A comparision of brain biopsy and CSF-PCR in the diagnosis of CNS lesions in AIDS patients

Twenty patients with AIDS who had intracranial lesions underwent both brain biopsy and cerebro-spinal fluid (CSF) examination to compare histological diagnosis with the polymerase chain reaction (CSF-PCR) for the identification of infectious agents. CSF-PCR was performed for herpes simplex virus, varicella zoster virus, cytomegalovirus (CMV), JC virus (JCV), Epstein-Barr virus (EBV), Toxoplasma gondii and Mycobacterium tuberculosis. A definitive diagnosis was obtained by brain biopsy in 14 patients (2 with astrocytoma, 12 with brain infection). CSF-PCR was positive for EBV DNA in 3 of 3 cases of primary cerebral lymphoma, positive for JCV DNA in 6 of 7 biopsy-proven (and one autopsy-proven) cases of progressive multifocal leukoencephalopathy (PML). CSF-PCR was positive for CMV DNA in one biopsy-proven and one autopsy-proven case of CMV encephalitis (the former also had PML) and positive for M. tuberculosis DNA in one case of tuberculous encephalitis. None of the five toxoplasmic encephalitis cases (one definite, four presumptive) were T. gondii DNA positive. There was close correlation between histology and CSF-PCR for CMV encephalitis, PML and PCL. Antitoxoplasma therapy affected the sensitivity of both histological and CSF-PCR methods. Received: 8 November 1995 Received in revised form: 9 July 1996 Accepted: 19 July 1996     

Peripheral blood CD3 and CD4 T-lymphocyte reduction correlates with severity of liver cirrhosis

Summary Immunological disturbances with impairment of immune function and a higher incidence of lymphoproliferative disorders and other malignancies have been described in liver cirrhosis patients. To investigate the pathogenetic mechanism(s) involved in such associated we looked for a possible imbalance in peripheral blood T-lymphocyte subpopulations in patients with liver cirrhosis of differing severity. Immunophenotyping and counts of peripheral blood T-lymphocyte subpopulations were carried out using monoclonal antibodies conjugated with different fluorochromes in 31 consecutive cirrhotic patients and 23 matched healthy volunteers. Univariate and multivariate analyses of lymphocyte phenotype counts were performed and odds ratios were computed. Statistically significant associations, according to both univariate and multivariate analyses, were found between case/control status and mean CD3 and CD4 T-lymphocyte counts (P<0.0001). A strong correlation was found between the Pugh’s index and CD3 and CD4 lymphocyte counts, with a clear reduction of these phenotypes with increasing liver cirrhosis. Median CD3 and CD4 values were 2,283 and 1,329/μl respectively among controls and 896, 801, and 492/μl and 515, 514, and 307/μl, respectively in categories A, B, and C of Pugh’s classification. Very high odds ratios were found using the median values of CD3 and CD4 as a threshold. There was a statistically significant decrease for each of the T-cell phenotypes studied (CD2, CD3, CD4, CD8, CD16, CD19, CD20, CD56, CD57) between patients and controls (P<0.0001). The progressive and severity-related decrease in mean peripheral blood CD3 and CD4 counts in liver cirrhosis suggests a progressive impairment of protective immune function and may be a factor facilitating malignancy in cirrhotic patients.     

Radiology of the foot in chronic alcoholism

The authors have reviewed the radiographic patterns of the foot in 28 patients affected by neuropathic joint disease complicating alcoholism, out of a series of 82 chronic alcoholic patients. Sixteen of them were also affected by diabetes mellitus. On the basis of X-ray findings, lesions were divided into three groups, reflecting the evolution of the disease: 1) early changes, especially affecting the soft tissues and joints; 2) definite lesions, consisting of fractures, osteolysis, bone destruction and amputation, periarticular debris; 3) "healing" signs, simulating degenerative joint disease, which cause severe and weakening deformities. Tabes dorsalis and diabetic osteoarthropathy must be differentiated from alcohol-induced syndrome. Even though a correct differential diagnosis is often difficult to reach, it must be kept in mind that focal/diffuse osteopenia is the most characteristic manifestation of alcoholic osteopathy, whereas different radiographic findings simulate chronic degenerative arthropathies.     

Rehabilitation of the knee after anterior cruciate ligament reconstruction

From the Kerlan-Jobe Orthopaedic Clinic, 501 E. Hardy Street, Suite 200, Inglewood, CA 90301. New information regarding the isometric placement of the anterior cruciate ligament (ACL) substitute, revascularization process, and biomechanical stresses have all contributed to and been incorporated in the rehabilitation program after ACL reconstruction. Treatment protocols specifically designed for the patient following ACL reconstruction are imperative to return the individual to his or her preinjury status. Care is taken to limit the amount of stress placed on the ligament substitute especially at end of range extension. A program incorporating techniques for developing range of motion and strength while still preserving stability at the knee joint is still of the utmost importance. This program is a revision of a previously reported regimen from this facility (Brewster, Moynes, Jobe, J Orthop Sports Phys Ther 5:121-126, 1983) and is based upon clinical experience and research information. J Orthop Sports Phys Ther 1989;11(1):8-18.     

ErbB2 and the antimetastatic nm23/NDP kinase in regulating serum induced breast cancer invasion

The erbB2 gene is often found amplified and/or overexpressed in breast cancer in which it has clinical relevance as prognostic and predictive factor. It is involved in growth regulation and has a role in the initial phases of cell proliferation, while in vivo and in vitro studies have suggested an involvement also in cell invasion and metastases. It is not clear if these two roles are mutually exclusive and little is known about the mechanisms by which erbB2 may be involved in the control of these processes. Our previous data on patient series suggested that erbB2 might be regulated in different ways depending on the neoplastic status of the cells and that it might be involved in different regulatory pathways. To test this hypothesis we have measured the serum-dependent regulation of erbB2 as a function of the expression of the antimetastatic gene, nm23, in a panel of breast cancer cell lines. The experimental model consisted of three cell lines having different proliferative and invasive potentials: a non-metastatic estrogen receptor (ER) positive cell line, MCF-7; a highly metastatic ER negative cell line, MDA-MB435; and the MDA-MB435 cell line transfected with the nm23-H1 antimetastatic gene (clone H1-177) which has lost the ability to invade and metastasize. We first analysed the serum concentration dependence of invasion and proliferation after 3-4 days of serum deprivation confirming the proliferative and invasive potential of the three cell lines. Modulation of erbB2 expression by different concentrations of serum was then studied. ErbB2 expression in MCF-7 cells showed a complex pattern due to serum modulation, whereas, it was not longer regulated by serum in the MDA-MB435 cell line. In H1-177 cells the erbB2 response to serum was restored and it was very similar to that observed in MCF-7. These data showed a tight association between nm23 and the regulation of erbB2 expression by serum factors suggesting that the role of erbB2 in invasion might be dependent on nm23 expression.     

Dependence of adaptation of the human vertical angular vestibulo-ocular reflex on gravity

We determined the spatial dependence of adaptive gain changes of the vertical angular vestibulo-ocular reflex (aVOR) on gravity in five human subjects. The gain was decreased for 1 h by sinusoidal oscillation in pitch about a spatial vertical axis in a subject-stationary surround with the head oriented left-side down. Gains were tested by sinusoidal oscillation about a spatial vertical axis while subjects were tilted in 15° increments from left- to right-side down positions through the upright. Changes in gain of the vertical component of the induced eye movements were expressed as a percentage of the preadapted values for the final analysis. Vertical aVOR gain changes were maximal in the position in which the gain had been adapted and declined progressively as subjects were moved from this position. Gain changes were plotted as a function of head orientation and fit with a sine function. The bias level of the fitted sines, i.e., the gravity-independent gain change, was –29±10% (SD). The gains varied around this bias as a function of head position by ±18±6%, which were the gravity-dependent gain changes. The gravity-dependent gain changes induced by only 1 h of adaptation persisted, gradually declining over several days. We conclude that there is a component of the vertical aVOR gain change in humans that is dependent on the head orientation in which the gain was adapted, and that this dependence can persist for substantial periods.     

Mapping antigenic sites of an immunodominant surface lipoprotein of Mycoplasma agalactiae, AvgC, with the use of synthetic peptides

As a first step toward the design of an epitope vaccine to prevent contagious agalactia, the strongly immunogenic 55-kDa protein of Mycoplasma agalactiae was studied and found to correspond to the AvgC protein encoded by the avgC gene. The avg genes of M. agalactiae, which encode four variable surface lipoproteins, display a significant homology to the vsp (variable membrane surface lipoproteins) genes of the bovine pathogen Mycoplasma bovis at their promoter region as well as their N-terminus-encoding regions. Some members of the Vsp family are known to be involved in cytoadhesion to host cells. In order to localize immunogenic peptides in the AvgC antigen, the protein sequence was submitted to epitope prediction analysis, and five sets of overlapping peptides, corresponding to five selected regions, were synthesized by Spot synthesis. Reactive peptides were selected by immunobinding assay with sera from infected sheep. The three most immunogenic epitopes were shown to be surface exposed by immunoprecipitation assays, and one of these was specifically recognized by all tested sera. Our study indicates that selected epitopes of the AvgC lipoprotein may be used to develop a peptide-based vaccine which is effective against M. agalactiae infection.     

Effect of hydrostatic pressure on ADH induced osmotic water flow in toad bladder

The effect of hydrostatic pressure (HP) on antidiuretic hormone (ADH) stimulated osmotic water flow (Jv) across the toad urinary bladder was evaluated. Jv for ADH-stimulated bladders was significantly reduced by an elevation of the serosal HP gradient to 1 cm H₂O. Subsequent elimination of the HP gradient resulted in a recovery of Jv. Serosal HP also caused a reversible increase in sucrose permeability (P sucrose). For ADH-treated bladders fixed with glutaraldehyde during serosal HP exposure, subsequent exposure to a mucosal or serosal HP gradient caused acceleration or inhibition of Jv, respectively. The reduction in ADH-associated Jv with serosal HP was apparently caused by a back-flux of water through a paracellular pathway. Jv and P sucrose were not affected by mucosal HP during ADH stimulation. The results suggest a specific sensitivity of a paracellular pathway to a small serosal HP gradient in bladders with ADH-stimulated water flow. The reversibility of this effect on P sucrose suggests that the elements comprising the apical junctions are dynamic structures capable of recovering at least some of their permeability properties.