Recurring Candida albicans esophagitis in a HIV-infected patient undergoing long-Term antiretroviral therapy, and with absent-negligible immunodeficiency.

A patient with HIV infection developed the first episode of AIDS-defining opportunism (severe Candida albicans esophagitis) with an underlying CD4+ lymphocyte count of 1,025 cells/microL. After treatment with a highly active antiretroviral therapy (HAART), taken with insufficient compliance and leaving a residual viral load, our patient suffered from two relapses of esophageal candidiasis, which occurred three months and seven years later, when his CD4+ lymphocyte count was 930 and 439 cells/microL, respectively, and a viral load slightly above 10(4) copies/mL was still present. Also in the HAART era, Candida esophagitis remains one of the most common AIDS-defining diseases, but a presentation with a concurrent CD4+ count above 1,000 cells/microL remains a rare exception, as well as the two isolated, subsequent relapses, occurred with a CD4+ count ranging from 439 to 930 cells/microL, and a residual HIV viremia due to insufficient adherence to the prescribed HAART regimens. Our case report represents the opportunity to revisit the epidemiology and, especially, the pathogenesis of this opportunistic fungal complication in HIV-infected patients and in other subjects at risk, on the ground of an extensive literature review, and to explore possible alternative supporting factors other than the crude absolute CD4+ lymphocyte count, with emphasis on the possible role of a persisting HIV viremia, and other potential contributing factors. Clinicians engaged with immunocompromised patients and subjects with HIV disease, should be aware that a Candida esophagitis may occur and relapse also when the cell-mediated immunity, as measured by a simple CD4+ cell count, do not show relevant abnormalities.     

Doppler echocardiography of 119 normal-functioning St Jude Medical mitral valve prostheses: a comprehensive assessment including time-velocity integral ratio and prosthesis performance index.

The purpose of this study was to provide, in a large number of patients, comprehensive Doppler echocardiographic assessment of normal St Jude Medical mitral valve prosthesis function using Doppler-derived hemodynamic variables, including the mitral valve prosthesis-to-left ventricular outflow tract time-velocity integral ratio and prosthesis performance index. The pressure half-time was less than 130 milliseconds in all patients, and all but one patient had either a peak early mitral diastolic velocity of 2 m/s or less or a mitral valve prosthesis-to-left ventricular outflow tract time-velocity integral ratio of less than 2.2. There was a significant (P < .001) negative correlation between the prosthesis performance index and prosthesis size. This negative correlation suggests that there is more efficient use of the in vitro geometric orifice area with smaller prostheses.     

Repetitive magnetic stimulation of cortical motor areas in Parkinson's disease: implications for the pathophysiology of cortical function.

We investigated the neurophysiological and clinical effects of repetitive magnetic stimulation (rTMS) delivered to the cortical motor areas in healthy subjects and patients with Parkinson's disease. rTMS was delivered with a high speed magnetic stimulator (Cadwell, Kennewick, WA) through a figure-eight coil centred on the primary motor area at a stimulus intensity of 120% motor threshold. Trains of 10 stimuli were delivered at frequencies of 5 Hz while subjects were at rest and during a voluntary contraction of the contralateral first dorsal interosseous muscle. In normal subjects at rest, the muscle evoked responses (MEPs) to each stimulus in a train of magnetic stimuli progressively increased in size during the train. rTMS left the MEPs unchanged in patients off therapy and had a small facilitatory effect in those on therapy. In normal subjects and patients, 5-Hz rTMS trains delivered during a voluntary contraction of the target muscle left the MEP unchanged in size. MEPs were followed by a silent period that increased in duration during the course of the train. The silent period duration increased to a similar extent in patients and controls. The reduced rTMS-induced facilitation of MEPs in patients with Parkinson's disease reflects a decreased facilitation of the excitatory cells in the cortical motor areas.     

CD4+ T-epitope repertoire on the human acetylcholine receptor alpha subunit in severe myasthenia gravis: a study with synthetic peptides.

The alpha subunit of the nicotinic acetylcholine receptor (AChR) seems crucial in the pathogenesis of the autoimmune paralysis myasthenia gravis (MG) because it contains both the epitopes that dominate the antibody response against the AChR and those recognized by CD4+ AChR-specific T helper (Th) cells. To define the repertoire of anti-AChR Th cells, we investigated the response of unselected blood CD4+ cells or total lymphocytes, or both, from 22 MG patients to 20-residue overlapping synthetic peptides, screening the complete sequence of human-muscle AChR alpha subunit. Several epitopes were identified. Only the most severely affected patients recognized alpha subunit epitopes, and they were mainly young women. Detection of in vitro AChR-specific CD4+ response was facilitated by removal of the CD8+ cells because in two patients a clear response to several alpha subunit peptide sequences could be detected when CD(8+)-depleted cells were used, while their total peripheral blood mononuclear cell population did not respond to any alpha subunit peptide. Although each patient had a unique pattern of peptide recognition, four immunodominant regions recognized by long-term AChR-specific CD4+ T-cell lines, or flanking peptide sequences, were recognized most frequently (residues 48-67, 101-137, 293-337, and 308-437).     

The first agonist and antagonist burst in patients with an upper motor neuron syndrome

Rapid elbow flexion movements were studied in patients with an upper motor neuron syndrome following a stroke. The velocity of movements was slower than normal. The initial bursts of electromyographic (EMG) activity in both the agonist and antagonist muscles were prolonged. As in normal subjects, the first agonist burst increased in duration with larger movements, but it generally remained about 40 ms longer than normal. The size of the first agonist burst also increased with larger movements. A fixed linkage between burst duration and level of motor unit recruitment, together with a deficient corticospinal command, could explain the prolonged burst duration with preserved ability to modulate the burst.     

FTIR spectra and chain conformations in the crystalline forms and clathrates of syndiotactic poly(p-methylstyrene)

Infrared spectra of syndiotactic poly(p-methylstyrene) (s-PPMS) samples, exhibiting various crystalline forms and clathrate structures, are reported in this contribution. Bands due to the syndiotactic stereostructure, bands typical of the two different chain conformations observed in the crystalline structures and bands sensitive to intermolecular interactions typical of the different modes of packing of chains are pointed out. The observed similarities with the case of syndiotactic polystyrene are alos indicated. A complete assignment, via FTIR analysis, of the chain conformations, is presented for all the known crystalline forms and clathrates of s-PPMS.     

Association of myopathy with large-scale mitochondrial dna duplications and deletions: Which is pathogenic?

We identified large-scale heteroplasmic mitochondrial DNA (mtDNA) rearrangements in a 50–year-old woman with an adult-onset progressive myopathy. The predominant mtDNA abnormality was a 21.2–kb duplicated molecule. In addition, a small population of the corresponding partially deleted 4.6–kb molecule was detected. Skeletal muscle histology revealed fibers that were negative for cytochrome c oxidase (COX) activity and had reduced mtDNA-encoded COX subunits. By single-fiber polymerase chain reaction analysis, COX-negative fibers contained a low number of wild-type or duplicated mtDNA molecules (ie, nondeleted). In situ hybridization demonstrated that the abnormal fibers contained increased amounts of mtDNA compared with normal fibers and that most of the genomes were deleted. We concluded that deleted mtDNA molecules were primarily responsible for the phenotype in this patient.     

HIV infection and AIDS in advanced age. Epidemiological and clinical issues, and therapeutic and management problems

The life expectancy of HIV-infected patients treated with highly active antiretroviral therapy (HAART) has increased and now approaches that of the general population, while also the definition of AIDS has lost most of its epidemiological and clinical significance, due to the immune recovery obtained by large-scale administration of potent antiretroviral combinations. The prolonged survival of subjects with HIV infection, and the late recognition of patients with occult disease, will contribute to a progressive increase in disease incidence in patients aged 50-60 years or more in the near future. Unfortunately, the large majority of therapeutic trials addressed to assess and compare novel antiretroviral molecules and associations, as well as studies regarding antimicrobial chemotherapy of prophylaxis of AIDS-related opportunistic infections, have just advanced age and/or underlying chronic disorders (i.e. liver or kidney failure) among main exclusion criteria, or do not allow the extrapolation of data regarding older subjects, compared with younger ones. The limited data available until now show that antiretroviral therapy has a similar virological efficacy in the elderly compared with younger patients. However, immune reconstitution is often slower and blunted according to age progression, although some well-designed studies have shown that the thymic function (which controls most quantitative and functional immune recovery) can be preserved in adults and even in advanced age. When facing older subjects, the Infectious Disease specialist has to pay careful attention to any chronic end-organ disorders, all possible pharmacological interactions, and overwhelming toxicity due to underlying drug therapies: all these issues may significantly interfere with HAART efficacy, patients' adherence to prescribed treatments, and frequency and severity of untoward events. Guidelines for antiretroviral therapy and treatment and prophylaxis of AIDS-associated illnesses should be appropriately updated, given the novel features due to the emerging increase in the mean age of the HIV-infected patient population.     

Cellulitis and soft tissue infection in patients with HIV disease: epidemiological and microbiological features

In order to assess the epidemiological, microbiological, and clinical features of cellulitis and soft tissue infection occurring during the course of HIV disease, clinical and laboratory data of 2221 hospitalizations carried out since 1991 were retrospectively examined, and 67 bacteriologically-proven episodes of cellulitis-soft tissue infection were identified (3.02% of overall admissions). Among the 92 cultured pathogens, Staphylococcus aureus was the most frequent (46 cases), followed by Pseudomonas spp., Escherichia coli, and Streptococcus pyogenes; 38.1% of patients had a polymicrobial infection. i.v. drug use (p<.02) and the male gender (p<.05), were significantly associated with the occurrence of these complications, while a great variation in the severity of underlying immunodeficiency was shown. An elevated rate (83.6%) of episodes of cellulitis or soft tissue infection were community-acquired in origin; the comprehensive frequency of these episodes significantly dropped during the highly active antiretroviral therapy (HAART) era (p<.01). Limbs were involved in over 80% of episodes, and an hematogenous dissemination of bacterial infection (which occurred in 25.4% of cases), proved significantly related to a CD4+ lymphocyte count <100 cells/microL (p<.03), and an absolute neutrophil count <1000 cells/microL (p<.05). S. aureus strains showed an elevated in vitro resistance rate to penicillin, ampicillin, and rifampin, and a 21.7% rate of methicillin-resistance, while among the 29 gram-negative microorganisms, resistance to ampicillin and first-generation cephalosporins, and that to amoxycillin-clavulanate and second-generation cephalosporin, occurred in over 90% and 60% of tested strains, respectively. All episodes of HIV-associated cellulitis and soft tissue infection were favorably treated in 5-16 days, in over 60% of cases with associated beta-lactam and aminoglycoside antibiotics; a recurrence of staphylococcal cellulitis occurred in 4 patients only, 6-17 months after the initial episode. Cellulitis and soft tissue infection are underestimated complications of HIV disease, but they have a broad etiological and clinical spectrum, are predominantly community-acquired, and are responsible for an appreciable morbidity, due to the supporting role of i.v. drug addiction, and the frequent hematogenous dissemination (which proved to be significantly related to the progression of immunodeficiency and underlying disease). The frequent polymicrobial etiology requires a combination antimicrobial therapy (to be guided by in vitro susceptibility studies), which may avoid a complicated and recurrent disease course in the great majority of cases.