Cross-feeding between Bifidobacterium infantis and Anaerostipes caccae on lactose and human milk oligosaccharides.

The establishment of the gut microbiota immediately after birth is a dynamic process that may impact lifelong health. At this important developmental stage in early life, human milk oligosaccharides (HMOs) serve as specific substrates to shape the gut microbiota of the nursling. The well-orchestrated transition is important as an aberrant microbial composition and bacterial-derived metabolites are associated with colicky symptoms and atopic diseases in infants. Here, we study the trophic interactions between an HMO-degrader, Bifidobacterium infantis and the butyrogenic Anaerostipes caccae using carbohydrate substrates that are relevant in the early life period including lactose and total human milk carbohydrates. Mono- and co-cultures of these bacterial species were grown at pH 6.5 in anaerobic bioreactors supplemented with lactose or total human milk carbohydrates. A. caccae was not able to grow on these substrates except when grown in co-culture with B. infantis, leading to growth and concomitant butyrate production. Two levels of cross-feeding were observed, in which A. caccae utilised the liberated monosaccharides as well as lactate and acetate produced by B. infantis. This microbial cross-feeding points towards the key ecological role of bifidobacteria in providing substrates for other important species that will colonise the infant gut. The progressive shift of the gut microbiota composition that contributes to the gradual production of butyrate could be important for host-microbial crosstalk and gut maturation.

Circulating free insulin-like growth factor (IGF)-I, total IGF-I, and IGF binding protein-3 levels do not predict the future risk to develop prostate cancer: results of a case-control study involving 201 patients within a population-based screening with a 4-year interval.

Recent studies have reported that serum IGF-I levels in the highest quartile of the normal range and IGF binding protein-3 (IGFBP-3) in the lowest quartile of the normal range are associated with an increased risk of future prostate cancer and/or presence of prostate cancer. It has also been suggested that the measurement of circulating total IGF-I concentrations might be a useful tool for the early detection of prostate cancer in men with moderately increased prostate-specific antigen (PSA) levels. To determine whether circulating free IGF-I, total IGF-I, and IGFBP-3 levels can predict future prostate cancer risk, we prospectively studied prostate cancer characteristics in a cohort of men during two rounds (mean interval, 4 yr) of a population-based screening study for prostate cancer. Two hundred one prostate cancer cases were detected at the second-round screening (aged 55-70 yr), and all these subjects were enrolled in the case group for the present study. Prostate cancer had been confirmed by biopsy in all cases. These 201 subjects were matched with the 201 nonprostate cancer cases by age, serum PSA range at the first-round screening (PSA < 2 ng/ml, n = 67; PSA = 2-3 ng/ml, n = 67; and PSA = 3-4 ng/ml, n = 67), and residence area. At baseline, total IGF-I, free IGF-I, and IGFBP-3 levels and prostate volume of cases with prostate cancer were not different from those of healthy controls. PSA velocity was significantly different between cases and controls (P < 0.001).Stepwise forward logistic regression analysis showed that only PSA levels at baseline and PSA at round 2 after 4 yr are good predictors of prostate cancer, whereas total IGF-I, free IGF-I, and IGFBP-3 did not predict the development of prostate cancer. Only one of the 201 subjects with prostate cancer had metastases. Within the subjects with prostate cancer, there were no differences of IGF-I parameters with different tumor node metastasis categories and/or Gleason scores. Our study suggests that the measurement of serum IGF-I and/or IGFBP-3 concentrations in addition to PSA does not improve the identification of men at high risk to develop early stages of prostate cancer. In addition, our results indicate that the endocrine IGF-I system is not directly involved in the growth of the early stages of prostate cancer.

Spectrophotometric analysis of CSF after subarachnoid hemorrhage: limitations in the diagnosis of rebleeding.

We studied the course of CSF xanthochromia after subarachnoid hemorrhage by serial spectrophotometric analysis of lumbar CSF in 15 patients without clinical or CT evidence of rebleeding. The xanthochromic index rose in some patients up to the seventeenth day, and the proportion of oxyhemoglobin or the absolute concentration of hemoglobin often fluctuated. Therefore, rebleeding can be demonstrated in lumbar CSF only by increased xanthochromia, if previous samples had shown a decrease. These criteria could be applied in only 6 of 17 consecutive patients with rebleeding as demonstrated by CT, and they were met in 5.

Disease monitoring by the tumour markers cyfra 21.1 and TPA in patients with non-small cell lung cancer.

We evaluated the use of two tumour markers Cyfra 21.1 and tissue polypeptide antigen (TPA) for disease monitoring. Assessment of response to WHO criteria was compared to response assessment according to changes in the tumour marker levels. The criteria defined for marker response were a 65% decrease for a partial response and a 40% increase for progressive disease. When response evaluations with a positive lead time were included, 72% of 115 evaluations for Cyfra 21.1 and 59% of 107 evaluations for TPA yielded the same result. Most discordant evaluations were caused by those evaluations whereby the patient achieved a partial response according to the WHO criteria and had normalisation of the marker. Less cases with a positive lead time, more negative lead times, and more patients with progressive disease without an increase of the marker were seen with TPA compared to Cyfra 21.1. In conclusion, Cyfra 21.1 follows the changes in the tumour load better than TPA. Rising levels of both markers nearly always indicate disease progression, and such knowledge easily obtained may prevent the continuation of ineffective treatment.

Prognostic significance of tissue polypeptide-specific antigen (TPS) in patients with advanced non-small cell lung cancer.

In this study, we evaluated the prognostic value of the tumour marker, tissue polypeptide-specific antigen (TPS), in 203 patients with non-small cell lung cancer (NSCLC), and related this to several other known prognostic factors. TPS was significantly correlated with lactate dehydrogenase (LDH), gamma-glutamyltranspeptidase and alkaline phosphatase, and the median level of TPS in patients with stage 4 disease was significantly higher as compared to stage 3A and 3B disease. In the univariate analysis, performance status, stage of disease, LDH, alkaline phosphatase, a histology of undifferentiated large cell carcinoma and TPS all had a statistically significant association with survival. Multivariate analysis showed that stage of disease, performance status, histology and TPS were the most important prognostic factors. TPS has prognostic significance for survival in patients with advanced NSCLC, independent from performance status and stage of disease.

Evaluation of tissue polypeptide antigen serum levels for monitoring disease activity during chemotherapy in patients with transitional carcinoma of the urinary tract.

In 28 patients with transitional carcinoma of the urinary tract, all treated with chemotherapy, serial measurements of serum tissue polypeptide antigen (TPA) were performed and correlated to clinical evaluations of response. At the start of chemotherapy elevated levels of TPA were found in 4 out of 14 patients with T2-4NO-2MO tumours and in 7 out of 14 patients with distant metastases. In most patients with elevated TPA levels who responded to chemotherapy, TPA levels rapidly returned to normal. False positive elevations of TPA were observed in 2 patients. It is concluded that serial measurement of TPA for monitoring disease activity has limited value because of the low sensitivity of TPA, especially for patients with early-stage cancer, and because of the occurrence of false positive results.

The value of screening tests in the detection of prostate cancer. Part I: Results of a retrospective evaluation of 1726 men.

OBJECTIVES: The ratio between free and total prostate-specific antigen (PSA) in serum (F/T ratio) was shown to improve the differentiation between prostate carcinoma and benign conditions in selected series of patients. In this study the F/T ratio was analyzed for its ability to improve the specificity of total serum PSA, digital rectal examination (DRE), and transrectal ultrasonography (TRUS) for the detection of prostate cancer in an unselected screening population of men identified in the Rotterdam population. METHODS: In 1726 men between 55 and 76 years old, 67 prostate carcinomas were detected by DRE, TRUS, and total serum PSA (Abbott IMx, Hybritech Tandem E). The DELFIA ProStatus PSA EQM and ProStatus PSA Free/Total assays (Wallac) were applied in retrospect to determine total and free serum PSA. Age, total prostate and inner zone volumes were taken into consideration. RESULTS: Sixty-seven carcinomas were detected, two by TRUS and three by DRE alone. Total serum PSA was the most important single predictor of prostate cancer, followed by DRE. The F/T ratio increased the specificity of total serum PSA in the PSA range between 4.0 and 10.0 ng/mL. However, this improved specificity was not significant, nor for gland volumes restricted to 50 mL or less. CONCLUSIONS: The combination of total serum PSA and DRE remains the standard for detection of prostate carcinoma in a screening population. Their specificity may be improved minimally by the F/T ratio, but not significantly in a sample of 1726 screened men. The threshold of the F/T ratio, and the optimal PSA range for its application, remains to be assessed prospectively.

The value of screening tests in the detection of prostate cancer. Part II: Retrospective analysis of free/total prostate-specific analysis ratio, age-specific reference ranges, and PSA density.

OBJECTIVES: The ratio between free and total prostate-specific antigen (PSA) in serum (F/T ratio) was shown to improve the specificity of total serum PSA for the detection of prostate carcinoma in selected populations. In this study, the value of the F/T ratio for screening of prostate cancer was compared with that of age-specific reference ranges for PSA and PSA density (PSAD) by a simulation experiment. METHODS: In 1726 men between 55 and 76 years old, 67 prostate carcinomas were detected by application of digital rectal examination (DRE), transrectal ultrasonography (TRUS), and total serum PSA. A serum PSA of 4.0 ng/mL or more, an abnormal DRE, or an abnormal TRUS were the indications to perform 308 biopsies. A simulation was performed in which an F/T ratio of 0.20 (ProStatus PSA Free/Total), age-specific PSA reference ranges, and a PSAD of 0.12 ng/mL/cc were used to study their capability to increase the specificity of total serum PSA in predicting prostate biopsy results. RESULTS: Using age-specific PSA reference ranges and DRE as indicators for biopsy, a reduction of 37% (113) of biopsies would have been obtained with a loss of detected cancers of 12% (11). For the use of PSAD and DRE, these numbers were 28% (96) and 11% (7), respectively. Application of a serum PSA of 4.0 ng/mL or more and an F/T ratio of 0.20 or less and an abnormal DRE as indicators for biopsy would reduce the number of biopsies by 37% (112) and the number of detected cancers by 11% (7). The biopsy to prostate cancer ratio of these simulations varied between 3.3 and 3.6. Minimal loss of cancer detection of 3% (2) with a reduction in the number of biopsies of 17% (53) is obtained when TRUS is omitted from the screening protocol. Selecting men by a total serum PSA value of 2.0 ng/mL for further diagnostic workup by TRUS and DRE would have reduced the number of biopsies by 30% (102), and the number of cancers detected by 6% (4). CONCLUSIONS: The most cost-effective protocol for screening prostate carcinoma appears to be prescreening by total serum PSA. The F/T ratio might be used to detect carcinomas in the PSA range below 4.0 ng/mL, but the best threshold remains to be assessed.

Analytical issues on prostate-specific antigen in relation to prostate cancer screening.

OBJECTIVE: Evaluation of the analytical performance of the Hybritech Tandem-E PSA assay as applied to the Rotterdam part of the European Randomized Study of Screening for Prostate Cancer (ERSPC) during 1994-1997. DESIGN AND METHODS: For assessment of test performance imprecision and accuracy contributing to clinical decision making was examined. Pre-analytical variables (specimen handling), long-term reagents stability and calibration check with the Stanford 90:10 PSA Calibrator were studied. RESULTS: Total prostate-specific antigen proved to be a stable marker. Provided correct storage at 4 degrees C, we were not able to find differences between samples analyzed directly after blood withdrawal and those analyzed the following day, with or without centrifugation. Day-to-day precision, we found during 1997 a coefficient of variation of 4.9% for concentration 1.8 micrograms/L and 4.2% for 4.8 micrograms/L (n = 182). The variation among the 21 Tandem-E reagent batches used during 1994-1997 proved to be small. Application of the Stanford 90:10 PSA Calibrator revealed 3% higher values for Tandem-E. CONCLUSION: The overall, long-term picture of Tandem-E PSA is reliable in our hands. Possible differences from the true PSA values, not specific for Tandem-E, need to be elaborated.

New developments in the standardization of total prostate-specific antigen.

OBJECTIVE: Analytical evaluation of the calibration of three recently launched assays for the measurement of total prostate-specific antigen, i.e., IMx Total PSA (Abbott), Elecsys PSA (Roche), and IMMULITE 3rd Generation PSA (DPC). DESIGN AND METHODS: For accuracy assessment two reference materials were applied namely, Stanford 90:10 PSA Calibrator and Certified Reference Material 613 Prostate-Specific Antigen. Dilutions of these preparations were analyzed with all assays. In addition, clinical specimens from known prostate cancer or benign prostate hyperplasia patients and samples taken from an ongoing prostate cancer screening study were used for comparison. RESULTS: Application of the Stanford Calibrator revealed results well within 10% of the calculated values for all assays. Regarding the CRM Calibrator only the IMx Total PSA proved to approach the line of identity. The IMMULITE results differed about 40% and the Elecsys about 18% from the calculated values. The comparison with clinical specimens showed statistically different results for the combination IMMULITE-IMx and for IMMULITE-Elecsys. The regression lines for both collections were: y(IMx) = 0.86x(IMMULITE) +0.12 (n = 104, r = 0.970, Sy/x = 0.883 microg/L) and y(Elecsys) = 0.98x(IMMULITE) +0.38 (n = 97, r = 0.976, Sy/x = 0.733 microg/L). In the lower measuring range (PSA <5.0 microg/L) as measured with the screening samples (n = 43), these differences were less pronounced. CONCLUSION: In analytical sense a difference was found for both reference preparations in the assays studied. Clinically, despite improvements in methodology, results for total prostate-specific antigen are still not interchangeable. The possible consequences need to be elaborated.

No transketolase abnormalities in Wernicke-Korsakoff patients.

Transketolase isoenzyme patterns of Wernicke-Korsakoff patients, relatives, alcoholics and controls, obtained by isoelectric focusing of purified erythrocyte transketolase, were all identical. After a series of investigations published by several authors little evidence remains to support the hypothesis of an inborn transketolase abnormality in Wernicke-Korsakoff patients.

Prostate-specific antigen: its clinical use and application in screening for prostate cancer.

Prostate cancer in most European countries is the second most frequent cancer in males and the second most frequent cause of cancer death. Prostate specific antigen (PSA) is an important tumour marker, which relates to many aspects of this disease. It has been shown that PSA is helpful in the early diagnosis of prostate cancer and in this respect is superior to other available tests like rectal examination and transrectal ultrasonography. PSA is also helpful in staging of locally confined disease. It can be used to identify or exclude local extension of disease, if combined with T category and grade of differentiation determined on biopsy. The same parameters also give an indication of the presence of lymph node metastases, which may prevent unnecessary and invasive staging procedures in certain groups of patients with favourable prognostic factors and a low PSA value. PSA is less suitable as a marker for metastatic disease. Progression of untreated prostate cancer in various stages can be monitored by PSA. The true value of the marker in this respect is still underexplored. It may be possible that PSA will be shown to differentiate effectively between aggressive and non-progressive disease. In this respect, it could become an essential tool to identify those patients that may not require treatment at all. PSA is also a useful marker for therapy response. An elevation of PSA after radical prostatectomy indicates local or metastatic progression, which will occur within 1-2 years. PSA is an androgen dependent enzyme and decreases under endocrine treatment. It is unexplained why in spite of its endocrine dependent character, PSA rises with endocrine independent progression of prostate cancer.

Experiences with a new assay for pancreas specific alpha-amylase.

The evaluation of an enzymatic colorimetric method to measure pancreas amylase activity in serum using two monoclonal antibodies that specifically inhibit salivary amylase is described. The assay is quick, easy to perform and can be automated easily. Within-run and day-to-day precision studies gave CVs of less than or equal to 1.5 p. cent and less than or equal to 2.6 p. cent respectively. The test is linear up to 2,150 U/L. Salivary amylase activities up to 20,000 U/L did not contribute more than 2 p. cent to pancreatic amylase activity present in a serum sample. A significant interference by bilirubin is found. Reference values were established for both pancreatic and total amylase activities in serum and used for interpreting the results of pancreatic amylase and total amylase in 72 randomly selected patients. Results obtained by this method agree well with a lectin inhibition method (r = 0.9886).

[Results of various analysis technics in relation to urinary calculi studies]. / De resultaten van verschillende analysetechnieken met betrekking tot urinesteenonderzoek.

The article describes the results of surveys on renal calculi analysis organised by the Dutch Quality Assessment Foundation (SKZL) over the years 1986-1989. Most of the Dutch laboratories apply wet chemistry, some of them infrared spectroscopy, some polarisation microscopy and one X-ray diffraction analysis. The results of the wet chemistry category are poor, the infrared spectroscopy and the polarisation microscopy group score moderately well while the X-ray diffraction analysis laboratory performs well. On the basis of the results it is suggested to promote the physical chemical methods for renal calculi analysis.

[Variability of values of prostate-specific antigen determined with 6 methods]. / Variabiliteit van uitslagen van prostaatspecifiek antigeen met 6 bepalingsmethoden.

OBJECTIVE: To illustrate the variability of serum Prostate Specific Antigen (PSA) and its causes in relevant clinical patient populations. SETTING: University Hospital Rotterdam, the Netherlands. DESIGN: Descriptive. METHODS: Six different methods of PSA analysis were applied to sera of 19 participants of a screening population, 20 patients after radical prostatectomy, and 15 newly diagnosed patients with a prostate carcinoma. The Hybritech Tandem-R value was chosen as the standard to compare the methods of analysis. Around a standard of 4.0 micrograms/l a range of 3.3 to 7.2 micrograms/l was found; around 10.0 micrograms/l a range of 8.7 to 18.5 micrograms/l. After radical prostatectomy the different methods of analysis agreed completely in only 5 out of 15 patients with respect to serum PSA. CONCLUSION: Because of a considerable variability in serum PSA values between different laboratories and methods of analysis, and of overlap between benign and malignant prostatic diseases, reference values of PSA should be handled with great care.

[The effect of immunoscintigraphy with monoclonal antibodies on assays of hormones and tumor markers. This is not the end of the matter!]. / De invloed van immunoscintigrafie met monoklonale antilichamen op bepalingen van hormonen en tumormerkstoffen. Een muis met een staartje!

The use of monoclonal antibodies in medicine for in-vivo diagnostic methods and for therapeutic purposes will increase in the future. Although monoclonal antibodies possess a high specificity, the animal origin of these antibodies remains a problem. Repeated administration of animal monoclonal antibodies (in vivo) may induce the formation of human antibodies against these monoclonal antibodies. Because animal monoclonal antibodies are also used in laboratory assays (in vitro), the presence of human antibodies against these animal monoclonal antibodies may cause spuriously elevated or depressed results of these assays. The clinician should be alert to this possibility. A case history is presented to demonstrate the problem.