ABSTRACT
BACKGROUND: Lesbian, bisexual, or gay individuals (LBGs) have an increased risk for mental health problems compared to heterosexuals, but this association has sparsely been investigated for psychotic disorders. The aim of this study was: (1) to examine whether LBG sexual orientation is more prevalent in individuals with a non-affective psychotic disorder (NAPD) than in people without a psychotic disorder; and if so, (2) to explore possible mediating pathways. METHODS: Sexual orientation was assessed in the 6-year follow-up assessment of the Dutch Genetic Risk and Outcome of Psychosis study (GROUP), a case-control study with 1547 participants (582 patients with psychotic disorder, 604 siblings, and 361 controls). Binary logistic regression analyses were used to calculate the risk of patients with a psychotic disorder being LBG, compared to siblings and controls. Perceived discrimination, history of bullying, childhood trauma (CT), and sexual identity disclosure were investigated as potential mediating variables. RESULTS: The proportion of individuals with LBG orientation was 6.8% in patients (n = 40), 4.3% in siblings (n = 26), and 2.5% in controls (n = 10). The age- and gender-adjusted odds ratio of LBG for patients was 1.57 (95% CI 1.08-2.27; p = 0.019), compared to siblings and controls. Discrimination, bullying, and CT all partially mediated this association. CONCLUSIONS: Adverse social experiences related to sexual minority status may increase the risk for NAPD. Sexual identity, behavior, and difficulties need more attention in everyday clinical practice.
Subject(s)
Psychotic Disorders/epidemiology , Psychotic Disorders/psychology , Sexual and Gender Minorities/psychology , Sexuality/psychology , Adolescent , Adult , Case-Control Studies , Female , Homosexuality/psychology , Humans , Male , Middle Aged , Netherlands/epidemiology , Risk Factors , Sexual and Gender Minorities/statistics & numerical data , Sexuality/statistics & numerical data , Young AdultABSTRACT
We investigated the effects of several modifications of the Western diet on a medium-sized rodent, Neotoma micropus, that lives in the area of the wildland-urban interface. We conducted a laboratory study of the response of N. micropus to high fat-high fructose (HFHF), high fat-high sucrose (HFHS), high fat-low sugar (HFLSu) and control (low fat-low sugar) diets. We found a significant increase in hepatic lipid deposition and a significant decrease in podocytes in those animals that consumed the HFHF and HFLSu diets compared to those on the HFHS and control diets. We found no significant differences in Bowman's space or hepatic collagen formation. We predict that N. micropus in the wild, with access to anthropogenic resources, will show similar effects as a result of the consumption of anthropogenic resources.
Subject(s)
Diet, Western/adverse effects , Dietary Carbohydrates/adverse effects , Dietary Fats/adverse effects , Lipid Metabolism/physiology , Liver/metabolism , Sigmodontinae/metabolism , Animal Nutritional Physiological Phenomena , Animals , Collagen , Fructose/administration & dosage , Fructose/adverse effects , Podocytes , Sucrose/administration & dosage , Sucrose/adverse effectsABSTRACT
BACKGROUND: Individuals with generalized social anxiety disorder (gSAD) exhibit attentional bias to salient stimuli, which is reduced in patients whose symptoms improve after treatment, indicating that mechanisms of bias mediate treatment success. Therefore, pre-treatment activity in regions implicated in attentional control over socio-emotional signals (e.g. anterior cingulate cortex, dorsolateral prefrontal cortex) may predict response to cognitive behavioral therapy (CBT), evidence-based psychotherapy for gSAD. METHOD: During functional magnetic resonance imaging, 21 participants with gSAD viewed images comprising a trio of geometric shapes (circles, rectangles or triangles) alongside a trio of faces (angry, fearful or happy) within the same field of view. Attentional control was evaluated with the instruction to 'match shapes', directing attention away from faces, which was contrasted with 'match faces', whereby attention was directed to emotional faces. RESULTS: Whole-brain voxel-wise analyses showed that symptom improvement was predicted by enhanced pre-treatment activity in the presence of emotional face distractors in the dorsal anterior cingulate cortex and dorsal medial prefrontal cortex. Additionally, CBT success was foretold by less activity in the amygdala and/or increased activity in the medial orbitofrontal gyrus during emotion processing. CONCLUSIONS: CBT response was predicted by pre-treatment activity in prefrontal regions and the amygdala. The direction of activity suggests that individuals with intact attentional control in the presence of emotional distractors, regulatory capacity over emotional faces and/or less reactivity to such faces are more likely to benefit from CBT. Findings indicate that baseline neural activity in the context of attentional control and emotion processing may serve as a step towards delineating mechanisms by which CBT exerts its effects.
Subject(s)
Amygdala/physiopathology , Attention/physiology , Cognitive Behavioral Therapy/methods , Emotions/physiology , Phobic Disorders/therapy , Prefrontal Cortex/physiopathology , Treatment Outcome , Adult , Executive Function/physiology , Facial Expression , Female , Humans , Magnetic Resonance Imaging , Male , Phobic Disorders/physiopathology , Young AdultABSTRACT
Theory predicts that the evolution of phenotypic plasticity depends upon cues that indicate environmental change. Predators typically induce plastic responses in prey. However, variation among populations of predators alters the frequency of predation and, possibly, the evolution of plasticity. We compared responses to predator cues in Daphnia ambigua from lakes where alewife (Alosa pseudoharengus) either do (anadromous) or do not (landlocked) migrate between marine and freshwater. In 'anadromous' lakes, Daphnia are abundant each spring but eliminated by alewives in summer, whereas Daphnia are constantly under the threat of predation in 'landlocked' lakes. Daphnia from 'anadromous' lakes grew faster, matured earlier and larger, produced more offspring and invested more in sex than Daphnia from landlocked lakes. We observed several significant lake type-by-predator treatment interactions. These interactions, whereby the differences between lakes were greater in predator-conditioned water, agree with theory and argue that Daphnia plasticity has been influenced by variation in alewives.
Subject(s)
Animal Migration , Biological Evolution , Daphnia/genetics , Escape Reaction , Fishes , Gene-Environment Interaction , Sexual Behavior, Animal , Animals , Clutch Size , Daphnia/physiology , Female , Fertility , Food Chain , Genetic Variation , Lakes , Linear Models , Male , Phenotype , Pheromones , ReproductionABSTRACT
There is a need to develop more potent oncolytic adenoviruses (Ads) that show increased antitumor activity in patients. The HYPR-Ads are targeted oncolytic Ads that specifically kill tumor cells, which express active hypoxia-inducible factor (HIF). While therapeutically efficacious, the HYPR-Ads showed attenuated replication and oncolytic activity. To overcome these deficiencies and improve antitumor efficacy, we created new HIF-activated oncolytic Ads, HIF-Ad and HIF-Ad-IL4, which have two key changes: (i) a modified HIF-responsive promoter to regulate the E1A replication gene and (ii) insertion of the E3 gene region. The HIF-Ads showed conditional activation of E1A expression under hypoxia. Importantly, the HIF-Ads show hypoxia-dependent replication, oncolytic and cellular release activities, and potent antitumor efficacy, all of which are significantly greater than that of the HYPR-Ads. Notably, HIF-Ad-IL4 treatment led to regressions in tumor size by 70% and extensive tumor infiltration by leukocytes resulting in an antitumor efficacy that is up to six-fold greater than that of the HYPR-Ads, HIF-Ad and wild-type Ad treatment. These studies show that treatment with an HIF-activated oncolytic Ad leads to a measurable therapeutic response. The novel design of the HIF-Ads represents a significant improvement compared with first-generation oncolytic Ads and has great potential to increase the efficacy of this cancer therapy.
Subject(s)
Adenoviridae/physiology , Antineoplastic Agents/metabolism , Basic Helix-Loop-Helix Transcription Factors/metabolism , Gene Expression Regulation , Genetic Therapy/methods , Genetic Vectors/standards , Virus Replication , Adenoviridae/genetics , Adenovirus E1A Proteins/genetics , Adenovirus E1A Proteins/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Cell Hypoxia/physiology , Genetic Therapy/standards , Genetic Vectors/genetics , HEK293 Cells , Humans , Interleukin-4/genetics , Interleukin-4/metabolism , Neoplasms/therapy , Oncolytic Viruses/genetics , Oncolytic Viruses/physiology , Tumor Cells, Cultured , Virus ReleaseABSTRACT
INTRODUCTION: Neuroimaging of the brain in the diagnostic work-up of patients with neurodevelopmental disorders is a matter of continuing debate. Recommendations range from performing brain imaging in all patients with neurodevelopmental disorders to performing an MRI only in those with indication on clinical examinations. Important indications for neuroimaging are head size abnormalities and focal neurological findings. METHODS: Patients with neurodevelopmental disorders of unknown origin (n = 410), referred to a specialized tertiary diagnostic center for neurodevelopmental disorders were included in a retrospective analysis. A 1-day work-up, including an MRI of the brain was performed. Studied were the: (i) yield of MRI scans of the brain and (ii) associations of specific clinical symptoms/signs with abnormal and diagnostic MRI scans. RESULTS: (i) In 30.7% of the 410 patients with neurodevelopmental disorders (n = 126), abnormal MRI scans were observed, leading to an etiological diagnosis in 5.4% of the patients (n = 22). (ii) Pyramidal disorders (P = 0.001), epilepsy (P = 0.04) and an abnormal head circumference (P = 0.02) were associated with an abnormal MRI scan. The presence of one of the following neurological symptoms/signs: movement disorders, pyramidal disorders, epilepsy, or an abnormal head circumference was associated with a diagnostic MRI scan (P < 0.001) (diagnostic MRI % in neurological versus no neurological symptoms/signs, 13.0% versus 1.9%). CONCLUSION: Neuroimaging of the brain in a tertiary care center for patients with neurodevelopmental disorders of unknown origin is useful, especially in case of neurological symptoms/signs.
Subject(s)
Brain/pathology , Developmental Disabilities/diagnosis , Magnetic Resonance Imaging , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Retrospective StudiesABSTRACT
The H5N1 virus currently circulating is continuing to evolve, and it has already resulted in the extension of its host and geographical range. It is likely that H5N1 will become a global problem for the poultry industry. How many of the recent H5N1 changes observed have been induced by changing patterns in poultry raising? A change in attitude on the use of high-quality vaccines is a change that would drastically help in the control of the current epidemic in the poultry industry. This article provides an overview of the changing properties that have been observed during the current H5N1 outbreaks.
Subject(s)
Birds/virology , Influenza A Virus, H5N1 Subtype/pathogenicity , Influenza in Birds/epidemiology , Influenza in Birds/virology , Influenza, Human/virology , Animals , Humans , Influenza, Human/transmission , VirulenceABSTRACT
Oculodentodigital dysplasia (ODDD) is a rare, autosomal dominant pleiotropic disorder, caused by mutations in the Connexin 43 (Cx43 or GJA1) gene. Described here is the case of a 10-year-old girl with enamel hypoplasia, typical facies and mental delay, initially thought to be related to an unknown metabolic disorder. Careful clinical re-evaluation revealed a type of ODDD, characterised by the predominance of facial and ophthalmological involvement with mandibular retrognathism, and by the absence of cutaneous hand or foot syndactyly. A novel single-sequence variation (Nt460A>G) in exon 2, resulting in the substitution of alanine for threonine at amino acid 154, was found. These findings confirm once again the highly variable phenotypic expression caused by Cx43 mutations.
Subject(s)
Abnormalities, Multiple/genetics , Connexin 43/genetics , Eye Abnormalities/genetics , Odontodysplasia/genetics , Retrognathia/genetics , Syndactyly/genetics , Child , Child, Preschool , Craniofacial Abnormalities/complications , Craniofacial Abnormalities/genetics , DNA Mutational Analysis , Dental Enamel Hypoplasia/genetics , Eye Abnormalities/complications , Facies , Female , Humans , Odontodysplasia/complications , Retrognathia/complications , Syndactyly/complicationsABSTRACT
PURPOSE: The problem of complex healthcare to MS patients, together with the rising prevalence of MS and escalating costs, has caused healthcare policy makers to consider innovative approaches to controlling costs and improving the quality of care. An integrated care approach may provide a means for better coordination and delivery of care. The aim is to review recent integrated care initiatives and their significance for MS patients. METHOD: A literature search was conducted to trace relevant literature on integrated care for MS patients published between 1995 and 2003. RESULTS: Although integrated care appears to offer potential for eliminating fragmentation and discontinuity in healthcare for MS patients, there are few published studies which have evaluated its implementation with MS patients. CONCLUSIONS: Even though the potential advantages of integrated care are well known, the applicability of this approach for MS patients has still to be demonstrated.
Subject(s)
Delivery of Health Care, Integrated , Multiple Sclerosis/rehabilitation , HumansABSTRACT
To visualize the topography of thin oxide films during growth, thereby enabling to study its growth behavior quasi real-time, we have designed and integrated an atomic force microscope (AFM) in a pulsed laser deposition (PLD) vacuum setup. The AFM scanner and PLD target are integrated in a single support frame, combined with a fast sample transfer method, such that in situ microscopy can be utilized after subsequent deposition pulses. The in situ microscope can be operated from room temperature up to 700 °C and at (process) pressures ranging from the vacuum base pressure of 10-6 mbar up to 1 mbar, typical PLD conditions for the growth of oxide films. The performance of this instrument is demonstrated by resolving unit cell height surface steps and surface topography under typical oxide PLD growth conditions.
ABSTRACT
Immunosuppression with rapid discontinuation of corticosteroids, usually with induction therapy, is safe in kidney transplant recipients. In 89 patients, we induced immunosuppression with basiliximab or rabbit antithymocyte globulin (17 and 72 patients, respectively). Selection criteria for basiliximab were age (>or=65 years), history (malignancy; chronic infection), and type 1 diabetes mellitus (eligible for pancreas transplant). Steroids were administered through posttransplantation day 4 (five doses); maintenance immunosuppression was with tacrolimus and mycophenolate mofetil. At last follow-up (average, 286 days), most patients were steroid-free (antithymocyte globulin, 90%; basiliximab, 88%). Protocol biopsies were performed at 1, 4, and 12 months posttransplantation. The overall risk of biopsy-proven acute rejection was 12%. At 6 months posttransplantation, acute rejection-free survival was 93% for antithymocyte globulin, 65% for basiliximab (P<.001). Median time to biopsy-proven acute rejection was 27 and 71 days, respectively. The low incidence of biopsy-proven acute rejection with steroid-avoidance immunosuppression may be further reduced with antithymocyte globulin.
Subject(s)
Antibodies, Monoclonal/adverse effects , Antilymphocyte Serum/adverse effects , Graft Rejection/epidemiology , Immunosuppressive Agents/adverse effects , Kidney Transplantation/immunology , Recombinant Fusion Proteins/adverse effects , Acute Disease , Adrenal Cortex Hormones , Adult , Aged , Animals , Basiliximab , Female , Humans , Male , Middle Aged , Patient Selection , Rabbits , Risk FactorsABSTRACT
Three neonates, all girls, were presented immediately after birth with severe hypotonia. Two of them needed artificial ventilation because of respiratory insufficiency. All three pregnancies had been complicated by reduced fetal movements and moderate cerebral ventricular dilatation and in two of the three there was also polyhydramnios and congenital talipes. In all three infants congenital myotonic dystrophy was suspected after diagnosing myotonia in the mother. This was done by observing that none of the mothers were unable to release their grip immediately on command after shaking hands. Ophthalmological examination of the women revealed polychromatic lens crystals characteristic of myotonic dystrophy. Congenital myotonic dystrophy was confirmed by DNA analysis, as well as myotonic dystrophy in the mothers. All had an expansion of the number of cytosine-thymine-guanine(CTG)-trinucleotides in a part of the myotonic dystrophy protein-kinase gene. The first two infants died after 2 days and 15 months respectively.
Subject(s)
DNA Mutational Analysis , Hand/physiopathology , Muscle Hypotonia/congenital , Myotonic Dystrophy/congenital , Fatal Outcome , Female , Hand Strength , Humans , Infant, Newborn , Muscle Hypotonia/diagnosis , Muscle Hypotonia/genetics , Myotonic Dystrophy/diagnosis , Myotonic Dystrophy/geneticsABSTRACT
In this study we investigated the expression of the Balb/c mouse alpha 1-acid glycoprotein genes. Mice, like humans, have two distinct alpha 1-acid glycoprotein mRNAs. As in humans and rats, mouse alpha 1-acid glycoprotein is a strong acute-phase reactant and its expression can be induced by acute-phase stimulatory agents such as bacterial lipopolysaccharides. Southern analysis and partial sequencing of different alpha 1-acid glycoprotein genomic clones indicated the existence of three distinct alpha 1-acid glycoprotein genes in the Balb/c genome. Using oligonucleotide hybridization, we showed that two of the three genes were expressed while the third gene was either not expressed or expressed at extremely low levels. The mRNA levels for the two expressed genes, alpha 1-acid glycoprotein-1 and alpha 1-acid glycoprotein-2, were both induced during the acute-phase response. However, alpha 1-acid glycoprotein-2 mRNA was present in at least 10-fold higher levels in both induced and uninduced mice. There were also differences in the developmental patterns of the two mRNAs in that the constitutive alpha 1-acid glycoprotein-1 mRNA levels increased 20-fold between 2 and 7 months, while alpha 1-acid glycoprotein-2 mRNA pools remained constant. During the acute-phase response in aged animals, there was an increase in the time required for both mRNAs to respond, and the maximum induced level of both mRNAs decreased. These studies set the stage for future experiments to determine the mechanisms by which the different alpha 1-acid glycoprotein genes are regulated during the acute-phase response and how aging affects these regulatory processes.
Subject(s)
Aging/genetics , Gene Expression , Inflammation/genetics , Orosomucoid/genetics , Animals , Base Sequence , Blotting, Northern , Blotting, Southern , DNA/genetics , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Nucleic Acid Hybridization , RNA, Messenger/analysisABSTRACT
Spinocerebellar ataxia type 7 (SCA7) represents a very rare and severe autosomal dominantly inherited cerebellar ataxia (ADCA). It belongs to the group of CAG-repeat or polyglutamine diseases with its underlying molecular genetical defect on chromosome 3p12-p21.1. Here, we performed a systematic study of the neuropathology on unconventional thick serial sections of the first available brain tissue of a genetically confirmed late-onset SCA7 patient with a very short CAG-repeat expansion. Along with myelin pallor of a variety of central nervous fiber tracts, we observed i) neurodegeneration in select areas of the cerebral cortex, and ii) widespread nerve cell loss in the cerebellum, thalamus, nuclei of the basal ganglia, and brainstem. In addition, upon immunocytochemical analysis using the anti-polyglutamine antibody 1C2, immunopositive neuronal intranuclear inclusions bodies (NI) were observed in all cerebellar regions, in all parts of the cerebral cortex, and in telencephalic and brainstem nuclei, irrespective of whether they underwent neurodegeneration. These novel findings provide explanations for a variety of clinical symptoms and paraclinical findings of both our and other SCA7 patients. Finally, our immunocytochemical analysis confirms previous studies which described the presence of NI in obviously degenerated brain and retinal regions as well as in apparently well-preserved brain regions and retina of SCA7 patients.
Subject(s)
Brain/pathology , Spinocerebellar Ataxias/pathology , Aged , Female , Humans , Immunohistochemistry , Nerve Degeneration/pathology , Retina/pathology , Spinocerebellar Ataxias/genetics , Trinucleotide Repeat ExpansionABSTRACT
Recent clinical trials have documented the short-term safety of steroid avoidance (SA) in kidney transplant recipients. Since July 2003, we have used a SA immunosuppression protocol for low-risk kidney transplant recipients. Eligibility criteria are age > or = 18, primary transplant (living or deceased donor), and tacrolimus started by postoperative day 3. Recipients were excluded if peak/current PRA was >50%/20%, or if they had a positive flow crossmatch, or if they had the recent use of corticosteroids (<6 months). All recipients received induction with rabbit anti-thymocyte globulin, total dose 6 mg/kg, or basiliximab. Recipients received 5 daily doses of corticosteroid and mycophenolate mofetil 1 gm twice daily starting on the day of transplantation. Tacrolimus was started when the serum creatinine level decreased by 20%, or by postoperative day 3. The goal for trough tacrolimus levels was 10-15 ng/mL for the first month, 8-12 ng/mL for months 2-3, and 5-10 ng/mL after month 3. Protocol biopsies (bx) were performed at reperfusion, 1 month, 4 months, and 12 months. Ninety-four kidney transplantations were performed during the study period. Sixty-seven recipients (71%) were eligible and enrolled in SA. Characteristics of the 67 SA recipients: mean age, 53 years (range, 26-70); 41% female; 67% Caucasian; 24% Hispanic; 15% African American; and 5% Native American. Also, 77% received a living donor kidney. The mean follow-up was 180 days (range, 10-360). At last follow-up, 91% remained steroid-free. Biopsy-proven acute rejection (BPAR) occurred in 5 recipients (7.5%). Three recipients (4.5%) had clinical BPAR and 2 had subclinical. One recipient died with pneumonia 4 months following transplantation. Posttransplantation diabetes mellitus (PTDM) occurred in 2 (5%) of 38 recipients. In the initial 41 recipients, 27 had protocol bx at 1 month and 13 at 4 months available for analysis. Chronic allograft nephropathy (CAN) was present on protocol bx in 48% at 1 month and 69% at 4 month. Actuarial (Kaplan-Meier method) patient and graft survival rates at 351 days were 97.8% and 96.8%, respectively. SA with anti-thymocyte globulin induction in low-immunologic risk kidney transplant recipients is safe and is associated with a low risk of BPAR. The incidence of PTDM appears to be lower.
Subject(s)
Adrenal Cortex Hormones/adverse effects , Immunosuppression Therapy/methods , Kidney Transplantation/immunology , Adult , Aged , Antilymphocyte Serum/therapeutic use , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Postoperative Complications/chemically induced , Postoperative Complications/prevention & control , Tacrolimus/therapeutic use , Transplantation, Homologous/immunologyABSTRACT
We studied the selection response of the freshwater grazing zooplankter, Daphnia galeata, to increased abundance of cyanobacteria in its environment. Cyanobacteria are a poor-quality and often toxic food. Distinct genotypes of D. galeata were hatched from diapausing eggs extracted from three time horizons in the sediments of Lake Constance, Europe, covering the period 1962 to 1997, a time of change in both the prevalence of planktonic cyanobacteria and levels of phosphorus pollution. We assessed whether the grazers evolved to become more resistant to dietary cyanobacteria by exposing genetically distinct clones to two diets, one composed only of the nutritious green alga, Scenedesmus obliquus (good food), and the other a mixture of S. obliquus and the toxic cyanobacterium Microcvstis aeruginosa (poor food). Genotype performance was measured as the specific rate of weight gain from neonate to maturity (gj). We evaluated evolutionary change in the Daphnia population using an analysis of reaction norms based on relative (log-transformed) changes in gj. Log(gj) is a measure of the proportional effect of dietary cyanobacteria on other fitness components of the Daphnia phenotype. For comparison, we also analyze absolute (i.e., nontransformed) changes in gj and discuss the interpretations of the two approaches. Statistical results using a general linear model demonstrate a significant effect of genotype (showing differences in gj among genotypes), a significant genotype x food-type interaction (showing differences in phenotypic plasticity among genotypes), and, in the case of log-transformed data, a significant sediment-genotype-age x food-type interaction. The latter shows that phenotypic plasticity evolved over the period studied. Two constraints act on response to selection in the D. galeata-Lake Constance system. First, gj on a diet containing poor food is highly correlated with gj on a diet of good food, thus evolving resistance also meant evolving an increase in gj on both diets. Second, because genotypes with a high gj also grow to a large adult body size, which in turn increases Daphnia vulnerability to fish predation, we suggest that selection only acted to favor genotypes possessing a high potential gj after cyanobacteria became prevalent. The presence of cyanobacteria depressed realized gj and led to animals of small adult body size even if their genotypes had the potential for high gj and large size. With realized gj reduced, genotypes with an inherently high value could be selected even in the presence of predatory fish. The joint action of selection by dietary cyanobacteria and vulnerability to fish predation provides an explanation for the observed evolution of resistance to poor food through reduced phenotypic plasticity.
Subject(s)
Biological Evolution , Cyanobacteria , Daphnia/physiology , Selection, Genetic , Animals , Daphnia/genetics , Daphnia/growth & development , Diet , PhenotypeABSTRACT
To examine a possible association between plasma viremia and interferon-alpha (IFN-alpha) in patients with the acquired immunodeficiency syndrome (AIDS), we performed IFN plasma immunoadsorption by apheresis (IFN-alpha apheresis) in four volunteers with AIDS who had sustained levels of endogenous plasma IFN-alpha. IFN-alpha apheresis with two plasma volume exchanges was performed daily for 5 days. Clinical signs and symptoms and hematologic, virologic, and immunologic parameters were monitored. Two subjects developed anemia from phlebotomy, and one had a catheter++-associated bacteremia. The IFN-alpha apheresis was effective only in transiently removing IFN-alpha: depletion of IFN-alpha led only to its rapid reconstitution. Cell-associated HIV-1 was unchanged, but three of four subjects had a modest decrease in culturable plasma virus burden following the procedures. The recovery of in vivo HIV-1-related IFN-alpha by apheresis allowed its biologic and biochemical characterization. The HIV-1 IFN-alpha showed characteristics on ELISA, western blot, and biologic assays similar to two subspecies of the natural protein. The natural, recombinant, and HIV-1-induced IFN-alpha s demonstrated nearly identical antiviral activities. The HIV-1 IFN-alpha eluted from the column was not acid labile. The inability of large amounts of plasma IFN-alpha found in some patients with AIDS to affect viral burden likely reflects properties of the virus or of host factors independent of IFN-alpha.
Subject(s)
Acquired Immunodeficiency Syndrome/blood , HIV-1 , Interferon-alpha/blood , Acquired Immunodeficiency Syndrome/immunology , Acquired Immunodeficiency Syndrome/virology , Adult , Base Sequence , Blood Component Removal/adverse effects , Female , Humans , Male , Middle Aged , Molecular Sequence Data , Virus ReplicationABSTRACT
UNLABELLED: Von Hippel-Lindau disease is an autosomal dominant inherited disorder causing hemangioblastomas of the central nervous system (CNS), retinal hemangiomas, renal cell carcinomas, pheochromocytomas, pancreatic and liver cysts, and epididymal cystadenomas. PURPOSE: Since 1976, we have periodically screened for the lesions in a large affected family and were able to evaluate new strategies in detection and treatment. PATIENTS AND METHODS: A total of 23 individuals underwent the screening program. A multidisciplinary team of physicians was involved. RESULTS: In 13 patients (7 females and 6 males), a total of 31 tumors was detected; hemangioblastoma of the CNS (9), retinal angioma (4), renal involvement (8), pheochromocytoma (4), pancreatic lesions (4), and liver lesions (2) were diagnosed by periodic family screening. On the basis of more than 10 years of experience and current literature, new criteria for diagnosis and treatment have been proposed. CONCLUSION: The von Hippel-Lindau disease gene appears to be a tumor suppressor gene, and its absence or a defect in its structure is responsible for the predisposition to the disease. Tumor development depends on a somatic second mutation in the homologous allele. That means, in disease-gene carriers, tumor growth may begin at any age. Most of the lesions can be treated successfully when diagnosed in time. Periodic screening by a multidisciplinary team has to be continued lifelong.
Subject(s)
von Hippel-Lindau Disease/diagnosis , von Hippel-Lindau Disease/genetics , Adult , Female , Genetic Linkage , Humans , Male , Middle Aged , Pedigree , von Hippel-Lindau Disease/complications , von Hippel-Lindau Disease/therapyABSTRACT
OBJECTIVES: To test the effects of a communication skills training intervention on older patients' discourse during a primary care interview. DESIGN: A quasi-experimental design involving two intervention conditions. SETTING: The Family Practice Center of a university-based clinic. PARTICIPANTS: Thirty-three patients averaging age 72 and 9 family practice physicians. INTERVENTION: A communication skills training booklet received approximately 3 days before the scheduled appointment and a 30-minute face-to-face follow-up session before seeing the physician. MEASUREMENTS: Patients' seeking, providing, and verifying of information were coded from transcripts of the 33 interviews. RESULTS: Trained patients engaged in significantly more seeking and providing of information than untrained patients. Additionally, trained patients obtained significantly more information from physicians than did untrained patients, both in terms of the number of total information units and the number of units per question asked. CONCLUSION: Patient communication skills training appears to be an effective means of enhancing patients' participation in the medical interview without increasing the overall length of the interview.
Subject(s)
Communication , Pamphlets , Patient Education as Topic , Physician-Patient Relations , Primary Health Care , Aged , Family Practice , Female , Humans , Male , Medical History Taking , Ohio , Patient ParticipationABSTRACT
OBJECTIVE: To examine the behavioral and functional problems of the cognitively impaired. DESIGN: A survey of a cohort of residents from six nursing homes. PARTICIPANTS: Subjects were randomly selected based on a minimum age of 70 years and a Resource Utilization Group (RUG) classification of the Physical or Behavioral type. Of those eligible, 44% (n = 366) agreed to participate. The participants and non-participants had similar demographics except for a higher incidence of mental illness in the non-participant group, which did not have a significant impact on agitation. SETTING: Six nursing homes in New York City, three voluntary non-profit and three proprietary. MEASUREMENT: The study used chart review, assessment of residents' cognitive and functional abilities, nursing assistants' ratings of residents' functional abilities, behavioral problems, and the amount of effort required in care, and time-motion observations of staff-resident interactions. RESULTS: Residents' level of cognitive impairment had a significant impact on problem behaviors during ADL tasks, along with supervision required in patient care (P < 0.05). These results were validated by time-motion analysis. Regression analysis revealed that for non-demented subjects, the best indicator of care needs was health status, while for demented residents the best indicator was cognitive status (P < 0.0001). CONCLUSIONS: The care needs of residents with dementia are better estimated by a mental status test for cognitive impairment then by ADL assessment alone. Greater agitation is associated with increasing cognitive impairment. Further, agitation and behavioral problems associated with care result in a need for increased staff supervision.