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Presence of abnormal synaptonemal complexes in heterothallic species of Neurospora.

Synaptonemal complex abnormalities are frequent in reconstructed meiotic prophase nuclei of Neurospora crassa and Neurospora intermedia. Three kinds of synaptonemal complex anomalies were seen: lateral component splits, lateral component junctions, and multiple complexes. The anomalies apparently are formed during or after the pairing process, as they were not seen in the largely unpaired early zygotene chromosomes. Their presence at all the other substages from mid-zygotene to late pachytene indicates that they are not eliminated before the synaptonemal complex decomposes at diplotene. Abnormal synaptonemal complexes were seen in all 19 crosses of N. crassa and N. intermedia that were examined, including matings between standard laboratory strains, inversions, Spore killers, and strains collected from nature. The frequency of affected nuclei and degree of abnormality within a nucleus varied in different matings. No abnormalities were present in the homothallic species Neurospora africana and Neurospora terricola. Structural chromosome aberrations, introgression, and heterozygosity have been eliminated as causes for pairing disorder. The abnormal synaptonemal complexes seemingly do not interfere with normal ascus development and ascospore formation. The affected nuclei are not aborted during meiotic prophase, nor are they eliminated by abortion of mature asci. The abnormal meiocytes do not lead to aneuploidy, as judged by the low frequency of white ascospores in crosses between wild type strains that have many abnormalities. Thus, the abnormal synatonemal complexes do not appear to prevent chiasma formation between homologues.

Cell Nucleus↗

Psychopathology in adolescent alcohol abuse and dependence.

Adolescents who abuse or are dependent on alcohol often have coexisting mental disorders. These disorders may both precipitate alcohol use disorders and result from them. In addition, both types of disorders may arise independently in adolescents at high risk. Mental disorders that commonly co-occur with alcohol use disorders in adolescents include antisocial disorders, mood disorders, and anxiety disorders. Treatment programs for adolescents with alcohol use disorders should seek not only to eliminate alcohol and other drug use but also to improve the symptoms of other mental disorders.

Adolescent↗

Diagnostic criteria for primary neuronal degeneration of the Alzheimer's type.

The diagnosis of patients presenting with memory or attentional deficits characteristic of dementia is a growing problem. Dementia may be symptomatic of a range of reversible medical and psychiatric conditions which appear to be indistinguishable from primary neuronal degeneration of the Alzheimer's type. While Alzheimer's disease is a neuropathological diagnosis, the importance of establishing a presumptive diagnosis which can be employed for investigational as well as clinical use is underscored. This paper proposes a diagnostic schema which reflects the current understanding of this disorder. There must be evidence of gradual progressive mental deterioration in attention, learning, memory, cognitive style, motivation, and higher order thinking. A comprehensive medical and psychiatric evaluation is obligatory to eliminate reversible physical illness, psychiatric disorder, or cerebrovascular condition as underlying causes of cognitive dysfunction.

Aged↗

Subcutaneous erythropoietin for treatment of refractory anemia in hematologic disorders. Results of a phase I/II clinical trial.

We have used recombinant human erythropoietin (rHuEPO) in a phase I/II clinical trial to evaluate its ability to reverse refractory anemia in hematologic disorders. rHuEPO was administered subcutaneously 5 days per week at escalating doses (50 to 150 U/kg per day). The aim of treatment was a hemoglobin (Hb) level greater than or equal to 10 g/dL without blood transfusion. Of 25 patients treated, 17 were evaluable, most of them with a regular need for transfusion. Eight of these had lymphoproliferative disorders (three cases of malignant lymphoma and five of monoclonal gammopathy) and were exposed to cytotoxic therapy. The other nine patients had hematopoietic stem cell disorders (four cases of myelodysplastic syndrome, three of idiopathic myelofibrosis, and two of chronic myelogenous leukemia). All patients with lymphoproliferative disorder had serum EPO levels inappropriately low for the degree of anemia, while patients with stem cell disorder showed variable values. Erythroid marrow activity was inadequate in all cases. Seven of eight patients with lymphoproliferative disorder responded to treatment maintaining Hb above 10 g/dL without transfusion. The median dose of rHuEPO required for correction of anemia was 75 U/kg. In four cases response was maintained with 50 U/kg, three times per week. There was no complete response among patients with hematopoietic stem cell disorder, although transfusion requirement was eliminated or reduced in four cases. Four patients developed functional iron deficiency during rHuEPO treatment and required iron supplementation to obtain response. Aggravation of splenomegaly was observed in two cases of myeloproliferative disorder. We conclude that: (1) subcutaneous administration of rHuEPO can be effective and safe in patients with lymphoproliferative disorder exposed to chemotherapy and showing inappropriate EPO response to anemia; (2) this is less likely in hematopoietic stem cell disorders, although favorable responses may be observed in occasional patients; and (3) functional iron deficiency as a cause of nonresponse to rHuEPO is frequent also in nonrenal anemia.

Adult↗

[Duration of antidepressive treatments].

In spite of the considerable amount of research undertaken in the field of biological psychiatry, there is currently no reliable guide allowing us to predict with accuracy the response of a patient to an antidepressant treatment. Moreover, owing to the heterogeneity of the spectrum of affective disorders, to the importance of eliminating the various factors involved in an apparent resistance to an antidepressant therapy, it seems aleatory, particularly for an individual patient, to foresee precisely the length of an antidepressant treatment, except may be in unipolar disorders. The quality of the physician-patient therapeutic relationship should never be neglected. The recent hypotheses pertaining to the etiopathogenesis of affective disorders, the advent of new psychotropic agents such as the specific serotonin uptake inhibitors, or other agents not acting through this mechanism and the MAOI, type A, as well as the utilization of corticosuppressor drugs, may pave the way to new therapeutic avenues that could, in the future, modify the prognosis and the duration of the treatment of the depressive affective disorders.

Antidepressive Agents, Tricyclic↗

The Role of High-Potency Benzodiazepines in the Treatment of Panic Disorder.

Medication plays a central role in the treatment of panic disorder, with the goal of eliminating panic attacks and restoring normal function (i.e., achieving full remission). Four drug classes have similar efficacy (tricyclic antidepressants, selective serotonin reuptake inhibitors [SSRIs], benzodiazepines, and monoamine oxidase inhibitors). Nonetheless, benzodiazepines remain the most prescribed medication for panic disorder in the United States. The high-potency benzodiaze-pines alprazolam (available as immediate- and extended-release tablets) and clonazepam (available as tablets and orally disintegrating wafers) are the only benzodiazepines approved by the U.S. Food and Drug Administration for the treatment of panic disorder. High-potency benzodiaze-pines, with their proven efficacy in panic disorder exerted through control of the central nervous system excitability by a selective and potent enhancement of inhibitory gamma-aminobutyric acid-mediated neurotransmission, are also a safe and well-tolerated option for potentiation of rapid treatment response when initiating treatment with SSRIs. Judicious use of high-potency benzodiazepines followed by a cautious taper and discontinuation may optimize the benefits and minimize any potential risk associated with this class of drugs.

Journal Article↗

Hematopoietic cell transplantation for congenital bone marrow failure.

PURPOSE OF REVIEW: Congenital bone marrow failure is rare and multifactorial. This review focuses on the outcome after allogeneic hematopoietic cell transplantation for the treatment of these disorders, with particular emphasis on recent discoveries and the challenges. RECENT FINDINGS: In the treatment of congenital bone marrow failure disorders, the goals are to eliminate or reduce early and late toxicities and the risk of graft-versus-host disease. Novel nonmyeloablative fludarabine-based preparative regimens have demonstrated low risks of toxicity and acceptable engraftment rates for several congenital bone marrow failure disorders. Although there seems to be less early toxicity, longer follow-up is needed to determine late effects, especially the development of malignancy. T cell depletion of the bone marrow or peripheral blood, or the use of umbilical cord blood, has decreased the risk of graft-versus-host disease. Together, reduced toxicity and low rates of graft-versus-host disease have at least minimized the morbidity early after transplantation, with promising early survival. SUMMARY: With marked improvement in rates of survival after allogeneic hematopoietic cell transplantation for selected congenital bone marrow failure disorders, emphasis is now being placed on improving quality of life and reducing late effects. Multicenter collaborative trials will determine the best treatment for these rare disorders.

Bone Marrow Diseases↗

Mutually exclusive versus co-occurring diagnostic categories: the challenge of diagnostic comorbidity.

Diagnostic comorbidity is the rule rather than the exception in both DSM-IV and ICD-10. Three types of comorbidity include true comorbidity (clinically distinct entities), artifactual comorbidity (a byproduct of the DSM/ICD strategy to split categorical diagnoses) and spurious comorbidity. DSM has established 'mutually exclusive' relationships between disorders to reduce such spurious comorbidity. Four types of mutually exclusive relationships are identified: (1) between disorders that are on different levels of the Kraepelinian-defined hierarchy (e.g., schizophrenia and major depressive disorder); (2) between categories with identical features that are split according to age or duration (schizophrenia and schizophreniform disorder); (3) between categories in which the defining features of one disorder are contained in the definition of more broadly-defined disorder (Asperger's disorder and autistic disorder), and (4) between categories in which the defining features of one disorder are an associated feature of another disorder (e.g., dysthymic disorder and schizophrenia). Although less comorbidity may be desirable to reduce diagnostic complexity, in the absence of knowledge about underlying pathophysiology, the trend in successive editions of the DSM has been to reduce diagnostic hierarchies and increase comorbidity (e.g., elimination of exclusion between panic disorder and major depression in DSM-III-R because of evidence of independence). It is important to understand that comorbidity in psychiatry does not imply the presence of multiple diseases or dysfunctions but rather reflects our current inability to apply Occam's razor (i.e., a single diagnosis to account for all symptoms).

Comorbidity↗

NIH conference. Rheumatoid arthritis: evolving concepts of pathogenesis and treatment.

Rheumatoid arthritis is a chronic inflammatory synovitis that primarily involves peripheral diarthrodial joints. Immunohistologic analysis of diseased synovium has shown a spectrum of abnormalities that resemble various stages of a cell-mediated, or delayed-type, immune reaction. The infiltrating mononuclear cells produce various factors that modulate adjacent tissues and appear to produce the characteristic destructive features of the disorder. Our understanding of the mechanisms of action of various therapeutic modes also indicates that the disease is primarily mediated by activated mononuclear cells. All effective therapies have been shown to affect either mononuclear cell function or the rates of production or elimination of these cells. The disorder likely represents the pathologic expression of a genetically controlled host immune response to an undefined causative stimulus. The stimulus could be an infectious agent(s), a product(s) derived from an infectious agent(s), a constituent(s) of synovial or connective tissue, or a combination of these.

Animals↗

Natural killer cells in connective tissue disorders.

NK cells may be important in the elimination of cells infected by virus, in the regulation of antibody production, and in tissue destruction. The significance of NK cells in rheumatic disorders is unknown, but NK cells and NK-like cells have been found in the peripheral blood and synovial tissues of patients with autoimmune disease. In particular, defects in NK cell activity have been reported in SLE, RA, PSS and SS. Of these diseases, SLE appears to be the best characterized with obvious abnormalities in NK cell numbers, impaired cytotoxicity of individual NK cells, decreased release of cytotoxic factors, deranged IFN modulation of the NK cell, and associated abnormalities in the IL-2 system. The association of these abnormalities with the underlying disease process is currently under investigation.

Arthritis, Rheumatoid↗

Perceived barriers to mental health service use among individuals with mental disorders in the Canadian general population.

BACKGROUND: Eliminating barriers to care is important for improving health service use. However, the barriers to mental health care have not been well investigated. OBJECTIVES: This study was designed to provide information about the barriers to mental health service use and to identify clinical factors associated with perceived barriers among individuals with depressive-, anxiety-, and substance use-related disorders in the communities. DESIGN: A cross-sectional analysis using data from the Canadian Community Health Survey-Mental Health and Well-being was instituted. SUBJECTS: Participants with depressive-, anxiety-, and substance use-related disorders in the past 12 months, assessed by the World Mental Health-Composite International Diagnostic Interview, were included (n = 4094). RESULTS: In participants with mental disorders, 19.5% reported barriers to mental health service use. The percentage of perceived barriers due to acceptability was higher than those for barriers due to accessibility and availability. Participants with comorbid mental disorders were more likely to have experienced barriers than those with one disorder in both mental health service users and in the nonusers. Role impairment was a significant factor predicting barriers to care, overall and in the service nonusers, in the groups having anxiety disorders only, having any depressive or anxiety disorders, and having any alcohol or drug dependence. CONCLUSIONS: Clinical characteristics play an important role in perceiving barriers to mental health care. Future efforts should pay particular attention to the needs of those with chronic and severe mental health problems and focus on improving the effectiveness of mental health services.

Adolescent↗

Males with Down's syndrome and nonneurogenic neurogenic bladder.

PURPOSE: We assessed the relationship of trisomy 21 with the most severe dysfunctional elimination syndrome, nonneurogenic neurogenic bladder or the Hinman-Allen syndrome. MATERIALS AND METHODS: We retrospectively reviewed our experience with children with Down's syndrome (trisomy 21) in a 10-year period and identified a subset who presented for the evaluation and treatment of urinary tract infections associated with severe disorders of urinary and fecal elimination. RESULTS: Four males 9 months, 14 years, 18 years and 21 years old met the criteria for review. All patients underwent radiological and urodynamic evaluation, and were diagnosed with hydronephrosis and prostatic urethral dilatation with pelvic floor spasticity. Renal function studies showed a creatinine of 0.7 mg./dl. in the 9-month-old, 1.2 mg./dl. in the 14-year-old, 1.9 mg./dl. in the 18-year-old and 2.2 mg./dl. in the 21-year-old patient. Three patients underwent surgical treatment to protect the upper urinary tract, including bladder augmentation cystoplasty and an appendiceal Mitrofanoff stoma in 2, and vesicostomy in 1. The remaining patient was treated conservatively with a behavioral modification program that included timed voiding and a bowel regimen. CONCLUSIONS: Boys with trisomy 21 may be at risk for the Hinman-Allen syndrome. Surgical intervention and clean intermittent catheterization for renal preservation and continence can be performed in this population despite intellectual impairment. Further evaluation is necessary to determine whether this relationship is more common than appreciated and whether this syndrome occurs in females with trisomy 21.

Adolescent↗

[Use of constant negative pressure around the chest for rehabilitation of external respiration in premature infants with respiratory disorders].

A study was of the effect produced by constant negative pressure around the chest on the clinical course and external respiratory function in premature infants with respiratory disorders. Application of constant negative pressure around the chest was followed by rapid elimination of the clinical manifestations of respiratory disorders, by the improvement of the characteristics of external respiratory function and blood gases.

Humans↗

The course of seizures after treatment for cerebral cysticercosis.

BACKGROUND: Worldwide, cerebral cysticercosis is one of the most common causes of seizure disorders. Modern cysticidal drugs can usually eliminate the parasite from the brain, but there have been doubts as to whether such treatment improves the seizure disorder. METHODS: We studied 240 patients with seizures and cysticercosis of the brain parenchyma. Of these patients, 118 received cysticidal therapy (albendazole, praziquantel, or both) for lesions without inflammation on imaging studies (group 1); 49 patients with similar lesions either were not offered or refused cysticidal medication (group 2). Another 58 patients with inflammation around cysts (making spontaneous resolution more likely) also did not receive cysticidal medication (group 3), whereas cysticerci were removed surgically in 15 patients (group 4). The 240 patients were followed for a mean (+/- SE) of 92 +/- 7 months. RESULTS: In the patients treated with cysticidal medications, there was an 82 percent reduction in the mean number of brain cysts (from 5.0 to 0.9) and a 95 percent reduction in the mean frequency of seizures (from 11.3 to 0.6 per year; P less than 0.001). After three years of follow-up, 64 patients in group 1 (54 percent) were seizure-free. By contrast, the untreated patients (group 2) averaged 10.9 seizures per year; none were seizure-free. Among those with inflamed cysts (group 3), there was a 74 percent reduction in the frequency of seizures (from 7.5 to 2.7 per year), and 18 patients (31 percent) became seizure-free. After surgical treatment (group 4), there was an 87 percent reduction in the frequency of seizures (from 12.8 to 1.7 per year), and six patients (40 percent) became seizure-free. CONCLUSIONS: After medical treatment of neurocysticercosis, there is usually remission or marked improvement in the associated seizure disorder.

Adult↗

[Differential diagnosis and therapy of abnormalities of the respiratory tract].

Congenital disorders of respiration, food intake and function of the voice indicate abnormalities in the rhinolaryngotracheal or oesophageal regions of the air passages and oesophagus. They immediately need differential diagnostic clarification in interdisciplinary cooperation. Methods of a sophisticated tubus endoscopy, applied also under emergency situations, play a vital role. The therapy aims at eliminating life-threatening ventilation disorders within a short time by pharyngotracheal intubation and within a longer period by tracheostomy in order to let prenatally inhibited developments postnatally come into effect, if need be to support these differentiation processes by endoscopic interventions or to perform plastically constructive operations at a prognostically convenient time.

Abnormalities, Multiple↗

[Agitation in the elderly (author's transl)].

Agitation in the elderly is a common behaviour disorder. The clinical picture is quite variable: aggressive reactions, anxious agitation, agitation associated with confusion: sometimes, the agitation occurs in episodes, especially during the night. These types of agitation have two basic causes: confusion and dementia. In some cases, they are the clinical expression of an angry, hostile or excited state. In agitation associated with confusion, one must eliminate an intoxication, a neurological disorder, an infection, and notably a past head injury which may have gone undetected. Therapeutic measures are discussed.

Aged↗

Genetic diseases of sheep and goats.

Congenital malformations and inherited disorders constitute a substantial proportion of the afflictions seen in sheep and goats. Of these, malformations tend to be similar in both species, whereas the genetic diseases encountered to date, with the exception of a few, are different. Of the 28 genetic diseases of sheep and goats described in this review, 60% and 62.5%, respectively, are monogenic disorders. For a majority of the monogenic recessive disorders encountered in these species, the carrier state is not detectable at present, whereas in others, in which a biochemical lesion is known (dermatosparaxis, erythrocyte glutathione deficiency, globoid cell leukodystrophy and glycogen storage disease), the carrier state is detectable with the aid of enzyme and surface protein markers. The latter group and the dominant disorders (anury, cataract, glomerulonephritis, and lethal grey in sheep; gynecomastia and anotia-microtia complex in goats) are easy to eliminate through selective breeding. The polygenic disorders (entropion, epidermolysis bullosa, hereditary chondrodysplasia, and muscular dystrophy of sheep, and udder problems in goats) are more difficult to eradicate, because the mutant genes responsible for these traits generally do not declare themselves until inbreeding brings together a critical concentration to create a health crisis in some, whereas others, which are only short of a few of these mutant genes, might go totally unaffected and therefore undetected. Chromosome defects of the structural nature (translocations) seen in sheep and goats generally create meiotic disturbances, which in a majority of cases lead to subfertility, whereas sex chromosome aneuploids are generally sterile.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗