A case of acute fulminant multiple sclerosis treated with alemtuzumab.

We describe the case of a woman who came to our attention for acute onset and very rapidly worsening left hemiplegia, vision loss and cognitive impairment. MRI, laboratory and clinical investigations were highly suggestive of an active inflammatory demyelinating disease. Following exclusion of other possible etiologies, a diagnosis of Marburg's variant multiple sclerosis was made. After repeated high-dose steroids and plasma-exchange, the patient was treated with a first course of alemtuzumab followed by improvement of the clinical and MRI picture. This is the first reported case of Marburg type multiple sclerosis treated with alemtuzumab.

[Herpetic viruses and renal transplantation]. / Virus erpetici e trapianto renale.

Over the last few years emerging evidence indicate the involvement of herpes viruses in the pathogenesis of several medical complications in transplanted patients. Herpes viruses are transmitted via inter-human contact and cause a primary infection, which commonly fails to give clinical signs and may persist even for years in a latent state in healthy subjects. In transplanted patients, herpes viruses may be transmitted through the transplanted organ or may be reactivated because of the use of powerful immunosuppressive drugs. Moreover, the persistence of immunosuppression greatly favours the clinical expression and severity of virus infection. Thus, herpes viruses seem to be involved in both acute and chronic deterioration of graft function, in the pathogenesis of post-transplant lymphoproliferative disorders and Kaposi sarcoma, and even in vessel atherosclerosis. This review will focus on relevant clinical aspects of herpes-virus infection, namely cytomegalovirus, EBV, herpes simplex 1 and 2, varicella zoster virus, HHV-6, HHV-7 and HHV-8, in kidney transplanted patients.

Effect of acetate-free biofiltration on the anaemia of haemodialysis patients: a prospective cross-over study.

BACKGROUND: The discussion about the pathogenesis of renal anaemia, whether it is primarily due to relative erythropoietin (Epo) deficiency or to uraemic inhibition of erythropoiesis, is still open. Although it has so far not been possible to identify or isolate a substance retained in uraemia with a suppressive action directed specifically against red-cell production, dialysis therapy can improve the effect of both residual endogenous Epo and exogenous rHuEpo. To what extent the mode and/or the dose of dialysis influence Epo efficacy is as yet poorly understood. METHODS: This study was performed as a single-centre trial. The protocol included a run-in period of 4 months followed by a prospective cross-over study including 6 months each of acetate-free biofiltration (AFB) with a high-flux biocompatible membrane and standard bicarbonate dialysis (BD) with a low-flux cellulosic membrane in a random sequence. AFB is a haemodiafiltration technique based on a continuous post-dilution infusion of a sterile isotonic bicarbonate solution. At the start of the run-in period (and for the entire length of the study), rHuEpo administration was withdrawn; patients whose haemoglobin (Hb) levels dropped at a level <8.0 g/dl at one single monthly check, had to be withdrawn from the study. A blood sample was collected every month for the blood gas analysis and for the determination of blood urea nitrogen, serum creatinine, sodium, potassium, calcium, phosphorus, Hb, erythrocyte, reticulocyte, leukocyte and thrombocyte cell counts, mean globular volume and haematocrit. An equilibrated single pool Kt/V(urea)>1.2 was mandatory in both treatment modalities. Serum iron, total iron-binding capacity, and ferritin were checked every 3 months. RESULTS: Twenty-three of 137 haemodialysis patients were considered eligible for the trial on the basis of the entry criteria. Of these, 15 volunteered and only 10 completed the study. No significant differences in the haematological indices, in the biochemical parameters assessing body iron stores, or in i.v. iron dosage was observed when comparing AFB with BD treatments. The equilibrated single pool Kt/V(urea) was always >1.2 and in no case was a significant difference observed when comparing AFB with BD treatments. Treatment time was significantly different between the two treatments (262+/-2 min in BD and 249+/-1 in AFB, P<0.0001). Neither pre- nor post-dialysis systolic and diastolic blood pressures, pre-dialysis serum bicarbonate and pH, pre-dialysis serum sodium, potassium, calcium, or phosphorus were significantly different when comparing the two treatment modalities. All 10 patients completed the 1-year follow-up without any major side-effects. CONCLUSIONS: Our study did not show any improvement of anaemia when treating a highly selected patient group, in the absence of any Epo therapy, with AFB compared with standard BD. Even though these conclusions cannot be extended in toto to the entire dialysis population, in which there is a large proportion of Epo-treated patients with Hb levels around 11 g/dl, we may nevertheless conclude that when patients are well selected, adequately dialysed, and not iron- and/or vitamin-depleted, the effect of a haemodiafiltration technique with a high-flux biocompatible membrane is less than might be expected from the results of uncontrolled studies.

Efficacy and safety of haemodialysis treatment with the Hemocontrol biofeedback system: a prospective medium-term study.

BACKGROUND: Hypovolaemia has been implicated as a major causal factor of morbidity during haemodialysis (HD). A model biofeedback control system for intra-HD blood volume (BV) changes modelling has been developed (Hemocontrol), Hospal Italy) to prevent destabilizing hypovolaemia. It is based on an adaptive controller incorporated in a HD machine (Integra), Hospal Italy). The Hemocontrol biofeedback system (HBS) monitors BV contraction during HD with an optical device. HBS modulates BV contraction rates by adjusting the ultrafiltration rate (UFR) and the refilling rate by adjusting dialysate conductivity (DC) in order to obtain the desired pre-determined BV trajectories. METHODS: Nineteen hypotension-prone uraemic patients (seven males, 12 females; mean age 64.5+/-3.0 SEM years; on maintenance HD for 80.5+/-13.2 months) volunteered for the present prospective study that compared the efficacy and safety of bicarbonate HD treatment equipped with HBS, as a whole, with the gold-standard bicarbonate treatment equipped with a constant UFR and DC (BD). The study included three phases: Medium-term studies started with one period of 6 months of BD and always had a follow-up period of HBS treatment ranging from 14 to 30 months (mean 24.0+/-1.6); short-term studies started in September 1999, when all patients went back to BD treatment for a wash-out period of 4 weeks and a short-term study period of a further 3 weeks (phase A). Afterwards, they once again started HBS treatment for a wash-out period of 4 weeks and a short-term study period of a further 3 weeks (phase B). Every patient underwent acute studies during a single HD run, once during phase A and once in phase B. Resistance (R) and reactance (Xc) measurements were obtained utilizing a single-frequency (50 kHz) tetrapolar bioimpedance analysis (BIA). Extracellular fluid volume (ECV) was calculated from R, Xc, and height and body weight measurements using the conventional BIA regression equations. RESULTS: The overall occurrence of symptomatic hypotension and muscle cramps was significantly less in HBS treatment in both medium- and short-term studies. Self-evaluation of intra- and inter-HD symptoms (worst score=0, best score=10) revealed a statistically significant difference, as far as post-HD asthenia was concerned (6.2+/-0.2 in HBS treatment vs 4.3+/-0.1 in BD treatment, P<0.0001). No difference was observed between the two treatments when comparing pre- and post-HD lying blood pressure, heart rate, body weights and body weight changes in medium- and short-term studies. The residual BV%/ Delta ECV% ratio, expression of the vascular refilling, was significantly higher during HBS treatment in acute studies. CONCLUSIONS: HBS treatment is effective in lowering hypovolaemia-associated morbidity compared with BD treatment; this could be related to a greater ECV stability. Furthermore, HBS is a safe treatment in the medium-term because these results are not achieved through potentially harmful changes in blood pressure, body weight, and serum sodium concentration.

Prevalence of Cryptosporidium in children with enteritis in southern Italy.

Cryptosporidium parvum is a protozoan which causes self-limiting diarrhea in immunocompetent subjects, and severe life-threatening disease in immunocompromised patients. Cryptosporidiosis is more common in developing countries and in infants. In this paper we have evaluated the prevalence of C. parvum in 368 hospitalized children with enteritis, of whom 359 were immunocompetent and 9 HIV-infected. Stool specimens were concentrated by sedimentation and stained with a modified Ziehl-Neelsen method. Cryptosporidium parvum oocysts were found in 7 (1.90%) out of 368 subjects. Six of these were immunocompetent (with an infection rate in this population of 1.67%) and 1 HIV-infected, asymptomatic except for diarrhea. In all children symptoms of enteritis and oocyst excretion cleared within 10 days. These results indicate that the prevalence of C. parvum as a causative agent of diarrheal illness in hospitalized immunocompetent children is rather low in our region (Apulia, South Italy).

Leishmania donovani lipophosphoglycan (LPG) inhibits respiratory burst and chemotaxis of dog phagocytes.

Lipophosphoglycan (LPG) is the major glycoconjugate of Leishmania promastigote surface membrane. Previous studies on human and murine models have demonstrated that this molecule is involved in the attachment and survival of Leishmania in the host cells. Dog is the main reservoir of Leishmania strains responsible for human leishmaniasis in Italy. Since no studies have been performed on the LPG-canine phagocyte interactions, we investigated the LPG effects on dog phagocyte functions by evaluating: 1) the chemotactic activity of peripheral monocytes and polymorphonuclear (PMN) cells, in terms of cellular polarization; 2) the PMN cell respiratory burst, by measuring superoxide anion and hydrogen peroxide production. Results demonstrated a significant reduction of metabolic and chemotactic activity in LPG-preincubated cells, thus emphasizing the ability of this molecule to impair also the canine phagocyte responses.

Intestinal microsporidiosis in AIDS patients with diarrhoeal illness in Apulia (south Italy)

Microsporidia are intracellular parasitic protozoa very common in immunocompromised patients in many parts of the world. There is a scarcity of data on the prevalence of these parasites in Italy. In this study we examined stool samples of 56 HIV+ patients with diarrhoea to find microsporidial spores, using the light microscopy Ryan modified trichrome stain. Microsporidia were found in one out of 56 patients, who was Cryptosporidium coinfected. Intestinal microsporidiosis seems to be less frequent in AIDS patients from Italy than in those from other countries.

Parasite escape mechanisms: the role of Leishmania lipophosphoglycan on the human phagocyte functions. A review.

Protozoan parasites of the Leishmania genus are the causative agents of important diseases in humans and animals. During their life cycle in vertebrate hosts, protozoa are able to live and proliferate within phagolysosomes of host phagocytic cells. The capacity to live in this hostile environment is likely due to the cell surface glycoconjugate expression. In particular, lipophosphoglycan (LPG), a major surface glycoconjugate of Leishmania promastigotes, has been reported to play an active role in protecting parasites within phagolysosomes via the impairment of killing mechanisms. In this review, the authors emphasize some novel LPG-mediated escape mechanisms of promastigotes from human phagocyte responses, such as the impairment of oxidative burst and of chemotactic activity. In the light of these findings, the knowledge of biological actions of LPG may be useful in order to prepare a vaccine against human leishmaniasis, using LPG defective avirulent mutant strains.

Cyclospora in AIDS patients: not always an agent of diarrhoic syndrome.

The present study reports the clinical features of two AIDS patients infected by Cyclospora. According to our observations, Cyclospora in AIDS can be responsible both for gastroenteritis and for asymptomatic infections with spontaneous rapid clearance. In addition, and undiagnosed circulation of this agent in Italy could be hypothesized: neither patient had a past history of foreign travel. These are the first two cases in AIDS described in Italy.

Hepatitis B virus infection in chronic uremia: long-term follow-up of a two-step integrated protocol of vaccination.

Active immunization is crucial for eradicating hepatitis B virus infection from dialysis units. A prospective study was performed in 63 consecutive chronic uremic patients, which included the following: (1) the intramuscular (IM) administration of 40 micrograms of a DNA-recombinant vaccine (Engerix-B, Smith Kline & French Laboratories, Milan, Italy) to all chronic uremic patients at 0, 1, 2, and 6 months; (2) the antibody titer determination at the seventh month (chronic uremic patients with a titer > 100 mIU/mL received an IM booster dose of 40 micrograms at 18 months [group A], and those with a titer < 100 mIU/mL received a further IM dose of 40 micrograms at 12 months [group B]); and (3) the intradermal inoculation of 5 micrograms of vaccine every 2 weeks until the protective titer (> or = 10 mIU/mL) was achieved, and then monthly for 6 months, in chronic uremic patients who did not have a protective titer even after 19 months (group C). Thus, 41, 17, and five chronic uremic patients were allocated to groups A, B, and C, respectively. All developed a protective titer: 79.4%, 84.0%, and 87.5% after the fourth, fifth, and sixth IM dose at 7, 13, and 19 months, respectively. Five chronic uremic patients (group C) achieved seroprotection after 3.8 +/- 0.5 (SEM) intradermal inoculations.(ABSTRACT TRUNCATED AT 250 WORDS)

Impairment of the human phagocyte oxidative responses caused by Leishmania lipophosphoglycan (LPG): in vitro studies.

Lipophosphoglycan (LPG), a surface glycoconjugate of Leishmania promastigotes, has been reported as playing an active role in protecting the parasite within phagolysosomes, by an impairment of monocyte oxidative responses. In this study the effect of LPG on the oxidative burst of human peripheral monocytes, eosinophils and neutrophils was evaluated. Our results demonstrated that either superoxide anion (O2-) or hydrogen peroxide (H2O2) release by LPG-pretreated cells was diminished, emphasizing the ability of this glycoconjugate to impair the oxidative activity of all phagocytes.

A successful two-step integrated protocol of anti-HBV vaccination in chronic uremia.

A prospective study was performed in 40 chronic uremics which included: (1) the intramuscular administration to all patients of 40 micrograms of a DNA-recombinant vaccine (Engerix-B) at 0, 1, 2, 6 months; (2) an intramuscular booster dose of 40 micrograms at 18 months in patients having an anti-HBs titer greater than 100 mIU/ml at the 7th month (group A); (3) a further intramuscular supplementary dose of 40 micrograms at 12 months (besides that at 18 months) in patients developing an antibody titer less than 100 mIU/ml at the 7th months (group B); (4) an intradermal course of 5 micrograms of vaccine every 2 weeks until the protective titer (greater than or equal to 10 mIU/ml) was achieved, and then every month for a total of 6 months in patients who did not develop a protective titer even after 19 months (group C). At the end of the study, all patients had developed a protective titer: 77.5% after the 4th intramuscular dose, 12.5% after the 5th and 10% after 3.5 +/- 0.5 (mean +/- SEM) intradermal inoculations. The mean antibody titers were 1,461 +/- 98 mIU/ml in group A, 594 +/- 684 in group B and 131 +/- 133 in group C. In conclusion, our two-step integrated protocol gives an anti-HBs protective titer in all our patients.

Confirmation of high prevalence of hepatitis C antibodies in hemodialysis patients by second generation immunoblot assay.

Sera from 209 dialysis patients were tested for antibodies to hepatitis C virus (anti-HCV) by a 2nd generation enzyme-linked immunoassay (ELISA 2) using nonstructural and core antigens. Confirmation of reactivity was obtained by a 2nd generation immunoblot assay (RIBA 2) for antibodies to 4 separate antigens (5-1-1, c100-3, c33c, c22-3). ELISA 2 was positive in 99 sera, 95 of which were confirmed by RIBA 2, thus accounting for an anti-HCV prevalence of 45.5%. Anti-HCV positivity was correlated to longer duration of dialysis therapy (p less than 0.001), higher number of transfusions (p less than 0.001), history of kidney transplant (p less than 0.001) and of serum alanine/aspartate aminotransferase (AST/ALT; p less than 0.001) or gamma-glutamyltransferase (GGT) (p less than 0.001) increments. The most frequent RIBA 2 patterns were: reactivity to all 4 antigens (34 patients) and to c33c and c22-3 (45 patients). The former patients, compared to the latter, had higher values of AST (p less than 0.08), ALT (p less than 0.02), GGT (p less than 0.005), IgG (p less than 0.05). It is possible that the reactivity to all 4 antigens of RIBA 2 is a clue of a greater activity of viral hepatic disease.

Large-bowel transit in paraplegic patients.

Severe constipation often follows spinal cord injury. The aim of this study was to evaluate transit of contents through the large bowel in patients with paraplegia after a complete transverse lesion of the spinal cord. Transit through the right colon, left colon, and rectum was evaluated in 11 patients (eight males, 3 females; 17 to 63 years old) and data were compared with that of 37 healthy control subjects. In all patients there was either no, or abnormally low, transit at the level of the left colon and rectum. A minor degree of transit delay at the level of the right colon was also present in eight patients. These data indicate that constipation in patients with paraplegia is due to abnormal transit, mainly at the level of the left colon and rectum, and transection of the spine between the C-4 and T-12 vertebral levels causes alteration of large-bowel motor activity mainly at the level of the segments innervated by the parasympathetic fibers of the sacral outflow.