Bacterial lipase and high-fat diets in canine exocrine pancreatic insufficiency: A new therapy of steatorrhea?

BACKGROUND & AIMS: Nutrients and properties of lipases affect survival of lipolytic activity during aboral gastrointestinal transit. Whether different doses and formulations of bacterial lipase and diets affect steatorrhea was tested in pancreatic-insufficient dogs. METHODS: A dose of 0-600,000 IU of powdered and 135,000 and 300,000 IU of liquid bacterial lipase was given with a standard meal to 5 dogs with ligated pancreatic ducts. In 4 dogs, 0 or 300,000 IU (normal 6-hour postprandial amount) of powder bacterial lipase was also given with five meals containing 850 kcal with different nutrient caloric densities (mixture design). Coefficients of fat absorption during 72- hour fecal balance studies were used to assess treatments. RESULTS: With the standard meal, powder bacterial lipase reduced steatorrhea in a dose-dependent manner (P = 0.03), and 135,000 and 300,000 IU of the liquid form decreased steatorrhea more than powder bacterial lipase (P = 0.017 and 0.057, respectively). Coefficients of fat absorption with 300,000 IU of powder bacterial lipase correlated (r2 = 0.79; P < 0.001) with increasing proportions of fat calories in diets. CONCLUSIONS: Liquid bacterial lipase decreases steatorrhea more than powder, and 300,000 IU of powder bacterial lipase ingested with high-fat meals corrects canine pancreatic steatorrhea. The combination of adequate mixing of small amounts (milligrams) of bacterial lipase and high-fat meals abolishes canine steatorrhea and may abolish human pancreatic steatorrhea. (Gastroenterology 1997 Jun;112(6):2048-55)     

A randomized controlled trial of electromagnetic therapy in the primary care management of venous leg ulceration

OBJECTIVE: The aim was to establish the potential efficacy, tolerabilityand side-effect profile of electromagnetic therapy as an adjunctto conventional dressings in the treatment of venous leg ulcers. METHOD: A prospective, randomized, double blind controlled clinicaltrial was carried out in a dedicated leg ulcer clinic basedin one urban general practice. Nineteen patients with leg ulcersof confirmed venous aetiology were assessed. The main outcomemeasures were rate and scale of venous leg ulcer healing, changesin patient-reported pain levels, quality of life, degree ofmobility, side effect profile and acceptability to patientsand staff. RESULTS: Sixty-eight per cent of patients attending this dedicated clinicachieved improvements in the size of their ulcer (4, 21%, healedfully) and in reduced pain levels (P < 0.05) during the trial,despite the chronicity of ulcer histories. Patients treatedwith electromagnetic therapy at 800 Hz were found at day 50to have significantly greater healing (P < 0.05) and paincontrol (P < 0.05) than placebo therapy or treatment with600 Hz. All patients reported improved mobility at the end ofthe study. The electromagnetic therapy was well tolerated bypatients, with no differences between groups in reporting adverseevents, and proved acceptable to staff. CONCLUSION: Despite the small numbers in this pilot study, electromagnetictherapy provided significant gains in the healing of venousleg ulcers and reduction in pain. Keywords. Electromagnetic therapy, RCT, leg ulcers, primary care.     

Communication on end-of-life decisions with patients wishing to die at home: the making of a guideline for GPs in Flanders, Belgium

BACKGROUND: Communication with patients on end-of-life decisions is a delicate topic for which there is little guidance.AIM: To describe the development of a guideline for GPs on end-of-life communication with patients who wish to die at home, in a context where patient autonomy and euthanasia are legally regulated. DESIGN OF STUDY: A three-phase process (generation, elaboration and validation). In the generation phase, literature findings were structured and then prioritised in a focus group with GPs of a palliative care consultation network. In the elaboration phase, qualitative data on patients' and caregivers' perspectives were gathered through a focus group with next-of-kin, in-depth interviews with terminal patients, and four quality circle sessions with representatives of all constituencies. In the validation phase, the acceptability of the draft guideline was reviewed in bipolar focus groups (GPs-nurses and GPs-specialists). Finally, comments were solicited from experts by mail. SETTING: Primary home care in Belgium. SUBJECTS: Participants in this study were terminal patients (n = 17), next-of-kin of terminal patients (n = 17), GPs (n = 25), specialists (n = 3), nurses (n = 8), other caregivers (n = 2) and experts (n = 41). RESULTS: Caregivers and patients expressed a need for a comprehensive guideline on communication in end-of-life decisions. Four major communication themes were prioritised: truth telling; exploration of the patient's wishes regarding the end of life; dealing with disproportionate interventions; and dealing with requests for euthanasia in the terminal phase of life. Additional themes required special attention in the guideline: continuity of care by the GP; communication on foregoing food and fluid; and technical aspects of euthanasia. CONCLUSION: It was feasible to develop a guideline by combining the three cornerstones of evidence-based medicine: literature search, patient values and professional experience.     

Dominant negative mutations in the C-propeptide of COL2A1 cause platyspondylic lethal skeletal dysplasia, torrance type, and define a novel subfamily within the type 2 collagenopathies

Platyspondylic lethal skeletal dysplasia (PLSD) Torrance type (PLSD-T) is a rare skeletal dysplasia characterized by platyspondyly, brachydactyly, and metaphyseal changes. Generally a perinatally lethal disease, a few long-term survivors have been reported. Recently, mutations in the carboxy-propeptide of type II collagen have been identified in two patients with PLSD-T, indicating that PLSD-T is a type 2 collagen-associated disorder. We studied eight additional cases of PLSD-T and found that all had mutations in the C-propeptide domain of COL2A1. The mutational spectrum includes missense, stop codon and frameshift mutations. All non-sense mutations were located in the last exon, where they would escape non-sense-mediated RNA-decay. We conclude that PLSD-T is caused by mutations in the C-propeptide domain of COL2A1, which lead to biosynthesis of an altered collagen chain (as opposed to a null allele). Similar mutations have recently been found to be the cause of spondyloperipheral dysplasia, a non-lethal dominant disorder whose clinical and radiographical features overlap those of the rare long-term survivors with PLSD-T. Thus, spondyloperipheral dysplasia and PLSD-T constitute a novel subfamily within the type II collagenopathies, associated with specific mutations in the C-propeptide domain and characterized by distinctive radiological features including metaphyseal changes and brachydactyly that set them apart from other type 2 collagenopathies associated with mutations in the triple-helical domain of COL2A1. The specific phenotype of C-propeptide mutations could result from a combination of diminished collagen fibril formation, toxic effects through the accumulation of unfolded collagen chains inside the chondrocytes, and alteration of a putative signaling function of the carboxy-propeptide of type 2 collagen.     

Mutation analysis of the BRCA1 and BRCA2 genes results in the identification of novel and recurrent mutations in 6/16 flemish families with breast and/or ovarian cancer but not in 12 sporadic patients with early-onset disease. Mutations in brief no. 224. Online

Since the identification of the BRCA1 and BRCA2 genes (MIM#s 113705 and 600185), more than hundred different mutations throughout both genes have been reported. Recurrent mutations are rare and mainly due to founder effects. We analyzed 12 sporadic female patients with breast cancer before age 35, as well as 16 unrelated families, presenting with either (i) at least 3 first degree relatives with breast and/or ovarian cancer diagnosed at any age, or (ii) at least 2 first and/or second degree relatives with breast and/or ovarian cancer before age 45 years. We performed a protein truncation test for BRCA1 exon 11 and BRCA2 exons 10 and 11 and heteroduplex analysis for all the remaining exons of BRCA1 and 2. Presence of genomic deletions encompassing exons 13 or 22 of BRCA1, known to be Dutch founder mutations, was investigated by PCR. In 6/16 (37.5%) unrelated families the causal mutation in either the BRCA1 or BRCA2 gene was identified. Four different mutations were found in the BRCA1 gene: IVS5+3A>G (intron 5), 1191delC (exon 11), R1443X (exon 13), IVS22+5G>A (intron 22) and two in the BRCA2 gene: 6503delTT (exon 11), 6831delTG (exon 11). 1191delC (BRCA1) and 6831delTG (BRCA2) are novel mutations. IVS5+3A>G in exon 5 of BRCA1 published by Peelen et al. (1997) as a novel Belgian mutation, was identified in one additional family, not fulfilling our inclusion criteria. In the group of 12 sporadic female patients no mutations were found.