Nosocomial spondylodiskitis with epidural abscess and CSF fistula cured with quinupristin/dalfopristin and linezolid.

Nosocomial infections after spinal surgery are relatively uncommon but potentially serious. The goal of diagnostic evaluation is to determine the extent of infection and identify the microorganism involved. Neuroimaging provides accurate information on correct topography, localization and propagation of the infection. Microbiological data are able to give aetiological causes. In this patient with severe, chronic polymicrobial spine infection with epidural abscess and CSF fistula due to multidrug-resistant organisms, the cure was achieved with long-term antimicrobial specific therapy with quinupristin-dalfopristin (50 days) and linezolid (100 days) with mild side effects. This positive result was due to combined medical and surgical treatment.

Fatal haemolytic uraemic syndrome in an AIDS patient with disseminated adenovirus and cytomegalovirus co-infection.

We describe a fatal case of haemolytic uraemic syndrome in a young woman with AIDS, and disseminated adenovirus (ADV) and cytomegalovirus (CMV) co-infection. We hypothesize that ADV/CMV co-infection may have a causative role in this clinical picture.

Relationship between expression of multiple drug resistance proteins and p53 tumor suppressor gene proteins in human brain astrocytes.

Multiple drug resistance occurs when cells fail to respond to chemotherapy. Although it has been established that the drug efflux protein P-glycoprotein protects the brain from xenobiotics, the mechanisms involved in the regulation of expression of multiple drug resistance genes and proteins are not fully understood. Re-entry into the cell cycle and integrity of the p53 signaling pathway have been proposed as triggers of multiple drug resistance expression in tumor cells. Whether this regulation occurs in non-tumor CNS tissue is not known. Since multiple drug resistance overexpression has been reported in glia and blood vessels from epileptic brain, we investigated the level of expression of multidrug resistance protein, multidrug resistance-associated proteins and lung resistance protein in endothelial cells and astrocytes isolated from epileptic patients or studied in situ in surgical tissue samples by double label immunocytochemistry. Reverse transcriptase-polymerase chain reaction and Western blot analyses revealed that multiple drug resistance, multidrug resistance protein, and lung resistance protein are expressed in these cells. Given that lung resistance proteins have been reported to be preferentially expressed by tumors, we investigated expression of tumor suppressor genes in epileptic cortices. The pro-apoptotic proteins p53 and p21 could not be detected in "epileptic" astrocytes, while endothelial cells from the same samples readily expressed these proteins, as did normal brain astroglia and normal endothelial cells. Other apoptotic markers were also absent in epileptic glia. Our results suggest a possible link between loss of p53 function and expression of multiple drug resistance in non-tumor CNS cells.

Mechanisms of glucose transport at the blood-brain barrier: an in vitro study.

How the brain meets its continuous high metabolic demand in light of varying plasma glucose levels and a functional blood-brain barrier (BBB) is poorly understood. GLUT-1, found in high density at the BBB appears to maintain the continuous shuttling of glucose across the blood-brain barrier irrespective of the plasma concentration. We examined the process of glucose transport across a quasi-physiological in vitro blood-brain barrier model. Radiolabeled tracer permeability studies revealed a concentration ratio of abluminal to luminal glucose in this blood-brain barrier model of approximately 0.85. Under conditions where [glucose](lumen) was higher than [glucose](ablumen), influx of radiolabeled 2-deoxyglucose from lumen to the abluminal compartment was approximately 35% higher than efflux from the abluminal side to the lumen. However, when compartmental [glucose] were maintained equal, a reversal of this trend was seen (approximately 19% higher efflux towards the lumen), favoring establishment of a luminal to abluminal concentration gradient. Immunocytochemical experiments revealed that in addition to segregation of GLUT-1 (luminal>abluminal), the intracellular enzyme hexokinase was also asymmetrically distributed (abluminal>luminal). We conclude that glucose transport at the CNS/blood interface appears to be dependent on and regulated by a serial chain of membrane-bound and intracellular transporters and enzymes.

Four drug-HAART in primary HIV-1 infection: clinical benefits and virologic parameters.

BACKGROUND: From a theoretical standpoint, primary HIV infection (PHI) represents a great chance to modify the natural history of the disease. In this study we purposed a four drugs regimen with zidovudine, lamivudine, ritonavir and saquinavir to treat aggressively the infection and achieve a complete immune reconstitution. METHODS: This is an Italian multicentric open label study. Adult patients with PHI were eligible for the study if they met at least one clinical criterion and one laboratory criterion of the following. Clinical criteria: Signs and symptoms of acute retroviral syndrome within the past 70 days, exposure to HIV-1 within the last 3 months, a preceding negative antibody test within the past 6 months. Laboratory criteria: Detectable p24 antigen with neutralization in serum; detectable HIV-RNA in plasma; indeterminate Western blot test with negative or low positive value HIV antibody in ELISA test. RESULTS: Since April 1997 to April 1999 40 patients with PHI have been enrolled; 80% of this cohort referred symptoms related to acute antiretroviral syndrome. Treatment has been withdrawn in 17 patients (12 for intolerance, 3 for toxicity and 2 for failure). At baseline the mean CD4+ T cells count and CD4/CD8 ratio were 537 (range 55-1287) and 0.58 (range 0.1-1.03) and the mean plasma HIV-RNA level was 5.9 log copies/ml (range 3-7.15). Plasmatic HIV-1 RNA levels of all patients dropped below 200 copies/ml in 68% of patients at week 12, 81% at week 24, 93% after 12 months and 100% after 18 months. Immunological parameters have been improved and have achieved normal range since 6th month. CONCLUSIONS: A rapid virologic suppression and immunological reconstitution are associated with PHI therapy. However early treatment should be weighted against the potential disadvantages such as immediate adverse events (intolerance and drug toxicity) and long term manifestation (metabolic disorders).

[Importation dengue]. / Dengue d'importazione.

We describe two cases of dengue fever (DF) serologicaly confirmed. In both, the clinical features are characterized by: fever, severe headache, myalgias and arthalgias, transient macule-papule rash, leukopenia and thrombocytopenia. The entire illness last few days and terminates abruptly without therapy. A history of travel to dengue-endemic areas and occurrence of other cases in a community are important reminders to include this disease in the differential diagnosis. The hemoagglutination inhibition test for DF at the Laboratory of Virology of the Istituto Superiore di Sanità on two collected sera, during the acute and convalescent phases, has showed a seroconversion. A problem is to advise patients to avoid endemic areas because the second exposure could induce DHF/dengue shock syndrome.

Thrombocytopenia in HIV infected patients. Prevalence and clinical spectrum.

We studied the prevalence, clinical spectrum and epidemiologic features of thrombocytopenia among 442 (333 male, 109 female) HIV infected patients. Thrombocytopenia was defined as a platelet count < 100,000/mmc and severe if platelet count was < or = 30,000/mmc. Intravenous drug abusers were 83% (369/442). At the first clinical evaluation according to Walter-Reed (WR) classification, 90% (396/442) of patients were in stage 1-5 and 10% (45/442) in stage 6. Severe thrombocytopenia (platelet count < or = 30,000/mmc) was present in 24% (11/45) of the entire thrombocytopenic population. Forty percent (18/45) of the thrombocytopenic patients were positive to: HBV (6), HCV (7), HBV+HCV (5). Mild bleeding was present in 16% (7/45) of the patients but one case, with severe thrombocytopenia, died of intracranial hemorrhage. Major hemorrhagic sequelae with even fatal events are possible, especially when a low platelet count is associated with other hemostatic abnormalities (e.g. haemophilia, liver disease, disseminated intravascular coagulation). Zidovudine therapy (range 500-1250 mg/day) is effective in normalizing the platelet count (platelets > 100,000/mmc) only in 29% (9/31) of the patients.

[Septicemia and systemic inflammatory response]. / Setticemia e risposta infiammatoria sistemica.

To determine the relation between endocarditis/septicemia and systemic inflammatory response syndrome (SIRS), septic shock, MODS, we performed a retrospective analysis in 196 HIV-negative patients, with endocarditis/septicemia. No deaths were observed between 20 patients with endocarditis without severe infective SIRS/septic shock. On the other hand among 10 patients with endocarditis with severe infective SIRS/septic shock we registered 3 deaths (P = 0.052). No deaths were registered among 93 patients with septicemia without severe infective SIRS/septic shock. Between 73 patients with septicemia and severe infective SIRS/septic shock 9 (12.3%) patients died and, precisely, 7/61 in severe infective SIRS (11.4%) and 2/.12 (16.6%) in septic shock (P = 0.003). The definition of septicemia according to Schottmüller (1914), as a generalized bacterial infection with a persistent bacteremia is still justified. The term "sepsis" has become ambiguous because it has been used as synonym of "acute response to infection", while in the past and presently, at least in Europe, it is synonym of septicemia, persistent bacteremia. The term of SIRS could avoid the misunderstanding. The words: "infective SIRS", "severe infective SIRS", may label properly the reactive events mounted by the host as a useful defence against infections but they become dangerous and bring about septic shock, organ failure and mortality when excessive.

[Tuberculosis and immigrants. A study of its prevalence in the Umbria region]. / Tubercolosi ed immigrati. Uno studio di prevalenza nella Regione Umbria.

In 1995, 463 patients were admitted in the medical service of Perugia (Sanitary District n. 6). Only 20% of them were enrolled in the TBC programme. Mantoux was: < 10 mm in 35%, 10-15 mm in 25%, > 15 mm in 40%. Chest Rx in 30 subjects demonstrated: normality in 19; old TBC in 7, active TBC in 4 (miliary, bilateral upper lobe pneumonitis, left subapical upper lobe pneumonitis and right lobitis of the upper lobe). All patients were admitted in hospital and showed positive sputum culture for Mycobacterium Tuberculosis. They were treated with isoniazid, rifampin, pyrazinamide, ethambutol/streptomycin for 2 months and with isoniazid, rifampin for other 4-8 months. Two patients showed Mycobacterium tuberculosis with isoniazid resistance. Seven patients were treated with isoniazid chemoprophylaxis without side effects. Migrants should receive information about health care service and be encourage to register themselves with a general practitioner. Skin test screening and chest radiographs for those with positive results should be provided at a convenient location.

Clonal spread of Acinetobacter baumannii in a general intensive care unit.

The epidemiological characterization of multiply resistant Acinetobacter baumannii isolates from a six-bed Intensive Care Unit (ICU) is described. Investigations for A. baumannii were performed in three subsequent surveillance studies. In the first study, surveillance cultures were taken from patients, health care personnel and the environment; in the second study surveillance cultures were taken at 0, 4, and 7 days from all patients admitted consecutively to the ward; and in the third study surveillance cultures were taken from patients, health care personnel and the environment. During the first study all four hospitalized patients were found to harbour A. baumannii. Hand cultures did not grow any A. baumannii when staff entered the ward from home, but 7 positive health care workers were identified out of 25 samples taken during work, and two cultures of environmental specimens grew A. baumannii. During the second study, 4 of 86 (4.6%) patients resulted colonized with A. baumannii. In the third epidemiological study, no A. baumannii was cultured from either patients, health care personnel or the environment. All isolates recovered from various patients or sources produced conserved macrorestriction Pulsed-Field Gel Electrophoresis (PFGE) patterns and showed the same antibiotic resistance; therefore, they can be considered indistinguishable. The same antibiotic resistance and macrorestriction patterns were observed in previously isolated A. baumannii strains in the ward during May 1997, suggesting the persistence of a single A. baumannii in the ICU. The present study confirms that molecular typing is an essential tool in the epidemiology and control of nosocomial infections, showing here the persistence of a single A. baumannii clone in the ICU. The origin of this strain remains unknown but, when basic infection control measures were reinforced, emphasizing the importance of hand antisepsis and judicious use of gloves, control of A. baumannii spread in the ward was achieved.

Detrimental effects of high-dose dexamethasone in severe, refractory, HIV-related thrombocytopenia.

OBJECTIVE: To report a case of HIV-related thrombocytopenia in which high-dose dexamethasone was ineffective and immunologically detrimental. CASE SUMMARY: A 39-year-old white man with persistent, severe, HIV-1-related thrombocytopenia was admitted for epistaxis, bleeding gums, petechiae, and bruising. Previous unsuccessful attempts to reverse the thrombocytopenia included zidovudine, prednisone, vincristine, interferon alfa, and intravenous immune globulins. Based on previous anecdotal reports of the effectiveness of high-dose dexamethasone in refractory, HIV-related thrombocytopenia, we instituted treatment with intravenous dexamethasone 40 mg/d for four sequential days every 28 days. After three cycles of therapy, the platelet count remained < 15 x 10(9)/L; however, the CD4+ lymphocyte count decreased progressively from 1447 x 10(6)/L at baseline to 560 x 10(6)/L three months after the third cycle. Due to persistent, severe thrombocytopenia and bleeding, the patient underwent splenectomy, resulting in normalization of the platelet count. DISCUSSION: High-dose dexamethasone has been proposed as treatment for patients with immune thrombocytopenia as an alternative to chronic oral corticosteroids and claimed to be associated with better effectiveness and fewer adverse effects. The results of this treatment in our patient show that this regimen may not only be ineffective, but may also be immunologically detrimental in HIV-infected patients. Although the deterioration of the immunologic status of our patient cannot be fully attributed to high-dose dexamethasone based on the Naranjo scale, the previous long-lasting stability of CD4+ cells and the temporal relationship of a decrease in the CD4+ cell count coinciding with administration of high-dose dexamethasone suggest a causative role of the treatment. CONCLUSIONS: A possible cause-effect relationship between the treatment and the decrease in the CD4+ cell count suggests that the use of high-dose dexamethasone may not be justified in patients with severe, HIV-related thrombocytopenia.

Acute sterile meningitis as a primary manifestation of pituitary apoplexy.

Pituitary apoplexy is a rare and underdiagnosed clinical syndrome. It results from hemorrhagic infarction of the pituitary gland. In its classical form it is characterized by acute headache, ophthalmoplegia, visual loss and pituitary insufficiency. Meningeal irritation signs, clinically indistinguishable from infectious meningitis, are considered rare and have not been reported as presenting signs. We report a 53-yr-old man who was admitted to hospital following acute headache, fever, neck stiffness and paresis of the left oculomotor and abducent nerves. A lumbar puncture revealed an increased number of polymorphs but with a sterile cerebral spinal fluid. Magnetic resonance imaging (MRI) showed an intrasellar mass with central necrosis in an enlarged sella. Endocrinological evaluation demonstrated insufficient thyroid, adrenocortical, and gonadal function. Necrosis within a chromophobe adenoma was found upon surgical decompression of the sella. After surgery anterior panhypopituitarism did not recover, while ophthalmoplegia subsided. The patient is now in good health under appropriate hormonal replacement therapy.