IL-10 producing regulatory and helper T-cells in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease characterised by the production of pathogenic autoantibodies against nuclear self-antigens. The anti-inflammatory and tolerogenic cytokine Interleukin-10 appears to play a paradoxical pathogenic role in SLE and is therefore currently therapeutically targeted in clinical trials. It is generally assumed that the pathogenic effect of IL-10 in SLE is due to its growth and differentiation factor activity on autoreactive B-cells, but effects on other cells might also play a role. To date, a unique cellular source of pathogenic IL-10 in SLE has not been identified. In this review, we focus on the contribution of different CD4+T-cell subsets to IL-10 and autoantibody production in SLE. In particular, we discuss that IL-10 produced by different subsets of adaptive regulatory T-cells, follicular helper T-cells and extra-follicular B-helper T-cells is likely to have different effects on autoreactive B-cell responses. A better understanding of the role of IL-10 in B-cell responses and lupus would allow to identify the most promising therapies for individual SLE patients in the future.

Evidence for a pathogenic role of extrafollicular, IL-10-producing CCR6+B helper T cells in systemic lupus erythematosus.

Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4+CCR6+IL-7R+T cells from human tonsils produced IL-10 following stimulation by naïve B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6+B helper T cells were phenotypically distinct from follicular helper T (TFH) cells and lacked BCL6 expression. In peripheral blood, a CCR6+T cell population with similar characteristics was identified, which lacked Th17- and TFH-associated gene signatures and differentiation-associated surface markers. CD4+CCR6+T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4+CCR6+IL-7R+T cells were associated with the presence of pathogenic anti-dsDNA (double-stranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10-producing CCR6+T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE.

Evaluation of phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome: results of an international multicentre study.

Objective A task force of scientists at the International Congress on Antiphospholipid Antibodies recognized that phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) might contribute to a better identification of antiphospholipid syndrome (APS). Accordingly, initial and replication retrospective, cross-sectional multicentre studies were conducted to ascertain the value of aPS/PT for APS diagnosis. Methods In the initial study (eight centres, seven countries), clinical/laboratory data were retrospectively collected. Serum/plasma samples were tested for IgG aPS/PT at Inova Diagnostics (Inova) using two ELISA kits. A replication study (five centres, five countries) was carried out afterwards. Results In the initial study ( n = 247), a moderate agreement between the IgG aPS/PT Inova and MBL ELISA kits was observed ( k = 0.598). IgG aPS/PT were more prevalent in APS patients (51%) than in those without (9%), OR 10.8, 95% CI (4.0-29.3), p < 0.0001. Sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratio of IgG aPS/PT for APS diagnosis were 51%, 91%, 5.9 and 0.5, respectively. In the replication study ( n = 214), a moderate/substantial agreement between the IgG aPS/PT results obtained with both ELISA kits was observed ( k = 0.630). IgG aPS/PT were more prevalent in APS patients (47%) than in those without (12%), OR 6.4, 95% CI (2.6-16), p < 0.0001. Sensitivity, specificity, LR + and LR- for APS diagnosis were 47%, 88%, 3.9 and 0.6, respectively. Conclusions IgG aPS/PT detection is an easily performed laboratory parameter that might contribute to a better and more complete identification of patients with APS.

Cognitive outcome as part and parcel of clinical outcome in brain tumor surgery.

Although validated tools (neuropsychological tests, patient reported outcomes, mood and psychological profile) were first introduced many years ago in clinical practice, the impact of the tumor itself on patient cognition has not been extensively studied. Furthermore, while outcome research is evolving in an attempt to adapt the use of different tools to the preoperative and postoperative phases, the standard guidelines for evaluating outcome after brain surgery, by neurological examination and complication assessment, are frequently neglected in the current literature. This article attempts to provide an appraisal of the evidence for the impact of surgical treatment on cognitive function of brain tumor patients within the context of general outcome.

Environmental electroactive consortia as reusable biosensing element for freshwater toxicity monitoring.

The development of tools to monitor water quality is mandatory in a scenario where clean water resources are decreasing. Here, the biosensing capability of an electroactive river sediment consortium was tested towards three model contaminants (glutaraldehyde, nickel(II) and chromium(III)). The proposed biosensor is a small membrane-less single chamber Microbial Fuel Cell (MFC), fabricated by 3D printing. Its semi-continuous mode of operation resulted in long-term current profile stability and reproducibility. A linear trend of response was obtained for glutaraldehyde in a concentration range of 5-1000 ppm. After the recovery of the electroactive consortium activity, the MFC-based biosensors were shown to be sensitive towards Ni(II) and Cr(III), at concentrations above 2 mg L-1. To effectively analyze biosensor response, a novel algorithm was proposed, offering advantages for the realization of energy-saving protocols for MFC-biosensor data transmission. Implementation of the device and method, from laboratory test to real environment, can offer a low cost in situ system for detection of water contaminants.

Pidotimod: a reappraisal.

Pidotimod (Polimod ) is a synthetic dipeptide molecule with biological and immunological activity on both the adaptive and the innate immune responses. In vitro studies, both from animal and human specimens, have documented a good activity on innate and adaptive immune responses and have been confirmed by in vivo studies. These activities have been applied in clinical studies demonstrating the efficacy of pidotimod in reducing the rate of recurrent infections of the upper respiratory and urinary tracts in children. The same results were obtained in recurrent respiratory tract infections in adults. Interestingly, these effects are more evident in the setting of immune defects such as senescence, Downs syndrome, and cancer.

Management of the controversial aspects of the antiphospholipid syndrome pregnancies: a guide for clinicians and researchers.

BACKGROUND: Recommendations for the treatment of aPL-positive patients with pregnancy morbidity are based on a limited number of well-designed clinical trials. However, the management of pregnant aPL-positive women still displays several open questions. OBJECTIVE: To determine the practice patterns of experienced physicians in the management of the controversial aspects of aPL pregnancies. METHODS: A questionnaire reproducing debated conditions was initially sent to the Advisory Board members (ABMs) of the 12th Congress of aPL and the Fifth Conference on Sex Hormones, Pregnancy and Rheumatic Diseases (Florence, Italy, April 2007), and then the same questionnaire was posted at the Hospital for Special Surgery (www.hss.edu) website and all attendees (ATS) of the above meetings were invited to participate via e-mail. Answers have been collected and analysed in a descriptive fashion and responses of the two groups evaluated by Chi-square or Fisher's exact test. RESULTS: As a whole 75 responses from the ABMs and ATS were included in the analysis. In general, there was no significant difference between the opinions of two groups. CONCLUSIONS: Management recommendations displayed reasonable consistence: (i) for the use of low-dose aspirin and low-molecular weight heparin during pregnancy and during ovarian stimulation for in vitro fertilization; (ii) against oestrogen-containing oral contraceptives; and (iii) for the use of anticoagulants in the post-partum period.

Accuracy of dielectric-dependent hybrid functionals in the prediction of optoelectronic properties of metal oxide semiconductors: a comprehensive comparison with many-body GW and experiments.

Understanding the electronic structure of metal oxide semiconductors is crucial to their numerous technological applications, such as photoelectrochemical water splitting and solar cells. The needed experimental and theoretical knowledge goes beyond that of pristine bulk crystals, and must include the effects of surfaces and interfaces, as well as those due to the presence of intrinsic defects (e.g. oxygen vacancies), or dopants for band engineering. In this review, we present an account of the recent efforts in predicting and understanding the optoelectronic properties of oxides using ab initio theoretical methods. In particular, we discuss the performance of recently developed dielectric-dependent hybrid functionals, providing a comparison against the results of many-body GW calculations, including G 0 W 0 as well as more refined approaches, such as quasiparticle self-consistent GW. We summarize results in the recent literature for the band gap, the band level alignment at surfaces, and optical transition energies in defective oxides, including wide gap oxide semiconductors and transition metal oxides. Correlated transition metal oxides are also discussed. For each method, we describe successes and drawbacks, emphasizing the challenges faced by the development of improved theoretical approaches. The theoretical section is preceded by a critical overview of the main experimental techniques needed to characterize the optoelectronic properties of semiconductors, including absorption and reflection spectroscopy, photoemission, and scanning tunneling spectroscopy (STS).

Diagnostic value of PRND gene expression profiles in astrocytomas: relationship to tumor grades of malignancy.

Doppel (PRND) is a paralogue of the mammalian prion (PRNP) gene. It is abundant in testis and, unlike PRNP, it is expressed at low levels in the adult central nervous system (CNS). Besides, doppel overexpression correlates with some prion-disease pathological features, such as ataxia and death of cerebellar neurons. Recently, ectopic expression of doppel was found in two different tumor types, specifically in glial and haematological cancers. In order to address clinical important issues, PRND mRNA expression was investigated in a panel of 111 astrocytoma tissue samples, histologically classified according to the World Health Organization (WHO) criteria (6 grade I pilocytic astrocytomas, 15 grade II low-grade astrocytomas, 26 grade III anaplastic astrocytomas and 64 grade IV glioblastoma multiforme). Real-time PRND gene expression profiling, after normalisation with GAPDH, revealed large differences between low (WHO I and II) and high grade (III and IV) of malignancy (P<0.001). Extensive differences in PRND gene expression were also found within each grade of malignancy, suggesting that PRND mRNA quantitation might be useful to distinguish astrocytoma subtypes, and important in disease stratification and in the assessment of specific treatment strategies.

Neuroprotective role of neurophysiological monitoring during endovascular procedures in the brain and spinal cord.

The goal of endovascular neurosurgery is to occlude aneurysms and arteriovenous malformations (AVMs) or to reduce the vascular supply to hypervascularized tumors, while preserving function in the normal neural tissue. However, the intra-arterial injection of embolizing materials into the cerebral or spinal circulation exposes to the risk of ischemic complications. Under general anesthesia, unless a wake-up test is performed, the only way to assess the functional integrity of sensory and motor pathways is to use neurophysiological monitoring. Somatosensory (SEPs) and muscle motor evoked potentials (mMEPs) can be used in combination with pharmacological provocative tests (PTs) to predict the effects of embolization. Amytal blocks neuronal activity, while lidocaine blocks axonal conduction. Therefore, a positive Amytal or lidocaine test (i.e. more than 50% decrease in SEP amplitude and/or mMEP disappearance) indicates that the vessel distal to the tip of the microcatheter supplies the functional gray or white matter of the spinal-cord respectively and cannot be embolized. Brain and spinal-cord vascularization and hemodynamics are extremely complex and even more unpredictable in the presence of a vascular malformation, but using a combined SEPs, MEPs and PTs protocol, morbidity related to endovascular procedures is very low. Given the high sensitivity of peripheral recordings to spinal-cord ischemia, experimental and clinical studies support the concept that whenever the mechanism of spinal-cord injury is purely ischemic, recording mMEPs may suffice. Reports on the use of PTs and neurophysiological monitoring during embolization of brain AVMs in critical areas are more anecdotal and mainly limited to the use of short-acting barbiturates. Our preliminary experience using lidocaine and combining SEP and mMEP monitoring is encouraging, since no false negative results were observed. Finally, if the sensitivity of this method is very high, its specificity has not been tested because embolization is abandoned whenever PTs are consistently positive. Accordingly, the possibility of false positive results cannot be excluded.

Monitoring of motor pathways during brain stem surgery: what we have achieved and what we still miss?

Intraoperative neurophysiological monitoring (IOM) has established itself as one of the paths by which modern neurosurgery can improve surgical results while minimizing morbidity. IOM consists of both monitoring (continuous "on-line" assessment of the functional integrity of neural pathways) and mapping (functional identification and preservation of anatomically ambiguous nervous tissue) techniques. In posterior-fossa and brainstem surgery, mapping techniques can be used to identify - and therefore preserve - cranial nerves, their motor nuclei and corticospinal or corticobulbar pathways. Similarly, free-running electromyography (EMG) and muscle motor-evoked potential (mMEP) monitoring can continuously assess the functional integrity of these pathways during surgery. Mapping of the corticospinal tract, at the level of the cerebral peduncle as well as mapping of the VII, IX-X and XII cranial nerve motor nuclei on the floor of the fourth ventricle, is of great value to identify "safe entry-zones" into the brainstem. Mapping techniques allow recognizing anatomical landmarks such as the facial colliculus, the hypoglosseal and glossopharyngeal triangles on the floor of the fourth ventricle, even when normal anatomy is distorted by a tumor. On the basis of neurophysiological mapping, specific patterns of motor cranial nuclei displacement can be recognized. However, brainstem mapping cannot detect injury to the supranuclear tracts originating in the motor cortex and ending on the cranial nerve motor nuclei. Therefore, monitoring techniques should be used. Standard techniques for continuously assessing the functional integrity of motor cranial nerves traditionally rely on the evaluation of spontaneous free-running EMG in muscles innervated by motor cranial nerves. Although several criteria have been proposed to identify those EMG activity patterns that are suspicious for nerve injury, the terminology remains somewhat confusing and convincing data regarding a clinical correlation between EMG activity and clinical outcome are still lacking. Transcranial mMEPs are also currently used during posterior-fossa surgery and principles of MEP monitoring to assess the functional integrity of motor pathways are similar to those used in brain and spinal-cord surgery. Recently, current concepts in muscle MEP monitoring have been extended to the monitoring of motor cranial nerves. So-called "corticobulbar mMEPs" can be used to monitor the functional integrity of corticobulbar tracts from the cortex through the cranial motor nuclei and to the muscle innervated by cranial nerves. Methodology for this purpose has appeared in the literature only recently and mostly with regards to the VII cranial nerve monitoring. Nevertheless, this technique has not yet been standardized and some limitations still exist. In particular, with regards to the preservation of the swallowing and coughing reflexes, available intraoperative techniques are insufficient to provide reliable prognostic data since only the efferent arc of the reflex can be tested.

Overexpression of N-ras oncogene and epidermal growth factor receptor gene in human glioblastomas.

Five human glioblastoma cell lines were analyzed for oncogene activation with a panel of probes. Abnormal expression of the epidermal growth factor receptor (EGFr) gene was detected in four of five lines; N-ras oncogene overexpression was found in all five cell lines. These results were subsequently confirmed with fresh brain tumor and nonneoplastic brain tissue biopsy samples; increased expression of the N-ras proto-oncogene was observed in five of five glioblastomas, all of which also showed EGFr gene overexpression, but not in well-differentiated gliomas or in nonneoplastic brain tissue specimens. No significant differences in Ha-ras and Ki-ras expression were observed. Preliminary histochemical observations showed that intracellular levels of transforming growth factor alpha, a putative biochemical link between these two oncogenes, were significantly higher in glioblastoma cells than in controls.

Investigation of resistance to DNA cross-linking agents in 9L cell lines with different sensitivities to chloroethylnitrosoureas.

The 9L-2, 9L-7, and 9L-8 cell lines, derived from the 9L in vivo rat brain tumor, were treated with nitrosoureas that can alkylate and cross-link DNA and carbamoylate intracellular molecules to various extents. Compared to 9L cells, 9L-2 cells were very resistant to the cytotoxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea, and to 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-deoxyglucopyranose. The sensitivity of 9L-7 and 9L-8 cell lines to these drugs was intermediate between 9L and 9L-2. Treatment of 9L, 9L-2, 9L-7, and 9L-8 cell lines with 1,3-bis(trans-4-hydroxycyclohexyl)-1-nitrosourea produced approximately the same level of cell kill. Compared to 9L cells, 9L-2 cells are 10-fold more resistant to the cytotoxic effects, 34-fold more resistant to the induction of sister chromatid exchanges, and have 40% fewer DNA interstrand cross-links caused by treatment with 3-(4-amino-2-methyl-5-pyrimidinyl)methyl-1-(2-chloroethyl)-1-nitrosourea . In contrast, treatment of 9L and 9L-2 cells with 1-ethylnitrosourea produced approximately the same level of cell kill and induction of sister chromatid exchanges. Our results suggest that the resistance of 9L-2, 9L-7, and 9L-8 cells is related to DNA cross-linking and not to alkylation or carbamoylation. We studied the effects of other agents that form DNA cross-links with structures different from those formed by treatment with chloroethylnitrosoureas (CENUs) in 9L and 9L-2 cells. In contrast to results obtained with CENUs, 9L-2 cells were 2-fold more sensitive to the cytotoxic effects, 2-fold more sensitive to the induction of sister chromatid exchanges, and had 3-fold more cross-links formed than 9L cells treated with nitrogen mustard. However, the amount of cell kill, number of sister chromatid exchanges induced, and the DNA cross-linking were the same for 9L and 9L-2 cells treated with cis-diamminedichlorplatinum(II). Our results indicate that cellular resistance to CENUs is highly specific and that the mechanism of resistance does not allow cross-resistance with other DNA cross-linking agents. These and other results suggest that when DNA repair processes mediate cellular resistance to CENUs, other cross-linking agents will not be cross-resistant unless they form alkylation products that are affected by repair processes that mediate resistance to CENUs.

SV40 early region and large T antigen in human brain tumors, peripheral blood cells, and sperm fluids from healthy individuals.

SV40 T antigen (Tag) coding sequences were detected by PCR amplification followed by Southern blot hybridization in human brain tumors and tumor cell lines, as well as in peripheral blood cells and sperm fluids of healthy donors. SV40 early region sequences were found in 83% of choroid plexus papillomas, 73% of ependymomas, 47% of astrocytomas, 33% of glioblastoma multiforme cases, 14% of meningiomas, 50% of glioblastoma cell lines, and 33% of astrocytoma cell lines and in 23% of peripheral blood cell samples and 45% of sperm fluids from normal individuals. None of the 13 normal brain tissues were positive for SV40 DNA, nor were seven oligodendrogliomas, two spongioblastomas, one neuroblastoma, one meningioma, or four neuroblastoma cell lines. Expression of SV40 early region was found by reverse transcription PCR, and SV40-specific Tag was detected by indirect immunofluorescence in glioblastoma cell lines. DNA sequence analysis, performed in four positive samples, confirmed that the amplified PCR products belong to the SV40 early region. Sixty-one % of the neoplastic patients positive for SV40 sequences had an age excluding exposure to SV40-contaminated polio vaccines, suggesting a contagious transmission of SV40. The possible role of SV40 Tag in the etiopathogenesis of human brain tumors and the spread of SV40 by horizontal infection in the human population are discussed.

Gamma knife radiosurgery in brain metastases from testicular tumors.

To our knowledge, there are no published reports on the effectiveness of radiosurgery in the management of brain metastases from testicular nonseminomatous germ cell tumor. The authors evaluate the results of gamma knife (GK) treatment in three patients with these unusual intracranial lesions. Between April 1995 and July 2001, three patients with brain metastasis from testicular nonseminomatous germ cell tumor underwent adjuvant radiosurgery at our department. The primary tumor had been surgically removed in all cases. At diagnosis, one patient was stage IB and two were stage III poor risk. Chemotherapy and whole brain radiotherapy were administered before radiosurgery in all cases. Pre-GK radiotherapy was administered with a daily fraction dosage of 1.8-2.0 Gy. The indications for radiosurgery were tumor volume <20 cm3, microsurgery too risky, refusal of surgery. All the lesions were located in eloquent brain areas. Post-GK high-dose chemotherapy with autologous peripheral-blood stem-cell rescue was administered in two cases due to systemic recurrence of the disease. All patients are still alive with a median and mean follow-up period after radiosurgery of 63 and 68.3 mo, respectively. They had no neurological deficits at the latest examination. Neuroradiological follow-up invariably showed tumor growth control (complete response in two cases and partial response in one) with typically delayed post-radiosurgical imaging changes (transient in two cases and long-lasting in one). In conclusion, GK seems to be highly effective and safe in brain metastases from testicular nonseminomatous germ cell tumor. In cases with diffuse metastatic brain involvement, the whole brain radiotherapy preceding radiosurgery should be delivered with 1.8 Gy daily fraction to prevent the risk of long-lasting post-radiosurgical imaging changes.

Stereotactic brain biopsy in human immunodeficiency virus-infected patients.

OBJECTIVE: To evaluate prospectively the diagnostic efficacy and safety of stereotactic brain biopsy and its impact on treatment, outcome, and survival in human immunodeficiency virus-infected patients with focal brain lesions. METHODS: Computed tomography-guided stereotactic brain biopsy was performed in 26 patients, of whom 17 failed to respond to a 2- to 3-week anti- Toxoplasma regimen. Exclusion criteria for biopsy were overt acquired immunodeficiency syndrome for 2 years or longer, Karnofsky score less than 50, and severe coagulopathies. RESULTS: A definitive diagnosis was obtained in 24 patients (92%), of whom 12 (46%) had primary brain lymphoma, six (23%) had progressive multifocal leukoencephalopathy, and four (15%) had Toxoplasma encephalitis. Two thirds of contrast-enhancing lesions on computed tomography were lymphoma and three fourths of contrast-negative lesions were leukoencephalopathy. Three patients had biopsy-related cerebral hemorrhages (morbidity, 11.5%). Median follow-up and survival for the entire group were 24 weeks (range, 6 to 135 weeks). Twenty patients (77%) received specific therapy and 13 (50%) responded to treatment. Of 11 patients with lymphoma undergoing irradiation treatment (whole-brain radiotherapy in seven and gamma-knife treatment in four), nine (82%) had clinical and radiologic response, with a median survival of 34 weeks (range, 13 to 57 weeks). CONCLUSIONS: Stereotactic brain biopsy has high diagnostic efficacy and clinical benefit in carefully selected human immunodeficiency virus-infected patients. The procedure should be performed essentially in patients with contrast-enhancing lesions on computed tomography who have a high frequency of treatable cerebral diseases.

Shape recovery and volume calculation from biplane angiography in the stereotactic radiosurgical treatment of arteriovenous malformations.

PURPOSE: A model for calculating the three-dimensional volume of arteriovenous malformations from biplane angiography. METHODS AND MATERIAL: Three-dimensional (3D) volume reconstruction is easily feasible with axial, coronal, or sagittal computer tomography (CT) and nuclear magnetic resonance (NMR) scans. On the other hand, radiosurgical treatment of arteriovenous malformations (AVM) is exclusively based on two orthogonal stereotactic projections, obtained with angiographic procedures. Most commonly, AVM volumes have been calculated by assimilating the nidus volume to a prolate ellipsoid. We present an algorithm dedicated to 3D structure reconstruction starting from two orthogonal stereotactic projections. This has been achieved using a heuristic approach, which has been widely adopted in the artificial intelligence domain. RESULTS: Tests on phantom of different complexity have shown excellent results. CONCLUSION: The importance of the algorithm is considerable. As a matter of fact: (a) it allows calculations of complex structures far away from regular ellipsoid; (b) it permits shape recovery; (c) it provides AVM visualization on axial planes.

Impaired immunocompetence in patients with malignant gliomas: the possible role of Tg-lymphocyte subpopulations.

T-lymphocyte subpopulations (Tg or "suppressor cells" and Tm or "helper cells") in the peripheral blood of 16 patients with malignant intracranial gliomas were analyzed. The number of Tm-lymphocytes was very close to normal in both pre- and postoperative samples, whereas Tg-lymphocytes were significantly increased preoperatively (18.55 +/- 1.11 vs. 12.72 +/- 1.19 p less than 0.001) and were still slightly higher than normal after operation and radiation treatment. These preliminary findings suggest a possible role of T-suppressor lymphocytes in the impairment of cell-mediated immunocompetence that has been observed repeatedly in patients with malignant gliomas.

Cyclic nucleotides in medulloblastomas: correlative study of tumoral and cerebrospinal fluid levels.

The tumoral and cerebrospinal fluid (CSF) levels of cyclic nucleotides and of the main adrenergic metabolites (homovanillic acid and 5-hydroxyindoleacaetic acid) were investigated in a group of children with posterior fossa medulloblastomas. A longitudinal evaluation of CSF change of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and adrenergic metabolites before and after surgical removal of the tumor mass is presented. Some preliminary patterns concerning correlative levels in the neoplastic tissue are discussed. The relevant increase of cGMP in medulloblastoma specimens and in CSF samples operation and the rapid decrease in the CSF after surgical removal of the tumor seem to suggest a possible role of cyclic nucleotides in the neoplastic growth of these tumors. (Neurosurgery, 7: 359-362, 1980).

Tuberculoma of the anterior optic pathways. Case report.

A tuberculoma, encasing the anterior optic pathways in a neoplastiform growth, was found in a 25-year-old man complaining of severe visual loss, diabetes insipidus, and sexual impotence following tuberculous meningitis. Following biopsy and anti-tuberculosis treatment, a satisfactory restoration of sight in one eye allowed the patient to resume an almost normal life.