Perinatal transmission and manifestation of hepatitis C virus infection in a high risk population.

We studied the perinatal transmission of hepatitis C virus (HCV) in 70 high risk mother/infant pairs. Seventy-six percent of the mothers (53 of 70) were coinfected with human immunodeficiency virus (HIV) and 79% (55 of 70) had a history of drug addiction. During the follow-up HCV RNA was detected in 14 of 70 (20%) infants: 12% (2 of 17) in infants born to HIV-negative mothers; and 23% (12 of 53) in infants to HIV-positive mothers. The rate of vertical transmission was significantly higher in vaginally delivered infants than in those delivered by cesarean section (32% vs. 6%; P < 0.05). All 56 uninfected infants lost passively acquired anti-HCV by age 9 +/- 4 months and only 2 of 56 infants (4%) had evidence of HIV infection. Four of 14 HCV RNA-positive infants (29%) had evidence of HIV coinfection. We observed 3 clinical patterns of HCV infection: a transient viremia in 2 infants; an acute pattern in 2 infants; and a chronic pattern in 10 infants. All 4 HIV-coinfected infants had chronic HCV infection. All infants with a chronic pattern, had increased alanine aminotransferase values for more than 6 months and 5 had a liver biopsy that showed signs of chronic persistent hepatitis. HCV perinatal transmission was more frequent in infants born to HIV-coinfected mothers than in infants born to HIV-noninfected women, particularly when delivered vaginally.

Cytocidal and filamentous response of Escherichia coli cells exposed to low concentrations of hydrogen peroxide and hydroxyl radical scavengers.

The hydroxyl radical scavengers thiourea, ethanol, and dimethyl sulfoxide significantly reduced the killing of Escherichia coli elicited by low concentrations of H2O2 (resulting in mode 1 killing) when treatments with the oxidant and the scavengers were performed in a complete growth medium (K medium) but not in M9 salts. In addition, thiourea efficiently prevented the toxic response to high concentrations of H2O2 (resulting in mode 2 killing) under both exposure conditions. Sod A cells, which do not respond with a bimodal pattern of toxicity when challenged with increasing concentrations of H2O2, were markedly protected by thiourea against the lethal action of various levels of the oxidant (which in the wild-type strain result in either mode 1 or mode 2 killing) under conditions of treatments in both K medium and M9 salts. In some experiments, wild-type cells were challenged with a low concentration of H2O2 (in the absence or presence of hydroxyl radical scavengers) and then postincubated in fresh K medium for various time intervals. It was found that scavengers were able to inhibit the filamentous response generated by exposure to the oxidant in K medium. Both the length and the number of filaments were markedly reduced. Treatment in M9 salts resulted in a limited number of very short filaments, and this response was slightly reduced by the scavengers.

Efficacy of macrolides used in combination with ethambutol, with or without other drugs, against Mycobacterium avium within human macrophages.

The activities of clarithromycin or roxithromicin used in combination with other antimicrobial drugs were tested in human macrophages experimentally infected with 23 strains of Mycobacterium avium. Overall, clarithromycin-ethambutol-rifampicin was the most active combination tested. The reduction in intracellular viable bacilli was found to be more than 1 log(10) for 95% and more than 2 logs(10) for 65% of the strains. The second most active combination was roxithromycin-ethambutol-rifampicin, which was found to be bactericidal for about 80% and highly bactericidal for 20% of the strains. Others combinations were only bacteriostatic or weakly bactericidal for many of the strains. The addition of a third drug did not necessarily promote enhanced bacterial killing inside the macrophage.

Cancer pain knowledge in Southern Italy: data from a postgraduate refresher course.

A survey of Italian physicians was conducted to assess knowledge, attitudes, and beliefs on cancer pain. Physicians attending a refresher course on cancer pain and symptom relief were given a questionnaire composed of 28 questions before starting the lectures. The physicians represented the different centers treating cancer pain, or were going to deal with cancer pain, and were from all the provinces of Sicily, a southern region of Italy. Insufficient knowledge and education of the physicians regarding the management of cancer pain was evidenced. Limited experience may be the principal reason. Most participants had difficulties in prescribing opioids (23%). Analgesics were frequently administered intramuscularly (46%), although the oral route was suggested by 86% of the physicians as the route of choice for opioids. Opioids were used in more than 75% of the patients by only 33% of the physicians. Opioid treatment was considered effective in more than 75% of the patients by only 63% of the physicians. An arbitrary maximum dose of opioids was reported by 35% of the respondents. Opioid spinal administration was mainly considered the most effective route, the first-choice route to start opioid therapy by 4% of the physicians, and the alternative route to the oral one in 29% of cases. Nausea and vomiting, and tolerance were considered the principal problem during opioid therapy. Antidepressants were the most common adjuvants associated with opioid therapy, and laxatives and antiemetics were frequently used to limit the side effects. Incident pain was rarely reported as a challenging pain syndrome. Examples of cancer pain syndromes were mainly reported correctly, although some definitions were disputable. Inadequate knowledge about cancer pain management limits appropriate treatment. Greater efforts should be made to improve medical education.

Dextropropoxyphene versus morphine in opioid-naive cancer patients with pain.

The role of opioids for moderate pain (so-called "weak" opioids) in the second step of the World Health Organization's analgesic ladder has been investigated in a prospective randomized study. Sixteen patients were administered dextropropoxyphene (DPP) in a dosage ranging from 120 mg to 240 mg daily (group 1), and 16 patients were administered the lowest doses (20 mg daily) of commercially available controlled-release morphine (group 2). Equianalgesic doses of oral morphine, pain relief, and symptoms during the first 10 days of therapy and during the last 4 weeks before death were assessed. Three of 16 patients maintained DPP until death, whereas three patients in group 2 were switched to DPP due to the occurrence of intolerable side effects. Intensity and frequency of nausea and vomiting, drowsiness, and dry mouth were higher in group 2 than in group 1 during the initial treatment. These results stress the role of "weak" opioids during the induction of opioid therapy in opioid-naive cancer patients.

Monitoring of opioid therapy in advanced cancer pain patients.

Until now, there have not been any parameters to monitor opioid therapy in cancer patients with pain. In this study, 325 consecutive advanced cancer patients were scheduled for a prospective longitudinal survey. After exclusions, 67 patients were surveyed. All included patients were advanced cancer patients with pain that required opioid therapy for more than 6 weeks before death. Opioid escalation, symptoms associated with opioid therapy, pain mechanism, and pain intensity were recorded. Indices were calculated to categorize the response to opioids. The opioid escalation index (OEI) was used to index the mean increase of the starting opioid dosage, expressed as a percentage or in mg. The length of the period of stable dose (MLD) and the effective analgesic score (EAS), that is, the analgesic consumption/pain relief ratio calculated at fixed intervals, were also used. Patients with a mean visual analogue scale score (VAS) of less than 4 and regular OEI and EAS were considered responsive; patients with a mean VAS less than 4 but with an OEI more than 5 or increases of more than 100% of EAS when compared to that calculated the week before were considered mildly responsive; and patients with a mean VAS more than 4 were considered unresponsive. Advanced age, female gender, and previous chemotherapy were all factors reducing OEI. Head and neck cancer was associated with a higher OEI. Regarding the influence of the opioid-related symptoms, an increased OEI was associated with the presence of confusion. Moreover the presence of confusion was associated with neuropathic pain. Neuropathic pain taken alone, however, did not influence this score. Gender-specific cancer, such as breast cancer, influenced the gender differences reported for MLD (significantly longer than that reported for males and other primary tumor). Good responsiveness was observed in 28 patients, partial responsiveness in 33 patients, unresponsiveness in six patients. Psychological factors were associated with poor pain relief, probably reducing the patient's compliance. The tools used in this study may be useful in monitoring the effects of opioid therapy in cancer pain patients. Simple numbers are easy to compare and make it possible to profile opioid responsiveness and differences among patients.

Home palliative care: results in 1991 versus 1988.

Home care is greatly expanding because of the savings it offers by avoiding unnecessary hospitalization and also because patients benefit from being in their own home environments. Since 1988, Societa Assistenza Malato Oncologico Terminale (SAMOT) has organized a pain relief and home palliative care unit for terminal cancer patients. Objectives, difficulties, protocols, and achievements of 4 years of experience were examined, and the findings of the various years were compared. Our results suggest that considerable progress has been made in home palliative care. There are still social and cultural difficulties to overcome, however.

In vitro toxicity and metabolism of 2',3'-dideoxycytidine, an inhibitor of human immunodeficiency virus infectivity.

U937 human monoblastoid cell growth was inhibited in a concentration-dependent manner by 2',3'-dideoxycytidine (ddCyd) (an antiretroviral drug) up to 500 microM. Cell growth inhibition was associated with a pronounced increase in cell volume, however this was not due to cell ATP or NAD+ depletion that could effect osmotic balance or DNA repair. This ddCyd toxicity paralleled the accumulation of ddCyd into acid soluble material where 2',3'-dideoxycytidine-5'-triphosphate (ddCTP) was the predominant labelled nucleotide up to an extracellular ddCyd concentration of 150 microM. At higher ddCyd concentrations, the amount of 2',3'-dideoxycytidine-5'-diphosphate (ddCDP) became predominant over ddCTP. This increase of phosphorylated dideoxycytidine in U937 cells was also associated with an increased incorporation of the drug into cell DNA suggesting a possible toxicity mechanism. That ddCyd does indeed become cytotoxic to human cell by incorporation into DNA was shown by incubating human resting and stimulated lymphocytes with ddCyd. While the drug does not affect cell viability in resting cells it strongly affects cell proliferation upon phytohemagglutinin (PHA) addition.

The effect of temperature or anoxia on Escherichia coli killing induced by hydrogen peroxide.

The cytotoxicity of hydrogen peroxide in Escherichia coli was investigated after various conditions of drug exposure. Two modes of killing were detected following a 15-min challenge with H2O2 under either aerated or anoxic conditions. Mode one killing occurred at levels below 2.5 mM and mode two killing at concentrations higher than 10 mM. Whereas mode one killing was similar at the two conditions of drug exposure, mode two lethality differed in that aerated cells were more sensitive than anoxic cells. Independently of O2 tension the hydroxyl radical scavenger, thiourea, prevented mode two but not mode one killing by H2O2. Cells treated with the drug at ice temperature did not display mode one killing and mode two lethality occurred only at very high concentrations. We suggest that hydroxyl radicals mediate mode two but not mode one killing by H2O2.

Comparison of colloidal bismuth subcitrate and metronidazole, both in combination with an H2-antagonist as therapy for Helicobacter pylori.

In this random study, the efficacy of either colloidal bismuth subcitrate (CBS) or metronidazole in combination with an H2-antagonist in the treatment of various gastric pathologies was evaluated, along with the trends in antibody levels. Among the 40 Helicobacter pylori-positive patients with various gastroduodenal pathologies who underwent chemotherapy, 27 were treated with CBS and 13 with metronidazole. H. pylori was eradicated in 48.14% of the patients treated with CBS and 53.8% of those treated with metronidazole. After therapy, no statistically significant or slight decrease in the serum levels of antibodies was found.

A circular diagram for representing symptom status in advanced cancer patients.

Symptom relief is the major goal of palliative care. Its assessment is essential and several methods have been described. To evaluate immediately the clinical situation, a circular diagram for a visual representation of the physical symptoms is proposed. Particular patterns derived from the given data emerge from the diagrams. Certain critical situations often observed in palliative care, especially in the last weeks of life, show specific patterns that are easily distinguished. Effective treatments may change the appearance of different pictures.

Molecular mechanisms of hydrogen peroxide cytotoxicity.

The molecular mechanisms of H2O2 toxicity have been investigated in both mammalian or bacterial cells. DNA breakage mediates cytotoxicity by low concentrations of H2O2 in mammalian cells, but DNA lesions do not appear as a direct consequence of the action of the hydroxyl radical; rather, these radicals may disturb intracellular Ca2+ homeostasis, which results in secondary reactions ultimately leading to DNA strand breakage and cytotoxicity. Studies that have used Escherichia coli (E. coli) as a cellular system have indicated that the two modes of killing detectable in cells exposed to increasing concentrations of H2O2 are mediated by different radical species. Mode-one killing seems to be produced by the superoxide anion whereas mode-two killing seems to be a consequence of the hydroxyl radical attack.

Salmonellosis diagnosed by the laboratory of the 'L. Sacco' Hospital of Milan (Italy) in patients with HIV disease.

We reviewed the cases of typhoid fever (3 cases) and non-typhoid salmonellosis (62 cases) diagnosed from 1987 to 1989 in the Laboratory of Clinical Chemistry and Microbiology of the 'L.Sacco' Hospital, Milan. Two cases of typhoid fever and 24 cases of non-typhoid salmonellosis occurred in patients without clinical symptoms of HIV infection. One case of typhoid fever and 38 cases of non-typhoid salmonellosis occurred in patients with clinical symptoms of HIV infection. In AIDS patients living in the Milan province the annual incidence of non-typhoid salmonellosis was estimated to be 100-fold greater than that observed in the general population. In patients with non-typhoid salmonellosis, bacteremias was found only in subjects with HIV disease (P = 0.0009). The frequency of bacteremia was higher in patients with AIDS than in patients with other manifestations of HIV disease (P = 0.0356). Finally, a significant difference between patients with and without HIV disease was found with regard to Salmonella serotypes distribution (P = 0.0196).

[Normal spirometric values in the Sicilian population]. / Valori spirometrici "normali" nella popolazione siciliana.

Principal spirometric parameters have been measured in a sample group of 1641 male subjects. Due to the significant difference in values often found when using the standards proposed by CECA (1983) (particularly in the medico-legal field) in order to obtain reference values as close as possible to the local norm the chosen subjects are clinically and functionally healthy and come from different parts of Sicily. The regression plots obtained using three independent variables (age, weight, height) other than demonstrating a good affinity with the original sample and an elevated predictivity level, underline the difference between obtained reference values and European ones (higher for VC and FEV 1; lower for FRC and RV) even though evolutive trend and ageing overlap. The above mentioned difference, found also for some parameters (VC and FEV 1) using normal Italian standards can be explained; not only by different evaluations of normal conditions, respiratory risk, smoking etc., but also by the existence of a different ethnic constitution which influences in various ways the ventilatory parameters.

Role of free radicals produced during the metabolism of mitomycin C in Escherichia coli inactivation.

1. The primary objective of this study was to assess whether reactive oxygen species produced during the metabolism of mitomycin C are responsible for, or contribute to, the induction of the cytotoxic response. 2. Escherichia coli wild-type and superoxide dismutase mutants were grown either anoxically or euoxically, in K medium or minimal glucose medium, and treated with mitomycin C in K medium or M9 salts. The cytotoxic response did not vary significantly between the wild-type and the SOD mutants. 3. The toxicity of mitomycin C was not affected by the hydroxyl radical scavengers, dimethyl sulphoxide or ethanol, whereas protection was afforded by thiourea. 4. It is concluded that oxygen radical species do not play a significant role in mediating mitomycin C inactivation of normally growing bacteria.

[Antibodies against the 15 amino acid sequence 599-613 of HIV-1 glycoprotein 41 in subjects at risk of HIV infection]. / Anticorpi contro la sequenza aminoacida 599-613 della glicoproteina 41 dell'HIV 1 in soggetti a rischio di infezione per il virus.

A peptide (called A-15) composed of 15 amino acids of the gp41 (from position 599 to position 613 of the sequence encoded by the env gene) of HIV-1 has been used as an antigen to search for antibodies in 347 sera of at-risk for HIV-1 infection subjects. The purpose was of comparing the prevalence of these antibodies with that of HIV-1 total EIA antibodies and HIV-1 immunoblotting antibodies. Assuming immunoblotting test as reference test for detecting a HIV-1 infection, the antibodies against peptide A-15 show the same sensitivity and specificity when compared with other HIV-1 total EIA antibodies tests.

Presence of enteroviruses and reoviruses in the waters of the Italian coast of the Adriatic Sea.

EEC directive 76/160 requires member states to apply microbiological and chemico-physical standards for the quality of recreational waters. In observation of this regulation, in the present study 144 samples of seawater were taken over a 12-month period and tested to determine viral contamination. The samples were collected from the coastal waters of the Italian town of Pesaro, which is located on the Adriatic Sea. Using cell culture techniques, 32.6% of the seawater samples were found to be contaminated with enteroviruses. Isolation of these viruses was most frequent in the summer months. Thus, our results indicate the need to increase the frequency of monitoring of these waters and to eliminate the sources of contamination.

Diffusion of thermophilic Campylobacter in the Pesaro-Urbino area (Italy) from 1985 to 1992.

The results of research on the spreading of campylobacter in the Pesaro-Urbino area carried out from 1985 to 1992 are presented. Materials of different origin were examined: 822 samples of human faeces, 533 animal rectal swabs, 192 samples of domestic sewage, 48 of river water, 96 of sea water and 632 of various types of food. Two hundred and nine strains of campylobacter were isolated (9%), most of which were Campylobacter jejuni (80%), with particular frequency in food products (chicken carcass 45.7%, ground meat and sausage 18.1%) and in river water (31.3%). In contrast, the samples of sea water and dairy cheese products were always negative. It may be concluded that the spreading of campylobacter in the Pesaro-Urbino area is mainly associated with food products of animal origin. Therefore, better controls in the processing of these products may be necessary.

Antipoliomyelitis immunity status in a cohort of young men drafted into military service, residing in the suburban Milan area.

The aim of this study was to verify the antipolio immune status of a cohort of eighteen year-olds residing in the suburban Milan area for whom vaccination histories were available. Seropositivity (titres of neutralizing antibodies > or = 1:8) for the three virus serotypes was detected in 89.2% of the 530 subjects tested, whereas simultaneous seronegativity for all three polioviruses was found for only 0.6% of the subjects.