The prognosis of incurable cachectic cancer patients on home parenteral nutrition: a multi-centre observational study with prospective follow-up of 414 patients.

BACKGROUND: The role of home parenteral nutrition (HPN) in incurable cachectic cancer patients unable to eat is extremely controversial. The aim of this study is to analyse which factors can influence the outcome. PATIENTS AND METHODS: We studied prospectively 414 incurable cachectic (sub)obstructed cancer patients receiving HPN and analysed the association between patient or clinical characteristics and surviving status. RESULTS: Median weight loss, versus pre-disease and last 6-month period, was 24% and 16%, respectively. Median body mass index was 19.5, median KPS was 60, median life expectancy was 3 months. Mean/median survival was 4.7/3.0 months; 50.0% and 22.9% of patients survived 3 and 6 months, respectively. At the multivariable analysis, the variables significantly associated with 3- and 6-month survival were Glasgow Prognostic Score (GPS) and KPS, and GPS, KPS and tumour spread, respectively. By the aggregation of the significant variables, it was possible to dissect several classes of patients with different survival probabilities. CONCLUSIONS: The outcome of cachectic incurable cancer patients on HPN is not homogeneous. It is possible to identify groups of patients with a ≥6-month survival (possibly longer than that allowed in starvation). The indications for HPN can be modulated on these clinical/biochemical indices.

Adaptation of the Psoriatic Arthritis Quality of Life (PsAQoL) instrument for Sweden.

OBJECTIVE: The Psoriatic Arthritis Quality of Life (PsAQoL) questionnaire is the first disease-specific patient-derived instrument for assessing QoL in patients with PsA and has been extensively validated in this population. The aim of the adaptation process reported here was to develop a Swedish version of the PsAQoL that was equivalent to, and met the same psychometric and acceptability standards as, the original instrument, which was developed in the UK. METHOD: Translation of the original questionnaire into Swedish was performed by a professional and a lay panel. Field testing for face and content validity was performed by interviewing 13 patients. Finally, 123 patients with PsA were included in a test-retest postal survey designed to test reproducibility and construct validity. The PsAQoL was administered on two occasions approximately 2 weeks apart. The Nottingham Health Profile (NHP) was used as a comparator instrument. RESULTS: The Swedish version of the PsAQoL questionnaire showed good reliability at both time points and, as expected, correlated with the NHP. The scale was able to distinguish between groups based on self-reported general health and flare-up. Patients with active symptoms of both arthritis and psoriasis had worse QoL. The results also indicated that duration of disease has a progressive impact on PsAQoL scores. CONCLUSIONS: This study provides evidence that the adapted PsAQoL can be used for clinical studies in Swedish patients. The instrument provides valuable information on the long-term effects of PsA on QoL.

Home enteral nutrition in adults: a European multicentre survey.

AIMS: This study was undertaken to report indications and practice of home enteral nutrition (HEN) in Europe. METHODS: A questionnaire on HEN practice was sent to 23 centres from Belgium (B), Denmark (D), France (F), Germany (G), Italy (I), Poland (P), Spain (S) and the United Kingdom (UK). This involved adult patients newly registered in HEN programme from 1 January 1998 to 31 December 1998. RESULTS: A total of 1397 patients (532 women, 865 men) were registered. The median incidence of HEN was 163 patients/million inhabitants/year (range: 62-457). Age distribution was 7.5%, 16-40 years; 37.1%, 41-65 years; 34.5%, 66-80 years and 20.9% >80 years. The chief underlying diseases were a neurological disorder (49.1%), or head and neck cancer (26.5%); the main reason for HEN was dysphagia (84.6%). A percutaneous endoscopic gastrostomy (58.2%) or a naso-gastric tube (29.3%) were used to infuse commercial standard or high energy diets (65.3%), or fibre diets (24.5%); infusion was cyclical (61.5%) or bolus (34.1%). Indications and feeds were quite similar throughout the different centres but some differences exist concerning the underlying disease. There was greater variation in the choice of tubes and mode of infusion. In F, G, I, S, and UK, costs of HEN are fully funded. In B, D, and P patients have to pay part or all of the charges. CONCLUSIONS: In Europe, HEN was utilised mainly in dysphagic patients with neurological disorders or cancer, using a standard feed via a PEG. However, there were important differences among the countries in the underlying diseases treated, the routes used, the mode of administration and the funding.

Vitamin D status and measurements of markers of bone metabolism in patients with small intestinal resection.

BACKGROUND AND AIMS: Vitamin D deficiency is common in patients with small intestinal resection and may lead to secondary hypersecretion of parathyroid hormone (PTH), which in turn may result in increased bone turnover rate and loss of bone mineral. The aims of this study were to investigate the prevalence of vitamin D deficiency, as assessed by low serum concentrations of 25-hydroxyvitamin D (25(OH)D) in patients with small intestinal resection and to explore the relation of 25(OH)D to PTH, markers of bone turnover rate, and bone mineral density (BMD) in these patients. PATIENTS: Forty two patients with small intestinal resection, a faecal energy excretion of more than 2.0 MJ/day, and a mean length of the remaining small intestine of 199 cm were included. Diagnoses were Crohn's disease (n=35) and other (n=7). METHODS: 25(OH)D was analysed by radioimmunoassay and bone turnover rate was assessed by measurement of serum osteocalcin, serum alkaline phosphatase, urine pyridinoline, and urine deoxypyridinoline. BMD was measured by dual energy x ray absorptiometry. RESULTS: Mean 25(OH)D concentration was 13.4 (SD 9.7) ng/ml, which was significantly below the reference mean of 26.4 (SD 13.2) ng/ml (p<0.001). Vitamin D deficiency (25(OH)D concentration

Pyoderma gangrenosum associated with crohn disease: effect of TNF-alpha blockade with infliximab.

Eight patients with pyoderma gangrenosum associated with Crohn disease were treated with infliximab. All had active mucosal inflammation indicated by endoscopic examination. Within 1-4 months, infliximab treatment resulted in complete healing of the pyoderma gangrenosum in 3 cases (1 parastomal, 2 lower limb), partial healing in 3 (2 parastomal, 1 lower limb) and temporary improvement in 2. Adverse effects such as skin rash, pneumonia and diarrhoea were seen in three patients. Our results imply that infliximab has a therapeutic potential on skin manifestations associated with inflammatory bowel disease, even though successful treatment may require repeat courses of infliximab infusions.

Short-term administration of glucagon-like peptide-2. Effects on bone mineral density and markers of bone turnover in short-bowel patients with no colon.

BACKGROUND: Glucagon-like peptide 2 (GLP-2) is a newly discovered intestinotrophic hormone. We have recently reported that a 5-week GLP-2 treatment improved the intestinal absorptive capacity of short-bowel patients with no colon. Additionally, GLP-2 treatment was associated with changes in body composition that included a significant increase in total body bone mass. This article describes the effect of GLP-2 on spinal and hip bone mineral density (BMD) and biochemical markers of bone turnover in these patients. METHODS: In an open-labelled pilot study, eight short-bowel patients (3M, 5F; mean age 49 years) with small-bowel resection and no colon received 400 microg s.c. of GLP-2 twice daily for 5 weeks. Four received home parenteral nutrition (mean length of residual jejunum 83 cm) and 4 did not (mean length of ileum resected 106 cm). The outcome measures were the mean percent change from baseline in spinal and hip BMD measured by dual-energy X-ray absorptiometry, changes in four biochemical markers of bone-turnover, PTH, 25-hydroxy vitamin-D, and the intestinal absorption of calcium. RESULTS: Mean +/- s(x) (SEM) percent changes in spinal and hip BMD were 1.1+/-0.4% (P < 0.05) and 1.9+/-0.8% (P = 0.06), respectively. The intestinal calcium absorption increased by 2.7% (P = 0.87). Serum ionized calcium increased in 5/8 patients with a concomitant decrease in serum PTH values. Three of the four markers of bone turnover decreased. CONCLUSION: A 5-week GLP-2 administration significantly increased spinal BMD in short-bowel patients with no colon. The mechanism by which GLP-2 affects bone metabolism remains unclear, but may be related to an increased mineralization of bone resulting from an improved intestinal calcium absorption.

Alendronate increases lumbar spine bone mineral density in patients with Crohn's disease.

BACKGROUND & AIMS: Low bone mineral density (BMD) is a common complication of Crohn's disease and may lead to increased morbidity and mortality because of fractures. We investigated the effect of treatment with the bisphosphonate alendronate on bone mass and markers of bone remodeling in patients with Crohn's disease. METHODS: A 12-month double-blind, randomized, placebo-controlled trial examined the effect of a 10-mg daily dose of alendronate. Thirty-two patients with a bone mass T score of -1 of the hip or lumbar spine were studied. The main outcome measure was the difference in the mean percent change in BMD of the lumbar spine measured by dual-energy x-ray absorptiometry. Secondary outcome measures included changes in BMD of the hip and total body and biochemical markers of bone turnover (S-osteocalcin, urine pyridinoline, and urine deoxypyridinoline excretion). RESULTS: Mean (+/-SEM) BMD of the lumbar spine showed an increase of 4.6% +/- 1.2% in the alendronate group compared with a decrease of 0.9% +/- 1.0% in patients receiving placebo (P < 0.01). BMD of the hip increased by 3.3% +/- 1.5% in the alendronate group compared with a smaller increase of 0.7% +/- 1.1% in the placebo group (P = 0.08). Biochemical markers of bone turnover decreased significantly in the alendronate group (P < 0.001). Alendronate was well tolerated, and there was no difference in adverse events among treatment groups. CONCLUSIONS: Treatment with alendronate, 10 mg daily, significantly increased BMD in patients with Crohn's disease and was safe and well tolerated.

Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European Cooperative Crohn's Disease Study VI.

BACKGROUND & AIMS: This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn's disease after surgical resection. METHODS: In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanlose, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohn's Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model. RESULTS: Cumulative relapse rates (+/-SE) after 18 months were 24.5% +/- 3.6% and 31.4% +/- 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively (P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% +/- 5.6% vs. 39.7% +/- 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease (P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003). CONCLUSIONS: Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohn's disease. Some relapse-preventing effect was found in patients with isolated small bowel disease.

Clinical nutrition in danish hospitals: a questionnaire-based investigation among doctors and nurses.

Specific nutrition standards are now developed by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) in order to improve the nutritional status in hospitalized patients. We investigated the use of clinical nutrition in Danish hospitals and compared it with the standards of JCAHO by doing a questionnaire-based investigation among doctors and nurses randomly selected in 40 hospitals including internal medicine, gastroenterology, oncology, orthopedic departments and intensive care units (ICU).Overall, 857 (43.4%) responded to the questionnaire (doctors: 395, nurses: 462). Seventy-seven percent stated that nutritional assessment ought to be performed on admission, but only 24% stated that it was a routine procedure. Forty percent found it difficult to identify risk-patients, and 52% needed specific screening tools. Twenty-two percent registered body weight in all patients, and 18% registered nutrient intake routinely. Eighty-four percent found that a nutrition plan should be described in the patient record, but 39% found it difficult to set up an individual plan, and 79% expressed a need for specific guidelines. Eighty-four percent would only accept a patient being on isotonic glucose and/or electrolyte infusion for < 5 days (42% for < 2 days), and 33% would only accept a weight loss of 5% before active nutrition was initiated. About 50% would be restrictive in supplying enteral or parenteral nutrition to patients with impaired liver or kidney function. Twenty-seven percent did not use active nutritional therapy at all. Seventy-six percent found that nutritional assessment should be performed during hospital stays, but only 23% monitored the nutritional status. Sixty-eight percent stated that responsibility should be assigned to one or more persons, but this was the case in only 20%The use of clinical nutrition in Danish hospitals did not fulfill the standards for nutrition support according to the criteria established by JCAHO. Special efforts should be aimed at education, specific screening tools and introduction of guidelines in clinical nutrition.

Home parenteral nutrition in adults: a european multicentre survey in 1997. ESPEN-Home Artificial Nutrition Working Group.

A retrospective survey on home parenteral nutrition (HPN) in Europe was performed from January to December 1997. Data were compared to a similar study performed in 1993. A questionnaire of HPN practice was designed by the members of the ESPEN-HAN group. This involved adult patients (older than 16 years) newly registered in an HPN program between 1 January and 31 December 1997 and included: number of patients, underlying diseases and a 6-12 month outcome. Incidence and prevalence (at 1.1.1998) of adult HPN were calculated according to the estimated total population in 1997 for the countries in which more than 80% of HPN patients were reported.A total of 494 patients were registered in 73 centres from nine countries (Belgium (B), Denmark (D), France (F), Poland (P), Spain (S), Sweden (Sw), United Kingdom (UK), The Netherlands (N) and Germany (G). The underlying diseases for HPN in 494 patients were cancer (39%), Crohn's (19%), vascular diseases (15%), radiation enteritis (7%), AIDS (2%), other diseases with intestinal failure (18%). Incidence (patients/million inhabitants/year) were in N (3), F. (2.9), D. (2.8), B. (2.6), UK (1. 2), S (0.7) and P (0.36), respectively. Prevalence were in D. (12.7). U.K. (3.7), N. (3.7), F (3.6), B (3.0), P (1.1), S (0.65). After this 6-12 months follow-up (n=284), the mortality was respectively 4% in Crohn's disease, 13% in vascular diseases, 16% in others, 21% in radiaton enteritis, 34% in AIDS, 74% in cancer. Incidences and prevalences modestly increased in these seven European countries in 1997 in comparison to 1993. The percentages of underlying diseases in these countries remained similar except for AIDS that significantly decreased (from 7% to 2%). Outcomes did not significantly differ in the 4-year period except for AIDS (34% instead of 88% mortality) and could have been related to newer, more efficacious therapy.

Selenium depletion in patients with gastrointestinal diseases: are there any predictive factors?

BACKGROUND: Patients with intestinal disease are at risk of developing selenium deficiency due to impaired intestinal absorption. The aim of the present study was to evaluate selenium status and to identify predictive factors of selenium depletion in patients with gastrointestinal disease. METHODS: The concentration of selenium and the activity of glutathione peroxidase in plasma and erythrocytes were measured by fluorometry and by spectrophotometry. Eighty-six patients with Crohn's disease, 40 patients with ulcerative colitis, and 39 patients with various other gastrointestinal diseases were studied. Twenty-seven patients (16%) received home parenteral nutrition. Stool mass, faecal fat, and vitamin B12 absorption were analysed in 100 patients. RESULTS: The plasma selenium concentration was decreased in 85% of the patients receiving supplementary parenteral nutrition and in 20% of the patients receiving oral nutrition, among them in 26% of the patients with Crohn's disease. Almost all patients with ulcerative colitis had normal selenium levels. A statistically significant correlation was found between plasma selenium and vitamin B12 absorption, stool mass, faecal fat excretion, body mass index, P-albumin, P-zinc, and the length of the remaining small bowel. Stepwise regression analyses showed that the strongest predictors of selenium deficiency were stool mass, vitamin B12 absorption, and the length of the small-bowel resection. CONCLUSION: Selenium deficiency is common in patients with severe gastrointestinal disorders. The deficiency is mainly related to malabsorption, and a low selenium level was almost invariably present in patients who needed parenteral supplementation due to gut failure.

Body composition by dual-energy X-ray absorptiometry in patients with Crohn's disease.

BACKGROUND: To study body composition at the whole-body level in patients with Crohn's disease and a history of intestinal resection compared with healthy controls, we performed a cross-sectional study using dual-energy X-ray absorptiometry (DXA). METHODS: Thirty-one patients, 13 men and 18 women, were included. They had a history of Crohn's disease for a mean period of 20 years (range, 4-45 years). All patients had undergone intestinal resections. The colon had been resected in 24 patients, and the mean length of the resected small intestine was 97 cm (range, 0-305 cm). At the time of investigation the Crohn's disease had been in remission for at least 24 months. Patients presented with significantly increased faecal volume and faecal fat excretion. A group of 69 women and 19 men were investigated with DXA and used as reference group. The fat-free mass (FFM), fat mass (FM), percentage fat mass (FM%), and total body mineral content (TBMC) were measured by DXA, and the results were expressed as a z-score. RESULTS: The mean z-score of the body mass index (BMI) was significantly reduced to -0.35 (P=0.036). The FFM was significantly reduced with a mean z-score of -1.74 (P=0.0001). The FM was unchanged (z-score, 0.12; P=0.42). However, FM expressed as percentage of body weight was significantly increased, with a z-score of 0.88 (P=0.001). The TBMC was significantly decreased, with a mean z-score of -1.42 (P=0.0001). There was positive direct correlation between the BMI and TBMC z-scores. There was no correlation between malabsorption and body composition variables. CONCLUSION: Patients with clinically quiescent Crohn's disease showed significant changes in body composition, with low BMI, significant loss of FFM, and unchanged FM. However, when expressed as percentage of body weight, FM was significantly increased. The TBMC was significantly reduced.

Adult patients receiving home parenteral nutrition in Denmark from 1991 to 1996: who will benefit from intestinal transplantation?

BACKGROUND: Small-bowel transplantation is an alternative to home parenteral nutrition (HPN) in patients with gut failure. Our aim was to report the indication, diagnosis, morbidity, mortality, and intestinal adaptation in the total cohort of Danish patients receiving HPN at any time during the 5 years between 1 January 1991 and 31 December 1995. The data were analysed against the option of transplantation. RESULTS: HPN was given to 129 patients; 59 (46%) had inflammatory bowel disease (15% died), 26 (20%) had cured cancers (42% died), and 44 (34%) had other diseases (dysmotility, surgical complications, infarcts, and so forth; 27% died). Of these, 60% were new in the HPN program, but only 19% received HPN all 5 years; 31 % had terminated HPN, 19% permanently, and 25% died. Only four deaths were HPN-related. In December 1995, 73 patients were receiving HPN in Denmark, for a prevalence of 13.9 per million, which is the highest in Europe but 10-fold lower than in the United States. CONCLUSIONS: Gut failure was the only indication for HPN in Denmark. Weight loss without gut failure, such as disseminated cancer and acquired immunodeficiency syndrome, was not an indication for HPN. Survival after small-bowel transplantation should be assessed against a sizeable mortality among candidates receiving HPN, and this depends on diagnosis and age. In an HPN population comparable with the Danish, a quarter is likely to die within a period of 5 years, a quarter will terminate HPN, and the others survive with HPN. Small-bowel transplantation can be a lifesaving procedure in the small fraction of foreseeable HPN-related deaths, mainly caused by liver failure. Transplantation will not improve survival in most adult HPN patients, and only an improved quality of life after transplantation justifies this procedure in most HPN patients.

Body composition changes measured by dual-energy X-ray absorptiometry in patients receiving home parenteral nutrition.

BACKGROUND: To monitor changes in body composition in patients receiving home parenteral nutrition (HPN) and to ascertain whether changes were related to the amount of energy supplied by HPN, we studied prospectively patients with gut failure maintained on HPN. METHODS: Patients were subjected to repeated measurement of body composition by dual-energy X-ray absorptiometry (DXA), the second investigation being performed after a mean period of 20 (range, 11-26) months. Thirty-two patients were included, one patient was excluded, and five patients died during the study period. At inclusion, the patients had received HPN for a mean period of 30 (range, 6-216) months. The indication for HPN was inflammatory bowel disease (n = 16), abdominal cancers (n = 5), and scleroderma and others (n = 11). The fat-free mass (FFM), fat mass (FM), and total body mineral content (TBMC) were measured by DXA. RESULTS: Mean body mass index decreased from 21.18 to 20.96 kg/m2 (P = 0.36). The mean FFM showed a small, insignificant increase to 37.68 kg (P = 0.71). Mean TBMC was unchanged at 2.28 kg, and mean FM decreased from 19.25 to 18.17 kg (P = 0.055). During the study period the mean daily energy supply by HPN was reduced from kcal 1195 to kcal 959 (P = 0.004). There was a direct positive correlation between the individual changes in HPN energy supply and body weight and FFM (r = 0.437, r = 0.410, P < 0.05). CONCLUSION: The body composition of HPN patients was stable, with no change in mean FFM, FM, or TBMC. Individual changes in body weight and FFM correlated with change in HPN energy supply.

Bone mineral content in patients with Crohn's disease. A longitudinal study in patients with bowel resections.

BACKGROUND: Low bone mineral content (BMC) has been reported in patients with inflammatory bowel disease. The aim of the present study was to measure BMC in patients with Crohn's disease. METHODS: BMC was monitored for a mean period of 5.5 years in 108 patients. The patients were divided into two groups: group A, patients with the colon preserved; group B, patients with a resected colon. The mean length of the resected small intestine was 90 cm. RESULTS: The BMC of the lumbar spine expressed as Z-score ((actual value-mean)/s) was significantly reduced: mean Z-score for group A, -0.51, P < 0.05; group B, -0.80, P < 0.001. The BMC of the femoral neck was significantly reduced: mean Z-score for group A, -1.24, P < 0.001; group B, -1.23, P < 0.001. A Z-score below -2.0 of spine or femoral neck BMC was found in 10% and 23% of the patients, respectively. The BMC of the femoral neck decreased significantly in both groups during the study period (group A, -2.2%, P < 0.001; group B, -1.21%, P < 0.05). The BMC of the lumbar spine did not change. There was an inverse correlation between the initial Z-score and the rate of change in BMC (P < 0.05). We found no correlation between Z-score or change in BMC and period of prednisolone treatment. Moreover, there was no correlation between the length of the resected small intestine and BMC or annual percentage change in BMC. CONCLUSION: At inclusion the BMC of the spine and femoral neck was low in patients with Crohn's disease. During the study significant bone loss was only demonstrated in the femoral neck. BMC or rate of change in BMC was not related to treatment with steroids or length of the resected small intestine.

Effect of parathyroid hormone on renal calbindin-D28k.

The present investigation was conducted to examine the effects of parathyroid hormone (PTH) and parathyroid hormone related peptide (PTHrP) on renal calbindin-D28k in rats. Four groups of studies were performed: (1) parathyroidectomy (PTX) or a sham operation followed by infusion of 1,25-dihydroxyvitamin D (1,25[OH]2D) or vehicle; (2) infusions of PTH(1-34), PTH(1-84), 1,25(OH)2D, or vehicle; (3) infusion of PTHrP(1-34), PTHrP (1-86), PTH(1-34), or vehicle; and (4) injections of calcium or vehicle. PTX reduced renal calbindin-D28k levels even when plasma concentrations of 1,25(OH)2D were kept constant by infusion of 1,25(OH)2D. Infusions of PTH(1-34), PTH(1-84), and 1,25(OH)2D all increased renal calbindin-D28k and plasma calcium, whereas PTHrP(1-34) and PTHrP(1-86) increased renal calbindin-D28k before an increase of plasma calcium took place. Hypercalcemia induced by the injection of calcium did not affect the levels of renal calbindin-D28k. The present data suggest that PTH and PTHrP exert a direct effect on renal calbindin-D28k, which is not mediated by changes of 1,25(OH)2D or calcium.

Calbindin-D9k gene expression during the perinatal period in the rat: correlation to estrogen receptor expression in uterus.

Calbindin-D9k (CaBP-9k) is a cytosolic calcium binding protein mainly expressed in duodenum, placenta and uterus. The gene encoding the rat CaBP-9k is subject to tissue specific induction by 1,25 dihydroxyvitamin D3 (intestine) and estradiol (E2) (uterus). Control of placental expression remains unknown. The expression of CaBP-9k mRNA during the perinatal period was studied (pregnancy day 21 (P21)-lactation day 4 (L4)). In uterus, maximal expression levels were found at P21 and maintained until L1. With the transition to L2, the CaBP-9k mRNA concentration dropped drastically below the detection limit as quantitated by Northern blot analysis. Measurements of E2 and progesterone (P) levels showed a gradual decrease at late pregnancy (P21; birth). Post partum E2 levels continued to decline and P concentrations increased slightly. Uterine estrogen receptor (ER) mRNA levels determined by cDNA/PCR analysis revealed close correlation between expression of ER and CaBP-9k mRNAs. ER mRNA levels were maximal at P22 and declined at parturition and with onset of lactation. At L2 and L3 ER mRNA levels were minimal and had decreased 5-fold compared to late pregnancy. CaBP-9k protein concentrations fluctuated only slightly dependent on the stage of the estrous cycle: estrus > proestrus > diestrus. During the perinatal period CaBP-9k concentration was overall lower than in non-pregnant uterus and revealed only a moderate increase at birth and decrease in early lactation. Similar to the uterine levels, placental CaBP-9k mRNA was highest at P21 and remained high until birth. Fetal duodenal CaBP-9k rose sharply just prior to birth and plateaued in the early postpartal period.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of calbindin-D9K in small intestinal biopsy specimens of children.

The vitamin D dependent intestinal calcium-binding protein (calbindin-D9K) was measured by an enzyme-linked immunoadsorbent assay in small intestinal biopsy specimens from 10 children (aged 15-126 months). The aim was to study the relationship between calcium-binding protein and age, bone age, and height. The patients were examined due to complaints of chronic diarrhea, but no evidence of malabsorption was found. The amount of calbindin-D9K per mg of soluble protein in the small intestinal biopsy specimens was higher than previously studied in normal adults. Calbindin-D9K correlated inversely with chronological age, bone age, and height of the children (p = -0.87, rho = -0.66, and rho = -0.66; p less than 0.05). A direct correlation was found between calbindin-D9K and intestinal alkaline phosphatase activity (p = 0.60; p less than 0.05). The decline in calbindin-D9K may indicate that the active vitamin D dependent intestinal calcium absorption decreases during childhood.

Calcium absorption and bone mineral content in patients subjected to ileal bypass because of familial hypercholesterolaemia.

Calcium absorption and bone mineral content were studied prospectively in 30 patients with familial hypercholesterolaemia subjected to partial ileal bypass surgery. One-third of the patients were followed up for 10 years after the operation. Six months postoperatively calcium absorption decreased significantly, from a median of 16% to 13%. The effect persisted up to 5 years of follow-up study. Ten years after the operation the absorption of calcium (median, 14.5%) was not significantly different from the preoperative calcium absorption (median, 16%). Bone mineral content, measured in 76% of the patients, was retained in all patients studied. A significant correlation was present between calcium absorption and urinary calcium. The reduction in calcium absorption did not correlate with increases in faecal fat. Other long-term side effects were persistent diarrhoea and moderate steatorrhoea. A significant weight loss was slowly regained in most patients. An increase of renal oxalate excretion was only small and transient in most patients. The study shows that bypass of the terminal 200 cm of ileum for familial hypercholesterolaemia causes moderate diarrhoea and steatorrhoea in most patients but only a slight reduction of intestinal calcium absorption and apparently no risk of bone demineralization. A benefit of a postoperative calcium and vitamin D supply cannot be excluded.

Measurement of the 10,000-molecular weight calcium-binding protein in small-intestinal biopsy specimens from patients with malabsorption syndromes.

Calcium-binding protein (CaBP) (molecular weight, 10,000) was measured in small-intestinal biopsy specimens from 36 patients with malabsorption syndromes: short-bowel syndrome (n = 13), untreated coeliac disease (n = 4), coeliac disease in remission (n = 7), patients with intestinal bypass owing to morbid obesity (n = 5), and in patients with chronic diarrhoea of unknown cause (n = 7). Twelve patients with no signs of malabsorption who had the irritable bowel syndrome were used as controls. Patients with small-bowel resections showed reduced concentrations of CaBP (p less than 0.01) and low intestinal calcium absorption (p less than 0.05). Small amounts of CaBP were found in intestinal specimens from patients with coeliac disease in remission (p less than 0.01), and CaBP was almost undetectable in patients with a newly diagnosed coeliac disease and avillous jejunal biopsy findings (p less than 0.001). Patients with chronic diarrhoea and patients with an intestinal bypass had CaBP concentrations comparable to those of the control group. A direct correlation was found between CaBP and the fractional calcium absorption in all patients (p less than 0.05). CaBP may therefore be considered an indicator of the efficiency of the small intestine to absorb calcium.