Search PubMed⌕ Search

Biomedical subjects

G Famularo

Publications and source records attributed to G Famularo.

At least 55 records · Page 3Linked to original sources
PubMed1999

Jugular vein thrombosis: a rare presentation of atypical chronic myeloproliferative disorder in a young woman.

Venous thromboembolism is common in subjects with chronic myeloproliferative disorders and is a recognized presenting feature of occult myeloproliferation. We report the case of a young woman who presented with acute thrombosis in the right jugular vein and pulmonary embolism. Splenomegaly and myeloid proliferation with bone marrow fibrosis, in the absence of the criteria for typical myeloproliferative disorders, allowed a diagnosis of an atypical form of chronic myeloproliferative disorder. This form carries a high risk of thrombosis and venous thromboembolism can be the presenting feature, though the course is often indolent. Acute thrombosis in the right jugular vein has not been so far described in these subjects. The outcome of young people with myelofibrosis is unpredictable, but a normal level of hemoglobin and the absence of blast cells and constitutional symptoms at presentation identifies subjects with a low probability of rapid disease progression.

Adult↗
PubMed1999

General anesthesia mode does not influence endocrine or immunologic profile after open or laparoscopic cholecystectomy.

To verify the impact on stress response and the influence of anesthesia on endocrine/immunologic changes, we have investigated the plasma level of norepinephrine, cortisol, TNFalpha, and IL-6 in 46 patients scheduled for laparotomy and laparoscopic cholecystectomy at 2, 6, 12, and 24 h after the operation. Among subjects who underwent open approach, 9 received fentanyl anesthesia and 13 received isoflurane anesthesia. In the laparoscopy group, 14 patients were given fentanyl anesthesia and 10 were given isoflurane anesthesia. The results obtained confirmed that laparoscopic cholecystectomy is associated with a lesser immunoendocrine response, and the two anesthesia models do not interfere with plasma changes of the assessed hormones and cytokines.

Anesthesia, General↗
PubMed1998

Effect of L-carnitine on human immunodeficiency virus-1 infection-associated apoptosis: a pilot study.

The Fas/Fas ligand system is involved in uncontrolled apoptosis, which ultimately leads to the loss of T lymphocytes in human immunodeficiency virus (HIV)-infected individuals. The signal transduced by Fas receptor involves the activation of an acidic sphingomyelinase, sphingomyelin breakdown, and ceramide production. Our recent reports have shown that L-carnitine inhibits Fas-induced apoptosis and ceramide production both in vitro and in vivo. The aim of this study was to study, in a preliminary fashion, the impact of long-term L-carnitine administration on CD4 and CD8 absolute counts, rate, and apoptosis in HIV-1-infected subjects. The generation of cell-associated ceramide and HIV-1 viremia was also investigated. Eleven, asymptomatic, HIV-1-infected subjects, who refused any antiretroviral treatment despite experiencing a progressive decline of CD4 counts, were treated with daily infusions of L-carnitine (6 g) for 4 months. Immunologic and virologic measures and safety were monitored at the start of the treatment and then on days 15, 30, 90, and 150. L-carnitine therapy resulted in an increase of absolute CD4 counts, which was statistically significant on day 90 and 150 (P = . 010 and P = .019, respectively). A positive, not significant trend was also observed even in the change in absolute counts of CD8 lymphocytes. L-carnitine therapy also led to a drop in the frequency of apoptotic CD4 and CD8 lymphocytes. This reduction occurred gradually, but changes in actual values between each time point and baseline were strongly significant (P = .001 at the end of the study compared with the baseline). A strong reduction (P = .001) in cell-associated ceramide levels was found at the end of the study. In general, HIV-1 viremia increased slightly. No toxicity related to L-carnitine therapy was observed and dose reductions were not necessary. In HIV-1-infected subjects, long-term infusions of L-carnitine produced substantial increases in the rate and absolute counts of CD4 and, to a lesser degree, of CD8 lymphocytes. This was paralleled by a reduced frequency of apoptotic cells of both subgroups and a decline in the levels of ceramide. No clinically relevant change of HIV-1 viremia was observed.

Adult↗
PubMed1998

Thrombolysis enters the race: a new era for acute ischaemic stroke?

Thrombolysis has been shown to be an effective treatment for ischaemic stroke. The major obstacles to more widespread use of this therapy are lack of awareness that treatment is possible and the short, less than 3 hours, therapeutic window. Even though the use of this therapy can be burdened by the occurrence of intracerebral haemorrhages, there is tantalizing evidence that thrombolysis is the only approach that has been so far demonstrated to improve the outcome of these patients. Early recognition of the onset of stroke, the immediate transfer to a suitably equipped facility and careful screening of a computed tomographic scan of the head for signs of early infarction are necessary for the safe administration of intravenous thrombolysis. There is mounting evidence that intra-arterial thrombolysis in combination with transluminal angioplasty has even a greater potential than intravenous thrombolysis and, possibly, a lower rate of intracerebral haemorrhages. Despite doubts having been raised about the use of thrombolysis in routine clinical practice, it appears that this therapy is most effective in those patients treated with careful adherence to published guidelines.

Acute Disease↗
PubMed1997

Apoptosis: mechanisms and relation to AIDS.

Infection with the human immunodeficiency virus (HIV) is considered to lead to the acquired immunodeficiency syndrome (AIDS) via the progressive loss of immune competence in the infected host. Recent research has highlighted that HIV may indirectly trigger an active cell suicide process, referred to as programmed cell death or apoptosis, that contributes to the decline in lymphocyte counts throughout the course of HIV infection. We review here the main host- and HIV-related factors actively involved in inducing lymphocyte apoptosis. Among them, the relationships linking HIV, the oxidant/antioxidant balance in the cellular redox system, tumor necrosis factor (TNF) and lymphocyte-associated ceramide generated through the activation of sphingomyelin pathway are receiving growing consideration. Recognizing the importance of apoptosis in AIDS pathogenesis may have a great impact on the design of new strategies for the treatment of the disease. Available data indicate that antioxidant compounds exert antiapoptotic activity. These compounds, in our opinion, should be used in combination regimens with antiretroviral drugs in the treatment of HIV-infected subjects.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Heat shock protein (HSP70) expression in septic patients.

PURPOSE: This study investigates heat shock protein 70 (HSP70) expression by peripheral blood mononuclear cells (PBMCs) of septic patients admitted to an intensive care unit and examines the possibility of a correlation between HSP70 levels and plasma tumor necrosis factor alpha (TNF-alpha) concentrations. Additionally, we evaluated whether the HSP70 production could be regarded as a prognostic factor for the development of septic shock as well as for patient survival. MATERIALS AND METHODS: Blood samples of 29 patients were taken 24 hours after the diagnosis of sepsis. HSP70 expression and TNF-alpha level were measured using indirect immunofluorescent analysis and a commercially available enzyme-linked immunosorbent assay method, respectively. RESULTS: PBMCs expressed significantly high levels of HSP70 (11.9 +/- 5.6 [sd]) compared with those of the healthy control group (3.2 +/- 2.1% positive cells). Such enhanced levels were correlated to plasma TNF-alpha concentrations (r = .99, P < .01). This study failed to demonstrate a relationship between HSP70 production and clinical outcome. CONCLUSION: These findings give further evidence that also in humans, heat shock response is activated during sepsis. The correlation observed between HSP70 overproduction and TNF-alpha plasma concentrations suggests that HSP70 exerts a possible protective effect against TNF-alpha cytotoxicity. Such hypothesis has not been confirmed by our clinical data.

APACHE↗
PubMed1997

Acetyl-carnitine deficiency in AIDS patients with neurotoxicity on treatment with antiretroviral nucleoside analogues.

OBJECTIVE: A severe dose limiting axonal peripheral neuropathy may develop in subjects on treatment with the nucleoside analogues didanosine (ddl), zalcitabine (ddC), and stavudine (d4T). The impairment of mitrochondrial DNA synthesis is crucial to the pathogenesis of this disorder although other mechanisms have not been ruled out. The depletion of acetyl-carnitine, which regulates the metabolism and function of peripheral nerves could contribute to the neurotoxicity of these compounds. DESIGN: Non-randomized, cross-sectional study of selected patients. METHODS: We measured the serum levels of acetyl- and total carnitine in 12 subjects with axonal peripheral neuropathy developed on treatment with different regimens of neurotoxic nucleoside analogues (ddl, ddC, d4T). Subjects who did not develop peripheral neuropathy while staying on treatment with ddl (n = 10) or zidovudine (n = 11) served as the control groups. HIV-negative subjects with axonal on demyelinating autoimmune neuropathies (n = 10) and healthy individuals (n = 13) were additional control groups. RESULTS: Subjects experiencing axonal peripheral neuropathy on treatment with ddl, ddC and d4T had significantly reduced levels of acetyl-carnitine in comparison to the control groups. No difference was observed in the levels of total carnitine between study subjects and the control groups. CONCLUSIONS: Our results demonstrate that subjects who developed peripheral neuropathy while staying on treatment with ddl, ddC and d4T had acetyl-carnitine deficiency. The normal levels of total carnitine in the study group appear to indicate the specificity of the defect and rule out coexisting relevant nutritional problems. The critical role of acetyl-carnitine for the metabolism and function of the peripheral nerves supports the view that the acetyl-carnitine deficiency found in these subjects may contribute to the neurotoxicity of ddl, ddC and d4T, even though the interference with mitochondrial DNA synthesis is regarded as the main cause of their toxicity.

Acetylcarnitine↗
PubMed1997

Effect of L-carnitine treatment in vivo on apoptosis and ceramide generation in peripheral blood lymphocytes from AIDS patients.

Lymphocyte apoptosis in HIV-infected individuals may play a role in T-cell depletion and therefore favor progression to AIDS. In this study, we examined the effects of a short-term (5-day) intravenous treatment with L-carnitine (6 g/day) on apoptosis of CD4 and CD8 cells from 10 AIDS patients. L-carnitine administration has been shown to induce a strong reduction in the percentage of both CD4 and CD8 cells undergoing apoptosis. Interestingly, the L-carnitine treatment, which did not show relevant side effects in four patients, led to a strong and significant reduction of peripheral blood mononuclear cell-associated ceramide, an intracellular messenger of apoptosis, that positively correlated with the decrease of apoptotic CD4- and CD8-positive cells. These results suggest that L-carnitine could be an effective antiapoptotic drug in the treatment of AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1997

[Ischemic stroke. What approach in the Emergency Department?].

Ischemic stroke remains worldwide one of the leading causes of death and disability. Current therapeutic approach is focusing upon the protection of neuronal metabolism in ischemic areas and early thrombolysis in selected subgroups of patients. There is evidence that all subjects with ischemic stroke should undergo a cerebral CT as soon as possible after clinical presentation. Taken all into account, Emergency Physicians appear to have a central role in the management of ischemic stroke.

Acetylcarnitine↗
PubMed1997

CD8 lymphocytes in HIV infection: helpful and harmful.

The part played by CD8 lymphocytes in the pathogenesis of human immunodeficiency virus infection (HIV) is much disputed and the relevant issue of the controversy ranges as to whether the functional activity of these cells is beneficial or detrimental to the host. Even though CD8 cells could efficiently suppress HIV replication through both major histocompatibility complex (MHC)-restricted cytotoxic killing of infected cells, particularly during primary infection, and HIV-suppressing soluble factors, there is evidence that tissue-infiltrating CD8 lymphocytes mediate injury in several organs of HIV-infected subjects. Furthermore, CD8 lymphocytes could contribute to the destruction of CD4 cells in vivo. Of note, the virus has the capability to escape the recognition by cytotoxic CD8 cells and the cytotoxic activity of CD8 cells and their counts decline with evolving HIV infection. Several mechanisms are proposed to explain this latter finding, including the direct in vivo infection of CD8 cells by the virus. It is likely that early during the course of HIV infection when viral loads are generally low an efficient CD8 cell response can control HIV replication whereas in subjects with evolving disease, who have very high viral loads, CD8 lymphocytes remove essential components of the immune response and mediate tissue injury.

Animals↗
PubMed1996

Cellular dysmetabolism: the dark side of HIV-1 infection.

The progression to disease in subjects infected with the human immunodeficiency virus type I (HIV-1) cannot be explained solely on the basis of the infecting HIV-1 species. There is recent evidence that abnormalities in the cellular metabolism are crucial to the progression of the infection through common pathways that involve the induction of apoptosis and oxidant stress. Conversely, the low propensity of lymphocytes to undergo apoptosis, a normal redox status, and a balanced ceramide metabolism appear to predict a slow progression, or the non-progression at all, of the infection. It is likely that the ability of the host to maintain over time a balanced cellular metabolism despite the chronic infection with the virus contributes to the especially favourable outcome of an otherwise fatal infection seen in a discrete subgroup of HIV-1-infected individuals (long-term non-progressors) who might never experience any of the adverse effects of HIV-1 infection and will never demonstrate disease progression. Furthermore, this background supports the hypothesis that adjunctive therapies directed at correcting certain abnormalities of cellular metabolism seen in the infected host should be given in combination with antiretroviral drugs in order to slow the progression of the infection.

Acquired Immunodeficiency Syndrome↗