Primary immunodeficiency disorders

The primary immunodeficiency diseases are a relatively rare group of congenital disorders that are linked by the expression of an excessive number, duration, or severity of infections. The clinical features of most of the primary immunodeficiency diseases have been well described by astute physicians over several decades and have provided important clues to our basic understanding of human immunology. In contrast, the genetic basis and potential life-saving therapies for many of these disorders have been established only over the past few years. These recent advances have resulted in the prognosis of many of these disorders being largely dependent on their rapid recognition and treatment. Increased awareness of the differentiating epidemiologic, clinical, laboratory and genetic features of these diseases hold the promise of both furthering our understanding of basic human immunology and providing improved care for this challenging group of patients.     

Immunoglobulin-secreting cells in primary immunodeficiency diseases

To assess immunoglobulin production in vivo, the numbers of immunoglobulin-secreting cells were measured in uncultured peripheral blood mononuclear cells (PBMCs) of patients with primary immunoglobulin deficiency. The numbers of immunoglobulin-secreting cells were found to be variable, and they were well correlated with the serum concentrations of all three major immunoglobulin classes. Our results suggest that measurement of immunoglobulin-secreting cells in PBMCs is useful in the assessment of the ability to produce immunoglobulin in vivo.     

Cancer and primary humoral immunodeficiency

The occurrence of cancers in patients with primary humoral immunodeficiency syndrome (X-linked agammaglobulinemia, common variable immunodeficiency, IgA deficiency) is more than mere coincidence. An increased risk of non Hodgkin's lymphoma and gastric adenocarcinoma, particularly for patients with common variable immunodeficiency, is well established. A literature review is presented on this subject with analysis of case reports, prospective and retrospective studies, and data from the Minnesota Immunodeficiency Cancer Registry.     

Gene therapy for primary immunodeficiency

The mechanisms by which monocytes from patients infected with human immunodeficiency virus (HIV) have reduced growth inhibitory activity against Cryptococcus neoformans was examined. Monocyte-enriched peripheral blood mononuclear cells from 12 HIV-seropositive donors with CD4 cell counts of 10-210 cells/mm3 (median, 85) and HIV-seronegative donors were compared in assays to determine the binding and phagocytosis of C. neoformans and the respiratory burst and degranulation in response to C. neoformans and zymosan. Monocytes from HIV-infected and uninfected persons bound and ingested C. neoformans equally well; however, generation of hydrogen peroxide and specific release of beta-glucuronidase in response to C. neoformans was significantly reduced in monocyte-enriched cells from the HIV-infected donors. The impaired anticryptococcal activity of monocytes from persons with HIV may be related to defects in both oxidative and nonoxidative effector pathways that occur after the binding and internalization of the organism.     

Emotional disorders in primary care.

Individuals with emotional disorders are more likely to use primary medical care than specialty mental health services, but these disorders are likely to be undetected or inadequately treated. Recognition of the importance of primary medical care for the treatment of mental disorder has resulted in pressing new research priorities. One set of issues concerns the adequacy of existing nosological systems for conceptualizing emotional disorder in primary care and identifying need for treatment. Another concerns the difficulties translating efficacious treatment into effective strategies that can be integrated into the competing demands of primary medical care. Psychologists have played only a limited role in defining and addressing emerging questions. Irreversible changes in mental health services have created the need for the development of a psychosocial perspective for what would otherwise be defined as narrowly biomedical issues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Primary biliary cirrhosis with sarcoid-like infiltrations in the lung

A women, 50 years old, has been observed for 4 years because of recurrent infiltrations in both lungs. Biopsy of those lesions revealed sarcoid-like granulomas. Tubercle baccilli were not present in those lesions nor in the sputum or bronchial washings. Anti-tuberculosis therapy was without effect. On admission to our hospital she was in good performance state. There was an infiltration in the base of the left lung. Hepatosplenomegaly was observed on USG examination. Aspartate aminotransferase was 49 UI/l, alanine aminotransferase 70 UI/l. Alkaline phosphatase was 167 UI/l and the titer of antimitochondrial antibodies was 1:2000. Primary biliary cirrhosis was suspected, but the patient refused liver biopsy. Prednisone in the dose of 60 mg per day was given to suppress the granuloma formation in the lungs. During this treatment there was a decrease in size of liver and spleen, lung lesion disappeared and the titer of antimitochondrial antibodies decreased to 1:40. After 3 months of treatment the dose of prednisone was reduced gradually. When she was receiving 15 mg of prednisone every other day the titer of antimitochondrial antibodies rose to 1:8000 and the activity of alkaline phosphatase to 448 UI/l. At this time she accepted liver biopsy. Primary biliary cirrhosis was diagnosed. The possible connection between sarcoid-like granulomas in the lungs and the primary biliary cirrhosis is discussed.     

Bone marrow transplantation in primary immunodeficiency syndrome and in osteopetrosis

The designation primary immunodeficiency embraces a multiplicity of diseases of which only the more severe constitute indications for BMT (bone marrow transplantation)--e.g. severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, familial haemophagocytic lymphohistiocytosis and malignant osteopetrosis. In cases of immunodeficiency, the outcome of BMT is strongly dependent on the patient's age, clinical status at transplantation and the type of immunodeficiency. In children with SCID who undergo BMT during the first few months of life, lasting cures can be obtained in almost 100 percent of the cases, whereas there is only a 15 percent probability of success if the child is older, infected, cannot undergo cytostatic preconditioning or cannot be given T-cell depleted bone marrow.     

Hodgkin''s disease-like lymphoproliferative disorders in patients with different underlying immunodeficiency states

An actuarial life-table approach was used to study the mortality of 277 calves born alive in 16 traditionally managed herds in Bauchi, Nigeria from 1993 to 1995. The proportion of calves in the herds surviving for the first 12 months was 53.8%. The probability of dying was greatest during the first month of life and decreased with age. The proportion of calves surviving in the herds has been increasing for the last 2 years. We suspect that this is probably due to improvements in management practices. Septicaemia, malnutrition and injury were the common causes of calf mortality. We recommend that more attention be given to improving the management of calves early in life in order to reduce mortality of calves and hence reduce economic losses to the herd owner.     

Prevalence of comorbid anxiety disorders in primary care outpatients

OBJECTIVE: To estimate the extent to which anxiety disorders (eg, panic disorder, phobia, and generalized anxiety disorder [GAD]) co-occur in patients with major medical and psychiatric conditions. DESIGN: Observational study. SETTING: Offices of primary care providers in three US cities, with mental health specialty providers included for comparative purposes. PATIENTS: Adult patients (N = 2494) with hypertension, diabetes, heart disease (congestive heart failure or myocardial infarction), current depressive disorder, or subthreshold depression. MEASURES: Current (past 12 months) and lifetime panic disorder, phobia, GAD, perceived need for help for emotional or family problems, and unmet need (ie, failure to get help that was needed). METHODS: Comparisons of the prevalence of anxiety comorbidity in medically ill nondepressed patients of primary care providers and in depressed patients of both primary care and mental health specialty providers. RESULTS: Among primary care patients, those with chronic medical illnesses or subthreshold depression had low rates of lifetime (1.5% to 3.5%) and current (1.0% to 1.7%) panic disorder, but those with current depressive disorder had much higher rates (10.9% lifetime and 9.4% current panic disorder). Concurrent phobia and GAD were more common (10.4% to 12.4% current GAD), especially among depressed patients (25% to 54% current GAD). Depending on the type of medical illness or depression, 14% to 66% of primary care patients had at least one concurrent anxiety disorder. Patient-perceived unmet need for care for personal or emotional problems was high among all primary care patients (54.6% to 72.9%). CONCLUSION: Primary care clinicians should be aware of the possible coexistence of anxiety disorders (especially GAD) among their patients with chronic medical conditions, but especially among those with current depressive disorder.     

Epithelioid granulomas in Hodgkin''s disease--prognostic significance

Liposome-entrapped dichloromethylene diphosphonate (Cl2MDP) was injected locally into the thymus of adult rats. This treatment, which has been found to deplete resident macrophages in other organs, also reduced the number of thymic macrophages. The depletion was evident in the cortex and the corticomedullary zone at 5, 13 and 23 days after Cl2MDP treatment, while the decrease in medullary macrophages only became significant 13 and 23 days after injection. However, the maximal reduction of macrophages was evident 13 days after this treatment. Thirty-five days after Cl2MDP treatment, macrophages repopulated the thymus. Our results suggest that the cortical and cortico-medullary macrophages have a high phagocytic activity consistent with their predominant role as scavengers of the large numbers of thymocytes that die under physiological conditions. It is concluded that liposome-mediated depletion of thymic macrophages can serve as an experimental model to study the roles of these cells.