Predicting haemorrhage in pre-hospital traumatic patients: evaluation of the novel heart-to-arm time index.

BACKGROUND: Early recognition of hypovolaemia in trauma patients is very important. However, the most often used clinical signs, such as hypotension and tachycardia, lack specificity and sensitivity. METHODS: We propose a non-invasive index of hypovolaemia, the heart to arm time (iHAT), based on a modified pulse transit time indexed to heart rate. Pulse transit time is the sum of pre-ejection period and vascular transit time. Following pre-load reductions due to hypovolaemia, ventricular diastolic filling time increases causing an increase in pre-ejection-period, pulse transit time, and hence iHAT. One hundred and four consecutive patients with suspected major trauma were enrolled. The primary aim was to evaluate the use of the iHAT for detecting haemorrhage in major trauma. The secondary end point was to compare the specificity and sensitivity of iHAT compared to commonly used indexes. RESULTS: iHAT was calculated in 84 subjects, 11 of whom were haemorrhagic. iHAT discriminated haemorrhagic from non-haemorrhagic group (46.8% vs. 66.9%, P < 0.0001). The cut-off for iHAT with the best compromise between sensitivity (90.9%) and specificity (100%) was reached at the 58.78% level. Comparing haemorrhagic and non-haemorrhagic patients, the area under the ROC curve was 0.952 for iHAT, 0.835 for heart rate, and 0.911 for systolic blood pressure, showing no significant differences. CONCLUSIONS: iHAT is a non-invasive index that can identify haemorrhage in trauma patients with high sensitivity and specificity. These data should be considered as an exploration, but any conclusion should be validated in a new set of consecutive patients.

[Disseminated histoplasmosis in patients with AIDS. 2 case reports]. / Istoplasmosi disseminata in pazienti affetti da AIDS. Descrizione di due casi.

Histoplasmosis is endemic in some areas of United States and in South America, and generally causes an acute self-limiting respiratory infection. In elderly and immunosuppressed patients the infection can spread through the blood, causing a severe systemic illness. Here we describe two cases of disseminated histoplasmosis in AIDS patients. The first was observed in an Italian woman who had never visited endemic countries, and was recognized only at autopsy; the second was observed in a trans-sexual patient, arrived in Italy from Brazil. Clinical suspicion of histoplasmosis is important in immunocompromised patients of non-endemic areas as symptoms are often aspecific and misdiagnosis is frequent.

Post-kala-azar dermal leishmaniasis during highly active antiretroviral therapy in an AIDS patient infected with Leishmania infantum.

We report a case of post-kala-azar dermal leishmaniasis (PKDL) in a woman with AIDS which occurred 13 months after a diagnosis of visceral leishmaniasis concomitantly with immunological recovery induced by highly active retroviral therapy. Cytokine pattern at the time of visceral leishmaniasis and PKDL diagnosis was studied and pathogenic implications were discussed.

Identification of two distinct subsets of long-term nonprogressors with divergent viral activity by stromal-derived factor 1 chemokine gene polymorphism analysis.

Stromal-derived factor (SDF)-1, the natural ligand for CXCR4, is present in a common polymorphic variant defined by a G-->A transition in the 3' untranslated region of the gene. In persons infected with human immunodeficiency virus type 1 (HIV-1), the homozygous genotype (SDF1-3'A/3'A) has been postulated to interfere with the appearance of T-tropic syncytium-inducing strains. The polymorphism of SDF1 was correlated with HIV-1 phenotype, plasma viremia, and unspliced and multiply spliced specific transcripts in 158 virologically characterized HIV-1-infected patients (39 recent seroconverters, 75 typical progressors, and 44 AIDS patients) and in 42 HIV-1-infected long-term nonprogressors (LTNPs). Analysis of SDF1 allele distribution revealed that SDF1-3'A/3'A status is associated with low CD4 cell count (P=.0449) but not with a specific HIV-1 phenotype. In LTNPs, SDF1-+/+ condition defined a subset of persons with lower HIV-1 replication than in heterozygous subjects. The low viral activity in SDF1-+/+ LTNPs suggests that other factors play a major role in vivo in determining the course of HIV-1 infection.

Redistribution of body fat in HIV-infected women undergoing combined antiretroviral therapy.

OBJECTIVES: To investigate the prevalence, metabolic features and risk factors of a particular pattern of fat redistribution (FR), characterized by a progressive enlargement of breast and abdominal girth associated with a wasting of the lower limbs, observed in HIV-infected women treated with combined antiretroviral (ARV) therapy. DESIGN: Cross-sectional study. SETTING: Outpatients attending the Institute of Infectious Diseases, University of Milan, Milan, Italy. PATIENTS AND METHODS: HIV-infected women treated with two or more ARV drugs, observed between December 1997 and February 1998. FR was confirmed by means of a physical examination and dual-energy X-ray absorptiometry (DEXA). The metabolic and endocrinological measurements in patients with FR were compared with those in FR-free women. RESULTS: FR was observed in 32 out of 306 women (10.5%). DEXA revealed more trunk fat (P < 0.01) and less leg fat (P < 0.001) in the patients with FR than in the matched controls. There were no significant differences in laboratory test results between the two groups. All of the FR patients were taking lamivudine-containing regimens; 20 of them were also taking a protease inhibitor (PI). The association of FR with lamivudine-including regimens was statistically significant (P = 0.017). Among the patients taking lamivudine, the risk associated with treatments including PI was 1.8 (95% CI 0.8-3.8, P = 0.12). A total duration of ARV therapy of more than 1000 days was associated with a greater risk of developing FR (OR 10.8; 95% CI 1.4-80.5; P = 0.0207). Stepwise logistic regression analyses indicated that prolonged ARV therapy and a viral load of more than 10000 copies per ml at the beginning of the last ARV regimen were the only variables that significantly and independently correlated with the risk of FR. CONCLUSIONS: The observed body modifications are caused by a redistribution of body fat without fat loss that is apparently not associated with hyperlipidemia, altered glucose metabolism or other endocrinological disorders. The development of FR in patients receiving only reverse transcriptase (RT) inhibitors suggests the presence of a PI-independent mechanism that deserves further investigation.

Lack of in vitro anti-gp160 antibody production is a correlate of nonprogression among HIV type 1-infected individuals.

The aim of our study was to investigate the possible correlation of in vitro antibody production (IVAP) directed to the gp160 protein of HIV-1 with CD4+ slopes, plasma viremia, and disease progression in long-term nonprogressors (LTNPs). Nineteen subjects with a long-term nonprogressive HIV-1 infection were studied and followed for 2 years. During the follow-up, in vitro anti-gp160 producers showed negative CD4+ slopes in the majority of cases (9 of 12), whereas 5 of 7 nonproducers showed positive CD4+ slopes. Plasma viremia values, which were not significantly different in the two groups at baseline, became significantly higher in anti-gp160 producers when compared with nonproducers during the follow-up (p = 0.012). Finally, a trend toward progression was observed in the group of producers but not in nonproducers. These findings suggest that the in vitro production of anti-gp160 antibodies by peripheral B cells is not a correlate of protection, and may represent an early predictor of progression in LTNPs.

[AIDS-related pulmonary Kaposi's sarcoma: role of high-resolution computerized tomography]. / Sarcoma di Kaposi polmonare nell'AIDS: ruolo della Tomografia Computerizzata con alta risoluzione.

INTRODUCTION: HIV-related Kaposi sarcoma (KS) is characterized by lesion multifocality, stronger progression and recurrent involvement of some internal organs. Pulmonary lesions are found in 18-47% of cases and not necessarily associated with skin involvement. Lung infections are potentially life-threatening and their early and prompt demonstration is a crucial step for both treatment planning and the prognosis of this severe disease. As a rapid recognition of a pulmonary condition leads to a complete or partial regression in at least 50% of cases, we investigated the role and the diagnostic yield of HRCT in depicting HIV-related KS. MATERIAL AND METHODS: The findings of thirty-nine patients with HIV-related pulmonary KS were retrospectively reviewed. We excluded the patients with associated diseases and incomplete radiologic findings and included 12 patients who had a chest radiograph and a HRCT scanning at least. HRCT showed parenchymal and subpleural micronodules (< 10 mm) and macronodules (> 10 mm), with the halo sign in some cases; perivascular and peribronchial infiltrates, linear or irregular opacities, pleural effusions and enlarged lymph nodes were also seen. Chemotherapy response was also evaluated. RESULTS: All 12 patients had advanced AIDS. The chest films showed abnormal patterns, such as peribronchial and perivascular infiltrates which were most often in midlower pulmonary lobes (88.9%) and often symmetric. Nodules were depicted in 50% of cases and were often associated with peribronchial and perivascular infiltrates; they were always bilateral and characterized by the presence of macronodules in most cases. Eleven of 12 HRCT examinations were considered sufficiently accurate for evaluation, while a pleural effusion prevented lung assessment in one case. Peribronchial and perivascular infiltrates were the most frequent abnormal findings (83.3%), with bilateral involvement in 80% and mostly in the midlower lobes (90%). Parenchymal and subpleural nodules were depicted in 58.3% of cases and always had irregular borders; the halo sign was seen around the nodules in 2 cases and macronodules were found in 2 cases. Pleural effusions were seen in 3 cases and enlarged lymph nodes in 4. Lung KS diagnosis was always confirmed at pathology. The response to chemotherapy (ABV protocol) was evaluated in 5 patients: transient and definitive regressions were observed in 1 and 2 cases, respectively, and disease progression was seen in 2 cases. CONCLUSIONS: HRCT allows the accurate assessment of pulmonary KS in its different stages detailing the disease and its spread, which makes biopsy easier. It also permits to avoid more invasive diagnostic procedures and it is useful in the follow-up after chemotherapy.

Prevalence of hepatitis G virus RNA in human immunodeficiency virus type 1-positive intravenous drug users.

OBJECTIVE: The aim of this study was to evaluate the prevalence of the new human flavivirus hepatitis G virus (HGV) in Italian intravenous drug users (IDUs) and its interaction with human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV). STUDY DESIGN/METHODS: Seventy-nine IDUs with different clinical stages of HIV-1 infection and 20 non-IDU patients with chronic HCV infection were included in the study. HGV RNA was detected by means of reverse transcription-polymerase chain reaction (RT-PCR) used for the amplification of two HGV-related sequences included in the 5'-noncoding (NCR) and NS5a regions. RESULTS: Eighteen (22.8%) of the 79 IDUs were positive for plasma HGV RNA; there was no difference in mean serum alanine aminotransferase (ALT) levels between the HGV-positive and HGV-negative patients. No significant correlation was observed between HGV and other viral markers (hepatitis B virus [HBV], HCV, human T-cell lymphotropic virus type II [HTLV-II]) or HCV genotype. The number of patients with symptomatic HIV-1 infection in whom HGV RNA was detected was significantly lower than the number of those who were asymptomatic (6 of 49 [12.2%] versus 12 of 30 [40%]; P = 0.004). The mean plasma HGV RNA titer was higher in the asymptomatic than in the symptomatic patients (4.6 versus 3.2 log PCR-amplified units in 1 mL of plasma sample [PU/mL]; P = 0.03). CONCLUSIONS: Our results show a considerable spread of HGV levels among Italian HIV-1-positive IDUs and do not indicate that HGV infection enhances liver impairment. We suggest that the greater prevalence of HGV RNA in IDUs with asymptomatic HIV-1 infection may reflect the relatively recent HGV infection in this population.

High prevalence of false-negative anti-HTLV type I/II enzyme-linked immunosorbent assay results in HIV type 1-positive patients.

A high frequency of false-negative anti-HTLV-I/II ELISA results has been reported by several authors. To verify the possible underestimate of the prevalence of HTLV-II infection in subjects infected by HIV-1, we used the PCR to investigate the presence of HTLV DNA in peripheral blood mononuclear cells (PBMCs) collected from a group of 67 HIV-1-positive anti-HTLV-I/II ELISA-negative individuals; the study population included 31 patients with HIV-1-related peripheral neuropathy (PN), 15 with non-Hodgkin lymphoma (NHL), and 23 without PN or NHL. Two subjects had both PN and NHL. All of the patients who were positive at PCR were investigated for the presence of serum anti-HTLV-I/II antibodies by means of Western blot (WB). Eighteen (26.9%) of the 67 anti-HTLV-I/II ELISA-negative patients had HTLV DNA in their PBMCs and WB-detectable serum antibodies directed against one or more HTLV antigens. The individuals affected by predominantly sensory polyneuropathy (PSP) had a significantly higher prevalence of HTLV DNA than the others. All of the patients in whom HTLV-I/HTLV-II discrimination was successful had HTLV-II, with the exception of one patient who was infected by HTLV-I. The present study confirms the possibility of HTLV infection in the absence of ELISA-detectable serum anti-HTLV-I/II antibodies, especially in the particular setting of HIV-1-infected individuals. Moreover, the fact that the prevalence of HTLV DNA was significantly higher in the subjects affected by predominantly sensory polyneuropathy further supports the possibility of an association between HIV-1-related PSP and HTLV-II.

High frequency of non-Hodgkin's lymphoma in patients with HIV-associated Kaposi's sarcoma.

OBJECTIVE: To evaluate, with the support of autopsy findings, the frequency of non-Hodgkin's lymphoma (NHL) among patients with AIDS-associated Kaposi's sarcoma (KS) in comparison with that of AIDS patients with other AIDS-defining diseases. METHODS: The study involved 363 consecutive patients with AIDS who were cared for and died at the Clinic of Infectious Diseases in Milan between May 1984 and December 1992. Clinical records and autopsy data of all of the patients were retrospectively reviewed. Kaplan-Meier product-limit estimates of the time to the development of NHL were calculated for all patients and by specific subgroups. Cox proportional hazards analyses were made to determine the factors associated with the development of NHL. RESULTS: In the majority of cases (82%), KS was diagnosed during life, whereas NHL was diagnosed before death in only 41.6% of cases. Taking the autopsy data into account, the cumulative incidence of the two tumours was 16.8% for KS and 16.5% for NHL. Among the 61 patients in whom KS was the index disease of AIDS, 16 also developed NHL. The probability of developing NHL was significantly higher in patients with KS at AIDS diagnosis than in patients with Pneumocystis carinii pneumonia (PCP), oesophageal candidiasis or other AIDS-related diseases (P = 0.004). Multivariate analysis of the factors associated with the development of NHL (such as sex, age, risk factors, AIDS-defining diseases and CD4+ cell counts) showed that the patients with KS as the index disease of AIDS had a 5.3-fold higher risk of developing NHL than the patients with PCP as the primary manifestation of AIDS. CONCLUSIONS: Our results confirm the higher incidence of malignant lymphoma in patients with AIDS-KS than in patients with other AIDS-related diseases. The importance of autopsy in assessing these data is underlined by the high percentage of NHL diagnosed only after death. These observations may support the hypothesis of a common aetiological agent, or of a common pathway, for the two neoplasms.

The AIDS epidemic.

AIDS epidemic began about 15 years ago; since then, the number of new cases have increased over time. By the end of 1994, 1,025,073 AIDS cases had been reported to the WHO, with a 20% increase in the number of cases since December 1993. As is now evident that the majority of cases occur in developing countries, under-diagnosis, under-reporting and delays in reporting explain the big difference existing between reported and estimated AIDS cases, giving a 4.5 million cumulative AIDS cases worldwide, as of late 1994. In the industrialized countries, the spread of HIV infection began in the late 1970's or early 1980's among homosexual men and IVDU's. Heterosexual transmission was, at first, very limited, though recent data has shown an increase in its diffusion. On the contrary, in Sub-Saharan Africa and the Caribbean, transmission was almost exclusively heterosexual. High rates of infection among young women led to a corresponding increase of perinatal transmission, infecting more than 1.5 million children since the beginning of the pandemic. The estimated number of HIV infections worldwide, as of late 1994, is of 17 millions. Thus, even if some evidence indicates a possible decline of the pandemic in industrialized countries over the next few years, probably because heterosexual transmission was less common, developing countries appear to present an increasing number of HIV infections in young people and, consequently, in children. The real impact of such an epidemic is stressed by the fact that HIV is becoming the leading cause of death among, young people, both in industrialized and developing countries.(ABSTRACT TRUNCATED AT 250 WORDS)

[One-year therapy with dihydroergocristine for treatment of impaired alertness and memory in elderly patients. Placebo-controlled multicenter study]. / Einjährige Therapie mit Dihydroergocristin zur Behandlung von Aufmerksamkeits- und Gedächtnisstörungen bei älteren Patienten. Plazebo-kontrollierte multizentrische Studie.

This double-blind study of dihydroergocristine (DHEC, CAS 17479-19-5) versus placebo was performed in 240 elderly patients affected by chronic cerebrovascular disease or organic brain syndrome. The therapy was carried on for one year. Results pointed out a decrease of SCAG total score and a significant improvement of the target items "confusion, mental alertness and memory performance" after DHEC versus placebo. Furthermore the data show that DHEC maintained its activity throughout the 12-month trial period. Very few and mild side-effects were reported for both groups, thus confirming the well known good safety of the compound. Based on results of this 1-year investigation, it is concluded that DHEC treatment should not be abruptly interrupted, but continued for as long as possible.

Multicenter study on the clinical efficacy of chronic ibopamine administration.

The purpose of this multicenter study was to evaluate the therapeutic efficacy of ibopamine (SB-7505), the 3,4-diisobutyrylester of N-methyldopamine, chronically administered to patients with severe congestive heart failure (CHF) in whom traditional therapy had been ineffective. 55 patients chronically treated with cardiac glycosides and diuretics were assigned to an investigation covering three stages each lasting 7 days. Stage A: continuation of traditional therapy (glycosides and diuretics). Stage B: addition of ibopamine to the glycoside/diuretic therapy. Stage C: withdrawal of ibopamine. Heart rate, blood pressure, body weight, diuresis and 8 target symptoms of CHF (clinical scores) and hematochemical parameters were recorded throughout the three stages. The addition of ibopamine to traditional therapy led to a significant improvement. By contrast, after ibopamine had been withdrawn patients worsened. No hematochemical parameters were modified during the trial. None of the patients experienced any significant side-effects.

[Ocular complications in patients undergoing long-term hemodialysis and renal transplants from cadavers]. / Le complicanze oculari nel paziente sottoposto ad emodialisi cronica e trapianto renale da cadavere.

In 36 subjects in chronic hemodialysis treatment and in 36 patients with a renal transplant, well functioning for more than one year, the ocular complications related to the specific form of treatment were evaluated and compared. In the group of the dialyzed subjects ocular pathology was composed by: lens opacities in 9 cases, corneal calcifications in 7 cases, hypertensive fundus in 8 cases. In no patient these lesions produced measurable visus reductions. In the transplant group ocular pathology was composed by: lens opacities in 28 patients, hypertensive fundus in 7 and intraocular hypertension in one. One case of herpes cheratytis and one case of endophtalmytis have also been observed. In 9 patients these lesions produced a remarkable visus reduction. In conclusion renal transplantation shows a greater incidence of ocular complications if compared to hemodialysis. This situation has not important consequences on the rehabilitation of the transplanted subject for the possibility of surgical correction of the cataract.

[Plasma and intra-erythrocyte variations in acid-base equilibrium in acute acidosis due to acetazolamide loading]. / Le variazioni plasmatiche ed intraeritrocitarie dell'quilibrio acido-base in corso di acidosi acuta da carico di acetazolamide.

Plasma and red cell acid-base equilibrium was studied in 14 healthy subjects following the induction of acidosis by means of i.v. acetazolamide. It was found that changes in red cell values were significantly less marked than those in plasma.

[Acid-base equilibrium changes associated with acute pulmonary edema. Intra-erythrocytic findings and comparison with plasma values]. / Variazioni dell'equilibrio acido-base associate all'edema polmonare acuto. Rilevazioni intra-eritrocitarie e confronto con i valori plasmatici.

A study was made of intra-erythrocyte acid-base balance in 7 subjects with metabolic and 3 with mixed acidosis in the course of acute haemodynamic pulmonary oedema. Comparison with plasma values showed that, in metabolic acidosis, the buffers (bicarbonate) are evenly involved in the maintenance of hydrogen ion balance, whereas in mixed forms a greater demand is made on non-bicarbonate bases. Examination of this phenomenon and its quantitative evaluation are geared to intra-erythrocyte determinations of the acid-base balance, particularly to the very important B.E. index.

Is there a real treatment for stroke? Clinical and statistical comparison of different treatments in 300 patients.

In the absence of universally accepted criteria for the medical treatment of stroke, we made a rigorously randomized comparative study of different treatments in 300 patients. One group of patients received only a general supportive treatment designed to ensure adequate supplies of water, electrolytes and calories, plus whatever was needed to prevent infection and correct extant associated pathology. Three other groups of patients were treated in the same way but were also given, respectively, one of the following medications: Hydergine (Sandoz) (a mixture of three ergot alkaloids), dexamethasone, and mannitol. No statistically significant difference emerged among any of the treatment groups and the reference group in terms of objective therapeutic results. The authors concluded that, at least with the dosage used in this study, none of the treatments proved more useful than conventional supportive therapy in the first 10 days after a stroke.