significance to emerge and guide the analysis. This novel research strategy is compared with standard ethnographic fieldwork, as well as with pre- and post-test design, in terms of its strengths and weaknesses. Strengths include access to an authentic "inside view" of Family House reality, as well as an unusually rich longitudinal record of daily life in the facility. Problems include danger of contaminating the data by means of the "feedback" provided to reward staff for their cooperation in the research effort. The author concludes, however, that since reactive effects are present in all designs, and since "feedback" is a normal feature of therapeutic milieux, validity is not unusually threatened. Finally, the purposes of evaluation research are scrutinized.

Islets of Langerhans from ob/ob mice were microdissected and stored for one week at 8 C or 37 C in a high-potassium "intracellular medium" or in a traditional culture medium (RPMI 1640 +/- fetal calf serum). Subsequent glucose-stimulated insulin release and islet morphology were best preserved by 8 C-storage in the high-potassium "intracellular medium". This suggests that normal, adult, mammalian tissues which do not readily divide in vitro may be better preserved for short periods of time at refrigerator temperatures in a high-potassium medium than by conventional culture at 37 C in a tissue culture medium.

Genetically diabetic mice (C57BL/KsJ-db/db) were used as a model to study the development of defects of insulin secretion in relation to common metabolic indicators (body weight, serum glucose and insulin, and islet insluin contant). Consistent with the idea of a protective effect of oestrogen on the pancreatic beta-cell, the female diabetic mice survived longer than the males. In males, while serum insulin decreased in the later stages of the disease, serum glucose increased progressively with age. Perfusion of the diabetic pancreases revealed a rise and subsequent fall with age of the basal insulin released at 3 mM glucose. Despite previous reports of beta-cell hyperplasia, progressive impairment of the insulin response to 20 mM glucose, or to 20 mM glucose and 1 mM 3-isobutyl-1-methylxanthine, was seen with increasing age in experiments with perfused pancreas or microdissected islets. Islet content of insulin also decreased progressively with age in the diabetic animals.

Data from all-night EEG sleep studies were used to distinguish normal subjects, primary depressed patients, and primary insomniac patients. In part 1, we compared 41 normal subjects, 56 depressed patients, and 18 insomniacs. In a univariate comparison with normal subjects, depressed patients showed less total sleep, longer sleep latency, more early morning awake time, more intermittent awake time, less delta sleep, less sleep efficiency, and shorter rapid eye movement (REM) latencies; compared with insomniacs, depressed patients showed greater early morning awake time, shorter REM latency, greater REM index, and greater REM density. Using multivariate discriminant analysis, 82% of the sample were correctly classified by diagnosis: 100% of the normal subjects, 72% of the depressed patients, and 77% of the insomniacs. Eight variables contributed to the multivariate separation of depressed individuals from insomniacs and normals: total sleep time, total recording period, sleep efficiency, sleep latency, early morning awake time, awake time, REM time and REM%. When the discriminant functions were applied to a second group of 18 primary depressed patients, 82% were correctly classified as depressed. These results suggest that primary depressed patients and primary insomniac patients may show relatively characteristic patterns of sleep abnormality.

Phosphate affects glucose tolerance, insulin release and peripheral insulin sensitivity. In the present study moderate changes in the phosphate concentration of the incubation medium from 0.3 to 2 mmol/l (i.e., within the physiological range) did not affect insulin release from isolated mouse islets in vitro. In addition, the vitamin-D status of the animals had no effect on the glucose-stimulated insulin response in the different phosphate concentrations. Therefore these data indicate that the impaired glucose tolerance seen in hypophosphatemic states is not due to a direct effect of phosphorus levels on the insulin-releasing B-cell.

The paper examines role of social support, structural-environmental and perceptual variables in explaining variation in illness behaviour in a sample of 240 adults with impaired hearing. The specific behaviour examined is physician visits over a 12 month period. We find that previous experience with illness and perceived health status are important variables with respect to illness behaviour and that the relevance of these variables and social support vary considerably by level of psychological distress. While the addition of psychological distress as an explanatory variable makes little contribution, the variation in the power of the model to explain variation in behaviour across levels of distress is substantial. Our findings argue strongly for increased awareness of the role of social and psychological factors in illness behaviour, particularly among those who plan and deliver health care services.