Early cytomegalovirus-specific T-cell response and estimated glomerular filtration rate identify patients at high risk of infection after renal transplantation.

BACKGROUND: Assessing the risk of cytomegalovirus (CMV) viremia in kidney transplant recipients (KTR) may be helpful to indicate in which patient it is worth starting antiviral treatment during preemptive strategy. METHODS: In 40 CMV-seropositive KTR preemptively treated with ganciclovir, we used interferon (IFN)-γ ELISpot test to evaluate whether monitoring T cells directed against phosphoprotein (pp) 65 and immediate early (IE)-1 antigens could predict the onset of viremia. RESULTS: CMV viremia occurred in 24 patients (60%) within 120 days after transplantation. Non-viremic patients had higher anti-pp65, anti-IE-1 T cells, and estimated glomerular filtration rate (eGFR) in the first 90 days after transplantation. At logistic regression, anti-pp65, anti-IE-1 T cells, and eGFR measured at day 30 were significantly associated with CMV infection. Cutoff values of 15 spot-forming cells (SFCs)/200,000 peripheral blood mononuclear cells (PBMCs) for anti-IE, 40 SFCs/200,000 PBMCs for anti-pp65, and 46.6 mL/min/1.73 m(2) for eGFR, respectively, predicted the risk of CMV infection with high sensitivity and specificity (area under the receiver operating characteristic curve >0.75). Using a classification tree model, we identified as high-risk patients those showing anti-pp65 <42 SFCs/200,000 PBMCs and eGFR <62 mL/min/1.73 m(2) , as well as anti-pp65 ≥42 and anti-IE-1 <6.5 SFCs/200,000 PBMCs. CONCLUSION: Monitoring CMV-specific T-cell responses and eGFR in the first month post transplant can identify patients at high risk of CMV infection, for whom preemptive antiviral therapy is recommended.

Future research and collaboration: the "SINERGIE" project on HCV (South Italian Network for Rational Guidelines and International Epidemiology).

The SINERGIE (South Italian Network for Rational Guidelines and International Epidemiology) project is intended to set up a collaborative network comprising virologists, clinicians and public health officials dealing with patients affected by HCV disease in the Calabria Region. A prospective observational data-base of HCV infection will be developed and used for studies on HCV natural history, response to treatment, pharmaco-economics, disease complications, and HCV epidemiology (including phylogenetic analysis). With this approach, we aim at improving the identification and care of patients, focusing on upcoming research questions. The final objective is to assist in improving care delivery and inform Public Health Authorities on how to optimize resource allocation in this area.

Diagnostic utility of LightCycler SeptiFast and procalcitonin assays in the diagnosis of bloodstream infection in immunocompromised patients.

Sepsis is an increasingly prevalent cause of death, and management in the early stage is a critical issue. However, microbiological findings are generally obtained late during the course of the disease. In this study, we evaluated the clinical utility of procalcitonin (PCT) in improving the diagnosis of bloodstream infections and the potential utility of the SeptiFast (SF) test, a multiplex pathogen detection system, in the etiological diagnosis of immunocompromised patients. Seventy-nine hospitalized immunocompromised patients were included in this study. Our results demonstrate that while the PCT value correlates highly with sepsis, the results do not discriminate adequately enough to justify its independent use as a diagnostic tool. The SF test, combined with blood cultures, improves microbiological data in immunocompromised patients, especially in cases of previous antibiotic therapy and invasive fungal infection.

Effects of switching from an AChE inhibitor to a dual AChE-BuChE inhibitor in patients with Alzheimer's disease.

OBJECTIVE: Cholinesterase (ChE) inhibitors are the only medications approved for the treatment of Alzheimer's disease (AD). The features of ChE inhibitors differ considerably. In addition to acetylcholinesterase (AChE) inhibition, rivastigmine also inhibits butrylcholinesterase (BuChE), providing dual AChE and BuChE inhibition. An observational study was performed to determine the response in routine clinical practice to switching AD patients to rivastigmine from a selective AChE inhibitor when that treatment no longer delivered a satisfactory clinical response. RESEARCH DESIGN AND METHODS: A prospective, multicentre, 3-month observational trial in patients with mild to moderately severe AD (adjusted Mini Mental State Examination [MMSE] score 10-26) deteriorating (at least 2 adjusted MMSE points in last 6 months) on selective AChE inhibitor treatment. Adjusted MMSE, activities of daily living (ADL) and instrumental activities of daily living (IADL), the Zarit caregiver burden and global function (short Clinical Global Impression of Change, CGIC) scores were noted before the switch and 3 months after the switch. RESULTS: 225 patients entered the study. The switches made were from donepezil to rivastigmine in (D-R) in 188 patients, galantamine to rivastigmine (G-R) in 33 patients and donepezil to galantamine (D-G) in four patients. Ten patients discontinued due to adverse events and eight for other reasons. More than half of the switches were within 36 hours of a patient's first treatment visit. In the D-R and G-R groups, 67.7% and 66.7% of patients responded (CGIC score < or = 4), respectively. In non-responders, worsening (CGIC score 5-7) was mild in approximately 80% or more of patients. Adjusted MMSE improved after the switch from both donepezil and galantamine to rivastigmine (+0.69 +/- 3.2, p = 0.008 and +0.6 +/- 1.6, p = 0.05, respectively). Mean ADL, IADL, and Zarit scores remained stable. The proportion of patients on concomitant antipsychotic therapy diminished by 30.5% and benzodiazepines were discontinued in all patients, except one. CONCLUSIONS: AD patients deteriorating on selective AChE inhibitor treatment can benefit from switching to a dual AChE-BuChE inhibitor, such as rivastigmine, in terms of stabilization of disease, improvement in cognitive function and reduction in the burden of concomitant psychoactive treatment. The switch was well tolerated. Confirmation of these results is required in a controlled study.

Presence and indigenous nature of Lyme disease in southern Italy.

Lyme disease is very common in the countries of the northern hemisphere. In Italy it is endemic in some regions of the northern part of the country and it is more frequent during summer. In Calabria (south Italy) no cases have been reported. To document the presence and indigenous nature of Lyme disease in this territory we conducted a study from 1999 to 2002. We defined as indigenous cases those with erythema migrans with the following characteristics: dimensions equal to or greater than 5 cm; localization on an area of the skin where there was a tick bite; appearance between 4 and 30 days after the tick bite; appearance in patients who had not resided out of Calabria in the previous 3 months. We found 23 patients with the necessary characteristics to be defined indigenous cases. Since 15 of these cases (65.2%) were observed in the October - December trimester and no case was found in the July - September trimester, we suspect that in Calabria the disease follows a seasonal distribution which differs with respect to countries where it is historically endemic.

[Polyomavirus BK nephropathy in renal transplant: 2 cases with different clinical expressions and review of the literature]. / Nefropatia da Poliomavirus BK nel trapianto renale: 2 casi con espressione clinica diversa e revisione della letteratura.

INTRODUCTION: Polyomavirus BK nephropathy is emerging as a significant cause of interstitial nephritis and allograft dysfunction (1-2). CASE REPORT: Two patients with renal transplants from cadaveric kidneys were treated with Tacrolimus plus Mycophenolate Mofetil (MMF) and Cyclosporine plus MMF, respectively. Their renal function gradually deteriorated eight to twelve months after the transplant. The renal biopsy of the first patient showed signs of significant interstitial tubulite, which necessitated the anti-rejection therapy with intravenous steroid pulses. After the pulses there was an additional dramatic increase in plasmatic creatinine, which suggested a revaluation of the kidney biopsy because of suspected Polyomavirus BK (BKV) nephropathy. In fact, after a more careful review, the suspicion of BKV infection was confirmed by the presence of intranuclear inclusions of tubular epithelium cells and marked denudation of the tubular basal membrane. The subsequent screening in both cases confirmed the presence of decoy cells in the urine, while the immunohistochemical analysis of the renal biopsy was strongly positive for the SV40 antigen. Our diagnosis was that of interstitial nephritis due to Polyomavirus BK that, in the first patient, was expressed by more aggressive clinical progress, probably due to enhanced immunosuppression from incorrect diagnosis of the interstitial rejection. The pre-transplant clinical outcome of the first patient was characterised by proteinuric nephropathy without any histological confirmation. Furthermore, we observed abundant pre-transplant residual diuresis and glucose intolerance. All these elements led us to hypothesise that native kidneys could have a fundamental role as viral reservoirs. CONCLUSION: Even though we reconfirm the decisive role of the immunosuppressive therapy and of the donor s kidney as the fundamental causes of Polyomavirus reactivation, we believe that it cannot be the result of a possible active role by the native kidney. In fact, as already noted, the SV40 genome is important in the pathogenesis of focal gomerulosclerosis. Furthermore, reports of polyoma nephropathy in not-yet-transplanted patients could accredit the role of the native kidneys as important viral reservoirs capable of inducing nephropathy in renal transplant patients.

Long-term treatment with idebenone and riboflavin in a patient with MELAS.

We report a patient with MELAS treated for 24 months with idebenone and riboflavin, during which no stroke-like episodes occurred. Moreover neurological symptoms clearly improved, and a recovery of brain MRI and EEG abnormalities was observed. We conclude that the combined treatment with idebenone and riboflavin may restore the metabolic impairment in MELAS, possibly improving the long-term prognosis in these patients.

Primary progressive aphasia: description of a clinical case with nine years of follow-up.

We describe the case of a woman with primary progressive aphasia who, over a period of nine years, has shown no signs of clinical deterioration and has only a symptomatic language disturbance. Neuropsychological follow-up has revealed progressive language impairment, with the integrity of praxis, visuoperceptive gnosia and short term visuospatial memory remaining intact; the only impairment was that revealed by long-term memory tests.

A prevalence study of carotid atherosclerotic disease in patients aged above 60.

The results of Doppler sonography and the echotomographic evaluation of extracranial arteries performed on 139 asymptomatic patients aged above 60 are presented. Atheromatous lesions were found in 54 (38.85%) of the subjects, though most had no hemodynamic effects. Statistical analysis showed an increase in both number and gravity of lesions with advancing age in females alone. No significant association was found between risk factors and atheromatous lesions, except for smoking in males.

[Dynamic ECG in cerebral ischemic vasculopathies]. / L'ECG dinamico nelle vasculopatie cerebrali ischemiche.

Fifty-four subjects suffering from TIA or Stroke underwent normal ECG and Holter ECG ten days after ischemic cerebral event in order to point out cardiac dysrhythmias as possible causes of TIA or Stroke. Holter ECG proved positive in 70.3% of subjects versus 38.8% of normal ECG (p < 0.001). We underline the utility of cardiological valuation in patients suffering from TIA or Stroke in order to search for cardiac causes of ischemic cerebral events and to prevent relapses.

Cerebral ischemia and livedo reticularis in a patient with impairment of coagulation factor VII and free protein S.

The association of ischemic cerebrovascular lesions with livedo reticularis is known as Sneddon syndrome. It affects young subjects, primarily women, and its neurological manifestations are TIAs, ischemic stroke, progressive dementia and epileptic seizures. Its etiopathogenesis has still to be clarified. Some authors have associated it with an antiphospholipid antibody syndrome. Recently it has been assumed that a defect in blood coagulation may be involved in its pathogenesis. Here we report a case in which both an increase in coagulation factor VII activity and a deficiency in free protein S were documented.

[Parkinsonian syndrome during viral meningoencephalitis]. / Sindrome parkinsoniana nel decorso di una meningoencefalite virale.

During a viral meningoencephalitis, a 60-year-old woman developed a full parkinsonian syndrome, unchanged four months after the onset. The viral researches demonstrated an increase of the anti-CMV antibodies, especially in the cerebrospinal fluid. CSF's and neuroimaging data are discussed.

[Paralysis of the parasympathetic ocular nerve after influenza syndrome]. / Paralisi del parasimpatico oculare dopo sindrome influenzale.

A 41 year-old-man developed diplopia, bilateral ptosis, paralysis of conjugate eye movement upwards and horizontal, with dilated and fixed pupils, after an influenza syndrome. Radiological, cerebrospinal fluid and electrophysiological data were normal, except BAEPs. The different aetiologies and pathogenesis are discussed.

[Amyotrophic lateral sclerosis with multiple myeloma]. / Sclerosi laterale amiotrofica in corso di mieloma multiplo.

Motor neuron diseases (MND) associations with paraproteinemia, lymphoma, hexosaminidase A deficiency and heavy-metal intoxication are of great interest. A case of amyotrophic lateral sclerosis (SLA) associated with multiple myeloma (monoclonal IgG paraproteinemia and K light chains) is reported. The detection of abnormal protein in 1988 and the increase of its serum level during 1989 were strictly correlated with the beginning and the worsening of the neurological disease. Shy and coll. in 1986 affirmed that association of paraproteins with MND is probably not merely the fortuitous association of a common laboratory abnormality and an uncommon disease. The reported case provides elements for a causal association between paraproteinemia and MND.

Clinical and electrophysiological findings in two cases of Miller Fisher syndrome.

Clinical, radiological and electrophysiological data in two patients with 'Miller Fisher syndrome' (MFS), characterized by ataxia, ophthalmoplegia and areflexia are reported. Of the many tests performed only the electrophysiological findings provided any clue to the site of the lesions and the structure involved, showing a significant pattern of brainstem dysfunction. The authors discuss the role of central and peripheral lesion theory in the light of these data and stress that electrophysiological findings lend considerable weight to the former and support the hypothesis that MFS should be recognize as a distinct clinical entity.

A pilot study with monosialoganglioside GM1 on acute cerebral ischemia.

Reported here are the results of an open controlled study on the use of GM1 in cases of ischemic strokes in its acute phase. A statistically significant improvement was observed in cases treated with GM1 for neurological deficits (assessed by Mathew's rating scale, modified by Fritz-Werner) at 21, 60 and 120 days and for disability at 120 days.

Spontaneous intracerebral hematoma in a adolescent with factor XIII deficiency. Case report.

A case of a spontaneous cerebral hematoma in the left capsulo-nuclear area in an adolescent girl with congenital deficiency of coagulation Factor XIII is described.

Spontaneous recanalization of carotid artery occlusion following non traumatic dissection.

We studied 7 patients with internal carotid occlusion following spontaneous arterial dissection. All presented strokes, in one associated with Horner's syndrome. The doppler examination showed carotid occlusion, but only angiography established the diagnosis of vascular disease. Spontaneous recanalization was observed in 6 cases, treated only by antiplatelet drugs.