Pseudoneurologic syndromes: recognition and diagnosis

Physicians may encounter patients with a collection of psychologic disorders that present with neurologic symptoms or signs, yet have no identifiable structural or functional etiology within the nervous system. These disorders comprise the so-called pseudoneurologic syndromes, which can mimic almost any organic disease. A careful history and physical examination often can identify the psychologic origin of the symptoms. Presenting syndromes can include pseudoparalysis, pseudosensory syndromes, pseudoseizures, pseudocoma, psychogenic movement disorders and pseudoneuro-ophthalmologic syndromes. These presentations may be distinguished from organic disease by observing signs and symptoms or eliciting test responses that are nonphysiologic and incompatible with organic disease. Once a pseudoneurologic syndrome is identified, patients require compassionate and understanding care to resolve underlying emotional problems.     

Genetic distribution of Bare-1-like retrotransposable elements in the barley genome revealed by sequence-specific amplification polymorphisms (S-SAP)

Acid anhydrides are highly reactive, low molecular weight compounds that are used widely in industry. Work-related exposure to this group of substances may cause occupational asthma. Because of low molecular weight, these compounds are not able to induce antibody responses without conjugating with human proteins. Acid anhydrides may act as haptens when conjugated with human serum albumin (HSA). The induction mechanism of immediate and late bronchial hyperresponsiveness to acid anhydrides appears to be at least partly mediated by IgE antibodies. Other clinical syndromes, which may be caused by acid anhydrides such as pulmonary disease-anemia (PDA), and late respiratory systemic syndrome (LRSS) associated with TMA exposure, appear to be associated with IgG antibodies to TMA as well as with IgE. Significant cross-reaction occurs between different compounds of this group, particularly regarding IgE antibodies. As inhalational exposure to acid anhydrides may result in serious pulmonary disease, adequate protection of potentially exposed workers or their removal, if affected, from exposure is essential.     

Sleep and rheumatic disease

Patients with rheumatic diseases often exhibit sleep disturbance. Identification of primary sleep disorders; medical, neurologic, and psychologic illnesses; circadian factors; and the use and effect of medications, drugs, and alcohol will provide a strong basis for pursuing both pharmacologic and nonpharmacologic intervention. Recent clinical research confirms the frequent comorbidity of sleep disturbance, pain, fatigue, stress, and mood disturbance in patients with rheumatic disease. It is essential for effective management to recognize these "symptom syndromes" that are often responsive to treatment (suggesting a common biologic action and effect of the drugs used) despite a continuing presence of underlying chronic disease. The pathophysiologic relationships of these comorbid symptoms are mostly unknown, so this is an area for further study.     

Human cancer syndromes: clues to the origin and nature of cancer

More than 20 different hereditary cancer syndromes have now been defined and attributed to specific germline mutations in various inherited cancer genes. Collectively, the syndromes affect about 1 percent of cancer patients. An individual who carries a mutant allele of an inherited cancer gene has a variable risk of cancer that is influenced by the particular mutation, other cellular genes, and dietary, lifestyle, and environmental factors. Though hereditary cancer syndromes are rare, their study has provided powerful insights into more common forms of cancer. Somatic mutations in sporadic cancers frequently alter the inherited cancer genes, and the functions of cell signaling pathways have been illuminated by study of the affected genes. Further investigation of inherited mutations that affect susceptibility to cancer will aid efforts to effectively prevent, detect, and treat the disease.     

Inflammatory bowel disease: Part I. Clinical features and diagnosis

Familial and epidemiologic studies of inflammatory bowel disease indicate a strong genetic predisposition that is modified by certain environmental factors. Abnormal submucosal immune activation may be important in the etiology of the disease. Yersinia enterocolitica infection, various "gay bowel syndromes" and other recently described enteric infections often mimic Crohn's disease. An initial barium study is useful in documenting the extent of disease and complications. Endoscopic biopsy confirms the surface appearance and histologic features of inflammatory bowel disease. Newer photodocumentation techniques are expected to improve the comparability of endoscopic observations. Complications of inflammatory bowel disease occur frequently, may involve any organ system and may precede the onset of bowel symptoms.     

Immune responses in patients with T-cell lymphoma treated with an anti-idiotype antibody mimicking a highly restricted T-cell antigen

We generated an IgG1 murine monoclonal anti-idiotype antibody (Ab2) to a highly restricted T-cell antigen designated glycoprotein (gp) 37 that is found on T-cell malignancies but not on normal cells. gp37 is identified by the murine monoclonal antibody SN2 (Ab1) against which the Ab2 was raised. Each of four patients with T-cell lymphoma predominantly confined to the skin received a minimum of four intracutaneous injections of aluminum hydroxide precipitated anti-idiotype murine monoclonal antibody (1 mg/injection) given every 2 weeks. For responding patients, injections were continued on a monthly basis. All tumors were measured along orthogonal major and minor axes, using a ruler and/or calipers, by the same observer. Tumor sizes were documented photographically. Three of the four patients developed specific idiotypic humoral immune responses, and two of the four patients also demonstrated idiotypic cell-mediated responses. Humoral responses included binding of the patients' sera to the anti-idiotype antibody as well as specific inhibition of binding of the SN2 antibody (Ab1) to the anti-idiotype antibody (Ab2). Anti-anti-idiotypic (Ab3) antibody from one patient's serum bound specifically to the gp37-positive cell line MOLT-4 and also to semipurified gp37 antigen. Cell-mediated responses were demonstrated by specific proliferative response to the aluminum hydroxide precipitated anti-idiotype antibody by patients' peripheral blood mononuclear cells. While three of the four patients had extensive disease and did not have clinical responses, one of the patients who had nine discrete skin tumors and peripheral blood involvement without other detectable disease had virtually complete disappearance of the tumors lasting over 11 months. Our results demonstrate that this particular anti-idiotype antibody can induce humoral and cellular immune responses, and at least in one patient led to a meaningful therapeutic response. Future trials should focus on immunocompetent patients with minimal disease.     

Suppression of male-specific cytochrome P450 isoforms by bisphenol A in rat liver

IBD results from the interaction of genetic and environmental factors (e.g., smoking). Clinical suspicion is the key to diagnosis, which then rests on colonoscopy, histopathological examination of multiple biopsy specimens, small bowel barium radiology and faecal examination. The primary goal of treatment is remission--histological in ulcerative colitis and symptomatic in Crohn's disease. Treating active disease and maintaining remission require different approaches. For active disease, short term corticosteroids are the mainstay of treatment, while immunosuppressive drugs are important in chronically active disease. For maintenance, mesalazine-delivering drugs and immunosuppressive agents are efficacious in both ulcerative colitis and Crohn's disease; patients with Crohn's disease should not smoke.     

Neuroleptic-induced acute extrapyramidal syndromes and tardive dyskinesia

Neuroleptic drug-induced acute extrapyramidal symptoms and later-onset tardive dyskinesia are major limitations to these valuable drugs. Each of these disorders can be described by special risk factors that include patient characteristics, drug factors, and temporal considerations. The limitations that derive from these motor side effects have been one of the major reasons propelling the search for neuroleptic drugs that are free of these side effects. Strategies for managing the acute and late-onset extrapyramidal syndromes are presented. Significantly more research is needed, however, on all these disorders before a unified and cohesive explanation can account for these seemingly disparate syndromes. New medications, which effectively treat schizophrenia and are free of acute extrapyramidal syndromes and tardive dyskinesia, will be a giant step forward in patient care and our knowledge of the mechanisms controlling both mental function and motor control.     

Genetic analysis of antibody responses of turkeys to Newcastle disease virus and Pasteurella multocida vaccines

Heritability (h2) of 16-wk BW and primary and secondary antibody responses and genetic and phenotypic correlations among these traits were estimated for 931 male and female turkeys vaccinated with Newcastle disease virus (NDV) and Pasteurella multocida. Turkeys from a line selected for 22 or 23 generations for increased 16-wk BW were vaccinated at 6 and 12 wk of age with blood samples collected 3 wk postvaccination. Antibody titers were determined using an ELISA method and transformed to log(e) for analysis. Heritability estimates for primary and secondary antibody responses to NDV were .380 +/- .070 (SE) and .296 +/- .063, respectively. For primary and secondary antibody responses to P. multocida, h2 estimates were .458 +/- .075 and .333 +/- .066, respectively. Heritability estimate for 16-wk BW was .404 +/- .071. The genetic correlation between primary and secondary antibody responses to NDV was .491 +/- .150. There was no genetic correlation between primary and secondary antibody responses to P. multocida. Although the genetic correlation between primary antibody responses to NDV and P. multocida was .292 +/- .159, the genetic correlation between secondary responses to the two antigens did not differ from zero. There were no genetic correlations between antibody responses and 16-wk BW. Similar results were observed for phenotypic correlations. Based on heritability and genetic correlation estimates, it would be possible to improve antibody responses to either NDV or P. multocida singularly; however, to improve antibody responses to both antigens, selection would have to be applied for each antigen.     

Anti-GD1a ganglioside antibodies in peripheral motor syndromes

High titers of anti-GD1a antibodies have been found in patients with Guillain-Barre syndrome or motor neuropathy. To determine the possible diagnostic relevance of these antibodies, we measured serum anti-GD1a IgG and IgM antibodies by enzyme-linked immunosorbent assay in 195 patients with different motor syndromes and in 335 control subjects. Moderately high antibody titers (1/1,280-1/5,120) were occasionally found in patients with chronic inflammatory demyelinating polyneuropathy (5%), multifocal motor neuropathy (18%), lower motor neuron disease (3.8%), or amyotrophic lateral sclerosis (1.8%) and in immunological control subjects (1.2%), while titers of 1/20,480 or higher were only found in 2 patients with Guillain-Barre syndrome (IgG in both) and 2 with motor neuropathy and IgM lambda monoclonal gammopathy improving with immunotherapy. In both motor neuropathy patients and the Guillain-Barre syndrome patient who were retested during recovery, anti-GD1a titers decreased concomitantly with clinical improvement. High anti-GD1a antibody titers may be found in several motor syndromes but only markedly increased anti-GD1a titers are strictly associated with potentially treatable dysimmune neuropathies.     

The diagnosis of gluten sensitivity and coeliac disease--the two are not mutually inclusive

The traditional definition of coeliac disease is inadequate because it includes only patients with abnormal small intestinal morphology. Gluten sensitivity is a systemic disorder whose common factor is an immune response to gluten in the context of the susceptible 'coeliac' HLA haplotype and possibly environmental triggers. Gluten sensitivity embraces traditional coeliac disease as well as subjects with normal small bowel morphology including latent coeliac disease, dermatitis herpetiformis, and symptomatic gluten intolerance. The diagnosis of gluten sensitivity and coeliac disease are not mutually inclusive. Small intestinal biopsy and clinical criteria are essential in diagnosing classical coeliac disease. IgA endomysial antibody is valuable in identifying gluten sensitivity and has particular value as a screening test. Serology should include total IgA levels to exclude selective IgA deficiency, a potential cause of false negative IgA endomysial antibody. A combination of histology, serology and clinical criteria will identify most cases of coeliac disease and gluten sensitivity.     

Methods of early diagnosis and prevention of occupational mercury poisoning

Five intraventricular injections of phytopreparations lohein and abisib in a dose of 0.2 or 0.5 ml stimulated dose-dependently the development of a T-dependent and T-independent immune responses in rats kept on the usual diet, and increased or normalized the development of these processes in rats kept on a atherogenic diet. The drugs lessened lipid peroxidation and the biochemical syndromes of hepatocyte affection in animals given an atherogenic diet. The immunomodulating effect of phytopreparations is mediated by cytokines of adherent and nonadherent splenic cells, the biochemical effects only by cytokines of adherent splenocytes.     

Treatment of Goodpasture syndrome with cyclophosphamide, prednisone and plasma exchange transfusions

Repeated plasm exchanges were performed in a 44-year-old man with Goodpasture syndrome, also treated with cyclophosphamide and prednisone. Improvement was observed within 3 weeks of starting the protocol, and by the 76th week, endogenous creatinine clearance had increased from 30 to 56 ml/min/1.73 M2 and serum albumin from 2.7 to 3.7 g/dl. Prior treatment with immunosuppressive drugs had not significantly influenced circulating antibody levels. But sustained suppression of antibody was achieved after the plasma exchanges were begun, suggesting that physical removal of circulating antibody combined with antiproliferative drug treatment may be a useful way to control undesirable humoral immune responses.     

A piece in the puzzle: an ion channel candidate gene for schizophrenia

Mutations in ion channels have been found to cause a variety of mendelian genetic diseases, and polyglutamine repeat expansion is a newly recognized pathogenic mechanism that causes several rare, genetic, late-onset neurological syndromes. Polymorphic polyglutamine tracts are present in a recently described human, calcium-activated potassium channel, KCNN3 (also known as hKCa3), and alleles of this gene that contain longer repeats have been associated with schizophrenia. The physiological function of the channel is consistent with an etiological role in this disease; drugs designed to target this channel might therefore provide novel psychotherapeutics.     

The antibody response in sheep vaccinated with experimental Nairobi sheep disease vaccines

The antibody responses to experimental Nairobi sheep disease vaccines have been assayed. The responses to an inactivated methanol precipitated vaccine were comperable with those following infection with virulent virus. The responses to attenuated vaccines were inadequate to protect against challenge with virulent virus.     

Management of HIV infection. A 1995-96 overview for the clinician

Although the challenges of HIV/AIDS care may seem overwhelming, we are better able than ever to positively affect the course of HIV for each individual patient. Treatment goals involve three areas: 1) Antiretroviral drugs aimed at retarding the rate of HIV replication, thus reducing the rate of damage to the immune system; 2) drugs used to treat or prevent opportunistic infections seen in the context of HIV-related immune deficiency; and 3) drugs used to treat symptoms or syndromes commonly seen in these patients (including dementia and wasting syndrome). The multitude of clinical problems seen in advanced HIV disease leads to significant polypharmacy and costs resulting in a very complex and confusing situation. I recommend that physicians with little HIV experience link up with an HIV specialist when caring for HIV-infected patients to optimize access to the best therapies or research studies currently available. With no cure in sight, physicians need to focus on educating the public and patients about how to avoid HIV infection and to identify persons who are infected to minimize spread.     

Common themes of antibody maturation to simian immunodeficiency virus, simian-human immunodeficiency virus, and human immunodeficiency virus type 1 infections

Characterization of virus-specific immune responses to human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) is important to understanding the early virus-host interactions that may determine the course of virus infection and disease. Using a comprehensive panel of serological assays, we have previously demonstrated a complex and lengthy maturation of virus-specific antibody responses elicited by attenuated strains of SIV that was closely associated with the development of protective immunity. In the present study, we expand these analyses to address several questions regarding the nature of the virus-specific antibody responses to pathogenic SIV, SIV/HIV-1 (SHIV), and HIV-1 infections. The results demonstrate for the first time a common theme of antibody maturation to SIV, SHIV, and HIV-1 infections that is characterized by ongoing changes in antibody titer, conformational dependence, and antibody avidity during the first 6 to 10 months following virus infection. We demonstrate that this gradual evolution of virus-specific antibody responses is independent of the levels of virus replication and the pathogenicity of the infection viral strain. While the serological assays used in these studies were useful in discriminating between protective and nonprotective antibody responses during evaluation of vaccine efficacy with attenuated SIV, these same assays do not distinguish the clinical outcome of infection in pathogenic SIV, SHIV, or HIV-1 infections. These results likely reflect differences in the immune mechanisms involved in mediating protection from virus challenge compared to those that control an established viral infection, and they suggest that additional characteristics of both humoral and cellular responses evolve during this early immune maturation.     

Spontaneous intracranial hypotension: spinal MR findings

Several melanosome glycoproteins have been shown to be antigenic in humans. Correlation of antigen-specific immune responses in patients with the autoimmune disease vitiligo, therapy-induced hypopigmentation, and cutaneous melanoma has not been well studied. We examined antibody responses to a melanocyte autoantigen, tyrosinase-related protein-2 (TRP-2), as it is highly expressed in cutaneous melanoma and melanocytes. TRP-2 recombinant protein was synthesized for western blot and affinity anti-TRP-2 enzyme-linked immunosorbent assay. We demonstrated that patients with malignant melanoma, vitiligo, and active-specific immunotherapy-induced depigmentation had significant anti-TRP-2 IgG titers. The highest level of anti-TRP-2 IgG response was found in vitiligo patients. Induction and enhancement of anti-TRP-2 IgG responses were observed in melanoma patients treated with a polyvalent melanoma cell vaccine containing TRP-2. Active-specific immunotherapy could induce and/or augment the TRP-2 IgG antibody titers. Melanoma patients who developed hypopigmentation and had improved survival after polyvalent melanoma cell vaccine had significantly augmented anti-TRP-2 antibody responses compared with patients with poor prognosis. This study demonstrates that TRP-2 autoantigen is immunogenic in humans. TRP-2 antibody responses provide a linkage between autoimmune responses by vitiligo patients and melanoma patients responding to immunotherapy who have induced hypopigmentation.     

Randomized controlled trial of ipratropium bromide and frequent low doses of salbutamol in the management of mild and moderate acute pediatric asthma

The standardized enzyme-linked immunosorbent assay (ELISA) for measurement of serum immunoglobulin G (IgG) antibody responses to meningococcal C polysaccharide has been modified to employ assay conditions that ensure specificity and favor detection primarily of high-avidity antibodies. The modified and standard assays were used to measure IgG antibody concentrations in sera of toddlers vaccinated with meningococcal polysaccharide vaccine or a meningococcal C conjugate vaccine. The results were compared to the respective complement-mediated bactericidal antibody titers. In sera obtained after one or two doses of vaccine, the correlation coefficients, r, for the results of the standard assay and bactericidal antibody titers were 0.45 and 0.29, compared to 0.85 and 0.87, respectively, for the modified assay. With the standard assay, there were no significant differences between the geometric mean antibody responses of the two vaccine groups. In contrast, with the modified assay, 5- to 20-fold higher postvaccination antibody concentrations were measured in the conjugate than in the polysaccharide group. Importantly, the results of the modified assay, but not the standard ELISA, paralleled the respective geometric mean bactericidal antibody titers. Thus, by employing conditions that favor detection of higher-avidity IgG antibody, the modified ELISA provides results that correlate closely with measurements of antibody functional activity that are thought to be important in protection against meningococcal disease.     

Isotype-specific antibody responses to foot-and-mouth disease virus in sera and secretions of "carrier' and "non-carrier' cattle

Isotype-specific antibody responses to foot-and-mouth disease virus (FMDV) were measured in the sera and upper respiratory tract secretions of vaccinated and susceptible cattle challenged with FMDV by direct contact or by intranasal inoculation. A comparison was made between cattle that eliminated FMDV and those that developed and maintained a persistent infection. Serological and mucosal antibody responses were detected in all animals after challenge. IgA and IgM were detected before the development of IgG1 and IgG2 responses. IgM was not detected in vaccinated cattle. Challenge with FMDV elicited a prolonged biphasic secretory antibody response in FMDV "carrier' animals only. The response was detected as FMDV-specific IgA in both mucosal secretions and serum samples, which gained statistical significance (P < 0.05) by 5 weeks after challenge. This observation could represent the basis of a test to differentiate vaccinated and/or recovered convalescent cattle from FMDV "carriers'.