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Biomedical subjects

Joseph R Berger

Publications and source records attributed to Joseph R Berger.

At least 19 recordsLinked to original sources
PubMed2007

Frequency and phenotype of JC virus-specific CD8+ T lymphocytes in the peripheral blood of patients with progressive multifocal leukoencephalopathy.

JC virus (JCV)-specific CD8+ cytotoxic T lymphocytes (CTL) are associated with a favorable outcome in patients with progressive multifocal leukoencephalopathy (PML) and cross-recognize the polyomavirus BK virus (BKV). We sought to determine the frequency and phenotype in fresh blood of CD8+ T cells specific for two A*0201-restricted JCV epitopes, VP1(p36) and VP1(p100), and assess their impact on JC and BK viremia and viruria in 15 healthy subjects, eight human immunodeficiency virus-positive (HIV+) individuals, and nine HIV+ patients with PML (HIV+ PML patients) classified as survivors. After magnetic pre-enrichment of CD8+ T cells, epitope-specific cells ranged from 0.001% to 0.022% [corrected] by tetramer staining, with no significant difference among the three study groups. By use of seven-color flow cytometry, there was no predominant differentiation phenotype subset among JCV-specific CD8+ T cells in healthy individuals, HIV+ subjects, or HIV+ PML patients. However, in one HIV+ PML patient studied in the acute phase, there was a majority of activated effector memory cells. BKV DNA was undetectable in all blood samples by quantitative PCR, while a low JC viral load was found in the blood of only one HIV+ and two HIV+ PML patients. JCV and BKV DNA were detected in 33.3% and 13.3% of all urine samples, respectively, independent of the presence of JCV-specific CTL. The detection of JCV DNA in the urine was associated with the presence of a JCV VP1(p100) CTL response. Immunotherapies aiming at increasing the cellular immune response against JCV may be valuable in the treatment of HIV+ individuals with PML.

Adult↗
PubMed2007

Acute central cord syndrome with bodybuilder sign.

We describe a 81-year-old man who after falling face forward and hyperextending his neck suffer an acute cervical spinal cord injury consistent with acute traumatic central cord syndrome (ATCCS) who developed a peculiar posture with arm abduction at the shoulders and flexion at the elbows and wrists resembling the pose of a bodybuilder.

Aged, 80 and over↗
PubMed2006

JC virus detection in bodily fluids: clues to transmission.

JC virus in saliva, oropharyngeal fluid, blood, and urine samples obtained from 58 human immunodeficiency virus-infected persons and 58 matched controls was investigated by performing quantitative polymerase chain reaction. JC virus was rarely present in oropharyngeal fluid and blood samples, even in those obtained from immunosuppressed individuals, but it was commonly detected in urine samples from both groups, suggesting that urine contributes to transmission.

Adult↗
PubMed2006

A placebo-controlled study of memantine for the treatment of human immunodeficiency virus-associated sensory neuropathy.

Distal sensory polyneuropathy (DSP) is the most frequent neurological complication of HIV infection. Neuropathic symptoms vary from mild paresthesias to severe pain that respond only partially to symptomatic treatment. Forty-five subjects with human immunodeficiency virus (HIV)-associated symptomatic DSP (SDSP) were enrolled in a randomized, multicenter, 16-week placebo-controlled study of memantine, an N-methyl-D-aspartate (NMDA) uncompetitive antagonist. Although memantine was well tolerated, no trend toward clinical benefit was observed. Results were similar to those of other pilot studies of memantine for neuropathic pain unrelated to HIV, suggesting that memantine is ineffective for the symptomatic treatment of HIV-associated SDSP.

Adult↗
PubMed2006

Persistent Coxsackie B encephalitis: Report of a case and review of the literature.

Although the diagnosis is rarely confirmed, enteroviruses are a common cause of meningitis. Coxsackie B is responsible for more than half of the cases of aseptic meningitis in infants less than 3 months old, but is less common as a cause of neurological disease in older persons. In addition to aseptic meningitis, Coxsackie B has been reported to cause a wide range of other neurological disorders, albeit rarely. The authors report a young adult with persistent Coxsackie B encephalitis that was heralded by focal seizures and evolved to intractable coma with multifocal myoclonus. The diagnosis was established by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) on tissue obtained at brain biopsy. Cerebrospinal fluid (CSF) viral cultures and PCR were negative for enteroviruses. This case highlights unusual features of a persistent infection that could easily have been mistaken for a neurodegenerative or other noninfectious process. It also emphasizes the importance of performing brain biopsy on individuals with neurological disease of obscure nature.

Adult↗
PubMed2006

High prevalence of multiple human herpesviruses in saliva from human immunodeficiency virus-infected persons in the era of highly active antiretroviral therapy.

Human immunodeficiency virus (HIV) infection is associated with an increased risk for human herpesviruses (HHVs) and their related diseases. Methods for limiting the transmission of HHVs require a better understanding of the prevalence and infectiousness of oral HHVs in HIV-infected patients. We performed quantitative PCR to investigate the prevalence, quantity, risk, and correlates of salivary HHVs from 58 HIV-seropositive individuals in a case control study. HHVs were significantly more prevalent in the salivas of HIV-seropositive persons than in those of the controls (odds ratios [ORs], 4.2 to 26.2; P<or=0.008). In HIV-infected patients, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), cytomegalovirus (CMV), and herpes simplex virus type 1 (HSV-1) were detected in 90%, 57%, 31% and 16% of samples, respectively, compared with 48%, 24%, 2%, and 2%, respectively, of samples from controls. Multiple HHVs were observed in 71% of HIV-seropositive persons and only 16% of controls (OR, 13.0; 95% confidence interval, 5.29 to 32.56). HIV-positive patients had significantly higher EBV loads than HIV-negative persons (P<0.0001). HIV-infected patients with CD4 counts above 200 cells/microl had increased probability for having HHV-8 in saliva (P=0.009) compared with patients whose counts were less than 200. In contrast, HSV-1, EBV, and CMV were detected more often when CD4 counts were low. High salivary HHV loads were detected for those (n=7) with oral lesions. These findings suggest that saliva is a potential risk factor for the acquisition of multiple HHVs, and several host factors may function to accelerate HHV reactivation or replication in patients with HIV infection.

Adult↗
PubMed2006

Progressive multifocal leukoencephalopathy: lessons from AIDS and natalizumab.

The dramatic increase in the incidence of progressive multifocal leukoencephalopathy (PML) that occurred as a consequence of the AIDS pandemic and the recent association of PML with the administration of natalizumab, a monoclonal antibody to alpha4 integrin that blocks inflammatory cell entry into the brain, has stimulated a great deal of interest in this previously obscure viral demyelinating disease. The etiology of this disorder is JC virus (JCV), a polyoma virus, observed in 80% of the population worldwide. Seroepidemiological studies indicate that infection with this virus typically occurs before the age of 20 years. No primary illness owing to JCV infection has been recognized and the means of spread from person to person remains obscure. Following infection, the virus becomes latent in bone marrow, spleen, tonsils and other tissues. Periodically the virus reactivates during which time it can be demonstrated in circulating peripheral lymphocytes. The latter is significantly more commonly observed in immunosuppressed populations than that in normal subjects. Despite the large pool of people infected with JCV, PML remains a relatively rare disease. It is seldom observed in the absence of an underlying predisposing illness, typically one that results in impaired cellular immunity. A variety of factors are likely responsible for the unique increase in frequency of PML in HIV infection relative to other underling immunosuppressive disorders. Preliminary data suggests that natalizumab appears to distinctively predispose recipients to PML relative to other infectious complications. Studies in these populations will be invaluable in understanding the mechanisms of disease pathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Natalizumab.

Medical therapeutics has entered a new and exciting era with the development of biological agents that target specific sites. In the studies performed to date, natalizumab, a humanized monoclonal antibody to alpha4 integrin, when administered intravenously at monthly intervals, appeared to be highly beneficial with respect to decreasing both relapse rate and contrast-enhancing lesions in multiple sclerosis. Salutary actions on other disease parameters were also observed. However, treatment with natalizumab was complicated by the development of a rare demyelinating disease of the brain--progressive multifocal leukoencephalopathy (PML)--that developed in three patients in clinical trials of the drug. Currently, the estimated incidence for the development of PML with natalizumab treatment is 1:1,000 after approximately 18 months of therapy; however, as the development of PML is a stochastic event, it is quite possible that higher rates will be observed after longer treatment courses. Curiously, other opportunistic infections were not observed at higher rates in the treated groups when compared to controls, suggesting a specific association between natalizumab, and perhaps other alpha4 integrin blockers, and PML. Postmarketing surveillance studies should answer this and other questions related to the use of natalizumab.

Antibodies, Monoclonal↗
PubMed2006

Ziconotide infusion for severe chronic pain: case series of patients with neuropathic pain.

Ziconotide intrathecal infusion was recently approved by the United States Food and Drug Administration for the treatment of intractable severe chronic pain. Patients with neuropathic pain make up a significant population among those who experience chronic pain for which there are less than optimal pharmacotherapeutic options. Published clinical trials provide a global view of ziconotide efficacy and safety. A subset of patients in clinical trials obtained complete pain relief, a remarkable finding given the history of drug treatment for neuropathic pain. To provide more information regarding those who respond to ziconotide therapy, we discuss three patients with neuropathic pain who received ziconotide infusion. Two patients with longstanding neuropathic pain, one with complex regional pain syndrome (formerly known as reflex sympathetic dystrophy) of the leg and one with lumbar radiculitis, achieved temporary but complete pain relief from single 5- and 10-microg epidural test doses. In the third case, a patient with longstanding bilateral leg and foot neuropathic pain from acquired immunodeficiency syndrome and antiretroviral drug therapy achieved considerable pain relief from a long-term continuous intrathecal infusion. The patients who received a single dose had mild central nervous system adverse effects such as sedation, somnolence, nausea, headache, and lightheadedness. The patient who received the intrathecal infusion experienced mild-to-severe adverse effects depending on the rate of infusion; these effects included sedation, confusion, memory impairment, slurred speech, and double vision. This patient could sense impending adverse effects and made rate adjustments or suspended infusion to avert untoward symptoms. In all three cases, patients achieved considerable pain relief that was long-lasting and persisted well after dose administration or suspension of infusion.

Analgesics, Non-Narcotic↗
PubMed2005

ALS syndrome in patients with HIV-1 infection.

BACKGROUND: A viral etiology of amyotrophic lateral sclerosis (ALS) has been proposed because of the selective vulnerability of motor neurons to certain viruses. During the last 20 years, at least 19 cases of ALS or ALS-like disease have been reported in HIV-1 (HIV) seropositive individuals. OBJECTIVE: To describe two cases of clinically definite ALS in patients with HIV infection and to review the previously reported cases of HIV-associated ALS syndrome. SETTING: A multidisciplinary ALS center and Neuro-AIDS clinic at a tertiary care university hospital. PATIENTS/DESIGN: We investigated and prospectively monitored two patients who had developed clinically definite ALS by El Escorial criteria several years after acquiring the HIV infection. The previously reported cases of ALS or ALS-like disease in patients with HIV infection were reviewed for comparison and contrast with the characteristics of sporadic ALS. RESULTS: The clinical course of ALS in our two HIV seropositive individuals mirrored that of classical sporadic ALS. A review of previously described 19 patients with ALS syndrome revealed clinically definite ALS in 4 cases and clinically probable or possible ALS in 15. ALS commenced at different stages of the HIV disease; in 7 patients, HIV infection was discovered contemporaneously with diagnosis of ALS. CD4+ T cell count ranged from 2 to 560 cells/mm3. Three (1 definite ALS) of the fatal cases were studied at autopsy and all exhibited pathology outside the motor neuron pool. Unlike our patients, 7 of 8 patients with HIV-associated ALS syndrome receiving HAART demonstrated at least partial recovery of their motor deficit. CONCLUSIONS: ALS-like syndrome can occur in association with HIV infection; however, the causal relationship remains uncertain. Patients with ALS syndrome related to HIV infection are generally younger in age and often demonstrate pathology outside the motor neuron system. Patients with HIV-associated ALS syndrome may improve following antiretroviral therapy. An aggressive HAART regimen to reduce viral load should be pursued in all such cases.

Adult↗
PubMed2005

Intravascular lymphomatosis presenting with sudden hearing loss.

Intravascular lymphoma (IVL) is a rare disorder characterized by the aggregation of malignant large cell lymphoma cells in small vessels. Neurological manifestations are typically the initial and, often the only, clinically obvious consequences of this malignancy. Diagnosis is dependent on biopsy or postmortem demonstration of the intravascular tumor. We report a patient in whom sudden hearing loss heralded IVL and propose that the hearing loss may have been the consequence of labyrinthine infarction consequent to the aggregation of malignant cells in the internal auditory artery.

Anti-Inflammatory Agents↗
PubMed2005

Brachial amyotrophic diplegia in a patient with human immunodeficiency virus infection: widening the spectrum of motor neuron diseases occurring with the human immunodeficiency virus.

Although amyotrophic lateral sclerosis and progressive spinal muscular atrophy have been recognized to occur in association with human immunodeficiency virus infection, to our knowledge, brachial amyotrophic diplegia, a form of segmental motor neuron disease, has not been previously reported. Brachial amyotrophic diplegia results in severe lower motor neuron weakness and atrophy of the upper extremities in the absence of bulbar or lower extremity involvement, pyramidal features, bowel and bladder incontinence, and sensory loss. We describe a human immunodeficiency virus-seropositive man without severe immunosuppression or prior AIDS-defining illnesses who had brachial amyotrophic diplegia. This disorder may represent one end of a spectrum of motor neuron diseases occurring with this retrovirus infection.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Cerebrospinal fluid proteomics and human immunodeficiency virus dementia: preliminary observations.

Protein profiling using mass spectrometry may be useful in identifying previously unknown protein markers in human immunodeficiency virus (HIV) dementia and provide insight into disease pathogenesis. Six samples of matched cerebrospinal (CSF) and blood serum from patients with no, mild, and moderate dementia were prepped for biomarker screening by the Ciphergen system. Chips were analyzed in the matrix-assisted laser desorption/ionization (MALDI) mass spectrometer at low mass (700 to 20,000 Da) and at higher mass (5000 to 100,000 Da). In both serum and CSF samples, differences in protein intensity appeared to correlate with degree of dementia. This preliminary study suggests that protein markers of HIV dementia may be detected by MALDI mass spectrometry.

AIDS Dementia Complex↗