Rapidly evolving hepatitis C virus-related cirrhosis in a human immunodeficiency virus-infected patient receiving triple antiretroviral therapy

The Tyr92-Pro93 peptide group of bovine pancreatic ribonuclease A (RNase A) exists in the cis conformation in the native state. From unfolding/refolding kinetic studies of the disulfide-intact wild-type protein and of a variant in which Pro93 had been replaced by Ala, it had been suggested that the Tyr92-Ala93 peptide group also exists in the cis conformation in the native state. Here, we report the crystal structure of the P93A variant. Although there is disorder in the region of residues 92 and 93, the best structural model contains a cis peptide at this position, lending support to the results of the kinetics experiments. We also report the crystal structure of the C[40, 95]A variant, which is an analog of the major rate-determining three-disulfide intermediate in the oxidative folding of RNase A, missing the 40-95 disulfide bond. As had been detected by NMR spectroscopy, the crystal structure of this analog shows disorder in the region surrounding the missing disulfide. However, the global chain fold of the remainder of the protein, including the disulfide bond between Cys65 and Cys72, appears to be unaffected by the mutation.     

Cerebellar degeneration associated with human immunodeficiency virus infection

Cerebellar disorders associated with HIV infection are typically the result of discrete cerebellar lesions resulting from opportunistic infections such as toxoplasmosis and progressive multifocal leukoencephalopathy or primary CNS lymphoma. Clinical symptoms and pathologic abnormalities related to the cerebellum may also be observed with HIV dementia. A primary cerebellar degeneration with HIV has not previously been reported. Ten patients were identified over an 8-year period at five medical centers. All patients had clinical, laboratory, and radiologic evaluations, and three had neuropathologic examinations. Patients presented with progressively unsteady gait, slurred speech, and limb clumsiness. Examination revealed gait ataxia, impaired limb coordination, dysarthria, and abnormal eye movements. Cognition, strength, and sensory function remained normal. CD4 lymphocyte counts varied between 10 and 437 cells/mm3. Neuroimaging studies showed prominent cerebellar atrophy. Neuropathology showed focal degeneration of the cerebellar granular cell layer and unusual focal axonal swellings in the brainstem and spinal cord. Cultures, histopathology, and immunochemical studies showed no conclusive evidence of infection. We report a syndrome of unexplained degeneration of the cerebellum occurring in association with HIV infection.     

Primary pulmonary hypertension associated with human immunodeficiency virus infection

Several cardiorespiratory diseases can complicate human immunodeficiency virus infection. Primary pulmonary hypertension is a rare clinical disorder which carries a bad prognosis. More than 90 cases of HIV-associated primary pulmonary hypertension have been reported to date. Although its pathogenesis remains unknown, some evidence suggests a possible role for the virus itself in its development. Genetic susceptibility may also be implicated. The clinical and histopathologic features of this entity do not differ from those of classic primary pulmonary hypertension. The diagnosis requires a high degree of clinical suspicion and a careful evaluation to rule out causes of secondary pulmonary hypertension. In addition to supportive measures, anticoagulation and vasodilators have been used to treat this disorder, although sufficient data regarding long-term results with these therapies are lacking.     

Intestinal mucosal inflammation associated with human immunodeficiency virus infection

The role of the human immunodeficiency virus type-1 (HIV) in producing intestinal disease was studied prospectively in 74 HIV-infected individuals with (43) or without (31) the acquired immunodeficiency syndrome (AIDS). Thirty-one subjects had enteric infections; all but one had AIDS. Alteration in bowel habits was the most common symptom and occurred independently of enteric infections. Abnormal histopathology was present in 69% of cases, and the finding was associated with altered bowel habits. An HIV-associated protein, p24, was detected in 71% of biopsies by ELISA assay. Tissue p24 contents varied with disease stage and were highest in HIV-infected individuals without AIDS (Walter Reed classes 3 and 4). Tissue p24 detection was associated with both altered bowel habits and histologic mucosal abnormalities. Tissue contents of the cytokines, tumor necrosis factor-alpha and interleukin-1 beta, were higher in HIV-infected individuals than in controls and their elevations were independent of enteric infection. We conclude that HIV reactivation in the intestinal mucosa may be associated with an inflammatory bowel syndrome in the absence of other enteric pathogens.     

Changes in CD8 cell subpopulations induced by antiretroviral therapy in human immunodeficiency virus infected patients

Although CD4+ T cells are the main target of HIV infection, CD8+ cells also play important roles in the interaction between HIV and the host immune system. The aim of this study was to analyze the effect of anti-HIV therapy on the relative proportion of some important CD8+ cell subpopulations. Five HIV-infected patients were enrolled, and blood samples were collected several times, within 90 days from the initiation of therapy. CD4+ cell count and HIV viremia were investigated, as well as the expression of CD38, HLA-DR, CD28, CD57, CD30, CD95 molecules on CD8+ cells. A complex remodeling of CD8+ cell subpopulations took place between week 2 and week 7 of treatment. This remodeling mainly consisted of: i) decrease of CD8+CD38+ and CD8+DR+ cells; ii) increase of CD8+CD28+ cells; and iii) decreased expression of the CD95/Fas molecule on CD8+ cells. Overall, these findings suggest that effective anti-HIV therapy induces changes of CD8+ subpopulations showing the reversal of the state of chronic activation that is caused by viral replication.     

Predictors of Staphylococcus aureus pneumonia associated with human immunodeficiency virus infection

This study is based on a retrospective logistic regression analysis of all human immunodeficiency virus (HIV)-infected patients with Staphylococcus aureus pneumonia (SAP) admitted to the Department of Infectious Diseases, Catholic University, Rome, Italy between January 1986 and December 1994. Nineteen patients with 24 episodes of SAP were enrolled in the study. A control group of 38 HIV-infected patients without pneumonia was included. The attack rate of SAP was 8.31/1000 HIV-related hospital admissions and the frequency, out of the total number of bacterial pneumonia observed in the study period, was 16% (24 of 154 patients). The large majority of SAP was community acquired. On the univariate analysis, intravenous drug abuse (IVDA) (P = 0.02), history of previous Pneumocystis carinii pneumonia (PCP) (P = 0.03) and cirrhosis (P = 0.03) were significant risk factors for SAP. In addition, IVDA and previous PCP were independent risk factors on multivariate analysis. All patients presented with fever associated with cough (74%), chest pain (26%) or shortness of breath (37%). Chest X-ray documented lobar pneumonia (78%), predominantly in the lower lobes, consolidation with cavitation (11%), and interstitial-nodular infiltrates (11%). Pleural effusion was present in 31% of patients. The response to therapy was favourable in 79% of patients. Recurrence occurred in 26% and death occurred in 21% of patients. Death was significantly associated with the low level (< 50 mm-3) of circulating T CD4+ cells (P = 0.03) and the recurrence of pneumonia (P = 0.03). In conclusion, the present study indicates that S. aureus is an important aetiologic agent of bacterial pneumonia in HIV-infected patients, especially if they are drug abusers with previous PCP.     

Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection

Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.     

Cerebral infarction associated with vasculitis due to varicella zoster virus in patients infected with the human immunodeficiency virus

Cases of herpes zoster ophtalmicus (HZO) with delayed contralateral hemiparesis caused by hemispheric stroke secondary to granulomatous angiitis have been reported and are a well-recognized complication of herpes zoster. Similar cases have been reported more recently during infection with human immunodeficiency virus (HIV). We describe two HIV+ patients without any clinical history of zoster dermatitis who developed a sudden hemiparesis followed 2 weeks later for one by an acute retinal necrosis. Computerized tomography (CT) scan, magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA) were performed and showed a hemispheric stroke with evidence of a segmental arteritis of the carotid syphon. Varicella zoster virus (VZV) was found in the cerebro spinal fluid (CSF) in the two patients and after puncture of the vitreous fluid of the patient with the acute retinal necrosis. These two cases exemplify the difficulty of diagnosis of stroke in HIV+ patients, which seems to be more frequent than in similarly aged non-infected patients and demonstrates that VZV needs to be taken in consideration and identified even without any past history of zoster dermatitis.     

Common variable immunodeficiency associated with autoimmune thrombocytopenia: anesthetic management

A 44-year-old man diagnosed of common variable immunodeficiency associated with thrombopenia due to autoimmunity required anesthesia for anal fissure repair and hemorrhoidectomy. Hemostatic complications developed after surgery, with extreme thrombopenia (1,000 platelets/pl) and analytical changes that necessitated administration of six units of platelets from apheresis, as well as immunoglobulins, antifibrinolytic agents (e-aminocaproic acid) and granulocytic colony stimulating factors. Anesthesia for such patients is reviewed, with emphasis on careful management of the airways, preparation of sufficient material for surgery (rapid transfusion equipment, large caliber intravenous catheters, sterile material) and orientation of anesthetic technique toward general anesthesia through a laryngeal mask.     

Clinical course of human immunodeficiency virus type 1 associated pulmonary tuberculosis during short-course antituberculosis therapy

PURPOSE: It was reported that Matrigel improved hatching of mouse blastocysts produced in vitro from F1 hybrid-derived zygotes. We investigated whether Matrigel would be similarly beneficial with outbred strain-derived embryos, which exhibit a "two-cell" block similar to the developmental blocks of other species. METHODS: Mouse embryo development was assessed with or without Matrigel in KSOM medium, which supports the development of blocking strain zygotes in vitro, and in human tubal fluid (HTF) medium, which normally does not but which is used for human IVF. RESULTS: Matrigel severely inhibited the development of zygotes to blastocysts in KSOM and did not improve culture in HTF. There was no effect on development from the two-cell stage. We were not able to replicate the previous finding of Matrigel's beneficial effect on hatching of F1-derived zygotes. CONCLUSIONS: Matrigel may be a deleterious addition to embryo culture or coculture systems.     

Myopathy associated with human immunodeficiency virus infection: report of a case

This paper explores nursing's current fascination with defining and exploring the term 'caring'. Fear of caring is proposed as the reason for this fascination. Factors at the root of this fear are identified and an expanded definition of caring (one which arises from the dispelling of such fear) is proposed. This expanded definition is given a new label--loving. For, as this author contends, has not loving always been at the heart of nursing?     

Lack of relation of granulocyte antibodies (antineutrophil antibodies) to neutropenia in children with human immunodeficiency virus infection

Based upon the literature, we discuss epidemiological, histopathological, clinical and treatment aspects of postirradiation sarcomas. The risk of postirradiation sarcoma is very low and negligible in comparison with the beneficial effect of radiotherapy, and it should not be a major factor influencing treatment decision in patients with cancer. The radical surgical approach of postirradiation sarcoma is the treatment which offers the best chance for cure.     

Bacillary angiomatosis associated with myositis in a patient infected with human immunodeficiency virus

PURPOSE: To report a patient with optic nerve avulsion caused by forceful rotation of the globe that occurred when his thumb penetrated the orbit while he was diving. METHODS: A 17-year-old boy was initially examined for sudden loss of vision after jumping feet first from a bridge 50 feet above a river. Upon hitting the water, he felt his right thumb push into his right globe. The patient underwent ophthalmologic and imaging examination. RESULT: Examination disclosed a tear of the optic nerve head from the sclera temporally in the right eye. CONCLUSION: Optic nerve avulsion occurs secondary to forceful rotation of the eye with tearing of the optic nerve as it exits the globe.