Viral contamination of food products: a poorly understood public health problem

Throughout the world there have been several epidemics of food-borne diseases (FBD) about which there is lack of sufficient information for public health institutions to take appropriate measures. This study was conducted for the purpose of contributing to the dissemination of information on these diseases and their etiologic agents, epidemiology, and control. The study was based on data from 61 sources, including review articles, reports of outbreaks, and databases. Results reveal considerable underregistration and lack of data on FBD throughout the various countries, with viruses being the second most important cause of FBD in the United States of America. Two agents, Norwalk virus and hepatitis A virus, were the fifth and sixth most frequent causes, respectively, although the former was the single most frequent cause of FBD in 1982 and the second most frequent cause of water-borne diseases during the period from 1986 to 1988. Despite the scarcity of information on the problem, rotavirus, poliovirus, hepatitis E virus, astrovirus, and small gastroenteric viruses are also important causes of FBD. We also discuss the importance of viral zoonoses, especially hemorrhagic fevers transmitted by contact with rodent feces and tick-borne viral encephalitides (Lassa fever). There is discussion of the controversial mad cow disease and its potential transmission through food products, as well as of dietary aspects of the management of AIDS and other viral infections. Finally, measures for the prevention and control of FBD are described.     

Early-response cytokine expression in adult middle ear effusions

We determined the diseases associated with extremely high levels of alkaline phosphatase in hospitalized patients. Computerized laboratory records of the Hospital of Saint Raphael identified all inpatients who had elevations of alkaline phosphatase above 1,000 U/l from April 1994 to September 1995. Thirty-seven inpatients with alkaline phosphatase levels above 1,000 U/l were identified. Six had bone involvement from malignancy or Paget's disease and were eliminated from further analysis, and 31 patients were included in the study. Levels of alkaline phosphatase ranged from 1,014 to 3,360 U/l. Ten patients had sepsis as the cause of the elevated alkaline phosphatase. These included gram-negative organisms, gram-positive organisms, and two patients with fungal sepsis. Seven of 10 patients with sepsis had an extremely high alkaline phosphatase level and a normal bilirubin, 3 of 10 patients with sepsis also had acquired immunodeficiency syndrome (AIDS). Eight patients had biliary obstruction, 7 with malignant obstruction and 1 with a common bile duct stone. Nine patients had AIDS. The cause of the elevated alkaline phosphatase in these included three with sepsis, three with mycobacterium avium intracellulare (MAI) infection, two with cytomegalovirus infection, and one with Dilantin toxicity. Three patients had diffuse liver metastases. Finally, four patients had benign intrahepatic disease, including one patient with liver hemangiomas, one patient with sarcoid hepatitis, one patient with lead toxicity, and one patient with drug-induced cholestasis. Extremely high elevations of alkaline phosphatase are most frequently seen in patients with sepsis, malignant obstruction, and AIDS. Patients with sepsis can have an extremely high alkaline phosphatase level and a normal bilirubin. A variety of other causes were also noted.     

Real-time visualization of PH domain-dependent translocation of phospholipase C-delta1 in renal epithelial cells (MDCK): response to hypo-osmotic stress

BACKGROUND: The aim of this study was to compare the prognostic efficacy of cardiac troponin T (cTnT) and I (cTnI) in patients with clinical unstable angina. METHODS: We studied 74 patients with chest pain at rest, electrocardiographic evidence of myocardial ischemia, and normal (<6.7 ng/mL) values of creatine kinase-MB. cTnT was measured with a commercial assay (cutoff level 0.1 ng/mL) and cTnI with a preliminary research application (cutoff level 3.1 ng/mL). All patients had blood drawn at baseline and 8 hours thereafter. The prospectively defined end point was the proportion of patients identified by each assay as having myocardial damage. RESULTS: cTnT and cTnI were elevated in the same percentage of patients (18 of 74; 24%). Overall, 23 patients had elevations of 1 or both markers. In 13 there were elevations of both. Ten patients had elevations of only one (5 for each marker). In 51 patients, no elevations were present. Death or nonfatal myocardial infarction was more frequent in patients with elevated cTnI (27.7% vs 5.3%; P =.02) than those with normal values. The prognostic influence of cTnT was less (17% vs 8.5%; P =.2). However, the difference between the 2 markers when compared directly was not statistically significant (27.7% vs 17%; P = NS). CONCLUSIONS: These data indicate that both markers identify myocardial damage in equal numbers of patients with clinical unstable angina. Patients with elevations had a worse short-term outcome. The significance of the minor differences in prognostic value will require additional studies.     

Croup syndrome

Common causes of acute laryngotracheobronchitis (LTB) are viral infections. More rarely, bacterial germs, unspecific irritants, foreign bodies, rachitic laryngospasm, mild malformation, tumours, C1 esterase inhibitor deficiency, bilateral vocal cord paralysis, and psychogenic laryngospasm may be responsible for croup. Symptoms similar to epiglottitis may occur in pharyngitis based on common bacterial tonsillitis or infectious mononucleosis and peritonsillar abscess. It is decisively important to establish a precise diagnosis to provide for an appropriate therapy. Viral croup of mild degree is often sufficiently treated by cold and moistened air and--if necessary--prednisolone. In serious disease, oxygen insufflation and adrenaline (epinephrine) are useful. Recurrent croup is due to an unspecific hyperreactivity of tracheobronchial mucosa. It often leads to asthma. Consequently, preventive measures have to be considered similar to patients with bronchial hyperreactivity. Vaccination with haemophilus influenzae type b vaccine has proved effective and safe. The disease has therefore become impressively less frequent.     

Neuropsychiatric adverse effects of antiparkinsonian drugs. Characteristics, evaluation and treatment

Parkinson's disease (PD) is a progressive neurological condition that causes considerable disability in the elderly. Drugs used to treat PD, such as levodopa, offer symptomatic relief but often have neuropsychiatric adverse effects, most prominently psychosis and delirium. Aged patients and those with dementia are particularly vulnerable to these adverse effects. Evaluating PD patients with drug-induced neuropsychiatric adverse effects is made difficult by their complex clinical presentations. The treatment of drug-induced psychosis and delirium begins with manipulating the antiparkinsonian drug regimen, but this frequently worsens motor function. Atypical antipsychotics such as clozapine have been successfully employed to treat the psychosis without worsening the motor disability. Patient intolerance of clozapine therapy has prompted open-label studies with newer agents such as risperidone, remoxipride, zotepine, mianserin and ondansetron.     

Perindopril-associated pneumonitis

We report two cases of perindopril-associated pneumonitis with typical drug-induced clinical features. In the first case, biopsies showed granulomatous sarcoid-like lesions; in the second, bronchial wall eosinophil infiltratf2p4was reported with increased blood eosinophil count. In these two cases, improvement was obtained by withdrawal of the drug and was completed with steroids. All other causes were ruled out. Angiotensin-converting enzyme inhibitor (ACEI)-induced pneumonitis is still rare but has to be recognized as a real side-effect.     

Tamoxifen in liver disease: potential exacerbation of hepatic dysfunction

Tamoxifen, a non-steroidal anti-estrogen, has been used successfully for a decade as post-operative adjuvant therapy for breast cancer. Tamoxifen is generally well tolerated with few side effects, especially at the typical dose of 10 mg twice daily. However, hepatic effects have been reported after tamoxifen administration and are usually found to be cholestatic in nature. Although previous reports concentrate on tamoxifen as a probable cause of drug-induced hepatotoxicity, very little attention has been focused on the use of tamoxifen in patients with pre-existing liver dysfunction and the possible need for dose adjustment. We present the case of a 48-year-old woman with an acute exacerbation of her pre-existing liver dysfunction and subsequent elevations of tamoxifen blood levels after approximately one year of tamoxifen therapy for adjuvant treatment of breast cancer. Tamoxifen dosing was adjusted based on serum levels.     

Drug-induced pseudolymphoma and hypersensitivity syndrome. Two different clinical entities

OBJECTIVE: To test the hypothesis that drug-induced pseudolymphoma and hypersensitivity syndrome are 2 distinct clinical entities. DESIGN: Retrospective study from 1980 to 1993. SETTING: Departments of dermatology and medicine of 5 referral universitary hospitals. PATIENTS: Twenty-four patients who met arbitrary criteria selected as being suggestive of lymphoma, with probable drug cause. Patients with other definite cutaneous drug-induced eruptions were excluded. INTERVENTION: None. MAIN OUTCOME MEASURES: Suspect drugs; clinical, biological, and pathological findings; and evolution of each case and of 110 published case reports. RESULTS: Two groups were separated according to their mode of onset and clinical aspect. Three patients (and 15 cases in the literature) had subacute papulonodular or infiltrated plaques, without visceral involvement. Skin biopsy specimens showed a dense lymphocytic infiltrate mimicking lymphoma. Healing was constant when the drug was stopped. The 21 remaining patients (and 95 published cases) had an acute widespread eruption, with fever, enlarged lymph nodes, and multivisceral involvement. Lymphocytosis, atypical lymphocytes, eosinophilia, hepatitis, and high levels of lactate dehydrogenase were frequent. Skin biopsy findings were usually not specific (lymphocytic infiltrate and keratinocyte necrosis) but sometimes mimicked lymphoma. Severe forms and relapses occurred, even after the drug was stopped. The inducing drugs were the same in the 2 groups. CONCLUSIONS: These 2 groups correspond to drug-induced pseudolymphoma and hypersensitivity syndrome. We think that they are 2 distinct entities with different clinical and biological features and outcome, even if the pathological findings are sometimes similar. Prospective studies are needed to confirm these facts, to evaluate the therapy, and to follow up patients.     

An anticancer drug-sensitive murine erythroleukemia clone: implications for the mechanism of action of antineoplastic drugs

The mechanism(s) by which anticancer drugs kill tumor cells remains obscure. The studies reported here were undertaken with the view that the mechanism may be understood in part through an analysis of anticancer drug-sensitive clones. We have isolated a murine (Friend) erythroleukemia clone in which drug sensitivity was correlated with increased differentiation, suggesting that anticancer drug-induced cell death may be based on differentiation or a differentiation-dependent mechanism. In addition, this clone showed a high propensity for constitutive differentiation and frequent appearance of large multinucleate cells. Morphologically similar large aberrant cells were observed after the treatment of parental (745A) cells with Adriamycin (or bleomycin). We attribute these morphological defects occurring in clone 3-1 or in the parental cell line after anticancer drug treatment to a defective or inhibited cell cycle function. We suggest that the putative cell cycle defect in clone 3-1 is coupled to the increased drug-induced differentiation and resulting cell death. From a broader perspective, the studies reported here suggest that the search for and design of new anticancer drugs be directed at agents that modulate differentiation functions.     

Hematologic aspects of heart transplantation

Heart transplantation is an accepted therapeutic method for end-stage heart failure. The aim of the presented paper is to provide a short review of haematologic problems of heart transplantation. Haemostatic disorders, cytopenias and lymphoproliferative diseases are the most frequent haematologic complications of this highly sophisticated procedure. Perioperative bleeding tendency is due to cardiopulmonary bypass, both qualitative and quantitative platelet disorders and hyperfibrinolysis are the main causes. Incidence of cytopenias (mono- and/or bi- and/or tricytopenia) reaches up to 70%. They are multifactorial as to etiology and coincidence with viral infection, antimicrobial and immunosuppressive therapy. Lymphoproliferative disease affects about 1.2% of patients during the first year after transplantation. Posttransplant lymphoproliferative diseases are highly variable as to manifestation and prognosis-ranging from indolent course to rapid, aggressive growth. Routine cytostatic therapy is generally ineffective. Crucial therapeutic measure is to turn off immunosuppressive therapy. (Tab. 3, Fig. 2, Ref. 41).     

Quinolinic acid and lymphocyte subsets in the intrathecal compartment as biomarkers of SIV infection and simian AIDS

Cerebrospinal fluid (CSF) samples were collected from monkeys infected with SIVmac251 (SIV) or HIV-1/SIVmac chimeric viruses (SHIV(HXBc2) and SHIV(89.6P)) to investigate quinolinic acid (QUIN) levels in the intrathecal compartment. CSF levels of QUIN were elevated in the SIV-infected monkeys, especially in animals with end-stage disease, and in those infected with pathogenic SHIV(89.6P), but not after infection with the nonpathogenic construct SHIV(HXBc2). QUIN elevations occurred in association with reduced CD4+ and increased CD8+ lymphocytes, cellular alterations that were more pronounced in CSF than in the blood. These findings support the view that the intrathecal compartment provides a unique window on viral infection, and are in keeping with the a priori prediction that QUIN increases primarily in response to more pathogenic viral strains.     

Resistance of interleukin-1beta-deficient mice to fatal Sindbis virus encephalitis

Interleukin-1beta (IL-1beta) concentrations are frequently elevated in central nervous system (CNS) viral infections, but the pathophysiologic significance of such elevations is not known. To examine the role of IL-1beta in CNS viral pathogenesis, we compared the natural histories of IL-1beta-deficient and wild-type 129 SV(ev) mice infected with a neurovirulent viral strain, neuroadapted Sindbis virus (NSV). We found that the incidence of severe paralysis and death was markedly decreased in NSV-infected IL-1beta-/- mice compared to NSV-infected wild-type mice (4 versus 88%, P < 0.001). Despite this marked difference in clinical outcome, no differences in numbers of apoptotic cells or presence of histopathologic lesions in the brains of moribund wild-type mice and those of clinically healthy IL-1beta-/- mice could be detected. These results suggest that IL-1beta deficiency is protective against fatal Sindbis virus infection by a mechanism that does not involve resistance to CNS virus-induced apoptosis or histopathology.     

Thalidomide and thalidomide analogs reduce HIV type 1 replication in human macrophages in vitro

Thalidomide is currently being evaluated for efficacy in alleviating some manifestations of HIV-1 infection. To determine whether thalidomide has any direct effects on HIV-1 infection, we investigated the effect of thalidomide and also of three structural analogs of thalidomide on HIV-1 replication in vitro in human monocyte-derived macrophages. The thalidomide analogs were previously shown to inhibit TNF-alpha production in vitro at much lower concentrations than thalidomide. In HIV-1-infected macrophages treated with thalidomide or thalidomide analogs, viral replication was reduced by 60 to 80% as determined by measuring viral RT activity in the culture supernatants. In all experiments the analogs inhibited HIV-1 replication more efficiently than did thalidomide. The drugs also reduced HIV-1 gag mRNA expression. Furthermore, the drugs caused a decrease in NF-kappaB-binding activity in nuclear extracts of HIV-1-infected macrophages. The role of NF-kappaB in the drug-induced inhibition of HIV-1 replication was confirmed using an NF-kappaB-defective mutant virus to infect macrophages.     

MMPI--A scores and high points of male juvenile delinquents: Scales 4, 5, and 6 as markers of juvenile delinquency.

The Minnesota Multiphasic Personality Inventory-Adolescent (MMPI--A) clinical, supplementary, and content scale score patterns for 655 male delinquents were examined. Low scores on Scale 5 (Masculinity/Femininity) were found to be the most frequent deviation, followed by elevations on Scales 6 (Paranoia) and 4 (Psychopathic Deviate). This is consistent with previous research, although the importance of Scale 5 deviations has been little noted because of the traditional focus on scale elevations only. Classification analysis indicated that a combination of MMPI--A scales discriminated between this delinquent sample and the normative sample, with a sensitivity of 90%-95% and a specificity of 80%-95%. This level of sensitivity was maintained in a replication sample (N=473). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immunological influences in attention-deficit disorder and schizophrenia; is there a link between these two conditions?

This paper aims to explore the influence of the immune system on the pathobiochemistry of movement disorders (Tourette syndrome, obsessive compulsive disorders and attention-deficit disorder, with and without hyperactivity) and schizophrenia. In children, a temporal relationship has been observed between contraction of a group A beta-hemolytic streptococcal infection and subsequent presentation with one of the movement disorders. Pathology investigations reveal that elevated antineuronal antibodies are associated with movement disorders. Similarly, elevations in interleukin-1 beta and interleukin-6 have been reported in schizophrenia. It is now known that the immune system can be activated by conditions other than a viral or bacterial infection, such as: neurological insult, neurotoxicity--endogenous and environmental, neurotransmitter and cholesterol dysregulation. These latter avenues of immune system activation will be explored with respect to schizophrenia.     

Elevated liver enzymes of unknown etiology

Elevated liver enzymes are a frequent clinical problem of varying significance. In otherwise healthy individuals the most frequent causes of elevated liver enzymes are toxins such as alcohol and drugs. In this situation, further studies are usually not needed; it is sufficient to control the relevant parameters after abstinence from alcohol or withdrawal of the drug(s). In patients with known, suspected or unknown nonhepatic diseases, elevated liver enzymes can be caused by cardiovascular diseases, obesity, endocrinopathies, infectious diseases, malignancies, collagen disorders, sarcoidosis and other diseases. In this situation, sonography or liver histology frequently will be diagnostic, revealing the cause of the underlying disease as well as of the elevated liver enzymes.     

Lungs are a major organ site of cytomegalovirus latency and recurrence

Recurrence of infectious virus from the latent viral genomes is the initiating event in the pathogenesis of cytomegalovirus (CMV) disease during states of immunodeficiency. Interstitial pneumonia is a frequent manifestation of posttransplantation CMV disease, in particular after bone marrow transplantation and heart and lung transplantations. Recurrence can occur within the transplant derived from a latent infected donor as well as within latently infected organs of the transplant recipient. The reason for a predilection of the lungs as a site of CMV pathology is so far unknown. In a murine model of CMV latency, the lungs were identified as an authentic site of latent infection, since the viral genome remained detectable in lung tissue even after it was cleared to an undetectable level in blood and bone marrow. A comparison between the lungs and the spleen, the previously most thoroughly investigated site of murine CMV latency, revealed a 10-fold-higher burden of latent viral genome for the lungs. Most important, the organ-specific risk of in vivo recurrence was found to correlate with the organ-specific viral genomic load. This new finding thus characterizes the lungs as a high-risk organ for CMV recurrence, and this fact may explain in part why interstitial pneumonia is a frequent manifestation of recurrent CMV infection.     

Medical treatment of migraine: from mechanisms of action to contraindications

Management of migraine patients with or without aura must include appropriate medication to treat the attack and long-term preventive therapy, especially if the frequency of the attacks is greater than 2-4 per month. In both cases the choice of treatment depends on its efficacy and side effects. With regard to acute drug therapy, group studies do not suggest that ergot derivatives and sumatriptan are superior to simple analgesics and anti-inflammatory drugs, particularly if a prokinetic agent is added. These new substances are indicated for severe attacks refractory to more conventional therapy. Chronic drug abuse may induce drug-induced or rebound headaches. As regards long-term prophylaxis, group studies suggest that calcium antagonists and 5-HT-influencing drugs are superior concerning attacks frequency to beta-blocking agents, but involve very frequent side effects (weight gain and somnolence). Interesting preliminary results have also been reported with valproate and enalapril, which will confirmation by controlled studies. Finally, the choice of drug must take into account the patient's comorbidities (cardiovascular diseases, asthma, diabetes etc).