Low efficacy of thalidomide in improving response after induction in multiple myeloma patients who are candidates for high-dose therapy.

Giving the impact of complete response (CR) on outcome of multiple myeloma patients addressed to high-dose melphalan, we explored the role of a pre-transplant intensification with 3 months thalidome plus dexamethasone therapy (Thal-Dex), after pulse-VAD induction. Seventy-four multiple myeloma patients (MM pts) uniformly treated, were retrospectively studied. The response rate after pulse-VAD were: CR 6%, VGPR 40%, PR 23%, MR 23%, and progression 8%. The response rate after Thal-Dex were similar: CR 11%, VGPR 39%, PR 17%, MR 9%, and progression 24%. Giving no advantage in terms of response rate with an additive toxicity, Thal-Dex does not seem useful for intensification before transplant.

Influence of different anaesthetics on extracellular aminoacids in rat brain.

We used different anaesthetic procedures to study the possible effects of anaesthesia on extracellular aminoacid concentration in rat brain. Glutamate, aspartate and glycine concentrations were determined by HPLC in samples collected from the right fronto-parietal region of the rat brain cortex by transcerebral microdialysis before and up to 2 h following anaesthesia induction. Anaesthesia induced by ketamine, alone or in association with xylazine, caused a significant decrease in the levels of glutamate, aspartate and glycine, compared to before anaesthesia values (range: 27-72% according to the time of sampling and to the anaesthetic used). Inhalation anaesthesia with halothane (3%) in N2O/O2 mixture produced no significant effects on aminoacid levels. Equitensine (pentobarbital in association with chloral hydrate and ethanol) and pentobarbital also had no significant effect on glutamate, aspartate and glycine levels during anaesthesia. This demonstrates that some anaesthetics alter excitatory aminoacid release and suggests that Equitensine may represent an easy and reliable method to induce a long lasting anaesthesia associated without changes in excitatory aminoacid extracellular concentration.

Primary cardiac lymphoma. A case report and review.

Primary cardiac lymphoma is classically defined as an extranodal non-Hodgkin's lymphoma exclusively located in the heart and/or pericardium. However, over the last few years, this definition has been extended to include other localizations on condition that these are clearly less important then a cardiac site, that must remain the first, during the illness course, and the most important for its entity. PCL is extremely rare in immunocompetent patients, accounting for 1.3% of all cardiac tumours and 0.5% of all extranodal lymphomas, but it has been encountered with increasing frequency in patients with AIDS or other severe immunodepressive syndromes. PCL is difficult to diagnose, especially during the early stage of the disease, because of its non-specific clinical manifestations, the limited possibility of using non-invasive diagnostic techniques, and difficulties or delays in applying invasive methods. The malignancy of its histotypes and its delicate location are responsible for its rapid and frequently unfavourable evolution. Successful treatment, which is mainly based on anthracycline-containing polychemotherapies, is heavily dependent on an early diagnosis. After a general review of the literature, the authors describe the clinical case of a patient with a PCL that had a secondary central nervous system location, treated with polychemotherapy and autologous peripheral blood stem cell transplantation. Emphasis is placed on the fact that it is more difficult to eradicate the disease from the central nervous system than from the heart.

Nitrite/nitrate balance during photoinduced cerebral ischemia in the rat determined by high-performance liquid chromatography with UV and electrochemical detection.

A specific and simple method for the direct simultaneous detection of extracellular nitrite (NO2-) and nitrate (NO3-) has been developed, using high-performance liquid chromatography separation with UV and electrochemical detection in series. These stable endproducts of nitric oxide (NO.) were determined in dialysis perfusate obtained through in vivo brain microdialysis during and after experimental photoinduced cerebral ischemia in rats. The chromatographic conditions were optimized with a reversed-phase column (250 x 46 mm) using 10 mM n-octylamine pH 6.0 as a mobile phase. Absorbance was measured at 220 nm for NO3- detection; electrochemical detection was performed at +0.7 V for NO2- evaluation. This assay system holds the advantages of in vivo consecutive measurements, high precision, good reproducibility, technical simplicity, fast response (about 7 min), and wide availability.

Study of factors affecting the determination of total plasma 7-fluorobenzo-2-oxa-1,3-diazole-4-sulfonate (SBD)-thiol derivatives by liquid chromatography.

A detailed investigation of the factors affecting the determination of total plasma 7-fluorobenzo-2-oxa-1,3-diazole-4-sulfonate (SBD)-thiol derivatives (i.e. cysteine, homocysteine and cysteinylglycine) is described. Essentially, this assay entails extracting specific thiols by plasma disulphide bond reduction, protein precipitation, sulphydryl compound derivatization with the thiol-specific fluorogenic reagent ammonium 7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate (SBD-F), and subsequent separation with isocratic reversed-phase high-performance liquid chromatography. By improving the reliability of several analytical parameters (composition of the mobile phase, pretreatment of the sample using different reducing and protein precipitation agents, and optimization of the derivatization of thiols with SBD-F), a number of critical issues can be identified and solved.

[Splenic lymphoma with villous lymphocytes. A clinical case]. / Linfoma splenico con linfociti villosi. Caso clinico.

Splenic lymphoma with circulating villous lymphocytes is a rare B-lymphoproliferative disorder of the elderly which has been only recently defined. Clinical features are spleen enlargement of various degree without lymphadenopathy and an indolent course, with a long survival, in most cases. Absolute lymphocytosis is present; atypical circulating lymphocytes show a medium or large size, a small prominent nucleolus and a few short and thin cytoplasmic protrusions and projections (villi), which are distributed at one or both poles of cell surface. Reaction for tartrate-resistant acid phosphatase is almost always negative. Immunological markers are as follows: CD 19+, CD 20+, CD 22+, CD 11c+/-, CD 5-, CD 23-, CD 25-, HLA DR+, SmIg+. Differential diagnosis with other chronic lymphoproliferative disorders, particularly chronic lymphocytic leukemia, hairy cell leukemia, prolymphocytic leukemia, follicular and mantle-cell lymphoma in leukemic phase, is based on clinical and immunocytomorphologic criteria. Bone marrow biopsy shows involvement of different degree and pattern; splenic involvement mostly occurs in the white pulp; hepatic nodules in portal areas may be present. Cytogenetic alterations are often present but not specific, such as increased serum LDH and monoclonal gammopathy. No therapy should be made in asymptomatic patients. In case of systemic symptoms, symptomatic splenomegaly or cytopenias, treatment may consist on splenectomy, splenic irradiation or alkylating agents. A case of splenic lymphoma with circulating villous lymphocytes is reported; differential diagnosis, particularly with other B lymphoproliferative disorders, is discussed.

[Colliculus hemorrhage]. / Hémorragies du colliculus.

We report the case of a patient with mesencephalic hematoma involving only the quadrigeminal plate. One case of superior and 3 cases of inferior colliculus hematoma have already been reported. Involvement of the quadrigeminal plate frequently follows a pontine or an anterior mesencephalic hemorrhage. The cause of these hematomas may be due to cryptic malformations of the quadrigeminal plate or primitive small size hemorrhages possibly related to the nature of the arterial system. Patients with inferior colliculus lesions present a typical symptomatology consisting of trochlear nerve palsy contralateral to the lesion or bilateral, contralateral hemiparesthesiae and acuphenes. Superior colliculus lesion causes upgaze palsy, visual blurring, dizziness and left upper lip paresthesiae. The cause of the different signs and symptoms in both types of lesion are discussed.

Reference values of neuroactive amino acids in the cerebrospinal fluid by high-performance liquid chromatography with electrochemical and fluorescence detection.

Sampling and HPLC analysis procedures for CSF amino acid determinations were evaluated. In order to increase sensitivity, a precolumn derivatization of amino acids by o-phthalaldehyde-mercaptoethanol reagent was used. By using fluorimetric and electrochemical detection in series, positive peak identification can be obtained in a single chromatographic run. It is recommended to analyze freshly collected CSF. Amino acids are stable for short periods over a wide range of temperature, but storage at -80 degrees C is recommended. The CSF samples for the calculation of the reference values were taken from 40 healthy subjects, hospitalized for lumbar disk herniation, placed on the same diet and kept drug-free for at least 1 week. The mean values (mumol/l) and the ranges (in parentheses) were: 0.27 (0.09-0.63), 0.62 (0.18-1.15), 5.32 (3.05-11.50), 6.16 (2.90-13.30), 0.16 (0.03-0.22) for aspartic acid, glutamic acid, glycine, taurine and gamma-aminobutyric acid respectively.

Disseminated encephalitis following streptococcal infection.

Various neurological disorders have been related to Streptococcus pyogenes infection. Only recently, and for the first time, it has been suggested that acute disseminated encephalitis may also complicate a streptococcal infection. The case reported in this paper seems to confirm this hypothesis.

EBVD and alternating MOPP/EBVD with or without localized field radiotherapy in advanced or unfavorably presenting Hodgkin's disease.

PATIENTS AND METHODS: Ninety-five patients with previously untreated, advanced or unfavorably presenting Hodgkin's disease were recruited in ten centers. Twenty-five patients with stage II-A-bulky disease received four courses of EBVD (epirubicin, bleomycin, vinblastine, dacarbazine) plus involved field radiotherapy (Group 1); 24 patients in stage I-B, II-B and III-A received 6 courses of EBVD (11 of them also received radiotherapy on bulky localizations (Group 2); 46 patients in stage III-AS > or = 3 nodes, III-B and IV received MOPP/EBVD 4 + 4 courses (Group 3). RESULTS: Eighty patients (84%) achieved CR, eight patients (8%) a PR, five patients did not respond and two progressed during therapy. CRs were achieved by 23/25 patients (92%) in Group 1, 21/24 (87%) in Group 2 and 36/46 (78%) in Group 3. The mean duration of follow-up was 33.3 months (range 5-69). There were three deaths from directly treatment-related causes. Twelve patients suffered chronic toxicity, including six who suffered lung toxicity and two who developed secondary myelodysplasia. CONCLUSIONS: The results achieved in this co-operative study are similar to those reported by most single-Institution trials and those with adriamycin-containing regimens. Long-term toxicity deserves careful consideration.

Bone marrow biopsy for the staging of non-Hodgkin's lymphoma: bilateral or unilateral trephine biopsy?

AIM: The occurrence of unilateral involvement in bilateral bone marrow trephine biopsies in non-Hodgkin's lymphomas (NHL) at disease onset (10-20% of cases) has been reported since the early 70s. Therefore, although these studies were based on small series, the use of bilateral bone marrow biopsies has become the rule. However, the clinical value of this procedure has never been clearly established. The aim of the present study was to ascertain the true value of bilateral bone marrow biopsy in the staging of NHL. STUDY DESIGN: We examined 368 cases of NHL (A-H according to the Working Formulation) (WF), without leukemic involvement of the peripheral blood, in order to evaluate: 1) the incidence of unilateral bone marrow involvement; 2) the percentage of patients who, as a result of unilateral bone marrow involvement, changed from stages I-II to stage IV; 3) assessment of response to therapy for patients with both bilateral or unilateral bone marrow involvement. RESULTS: In the A-C NHL groups of WF there was a unilateral bone marrow involvement of 8.8%. Overall, bone marrow involvement induced a change from clinical stages I-II to stage IV in 5.6% of cases, a figure which would correspond to a false negative rate of 2.8%, if unilateral bone marrow biopsy was performed. In the D-F and G, H groups of WF, unilateral involvement was 10.1% and 8.5% respectively; the change in stage from I-II to IV by unilateral bone marrow involvement respectively amounted to 1.4% and 2.8%, which correspond to respective false negative rates of 0.7% and 1.4%. CONCLUSIONS: On the basis of these results and of the present therapeutic strategies, we propose: bilateral bone marrow biopsy for clinical stages I-II of all NHL; no bone marrow biopsy at disease onset for clinical stages III and IV of A to H histologic subtypes of the WF; unilateral bone marrow biopsy (A-C subtypes of the WF) or bilateral (D-H of the WF), after the regression of extramedullary localizations.

A cooperative study of epirubicin with cyclophosphamide, vincristine and prednisone (CEOP) in non-Hodgkin's lymphoma.

BACKGROUND: The purpose of our cooperative trial was to investigate whether epirubicin (EPI) at 90 mg/m2 in a CHOP-like combination (called CEOP) could increase complete response (CR) and survival rates in non-Hodgkin lymphoma (NHL) patients while maintaining a tolerable degree of toxicity. METHODS: Between September 1986 and July 1992, 218 patients from 12 Centers in Lombardy entered this study. The inclusion criteria were: a histological diagnosis of intermediate or diffuse large cell (DLC) NHL and no previous radio-chemotherapy. The patients in stages IA and IIA (both intermediate and DLC) received four CEOP courses followed by local/regional radiotherapy; those with intermediate NHL in stages IB, IIB, III A and B and IV A and B received six CEOP courses and, if they achieved CR, three further courses as consolidation. RESULTS: Among the 160 evaluable patients, CR was observed in 90% of the subjects with DLC-NHL (stages IA and IIA) and in 59% of those with intermediate-grade NHL (all clinical stages). If the clinical stages are considered separately, the CR rates were 92% for stages IA, IIA and 53% for stages IB, IIB, III A and B, IV A and B. Relapses occurred in 20% of the patients treated with four CEOP courses plus radiotherapy and in 31% of those who received nine CEOP courses because of the advanced stage of their disease. As of May 1994, the median follow-up was 42 months. If all of the patients are considered together, the 7-year overall survival (OS) probability was 64% and the 7-year disease-free survival (DFS) probability 67%. In comparison with stages III/IV, the patients in stages I-II had better DFS (7-year chance 77% vs 56%, p < 0.03). Hematological toxicity was acceptable, and a delay in the administration of CEOP chemotherapy was required in only three patients. No life-threatening infections were recorded. CONCLUSIONS: Our cooperative study of the use of the CEOP combination in NHL patients shows that response rates and the length of DFS are equal to the best results obtained with CHOP and more intensive programs, although further confirmation must be provided by means of a longer follow-up and a more careful analysis of prognostic factors according to the recently proposed international index. In our experience, an EPI dose of 90 mg/m2 has negligible toxicity (particularly on bone marrow), even in elderly patients. These findings are interesting since it is well known that myelotoxicity is the principal limiting factor for the majority of anthracycline-containing regimens used in the treatment of potentially curable NHL.

Aminoacid recovery via microdialysis and photoinduced focal cerebral ischemia in brain cortex of rats.

A photochemical method using the Rose Bengal dye as thrombogenic agent was employed to induce focal cerebral ischemia in frontoparietal cortex of rats. A transcerebral microdialysis probe was used to collect samples from ischemic cortical area. An increase in glutamate (6-fold) and in taurine (4-fold) within the first hour occurred. Neuropathological investigations demonstrate a reproducible damaged area surrounded by a thin peripheral area showing neuronal apoptotic phenomena. The method represents a reproducible model of focal cerebral ischemia with neuropathological aspects superimposable to those characteristic of thrombogenic stroke in man. This method could also be relevant in the study of neurotransmitters during the evolution of ischemia. Furthermore, the presence of apoptotic phenomena in the perilesional halo confirms an ischemic penumbra suggesting the significance of preclinical pharmacological trials.

Elongated styloid process and Eagle's syndrome.

A controversial entity, Eagle's syndrome, is reviewed. After an anatomical description of the maxillo-vertebro-pharyngeal region we summarize the causative, diagnostic and therapeutic aspects of the syndrome. Two different conditions are often reported as Eagle's syndrome: one characterized by dysphagia and unilateral pharyngeal pain radiating to the ear and worsened by swallowing; the other characterized by pain in the head and neck region due to compression of the neurovascular structure by an elongated styloid process. The latter also includes typical cranial neuralgias (such as glossopharyngeal neuralgia) and carotidynia. We believe that the term "Eagle's syndrome" is legitimate only in the first case and in those "atypical" painful head and neck conditions related to an elongated styloid process and relieved by styloidectomy. We believe Eagle's syndrome deserves consideration in the International Headache Classification.

Familial hemiplegic migraine versus migraine with prolonged aura: an uncertain diagnosis in a family report.

Four of five members of a family complained of repeated attacks of hemiplegic migraine, migraine with aura of different types, or migraine without aura. The hemiplegia always outlasted the headache and was often accompanied by altered consciousness, aphasia, and, in one patient, coma; in this latter patient, the ictal EEG, recorded during two attacks, showed delta activity in the hemisphere contralateral to the hemiplegia. At least 2 months after their latest attacks, three patients showed dyscalculia, attentional disturbances, and impaired long-term verbal memory on neuropsychologic assessment. There were no cognitive disturbances in the unaffected relative. The severity of cognitive impairment appears to be correlated with migraine history. We attempt to classify these cases according to the criteria of the International Headache Society.

A cooperative study on ProMACE-CytaBOM in aggressive non-Hodgkin's lymphomas.

Chemotherapy using cyclophosphamide, doxorubicin, etoposide, cytarabine, bleomycin, vincristine, methotrexate with leucovorin, and prednisone (ProMACE-CytaBOM) for patients with intermediate or high grade non-Hodgkin lymphomas (G, H and K according to the Working Formulation), was tested by the Gruppo Cooperativo Lombardo to confirm the activity of the regimen and to test the feasibility and safety of administering third-generation drug regimen in a cooperative group setting. Among 64 previously untreated patients, aged between 20 and 71 years, 7 had stage IB-IIB, 12 had stage IIIA-B, 45 (67%) had stage IVA-B. There were 44 complete remissions (CRs) (69%) and 14 partial remissions (22%); the difference between patients in stage I-II-III (84% complete remissions) and those in stage IV (62% complete remissions) was statistically significant. The median length of follow up was 20 months (range 1-60 months), with 56% of patients alive at 60 months and 53% of CRs patients free of disease at 60 months. Patients in stage I-II-III have the best survival and disease free survival compared to stage IV, 87% versus 42% and 72% versus 32% respectively (both with high statistical significance). Grade 3-4 (WHO) haematological toxicity was observed in 39% of patients, with 3 septic deaths. Two more patients died with chemotherapy related toxicity (1 stroke and 1 acute renal insufficiency). Administration of ProMACE-CytaBOM is a feasible and safe regimen although it presents moderate toxicity. ProMACE-CytaBOM may represent improved treatment for aggressive lymphomas, in terms of duration of response and survival, but a longer follow up is needed.

Melatonin and cortisol circadian secretion during ethanol withdrawal in chronic alcoholics.

Changes in central neurotransmission and in hypothalamo-pituitary function occur in both ethanol (ETOH) intake and withdrawal. Melatonin (MLT) secretion is regulated by the noradrenergic system, which is activated upon ETOH withdrawal. Experimental evidence exist that pineal gland may have a role in ETOH intake and preference in rats. Twenty-four hour urinary excretion of MLT was found to be increased during ETOH intake in chronic alcoholics. In this study we have determined 24h plasma levels of MLT and cortisol in 8 chronic alcoholic males hospitalized for a detoxication program and in 8 healthy controls. The study was performed just after admission, on the first day of ETOH withdrawal and after 14 days of controlled abstinence. Circadian periodicity has been evaluated by the cosinor method. The initial determinations corresponded to the acute withdrawal phase. Twenty-four hour plasma MLT mean levels on acute withdrawal were higher than after 14 days abstinence and than those found in controls. Large interindividual differences prevented the detection of statistical significance. The cosinor analysis disclosed the loss of circadian periodicity in the acute withdrawal. Significant 24h periodicity was restored after 14 days abstinence. Cortisol levels were significantly higher than those found on day 14 and in healthy controls. Twenty-four hour periodicity was maintained in both alcoholics series. A delay in cortisol acrophase occurred in acute withdrawal. The effects of Corticotropin Releasing Hormone infusion on cortisol secretion were significantly enhanced in the acute withdrawal phase in comparison with those occurring when patients were retested and with healthy controls.

A case of parietal atrophy: etiopathogenetic evaluation.

We report on the case of a patient presenting a muscle atrophy of the right hand and a left parietal neoplastic lesion rapidly progressing. EMG findings showed no signs of denervation nor sensory-motor conduction impairments. Parietal lesions might interrupt sensory control mechanisms of motor activity.