Accelerated Schedule for Hepatitis B Immunization.

Background: A considerable number of people remain unprotected against hepatitis B. These people may require immunization at short notice before being exposed to situations or locations where a risk of infection is present. Currently, full active immunization against hepatitis B, when administered according to recommended schedules, takes 2-6 months. This open, randomized multicentric study evaluated the reactogenicity and immunogenicity of a recombinant hepatitis B vaccine in adults when it was administered according to three different rapid vaccination schedules. Methods: Five hundred and twenty four healthy adults (aged 18-59 years) were randomly divided into three groups. Hepatitis B vaccine was given intramuscularly in the deltoid muscle at months 0, 1, and 2 (group A); weeks 0, 14, and 28 (group B); and weeks 0, 7, and 21 (group C). Symptoms were recorded by the subjects on individual diary cards. AntiHBs were measured using radioimmunoassay (Ausab-Abbott); a seroprotective titer was defined as 10 IU/L. Results: At day 28, no significant difference in seroprotection rates (SPRs) i.e., seroconversion >= 10 IU/L,was observed, between groups B (55.6%) and C (65.2%), but both these groups had significantly greater SPRs than group A (15.0%). Although not significant (p=.07), groups B and C also had higher SPRs than group A (78.5% and 76.4% versus 65%) at day 56. One month after completing the three dose schedules, the SPRs were as follows: 89.0% (group A); 78.5% (group B); and 76.4% (group C), increasing to > 94% at month 7 to 8 in all three groups. The SPRs at month 13 were 95.8%, 98.9%, and 98.6%, respectively. Among the three groups, no significant differences were observed from month 2 onwards in either SPRs or geometric mean titers. In groups A, B, and C, 3.7%, 5.0%, and 7.1% of the vaccine injections were associated with local symptoms. Also 8.3%, 6.2%, and 6.3% of subjects exhibited general symptoms following each vaccine dose; all symptoms were transient and resolved spontaneously. Conclusions: This recombinant hepatitis B vaccine administered at weeks 0, 7, 21, or at weeks 0, 14, 28, rapidly elicits high rates of seroprotection, which persist at least until month 12.

Differences in intravenous and subcutaneous application of recombinant human erythropoietin: a multicenter trial.

The aims of this clinical study were to compare the maintenance doses for intravenous (i.v.) and subcutaneous (SC) administration of recombinant human erythropoietin (rhEPO) and to investigate whether there is any difference in the increase of the packed cellular volume (PCV) per week under i.v. and SC administration of rhEPO from two production sites (Genetics Institute, Cambridge, USA; and Boehringer Mannheim, Penzberg, Germany). A total of 90 patients suffering from end-stage renal disease were included in the study. All patients had already been treated for at least 6 months with chronic hemodialysis. The study was carried out as a randomized, multicenter parallel group comparison study with a 1-week pretreatment phase, a subsequent 8-week double-blind phase, and a final open phase. The final open phase consisted of a correction phase and a maintenance phase. The production site had no influence on the PCV increase per week, and there were no differences with respect to tolerability. The median rhEPO dose required to maintain the target PCV of 30 to 35 vol.% was 33 U/kg body weight three times a week in the i.v. group compared with 22 U/kg in the SC group (i.e., an average of 30% less with SC administration). Development or aggravation of hypertension under rhEPO therapy was observed, especially during the correction phase and more frequently in the SC group than in the i.v. group. During the maintenance phase, there was no essential difference between the two groups.

Diagnostic sensitivity of different techniques in the diagnosis of lung tumors with the flexible fiberoptic bronchoscope. Comparison of brush biopsy, imprint cytology of forceps biopsy, and histology of forceps biopsy.

Brush and forceps biopsies were done consecutively in 186 cases of pulmonary neoplasia with a flexible fiberoptic bronchoscope guided by x-ray television fluoroscopy. Imprint and histologic sections were prepared from all forceps biopsy specimens. The three techniques were compared for their diagnostic sensitivity. As a result 84.9% of all imprints, 80.6% of brush biopsy specimens, and 62.9% of histologic sections were positive for malignancy. The sensitivity of brush biopsy specimens was independent of the location and morphology of the tumors, but the sensitivity of forceps biopsy specimens was lower in neoplasms unidentified by bronchoscopy. The sensitivity of the diagnostic accuracy when all three methods were used jointly was 97.3%, and the specificity was 100%. Agreement in the final morphologic tumor type was found in 130 of 150 cases (86.7%) by positive brush biopsy specimens, in 136 of 158 cases (86.1%) by positive imprint cytology, and in 104 of 117 cases (88.9%) by positive histology from forceps biopsy specimens. For routine bronchoscopy, all three methods should be used in combination to obtain the highest diagnostic yield.

Autopsy pathology and disease patterns in Shiraz, Iran, 1960-1974.

The impact of 4300 serial autopsies performed in Shiraz, Iran, on scientific and clinical medicine is discussed. These studies in geographic pathology led to the recognition of the importance in disease patterns of persistent, life-long changes in the human immune response brought about by serious perinatal infection and/or malnutrition. Elucidation of the pathogenesis of primary upper small intestinal lymphoma serves as an example of the importance of the field of geographic pathology for the understanding of disease processes. The immune response in infantile infection with Pneumocystis carinii with interstitial plasma-cell pneumonia helped to elucidate the basic conditions and mechanisms underlying all forms of pneumocystosis. The first effective prophylaxis of pneumocystosis was thus developed. The response of the gut to different forms of nutritional deficiency and its relationship to gastroenterological cancer was also investigated.

[Reform of medical education as an international trend]. / Die medizinische Studienreform im internationalen Trend.

The strengths and weaknesses of the present Austrian Medical Curriculum are compared with other systems. The medical curriculum is part of the educational system and must be seen in that context. The goal is the qualitative and quantitative fulfillment of the manpower needs of the health system. Graduation should follow proper practical training, not only in universities, but also in the community setting. Personal contact on all levels must complement and supersede "multiple choice" thinking. Austrian should not just follow foreign models, but lead the international reform movement in medical education.

Pneumocystis carinii infection and interstitial plasma cell pneumonia: what does history teach?

Pneumocystis carinii is a special organism that causes a variety of host reactions depending on the resistance and immune response. The disease was originally observed in premature and newborn infants, associated with interstitial plasma cell infiltrates, which lead to rapid suffocation of the infant. An understanding of all aspects of the disease and all its patterns is required in view of the worldwide epidemic of immune deficiency of various etiologies associated with the nearly ubiquitous infestation with Pneumocystis carinii.

[The high autopsy rate in Vienna]. / Zur hohen Autopsierate in Wien.

In 1983 34% of all persons who died in the Republic of Austria were autopsied. We examined the frequency of postmortem examinations in the capital city, Vienna, between 1983 and 1987 in view of this high overall autopsy rate. The annual autopsy rate in all 9 pathology institutes and the department of legal medicine of the University of Vienna was on average 51 to 53%. There was a slight statistically verifiable decline in 1987. The reason for this high necropsy rate is that Austrian law permits the autopsies without the consent of next of kin if it appears indicated for medical, scientific or educational reasons; further more the fact, that the chairman of the department is at the same time the coroner for the hospital. A high autopsy rate is necessary to maintain a high standard of diagnostic accuracy even in modern medicine. The diagnoses were inaccurate or incomplete in 15% of all cases. The high autopsy rate is the basis for extremely accurate mortality and morbidity statistics and provides the basis for long range public health planning. Medical students develop an insight in disease patterns, which cannot be gained in any other way. The pathology departments of Vienna introduce a new city-wide computer-supported diagnostic file system, which will provide a baseline for comparative scientific studies.

Retinyl ester retention in chronic renal failure. Further evidence for a defect in chylomicron remnant metabolism.

The metabolic remnants of triglyceride-rich lipoproteins are atherogenic in man and experimental animals. Particles resembling lipoprotein remnants have been found in plasma from patients with chronic renal failure (CRF). In this study we took advantage of the observation that retinyl esters are transported only by lipoproteins that originate in the intestine, that is, by chylomicrons (CM) and their remnants. To investigate further remnant metabolism in CRF, plasma RE were measured by reverse-phase high performance liquid chromatography in 20 non-diabetic hemodialyzed patients with CRF and 20 hospitalized non-diabetic control subjects 12-15 h after the administration of retinyl ester, 25000 IU orally. Total plasma RE were increased 3-fold in the CRF patients (P less than 0.001). Quantitative analysis of retinoids and lipids in fractions separated by unit-gravity flotation and flocculation in 3% polyvinylpyrrolidone indicated that the plasma RE were not contained among intact CM. Mean plasma retinol in CRF was also elevated consistent with previous observations and the known role of the kidney in retinol-binding protein metabolism. Although postabsorptive RE concentration was correlated positively and significantly with plasma triglyceride concentration in both groups, RE were higher in CRF patients at comparable plasma triglyceride concentrations. These data support the proposal that atherogenic lipoprotein remnants accumulate in the plasma of patients with CRF.

Immunoproliferative small intestinal disease and primary small intestinal lymphoma. Relation to alpha chain protein.

Forty-three patients with immunoproliferative small intestinal disease and primary small intestinal lymphoma were studied prospectively. Eighteen patients in whom alpha-chain protein was detected in the serum had significantly more features of malabsorption, and disease was localized more commonly in the jejunum. In all of these patients, a diffuse lymphoplasmacytic infiltrate was found in the intestine; in three patients lymphoma was found only in mesenteric lymph nodes. Twenty-five patients with lymphoma in whom alpha-chain protein failed to be detected had significantly more features of intestinal obstruction, and disease was found more commonly in the ileum. Five of these patients had lymphoma associated with a diffuse mucosal infiltrate that was indistinguishable from the first group. In patients available for follow-up, no difference was found in cumulative survival over 30 months in the two groups, with approximately 40% mortality at 6 months.

Tubular dysfunctions in the diagnostic differentiation of glomerulonephritis, pyelonephritis, and diabetic nephropathy.

Concentration and acidification capability was tested in 41 patients with chronic pyelonephritis (PN), 14 patients with chronic glomerulonephritis (GN), 16 patients with diabetic nephropathy (DNP) and 12 healthy controls. Significant differences appeared between PN and GN, PN and DNP comparing a quotient between percent of normal osmolarity and percent of normal creatinine clearance. Similar results were obtained using a quotient creatinine clearance/ammonia excretion, which enabled the differentiation of PN from the other groups. The tubular functions of concentration and ammonia excretion in relation to creatinine are clinically useful in the differentiation of pyelonephritis from glomerular kidney diseases.

Immunoperoxidase in lymphomas induced by host-versus-graft (HVG) reaction.

It appears that the development and type of lymphoid neoplasm in mice depends on the ratio of T cell subsets and the repeated stimulation of the lymphoid systems as well as a genetic predisposition. Mice with HVG disease developed lymphomas in an average of 462 days versus 567 days for normal mice. Murine leukemia virus was detected in the HVG mice perinatally at 3 weeks of age and three months earlier in the noninjected mice. The immunoglobulins were IgA and IgM or IgM alone and IgG in three cases. No IgA was detected.

[Results of sonographic kidney diagnosis]. / Ergebnisse der sonographischen Nierendiagnostik.

In a prospective study of the examination of the accuracy of the ultrasound tomography in the renal diagnostics the kidneys of 361 patients could be demonstrated as at 100% sufficiently to be judged. Tumours, congestion kidneys, cystic kidneys/renal cysts and cirrhoses of the kidney were diagnosed with an efficiency of 0.92-0.96-0.97-1.0. The sensitivity was in the same order 0.90-0.96-0.99-1.0 and the specificity 0.94-1.0-0.95-1.0. Insufficient results were obtained by the sonographic search for renal calculi. As non-invasive and rapid method of diagnostics the sonography in a valuable way contributes to the differentiation of the symptom "quiescent kidney" and oligo-anuria.

Neonatal infection with mouse thymic virus: spleen and lymph node necrosis.

Mouse thymic virus (TA) is a naturally occurring herpesvirus of laboratory and wild mice, which produces massive thymic necrosis when inoculated into newborn mice. Our histopathological study showed necrosis not only of the thymus but also of the spleen and lymph nodes which was noticeable by day 7 and complete by day 14. Both spleen and lymph nodes regenerated to an almost normal histological pattern by day 70. The results show that TA infects multiple lymphoid tissues causing massive necrosis in all, and is not limited to a single site, the thymus. TA infection was found to be a persistent herpesvirus infection in both the lymph nodes and spleen. During the period of acute infection, as necrosis increased, the response of cell suspensions of lymph nodes to the T cell mitogens concanavalin A and phytohaemagglutinin was virtually non-existent. Activity returned to normal as the histological repair progressed.

Modification of radiation carcinogenesis by marihuana.

Male, female, and ovariectomized female Sprague-Dawley rats were irradiated with 400 rads, 150 rads, or 300 rads, respectively, of 60Co gamma rays when they were between 40 and 50 days of age. The animals were injected three times weekly with either marihuana extract or with alcohol-emulphor carrier. Comparable unirradiated groups were similarly injected. Mean survival time in males was significantly shorter in the 400 rad + marihuana group compared with the three other groups whose mean survival times did not differ. Through the 546 days that the males were observed, the total number of tumors other than fibrosarcomas was significantly greater following radiation and marihuana (22) than radiation alone (6). Fifteen of the tumors were of breast or endocrine tissues. No differences were seen in the unirradiated groups. In the females, which were observed for 635 days, the total number of breast tumors was greater with the combined treatment (38) compared with radiation alone (22). This was entirely due to a marked difference in the adenocarcinoma incidence, which was 21 (radiation + marihuana) compared with four (radiation alone). The number of adenofibromas was similar in the two groups. In the unirradiated female groups the breast adenocarcinoma incidence was eight in the marihuana group and two in the control group. Ovariectomy resulted in a lower breast tumor incidence in all groups. Nonbreast tumors were more frequent in the ovariectomized-irradiated groups. Radiation plus marihuana produced more nonbreast tumors (25) than radiation alone (17) in the ovariectomized females.

Immunoproliferative small intestinal disease with duodenojejunal lymphoma: radiologic changes.

The radiologic changes in 1090 cases of lymphoma of the small bowel were analyzed and correlated with the pathologic findings. The material was collected in Iran, a high incidence area for immunoproliferative small bowel disease (IPSID). Of 100 cases of primary intestinal lymphoma associated with IPSID, 48 involved the duodenum and upper jejunum. They were associated with a characteristic spruelike radiologic pattern of the nonlymphomatous segments of the gut, the intensity of which decreased distally. However, the radiologic features of the lymphoma associated with IPSID were identical with those described in other forms of primary small intestinal lymphoma, regardless of histologic type or the presence and absence of alpha-heavy chain secretion.