A biopsy-based quick test in the diagnosis of duodenal hypolactasia in upper gastrointestinal endoscopy.

BACKGROUND AND STUDY AIMS: The usefulness of a new quick test for endoscopic diagnosis of adult-type hypolactasia was tested in duodenal biopsies. In this test, an endoscopic biopsy from the postbulbar duodenum is incubated with lactose on a test plate, and a color reaction develops within 20 min as a result of hydrolyzed lactose (a positive result) in patients with normolactasia, whereas no reaction (a negative result) develops in patients with severe hypolactasia. PATIENTS AND METHODS: Two postbulbar duodenal biopsies were taken from 80 prospectively enrolled adult outpatients with dyspepsia. The biopsies were used for the Quick Lactase Test (Biohit PLC, Helsinki, Finland) and in biochemical disaccharidase (lactase, sucrase, and maltase) assays. In addition, the C/T (-13,910) genotype was determined from DNA extracted from gastric antral biopsies using polymerase chain reaction sequencing in genomic analysis of adult-type hypolactasia. RESULTS: Twenty-one of 22 patients (95 %; 95 % CI, 87 - 100 %) with biochemical lactase activity < 10 U/g protein, but none of the 58 patients with lactase activity of 10 U/g protein or more had a negative result in the Quick Lactase Test. Seven of the 80 patients (9 %; 95 % CI, 3 - 15 %) had a Quick Lactase Test result that indicated mild hypolactasia (a mild color reaction). All patients with celiac disease (n = 6) had a negative Quick Lactase Test result. Nine of 74 patients (six patients with celiac disease were excluded) had a CC (-13,910) genotype in genomic testing, indicating adult-type hypolactasia. All of them had negative test results with the Quick Lactase Test. Twenty-six patients had a TT genotype, indicating normolactasia, and none of these patients had a negative test result in the Quick Lactase Test. Six of 39 patients (15 %; 95 % CI, 4 - 27 %) with a CT genotype had a negative result in the Quick Lactase Test. CONCLUSIONS: The Quick Lactase Test effectively identifies patients with severe duodenal hypolactasia. In comparison with CC (adult-type hypolactasia) and TT individuals (normolactasia), the sensitivity and specificity of the Quick Lactase Test result was 100 %. In comparison with biochemical lactase assays, the sensitivity and specificity of a negative Quick Lactase Test for indicating hypolactasia (lactase activity < 10 U/g protein) were 95 % (95 % CI, 87 - 100 %) and 100 %, respectively.

Diagnosis of atrophic gastritis from a serum sample.

On the basis of the levels of serum pepsinogen I (S-PGI) and gastrin-17 (S-G-17) as well as Helicobacter pylori antibodies it is possible to establish with high sensitivity and specificity whether the patient has gastritis, whether the gastritis is atrophic or not and in which part of the stomach the atrophic changes are located. The tests enable the identification of patients whose risk of gastric cancer, consequences of vitamin B12 deficiency or peptic ulcer is increased considerably and who should therefore undergo gastroscopy. They also facilitate diagnosis of non-atrophic Helicobacter gastritis enabling treatment before endoscopy.

Prevalence of low vitamin B12 and high homocysteine in serum in an elderly male population: association with atrophic gastritis and Helicobacter pylori infection.

BACKGROUND: Deficiency of vitamin B12 raises the serum and tissue levels of homocysteine. Atrophic corpus gastritis results in impaired secretion of intrinsic factor and may lead to malabsorption of vitamin B12 in the intestine. We examined how common an undiagnosed vitamin B12 deficiency is among elderly men in the general population and, in particular, how often this deficiency is related to atrophic corpus gastritis. METHODS: The serum level of pepsinogen I (S-PGI) was assayed in a population-based sample of 12,252 men (age 51-65 years) from two cities in Finland. In this sample, all 635 men with S-PGI < 25 microg/l formed Series A ('males with atrophic corpus gastritis'). Series C (controls--'males without atrophic corpus gastritis)' with a non-atrophic gastric corpus was formed as a random sample of men (n = 402) with S-PGI > or = 50 microg/l. Serum levels of vitamin B12 (S-B12), folate (S-Fol), total homocysteine (S-Hcy) and Helicobacter pylori antibodies (S-HpAb) were assayed in all, or in large subsamples, of the men in Series A and C. RESULTS The men in Series A had significantly lower S-B12 and S-Fol levels than those in Series C. In Series A, 172 of 613 men tested (28%) had S-B 12 < 170 pmol/ 1, and 133 men (22%) had S-B 12 in the range 170-219 pmol/l. The corresponding prevalences were 7% (P < 0.001) and 17% (P < 0.001) in Series C, respectively. The mean S-Hcy was significantly higher in Series A in men with low S-B12 than the mean S-Hcy in Series C in men with normal S-B12. The prevalence of S-Hcy > 15 ,micromol/l was 27% in Series A and 15% in Series C (P < 0.05; chi2 = 4.63). Among subjects with S-B 12 < 220 pmol/l, 46% (104 of 226 men tested) in Series A and 16% (16 of 99) in Series C had S-Hcy > or = 15 micromol/l (P < 0.001). The mean S-Hcy was significantly (P < 0.001) higher in men with S-B12 in the range 170-219 pmol/l in Series A (mean 14.6 +/- 5.0 micromol/l) than in Series C (11.3 +/- 3.0 micromol/l). It was extrapolated that 2.5% of men in the age group 51-65 years in the present study population had a low S-B12 (< 220 pmol/l) level that associated with atrophic corpus gastritis. Of these men, 72% (128 of 179 tested) had an elevated S-HpAb level. CONCLUSIONS: Low S-B12 related to atrophic corpus gastritis is relatively common (prevalence 2.5%) among elderly males in the general population. An ongoing H. pylori infection occurs in three-fourths of these cases.

Serum levels of amidated gastrin-17 and pepsinogen I in atrophic gastritis: an observational case-control study.

BACKGROUND: Helicobacter pylori infection is often diagnosed with non-endoscopic methods, such as serology or breath or antigen stool tests. These tests provide information on the presence or absence of the H. pylori gastritis only. We investigated whether atrophic gastritis can be diagnosed and typed non-endoscopically if the serum levels of pepsinogen I (S-PGI) and gastrin-17 (S-G-17) are assayed in connection with H. pylori testing. METHODS: The present investigation is an observational case-control study comprising 100 selected dyspeptic outpatients with (cases) or without (controls) advanced (moderate or severe) atrophic gastritis. Before the blood tests, all patients underwent a diagnostic gastroscopy with multiple biopsies. The series of cases includes 56 patients. Eight had an advanced antrum limited atrophic gastritis, 13 had resected antrum (in two of whom the corpus mucosa in the stump was atrophic), and 30 had corpus-limited atrophic gastritis. Four patients had an advanced atrophic gastritis in both the antrum and corpus (multifocal atrophic gastritis), and the whole stomach was removed in one patient. Twenty of the 44 controls had a non-atrophic H. pylori gastritis. Both the antrum and corpus were normal and healthy in 24 patients. The S-PGI and S-G-17 were determined with EIA methods using monoclonal antibodies to PGI and amidated G-17. Postprandial S-G-17 (S-G-17prand) was measured 20 min after a protein-rich drink. The H. pylori antibodies were assayed with a polyclonal EIA method. RESULTS: A low S-PGI (<25 microg/l; an empirical cut-off with best discrimination) was found in 31 of 37 patients (84%) with and in 3 of 63 patients (5%) without corpus atrophy in the biopsy specimens. A low S-G-17prand (<5 pmol/l) was found in all 8 patients with H. pylori-associated antral atrophy and in 11 of 14 patients (79%) with resected antrum but in 3 of 20 control patients (15%) with H. pylori-related non-atrophic gastritis. Median and mean values of both S-G-17prand and S-PGI decreased with increasing grade of antral and corpus atrophy, respectively. Among all patients with atrophic gastritis (multifocal atrophic gastritis, or atrophic gastritis limited to antrum or corpus) or resected stomach, 50 of 56 patients (89%; Cl 95%: 81%-97%) had a low S-PGI and/or a low S-G-17prand with positive H. pylori serology. Such low values werc found in 3 of the 44 control patients (7%; CI 95%: 0%-14%). CONCLUSIONS: Low serum levels of G-17prand and PGI are conceivable biomarkers of atrophic antral and corpus gastritis, respectively. A low S-G-17prand is a sign of the multifocal or antrum-limited atrophic gastritis in patients infected with H. pylori.

The effect of Helicobacter pylori eradication on the natural course of atrophic gastritis with dysplasia.

BACKGROUND: There are few data on the natural course of Helicobacter pylori-related atrophic gastritis. AIM: To investigate the effect of H. pylori eradication on advanced atrophic gastritis in the corpus. METHODS: Twenty-two elderly men with H. pylori infection and moderate or severe atrophic corpus gastritis formed the study population. These men were under endoscopic surveillance because of the presence of indefinite or definite dysplastic gastric lesions in addition to atrophic corpus gastritis. The men were gastroscopically and bioptically examined four times before they received H. pylori eradication therapy (mean follow-up time, 7.5 years), and once again 2.5 years after eradication therapy. Serum levels of pepsinogen I and H. pylori antibodies were analysed at baseline, immediately before and 2.5 years after eradication therapy. RESULTS: During the 7.5-year period prior to eradication therapy, no significant changes were observed in the mean atrophy and intestinal metaplasia scores or in the mean serum level of pepsinogen I. However, a significant improvement occurred in the mean histological scores of inflammation (from 2.2 to 0.5), atrophy (from 2.2 to 1.2) and intestinal metaplasia (from 1.6 to 1.1) in the corpus mucosa after H. pylori eradication. In addition, the mean serum level of pepsinogen I increased from 16.3 to 25.7 microg/L (P=0.0071, Wilcoxon signed rank test) after eradication therapy. CONCLUSIONS: The results suggest that advanced atrophic corpus gastritis (and intestinal metaplasia) improves and may even heal after the eradication of H. pylori.

Increased risk of developing atrophic gastritis in patients infected with CagA+ Helicobacter pylori.

BACKGROUND: To clarify the possible role of CagA positive (CagA+) Helicobacter pylori strains in the development of atrophic gastritis, the prevalence of antibodies to H. pylori and CagA (120 kD protein) was studied among subjects with atrophic and non-atrophic gastritis. METHODS: The study population was randomly selected among 12,252 Finnish men who were screened for atrophic corpus gastritis with serum pepsinogen I-assay (S-PGI). S-PGI level was used as a selection criterion. Group A consisted of 295 subjects with S-PGI <25 microg/l (low), group B of 320 subjects with S-PGI 25-100 microg/l (normal) and group C of 338 subjects with S-PGI >100 microg/l (high). Antibodies to H. pylori were measured with EIA and immunoblot analysis and antibodies to CagA with immunoblot analysis. Endoscopical and histological examinations were performed for 203 patients from group A. RESULTS: The prevalence of antibodies to H. pylori was significantly lower in group B than in groups A or C (P < 0.0001, chi-squared test). There was a significant association between the prevalence of antibodies to CagA and the lowered level of S-PGI (P < 0.0001, Jonckheere-Terpstra trend test). There was also a linear decrease in the prevalence of antibodies to CagA as the atrophic corpus gastritis became more severe (P < 0.0001, linear-by-linear trend test). CONCLUSION: The presence of antibodies to CagA seems to be associated with development of atrophic corpus gastritis.

Expression of cyclooxygenase-2 in dysplasia of the stomach and in intestinal-type gastric adenocarcinoma.

PURPOSE: Cyclooxygenase (Cox) is the key enzyme in conversion of arachidonic acid to prostanoids. Two Cox genes have been cloned, and expression of Cox-2 mRNA and protein has been shown to be elevated in several human malignancies and in animal models of carcinogenesis. The purpose of this study was to investigate Cox-2 protein expression in human gastric dysplasias and adenocarcinomas. EXPERIMENTAL DESIGN: Performance of several Cox-2 antibodies was evaluated, after which Cox-2 protein expression was studied in 67 gastric cancer specimens and in eight definitive dysplasias by using immunohistochemistry. RESULTS: Cox-2 positivity was detected in 58% (25/43) of the intestinal-type (well-differentiated) tumors and 6% (1/18) of diffuse-type (poorly differentiated) tumors. Consistent with these data, we detected higher expression of Cox-2 mRNA, protein, and enzymatic activity in well-differentiated gastric cancer cell lines (MKN-28 and MKN-74) when compared with poorly differentiated cell lines (HSC-39 and KATO III). Cox-2 immunoreactivity was localized to the carcinoma cells, but the stroma of the tumors was negative. However, strong Cox-2 positivity was consistently detected in stromal cells at sites of erosions and ulcerations. Furthermore, four of nine (44%) definitive dysplasias of the stomach that showed no evidence of invasion were positive for Cox-2. CONCLUSIONS: Cox-2 is expressed by the neoplastic cells in the intestinal-type gastric adenocarcinoma and by precarcinogenic (dysplastic) lesions leading to this disease.

ATP, phosphocreatine and lactate in exercising muscle in mitochondrial disease and McArdle's disease.

We studied exercise-induced changes in the adenosine triphosphate (ATP), phosphocreatine (PCr), and lactate levels in the skeletal muscle of mitochondrial patients and patients with McArdle's disease. Needle muscle biopsy specimens for biochemical measurement were obtained before and immediately after maximal short-term bicycle exercise test from 12 patients suffering from autosomal dominant and recessive forms of progressive external ophthalmoplegia and multiple deletions of mitochondrial DNA (adPEO, arPEO, respectively), five patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) 3243 A-->G point mutation, and four patients with McArdle's disease. Muscle ATP and PCr levels at rest or after exercise did not differ significantly from those of the controls in any patient group. In patients with mitochondrial disease, muscle lactate tended to be lower at rest and increase more during exercise than in controls, the most remarkable rise being measured in patients with adPEO with generalized muscle symptoms and in patients with MELAS point mutation. In McArdle patients, the muscle lactate level decreased during exercise. No correlation was found between the muscle ATP and PCr levels and the respiratory chain enzyme activity.

Ethanol infusion increases ANP and p21 gene expression in isolated perfused rat heart.

Whether alcohol-induced heart failure is caused by a direct toxic effect of ethanol, metabolites, or whether it is a secondary result of neurohumoral, hormonal, or nutritional factors is not clear. To address this question a Langendorff retrograde coronary perfusion model of rat heart was used to study the effect of 0.5% (v/v) ethanol (n = 7) and 0.5 mM acetaldehyde (n = 9) on left ventricular expression of ANP, BNP, p53, p21, TNF-alpha,bax, bcl-2 as well as on DNA-fragmentation. Ethanol infusion of 150 min duration significantly induced both ANP and p21 mRNA expression of ventricular myocardium compared with hearts infused with vehicle (n = 8). Acetaldehyde did not exert any significant effects on any of the parameters studied, although the mean expression of TNF-alpha tended to be lower in the acetaldehyde-treated hearts than in control hearts. No evidence of increased DNA-fragmentation was found in ethanol or acetaldehyde treated groups. We conclude that ethanol per se is capable of inducing genes associated with hypertrophy and impaired function of the heart whereas a significant apoptosis is not involved in the initial phase of alcohol-induced cardiac injury.

Predictors and clinical significance of declining plasma dehydroepiandrosterone sulfate in old age.

Dehydroepiandrosterone sulfate (DHEAS) was measured in random persons of three age cohorts (75, 80 and 85 years, N=271) at five-year intervals in order to find out predictors and significance of declining DHEAS in old age. The mean values decreased from 2.88 micromol/L to 2.39 micromol/L in men (p<0.001), and from 1.93 micromol/L to 1.73 micromol/L in women (p<0.05) at entry. Strong correlations were found between the baseline levels of DHEAS and those measured after five years both in men (r=0.727, p<0.001) and women (r=0.605, p<0.001), and the changes in DHEAS were associated with DHEAS levels at entry (r=-0.418, p<0.05). Baseline DHEAS was higher (2.47 micromol/L vs 2.05 micromol/L, p<0.05) and the decline more pronounced (-0.50 micromol/L vs 0.20 micromol/L, p<0.05) in the healthy subjects than in those suffering from diseases at entry, but the percentage five-year decline was similar (-6.5% and -5.2%) in both groups. The five-year decline in DHEAS was predicted neither by the baseline levels of risk indicators, e.g., serum lipids, body mass index, electrocardiographic, nor echocardiographic findings at entry. The age-and gender-adjusted baseline levels of DHEAS predicted neither mortality nor cognitive decline with 5- and 10-year follow-up periods. The 5-year decline in DHEAS was significant (p<0.05) in the subjects who died or developed cognitive decline during the subsequent 5-year follow-up. However, the changes did not differ significantly from those with favorable prognosis. The data indicate that the decline in DHEAS is primarily a gender-specific aging phenomenon, and only partly a consequence of actual diseases and frailty.

Implications of serum pepsinogen I in early endoscopic diagnosis of gastric cancer and dysplasia. Helsinki Gastritis Study Group.

BACKGROUND AND AIMS: The risk of gastric cancer (GCA) is increased in atrophic gastritis. A low serum pepsinogen group I (SPGI) level is a good serologic indicator of atrophic gastritis of the gastric corpus and fundus, and can be used for diagnosis of subjects with atrophic gastritis and of increased risk for GCA. The present study was undertaken to investigate whether SPGI assay and a diagnostic gastroscopy could enable the diagnosis of GCA at an early stage. MATERIAL AND METHODS: The study was carried out as part of the Alpha-Tocopherol, Beta-Carotene Cancer prevention study (ATBC study) in Finland, in which 22,436 male smokers aged 50-69 years were screened by SPGI. Low SPGI levels (< 25 microg/l) were found in 2196 (9.8%) men. Upper GI endoscopy (gastroscopy) was performed in 1344 men (61%) and 78% of these had moderate or severe atrophic corpus gastritis in endoscopic biopsies. A control series of 136 men from the ATBC study cohort with abdominal symptoms, but with SPGI > or = 50 microg/l were similarly endoscopied, and 2.2% of these had corpus atrophy. RESULTS: Neoplastic alterations were found in 63 (4.7%; 95% CI: 3.6%-5.8%) of the 1344 endoscopied men with low SPGI levels. Of these, 42 were definite dysplasias of low grade, 7 dysplasias of high grade, 11 invasive carcinomas, of which 7 were 'early' cancers, and 3 carcinoid tumors. In the control series, 1 man (0.7%) of the 136 men had a definite low-grade dysplasia. Thus, 18 (1.3%; 95% CI 0.7%-2.0%) cases with 'severe' neoplastic lesions (4 advanced cancers, 7 early cancers and 7 dysplasias of high grade) were found in the low SPGI group, but there were none in the control group. All four patients with advanced cancer died from the malignancy within 5 years (mean survival time 2.5 years), whereas surgical treatment in all those with early cancer or high-grade dysplasia was curative. One of the seven patients with early cancer and two of the seven with high-grade dysplasia died within 5 years, but none died from the gastric cancer. Thus, curative treatment was given to 14 of 18 men in whom a malignant lesion was found in gastroscopy. This is about 15% of all gastric cancer cases (92 cases) which were diagnosed within 5 years after SPGI screening in the 22,436 men. Among the gastric cancer cases of the main ATBC study, the 5-year survival rate was 33% (85% of the non-survivors died from gastric cancer). CONCLUSIONS: We conclude that assay of SPGI followed by endoscopy is an approach which can enable the early diagnosis of gastric cancer at a curable stage.

Myosin heavy chain mRNA and protein distribution in immobilized rat skeletal muscle are not affected by testosterone status.

The effects of testosterone treatment and gonadectomy on myosin heavy chain (MHC) messenger RNA (mRNA) and protein expression after 1 week's immobilization were studied in male rat gastrocnemius muscle. In the testosterone-treated group silastic testosterone capsules were implanted subcutaneously before immobilization. The gonadectomized animals were castrated at 5 weeks of age. One group of eugonadal animals served as the immobilized control group, and another as the sedentary control group. Immobilization was performed at 9 weeks of age by bilateral hindlimb casting. The body and muscle masses, and the amount of type IIa MHC mRNA decreased significantly (P<0.01) in the immobilized animals by approximately 30, 40 and 50%, respectively, regardless of the serum testosterone levels which ranged from 1.1+/- 0.4 to 59+/-14 nmol L(-1). In the immobilized testosterone-treated group the proportion of type IIx MHC mRNA increased to 14% of the total MHC mRNA (P=0.02, compared with control). The MHC protein distribution did not change significantly. There were no significant differences in any parameters between the three immobilized groups. In conclusion, neither the lack nor excess of testosterone significantly altered the changes caused by immobilization. Therefore, it seems that lack of mechanical loading is a far more important determinant of MHC expression than the male sex hormone status.

Role of acetaldehyde in the induction of heart left ventricular atrial natriuretic peptide gene expression in rats.

We studied the effects of ethanol and acetaldehyde on myocardial gene expression of atrial natriuretic peptide (ANP) and growth of rats. Combined ethanol and calcium carbimide treatment increased blood-acetaldehyde levels and ANP mRNA levels by 40-60% in 2-8 day experiments, compared to the controls. The results suggest a role for acetaldehyde in the development of alcoholic heart dysfunction.

The effect of physical training on skeletal muscle in patients with chronic heart failure.

BACKGROUND: The improvement of exercise capacity in patients with chronic heart failure (CHF) by physical training has been connected with reversal of the abnormalities in muscle fiber distribution and with the reduced activity of the enzymes of oxidative metabolism in skeletal muscle. However, the change in fiber type distribution induced by training is controversial and in previous studies the activities of the rate-limiting enzymes of the metabolic pathways have not been measured. AIMS: To examine the effect of dynamic training on percentage distribution of muscle fibers, on activities of the rate-limiting enzymes of the metabolic pathways and on electrophysiology in skeletal muscle. METHODS: A total of 27 patients with stable CHF (NYHA class II-III) were randomized to a training (N=12) or a control (N=15) group. The training group exercised on a bicycle ergometer for 30 min three times a week for 3 months using a load corresponding to 50-60% of their peak oxygen consumption. This was followed by a 3-month training period at home according to personal instructions. The control group did not change its physical activities. We studied muscle histology and measured the activities of the rate-limiting enzymes of anaerobic glycolysis (phosphofructokinase, PFK), glycogenolysis (phosphorylase), citric acid cycle (alpha-ketoglurate dehydrogenase, KGDH) and fatty acid oxidation (carnitinepalmitoyl transferase I and II, CPT I and II) from biopsies of the vastus lateralis muscle at baseline and after 3 and 6 months. Muscle strength and strength endurance with surface EMG and macro EMG of the right knee extensors were also determined. RESULTS: Exercise capacity, particularly submaximal, improved in the training group. The activity of PFK rose significantly but that of the other enzymes did not when compared with the change in the controls. Training had no effect on the percentage distribution of slow-twitch and fast-twitch muscle fibers or on capillary density around these fibers in skeletal muscle. Maximum voluntary force, strength endurance and the function of motor units remained unaffected. CONCLUSIONS: Dynamic training results in improved exercise endurance in CHF. In skeletal muscle, the capacity of anaerobic glycolysis is increased but that of the citric acid cycle and fatty acid oxidation is not. Furthermore, the improvement in exercise endurance seems to be independent of changes in the percentage distribution of muscle fibers, capillarity or electrophysiological factors.

The effect of androgen status on skeletal muscle myosin heavy chain mRNA and protein levels in rats recovering from immobilization.

Immobilization rapidly alters skeletal muscle. The aim of the present study was to determine whether testosterone administration or, in contrast, hypogonadism affects the recovery of muscle mass and myosin heavy chain (MHC) profile at both the mRNA and protein level, after 1 week of immobilization. Male rats were assigned to one of five groups: control (C), hindlimb-immobilized (IMM), and recovery (REC; where animals were allowed 2 weeks of free cage-activity after immobilization). The recovery group was further divided to eugonadal (REC-C), castrated (REC-GDX), and a testosterone-treated (REC-T). In all groups except REC-T, the body masses after immobilization were smaller than in C, although after immobilization the body mass in REC-T recovered at a slower rate than in the other two REC groups. The gastrocnemius mass and the amount of type IIa MHC mRNA decreased during immobilization, but the control levels were regained after recovery. The amount of type IIb mRNA was reduced in REC-GDX compared to C and IMM. The changes in the relative distribution of MHC mRNA were in line with these results. After recovery, the proportion of type IIx MHC protein increased and type IIb protein decreased, although in REC-T the changes were not statistically significant. The proportion of type IIa MHC protein increased only in REC-GDX. In summary, during recovery from immobilization it seems that muscle mass increases and the MHC mRNA and protein profile tend to change toward a slower phenotype, primarily as a result of the decrease in type IIb MHC. However, these changes occur rather independently of the testosterone status.

Thyroid function in cord blood.

OBJECTIVE: To determine the biochemical parameters of thyroid function in the cord blood of Saudi infants. METHODS: Cord blood samples sent to the Pathology Department for screening for congenital hypothyroidism were used to determine the reference ranges for thyrotropin, free thyroxine, free triiodothyronine, thyroxine-binding globulin and thyroglobulin. All the measurements were carried out by immunoassay (Elisa, microparticle enzyme immunoassay or chemiluminescence immunoassay). Reference ranges were calculated after exclusion of outliers. RESULTS: Reference ranges for thyrotropin, free thyroxine and thyroxine-binding globulin were similar to published values, whereas those for free triiodothyronine and thyroglobulin were different. CONCLUSION: For correct interpretation of the parameters of thyroid function in cord blood it is essential to have reference ranges based on the laboratory's current methods and derived from the local population.

Levofloxacin in the empirical treatment of patients with suspected bacteraemia/sepsis: comparison with imipenem/cilastatin in an open, randomized trial.

An open, randomized, multinational, multicentre study was conducted to compare the efficacy, safety and tolerability of levofloxacin 500 mg twice daily with imipenem/cilastatin 1 g iv three-times daily in the treatment of hospitalized adult patients with clinically suspected bacteraemia/ sepsis. Levofloxacin patients could change from iv to oral administration after a minimum of 48 h iv treatment if clinical signs and symptoms of sepsis had improved. The primary efficacy analysis was based on the clinical and bacteriological response at clinical endpoint. A total of 503 patients were randomized and 499 included in the intent-to-treat population. The per-protocol population comprised 287 patients with bacteriologically proven infection. Clinical cure rates at clinical endpoint in the intent-to-treat population and per-protocol population were 77% (184/239) and 89% (125/140), respectively, for levofloxacin and 68% (178/260) and 85% (125/147), respectively, for imipenem/cilastatin. At follow-up, the cure rates in the per-protocol population were 84% for levofloxacin and 69% for imipenem/cilastatin. The 95% confidence interval for both populations showed that levofloxacin was as effective as imipenem/cilastatin. A satisfactory bacteriological response was obtained in 87% (96/110) of levofloxacin patients and 84% (97/116) of imipenem/cilastatin patients at clinical endpoint. Adverse events possibly related to the study drug were reported in 74 (31%) levofloxacin patients and 79 (30%) imipenem/cilastatin patients. There were no clinically appreciable differences between the treatment groups. Levofloxacin 500 mg twice daily, either iv or as sequential iv/oral therapy, was as effective and well tolerated as imipenem/cilastatin 1 g iv three-times daily in the treatment of hospitalized patients with suspected bacteraemia/sepsis.

Dehydroepiandrosterone sulfate, diseases and mortality in a general aged population.

Dehydroepiandrosterone sulfate (DHEAS) was measured in a five-year follow-up study of random persons of three age cohorts (75-, 80-, and 85-years, N = 571) in order to investigate its associations with clinical diseases and their risk indicators, as well as its prognostic significance in old age. DHEAS was higher in men (3.1 mumol/L) than in women (1.9 mumol/L) in the 75-year age group. It decreased in men up 85 years. Compared to healthy men, DHEAS was lower in men with a history of or manifest vascular diseases, presence of dementia, diabetes mellitus, malignancies and musculoskeletal disorders, but was similar in all these disease groups. No differences were found in women. DHEAS did not relate to cardioechographic findings, cardiovascular risk factors or predictors of impaired survival prognosis. After controlling for age, DHEAS tended to be lower in the non-surviving than in the surviving men (2.28 mumol/L vs 2.65 mumol/L, p = 0.065). After controlling for disease, DHEAS did not predict increased risk of all-cause or cardiovascular mortality during the 5-year follow-up. In this study, gender differences in DHEAS persisted up to the age of 75 years. Low plasma DHEAS appears to be a secondary phenomenon rather than a specific risk indicator of common diseases in old age.

The effect of physical training on hormonal status and exertional hormonal response in patients with chronic congestive heart failure.

BACKGROUND: Physical training improves exercise capacity in patients with chronic heart failure. It decreases plasma noradrenaline at rest, which may be prognostically favourable. The effect on atrial natriuretic peptide, another prognostic factor, and on catabolic and anabolic hormones remains unknown. Furthermore, to our knowledge, the contribution of exertional hormonal responses to the improved exercise capacity has not been evaluated. METHODS: 27 patients with stable chronic heart failure (New York Heart Association class II-III) were randomized to training (n=12) and control (n=15) groups. The training group exercised on a bicycle ergometer for 30 min three times a week for 3 months. The load corresponded to 50-60% of their peak oxygen consumption. For the next 3 months they exercised at home according to personal instructions. The control group did not change its physical activities. The levels of hormones regulating the cardiovascular system and metabolism were determined at rest and after graded maximal exercise and during exercise with constant submaximal workload. RESULTS: Submaximal exercise capacity increased significantly and peak oxygen consumption tended to improve by 12% in the training group. The plasma noradrenaline at rest tended to decrease by 19%. The plasma level of N-terminal pro atrial natriuretic peptide did not change. Serum cortisol, a catabolic hormone, was normal at baseline and remained unchanged. The serum levels of anabolic hormones, growth hormone and insulin, as well as dehydroepiandrosteronesulfate and free testosterone were within a normal range at baseline. They were not altered by training. The dehydroepiandrosteronesulfate/cortisol, and the free testosterone/cortisol ratios, reflecting anabolic/catabolic balance, did not change, either. Training resulted in a higher peak noradrenaline response during graded maximal exercise. The rise in serum cortisol during exercise tended to attenuate. CONCLUSION: Physical training, which improves exercise capacity, does not have an unfavourable effect on anabolic/catabolic balance or neurohumoral activation in patients with congestive heart failure. It decreases plasma noradrenaline at rest. Minor changes in hormonal responses during exercise emerged after physical training which unlikely contribute to the improved exercise capacity.