T-cell response to HIV in natural infection: optimized culture conditions for detecting responses to gag peptides

We report a case of successful laparoscopic resection of a solitary schwannoma of the gastric fundus performed on emergency. The patient was a 52-year-old man who presented with an upper gastrointestinal hemorrhage. At admission, the endoscopy and hydro-CT scan showed a submucosal tumor, 2.5 cm in maximum diameter, with an area of central ulceration arising from the anterior wall of the gastric fundus. A wedge laparoscopic resection of the gastric wall was performed under endoscopic guidance. The defect in the anterior wall was repaired in part by linear stapler and in part using a continuous suture. The postoperative recovery was uneventful and the patient was discharged on the 4th postoperative day. Laparoscopic approach represents a safe and efficient approach for the treatment of benign tumors of the stomach, also on emergency basis.     

T lymphocytes and their cytokines in human immunodeficiency virus (HIV) infection: implications for associated neoplasias

Infection with the human immunodeficiency virus (HIV) results in gradual immunosuppression due to the loss of CD4+ T cells. In the wake of immune system breakdown, infected individuals may acquire multiple opportunistic infections and develop certain malignancies which ultimately account for the vast majority of deaths in these persons. A limited number of malignancies are directly associated with HIV infection and suggest a common tie between these tumors. Inappropriate immune surveillance resulting in insufficient inhibition of virus replication and inadequate control of the growth of transformed cells may contribute to the development of malignancies in HIV-infected individuals. Alternatively, malignancies in HIV infection may be the consequence of immune dysregulation. Cellular immune responses mediated by antigen-specific cytotoxic T lymphocytes (CTL) are of particular importance for immunologic control of viral infections and substantial information has been gathered about theses cells in HIV infection. The goal of this review is therefore to summarize recent findings regarding the cellular immune response to HIV with a particular focus on cytokines released by HIV-specific CTL.     

Thrombocytopenia in HIV infection

Thrombocytopenia commonly occurs in individuals with HIV disease. However, profound thrombocytopenia, occurring in only 1.5% of cases, is relatively rare. The mechanisms of thrombocytopenia appear to be multifactorial: profound thrombocytopenia in HIV disease is related to an immune destruction either by antiplatelet antibodies or by immune complexes. In addition, a defect in platelet production is quite frequent both in immune thrombocytopenia (ITP) and in mild thrombocytopenia. This impaired platelet production may be due to an HIV infection of megakaryocytes that express a functional CD4 molecule. Treatment of HIV-associated thrombocytopenia is quite similar to that of non-HIV ITP. However, zidovudine increases the platelet count without correlation with its antiviral effect. In animal models and HIV patients, this enhancement of platelet count appears to be due to a stimulation of platelet production, the precise mechanism of which remains unknown. Splenectomy is as effective in severe HIV thrombocytopenia as in non-HIV ITP and has no significant adverse effects on HIV disease.     

Macroamylasemia in HIV infection

A case of macroamylasemia was seen in a 40-year-old HIV-positive bisexual male treated at the Fort Worth-Tarrant County Health Department (Ryan White Clinic). Macroamylasemia is a rare condition encountered sometimes in persons with HIV infection. Apart from the setting of HIV infection and acquired immunodeficiency syndrome, macroamylasemia is seen also in various conditions including liver disease, diabetes, cancer, malabsorption, and autoimmune disorders. Although this biochemical phenomenon requires no therapy, it should be considered in the differential diagnosis of patients who have persistently high levels of serum amylase and yet do not exhibit any clinical symptoms of pancreatitis or salivary gland inflammation.     

Toxoplasma gondii infection in advanced HIV infection

OBJECTIVE: To study Toxoplasma encephalitis (TE) in advanced HIV infection, including predictive factors, possible prophylactic regimens and impact on survival. DESIGN: Epidemiological analysis of data collected prospectively during the Alpha study, a double-blind, randomized clinical trial, comparing two doses of dideoxyinosine in patients with advanced HIV disease. PATIENTS: First episode of TE occurred in 75 out of 499 patients participating in the trial. METHODS: Kaplan-Meier estimates and semi-parametric Cox's model were used. RESULTS: A low CD4 cell count and a positive Toxoplasma serology were strongly predictive of the occurrence of TE. In patients with CD4 counts < 100 x 10(6)/l and a positive Toxoplasma serology at entry to the study, the 12-month TE incidence was 25.4%. Patients who were receiving at entry any of the following potentially antitoxoplasmic drugs: trimethoprim-sulphamethoxazole, pyrimethamine, dapsone, pyrimethamine-sulphadoxine or sulphadiazine, had a lower TE incidence than those who were not; 6.2 versus 18.8%, respectively (P < 0.001). The rate of survival 12 months after TE was 29.6%. Even after adjusting the major prognostic covariates, TE was predictive of death (P < 0.001; relative risk, 1.8). CONCLUSIONS: The high HIV incidence, morbidity and mortality in high-prevalence areas suggests that primary prophylaxis should be given in patients at high risk for toxoplasmic reactivation.     

Beta-carotene in HIV infection: an extended evaluation

OBJECTIVE: Several small short-term intervention studies have suggested that beta-carotene supplementation in HIV-infected patients can increase the number of various immune cells including CD4 cells. This prospective double-blinded study was designed to investigate whether beta-carotene supplementation would result in this immuno-enhancement in a larger number of patients over a longer time period. METHODS: HIV-positive patients were randomly assigned to receive either 60 mg beta-carotene orally three times daily or a matched placebo. In addition, all patients received a multivitamin supplement. Patients were evaluated at baseline, 1 month, and 3 months for T-cell quantitative subsets, natural killer cells, HIV p24 antigen, beta-carotene levels, complete blood counts and chemistry batteries. Body weights and Karnofsky scores were evaluated at each visit. RESULTS: Seventy-two patients signed informed consent forms and entered the study. Except for serum beta-carotene concentration, there were no statistically significant differences (P < 0.05) between the treatment (60 mg beta-carotene three times daily and multivitamins) and placebo (placebo and multivitamins) groups at baseline or after either 1 or 3 months of treatment. DISCUSSION: Earlier studies suggesting that beta-carotene supplementation increased levels of immune cells in HIV-infected patients were not replicated in this study. The addition of a multivitamin supplement to both arms of this study may have masked any difference between the two groups. However, on the basis of the results of this study, we would not recommend supplementation with high doses of beta-carotene for HIV-infected patients.     

Lithium homeostasis in Xenopus oocytes: implications for the study of signal transduction

The Xenopus oocyte has been shown to be a useful model for the study of signal transduction pathways. The present study investigated whether or not the oocyte could be used to study the effects of lithium on signal transduction mechanisms by comparing the dynamics of lithium homeostasis in the oocyte and a human immortalized hippocampal cell line using Flame Atomic Emission Spectroscopy (FAES). A biphasic pattern of lithium uptake was observed in the oocyte in the presence of 5 mM extracellular lithium. The late phase of lithium uptake, which started after 30 minutes of incubation time, was sensitive to phloretin, an inhibitor of Na+/Li+ counter-transport. Differences in lithium efflux kinetics further characterized the two observed phases of accumulation and also suggested that lithium might be distributed in different pools within the oocyte, including one sequestered in organelles or associated with cytosolic proteins. An analogous sequestered pool was not, however, observed in the hippocampal cell line indicating that lithium is distributed differently in these cell types. This suggests that the Xenopus oocyte might not be a suitable model for evaluating the effects of lithium on signal transduction pathways because of the unknown contribution of the sequestered pool on predicting relevant physiological effects.     

Primary HIV infection

Up to 70% of individuals with primary HIV infection will develop symptoms of an acute illness. The most common symptoms reported are fever, generalized lymphadenopathy, arthralgia and myalgia, headache, pharyngitis, enanthema, skin rash, diarrhoea, and mucocutaneous ulcerations. More rarely, oesophageal candidiasis, meningoencephalitis, rhabdomyolysis and epiglottitis have been reported. The diagnosis of the acute HIV infection syndrome can be established by demonstrating antibodies to HIV or by demonstration of HIV antigen positivity. Detection of virus through culture or PCR may prove to be more sensitive, but are not yet used as routine methods. The course of the primary infection has prognostic importance for the subsequent course of HIV infection. This probably reflects the importance of both the viral phenotype and of the initial immune response to HIV. Primary HIV infection should be considered in any patient with possible exposure to HIV presenting with fever of unknown cause.     

Paediatric HIV infection

HIV infection in children is a family disease, with social, economic and medical aspects that make it one of the most challenging diseases of our time. Knowledge about the factors involved in mother-to-child transmission and the natural history of the disease is gradually increasing although there is still much to understand. As the majority of children become infected through mother-to-child transmission, perinatally acquired infection will parallel increases in heterosexual transmission and the numbers of infected women of childbearing age. Current estimates of the rate of vertical transmission range from 14% to 39% in different studies. The relative proportion of transmission occurring in utero, peripartum or postpartum may vary in different localities and remains unclear. A study recently carried out in the USA showed that zidovudine given late in pregnancy, peripartum and in the neonatal period decreases HIV transmission from 25% to 8%. The clinical presentation of HIV infection in children depends in part on exposure to different infections. In developing countries the children usually present with nonspecific signs and symptoms, such as failure to thrive, chronic diarrhoea, cough and recurrent bacterial infections. Other common presentations include generalized lymphadenopathy, oropharyngeal candidiasis, dermatitis, enlargement of parotid glands and neurological problems, including delayed development.     

Muscular complications in HIV infection

Skeletal muscle involvement may occur at all stages of HIV-infection and represents the first manifestation of the disease into some patients. We usually classify muscle involvement in HIV-infected patients in one of the following categories: HIV-associated myopathy, a myopathy that meets the criteria for polymyositis in a majority of patients, and those for acquired nemaline myopathy in some cases (1); zidovudine myopathy, a reversible mitochondrial myopathy (2); HIV-wasting syndrome and other AIDS-associated cachexias (3); opportunistic infections and tumor infiltrations of the skeletal muscle (4); vasculitic processes and iron pigment deposits (5); HIV-associated myasthenia gravis (6) and rhabdomyolysis (7). Immunohistology for major histocompatibility complex class I antigen and histochemical reaction for cytochrome coxidase are helpful in the correct classification of a myopathy as HIV polymyositis or zidovudine myopathy.     

Secretory immunity in HIV infection

Secretory IgA plays a crucial role in the defense of pathogens at mucosal surfaces. As CD4+ T cells are lost early in the mucosa of human immunodeficiency virus (HIV)-infected patients and as CD4+ T cells play an essential role in the regulation of specific IgA responses to pathogenic agents at mucosal sides, it could be expected that this first line of defense is impaired in HIV-infected patients. Therefore, several studies were undertaken to characterize the humoral immune response at mucosal surfaces. However, the results obtained so far are in part contradictory. For intestinal IgA, reduced, increased and no changes compared to controls were described. The different results may be due to different methods applied. In most studies an abnormal predominance of HIV-specific IgG over IgA response was found in the intestine of HIV-infected patients. Studies on cytomegalovirus-specific intestinal antibodies indicate a complete lack of a specific intestinal IgA response. However, in cryptosporidiosis of HIV-infected patients, diarrhea persists despite a secretory IgA response indicating that other factors are also important for the clearance of this pathogen.     

HIV infection in surgical practice

When HIV is mentioned in a surgical forum a debate will often follow about "universal testing" and "barrier precautions". Unfortunately, there is little discussion of the many ways that HIV-infected patients may present primarily to the surgeon. Although lifestyle risk factors are important clues, unusual clinical features of a relatively common surgical disease should raise the suspicion of HIV infection.