Effects of pegfilgrastim on normal biodistribution of 18F-FDG: preclinical and clinical studies.

The purpose of this study was to evaluate the effects of pegfilgrastim, a long-acting granulocyte colony-stimulating factor, on the normal biodistribution of (18)F-FDG in an animal model and in humans. METHODS: Two groups of 12 rats received a single subcutaneous injection of either normal saline or pegfilgrastim. One, 7, 14, and 21 d after injection, biodistribution studies were performed 1 h after (18)F-FDG injection. Sixteen breast cancer patients underwent baseline (18)F-FDG PET/CT and, approximately 1 wk after receiving 1 dose of docetaxel and adjunctive pegfilgrastim, follow-up (18)F-FDG PET/CT (scan 2). Standardized uptake values corrected for lean body mass (SUL) were determined for several normal organs before and after therapy. RESULTS: In rats, bone marrow (18)F-FDG uptake (standardized uptake value) was higher in the pegfilgrastim group 1 d after injection (mean +/- SD, 8.3 +/- 4.1 vs. 2.5 +/- 0.2, P < 0.05), whereas (18)F-FDG uptake in blood was lower (0.41 +/- 0.06 vs. 0.49 +/- 0.01, P < 0.05). In patients, mean SUL was higher in bone marrow (4.49 +/- 1.50 vs. 1.33 +/- 0.22, P < 0.0001), spleen (3.29 +/- 0.83 vs. 1.23 +/- 0.23, P < 0.0001), and liver (1.45 +/- 0.25 vs. 1.31 +/- 0.23, P = 0.01) but lower in brain (4.18 +/- 0.76 vs. 5.14 +/- 1.44, P < 0.01) on scan 2 than on the baseline scan. CONCLUSION: In both the animal model and humans, pegfilgrastim markedly increased bone marrow uptake of (18)F-FDG and reduced (18)F-FDG uptake in some normal tissues. These profound alterations in (18)F-FDG biodistribution induced by pegfilgrastim must be considered when one is evaluating quantitative (18)F-FDG PET scans for tumor response to therapy.     

The cholecystohepatic circulation of trichloroethylene and its metabolites in dogs

In order to examine the cholecystohepatic circulation of trichloroethylene (TRI) and its metabolites, we injected the gallbladder with TRI and its metabolites, i.e. chloral hydrate (CH), free-trichloroethanol (F-TCE), trichloroacetic acid (TCA) and conjugated-trichloroethanol (Conj-TCE), using anesthetized dogs. The absorption rates of water from the gallbladder were 25-30% 2 h after administration for all substances. The absorption rates of substances were 65-70% in the CH, F-TCE and TRI groups, and 40-50% in the Conj-TCE and TCA groups 2 h after the administration. Conj-TCE in the blood absorbed from the gallbladder has a tendency to be directly transported to the venous system rather than to be taken into hepatocytes in the liver. All of the administered substances, in particular, F-TCE might be metabolized to other substances in the gallbladder.     

Traumatic Injury of the Superior Mesenteric Vein: Ligate,Repair or Shunt?

Abstract We report a case of SMV injury in a critically ill patient. The patient was a 19-year-old woman involved in a motor vehicle collision. Her injuries included grade II splenic and renal lacerations, devascularized and lacerated right and transverse colon, a transected transverse mesocolon, a massive shear injury of her abdominal wall, and two partial SMV transections. At initial damage control laparotomy, the SMV was ligated, the devascularized bowel resected and a temporary abdominal closure applied. At re-operation, a mesocaval shunt using saphenous vein was employed. The shunt failed and the patient required a saphenous vein jump graft. Although visceral vascular injuries are rare, ligation of the SMV in a damage control situation is acceptable. This case study is the first to discuss appropriate treatment when interruption to a patient's collateral visceral venous drainage limits the surgeon’s ability to ligate. In these situations, bypass shunts may be successful.     

Policy Perspective on Housing and HIV/AIDS

For persons battling HIV/AIDS a stable place to live may decide the length and quality of life itself. It is nearly impossible for a person on the streets to engage in a needed continuous AIDS treatment regimen when the very basic question of where that person will rest his or her head when darkness comes in just a few hours is unresolved. When danger lurks on the streets, when cold numbs the limbs, when tiredness overwhelms the mind, when fear breaks the spirit, a place to call home would make all the difference.     

Nonspecific mitochondrial disease with epilepsy in children: diagnostic approaches and epileptic phenotypes

OBJECTIVES: This study sought to characterize epileptic phenotypes in children with nonspecific mitochondrial disease (MD) and to evaluate MD diagnostic approaches. METHODS: A retrospective analysis of the medical, electroencephalogram, and laboratory records of 142 patients with epilepsy was performed. The patients were evaluated for MD, and 124 patients were included in the final cohort. The MD criteria used included an oral glucose lactate stimulation test (OGLST) and urine organic acid/plasma amino acid (UOA/PAA) assays as metabolic indicators of modified Walker criteria, as suggested by Bernier et al. (Neurology 59:1406-1411, 2002). RESULTS: Twenty-two patients were classified as having definite MD (9), probable MD (5), possible MD (6), or pyruvate dehydrogenase (PDH) deficiency (3), including one patient which showed a respiratory chain (RC) defect and PDH deficiency. Seven out of eight patients in whom significant RC defects were observed showed complex I defects. In 14 patients, epileptic seizures start at infantile ages. Of 17 patients who substantially presented generalized seizures, 4 patients started with partial seizures. Five patients consistently presented only partial seizures. The OGLST and UOA/PAA assays were useful for a more precise diagnosis of MD, although low positive predictive value of the OGLST was regrettable. No patient was classified as definite MD by Walker's original criteria, but the use of our revised MD criteria resulted in the classification of nine additional patients as definite MD. CONCLUSIONS: MD manifested considerable diverse epileptic phenotypes and should be considered in the differential diagnosis of epilepsy in children with unexplained encephalomyopathy and progressive and fluctuating clinical courses.     

Paradigm shift in hydrocephalus research in legacy of Dandy’s pioneering work: rationale for third ventriculostomy in communicating hydrocephalus

Objective This study aims to question the generally accepted cerebrospinal fluid (CSF) bulk flow theory suggesting that the CSF is exclusively absorbed by the arachnoid villi and that the cause of hydrocephalus is a CSF absorption deficit. In addition, this study aims to briefly describe the new hydrodynamic concept of hydrocephalus and the rationale for endoscopic third ventriculostomy (ETV) in communicating hydrocephalus. Critique The bulk flow theory has proven incapable of explaining the pivotal mechanisms behind communicating hydrocephalus. Thus, the theory is unable to explain why the ventricles enlarge, why the CSF pressure remains normal and why some patients improve after ETV. Hydrodynamic concept of hydrocephalus Communicating hydrocephalus is caused by decreased intracranial compliance increasing the systolic pressure transmission into the brain parenchyma. The increased systolic pressure in the brain distends the brain towards the skull and simultaneously compresses the periventricular region of the brain against the ventricles. The final result is the predominant enlargement of the ventricles and narrowing of the subarachnoid space. The ETV reduces the increased systolic pressure in the brain simply by venting ventricular CSF through the stoma. The patent aqueduct in communicating hydrocephalus is too narrow to vent the CSF sufficiently.