A canarypox vector-expressing cytomegalovirus (CMV) phosphoprotein 65 induces long-lasting cytotoxic T cell responses in human CMV-seronegative subjects.

The major matrix phosphoprotein 65 (pp65) of cytomegalovirus (CMV) is an important target of HLA-restricted cytotoxic T cells (CTL) after natural infection. A canarypox-CMV pp65 recombinant was studied for its ability to induce CMV pp65-specific CTL, helper T lymphocytes, and antibodies in a phase I clinical trial. Twenty-one CMV-seronegative adult volunteers were randomized to receive immunizations at months 0, 1, 3, and 6 with either canarypox-CMV pp65 or placebo. In canarypox-CMV pp65-immunized subjects, pp65-specific CTL were elicited after only 2 vaccinations and were present at months 12 and 26 in all subjects tested. Cell-depletion studies indicated that the CTL were phenotype CD8(+). Peripheral blood mononuclear cells proliferated in response to stimulation with purified pp65, and antibodies specific for pp65 also were detected. Canarypox-CMV pp65 is the first recombinant vaccine to elicit CMV-specific CTL responses, which suggests the potential usefulness of this approach in preventing disease caused by CMV.

A canarypox vector expressing cytomegalovirus (CMV) glycoprotein B primes for antibody responses to a live attenuated CMV vaccine (Towne).

To develop a vaccine against cytomegalovirus (CMV), a canarypox virus (ALVAC) expressing CMV glycoprotein (gB) was evaluated alone or in combination with a live, attenuated CMV vaccine (Towne). Three doses of 106.5 TCID50 of ALVAC-CMV(gB) induced very low neutralizing or ELISA antibodies in most seronegative adults. However, to determine whether ALVAC-CMV(gB) could prime for antibody responses, 20 seronegative adults randomly received either 106.8 TCID50 of ALVAC-CMV(gB) or 106.8 TCID50 of ALVAC-RG, expressing the rabies glycoprotein, administered at 0 and 1 month, with all subjects receiving a dose of 103.5 pfu of the Towne vaccine at 90 days. For subjects primed with ALVAC-CMV(gB), neutralizing titers and ELISA antibodies to CMV(gB) developed sooner, were much higher, and persisted longer than for subjects primed with ALVAC-RG. All vaccines were well tolerated. These results demonstrate that ALVAC-CMV(gB) primes the immune system and suggest a combined-vaccine strategy to induce potentially protective levels of neutralizing antibodies.

[Changes in amino acids in a regular dialysis program]. / Aktuální zmeny aminokyselin v pravidelném dialyzacním programu.

BACKGROUND: Dialyzed patients are chronically in a state of negative nitrogen balance, and amino acids, their building stones, are also significantly affected by dialysis. The purpose of the present investigation was to assess whether they should be supplied, how frequently and for how long and how they are influenced by the usual diet of patients. METHODS AND RESULTS: The examination was made in a group of 13 patients included in a regular haemodialysis programme. Their mean age was 53.2 +/- 12.4 years, they were dialyzed for an average period of 55 months, maximum 163 months. The patients were dialyzed three times per week for four hours, bicarbonate dialysate was used. The patients' diet was not modified in any way. A total of 52 haemodialysis were examined: losses of alpha-amino nitrogen were monitored as well as changes of serum concentrations of different amino acids. Their mean losses were 119 +/- 54.69 mmol/4 h: this corresponds to 10.5 +/- 4.8 mg amino acids. The dialysis clearance was on average 122.7 +/- 63.2 ml/min. This value did not differ significantly from the dialysis clearance of urea, but it was significantly higher than creatinine clearance (p < 0.05). During dialysis a significant drop (p < 0.001) of the plasma concentration of amino nitrogen occurred, however, the changes of serum concentrations of amino acids differed. A significant drop was recorded in serum concentrations of histamine, lysine, cysteine, methionine, tyrosine, glycine, asparagine, citrullin, glutamine, taurine. Before the beginning of dialysis the values of valine, lysine, threonine, serine, alanine and asparagine were lower than corresponds to the reference interval in healthy subjects. CONCLUSIONS: Changes of serum concentrations of individual amino acids are significantly influenced not only by their losses into the dialysate but also by their shift from cells into the extracellular fluid and by resorption from the digestive tract during protein intake in the course of dialysis. An adequate supply of high quality protein can compensate for these losses. Investigation of serum concentration of individual amino acids does not record their kinetic changes but can give an idea on the effectiveness of the dietary regime.

Upper gastrointestinal bleeding as a complication in end stage renal disease patients.

The commonest pathological findings in the upper gastrointestinal tract have been verified by studying 320 autopsies as related to chronic renal failure through the 20-year span. In our series of 99 patients having been hospitalized within the period of 1989 to 1990, lesions of upper gastrointestinal tract were summarized that might be responsible for bleeding in the course of the dialysis and after renal transplantation. In accordance with literature sources, the investigated group showed gastric and duodenal mucosal lesions to be the most frequent sources of hemorrhages. For both the early diagnosis and therapy all patients have to be examined prior to the initiation of a regular maintenance dialysis. Gastroscopy is also indicated in all patients without any exception. Subsequent conservative treatment should be performed in an intensive and accurate way. While unsuccessful, the surgery is indicated. Authors referred to indicatory criteria based on surgical management of gastroduodenal ulcer. Both the early diagnosis and indication to surgery were stated to be of crucial importance for patient's destiny when the conservative treatment has failed. The present study should contribute to a closer collaboration of nephrologists, gastroenterologists and surgeons in order to prevent such serious complications that are represented by gastrointestinal bleeding in patients with chronic renal failure.

Antibody response of adults to an aluminum hydroxide-adsorbed Neisseria meningitidis serotype 2b protein-group B polysaccharide vaccine.

A group B Neisseria meningitidis serotype protein vaccine was studied clinically in adults. The vaccine comprised lipopolysaccharide-depleted outer membrane vesicles from a serotype 2b strain, 3006-M2, noncovalently complexed with group B meningococcal polysaccharide. Volunteers received 25 micrograms each of protein and polysaccharide administered intramuscularly either in 0.9% NaCl or adsorbed onto aluminum hydroxide on weeks 0 and 6. Most individuals experienced mild local reactions, but there were no systemic reactions. Both vaccine formulations stimulated antibodies to the outer membrane proteins of serotypes 2a:P1.2 and 2b:P1.2, but higher levels were achieved with the aluminum hydroxide-adsorbed vaccine after two immunizations. Vaccine-induced antibodies were primarily IgG and were bactericidal for both a serotype 2a and a serotype 2b strain. Induction of bactericidal antibodies has been shown to be a major predictor of protection against meningococcal disease.

Hepatic cysts of periductal gland origin presenting as obstructive jaundice.

Retention cysts may arise from periductal glands of the hepatic ducts. These cysts are usually asymptomatic. Presented here is the first case with jaundice secondary to obstruction of the hepatic ducts by periductal cysts. Two other cases involved asymptomatic cysts in the presence of cirrhosis, portal vein thrombosis, and hepatocellular carcinoma. This confirms the previously noted association of cysts and portal vein thrombosis. The possibility of obstruction caused by benign cysts should be considered when investigating patients with intrahepatic bile duct obstruction.

Adenovirus pneumonia.

Adenoviruses are ubiquitous DNA viruses that cause a wide variety of illnesses, including pneumonia, in children and adults. Forty-one distinct human sero-types have been identified, yet only about six of these serotypes are associated with the majority of the cases of adenovirus-induced pneumonia. Adeno-virus infection accounts for up to 20% of childhood pneumonias, primarily in those children younger than 5 years of age, but such pneumonias occur infrequently in the nonmilitary adult population. Roentgenologic findings include patchy or diffuse infiltrates, consolidation, and occasionally, pleural effusion. Histopathologic examination of lung tissue frequently reveals a necrotizing bronchitis and bronchiolitis. Such pulmonary destruction results in abnormal pulmonary function in up to 60% of these patients. Mortality rates vary with the population studied and the etiologic serotype, reaching as high as 60% in immunocompromised patients and 15% to 20% of the children with adenovirus type 7 pneumonia. Diagnosis requires either virus isolation or detection of a four-fold or greater rise in serum antibody over a 2- to 3-week period of time. Treatment consists primarily of symptomatic care, while prevention of infection relies upon the selected use of serotype-specific, enteric-coated, live adenovirus vaccines.

Adenovirus infection in the immunocompromised patient.

Illness associated adenovirus infection is described in 15 immunocompromised patients. Patients were immunocompromised by severe underlying disease, immunosuppressive or corticosteroid therapy or by age (prematurity). Evidence of adenovirus infection was obtained by either viral isolation or, in two cases, characteristic adenovirus inclusion bodies at postmortem study. All clinical illness was associated with high fever (temperature greater than 39 degrees C). Eighty per cent of the patients had severe systemic complaints including malaise, lethargy, fatigue and night sweats; a similar number of gastrointestinal symptoms. Pulmonary complaints were described in 11 of 15 cases and included cough (67 per cent) and tachypnea (53 per cent). Roentgenologic evidence of pneumonia was demonstrated in 12 of 15 patients (80 per cent). Elevation of serum hepatic enzyme levels (serum glutamic pyruvic transaminase (SGPT)) occurred in eight of 11 patients (73 per cent) and was moderate to severe (serum glutamic pyruvic transaminase greater than 450 IU/liter) in five of 11 (45 per cent). Nine patients died; seven after a rapid downhill course and two after a prolonged illness. Evidence of adenovirus infection microscopically by autopsy in the lung, liver or both is demonstrated in four patients with fulminant systemic illness. Adenovirus infection should be considered in the etiology of severe overwhelming illness in the immunocompromised host.

Adenovirus hepatitis in an immunosuppressed adult patient.

The role of adenovirus as an etiologic agent of hepatic damage has been controversial. A fatal case of adenovirus infection with fulminant hepatitis in a young immunosuppressed adult patient is presented. Intranuclear inclusions were confined to the liver. Electron microscopy revealed crystalline arrays of virions within hepatocytes. This is apparently the first reported case of adenovirus hepatitis occurring in an adult. Adenovirus hepatitis represents another hazard for the immunosuppressed patient.