Acromelic frontonasal dysostosis and ZSWIM6 mutation: phenotypic spectrum and mosaicism.

Acromelic frontonasal dysostosis (AFND) is a distinctive and rare frontonasal malformation that presents in combination with brain and limb abnormalities. A single recurrent heterozygous missense substitution in ZSWIM6, encoding a protein of unknown function, was previously shown to underlie this disorder in four unrelated cases. Here we describe four additional individuals from three families, comprising two sporadic subjects (one of whom had no limb malformation) and a mildly affected female with a severely affected son. In the latter family we demonstrate parental mosaicism through deep sequencing of DNA isolated from a variety of tissues, which each contain different levels of mutation. This has important implications for genetic counselling.

Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis.

Oculoectodermal syndrome (OES) and encephalocraniocutaneous lipomatosis (ECCL) are rare disorders that share many common features, such as epibulbar dermoids, aplasia cutis congenita, pigmentary changes following Blaschko lines, bony tumor-like lesions, and others. About 20 cases with OES and more than 50 patients with ECCL have been reported. Both diseases were proposed to represent mosaic disorders, but only very recently whole-genome sequencing has led to the identification of somatic KRAS mutations, p.Leu19Phe and p.Gly13Asp, in affected tissue from two individuals with OES. Here we report the results of molecular genetic studies in three patients with OES and one with ECCL. In all four cases, Sanger sequencing of the KRAS gene in DNA from lesional tissue detected mutations affecting codon 146 (p.Ala146Val, p.Ala146Thr) at variable levels of mosaicism. Our findings thus corroborate the evidence of OES being a mosaic RASopathy and confirm the common etiology of OES and ECCL. KRAS codon 146 mutations, as well as the previously reported OES-associated alterations, are known oncogenic KRAS mutations with distinct functional consequences. Considering the phenotype and genotype spectrum of mosaic RASopathies, these findings suggest that the wide phenotypic variability does not only depend on the tissue distribution but also on the specific genotype.

Phenotype in 18 Danish subjects with genetically verified CHARGE syndrome.

CHARGE (coloboma of the eye, heart defects, choanal atresia, retarded growth and development, genital hypoplasia and ear anomalies and/or hearing loss) syndrome is a rare genetic, multiple-malformation syndrome. About 80% of patients with a clinical diagnose, have a mutation or a deletion in the gene encoding chromodomain helicase DNA-binding protein 7 (CHD7). Genotype-phenotype correlation is only partly known. In this nationwide study, phenotypic characteristics of 18 Danish CHD7 mutation positive CHARGE individuals (N = 18) are presented. We studied patient records, clinical photographs, computed tomography, and magnetic resonance imaging (MRI). Information was not available for all traits in all subjects. Therefore, the results are presented as fractions. The following prevalence of cardinal symptoms were found: coloboma, 16/17; heart defects, 14/18; choanal atresia, 7/17; retarded growth and development, 11/13; genital abnormalities, 5/18; ear anomalies, 15/17 and sensorineural hearing loss, 14/15. Vestibular dysfunction (10/13) and swallowing problems (12/15) were other frequent cranial nerve dysfunctions. Three-dimensional reconstructions of MRI scans showed temporal bone abnormalities in >85%. CHARGE syndrome present a broad phenotypic spectrum, although some clinical features are more frequently occurring than others. Here, we suggest that genetic testing for CHD7 mutation should be considered in neonates with a specific combination of several clinical symptoms.

Osteopathia striata congenita with cranial sclerosis and intellectual disability due to contiguous gene deletions involving the WTX locus.

Osteopathia striata congenita with cranial sclerosis (OSCS) is a skeletal dysplasia caused by germline deletions of or truncating point mutations in the X-linked gene WTX (FAM123B, AMER1). Females present with longitudinal striations of sclerotic bone along the long axis of long bones and cranial sclerosis, with a high prevalence of cleft palate and hearing loss. Intellectual disability or neurodevelopmental delay is not observed in females with point mutations in WTX leading to OSCS. One female has been described with a deletion spanning multiple neighbouring genes suggesting that deletion of some neighbouring loci may result in abnormal neurodevelopment. In this cohort of 13 females with OSCS resulting from deletions of WTX, a relationship is observed where deletion of ARHGEF9 and/or MTMR8 in conjunction with WTX results in an additional neurodevelopmental phenotype whereas deletion of ASB12 along with WTX is associated with a good neurodevelopmental prognosis.

Placental transfer and vascular effects of pharmaceutical drugs in the human placenta ex vivo: A review.

At least 80% of pregnant woman in Europe use at least one medication during their pregnancy. The majority of these drugs are prescribed off-label. A better understanding of drug transport and effects in the placenta can provide an improved pharmacological basis to rationalize drug and dose selection for prescription. Here we provide a narrative review of studies that used the ex vivo placenta perfusion model to study placental drug transport and vascular effects of pharmaceuticals. For studies on placental transfer, we found that the methodology used varied substantially between studies as well as the way in which data was reported. Across the different therapeutic groups, ex vivo measurements of transfer generally corresponded well to in vivo findings. Still, further standardization of the perfusion technique would facilitate a broader use of perfusion data, e.g. in the context of quantitative systems pharmacology models as has been explored in recent years. Only few studies investigated the effects of drugs on the vascular tone using the ex vivo dual-side perfusion model. The model was particularly applied to study vasodilatory effects of pharmaceuticals in the fetoplacental circulation. In conclusion, the ex vivo dually perfused human cotyledon provides a relevant system to gain insights in placental drug disposition and study effects on the fetoplacental vasculature.

Prediction of Maternal and Fetal Doravirine Exposure by Integrating Physiologically Based Pharmacokinetic Modeling and Human Placenta Perfusion Experiments.

BACKGROUND AND OBJECTIVE: Doravirine is currently not recommended for pregnant women living with human immunodeficiency virus because efficacy and safety data are lacking. This study aimed to predict maternal and fetal doravirine exposure by integrating human placenta perfusion experiments with pregnancy physiologically based pharmacokinetic (PBPK) modeling. METHODS: Ex vivo placenta perfusions were performed in a closed-closed configuration, in both maternal-to-fetal and fetal-to-maternal directions (n = 8). To derive intrinsic placental transfer parameters from perfusion data, we developed a mechanistic placenta model. Next, we developed a maternal and fetal full-body pregnancy PBPK model for doravirine in Simcyp, which was parameterized with the derived intrinsic placental transfer parameters to predict in vivo maternal and fetal doravirine exposure at 26, 32, and 40 weeks of pregnancy. The predicted total geometric mean (GM) trough plasma concentration (Ctrough) values were compared with the target (0.23 mg/L) derived from in vivo exposure-response analysis. RESULTS: A decrease of 55% in maternal doravirine area under the plasma concentration-time curve (AUC)0-24h was predicted in pregnant women at 40 weeks of pregnancy compared with nonpregnant women. At 26, 32, and 40 weeks of pregnancy, predicted maternal total doravirine GM Ctrough values were below the predefined efficacy target of 0.23 mg/L. Perfusion experiments showed that doravirine extensively crossed the placenta, and PBPK modeling predicted considerable fetal doravirine exposure. CONCLUSION: Substantially reduced maternal doravirine exposure was predicted during pregnancy, possibly resulting in impaired efficacy. Therapeutic drug and viral load monitoring are advised for pregnant women treated with doravirine. Considerable fetal doravirine exposure was predicted, highlighting the need for clinical fetal safety data.

RUNX2 analysis of Danish cleidocranial dysplasia families.

Cleidocranial dysplasia (CCD) is an autosomal dominant inherited disease caused by mutations in the Runt gene RUNX2. Screening of 19 Danish CCD families revealed 16 pathogenic mutations (84%) representing 8 missense mutations, 2 nonsense mutations, 4 frame-shift mutations and 2 large deletions in the RUNX2 locus. Eight mutations were novel, two were found twice, and polymorphisms were found in the promoter region and in the conserved polyglutamine/polyalanine repeat. A large duplication downstream of RUNX2 found in one patient suggests a possible regulatory RUNX2 element. The CCD phenotypes and genotypes adhere to the large phenotypic variability reported in previous CCD studies. Identification of large chromosome aberrations in or near the RUNX2 locus in 3 of the 19 cases suggests copy number analyses to be included in future RUNX2 mutation analyses.

Transfer of uremic solutes across the human term placenta: An ex vivo study in the dual-side perfused cotyledon.

INTRODUCTION: An increasing number of women becomes pregnant while suffering from chronic kidney disease (CKD). As a result of decreased renal function, uremic solutes circulate at high levels in the maternal circulation. This study aimed to acquire more knowledge about the placental transfer of uremic solutes across the human placenta. METHODS: Placental transfer was studied in healthy term placentas, via the ex vivo dual-side human cotyledon perfusion technique (closed-closed set-up for both maternal and fetal circulations). Uremic solute concentrations in maternal and fetal perfusates were measured via LC-MS/MS over 180 min of perfusion. RESULTS: We found that the studied compounds demonstrated different degrees of placental transfer. Fetal-to-maternal perfusate ratios at t = 180 min were for anthranilic acid 1.00 ± 0.02, indole-3-acetic acid 0.47 ± 0.08, hippuric acid 0.36 ± 0.18, l-arabinitol 0.33 ± 0.04, indoxyl sulfate 0.33 ± 0.11, neopterin 0.28 ± 0.14 and kynurenic acid 0.13 ± 0.03. All uremic solutes studied also emerged in the perfusates when cotyledons were perfused in the absence of uremic solute concentrations added to the maternal reservoir. For kynurenin these concentrations were so high, it complicated the calculation of a transfer ratio for the exogenously administered compound. DISCUSSION: After 180 min of exposure the extent of placental transfer differs substantially for the solutes studied, reflecting different transfer rates. Future studies should investigate to what extent specific uremic solutes reach the fetal circulation in vivo and how they may interfere with organ function and development of the unborn child.

Skin signs in Ehlers-Danlos syndrome: clinical tests and para-clinical methods.

OBJECTIVE: The criteria for Ehlers-Danlos syndrome (EDS) and the hypermobility syndrome (HMS) should be reliable. Examination for general joint hypermobility has high reliability but there is only sparse information on the reliability of skin tests, and no information on the level of normal skin extensibility. The present study aimed to assess skin signs by means of clinical and para-clinical methods. METHODS: A total of 31 EDS patients and 28 healthy controls were examined blinded and in random order. Inter-examiner analysis of clinical tests for skin extensibility, consistency, scarring, and bruising was performed, followed by analyses of extensibility with the suction cup (SC), consistency with a soft tissue stiffness meter (STSM), and thickness with ultrasonography (US). Semi-quantitative assessment of skin extensibility in healthy controls was incorporated in the tests. RESULTS: The clinical analyses demonstrated kappa values of: 0.72 for extensibility, 0.23 for consistency, 0.53 for scarring, and 0.63 for bruising. Skin extensibility measurements in healthy controls (n = 28) were 2.79 and 2.93 cm (mean + 2 SD), respectively, by the two examiners. There were significant differences between patients with classical-type EDS and controls with respect to skin extensibility by SC (4.91 vs. 12.52 kPa/mm) and skin consistency by STSM (0.59 vs. 0.76 N). We found no difference in skin thickness. CONCLUSION: The reproducibility of the clinical skin tests was substantial to good, apart from the consistency measurements. We suggest that skin consistency is withdrawn as a diagnostic criterion. The upper level for normal skin extensibility should be 3 cm. SC and STSM are promising para-clinical methods, but their diagnostic sensitivity and specificity need to be determined.

Prenatal 3D ultrasound diagnostics in cleidocranial dysplasia.

A 34-year-old Caucasian woman with cleidocranial dysplasia (CCD) and a known family history of CCD was referred for an ultrasound examination in the first trimester of her second pregnancy. Molecular genetic analysis of the RUNX2 gene was non-informative. A routine 2D ultrasound examination carried out at a local hospital at gestational age 12 weeks showed no signs of CCD. A 3D ultrasound examination in week 15+4 showed a fetus with typical CCD features including large fontanelles, lack of nasal bones, clavicles without the typical S-form, as well as severe delay in calvarial ossification, especially in the midline. Serial 3D ultrasound examinations during pregnancy confirmed the diagnosis, and over time the manifestations became even more distinct. The diagnosis was clinically confirmed at birth. This case suggests that the typical craniofacial CCD traits, including wide unmineralized areas in the calvarial midline and missing nasal bones, are easily recognizable using 3D ultrasound as early as in week 15.

An echo-poor spine at 13 weeks: an early sign of cleidocranial dysplasia.

OBJECTIVE: Early prenatal diagnosis of cleidocranial dysplasia (CCD) in a case in which molecular genetic analysis of the RUNX2 gene was non-informative. METHODS: 2D ultrasound examination. RESULTS: At week 13+6, a 2D ultrasound examination revealed a fetus with severely delayed ossification of the vertebral spine. The clavicles were barely seen and the calvarial bones were significantly less ossified than expected for gestational age. The fetus had otherwise normal anatomy and biometry. Serial ultrasound examinations during pregnancy confirmed the diagnosis, but the manifestations became less distinct. The diagnosis was confirmed clinically at birth. CONCLUSION: This case illustrates an early easily recognizable pattern of severely delayed ossification of the vertebral spine, which is probably a characteristic of CCD.

Effect of lactic acid bacteria on the intestinal production of lactate and short-chain fatty acids, and the absorption of lactose.

The characteristic fermentation pattern seen with specific saccharides in incubations with pure cultures of Lactobacillus acidophilus and Bifidobacterium bifidum disappeared when incubated in 16.7% fecal homogenate. The productions of lactate and short-chain fatty acids in mixed bacterial-fecal incubations were similar to productions in fecal homogenates without L acidophilus and B bifidum and were mainly associated with the specific mono-, di-, and polysaccharides added to the incubate. B bifidum was cultured from ileostomic contents in eight of nine ileostomists after oral administration (2.4 x 10(10) cells), but did not influence the concentrations and productions of DL-lactate and short-chain fatty acids in the ileostomic outputs and incubates. Large amounts of ingested lactic acid bacteria (4.2 x 10(10) cells) did not ameliorate lactose malabsorption measured by the breath-hydrogen test in 12 lactose malabsorbers. This study shows that ingested lactic acid bacteria are indeed present in the colon, but it does not support the theory that they change the pattern of colonic fermentation or the degree of intestinal lactose malabsorption.

Lactic acid bacteria and the human gastrointestinal tract.

OBJECTIVE: This review summarises the effects of lactic acid bacteria on lactose malabsorption, bacterial/viral or antibiotic associated diarrhoea, and describes the impact of lactic acid bacteria on cancer and the fermentative products in the colon. RESULTS: Eight studies (including 78 patients) demonstrated that lactase deficient subjects absorbed lactose in yogurt better than lactose in milk, while two studies (25 patients) did not support this. Two studies (22 patients) showed that unfermented acidophilus milk was absorbed better than milk, while six studies (68 patients) found no significant differences. Addition of lactose hydrolysing enzyme, lactase, to milk improved lactose malabsorption in seven studies (131 lactose malabsorbers), while one study (10 malabsorbers) demonstrated no improvement. Lactic acid bacteria alleviated travellers' diarrhoea in one study (94 individuals) while a study including 756 individuals was borderline statistically significant. One study (50 individuals) did not find an effect of lactic acid bacteria on travellers' diarrhoea. Six studies (404 infants) demonstrated a significant effect of lactic acid bacteria on infant diarrhoea, while one study (40 infants) did not. Lactic acid bacteria moderated antibiotic associated diarrhoea in three studies (66 individuals), while two studies (117 individuals) were insignificant. CONCLUSIONS: Lactase deficient subjects benefit from a better lactose absorption after ingestion of yoghurt compared with milk and from milk added lactase, whereas ingestion of unfermented acidophilus milk does not seem to improve lactose absorption. The majority of studies support that lactic acid bacteria alleviate bacterial/viral induced diarrhoea, especially in infants, while the effect on antibiotic associated diarrhoea is less clear. Experimental studies indicate an effect of lactic bacteria on human cell cancer lines, but clinical evidence is lacking. A 'stabilising' effect of lactic acid bacteria on the colonic flora has not been documented.

Colonic fermentation of ispaghula, wheat bran, glucose, and albumin to short-chain fatty acids and ammonia evaluated in vitro in 50 subjects.

The production of short-chain fatty acids and ammonia was measured in 16.6% fecal homogenates from 50 subjects incubated at 37 degrees C for 6 and 24 hours. All 50 homogenates produced ammonia and short-chain fatty acids of any chain length (C2-C5). Incubation for 24 hours with dietary fiber (ispaghula husk or wheat bran), albumin, or glucose (10 mg/mL) increased the short-chain fatty acid production (43.6 +/- 2.8, 45.4 +/- 2.0, 60.3 +/- 3.2, and 65.8 +/- 3.1 mmol/L, respectively) compared with controls (21.4 +/- 1.3 mmol/L). The degradation of different substrates was associated with the production of different amounts of ammonia and short-chain fatty acids. Ispaghula, wheat bran, albumin, and glucose were fermented to acetate (> 2 mmol/L; 24-hour incubations) in 86%, 96%, 98%, and 98% of the homogenates, to propionate in 80%, 76%, 100%, and 68%, and to butyrate in 32%, 94%, 88%, and 54% of the homogenates, respectively. Isobutyrate, valerate, and isovalerate were produced from albumin in all (100%) of the homogenates, but only in 2 to 4% of the homogenates incubated with ispaghula or glucose. Ammonia was always (100%) produced after the addition of albumin and always (98%) consumed (assimilated) when glucose was fermented. Surgery (sigmoid or right- or left-sided colonic resection) did not change the pattern of ammonia and short-chain fatty acid production from these substrates. This study suggests that the different colonic flora from a large number of subjects share general biochemical characteristics, which metabolize different substrates to specific patterns of ammonia and short-chain fatty acids.

Levels of synthetic antioxidants (ethoxyquin, butylated hydroxytoluene and butylated hydroxyanisole) in fish feed and commercially farmed fish.

Several synthetic antioxidants are authorized for use as feed additives in the European Union. Ethoxyquin (EQ) and butylated hydroxytoluene (BHT) are generally added to fish meal and fish oil, respectively, to limit lipid oxidation. The study was conducted to examine the concentrations of EQ, BHT and butylated hydroxyanisole (BHA) in several commercially important species of farmed fish, namely Atlantic salmon, halibut and cod and rainbow trout, as well as concentrations in fish feed. The highest levels of BHT, EQ and BHA were found in farmed Atlantic salmon fillets, and were 7.60, 0.17 and 0.07 mg kg(-1), respectively. The lowest concentrations of the synthetic antioxidants found were in cod. The concentration of the oxidation product ethoxyquin dimer (EQDM) was more than ten-fold higher than the concentration of parent EQ in Atlantic salmon halibut and rainbow trout, whereas this dimer was not detected in cod fillets. The theoretical consumer exposure to the synthetic antioxidants EQ, BHA and BHT from the consumption of farmed fish was calculated. The contribution of EQ from a single portion (300 g) of skinned fillets of the different species of farmed fish would contribute at most 15% of the acceptable daily intake (ADI) for a 60 kg adult. The consumption of farmed fish would not contribute measurably to the intake of BHA; however, a 300 g portion of farmed Atlantic salmon would contribute up to 75% of the ADI for BHT.

Short-chain fatty acids in the non-adapted and adapted pelvic ileal pouch.

BACKGROUND: Adaptation to colonic conditions occurs in the bacterial flora and faecal short-chain fatty acids (SCFAs) of the pelvic ileal pouch. METHODS: Faecal SCFAs were studied in 14 J-pouch patients within 10 days after closure of the ileostomy (non-adapted pouch) and more than 6 months after ileostomy closure (adapted pouch). RESULTS: Concentrations of faecal SCFAs were low in non-adapted pouches (mean +/- SE, 20.3 +/- 3.4 mmol/l), increasing to intermediate levels, 53.3 +/- 8.4 mmol/l, between 6 months and a year after ileostomy closure, and to 96.3 +/- 7.9 mmol/l, after more than a year of adaptation. Production of SCFAs in faecal homogenates was correspondingly low in non-adapted (6.3 +/- 2.0 mmol/l) compared with adapted pouches (32.0 +/- 3.6 mmol/l; p = 0.001) and could not be overcome by the addition of fermentable carbohydrates. Percentages of the predominant SCFAs (acetate, propionate, butyrate) were not affected by adaptation, nor were production and concentration of lactate. Stool volume decreased from 1019 +/- 134 to 603 +/- 77 ml/24 h (p = 0.02) during adaptation, sodium excretion decreased from 132 +/- 19 to 67 +/- 11 mmol/24 h (p = 0.02), and osmolality increased from 316 +/- 6 to 398 +/- 13 (p = 0.001). Excretions of carbohydrates, nitrogen, and potassium were not altered. CONCLUSIONS: The bacterial production of SCFAs is low in non-adapted pouches, resulting in low concentrations of SCFAs comparable to concentrations found in conventional ileostomies. Pouch adaptation gradually increases SCFA production and concentration severalfold and reaches concentrations normally found in non-colectomized individuals after approximately 1 year.

Colonic lactate metabolism and D-lactic acidosis.

D-Lactic acidosis is seen in patients with intestinal bypass or short bowels in whom colonic produced D-lactate accumulates. An intestinal bypassed patient with D-lactic acidosis had higher fecal D-lactate (122.4 mmol/liter) and L-lactate (90.1 mmol/liter) than described before in humans. D-Lactate fluctuated between 0.5 and 3.1 mmol/liter in plasma (normal < 0.1 mmol/liter) and between 1.1 and 52.8 mmol/liter in urine (normal < 0.7 mmol/liter) within a few hours, indicating that the human organism do metabolize and excrete D-lactate. The patient with D-lactic acidosis had a 10-fold increased DL-lactate production from glucose in fecal homogenates compared to 14 healthy controls and a patient with intestinal bypass, who did not have D-lactic acidosis. A 67% carbohydrate (starch)-enriched diet resulted in a minor elevation of fecal and plasma lactate, whereas 50 + 100 + 150 g of ingested lactose increased D-lactate in feces (84.0 mmol/liter) and plasma (2.3 mmol/liter) considerably in the patient with D-lactic acidosis. Intestinal prolongation (22 cm ileum) had a temporary effect on fecal and plasma D-lactate, but intestinal continuity was reestablished 26 months later because D-lactic acidosis recurred (plasma 8.6 mmol/liter, urine 101.3 mmol/liter). Large amounts of lactulose (160 g/day) to 12 normal individuals increased D-lactate to 13.6 +/- 3.5 mmol/liter in feces, but never increased D-lactate in plasma or urine. The in vitro fermentation of glucose in fecal homogenates increased DL-lactate, which disappeared after complete metabolization of the glucose. L-Lactate was converted to D-lactate and vice versa, and both were degraded to the short-chain fatty acids acetate, propionate, and butyrate. An infrequent, but elevated ability of the colonic flora to produce lactate may be a prerequisite for D-lactic acidosis to occur and may explain why the syndrome is so seldom seen even in patients with intestinal bypass or short bowels. The suggestion that D-lactate is not metabolized and hence accumulates is probably not valid.

Influence of intestinal inflammation (IBD) and small and large bowel length on fecal short-chain fatty acids and lactate.

Treatment with short-chain fatty acids (SCFAs) seems promising in ulcerative colitis and changes in colonocyte oxidation of butyrate have been suggested to be of importance for the development of this disease. The influence of small and large bowel length after surgery on SCFAs is only partly known. SCFAs and lactate were measured in consecutive fecal samples from 300 patients with ulcerative colitis (103), Crohn's disease (127), and noninflammatory bowel disease (70); 205 had had surgery, 52 had short bowels (< 200 cm). Lactate (mainly the L-isomer) was elevated in ulcerative colitis patients with pancolitis (mean +/- SEM, 17 +/- 5 mmol/liter) and proctitis (12 +/- 3 mmol/liter) compared with quiescent ulcerative colitis (3 +/- 1 mmol/liter, P < 0.01), and correlated with the index of Truelove (R = 0.52, P < 0.0005). Lactate was also increased in Crohn's colitis (21 +/- 8 mmol/liter), but not in isolated ileitis (4 +/- 2 mmol/liter), compared with quiescent Crohn's disease (7 +/- 2 mmol/liter, P < 0.02), but did not correlate with the activity index (CDAI; R = 0.18, P = 0.12). In contrast to earlier reports, SCFAs (including butyrate) did not correlate with inflammatory activity or localization in either ulcerative colitis or Crohn's disease. The length of the small bowel had no influence on SCFAs and lactate in patients with either no colonic function (ileostomies), or with > 50% and < 50% preserved colorectal length, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A GENERIC REVISION OF THE BRACKISH-WATER SERPULID FICOPOMATUS SOUTHERN 1921 (POLYCHAETA: SERPULINAE), INCLUDING MERCIERELLA FAUVEL 1923, SPHAEROPOMATUS TREADWELL 1934, MERCIERELLOPSIS RIOJA 1945 AND NEOPOMATUS PILLAI 1960.

The brackish water serpulid genera Mercierella, Mercierellopsis, Neopomatus and Sphaeropomatus are synonymized with Ficopomatus, including four species: F. enigmaticus, F. macrodon, F. miamiensis and F. uschakovi. The geographical distributions of the species are illustrated, and the confused identity of tropical specimens has been clarified, at least in part. The generic position of Ficopomatus capensis is discussed. Fossil records of Mercierella and related genera most probably do not belong to the genus Ficopomatus.

Lactate and pH in faeces from patients with colonic adenomas or cancer.

Earlier studies have reported that faecal pH is more alkaline in patients with colonic cancer, indicating a reduction in colonic carbohydrate fermentation to organic acids. The pH of faeces from 11 pre and 14 postoperative, selected colonic cancer patients without intestinal obstruction, major loss of appetite or weight, not treated with antibiotics, and without signs of dissemination or recurrence of the cancer, did not differ, however, from faecal pH in 17 patients with previous colonic adenomas removed by polypectomy and faecal pH in 17 age matched (mean 61 years) healthy controls (mean (SE) 7.03 (0.10), 7.15 (0.11), 7.20 (0.12), 7.11 (0.12) respectively; p = 0.82). Faecal pH in 20 younger (mean 32 years) healthy controls tended to be lower (6.89 (0.07) compared with the older age matched control group (p < 0.06). Faecal concentrations of D-, L- or total D+L-lactate did not differ between the patients with present or previous colonic cancer, adenomas, and the healthy controls (D+L-lactate mean (SE) 3.2 (0.5), 3.1 (0.3), 3.5 (0.7), 4.1 (1.0) mmol/l respectively; p = 0.72), and the production pattern of lactate from different carbohydrates (glucose and dietary fibre) in 16.6% faecal homogenates was similar in all the three groups of patients and the healthy controls. Faecal pH was changed within days by modifications of the diet. An enteral diet free of fibre, starch, and lactose increased faecal pH within three days, whereas pH decreased when the colonic load of carbohydrates was increased by lactulose. Therefore, the reported alkaline faecal pH in patients with colonic cancer may reflect short term reduction in dietary intake and colonic fermentation secondary to the presence of the cancer, especially in patients with advanced disease, rather than long term differences in the precancer dietary habits.