Type-specific enzyme immunoassay for detection of pneumococcal capsular polysaccharide antigens in nasopharyngeal specimens.

We developed a new competitive EIA method for the demonstration of pneumococcal capsular polysaccharides from respiratory samples. The pediatric types 4, 6B, 9V, 14, 18C, 19F and 23F were selected for this study, because these capsular polysaccharides were included in the first heptavalent pneumococcal conjugate vaccines, which were used in the Finnish Otitis Media Vaccine Trial. Sensitivity of the EIA tests for purified polysaccharide antigens varied between 5 and 100 ng/ml, depending on the type. The assays performed well in 100 nasopharyngeal samples (NPS) samples processed through an enrichment culture, with an almost 100% sensitivity compared with routine culture. The method appeared type-specific, except that EIA for 6B capsule also detected 6A. The method is applicable for type-specific identification of pneumococcus in carriage studies.

Pneumococcal pneumonia diagnosis by demonstration of pneumolysin antibodies in precipitated immune complexes: a study in 350 Philippine children with acute lower respiratory infection.

In searching for suitable methods for aetiological diagnosis of pneumococcal disease we determined capsular polysaccharide, C-polysaccharide and pneumolysin antibodies bound in immune complexes (IC) in Filipino children. Sera were obtained from 150 healthy infants (all under 12 months old) and from 350 paediatric patients (mean age 18 months) hospitalized with severe pneumonia. The findings in healthy children were not associated with age, sex or pneumococcal carrier status; 3-7% exceeded the cut-off limits for positivity in different antibody assays. By contrast, 97 (51%) of the 190 patients with a complete 3-sample series exceeded the cut-off limit for IC-bound pneumolysin-IgG in at least 1 of the serum samples studied. Positivity rates for IC-bound pneumolysin-IgG in the admission day, in-patient and convalescent sample of the 350 patients were 25%, 25% and 34%. Pneumolysin-IgM, capsular polysaccharide and C-polysaccharide antibodies in the IC were positive in only 4-6% of the patients' samples. IC-bound pneumolysin-IgG antibody assay seem to be a useful method for species-specific diagnosis of pneumococcal infections.

Influence of estrogen-progestin replacement therapy and exercise on lumbar spine mobility and low back symptoms in a healthy early postmenopausal female population: a 2-year randomized controlled trial.

The purpose of this study was to examine the influence of estrogen-progestin replacement therapy and exercise on the lumbar spine mobility and back symptoms of early postmenopausal women. The population sample consisted of 78 healthy, 49- to 55-year-old women, 0.5-5 years after menopause, who were randomized into three groups, two receiving different protocols of estradiol valerate combined with medroxyprogesterone acetate replacement therapy, and the third group a placebo. These groups were then randomized into exercise and control cases and monitored for 2 years. The mobility of the lumbar spine was measured and symptoms investigated using the Million and Oswestry pain and disability questionnaires and pain drawings at the baseline and after 1 and 2 years. During the follow-up, the mobility of the lumbar spine decreased in all six groups. The decrease was most evident in those who had been the most flexible at baseline (P < 0.0001). The decrease was less notable in the hormone replacement therapy groups than in the control group. When the replacement therapy groups were pooled together, the difference was significant at a P < 0.05 level. No difference was seen between the hormone combinations. The exercise intervention was insufficient to influence lumbar spine mobility. Only sporadic cases of back symptoms appeared and disappeared among the subjects during the follow-up, and no preventive or aggravating effects of hormone replacement therapy or the exercise program on symptoms were detected.

Clinical evaluation of new pneumococcal vaccines: the Finnish approach.

Clinical evaluation of a new vaccine should be based on information about the epidemiology and pathogenesis of the infection to be prevented, the protective immunity to this infection, and the immunological properties of the vaccine to be evaluated. In this review we describe one approach to evaluate a new vaccine, using our experience with pneumococcal conjugates as an example. Information on the epidemiology, pathogenesis and host responses was collected mainly during 1987-1992, improvement in diagnostic methods was carried out during 1990-1995, and the immunogenicity of vaccine candidates was tested during 1992-1995. Based on these factors, a randomized, controlled, blinded efficacy trial of two pneumococcal conjugate vaccines against acute otitis media was started in Finland in 1995. Enrolment of 2,497 infants has now been completed by April 1997, and the follow-up phase will continue until 1999.

Transdermal oestradiol gel in the treatment of the climacterium: a comparison with oral therapy.

OBJECTIVE: To compare two doses of a transdermal oestradiol gel (Divigel/Sandrena) plus oral sequential medroxyprogesterone acetate (MPA) with oral oestradiol valerate plus oral sequential MPA (Divina/Dilena). DESIGN: Two year, randomised, open-label, comparative study. SETTING: Menopausal outpatient clinic in Helsinki. SUBJECTS: Postmenopausal women with climacteric complaints or already using HRT. INTERVENTIONS: (1) One gram gel containing 1 mg oestradiol for 3 months plus 20 mg oral MPA during the last 14 days; (2) 2 g gel containing 2 mg oestradiol for 21 days plus 10 mg oral MPA during the last 14 days; (3) 2 mg oestradiol valerate tablets for 3 weeks plus 10 mg oral MPA during the last 10 days. In all groups, each treatment period was followed by a 7-day medication-free interval. MAIN OUTCOME MEASURES: Climacteric complaints, bleeding control, bone mineral density, biomarkers of bone metabolism, lipid profile, tolerability and safety. RESULTS: With each preparation, climacteric complaints were significantly reduced and good bleeding control was obtained. In addition, maintenance of bone mineral density as well as a reduction of bone turnover was achieved in all groups. Lipid parameters showed no unfavourable changes. Continuation rates were similar in all groups with overall 74% of patients completing the first year, whereas 94% of patients who elected to continue completed the second year. Tolerability of the gel was good: only 1.7% of patients discontinued treatment due to skin irritation. CONCLUSIONS: Transdermal oestradiol gel and oral oestradiol valerate tablets, used in combination with oral sequential MPA, are effective regimens of HRT in postmenopausal women. Transdermal oestradiol gel is an efficient, well-tolerated form of HRT.

HRT and exercise: effects on bone density, muscle strength and lipid metabolism. A placebo controlled 2-year prospective trial on two estrogen-progestin regimens in healthy postmenopausal women.

OBJECTIVES: To evaluate the effect of 1- or 3-monthly sequential combinations of estradiol valerate (E2V) and medroxyprogesterone acetate (MPA) on menopausal symptoms, bone density, muscle strength and lipid metabolism in postmenopausal women. METHODS: Changes in bone mineral density (BMD), isometric muscle strength, serum lipids and climacteric symptoms were evaluated in 78 women, 49-55 years of age, with a spontaneous menopause 0.5-3 years earlier. Treatment group I received 2 mg E2V tablets for 11 days, followed by 2 mg E2V + 10 mg MPA for 10 days and placebo for an additional 7 days; treatment group II received 2 mg E2V for 70 days, 2 mg E2V + 20 mg MPA for 14 days, and placebo for 7 days. The placebo group received placebo continuously for 24 months. Each group was further randomised to exercise and non-exercise subgroups. RESULTS: Both hormone regimens significantly reduced menopausal symptoms, and prevented equally well the decrease of BMD both in the lumbar spine and proximal femur. A positive effect of exercise on BMD was observed in the placebo group. No synergistic effect of exercise and estrogen on BMD could be shown. Both hormone regimens increased the isometric strength of back extensor muscles. Serum total and LDL cholesterol decreased during the first year with both estrogen regimens. CONCLUSIONS: Estrogen-progestin regimens were equally effective in the control of menopausal symptoms and preventing bone loss, increasing muscle strength and lowering serum cholesterol.

Pneumococcal capsular antigen detection after enrichment culture: an alternative to culture methods in epidemiologic research.

Bacterial culture of Streptococcus pneumoniae followed by serotyping is not always feasible under field conditions. Antigen detection methods could be an alternative, but they are associated with sensitivity problems. In an effort to improve their sensitivity, we introduced an enrichment phase before antigen detection and compared the results with direct bacterial culture, using nasopharyngeal swabs from 95 children with symptoms of acute respiratory infection. Antigen detection was performed by latex agglutination and counterimmunoelectrophoresis. Streptococcus pneumoniae was found in 29 (30%) of the samples by culture, and in 42 (44%) by antigen detection after enrichment, an excess of 45% over culture findings. This excess was shown to represent true positive samples since pneumococcal DNA could be detected by polymerase chain reaction in all 15 antigen-positive, culture-negative samples. Two culture-positive samples were antigen-negative; in one of these the bacteria were nonencapsulated. We conclude that for type-specific demonstration of S. pneumoniae, detection of pneumococcal antigen after an enrichment step is a sensitive method that can be applied for epidemiologic study purposes, e.g., in vaccine trials, in areas without ready access to a good microbiology laboratory.

Pneumococci in nasopharyngeal samples from Filipino children with acute respiratory infections.

The presence of Streptococcus pneumoniae in the upper respiratory tract was studied in 318 Filipino children less than 5 years old with an acute lower respiratory tract infection. Nasopharyngeal samples were obtained from 292 children. With both quantitative bacterial culture and detection of capsular polysaccharide antigens by coagglutination, counterimmunoelectrophoresis, and latex agglutination, pneumococci were found in 160 (70%) of the 227 samples eligible for analysis. Culture was positive in 115 samples and antigen was positive in 140 samples. The culture isolation rate was significantly lower if the patient had received antimicrobial agents in the 48 h prior to the sampling. The seven most common types or groups of pneumococci were 6, 14, 19, 23, 15, 7, and 11, which together accounted for 64% of all pneumococcal findings.

Hepatic safety of erythromycin acistrate in 1549 patients with respiratory tract or skin infections.

Erythromycin acistrate is a new 2'-acetyl esther prodrug of erythromycin, whose structure resembles that of erythromycin estolate. However, in toxicological studies, it does not have the problems of hepatotoxicity. To assess its effects on hepatic functions in clinical practice, the liver parameters of patients with respiratory tract or skin infections were monitored during therapy. In total 1549 patients were treated for 7-14 days. In addition, 127 patients with suspected viral infections served as controls. There were no significant differences in serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyltransferase (gamma-GT) or alkaline phosphatase (APHOS) values between the erythromycin acistrate or control groups at the beginning or end of therapy. ASAT values increased moderately in 2.4% and clearly in 0.3% of patients treated, but also decreased in 2.0%. ALAT values were moderately increased in 9.9%, clearly increased in 0.6% and normalized in 3.5% of the patients. gamma-GT values increased moderately in 3.5% and and clearly in 0.3%, but decreased to normal in 3.3% of the patients. APHOS was moderately elevated in 1.0% of the patients and normalized in 1.3%. The correlation of changes between the different liver enzymes was poor. Only ten patients (0.6%) had two or more clearly elevated liver enzyme values by the end of the therapy, of whom five had increased liver enzyme activities before the treatment, two had underlying disease explaining the changes and in only three patients out of 1549 (0.2%) could hepatic changes be attributed to erythromycin acistrate therapy. These changes were reversible. The results demonstrate the hepatic safety of erythromycin acistrate in clinical practice. Concomitant food intake did not affect the safety profile.