AIDS-associated cryptococcosis: a comparison of epidemiology, clinical features and outcome in the pre- and post-HAART eras. Experience of a single centre in Italy.

Objectives To assess the prevalence, clinical and immunological characteristics, risk factors and survival of patients with AIDS-related cryptococcosis in the era of highly active antiretroviral therapy (HAART). Methods All newly diagnosed cryptococcosis cases identified retrospectively from among a series of AIDS patients hospitalized consecutively at a single institution in Italy in 1985-1996 (pre-HAART period, n=165) and 1997-2006 (post-HAART period, n=40) were analysed comparatively. Results The prevalence of cryptococcosis decreased from 4.7% (165/3543) to 2.2% (40/1805) between the pre- and post-HAART periods (P=0.0001). There were no differences in the clinical features or immunological status of the patients between the two cohorts. The variables associated with the occurrence of cryptococcosis in the post-HAART era were older age (P<0.001), no previous diagnosis of HIV infection (P<0.001) and infection in homosexual males (P=0.004). During the post-HAART period, immune reconstitution inflammatory syndrome associated with cryptococcosis was observed in five patients (19.3%) a median of 15 weeks after the start of HAART. Thirty-day survival (P=0.045) and overall survival (P=0.0001) were significantly better among patients diagnosed with cryptococcosis in the post-HAART compared to those diagnosed in the pre-HAART era. Conclusions The AIDS-associated cryptococcosis observed in Western countries in the HAART era has similar clinical and immunological characteristics to that observed in the pre-HAART era, but a significantly better outcome.

Vinorelbine is an effective and safe drug for AIDS-related Kaposi's sarcoma: results of a phase II study.

PURPOSE: To assess the safety and efficacy of vinorelbine in patients with AIDS-related Kaposi's sarcoma (KS). PATIENTS AND METHODS: From December 1994 to May 1997, within the Italian Cooperative Group on AIDS and Tumors, we enrolled 36 patients with AIDS-related KS who experienced disease progression after one or more regimens of systemic chemotherapy. Patients were treated with vinorelbine 30 mg/m(2) every 2 weeks by intravenous bolus. RESULTS: Of 35 assessable patients, three (9%) had a clinical complete response and 12 (34%) had a partial remission, for an overall objective response rate of 43% (95% confidence interval, 26% to 61%). For the 15 patients with objective responses, the median duration of response from the beginning of therapy until the development of progression was 176 days, whereas the median progression-free survival and the median survival durations for 35 assessable patients were 151 days and 216 days, respectively. Vinorelbine also induced responses in patients who had become resistant to regimens that included other vinca alkaloids. Overall, vinorelbine was well tolerated. Toxicity, including neurologic toxicity, was mild and reversible. Neutropenia was the most frequent dose-limiting toxicity. CONCLUSION: Vinorelbine is safe and effective in the treatment of patients with advanced KS who have been previously treated with one or more chemotherapy regimens.

Role of brain biopsy in the management of focal brain lesions in HIV-infected patients. Gruppo Italiano Cooperativo AIDS & Tumori.

In this multicenter, retrospective study of 160 brain biopsies in the assessment of HIV-related focal brain lesions, diagnostic sensitivity was acceptable (87%), but the procedure carried considerable morbidity (7.5%) and mortality (3.1%). Moreover, it is not always possible to initiate the changes in therapy indicated by the results, and overall survival remains poor, with a median of 2 months. Criteria for brain biopsy for the diagnosis of focal brain lesions should be redefined to include selected patients for whom a less invasive approach does not yield a definitive diagnosis.

A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. II-Subjective and objective measures of effects. An international comparative trial.

Comparative clinical trials of 2 sizes of contraceptive vaginal rings and of an oral contraceptive were undertaken at 8 investigational sites (9 clinics). More than 500 women enrolled on each of the 3 study regimens. Side effects of the rings and of Nordette, the oral contraceptive, were evaluated by noting spontaneous complaints, by recording medications taken and by physical examination. Inquiries about changes in the frequency of specific conditions were made at the end of the subjects participation in the first year of the study. The incidence of spontaneous complaints was similar among users of the 2 different-sized rings and of the pill.

A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. III-Menstrual patterns. An international comparative trial.

Menstrual events among users of contraceptive vaginal rings (CVRs), releasing levonorgestrel and estradiol, were studied in comparison with a combined oral contraceptive, Nordette, in multicentered trials. CVRs were made with outside diameters of 50 and 58 mm and released about 250 micrograms and 290 microgram of levonorgestrel and 150 microgram and 180 microgram of estradiol per day, respectively. The CVRs were used continuously for 3 weeks and then removed for 1 week. Both the CVRs and Nordette were perceived to reduce menstrual flow and days of menstrual bleeding. Twenty to 25% of CVR users perceived increased intermenstrual bleeding or spotting. Diaries indicate, however, that on average, CVR users experienced about 1 day per month of bleeding or spotting with the ring in place. CVRs and Nordette produced approximately the same total number of bleeding and spotting days during 6 cycles of use, 27-29, but the small (50-mm OD) ring was associated with somewhat more spotting. This ring was also associated with somewhat more prolonged bleeding and spotting runs and with more prolonged nonbleeding intervals than reported by users of the larger (58-mm OD) ring or of Nordette. Differences among regimens, however, tended to be small even when statistically significant. Evidence from menstrual diaries indicates that these CVRs, and in particular 58-mm ring, provide control over the menstrual cycle comparable to the Nordette.

A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. I-Use effectiveness. An international comparative trial.

PIP: Contraceptive vaginal rings (CVRs), with approximate daily release rates of 250-290 mcg of levonorgestrel and 150-180 mcg of estradiol and manufactured in a shell design, were studied for effectiveness and acceptability in multicentered trials involving 1103 ring users in Brazil, Chile, Dominican Republic, Sweden, U.S., Denmark/Finland, and Nigeria. A comparison group of 533 women used the oral contraceptive Nordette. Both 1st and all segment 1 year gross pregnancy rates among CVR users were less than 3/100, rates similar to Nordette users. Continuation at 1 year was 50/100 users of the ring (all segments) and 38/100 among Nordette users, more of whom were lost to follow-up. Gross 1 year rates of termination for medical reasons ranged from 25-29/100. Ring users were more likely to terminate for vaginal problems and pill users for headache, nausea, and associated reasons. These trials indicate that CVRs of this design are as effective and have continuation rates equal to and possibly superior to Nordette under the same study conditions.^ieng

[Seroepidemiologic survey of the spread of rotavirus infection in a Milan population]. / Indagine sieroepidemiologica sulla diffusione dell'infezione da rotavirus nella popolazione milanese.

The increasing evidence of involvement of Rotaviruses in the etiology of viral gastroenteritis prompted us to carry on a seroepidemiological survey on the population of Milan. The aim was to get informations on the extension of the circulation of these agents in our population. Utilising a commercial antigen prepared with the "Oslo" bovine strain, c.f.a. were titrated in sera from 575 healthy subjects (age 0 to > 60 years). Of them 232 were children under 4 years of age homogeneously distributed into 6 age classes: at birth, 1 day to 3 months, 4-6 months, 7-12 months, 13-24 months, 2-4 years. Rotavirus infection appears very common. About 80% of the subjects over 10 years have c.f.a. As it is shown by the sharp increase of antibody acquisition after an initial drop in the first 6 months (82% positive at birth and 41% between 4-6 months), the infection seems to occur very early in life, as much as the plateau is reached under 10 years of age. Moreover consistent antibody titers (greater than or equal to 1:32), which could indicate recent infection, first appear in babies 4 to 12 months of age. Such titres are absent in the adults and could be found again in people over 50. Positivity was significantly higher in females than in males (0.01 < P < 0.025). Transplacental c.f.a. passage was studied in paired sera of 37 women at delivery and in cord blood sera of their babies; 28 matched pairs of sera had coincidental titres, but there were additional three cord blood specimens with c.f.a. from newborns whose mothers were negative.

[Role of the virologic laboratory in the diagnosis of subacute sclerosing panencephalitis. Report of 12 cases studied between May, 1977 and March, 1978]. / Il ruolo del laboratorio virologico nella diagnosi della PESS. Osservazioni su 12 casi studiati tra il maggio 1977 ed il marzo 1978.

Measles h.i.a. and c.f.a. were titrated in serum and cerebrospinal fluid of 12 SSPE patients. Specific IgM h.i.a. in the same specimens were also determined. Pretreatment of the sera by monkey red blood cell absorption, by kaolin or by heparin MnCl2, did not significantly affect h.i.a. titres, but h.i.a. were no more demonstrable in cerebrospinal fluids after kaolin and titres were somewhat lowered by heparin-MnCl2 treatment. By both h.i. and c.f. tests measles antibody were found at much higher titres in sera of SSPE patients than in controls of the same age. H.i.a. and, with one exception, c.f.a. were found in each of the 9 available cerebrospinal fluids from patients, but in none of the 6 specimens from non-SSPE cases. Ratio GM titers h.i.a. over GM titers c.f.a. in sera of SSPE patients was about 1, a value far from that found under different immunization conditions. In control sera, for instance, the ratio was 5.3. Specific IgM were never found in the cerebrospinal fluids and in only 2 out of the 10 sera examined.

[Serum and cerebrospinal fluid antibodies against measles virus in patients with multiple sclerosis]. / Anticorpi sierici e liquorali verso il virus del morbillo in pazienti affetti da sclerosi multipla.

Measles c.f.a. and h.i.e. were titrated in sera and, when possible, in the cerebrospinal fluids of 183 SM patients and in sera from a control group of subjects. No significative difference was found by the h.i. test, whereas significantly higher was the frequence of positives by the c.f. test in the SM group, with no correlation with the therapy to which the patients were subjected. The presence of c.f.a. in 13 of 48 cerebrospinal fluids tested, together with a low value of the serum/CSF antibodies ratio and with the lack of CSF antibodies against other viral antigens tested (HSV, rubeola), could indicate an intra CNS production of measles antibodies. To sum up, our results suggest an involvement of measles virus at least in some of the MS patients considered.

[Serologic survey of human type A influenza virus infection following 10-year periods of prevalence of H3N2 strains]. / Ricapitolazione sierologica delle passate infezioni con virus influenzali di tipo A dopo circa un decennio di prevalenza degli stipiti H3N2.

Distribution of h.i.a. against A/New Jersey/8/76 (Hsw1N1), A/PR/8/34 (H0N1), A/FM/1/47 (H1N1), A/Japan/305/57 (H2N2) influenza virus strains was determined in 553 serum samples, previously tested for A/Hong Kong/1/68 virus, collected in the late summer of 1977 in Milan and Bari. For all variants, distinctive antibody patterns were obtained which reflect periods of prevalence of these viruses in man. So, the peak of positivity and the higher h.i.a. levels were found for A/New Jersey/8/76 strain in subjects born between 1907 and 1916, in the case of A/PR/8/34 virus for the birth years 1927-36, ten years later (1937-46) for A/FM/1/47 strain and for A/Japan/305/57 and A/Hong Kong/1/68 variants respectively for the birth years 1947-56 and 1962-66. The presence of antibodies to influenza A viruses not supposed to have been current during the person's lifetime has been discussed.

Measles antibodies in multiple sclerosis patients.

The Authors have assayed in this work the antimeasles antibodies in serum and CSF in subject affected by M.S. and controls. The M.S. patients have been subdivided in two groups with and without immunosuppressive therapy. In 27% out of 48 patients production intrathecal antimeasles antibodies was demonstrated.

Non-Hodgkin's lymphoma and AIDS: frequency of gastrointestinal involvement in a large Italian series.

Even though the close association between AIDS and non-Hodgkin's lymphoma (NHL) is widely known, few studies have evaluated the frequency of gastrointestinal involvement in a large series of AIDS patients with heterogeneous risk factors. We therefore reviewed the demographic and clinical features of patients with AIDS and NHL seen at our institution over a period of 5 years. NHLs complicated AIDS in 70 of 786 (9%) cases in our study. All but one of the tumours were of high- or intermediate-grade histologic subtype, and 80% of 56 patients with diagnosis made during lifetime had disease stages III or IV, most with extranodal localization. The gastrointestinal tract was involved in 23 cases (33%), 13 of whom had an antemortem diagnosis. All these patients complained of significant symptoms, the most frequent being GI bleeding followed by recurrent abdominal pain with or without masses. Three patients had evidence of lymphomatous disease along both the upper and lower GI tract, but more often a single localization was present. Prognosis of patients with NHLs was very poor, and there was no significant difference in survival between patients with and without GI localization at the time of initial diagnosis.

Contraceptive choice in an urban clinic in Nigeria.

PIP: Contraceptive choice in the 1st 1075 acceptors at an urban clinic in Lagos, Nigeria is studied using clinical notes of all patients who attended the clinic between September 1, 1980 and August 31, 1983. Details of previous and current contraception, age, parity and level of education are analyzed. The IUD was the most popular choice followed by the injectable contraceptive and the pill. Interval tubal ligation was chosen by some patients. Acceptors of injectables were older women of high parity and lower educational standard while pill acceptors were of lower parity and higher educational level. The IUD was acceptable to all ages and parities except those with only 1 child or none. Loss to follow-up and the wish to plan another pregnancy were the commonest reasons for discontinuing contraception. Medical reasons for discontinuing the IUD were pain, menstrual disorder, accidental pregnancy and expulsion/perforation; for discontinuing injectables the reasons were menstrual disorder, accidental pregnancy and raised blood pressure. Of acceptors of the 3 main methods, former pill and IUD users were more likely to choose the same method again. A strategy should be devised to encourage patients of lower parities and age to use contraceptives, while sterilization in patients of parity 3 and above should be even more actively advocated. Greater effort should be made to support patients through the 1st 6 months after starting any method as this is the time when a large number of discontinuations occur.^ieng

Lipid-based amphotericin B in the treatment of cryptococcosis.

Amphotericin B is the only antifungal drug which, despite its dose-limiting toxicity, can be given intravenously when an aggressive treatment is required. In an attempt to reduce the drug toxicity while retaining its therapeutic efficacy, new formulations of amphotericin B have been developed. The most promising have employed lipid vehicles such as liposomes. Three lipid-based amphotericin B formulations have been developed by pharmaceutical companies and are under active clinical investigation. Efficacy and safety data of these derivatives in animals and humans are reviewed, with particular concern to cryptococcal infection. The authors' experience with a small unilamellar liposomal amphotericin B formulation, AmBisome, in the primary therapy of cryptococcosis is reported. Nine AIDS patients affected with cryptococcosis, seven of whom had meningitis, were given AmBisome (3 mg/kg/day) for 3-6 weeks. Complete response was obtained in six patients, marked improvement in two, and failure in one. AmBisome was well tolerated and shortened the time to clinical and mycological response suggesting a further improvement in the management of cryptococcosis in AIDS patients.

Severe abdominal pain in patients with AIDS: frequency, clinical aspects, causes, and outcome.

BACKGROUND: The exact prevalence of abdominal pain in AIDS patients, as well as the entire spectrum of causative disorders, has not yet been well defined. In addition, the existing data derive almost exclusively from surgical series describing only those patients who have undergone emergency surgical procedures. METHODS: We reviewed our experience with patients presenting with severe abdominal pain from a large series of non-selected consecutive AIDS patients seen at our institution over a period of 4 years. RESULTS: Of 458 patients, 71 (15%) had severe abdominal pain, and its occurrence was associated with a reduced patient survival. Specific diagnoses were made premortem in 42 patients (59%), potential causes of pain were identified at postmortem examination in 23 patients (33%), whereas no specific causes were found in 6 patients (8%). Most of the causative disorders (65%) were AIDS-related, whereas HIV-independent pathologic conditions were found in only 18% of the patients. The predominant site of pain, combined with a few key symptoms, had a high predictive diagnostic value in nearly half of the patients. The indications for emergency laparotomy were limited and substantially similar to those of the non-HIV population. CONCLUSIONS: Severe abdominal pain frequently complicates the course of AIDS, and its occurrence is associated with reduced survival. In most patients it is due to disorders closely associated with the HIV infection. Specific causes of pain may be identified in most of the cases by an appropriate diagnostic evaluation.

Long-term remission of Kaposi sarcoma-associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy.

Kaposi sarcoma-associated herpesvirus (KSHV)-related multicentric Castleman disease (MCD) is potentially lethal. Growing evidence indicates that, as in Epstein-Barr virus-driven lymphoproliferative disorders after transplantation, KSHV DNA burden in peripheral blood mononuclear cells (PBMCs) may represent the most accurate marker of disease activity. This report describes a patient with human immunodeficiency virus who was followed up clinically and by quantitative polymerase chain reaction for KSHV DNA sequences in PBMCs for more than 3 years following the diagnosis of KSHV-related MCD. Therapy with the antiherpesvirus agent cidofovir, antihuman interleukin-6 antibody BE-8, antiblastic chemotherapy, and combination antiretroviral agents did not achieve durable clinical or virologic remission of the disease. By contrast, administration of the anti-CD20 monoclonal antibody rituximab was well tolerated and allowed a 14-month remission of clinical symptoms and KSHV viremia. Rituximab should be added to the therapeutic armamentarium for KSHV-related MCD.