Localization of pancreatic insulinoma: comparison of pre- and intraoperative US with CT and angiography

Methods of preoperative radiologic localization of insulinoma were compared in 52 patients, 44 of whom had solitary tumors. Examinations performed in these 44 patients were preoperative ultrasonography (US) in 28, angiography in 26, and computed tomography in 23. Prospective sensitivities were 61%, 54%, and 30%, respectively. Imaging sensitivities were lower for the eight patients with multiple insulinomas. In 28 of the 44 patients, intraoperative US was performed without the examiner being aware of the surgical findings. The sensitivity was 84%. Four insulinomas were not palpable but were visualized sonographically. The combined sensitivity of intraoperative US and surgical palpation for detecting solitary insulinomas was 100%. High-frequency intraoperative US is valuable for detecting occult solitary insulinomas and considerably useful for determining the proximity of insulinomas to the pancreatic and bile ducts.     

Prevention of bedrest-induced physical deconditioning by daily dobutamine infusions. Implications for drug-induced physical conditioning.

The effects of intermittent infusions of dobutamine were studied in young normal male subjects during a period of bedrest deconditioning to determine whether this synthetic catechol affects physical conditioning processes in humans. 24 volunteers were placed at bedrest and randomized to daily 2-h treatments of saline infusions (control), dobutamine infusions, or maintenance exercise (control). Exercise, hemodynamic, and metabolic studies were performed at base line and at the termination of the 3-wk treatment period. Maximal exercise (duration, oxygen consumption, and workload) fell for the saline group and remained unchanged for the dobutamine and exercise groups. Hemodynamics during exercise were maintained the same as pretreatment base line for the dobutamine and exercise groups, whereas stroke volume and cardiac output dropped and heart rate rose for the saline group. The metabolic profile showed an increased blood lactate response at rest and during submaximal exercise after 3 wk of bedrest for the saline group, and essentially no change for the exercise and the dobutamine groups. Extraction of oxygen across the exercising lower limb rose for the dobutamine group, as did the activity of the skeletal muscle oxidative enzymes, citrate synthetase, and succinate dehydrogenase. In contrast to the exercise control group, the saline and dobutamine groups developed orthostatic hypotension, tachycardia, and accentuation of the renin-aldosterone response over the 3-wk treatment period; for the saline group, this is best explained by the observed fall in blood volume and for the dobutamine group, by the blunting of vascular vasoconstrictive responses. During a period of bedrest deconditioning in humans, infusions of dobutamine maintain many of the physiologic expressions of physical conditioning.     

Complicated pancreatic abscesses: problems in interventional management

Twenty-five patients with grade D or E pancreatitis underwent percutaneous drainage. These patients required multiple computed tomography (CT) examinations, multiple catheter insertions, multiple catheter manipulations, and long-term catheter drainage. Eight of the 25 patients were successfully treated with catheter drainage alone. Sixteen underwent surgical drainage, ten after attempts at percutaneous drainage and six prior to radiologic drainage. Of the ten patients who had initial percutaneous drainage, only four were clinically improved from the drainage procedure alone. Although the fluid component of the abscess was often adequately drained in all ten patients, surgery was required to remove pieces of necrotic debris. Six patients who underwent surgical debridement had residual abscesses in the post-operative period and were all successfully treated with percutaneous drainage. One patient died from unrelated causes. Successful interventional management of patients with pancreatic abscesses requires intensive radiologic intervention and monitoring and may be better served by a combination of radiologic and surgical means.     

A novel His158Arg mutation in TIMP3 causes a late-onset form of Sorsby fundus dystrophy

PURPOSE: To describe the phenotype and genotype of a family with suspected Sorsby fundus dystrophy (SFD). DESIGN: Case reports and results of deoxyribonucleic acid (DNA) analysis. METHODS: Clinical features were determined by complete ophthalmologic examination or by review of medical records. Mutational analysis of the tissue inhibitor of metalloproteinase (TIMP)3 gene was performed by DNA resequencing. Biochemical properties of the mutant TIMP3 protein were studied, and phylogenetic and molecular modeling analyses of TIMP proteins were performed. RESULTS: Fundi of four affected family members demonstrated active or regressed bilateral choroidal neovascularization, whereas another affected individual displayed severe diffuse pigmentary degeneration associated with nyctalopia characteristic of SFD. Onset of disease occurred in the fifth to seventh decades of life. A heterozygous His158Arg mutation was found in seven affected family members and was absent from an unaffected member and 98 unrelated controls. Bioinformatic analyses indicate that histidine 158 is an evolutionarily conserved residue in most vertebrate TIMP homologs and predict that substitution by arginine disrupts TIMP3 function. The mutant protein appears to be expressed by fibroblasts from an affected family member. Molecular modeling suggests that TIMP3 residue 158 may be part of a protein-protein interaction interface. CONCLUSION: A novel mutation in TIMP3 causes a late-onset form of SFD in this family. His158Arg is the first reported TIMP3 SFD coding sequence mutation that does not create an unpaired cysteine. Further study of this unusual mutation may provide insight into the mechanism of SFD pathogenesis.