Strontium ranelate does not stimulate bone formation in ovariectomized rats.

INTRODUCTION: Strontium ranelate (SrR) is suggested to function as a dual-acting agent in the treatment of postmenopausal osteoporosis with anti-resorptive and anabolic skeletal benefits. We evaluated the effects of SrR on the skeleton in ovariectomized (OVX) rats and evaluated the influence of dietary calcium. METHODS: Three-month old virgin female rats underwent ovariectomy (OVX, n = 50) or SHAM surgery (SHAM, n = 10). Four weeks post-surgery, rats were treated daily by oral gavage with distilled water (10 ml/kg/day) or SrR (25 or 150 mg/kg/day) for 90 days. Separate groups of animals for each dose of SrR were fed a low (0.1%) or normal (1.19%) calcium (Ca) diet. Static and dynamic histomorphometry, DXA, mu-CT, mechanical testing, and serum and skeletal concentrations of strontium were assessed. RESULTS: SrR at doses of 25 and 150 mg/kg/day did not increase bone formation on trabecular or periosteal bone surfaces, and failed to inhibit bone resorption of trabecular bone regardless of Ca intake. There were no improvements in bone mass, volume or strength with either dose of SrR given normal Ca. CONCLUSION: These findings demonstrate that SrR at dosages of 25 and 150 mg/kg/day did not stimulate an anabolic bone response, and failed to improve the bone biomechanical properties of OVX rats.

Complications of removing percutaneous endoscopic gastrostomy tubes in children.

BACKGROUND: Little information has been reported regarding the frequency and type of complications arising from removal of percutaneous endoscopic gastrostomy (PEG) tubes in children. METHODS: The records of 397 patients who had PEG tubes placed from 1993 through 1998 were reviewed for complications after removal. Data collected included length of time the tube was in place, age of the patient at insertion, type of tube removed, and patient diagnosis. RESULTS: Fifty-four children had the PEG tube removed by traction or endoscopy. The only complication was persistent leaking through a gastrocutaneous fistula in 13 patients (24%). Leaking ceased in 6 children coincident with H2-antagonist therapy and silver nitrate cautery, and surgical closure of the fistula was required in 7 patients. Comparison of these 7 children with those who did not require surgery (n = 47) showed a longer duration of tube placement (mean +/- SE of 20.6+/-3.6 months, range 11-31 months vs. 11.1+/-1.3 months, range 1-35 months; P<0.05). Further analysis showed no child with a PEG tube removed before 11 months (n = 23) after insertion required surgery, whereas 7 (23%) of 31 children with a PEG tube removed after 11 or more months required surgery. Age at insertion, type of feeding device removed, and patient diagnoses were not different between the two groups. CONCLUSIONS: These data indicate that persistent leaking necessitating surgical closure of a gastrocutaneous fistula does not occur in children with a PEG tube removed within 11 months of insertion. In contrast, 23% of children with a PEG tube removed 11 or more months after insertion require surgery. In patients identified as candidates for tube removal, this time frame may be important in clinical decision making.

Retrograde esophagoscopy for foreign body removal.

Foreign bodies of the esophagus may penetrate the wall and migrate extraluminally, requiring a thoracotomy for removal. We report two children who swallowed coins that went undetected for several months and slowly eroded into the esophageal wall. These coins could not be retrieved by upper endoscopy, because of proximal strictures and granulation tissue at the perforation sites. Following surgical gastrostomy and retrograde flexible endoscopy, the coins were successfully removed. Retrograde endoscopy should be considered for removal of foreign esophageal objects before undertaking a thoracotomy.

A new variant of type IV glycogenosis: deficiency of branching enzyme activity without apparent progressive liver disease.

Type IV glycogenosis is due to branching enzyme deficiency and is usually manifested clinically by progressive liver disease with cirrhosis and hepatic failure between the second and fourth years of life. We describe a 5-year-old boy who, following an acute febrile illness at 2 years of age, was first noted to have hepatomegaly with mildly elevated serum transaminase levels. Liver biopsy revealed hepatic fibrosis with periodic-acid Schiff-positive, diastase-resistant inclusions in hepatocytes and fibrillar inclusions characteristic of amylopectin by electron microscopy. Enzymatic assay revealed deficient hepatic branching enzyme activity with normal activity of glucose-6-phosphatase, debranching enzyme and phosphorylase activities. During the succeeding 3 years, he grew and developed normally with apparent resolution of any clinical evidence of liver disease and only intermittent elevation in serum transaminase levels associated with fever and prolonged fasting. Repeat liver biopsy at 4 years of age showed persistence of scattered hepatocellular periodic-acid Schiff-positive, diastase-resistant inclusions, but no progression of hepatic fibrosis in spite of persistent deficiency of hepatic branching enzyme activity. Skeletal muscle and skin fibroblasts from the patient also showed deficient enzyme activity. Skin fibroblasts from both parents exhibited half the normal control activity, suggesting a heterozygote state. This is the first documented patient with deficiency of branching enzyme but without evidence of progressive hepatic disease. This patient, coupled with reports of other patients with late onset hepatic or muscle disease with branching enzyme deficiency, suggests that the defect resulting in Type IV glycogen storage disease is more heterogenous and possibly more common than previously suspected.

Watery diarrhea, hypokalemia, achlorhydria syndrome in an infant: effect of the long-acting somatostatin analogue SMS 201-995 on the disease and linear growth.

An 8-week-old infant presented with vomiting and failure to thrive due to small bowel obstruction caused by a diffusely enlarged pancreas. Surgical bypass of the obstruction was followed by secretory diarrhea, hypokalemia, and dehydration. Plasma vasoactive intestinal peptide (VIP) (823pg/ml), pancreatic polypeptide (4,500 pg/ml), and neurotensin (680 pg/ml) concentrations were markedly elevated. No neoplastic process was identified. Therapy with the long-acting somatostatin analogue SMS 201-995 was followed by decline in VIP concentrations (900 to 200-300 pg/ml), decrease in stool frequency, and normalization of serum electrolytes. During 12 months of somatostatin analogue therapy, length and weight progressed along the 3rd percentile on the Tanner growth chart.

The effect of bile duct obstruction on the clearance of circulating IgA immune complexes.

The clearance of circulating IgA immune complexes following acute bile duct obstruction was investigated in this study. IgA immune complexes were formed in vitro from MOPC-315, an IgA M-component with anti-dinitrophenyl (DNP) specificity, and 125I-DNP10 bovine serum albumin (BSA). Eighteen hours after laparotomy during which the common bile duct was either identified only or identified and ligated, the IgA immune complexes were injected intravenously. Groups of bile duct-ligated and bile duct-patent rats were also injected intravenously with IgG anti-DNP-125I-DNP10BSA immune complexes and 125I-bovine liver beta-glucuronidase to assess the hepatic clearance of materials not dependent on an intact biliary system. Clearance of IgA immune complexes was delayed after bile duct ligation. Although the clearance of IgA immune complexes was delayed, only 10% of these complexes remained in the circulation at 3 hr. The clearance of IgG immune complexes and beta-glucuronidase was not affected by ligation. These experiments demonstrate the physiologic importance of a patent bile duct in the normal clearance of IgA immune complexes in the rat. The observation that clearance is delayed, but not completely inhibited by bile duct ligation suggests that alternate mechanisms exist for removing IgA immune complexes from the circulation.

Food allergy. Cow milk and other common culprits.

Intestinal allergic states are common, but so are misconceptions about them. Since cow milk is one of the most common foods to produce an adverse immunologic reaction, it serves here as a prototype of food allergy in general. The mechanism of this reaction and its clinical and laboratory manifestations vary considerably from patient to patient. Once the diagnosis is established, however, treatment is relatively straightforward.