DSFit: a feasibility pilot study of a group exercise programme for adolescents with Down syndrome.

BACKGROUND: While past research has underscored the benefits of physical activity for people with Down syndrome (DS), exercise programming that is customised to and/or accessible for children and adolescents with DS is limited. The objectives of this pilot were to (1) develop and refine an engaging exercise programme for adolescents with DS, called DSFit; (2) assess feasibility over the course of two pilot iterations; and (3) examine participant and parent feedback regarding exercise priorities and the DSFit exercise programme. METHOD: Participants were 12 unique adolescents (ages 11-17 years) with DS. Both pilot iterations of the programme consisted of weekly group exercise sessions and home exercises to complete between sessions. Physical fitness and mood/behaviour were assessed at baseline and at the end of the intervention. Parent and child goal-setting and feedback surveys were collected before and immediately after the intervention, and a 2-month follow-up assessed physical activity and exercise attitudes. Quality improvement methodology and participant/parent feedback were used to modify the second iteration to better meet the needs of our study population. Changes included an expanded age range, modified physical assessments, decreased burden of questionnaires, and video-recorded group sessions for at-home practice. RESULTS: Physical fitness evaluation of core/trunk strength and stability, lower- and upper-body strength, balance, flexibility, and walking was feasible, and the majority of participants in both pilot iterations improved in at least one category of physical assessment between baseline and end of intervention. Assessment of symptoms of anxiety, depression and behavioural concerns was also feasible and results showed slight improvements in some participants. Both parent and participant feedback indicated that participants enjoyed the programme and appreciated the opportunity to start developing sustainable exercise habits. CONCLUSIONS: A group exercise programme with supported at-home components is feasible for adolescents with DS. Future iterations will continue to examine programme efficacy with improved fitness testing and larger sample sizes. Strategies to increase at-home compliance, such as virtual sessions and parent/guardian-guided physical fitness assessments, will also be incorporated.

Hypercapnia and hyperlactatemia were positively associated with higher-grade arrhythmias during peak exercise in horses during poor performance evaluation on a high-speed treadmill.

Cardiac arrhythmias are common in horses during exercise, especially immediately post-exercise. The objectives of this study were to: (1) describe the frequency and type of cardiac arrhythmias detected in horses during incremental high-speed treadmill exercise testing (ITET); (2) determine if arterial blood gas (ABG) changes at peak and immediately post-exercise were associated with arrhythmias; and (3) determine whether upper or lower airway disease was associated with exercising cardiac arrhythmias. Horses (n = 368) presenting for an ITET underwent resting and exercising upper airway endoscopy, resting, exercising and post-exercise electrocardiography, resting and post-exercise echocardiography and exercising ABG. Arrhythmias were graded by the most severe arrhythmia present. Grade 1 arrhythmias were defined as one or two atrial (APCs) or ventricular premature complexes (VPCs), or one APC and one VPC, detected in 6.9% at peak and 16% at 0-2 min post exercise.. Grade 2 arrhythmias were >2 APCs or VPCs, or both, detected in 5.8% at peak and 16.6% at 0-2 min post exercise. Grade 3 included complex arrhythmias (couplets, triplets, R on T, multiform complexes or paroxysmal atrial or ventricular tachycardia), detected in 4.4% at peak and 7.3% at 0-2 min post exercise. Both partial pressure of arterial CO2 (PaCO2; P = 0.008) and lactate (P = 0.031) were significantly associated with arrhythmias occurring at peak exercise, but not immediately post-exercise. As PaCO2 and lactate increased, arrhythmia severity increased. Blood pH was significantly associated with grades 2 and 3 arrhythmias at 0-2 min post ITET (OR = 0.0002; P < 0.001). There was no significant association between grades 2 and 3 cardiac arrhythmias, inflammatory airway disease (IAD), or exercise-induced pulmonary hemorrhage (EIPH). When adjusted for lactate concentration (P = 0.06), higher PaCO2 concentrations in horses with and without exercising upper respiratory tract (URT) obstruction were associated with higher likelihood of grades 2 and 3 arrhythmias (P < 0.01). This study demonstrated that at peak exercise, with severe hypercapnia and hyperlactatemia, there was increased risk for grades 2 or 3 cardiac arrhythmias and, as the PaCO2 and lactate values increased further, the severity of those arrhythmias increased.

Epigenetic marks of in utero exposure to gestational diabetes and childhood adiposity outcomes: the EPOCH study.

AIMS: To identify gestational diabetes mellitus exposure-associated DNA methylation changes and assess whether such changes are also associated with adiposity-related outcomes. METHODS: We performed an epigenome-wide association analysis, using Illumina 450k methylation arrays, on whole blood collected, on average, at 10.5 years of age from 81 gestational diabetes-exposed and 81 unexposed offspring enrolled in the EPOCH (Exploring Perinatal Outcomes in Children) study, and on the cord blood of 31 gestational diabetes-exposed and 64 unexposed offspring enrolled in the Colorado Healthy Start cohort. Validation was performed by pyrosequencing. RESULTS: We identified 98 differentially methylated positions associated with gestational diabetes exposure at a false discovery rate of <10% in peripheral blood, with 51 loci remaining significant (plus additional 40 loci) after adjustment for cell proportions. We also identified 2195 differentially methylation regions at a false discovery rate of <5% after adjustment for cell proportions. We prioritized loci for pyrosequencing validation and association analysis with adiposity-related outcomes based on strengths of association and effect size, network and pathway analysis, analysis of cord blood, and previous publications. Methylation in six out of nine (67%) gestational diabetes-associated genes was validated and we also showed that methylation of SH3PXD2A was significantly (P<0.05) associated with multiple adiposity-related outcomes. CONCLUSIONS: Our findings suggest that epigenetic marks may provide an important link between in utero exposure to gestational diabetes and obesity in childhood, and add to the growing body of evidence that DNA methylation is affected by gestational diabetes exposure.

Identification and characterization of a loss-of-function human MPYS variant.

MPYS, also known as STING and MITA, is an interferon (IFN)ß stimulator essential for host defense against RNA, DNA viruses and intracellular bacteria. MPYS also facilitates the adjuvant activity of DNA vaccines. Here, we report identification of a distinct human MPYS haplotype that contains three non-synonymous single nucleotide polymorphisms (SNPs), R71H-G230A-R293Q (thus, named the HAQ haplotype). We estimate, in two cohorts (1,074 individuals), that ∼3% of Americans are homozygous for this HAQ haplotype. HAQ MPYS exhibits a > 90% loss in the ability to stimulate IFNß production. Furthermore, fibroblasts and macrophage cells expressing HAQ are defective in Listeria monocytogenes infection-induced IFNß production. Lastly, we find that the loss of IFNß activity is due primarily to the R71H and R293Q SNPs in HAQ. We hypothesize that individuals carrying HAQ may exhibit heightened susceptibility to viral infection and respond poorly to DNA vaccines.

Exercising upper respiratory videoendoscopic evaluation of 100 nonracing performance horses with abnormal respiratory noise and/or poor performance.

REASONS FOR PERFORMING STUDY: Although well documented in racehorses, there is paucity in the literature regarding the prevalence of dynamic upper airway abnormalities in nonracing performance horses. OBJECTIVE: To describe upper airway function of nonracing performance horses with abnormal respiratory noise and/or poor performance via exercising upper airway videoendoscopy. METHODS: Medical records of nonracing performance horses admitted for exercising evaluation with a chief complaint of abnormal respiratory noise and/or poor performance were reviewed. All horses had video recordings of resting and exercising upper airway endoscopy. Relationships between horse demographics, resting endoscopic findings, treadmill intensity and implementation of head and neck flexion during exercise with exercising endoscopic findings were examined. RESULTS: Dynamic upper airway obstructions were observed in 72% of examinations. Head and neck flexion was necessary to obtain a diagnosis in 21 horses. Pharyngeal wall collapse was the most prevalent upper airway abnormality, observed in 31% of the examinations. Complex abnormalities were noted in 27% of the examinations. Resting laryngeal dysfunction was significantly associated with dynamic arytenoid collapse and the odds of detecting intermittent dorsal displacement of the soft palate (DDSP) during exercise in horses with resting DDSP was only 7.7%. Exercising endoscopic observations were different from the resting observations in 54% of examinations. CONCLUSIONS: Dynamic upper airway obstructions were common in nonracing performance horses with respiratory noise and/or poor performance. Resting endoscopy was only helpful in determining exercising abnormalities with recurrent laryngeal neuropathy. POTENTIAL RELEVANCE: This study emphasises the importance of exercising endoscopic evaluation in nonracing performance horses with abnormal respiratory noise and/or poor performance for accurate assessment of dynamic upper airway function.

Prime-boost vaccination strategy in women with high-grade, noncervical anogenital intraepithelial neoplasia: clinical results from a multicenter phase II trial.

The objective of this study was to determine the clinical effectiveness of a prime-boost human papillomavirus (HPV) vaccine regimen. A nonrandomized phase II prime-boost vaccine trial was conducted. Women with biopsy-proven anogenital intraepithelial neoplasia (AGIN) 3 were vaccinated with three doses of a recombinant fusion protein comprising HPV 16, E6/E7/L2 (TA-CIN) followed by one dose of a recombinant vaccinia virus encoding HPV 16 and 18 E6/E7 (TA-HPV). Clinical responses were evaluated by serial photographs, symptomatology, and biopsies before and after vaccination. Twenty-nine women were vaccinated; 27 with vulval intraepithelial neoplasia 3 and 2 with vaginal intraepithelial neoplasia grade 3. Clinical responses were seen in five women (17%), with one complete and five partial responses. Fifteen women (62%) had symptomatic improvement. No serious adverse effects were recorded. This is the first trial of a prime-boost vaccination regimen using heterologous HPV vaccines (TA-CIN followed by TA-HPV) in the management of AGIN. Since the prime-boost approach in this cohort offered no significant advantages over single TA-HPV vaccination, there are no further studies planned using this protocol. Future studies are warranted to define responders to immunotherapy.

Correlations between exercising arterial blood gas values, tracheal wash findings and upper respiratory tract abnormalities in horses presented for poor performance.

REASONS FOR PERFORMING STUDY: There are limited data on the correlations between arterial blood gas (ABG) values, tracheal wash (TW) cytology and upper respiratory tract (URT) abnormalities. OBJECTIVES: To identify horses with abnormal exercising ABG, and compare the proportions of horses with abnormal ABG and TW cytology, mucus or URT dysfunction with those with normal ABG results and abnormal TW cytology, mucus or URT dysfunction. METHODS: Medical records of 813 horses presenting to the treadmill facility that had a complete treadmill examination, including ABG analysis, TW and URT endoscopy were selected. Diagnoses, ABG results, TW cytology and URT endoscopy were compared. RESULTS: Two hundred and eleven horses met the study criteria of a complete treadmill examination and could have ABG evaluated. There were no significant differences in the age distribution of horses having normal and abnormal ABG or upper respiratory tract (URT) examinations. There was a significantly higher percentage of geldings with abnormal ABG analysis. In the horses with abnormal URT examinations, there were no differences in the proportion of horses having mucus vs. no mucus. However, in the horses with normal URT, there were a higher percentage of horses with visible mucus in the group with abnormal ABG analysis. The majority of horses had abnormal TW cytology and evidence of prior EIPH, with no differences in proportions between the groups. CONCLUSIONS: Because such a large percentage of horses had evidence of inflammation and/or evidence of prior EIPH on TW cytology, it was not possible to determine the effect of these findings on gas exchange. Mucus was present in a larger percentage of cases with abnormal ABG analysis and normal URT examinations, suggesting that the presence of mucus may affect gas exchange. Standardbreds may be more likely to have abnormal gas exchange than Thoroughbreds. A larger number of horses is needed to determine the significance of these findings. POTENTIAL RELEVANCE: Abnormal TW cytology and endoscopic visualised mucus may contribute to impairment of gas exchange, but they do not specifically predict abnormal ABG analysis.

Dynamic pharyngeal collapse in racehorses.

REASON FOR PERFORMING STUDY: Dynamic pharyngeal collapse (PC) is a condition seen in racehorses that can be career-ending. OBJECTIVES: To characterise and grade PC and describe the effects of PC on athletic performance. METHODS: Medical records were reviewed for 828 horses, of which 49 (6%) records were identified as horses with a primary diagnosis of PC. Tapes of video-endoscopy of the pharynx during exercise were reviewed. Each video recording was assigned a grade (0-4) reflecting the degree of PC and a classification for severity of upper airway obstruction. Earnings per race prior to diagnosis of PC were compared to earnings per race after diagnosis of PC for all horses, as well as performance index (PI). Available exercising arterial blood gases were reviewed for horses with PC. RESULTS: There were 35 (80%) Thoroughbreds (TB), and 9 (20%) Standardbreds (STD). 32 (73%) had a history of making an upper respiratory noise. 4 (9%) grade 1 PC, 8 (18%) grade 2 PC, 26 (59%) grade 3 PC, and 6 (14%) grade 4 PC. Seven (16%) horses were classified as mild PC, 18 (41%) as low-moderate PC, 14 (32%) as high-moderate PC, and 5 (11%) as severe PC. Of 30 horses 11 had abnormally decreased PaO2 and 8 horses had abnormally elevated PaCO2. A significant decrease was found in earnings per race prediagnosis when compared to post diagnosis earnings per race in horses > or =4 years of age (P = 0.003). A significant decrease was also observed for earnings per race prediagnosis when compared to post diagnosis earnings per race in horses with grade 3 PC (P = 0.03) No significant differences were observed in PI before or after diagnosis of PC. CONCLUSIONS: There was a trend for PC to be observed in more TB than STD, and more males than females compared to the general hospital population. Horses with PC significant had decreases in arterial oxygenation. Racing records after a diagnosis of PC in all horses > or = 4 years of age suggesting that older horses have a guarded prognosis for continued success. POTENTIAL RELEVANCE: This study provides a classification system for dynamic pharyngeal collapse and suggests that older racehorses (> or = 4 years of age) diagnosed with PC and all horses with grade 3 PC have a poor prognosis for return to previous level of performance.

Incomplete sagittal fracture of the talus in 11 racehorses: outcome.

REASONS FOR PERFORMING STUDY: Little information exists regarding talus fractures in the horse and there have been no previously published case series of racehorses diagnosed with incomplete sagittal fracture of the talus. OBJECTIVE: To describe the diagnosis, treatment and post injury performance of horses with incomplete sagittal fracture of the talus. METHODS: Medical records of 11 racehorses (8 Standardbreds and 3 Thoroughbreds) admitted between January 1992 and January 1999 were reviewed. Subject details, anamnesis, results of lameness examination, radiographs and nuclear scintigraphic findings were evaluated. Racing performance was assessed by comparing pre- and post injury race records. RESULTS: Nuclear scintigraphic examination, performed in 8 of the 11 horses, revealed focal increased radiopharmaceutical uptake in the proximal aspect of the affected talus. Fractures could best be seen on dorsal 10-20 degrees lateral-plantaromedial oblique radiographs; all had raced pre-injury. All horses were treated conservatively and follow-up information was available for 8 horses, of which 7 raced after injury. Performance in 3 horses was improved, in 1 it was unchanged and in 3 horses performance declined. CONCLUSIONS: Horses with incomplete fracture of the talus have a good prognosis for return to racing after conservative management. POTENTIAL RELEVANCE: Incomplete sagittal fracture of the talus should be considered as a cause of hindlimb lameness in racehorses. Further research is necessary to determine the pathophysiology of these fractures.

Effect of TA-CIN (HPV 16 L2E6E7) booster immunisation in vulval intraepithelial neoplasia patients previously vaccinated with TA-HPV (vaccinia virus encoding HPV 16/18 E6E7).

Heterologous prime-boost vaccination schedules employing TA-HPV, a vaccinia virus encoding HPV 16/18 E6 and E7, in combination with TA-CIN, an HPV 16 L2E6E7 fusion protein, may offer advantages over the use of either agent alone for the immunotherapy of human papillomavirus (HPV) type 16-associated vulval intraepithelial neoplasia (VIN). In the present study, 10 women with HPV 16-positive high grade VIN, previously primed with TA-HPV, received three booster immunisations with TA-CIN. All but one demonstrated HPV 16-specific proliferative T-cell and/or serological responses following vaccination. Three patients additionally showed lesion shrinkage or symptom relief, but no direct correlation between clinical and immunological responses was seen.

Minichromosome maintenance (Mcm) proteins, cyclin B1 and D1, phosphohistone H3 and in situ DNA replication for functional analysis of vulval intraepithelial neoplasia.

Vulval intraepithelial neoplasia (VIN) is defined histopathologically by distinctive abnormalities of cellular maturation and differentiation. To investigate the functional properties of VIN, the expression of several proteins involved in the regulation of the cell cycle as well as in situ DNA replication competence was analysed by immunohistochemistry. Snap-frozen vulval biopsies were graded as normal squamous epithelium (n=6), undifferentiated HPV positive VIN 1 (n=3), VIN 2 (n=8) and VIN 3 (n=20). Immunohistochemistry was performed using the following markers: cyclin D1 (expressed in middle/late G1), cyclin B1 (expressed in G2/early M), phosphorylated histone H3 (expressed during mitosis) and minichromosome maintenance (Mcm) proteins 2 and 5 (expressed during the cell cycle, but not in differentiated or quiescent cells). In situ DNA replication competence was used to identify S-phase cells. The percentage of positively stained nuclei in three representative microscopic fields was calculated per biopsy. In normal vulva, the expression of all markers was restricted to the proliferative compartment of the basal layer of the epithelium. In contrast in high-grade VIN, the majority of epithelial cells expressed the Mcm proteins from basal to superficial layer. The detection of cyclins B1 and D1, phospho-histone H3 and in situ DNA replication was also found through the full thickness of these lesions but by a lower proportion of the cells. This is consistent with these markers providing a series of 'snapshots' of the cell cycle status of individual cells. The low-grade VIN showed reduced expression of the cell cycle markers in relation to the level of dysplasia. The combination of these analyses establishes that the majority of VIN cells remain in a functional replicative or prereplicative state of the cell cycle. Clinical application of these analyses may provide a basis for improved diagnosis of VIN.

An observational study of women with positive HPV-DNA tests and normal cytology and colposcopy.

PURPOSE: High risk human papillomaviruses (HPV) are implicated in the aetiology of malignant cervical disease. The usefulness of HPV DNA tests in identifying women at risk of cervical cancer as an adjunct to cervical cytology is under evaluation. PATIENTS AND METHODS: This is a retrospective analysis of 47 women positive for high risk HPV but with negative cytology and negative colposcopy at the start of the study. Women were observed for three years or more (in 96% cases) using six-monthly combined HPV DNA tests, cytological and colposcopic evaluation. RESULTS: At the end of follow-up, 29/47 (62%) women were still positive for high risk HPV, 45/47 (96%) women had normal cytology and 47/47 (100%) women continued to have normal colposcopy. CONCLUSIONS: Normal colposcopy has an excellent negative predictive value for HPV positive women with normal cytology. These women can be safely screened cytologically on a three-yearly basis.

Human T cell responses to HPV 16 E2 generated with monocyte-derived dendritic cells.

Persistent infection with human papillomavirus (HPV) type 16 has been implicated in the etiology of cervical cancer. The E2 protein is required early in viral infection and therefore may serve as a useful immune target for a vaccine aimed at prevention or therapy of premalignant lesions. Dendritic cells (DC) prepared from monocytes and pulsed with bacterially produced HPV 16 E2 C-terminus protein were used to stimulate autologous T cells over several rounds of stimulation. T cells were tested for gamma-interferon release by ELISPOT and for cytotoxic activity by (51)chromium release assays. To generate E2-expressing target cells for cytotoxicity assays, we constructed a recombinant vaccinia virus encoding HPV 16 E2, which was used to infect autologous Epstein-Barr virus-transformed lymphoblastoid cell lines (LCL). The results show that DC pulsed with E2 C-terminus protein induce gamma-interferon-releasing T cells as demonstrated by ELISPOT. Furthermore, we demonstrate E2-specific lysis of vaccinia-E2 infected autologous LCL by CD8+ cytotoxic T lymphocytes (CTL). E2-specific CTL did not lyse untreated autologous LCL or LCL infected with wild-type vaccinia and showed low levels of cytotoxicity against natural killer cell-sensitive K562 cells. In addition, T cells stimulated with DC in the absence of E2 failed to demonstrate lysis of vaccinia-E2-labeled targets. Phenotypically, CTL populations were CD3+/CD8+. These results will facilitate the study of naturally occurring T-cell responses to HPV E2 in patients with cervical intraepithelial neoplasia and the development of immunotherapeutic strategies designed to treat this and other HPV-associated diseases.

The role of human papillomavirus vaccines in cervical neoplasia.

Cervical cancer is the second most common cause of cancer-related death in women, in some developing countries accounting for the highest cancer mortality. The evidence for the association of high-risk human papillomavirus types with the aetiology of cervical neoplasia is firmly established, human papillomavirus being detected in virtually all cervical cancers. The risk of progression of precursor cervical intra-epithelial neoplasia lesions is associated with persistence of human papillomavirus infection. One strategy for the management of cervical neoplasia worldwide could be the development of prophylactic and/or therapeutic human papillomavirus vaccines. This chapter will discuss the natural history of human papillomavirus infection, viral immunity and the clinical course of resultant disease as the background to the effective design and use of human papillomavirus vaccines for protection or therapy. The progress of ongoing phase I and II clinical trials for several different vaccine preparations and the challenges for establishing their future use will be discussed.

Planning and managing computerized order entry: a case study of IT-enabled organizational transformation.

This article uses a model for technology-enabled organizational transformation to analyze a case study of computerized order entry at a medium-sized, urban hospital. The hospital achieved initial goals for direct order entry by physicians and improvements in patient care and is now using the system to implement disease management policies. The authors use the model to examine decisions and actions that facilitated or constrained effective implementation of the system and discuss the model's implications for managing implementation of computerized order entry technologies in health care systems.

Prenatal toxicity studies in rats and rabbits with the calcium channel blocker diproteverine.

In prenatal toxicity studies, diproteverine, a calcium channel blocker with demonstrated antianginal properties, produced an unusual pattern of digital, heart, tail, and vertebral defects in rat fetuses from mothers treated during the major period of organogenesis, but only a very low incidence of heart abnormalities was seen in the rabbit. Heart changes were rarely seen in association with digital defects. The findings were consistent with those seen with other calcium channel blockers and add weight to the suggestion of Danielsson and colleagues (5) that digital malformations are a class effect for this type of compound, the effects being related to reduced uteroplacental blood flow. In addition, it is proposed that cardiovascular malformations are also a class response with calcium channel blockers. The distribution of fetal death and hemorrhages and the varying association between cardiovascular, digital, and tail abnormalities seen in the rat with increasing doses of diproteverine fits the pattern of changes reported following hypoxia in the chick embryo. Reduced uteroplacental blood flow with resultant embryonic hypoxia secondary to pharmacologic action is considered a probable mechanism of action for the induction of abnormalities produced by calcium channel blockers.

Expression of mRNA and immunocytochemical localization of inhibin alpha- and inhibin beta A-subunits in the fetal sheep testis.

In order to investigate the ontogeny of gonadal inhibin production in the male fetal sheep, testes were collected from male fetuses at days 70, 100, 130 and 140 of gestation (term = 145 days). The expression and localization of inhibin alpha- and inhibin beta A-subunit mRNA and protein were evaluated using in situ hybridization and immunocytochemistry. The expression of inhibin alpha-subunit mRNA was localized within the seminiferous cords of the developing fetal testis and progressively increased with gestational age. Immunostaining corresponding to immunoreactive inhibin alpha-subunit was detected in Sertoli cells within the seminiferous cords at days 100, 130 and 140 of gestation. In addition, immunostaining was detectable in a small proportion of Leydig cells. No expression of inhibin beta A-subunit mRNA or immunoreactivity was detected in any testicular tissue at any stage of gestation. These data show that the Sertoli cells of the developing fetal sheep testis have the capacity to produce inhibin alpha-subunit by day 100 of gestation and that production increases during late gestation.

Personality disorder in patients infected with HIV: a controlled study with implications for clinical care.

OBJECTIVE: Previous studies of psychiatric illness in populations infected with or at risk for HIV have not included systematic evaluation for personality disorders. The authors present the first controlled study of 1) personality disorders in HIV-positive and HIV-negative homosexual men and 2) the impact of personality disorder on coping, social support, and mood in asymptomatic HIV-positive homosexual men. METHOD: The authors studied 58 asymptomatic HIV-positive and 53 HIV-negative homosexual men living outside the high-prevalence epicenters of the AIDS epidemic. Personality disorder was assessed with a clinician-administered interview, the Structured Clinical Interview for DSM-III-R. RESULTS: There was a significantly higher prevalence of personality disorder in the HIV-positive (33%) than in the HIV-negative (15%) subjects. In the HIV-positive subjects, those with a personality disorder (compared to those without a personality disorder) showed 1) significantly greater mood disturbance, with higher scores on the Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Profile of Mood States Total Mood Dysfunction, and the Beck Hopelessness Scale, 2) greater use of denial and helplessness when coping with the threat of AIDS, and 3) greater social conflict. CONCLUSIONS: These findings suggest that personality disorder is common in the HIV-positive population. Compared with HIV-infected patients without a personality disorder, patients with a personality disorder may experience greater dysphoria and be more likely to cope with the threat of AIDS in a dysfunctional way. Recognition of the impact of personality disorder on coping with HIV infection is important for comprehensive, sensitive, and effective clinical care.

Decisions for and against resuscitation in an acute geriatric medicine unit serving the frail elderly.

Recent studies indicate continuing controversy over the appropriateness of intensive care in various clinical settings, particularly for very young and very old patients. We studied decisions regarding cardiopulmonary resuscitation (CPR) and the associated clinical course in an acute geriatric unit serving the frail elderly. Despite multiple acute and chronic conditions, advanced age, and functional impairment, patients overwhelmingly preferred CPR. The patients with do-not-resuscitate (DNR) orders were more functionally dependent, more acutely and chronically ill, and less likely to participate in the decision regarding CPR. The majority of DNR orders were made by surrogates, while the majority of CPR directives were made by the patients themselves. Other forms of acute and supportive care, such as parenteral antibiotics, artificial feeding, and transfusions were not withheld from the DNR patients unless a separate decision to limit a specific treatment was undertaken following consultation between the attending physician and the patient or family. Acuity of illness greater than two SDs above the unit mean and the presence of a surrogate decision maker predicted the majority of DNR orders. Length of stay averaged 28 days for all unit patients, 24 days for patients choosing CPR, and 46 days for patients with DNR orders. The four patients who were resuscitated but died stayed an average of 25 days, while the two survivors of resuscitation stayed 20 and 53 days, respectively. The findings indicate that patients and their families considered appropriate clinical criteria including severity of illness when making their decisions about CPR. Nevertheless, the majority chose to be resuscitated in the event of an arrest. Further studies are needed to explore medical decision making by elderly inpatients and their surrogates and to describe the associated clinical course.