A review of the evidence to inform pneumococcal vaccine recommendations for risk groups aged 2 years and older.

For decades, vaccination with the 23-valent polysaccharide pneumococcal vaccine (PPV23) has been available for risk groups aged ⩾2 years to prevent invasive pneumococcal disease (IPD). Recently, a 13-valent pneumococcal conjugated vaccine (PCV13) has been licensed for use in all age groups. PCV13 may induce better protection than PPV23 because of different immunogenic properties. This called for a revision of vaccine recommendations for risk groups. We therefore reviewed literature on risk groups for IPD, and effectiveness and safety of pneumococcal vaccines and supplemented that with information from public health institutes, expert consultations and data on IPD epidemiology. We included 187 articles. We discuss the implications of the heterogenic vulnerability for IPD within and between risk groups, large indirect effects of childhood immunization, and limited knowledge on additional clinical benefits of PCV13 in combination with PPV23 for the Norwegian recommendations. These are now step-wise and consider the need for vaccination, choice of pneumococcal vaccines, and re-vaccination interval by risk group.

Biochemical properties of tissue polypeptide antigen.

Tissue polypeptide antigen (TPA) is a complex protein which has been originally identified in extracts of pooled tumors using horse antisera raised against the insolubles of human tumor cells. The antigen is now routinely detected and measured by a previously described hemagglutination inhibition assay. It has been shown by this method that the concentration of the antigen is higher in tumor tissues and in sera of cancer patients as compared to normal tissues or normal sera, respectively. In aqueous solutions, pH 2-12, TPA has a tendency to form high molecular weight aggregates. However they can be dissociated in sodium dodecyl sulfate into subunits, each appearing as a single chain peptide: B1 (Mr 4.3 x 10(4)), B2 (Mr 3.0 x 10(4)), C (Mr 1.7 x 10(4)). The subunits saturate anti-TPA serum indistinguishably from TPA. Amino acid composition of TPA and subunits is dominated by glutamic acid, aspartic acid and leucine, cysteine being absent in subunit B1. The isoelectric point of the main subunit, B1, is 4.4-4.6. Sedimentation and diffusion analyses indicate that pure subunit B1 in aqueous solution exists in distinct oligomeric states.

Diurnal variations in plasma concentrations of tryptophan, tryosine, and other neutral amino acids: effect of dietary protein intake.

The effect of dietary protein content on the diurnal variations in plasma neutral amino acid levels was studied in normal human subjects. For three consecutive 5-day periods, subjects consumed diets containing 0, 75, or 150 g of egg protein per day. Blood samples were drawn at 4-hr intervals on the 4th and 5th days of each period. Consumption of the protein-free diet caused plasma concentrations of all amino acids studied to fall in the late morning and afternoon, while the 150-g protein diet elicited increases in these levels during the daytime. Ingestion of the diet containing 75 g of egg protein tended to diminish the amplitudes of the daily rhythms in plasma amino acid levels, but most amino acids still exhibited small but significant elevations late in the evening. At all times of day, plasma concentrations of the large neutral amino acids studied (i.e., aromatic and branched-chain amino acids, and methionine) varied directly with the protein content of the diet. In contrast, the relationships between dietary protein content and the plasma concentrations of glycine and alanine, two small neutral amino acids, were inverse. The ratios of plasma tryptophan, tyrosine, and phenylalanine levels to the sum of the concentrations of other large neutral amino acids tended to fall as the protein content of the diet was increased. The corresponding ratio for valine increased as protein was added to the diet, while the leucine and isoleucine ratios were not correlated with dietary protein content. Since diet-induced changes in plasma trypotphan and tyrosine ratios in animals are known to cause parallel alterations in brain tryptophan and tyrosine levels, and thus in the rates of brain serotonin and catecholamine synthesis, our data suggest that ingestion of carbohydrates and protein may also normally affected brain monoamine synthesis in humans.

Diurnal variations in plasma neutral amino acid concentrations among patients with cirrhosis: effect of dietary protein.

The effect of varying dietary protein content on the daily rhythms in plasma neutral amino acid concentrations was studied in patients with chronic cirrhosis. For two consecutive 5-day periods, subjects consumed diets containing either 0 or 75 g of protein per day. Blood samples were drawn at 4-hr intervals on the 4th and 5th days of each dietary period. For most of the neutral amino acids, the changes in plasma concentration associated with time of day or with variations in dietary protein content were similar to those observed previously in normal subjects. Ingestion of the protein-free diet caused significant reductions in the daytime level of all amino acids studied, except for tryptophan, the concentration of which did not change during the 24-hr period. Ingestion of the 75-g protein diet caused plasma levels of most of theamino acids to increase slightly during the day; these increments were not statistically significant for tryptophan, tyrosine, leucine, and methionine. The absolute plasma concentrations of most of the neutral amino acids were also in the normal range; exceptions included methonine, tyrosine, and phenylalanine, whose plasma levels were significantly elevated above normal valves. The plasma ratios of tryptophan, tyrosine, and phenylalanine concentrations to the sum of the concentrations of other large neutral amino acids increased during the day uhen the protein-free diet was ingested; this effect was moderated by the addition of protein to the food. The plasma ratios for the branched-chain amino acids were depressed below normal; those for tyrosine, phenylalanine, and methionine were significantly increased. The plasma tryptophan ratio was within the normal range. These findings provide a basis for anticipating that the uptake from blood into brain of several of the large neutral amino acids may be modified in patients with chronic cirrhosis.

Neurotensin increases net fluid secretion and transit rate in the small intestine of man.

In a double-blind study with six patients, who previously had undergone proctocolectomy for ulcerative colitis, the ileostomy discharge significantly increased from 110 to 295 ml X 4 h-1 during infusion of neurotensin, 3 pmol X kg-1 X min-1 for 4 h. Transit defined as the passage of a perorally ingested unabsorbable marker (polyethylene glycol, PEG 4000) was significantly increased during the last hour of neurotensin infusion. The dose of neurotensin used in this study has previously been shown to result in plasma levels of neurotensin-like immunoreactivity within the range obtained after a fatty meal. Thus, the present data indicate that neurotensin in man may exert a physiological function by increasing net fluid secretion in the small intestine as well as increasing the intestinal transit rate.

Evaluation of the UBC test in the urine of healthy individuals, patients with benign disorders and urinary bladder cancer.

Using the UBC test, the specificity, sensitivity and prognostic information were evaluated in patients with recently diagnosed transitional cell carcinoma (TCC) and in a control group consisting of apparently healthy individuals and individuals with benign disorders. Frozen urine samples from the 485 individuals in the control group and 100 newly diagnosed TCC patients were analyzed with the UBC test, specific for epitopes on cytokeratin fragments released from the urothelial cells. All the samples were analyzed and corrected for creatinine. No significant concentration difference was found between males and females (p=0.65) and there was no age dependent relation. The median concentration for the entire control group was estimated at 3.7 microg/g and the 95th percentile was calculated at 53.0 microg/g. The apparently healthy individuals in the control group had a median value of 3.4 microg/g with a 95th percentile of 24.3 microg/g. An increased frequency of elevated UBC concentrations was found in some benign disorders e.g., anemia, thyroid disorders, diabetes mellitus, hyperlipemia, urosepsis and cystitis. Patients with superficial tumors exhibited a 66% sensitivity (at 95% specificity), and the UBC concentrations did not differ statistically (p=0.16) from those patients with muscle invasive lesions with a 52% sensitivity. When the UBC concentrations were related to histopathological grade, a significant concentration difference (p<0.004) was found between low grade tumors (sensitivity 41%) and high grade tumors (sensitivity 72%). Survival analysis showed that patient with muscle invasive tumors, high-grade tumors and high UBC concentrations have a significantly reduced survival (five-year survival was estimated to 30%, 35% and 30% respectively) compared to patients with superficial tumors, low-grade tumors or low UBC concentrations (five-year survival, 60%, 85% and 75% respectively). The UBC test showed good accuracy and repeatability. Clinically the test could assist in tumor grading and the detection of recurrent disease, which in turn could assist in treatment selection for the individual patient and possibly improve prognosis.

Diurnal variations in plasma insulin concentrations in normal and cirrhotic subjects: effect of dietary protein.

Concentrations of immunoreactive insulin and of glucose were measured in plasma samples taken at 4-hour intervals from cirrhotic and normal control subjects ingesting diets containing various amounts of protein. In both groups, insulin levels were highest after meals, between 11 a.m. and 7 p.m.; in cirrhotic subjects, but not in controls, plasma glucose levels were also higher at these times. Insulin and glucose concentrations in plasma from cirrhotic subjects were higher than those from control subjects at all times measured. Peak daytime insulin levels were about 150 muU/ml in plasma from cirrhotic subjects, and 40--50 muU/ml in plasma from controls; nocturnal levels were 20--30 muU/ml in cirrhotics versus 10 muU/ml or less in controls. The protein content of the diet was unrelated to plasma insulin levels at all times of day or night examined. These data thus show that plasma insulin levels are persistently elevated in cirrhotics, remaining higher than normal throughout the 24-hour period.

Cytokeratin 8 and 18 fragments measured in serum and their relation to survival in patients with non-small cell lung cancer.

BACKGROUND: In this study we investigated if the newly developed monoclonal antibodies against Cytokeratin 8 and 18 fragments (Cyk 8/18) have prognostic information in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Serum from 69 patients with NSCLC was investigated using a sandwich ELISA, Cyk 8/18, provided by IDL Biotech, Sollentuna Sweden. RESULTS: Cyk 8/18 levels varied between 0.34-14.2 ng/mL, compared with a cut-off value of 1.0 ng/mL for healthy individuals (95% specificity). Using that cut-off value, 80% of NSCLC patients had elevated levels. A statistically significant diminished survival was found for Cyk 8/18 values of 8.0 ng/mL or higher (p = 0.0001). When survival data and Cyk 8/18 levels were analysed according to continuous Cox regression analysis, increased levels of Cyk 8/18 were significantly related to decreased survival (p = 0.016). CONCLUSIONS: The Cyk 8/18 monoclonal antibody had in this study prognostic information regarding survival in patients with NSCLC.

Note on a method for individual recognition in feed pecking in free running groups of hens.

A system for automatic registration and individual recognition of feed pecking (activity and quantity) in groups of free running hens was tested. A PIT (Passive Integrated Transponder)-tag system was used to separate and register individuals when they were feeding. An electronic balance system placed under the feeder registered the amount eaten by each individual on a PC. A test with two different feed stuffs; oat and wheat was performed on three hens during a total of 6 weeks.

[Blood lipid derangement common in peripheral artery disease. Lipid-lowering agents may alleviate symptoms and slow the atherosclerotic process]. / Vanligt med blodlipidrubbning vid benartärsjukdom. Lipidsänkare kan lindra symtom och ge långsammare aterosklerosutveckling.

In the new guidelines from the Swedish Medical Products Agency, an aggressive approach is recommended for the treatment of hyperlipidemia in all patients with manifest atherosclerotic disease. Patients with intermittent claudication should therefore receive lipid-lowering treatment on the same indications as patients with coronary artery disease. The present article reviews our knowledge of hyperlipidemia as a risk factor for the development of peripheral artery disease. Hyperlipidemia is frequently found in these patients and the most common lipid derangements are low levels of HDL-cholesterol and hypertriglyceridemia. Hard end-point data concerning morbidity and mortality during lipid-lowering treatment in this specific population is largely lacking, although previous studies indicate that lipid-lowering treatment slows the atherosclerotic process and induces pain relief.

Patients with atherosclerosis may have increased circulating levels of 27-hydroxycholesterol and cholestenoic acid.

Extrahepatic sterol 27-hydroxylase (CYP27) appears to have a role in the elimination of excess cholesterol from various cells, particularly macrophages, and there is a net flux of 27-hydroxyycholesterol and its metabolites from different extrahepatic sources to the liver. In this study we tested the hypothesis that patients with advanced atherosclerosis may have higher levels of 27-oxygenated products in the circulation than control subjects. Concordant with previous studies, a strong correlation was observed between circulating levels of 27-hydroxycholesterol and cholesterol, in both healthy subjects and subjects with hypercholesterolemia and documented atherosclerosis. A group of male subjects with normal or only slightly elevated serum cholesterol and rapidly progressing carotid atherosclerosis (n = 20) had serum levels of 27-oxygenated cholesterol not statistically different from those of a matched group of subjects with little or no development of atherosclerosis (n = 20). The situation was similar in a group of patients (n = 20) with advanced general atherosclerosis associated with severe clinical symptoms. Among the two groups of patients with atherosclerosis, a few patients had relatively high levels of 27-oxygenated products. Among the healthy controls, two healthy volunteers (brother and sister) were found to have high levels of 27-hydroxycholesterol, most probably due to genetic reasons. The possibility is discussed that the high levels of 27-oxygenated products in the circulation of a few patients with atherosclerosis may be related to high amounts of active macrophages present in atherosclerotic lesions. In view of the number of factors that could affect the levels in the circulation, other explanations cannot be ruled out. At the present state of knowledge, measurements of circulating levels of 27-oxygenated metabolites do not seem to add useful information about the atherosclerotic process.

Fate of weight. Ten-year observations after jejunoileal bypass for obesity.

In 182 patients weight results up to ten years after various types of jejuno-ileal bypass for obesity are presented. Initially end-to-end operated patients had a significantly greater weight loss than end-to-side operated but the significance disappeared from six years and on. Five years after the operation 19% of the patients were still losing weight. Mean weight loss after this time was 33% and 36% of the patients had a body weight at or below Broca's index 1.25 which is considered excellent or good. Median regain of lost weight was 22% five years after minimum.

Experiences with antireflux valves in jejunoileal bypass surgery.

Intussusception valves were created in the small intestine of jejunoileal bypass-operated dogs and patients with the intention to prevent reflux of chyme into the excluded intestinal loop and thereby increase weight loss. In the dogs the valves were shown to withstand a pressure of at least 100 cm of water. All patients with end-to-side bypass were at X-ray examination found to have sufficient valves whereas only four of fourteen with end-to-end bypass, where the defunctionalized loop was implanted into the cecum, had tight valves. During five years of observation no significant difference in weight loss was seen between the patients with valves and control groups without valves. It is concluded that reflux of chyme only plays a minor role for weight loss after jejunoileal bypass for obesity.

Neurotensin-like immunoreactivity in plasma after fat intake in normal and obese subjects and after jejunoileal bypass.

The plasma concentration of neurotensin-like immunoreactivity (p-NTLI) was measured after oral intake of fat in (a) healthy non-obese volunteers, (b) grossly obese but otherwise healthy persons, and (c) patients who had undergone jejunoileal bypass because of gross obesity. In addition, p-NTLI was measured after intravenous infusion of fat in healthy non-obese volunteers. Basal p-NTLI levels were significantly higher in the patients with bypass than in the obese group. After oral intake of fat, the increase in p-NTLI was much greater and more sustained in the bypass group than in the two other groups. The type of bypass (end-to-end, end-to-side or biliointestinal) and the time after the operation did not correlate with the p-NTLI response. Intravenous infusion of fat evoked no increase in p-NTLI. To produce a rise in p-NTLI level, therefore, the fat does not have to be absorbed and hematogenously distributed to the N-cells (neurotensin-storing cells). This observation may suggest that direct contact between chyme and the N-cells, or local neural or hormonal factors, are required to stimulate release of NTLI. The authors suggest that increase in the postprandial release of neurotensin may promote the diarrhoea after bypass operations, and possibly has other physiologic effects in such patients.

Stomach rupture following ingestion of sodium bicarbonate.

Spontaneous rupture of the stomach is an uncommon condition with a usually poor prognosis. The rupture occurs as a result of a closed loop obstruction with increased pressure against the stomach wall. A case of stomach rupture occurring after hyperdistention of the stomach following ingestion of sodium bicarbonate is described and the pathophysiological mechanism is discussed.

Studies in man on the mechanism by which fat increases the plasma concentration of neurotensin-like immunoreactivity.

We measured the plasma concentration of neurotensin-like immunoreactivity (p-NTLI) after administration of Intralipid (mainly triglycerides), or oleic acid perorally, into the intact proximal jejunum, intact distal jejunum or proximal ileum and together with partly digested Intralipid into an isolated ileal loop in man. Administration per os or into the proximal jejunum gave the highest p-NTLI responses, administration into the intact distal jejunum or proximal ileum gave a lower response and administration into the isolated ileal loop gave no response at all, although approximately 25 percent of the neurotensin producing cells should be located there. As estimation of intestinal tissue content of NTLI showed that in small intestine which for a long time had been out of contact with food there was no sign of depletion of NTLI, we suggest that nervous, humoral or luminal factors provoked by fat in the upper gastrointestinal tract must trigger the N-cells before NTLI can be released by fat exposition.

Acute arterial occlusion.

During the years 1969--1976, 66 patients were subjected to surgery for acute arterial occlusion. Arterial occlusion was due to emboli in 67% of the patients, and to acute thrombosis in 33%. There was no difference in the mean age for the two groups. More than 50% of the occlusions, embolic as well as thrombotic, were located in the femoral artery. In the embolic group limb salvage rate was 93% and patient survival rate 82%. The corresponding figures for the thrombotic group were both 73%. There was no direct correlation between the number of amputations and the time interval from occlusion to operation in either of the two groups. In the embolic group, adequate backflow was reestablished in 82%, while the corresponding figure in the thrombotic group was only 45%.

Reconstruction of the deep femoral artery.

Deep femoral artery reconstruction was performed on 54 extremities. Best results were obtained in patients with severe rest pain and minor ischemic ulcerations. Intermittent claudication generally did not improve significantly. The mean operative flow to deep femoral artery was 170 mg/min. and the increase in peripheral pressure 20 mm Hg.

Chemical studies of tissue polypeptide antigen (TPA). III. on the nature of the antigenic determinant(s) of TPA subfraction B1.

Tissue Polypeptide Antigen (TPA)*** which is a protein isolated from e.g. human carcinoma cells, has previously been separated into subfractions and studied with biochemical methods. Gel diffusion studies show that the antigenic determinants are retained through the isolation and purification procedures. Specific modifications of the amino acid residues lysine, tyrosine, trytophan and arginine in subfraction B1 have been related to the change in the capacity of the antigen to bind to horse anti-HeLa serum. Complete although reversible loss of binding capacity resulted from blocking of arginine and a minor loss was noted upon modification of tyrosine. No measurable influence was noted upon modification of lysine or tryptophan. No cysteine has been detected in subfraction B1. Circular dichroism measurements show that TPA subfraction B1 is largely alpha-helical in solution, and that no correlation could be detected between antigenic activity and conformation.