Diagnosis and treatment of iron-deficiency anaemia in pregnancy and postpartum.

Iron deficiency occurs frequently in pregnancy and can be diagnosed by serum ferritin-level measurement (threshold value < 30 µg/L). Screening for iron-deficiency anemia is recommended in every pregnant women, and should be done by serum ferritin-level screening in the first trimester and regular hemoglobin checks at least once per trimester. In the case of iron deficiency with or without anaemia in pregnancy, oral iron therapy should be given as first-line treatment. In the case of severe iron-deficiency anemia, intolerance of oral iron, lack of response to oral iron, or in the case of a clinical need for rapid and efficient treatment of anaemia (e.g., advanced pregnancy), intravenous iron therapy should be administered. In the postpartum period, oral iron therapy should be administered for mild iron-deficiency anemia (haemorrhagic anemia), and intravenous iron therapy for moderately severe-to-severe anemia (Hb < 95 g/L). If there is an indication for intravenous iron therapy in pregnancy or postpartum, iron-containing drugs which have been studied in well-controlled clinical trials in pregnancy and postpartum such as ferric carboxymaltose must be preferred for safety reasons. While anaphylactic reactions are extremely are with non-dextrane products, close surveillance during administration is recommended for all intravenous iron products.

Establishment of Over-The-Scope-Clips (OTSC®) in daily endoscopic routine.

BACKGROUND: Alongside the evolution of interventional endoscopy, the need for a more sophisticated closure tool tailored to the treatment of new challenging indications has been increasing rapidly. METHODS: We here present our collected data on 262 Over-The-Scope-Clip (OTSC®) placements in a total of 233 interventions at our institution. Follow-up was focused on clinically lasting success with regards to different indications. RESULTS: Immediate success of OTSC® treatment was observed in 87.1% of all sessions (203/233). The success rates per indication were as follows: spontaneous bleeding 84.8% (28/33); iatrogenic bleeding 100% (20/20); acute perforation 90.3% (65/72); prophylaxis for perforation 100% (24/24); anastomotic leakage 61.1% (11/18); fistulae 80.7% (46/57); diameter reduction of the gastrojejunal anastomosis 100% (6/6); and stent fixation 100% (3/3). At 30-day follow-up, the overall success rate was 67.4% (157/233). The success rates per indication were as follows: spontaneous bleeding 69.7% (23/33); iatrogenic bleeding 90% (18/20); acute perforation 86.1% (62/72); prophylaxis for perforation 100% (24/24); anastomotic leakage 33.3% (6/18); fistulae 29.8% (17/57), diameter reduction of the gastrojejunal anastomosis 83.3% (5/6); and stent fixation 66% (2/3). CONCLUSIONS: Our cohort confirms previous data on the clinical usefulness of the OTSC® in daily routine practice.

Use of intraoperative stereomicroscopy for preventing loss of metastases during frozen sectioning of sentinel lymph nodes in breast cancer.

AIMS: Optimal detection of metastases in sentinel lymph nodes (SLN) remains controversial. To determine the reliability of intraoperative frozen sections, SLN protocol with one frozen section was compared with macroscopic SLN evaluation with consecutive complete SLN embedding. METHODS AND RESULTS: SLN from 135 consecutive breast cancer patients were analysed under a sereomicroscope. Frozen sections were performed in suspicious or clearly involved SLN on cut surface. One control group (n = 143) underwent one intraoperative frozen section on each SLN. The second control group (n = 90) was subjected to stereomicroscopy and one intraoperative frozen section on each SLN. A conventional SLN protocol with cytokeratin immunohistochemistry was performed postoperatively in all cases. All groups were statistically comparable. In the study group metastases were suspected in 21 SLN (16%) under the stereomicroscope and all were confirmed histologically. The negative SLN rate was significantly lower in the study group than in the main control group (47% versus 64%, P = 0.008), suggesting loss of metastases during frozen sections. More macrometastases were detected in the study group (30% versus 15%, P = 0.006); there were no differences in isolated tumour cells or micrometastases. The false-negative rate was significantly lower in the control groups (29% versus 13% and 12%, P = 0.001). CONCLUSIONS: Frozen sections potentially lead to loss or reduced size of metastatic deposits in SLN. Avoiding intraoperative frozen sections on grossly inconspicuous SLN may therefore be justified.

[Loss of metastatic deposits in breast sentinel lymph nodes during intra-operative frozen section analysis]. / Potentieller Verlust von Metastasen in Sentinel Lymphknoten während der Schnellschnitt Untersuchung.

The intraoperative evaluation of sentinel lymph nodes is an ongoing debated issue. In this review we discuss different approaches to sentinel lymph node processing in an intra operative setting and in the consecutive embedding in paraffin. We propose a method, which uses routine intra operative examination of lymph nodes with stereo microscopy with selected frozen section analysis. We demonstrate preliminary data on a larger patient collective along with data on a control group. We could show in our study that a higher rate of metastates can be achieved avoiding intra operative frozen sections on grossly inconspicuous sentinel lymph nodes.

[Screening of Chlamydia trachomatis: is the diagnostic efficacy good enough?]. / Chlamydienscreening: Ist das Nachweisproblem gelöst?

OBJECTIVE: In the background of discrepant results of C. trachomatis testing in women with suspected genital infections, three different tests have been compared. METHOD: 594 endocervical swabs were collected from women visiting the family planning clinic in Aarau. Each of the following tests was evaluated: Cobas Amplicor Chlamydia trachomatis, IF Chlamyset, and Chlamydia IF direct. If one of these three tests was positive, the fixed material on the slides was scraped off, and a PCR was performed. RESULTS: 15 out of 594 samples were "true'-positive. PCR recognized 14 of them, the IF Chlamyset 13, and the Chlamydia IF 8. With the IF Chlamyset 37 samples were false-positive. CONCLUSIONS: PCR testing exhibits a good sensitivity and a high specificity, but we think that the sensitivity can be increased by improving the sample preparation step. The Chlamydia IF direct has a good specificity, but a rather low sensitivity. It should be noted that the PCR has the potential to become a new gold standard for the detection of C. trachomatis.

Extracellular antioxidants and amino acids in the cortex of the rat: monitoring by microdialysis of early ischemic changes.

Extracellular concentrations of ascorbic acid, glutathione, cysteine, uric acid, tyrosine, and tryptophan were monitored using intracerebral microdialysis in the left frontoparietal cortex of spontaneous hypertensive rats before, and for 3 h after, either focal ischemia [left middle cerebral artery occlusion (MCAO)] or sham operation. The size of the ischemic area and the position of the microdialysis probe were checked using the enzyme histotopochemical acid phosphatase reaction. The probe was always located in the cortex inside the stained area. Ascorbic acid levels rose immediately after MCAO and remained at about 12-fold for 3 h. There was a transient release of glutathione during 1-1.5 h. Uric acid concentrations were also increased but the differences did not reach significance. The levels of the amino acids tyrosine and tryptophan increased steadily after MCAO. The increases in cysteine were variable but significant. In some experiments, the pH of the dialysate was measured online. The parameters ascorbic acid, glutathione, cysteine, and pH are suitable for the early detection of cortical ischemic events by microdialysis.

[Interlocking intramedullary nailing of the femur: is the advantage of early mobilization gained by risking a malposition?]. / Die Verriegelungsmarknagelung am Femur: Wird der Vorteil der Frühbelastungsfähigkeit mit dem Risiko einer Fehlstellung erkauft?

We report a follow-up of 57 consecutive femoral fractures treated by internal fixation with the AO Universal Interlocking Nall. All fractures (91% follow-up) had healed within a mean of 22 months (range 9-50) after operation. Full weight-bearing was possible after an average of 9 weeks (range 2-20). The only infection occurred after a secondary open lengthening osteotomy. In 5 cases a rotational malposition or length discrepancy had to be corrected shortly after initial surgery. Rotational malposition in excess of 10 degrees occurred in 26% of cases (mostly external rotation) and length discrepancy exceeding 1 cm in 13% (mostly shortening). The frequency of malposition is explained by the absence of rotational or length control during operation. We recommend that malposition be correlated without delay by reoperation.

Some pathophysiological aspects of experimental autoimmune encephalomyelitis.

Three aspects of the pathophysiology of experimental autoimmune encephalomyelitis (EAE) are discussed: firstly, the possible electrophysiological effects in the CNS of myelin basic protein, which is released during demyelination; secondly, the partial degeneration of monoaminergic and glutamatergic neurons which occurs during an attack of EAE in addition to demyelination; thirdly, the importance of ischemic events, accompanied by free radical release, in EAE. Especially the third aspect could have therapeutic implications. Treatment with radical scavengers, N-methyl-D-aspartate receptor blockers, or calcium blockers (as suggested for ischemia) might prove effective for EAE. Our present aim is to investigate whether these results are also relevant for MS, for which EAE is an animal model.

Changes in amino acid contents in the spinal cord and brainstem of rats with experimental autoimmune encephalomyelitis.

The effects of experimental autoimmune encephalomyelitis (attack and recovery) on levels of six amino acids have been investigated in nine regions of the Lewis rat spinal cord between segments C3 and Co1 and in the brainstem. Amino acids were analyzed by separation of their 4'-dimethylaminoazobenzene-4-sulfonyl chloride derivatives on a reversed-phase column using a ternary gradient. Glutamate and gamma-aminobutyric acid were reduced by 10-30% in all segments during the attack, whereas taurine, lysine, glutamine, and glycine were all greatly increased (up to 300%). Most values except those of taurine, as well as glutamate in certain segments, returned to normal on recovery. Because some of these compounds have neurotransmitter function, these changes may contribute to the neurological symptoms of experimental autoimmune encephalomyelitis.

Monoamines and related substances in brainstem and spinal cord of Lewis rats during the attack and recovery of experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis influenced catecholaminergic and indoleaminergic neurotransmitter systems in the central nervous system of Lewis rats. During paralysis, serotonin and noradrenaline were significantly reduced compared to animals injected with complete Freund's adjuvant in the posterior dorsomedial brainstem and in lower spinal cord segments. These diminutions remained after recovery from neurological signs in T11-S1. The serotonin metabolite 5-hydroxyindoleacetic acid was greatly augmented during the attack in all segments but was depleted during recovery in the lumbar spinal cord, which may indicate a normalized turnover at a reduced serotonin level. These results suggest functional impairment of monoaminergic neurons of the brainstem and spinal cord followed by permanent damage to some monoaminergic fibers in the spinal cord.

Quantitative determination of water- and lipid-soluble antioxidants in neoplastic and non-neoplastic human breast tissue.

Ascorbic acid, cysteine, glutathione and uric acid were determined by reverse-phase high-pressure liquid chromatography (HPLC) in 46 breast tissue samples [neoplastic (C) and non-neoplastic (N) from the same patient]. Cholesterol, alpha-tocopherol and gamma-tocopherol were quantified in 64 similar samples by extraction into heptane followed by direct-phase HPLC. DNA was measured in all samples and the percentages of epithelium, fat and connective tissue were estimated in sections adjacent to the sample. Results confirm previous findings that ascorbic acid and glutathione, expressed as mumol/g DNA, were greatly increased in the epithelium of neoplastic tissue. Similar increases in cysteine could be accounted for by the presence of inflammatory cells. Although values of alpha- and gamma-tocopherol correlated with the percentage of fat in both types of tissue, these compounds were also present in the epithelium. Because of the varying amounts of fat in the samples, no significant difference could be found between N and C values. Cholesterol correlated with fat in N and epithelium in C. Consideration of 10 cases with equal amounts of fat in C and N tissue suggests that cholesterol is reduced in C in the epithelial cells.

Measurement of free radical scavengers in the spinal cord of rats with experimental autoimmune encephalomyelitis.

Antioxidants (ascorbic acid, glutathione, cysteine, alpha-tocopherol) and uric acid were measured using two high-pressure liquid chromatographic methods in 3 regions (cervical, thoracic, lumbar) of the spinal cord and in blood of Lewis rats during the attack and recovery of experimental autoimmune encephalomyelitis (EAE). Uric acid, which is thought to be a marker of free radical release, was greatly increased and glutathione correspondingly decreased in lumbar and thoracic regions. Cysteine and ascorbic acid were practically unchanged, whereas alpha-tocopherol was significantly increased during attack and recovery. Results, which could have therapeutic implications, generally support the hypothesis that free radicals are released during EAE.

Interleukin-1 induces changes in norepinephrine metabolism in the rat brain.

Interleukin-1 (IL-1) is a hormone that, apart from playing a key role in immune and inflammatory processes, can also affect mechanisms under brain control. To gain a better understanding of the action of this cytokine on the CNS, its effects on the contents of norepinephrine (NE), dopamine (DA) and serotonin (5-HT), and their main metabolites and precursors, were evaluated in different regions of the forebrain, brain stem, and spinal cord. Following administration of human recombinant IL-1 (beta form) to rats, a modest decrease in the content of NE was observed in the hypothalamus as well as in the dorsal posterior brain stem. However, the most relevant finding was that 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the main NE metabolite, and the relation MHPG/NE were increased in all the regions studied, revealing a stimulatory effect of IL-1 on NE metabolism in the CNS. This effect seems to be specific for NE since no comparable changes in the brain content of DA, 5-HT, or its metabolite, 5-hydroxyindole acetic acid, were detected after administration of the cytokine. However, tryptophan was significantly increased in all brain regions and in the cervical spinal cord. The capacity of IL-1 to affect the metabolism of NE, a neurotransmitter involved in the control of a variety of brain functions, provides further proof for the relevance of this cytokine in brain-immune interactions.

Quantitative determination of water-soluble scavengers in neoplastic and non-neoplastic human breast tissue.

The water-soluble scavengers ascorbic acid (Asc), cysteine (Cys), glutathione (GSH) and uric acid (UA) as well as DNA content were determined in 40 breast tissue samples (neoplastic and non-neoplastic tissues from 20 patients). To allow proper homogenization to take place, a fixed number of sections was cut from a tissue cylinder of known diameter. Adjacent sections were stained with hematoxylin-eosin and the fractions of epithelium, fat and connective tissue were estimated as a percentage of the section area. Protein-free extracts were injected into a reverse-phase high-pressure liquid chromatography system and scavengers quantified with 2 electrochemical detectors (gold and glassy carbon). DNA and all scavengers, except UA, were greatly increased in cancer tissues in nearly all cases. Amounts of Asc and GSH in neoplastic tissue correlated closely with DNA values and percentage of epithelium, those of Cys not so closely and those of UA not at all. We assume that Asc and GSH were located mainly in the epithelium, UA mainly in the extracellular space and Cys in both spaces. When values were expressed as mumol/g DNA, a parameter related to content per cell, values were higher in neoplastic than in non-neoplastic tissue for Asc (18/20 cases), GSH (17/20) and Cys (14/20) and lower in neoplastic tissue for UA (19/20). It is known that increased GSH protects cells against certain drugs in tissue cultures. For in vivo treatment the presence of increased Asc (and to a lesser extent Cys) in addition to GSH could be of importance.

Effects of peptides from bovine myelin basic protein on the bioelectrical activity of the frog spinal cord.

Both bovine and human myelin basic protein (MBP) have been shown to have electrophysiological activity. As MBP is susceptible to proteolytic degradation, our aim was to discover whether the resulting peptides retained this activity. Bovine MBP was completely cleaved by plasmin into at least nine peptides. The electrophysiological activities of this peptide mixture and of bovine MBP were directly compared on the hemisected frog spinal cord. The peptide mixture and intact bovine MBP had quantitatively and qualitatively similar effects (dose-dependent long-lasting depolarization, about 100 times more active than glutamate). Four peptides (molecular weights 14,000, 10,500, 8,000, 4,500) from thrombin or cathepsin D cleavage of bovine MBP also showed electrophysiological activity, positively correlated to their molecular weights. As MBP-like material occurs in increased concentrations in the cerebrospinal fluid during demyelinating diseases, peptides resulting from proteolytic degradation of MBP, e.g. in demyelinating foci of multiple sclerosis, might cause neuronal disturbances.

T lymphocytes affect the development of sympathetic innervation of mouse spleen.

We investigated whether the development of sympathetic innervation of the spleen is affected by lymphoid cells. Splenic noradrenaline (NA) levels of athymic nude mice (nu/nu) and normal thymus-bearing littermates (nu/+) were determined at different times during ontogeny. While no differences were detected at birth, higher splenic NA levels were found in 7-, 11-, and 21-day-old athymic mice. Thymus transplantation or thymocyte injection to newborn nude mice resulted in splenic NA levels comparable to those of normal nu/+ mice. Histochemical studies fully confirmed such differences. Taken together with previous studies, these results suggest that T lymphocytes or their products exert an inhibitory influence on sympathetic nerve fibers, thus leading to decreased NA content in the spleen. The data also illustrate the capacity of a nonneuronal cell in a peripheral organ to affect the process of autonomic innervation of this organ.

Changes of neurotransmitter systems in chronic relapsing experimental allergic encephalomyelitis in rat brain and spinal cord.

Catecholamine and indoleamine neurotransmitters, together with some of their precursors and metabolites, were determined using HPLC in three brain and two spinal cord regions of Lewis rats with chronic relapsing allergic encephalomyelitis and of control rats injected with complete Freund's adjuvant. Three attacks and two recovery phases were investigated. Changes are found mainly in the spinal cord. In the lumbosacral region both 5-hydroxytryptamine and noradrenaline are reduced during the entire course of the disease, whereas in the craniothoracal region 5-hydroxytryptamine is unchanged and only noradrenaline is reduced during the attacks, returning to normal during the first recovery. The precursors tyrosine and tryptophan are greatly elevated during the first two attacks in both regions. The 5-hydroxytryptamine turnover marker 5-hydroxyindoleacetic acid is increased in the first attack in both regions, then it decreases in the later stages, indicating destruction of nerve fibers. On the fourth and seventh days after inoculation values are generally not significantly different from controls in all regions. The possible correlation of neurochemical results with neurological signs is discussed.