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)     

Intracerebroventricular infusion of aldosterone induces hypertension in rats

There is suggestive evidence for the direct participation of mineralocorticoids in the production of centrally mediated hypertension. Unilaterally nephrectomized Sprague-Dawley rats received a continuous infusion for 30 days using implanted osmotic minipumps with 1) artificial spinal fluid (CSF) intracerebroventricularly (icvt); 2) 0.005 micrograms aldosterone/h icvt; 3) 0.005 micrograms aldosterone/h sc; 4) 0.5 micrograms aldosterone/h sc. There was no significant difference between the groups in average weight gain (52 +/- 2 g) or organ weight to body weight, nor was urine volume increased above normal except in the group receiving the high sc dose of aldosterone. Blood pressure was significantly elevated only in those animals receiving 0.005 micrograms aldosterone/h icvt and 0.5 micrograms aldosterone/h sc. A second experiment was done using a specific spironolactone-type mineralocorticoid antagonist, prorenone. The rats were grouped as follows: 1) CSF icvt; 2) 0.005 micrograms/h aldosterone icvt; 3) 0.005 micrograms/h aldosterone plus 0.005 micrograms/h prorenone icvt; 4) 0.005 micrograms/h aldosterone plus 0.02 micrograms/h prorenone icvt; 5) 0.02 micrograms/h prorenone icvt. This study confirmed that this minute dose of aldosterone infused icvt produced a statistically significant increase in blood pressure with no increase in urine volume. Both the low, 0.005 micrograms/h, and high, 0.02 micrograms/h, doses of prorenone antagonized the pressor effect of aldosterone when infused with aldosterone into the lateral cerebral ventricle. The groups receiving 0.02 micrograms/h prorenone icvt or CSF icvt did not differ significantly in those parameters measured. A dose of aldosterone that was too small to produce changes in blood pressure when infused systemically was found to produce hypertension without polydypsia/polyuria when infused intrathecally. This pressor effect could be blocked by the concomitant infusion of a specific antagonist, prorenone. The study presented offers strong circumstantial evidence supporting a direct hypertensinogenic effect of aldosterone within the central nervous system.     

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.     

The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children

OBJECTIVE: The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of children with difficult to control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. This prospective study sought to determine the ketogenic diet's effectiveness and tolerability in children refractory to today's medications. METHODS: One hundred fifty consecutive children, ages 1 to 16 years, virtually all of whom continued to have more than two seizures per week despite adequate therapy with at least two anticonvulsant medications, were prospectively enrolled in this study, treated with the ketogenic diet, and followed for a minimum of 1 year. Seizure frequency was tabulated from patients' daily seizure calendars and seizure reduction calculated as percentage of baseline frequency. Adverse events and reasons for diet discontinuation were recorded. RESULTS: The children (mean age, 5.3 years), averaged 410 seizures per month before the diet, despite an exposure to a mean of 6.2 antiepileptic medications. Three months after diet initiation, 83% of those starting remained on the diet and 34% had >90% decrease in seizures. At 6 months, 71% still remained on the diet and 32% had a >90% decrease in seizures. At 1 year, 55% remained on the diet and 27% had a >90% decrease in seizure frequency. Most of those discontinuing the diet did so because it was either insufficiently effective or too restrictive. Seven percent stopped because of intercurrent illness. CONCLUSIONS: The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.     

CDw60 glycolipid antigens of human leukocytes: structural characterization and cellular distribution

Monoclonal CDw60 antibodies recognize glycolipid antigens with restricted surface expression on human leukocytes. They allow us to define new functional subpopulations of T lymphocytes and are able to induce costimulatory signals. In this report, we describe the molecular composition of CDw60 glycolipid antigens derived from different human leukocyte subpopulations. The glycolipids were isolated and their structures were identified by immunochemical methods. All molecules containing the CDw60 determinant were found in the disialoganglioside fraction. They were O-acetylated derivatives of the gangliosides II3 (Neu5Ac)2-LacCer (GD3), IV3 (Neu5Ac)2-nLc4Cer (DSPG), and VI3 (Neu5Ac)2- nLc6Cer (DSnHC), respectively. The most common CDw60 glycolipid antigen in human leukocytes was 9-O-acetyl GD3. In a comparison of various cell types, the highest concentration of 9-O-acetyl GD3 on a per cell basis was determined in granulocytes and in blood T lymphocytes, whereas B lymphocytes, thymus cells, and monocytes contained considerably smaller amounts of this molecule. Polar CDw60 antigens such as 9-O-acetyl DSPG and 9-O-acetyl DSnHC were only detected in granulocytes.     

Phospholipase A2 levels in acute chest syndrome of sickle cell disease

Acute chest syndrome (ACS) is associated with significant morbidity and is the leading cause of death in patients with sickle cell disease (SCD). Recent reports suggest that bone marrow fat embolism can be detected in many cases of severe ACS. Secretory phospholipase A2 (sPLA2) is an important inflammatory mediator and liberates free fatty acids, which are felt to be responsible for the acute lung injury of the fat embolism syndrome. We measured SPLA2 levels in 35 SCD patients during 20 admissions for ACS, 10 admissions for vaso-occlusive crisis, and during 12 clinic visits when patients were at the steady state. Eleven non-SCD patients with pneumonia were also evaluated. To determine if there was a relationship between sPLA2 and the severity of ACS we correlated SPLA2 levels with the clinical course of the patient. In comparison with normal controls (mean = 3.1 +/- 1.1 ng/mL), the non- SCD patients with pneumonia (mean = 68.6 +/- 82.9 ng/mL) and all three SCD patient groups had an elevation of SPLA2 (steady state mean = 10.0 +/- 8.4 ng/mL; vaso-occlusive crisis mean = 23.7 +/- 40.5 ng/mL; ACS mean = 336 +/- 209 ng/mL). In patients with ACS sPLA2 levels were 100- fold greater than normal control values, 35 times greater than values in SCD patients at baseline, and five times greater than non-SCD patients with pneumonia. The degree of SPLA2 elevation in ACS correlated with three different measures of clinical severity and, in patients followed sequentially, the rise in SPLA2 coincided with the onset of ACS. The dramatic elevation of SPLA2 in patients with ACS but not in patients with vaso-occlusive crisis or non-SCD patients with pneumonia and the correlation between levels of SPLA2 and clinical severity suggest a role for SPLA2 in the diagnosis and, perhaps, in the pathophysiology of patients with ACS.     

Thrombospondin mediates the cytoadherence of Plasmodium falciparum- infected red cells to vascular endothelium in shear flow conditions

Cerebral malaria is thought to involve specific attachment of Plasmodium falciparum-infected knobby red cells to venular endothelium. The nature of surface ligands on host endothelial cells that may mediate cytoadherence is poorly understood. We have investigated the effects of soluble thrombospondin, rabbit antiserum raised against thrombospondin, and human immune serum on cytoadherence of parasitized erythrocytes in ex vivo mesocecum vasculature. Preincubation of infected red cells with soluble thrombospondin or human immune serum inhibits binding of infected red cells to rat venular endothelium. Infusion of the microcirculatory preparation with rabbit antithrombospondin antibodies before perfusion of parasitized erythrocytes also resulted in decreased cytoadherence. In addition, incubation of infected cells with human immune sera obtained from malaria patients significantly inhibited the observed cytoadherence. Our results indicate that thrombospondin mediates binding of infected red cells to venular endothelium and may thus be involved in the pathogenesis of cerebral malaria.