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     

Right internal thoracic artery through the transverse sinus in myocardial revascularization

Background. A major concern in evaluating dynamic cardiomyoplasty has been whether the synchronous stimulation of latissimus dorsi muscle is essential for benefit or not. We studied 10 patients to determine the efficacy of the systolic augmentation generated by the synchronous electrical stimulation of the latissimus dorsi muscle.

Methods. Left ventricular ejection fraction, end-systolic and end-diastolic volume indexes, and stroke volume index obtained during resting, peak exercise, and recovery periods (“on” values) were compared with those obtained 1 week after cessation of electrical stimulus (“off” values). Double product and estimated total body oxygen consumption at peak exercise were also calculated and compared.

Results. Higher ejection fractions (0.36 ± 0.07 versus 0.33 ± 0.06 at rest, 0.40 ± 0.07 versus 0.33 ± 0.07 peak exercise, and 0.37 ± 0.06 versus 0.31 ± 0.06 at recovery) and lower end-systolic volume indexes with relatively constant end-diastolic volume indexes were observed with the cardiomyostimulator on. Further, exercise response was better with the cardiomyostimulator on. Double product indirectly reflected better myocardial oxygen supply/demand ratio when on at peak exercise (17 ± 2.2 mm Hg × beats/min × 10⁻³ for on versus 19 ± 2.6 mm Hg × beats/min × 10⁻³ for off). Estimated total body oxygen consumption was improved at peak exercise when the cardiomyostimulator was functional (12 ± 2.7 mL · kg⁻¹ · min⁻¹ versus 11 ± 2.6 mL · kg⁻¹ · min⁻¹).

Conclusions. Current data suggest a true systolic assist during synchronous contractions of the latissimus dorsi muscle. It is thought, therefore, that synchronous electrical stimulation is essential for maximum benefit and all the beneficial effect of cardiomyoplasty certainly cannot be attributed to simple wrapping itself.     

Dopamine receptors on human T- and B-lymphocytes

The presence of functional dopamine receptors on differentiated cells of the mammalian immune system is still under discussion. This study has utilized (-)-[³H]sulpride as a ligand to detect the presence of recognition sites of the dopamine D₂ receptor family on human T- and B-lymphocytes. The (-)-[³H]sulpiride binding was of high affinity (K_d 0.9 nM ± 0.2 nM, specific, saturable (B_max 10.2 ± 1.4 fmol/10⁶ cells) and reversible. The pharmacological characterization of the recognition site suggests, similarities mainly with the D₂ and D₄ rather than D₃ subtype of dopamine receptor. Furthermore, dopamine treatment was able to reduce the intracellular cAMP levels of lymphocytes stimulated with forskolin, thus suggesting a potential functional significance of this dopamine receptor in mediating neural-immune interactions.     

Effect of verapamil on doxorubicin activity and pharmacokinetics in mice bearing resistant and sensitive solid tumors

Summary The effect of the combined administration of verapamil (i.p. twice daily) and doxorubicin (i.v once weekly) was tested in mice bearing the following: (a) a tumor with induced resistance to doxorubicin (B16VDXR melanoma line); (b) a tumor inherently resistant (MXT mammary carcinoma); and (c) four solid tumors sensitive to doxorubicin (B16 melanoma, B16V melanoma line, M5076 reticulum cell sarcoma, and Lewis lung carcinoma). Verapamil, given according to this treatment schedule, reached peak plasma concentrations of 3 M. Such treatment did not enhance doxorubicin activity on either inherently or induced resistant tumors, whereas it significantly enhanced doxorubicin growth inhibition in all the sensitive tumors except the Lewis lung carcinoma. Doxorubicin pharmacokinetics after administration of the drug alone and in combination with verapamil was analyzed after the first and repeated treatments in animals bearing B16 melanoma or its resistant subline B16VDXR. The resistance of the B16VDXR line was associated with the ability of the tumor to retain less doxorubicin (AUC=83 g h/g) than the sensitive tumor B16 (AUC=204 g h/g) in spite of similar initial levels. The potentiating effect of doxorubicin activity by, verapamil in B16 melanoma was not associated with increased doxorubicin levels or retention in the tumor, nor were differences in doxorubicin levels or retention found in the B16VDXR line. The combined treatment did not modify doxorubicin pharmacokinetics in plasma, heart, or spleen. These studies suggest that verapamil in vivo is ineffective in potentiating doxorubicin activity in tumors against which doxorubicin is inactive, that sensitive tumors are heterogeneous in their sensitivity to modulation by verapamil, and that this effect is not associated with modification of doxorubicin pharmacokinetics.This work was supported by grant no. 84.00855.44 of the Finalized Project Oncologia from the Consiglio Nazionale delle Ricerche, Rome     

Prevalence of hereditary ataxias and spastic paraplegias in Molise,a region of Italy

Summary An epidemiological survey of hereditary ataxias and paraplegias was conducted in Molise, a region of Italy (335, 211 inhabitants on 1 January 1989). Total prevalence was 7.5 x 10^–5 inhabitants (95% confidence limits 4.8–11.1). There were 7 patients with Friedreich's disease, 5 with early onset cerebellar ataxia with retained tendon reflexes, 4 with ataxia-telangiectasia, 9 with hereditary spastic paraplegias (2 autosomal dominant and 7 autosomal recessive cases). There was no patient with autosomal dominant cerebellar ataxia.     

Friendships in later life: definitions and maintenance patterns

This study examined the meaning and maintenance of friend relationships in later life. The sample consisted of forty-one males and seventy-four females, sixty years of age or older. Participants were asked a series of open-ended questions regarding their past and present relationships with their friends. While older men and women tended to agree on the characteristics of a friend, gender differences emerged when they were asked to differentiate between a "friend" and a "close friend." Older women were more likely to consider friends made earlier in their lives as still part of their friend network than were older men. Perceptions of current involvement with friends also differed depending upon the gender of the respondent. Discussion centered on the definition of friends in later life and gender differences found in maintenance patterns.     

Phenotypic and functional characteristics of tumor-associated lymphocytes in patients with malignant ascites receiving intraperitoneal infusions of recombinant interleukin-2 (rIL-2)

In the course of a phase I trial, in which recombinant IL-2 (rIL-2) was infused intraperitoneally (i.p.) in patients with peritoneal carcinomatosis, we evaluated the effect on "tumor-associated lymphocytes" (TAL) isolated from the ascitic fluid. No major changes in the percentages of cells expressing the CD3, CD4, CD8, Leu-7, OKM1 and WT-31 antigens were detected either in TAL or in peripheral blood lymphocytes (PBL) after 7 days of rIL-2 infusion. In contrast the percentages of TAL (but not PBL) expressing surface IL-2 receptor (Tac), or LAK-1 antigen were sharply increased. Analysis of cytolytic functions showed a potentiation of the lytic activity against natural-killer (NK) sensitive K562 target cells and the de novo appearance of lytic activity against fresh melanoma cells. In one patient IFN-gamma was detected in the ascitic fluid following rIL-2 infusion. T-cell clones derived from the patient were analyzed for the IFN-gamma production. While only approximately 40% of PB-derived control clones produced medium to low amounts of IFN-gamma, all of the TAL-derived clones produced medium to high amounts of the lymphokine.