Long-term,low-level exposure of guinea pigs and marmosets to sarin vapor in air: lowest observable effect level

Realistic scenarios for low-level exposure to nerve agents will often involve exposures over several hours to extremely low doses of agent. In order to expose animals to the lowest controllable concentrations of agent and to increase exposure times until a lowest observable effect level (LOEL) becomes measurable, a validated system was developed for exposing conscious animals to 0.05-1.0 microg/m(3) (8-160 ppt) of sarin and other nerve agents. Based on cold trapping of sarin from the exposure air, the concentration could be measured semicontinuously, at 4-min time intervals by means of gas chromatography. We found that the LOEL upon a 5-h whole body exposure of guinea pigs and marmosets to sarin vapor corresponds with the measurement of an internal dose by means of fluoride-induced regeneration of sarin from phosphylated binding sites in plasma, mostly BuChE. For guinea pigs the LOEL was observed at Ct = 0.010 +/- 0.002 mg/min/m(3), whereas a Ct of 0.04 +/- 0.01 mg/min/m(3) was established for the LOEL in marmosets. These levels are several orders of magnitude lower than those based on classical measurement of depressed cholinesterase activities. At low exposure levels of guinea pigs and marmosets (< or =1 microg/m(3)), a reasonable linearity was observed between exposure dose and internal dose. The data were addressed in the light of the recently recommended occupational exposure limits to sarin for workers without respiratory protection, which suggests that the exposure limits should be reconsidered if the slightest inhibition of cholinesterases should be prevented.     

Effects of voice therapy as objectively evaluated by digitized laryngeal stroboscopic imaging

Objective measurements derived from digitized laryngeal stroboscopic images were used to demonstrate changes in vocal fold vibration and in the size of benign lesions after 3 months of voice therapy. Forty chronically dysphonic patients were studied. By means of a rigid stroboscope, pretreatment and posttreatment recordings were made of the vocal folds at rest and under stroboscopic light during phonation. From each recording, images of the positions at rest and during vibration at maximal opening and at maximal closure were digitized. The surface areas of any lesions and of the glottal gap were independently measured in the digitized images by 2 experienced laryngologists. Referential distances were determined in order to compensate for discrepancies in magnification in the various recordings. After 3 months of voice therapy, significant improvement in lesion size and degree of maximal closure during vibration could be demonstrated in about 50% of the patients. The degree of maximal opening did not prove to be a significant parameter.     

Proximal and distal hyperattenuating middle cerebral artery signs at CT: different prognostic implications

PURPOSE: To determine whether a proximal (M1-segment) or distal (M2- and/or M3-segment) hyperattenuating middle cerebral artery (MCA) sign in patients with ischemic infarction in the territory of the MCA indicates a worse short-term prognosis than that in patients without a hyperattenuating MCA sign. MATERIALS AND METHODS: We retrospectively reviewed the records of 352 patients who were diagnosed with ischemic brain infarction in the territory of the MCA. Of these patients, 186 patients met our final criteria and were included in this study. Nonenhanced computed tomography (CT) was performed for the entire brain, with a 5-mm section thickness in all patients, within 24 hours after symptom onset. The presence and location of a hyperattenuating MCA sign was correlated with neurologic deficit at discharge from the hospital (ie, short-term prognosis) by using the chi(2) test to detect differences between patient groups. RESULTS: Patients with a hyperattenuating MCA sign at CT have a worse short-term prognosis than do patients without a hyperattenuating MCA sign (P <.05). Patients with a proximal hyperattenuating MCA sign have a significantly (P <.01) worse short-term prognosis than do patients with a distal hyperattenuating MCA sign. CONCLUSION: A proximal hyperattenuating MCA sign is a reliable predictor of poor short-term prognosis in patients who experience acute stroke.     

Hepatic vein reconstruction for resection of hepatic tumors

SUMMARY BACKGROUND DATA: Involvement of the hepatic veins requiring reconstruction has traditionally been considered a contraindication to resection for advanced tumors of the liver because the surgical risks are high and the long-term prognosis poor. Recent advances in liver surgery gleaned from split and live donor liver transplantation that necessitate hepatic vein reconstruction can be applied to hepatic resection in some cases. METHODS: Sixteen patients who underwent hepatic resection requiring hepatic vein reconstruction from 1996-2001 were reviewed. The mean age was 43 years (range 2-61). Nine patients were resected for hepatocellular carcinoma (HCC), five patients for colorectal metastases, and one patient each for hepatoblastoma and cholangiocarcinoma. In six patients with HCC and cirrhosis, the right hepatic vein was reconstructed to provide venous outflow to liver segments not adequately drained by a remaining major hepatic vein. Four of these six patients required the use of Gore-Tex (W. L. Gore & Associates, Inc., Newark, DE) interposition grafts. In the 10 other cases the entire venous outflow from the remnant liver was reconstructed or reimplanted into the inferior vena cava primarily (n = 8) or using segments of the portal vein from the resected side of the liver as a graft (n = 2). Ex-vivo procedures with the use of veno-venous bypass were required in two cases and in-situ cold perfusion of the liver was used in one case. RESULTS: There were two perioperative deaths (12%). One patient died of liver failure 3 weeks after right trisegmentectomy with reconstruction of the left hepatic vein and one patient died at 3 months after resection due to sepsis from a segment of small bowel that perforated into a diaphragmatic hernia. Four patients had evidence of postoperative liver failure that resolved with supportive management and one patient required temporary dialysis. All vascular reconstructions were patent at last followup. With median followup of 23 months, 3 patients have died of recurrent malignancy at 14, 18 and 30 months, while an additional patient went on to die of progressive liver failure at 22 months. Actuarial 1 and 3 year survival was 88% and 50% respectively. CONCLUSION: Hepatic vein involvement by hepatic malignancy does not necessarily preclude resection. Liver resection with reconstruction of the hepatic veins can be performed in selected cases. The increased risk associated with the procedure appears to be balanced by the possible benefits, particularly when the lack of alternative curative approaches is considered.     

ATP release in human kidney cortex and its mitogenic effects in visceral glomerular epithelial cells

BACKGROUND: In chronic renal failure the sympathetic nervous system is activated. Sympathetic cotransmitters released within the kidney may contribute to the progression of renal disease through receptor-mediated proliferative mechanisms. METHODS: In human renal cortex electrical stimulation induced adenosine 5'-triphosphate (ATP; luciferin-luciferase-assay) and norepinephrine (HPLC) release was measured. ATP release also was induced by alpha1- and alpha2-adrenergic agonists. [3H]-thymidine uptake was tested in human visceral glomerular epithelial cells (vGEC) and mitogen-activated protein kinase (MAPK42/44) activation in vGEC and kidney cortex. The involved P2-receptors were characterized pharmacologically and by RT-PCR. RESULTS: Sympathetic nerve stimulation and alpha-adrenergic agonists induced release of ATP from human kidney cortex. Seventy-five percent of the ATP released originated from non-neuronal sources, mainly through activation of alpha2-adrenergic receptors. ATP (1 to 100 micromol/L) and related nucleotides (1 to 100 micromol/L) increased [3H]-thymidine uptake. The adenine nucleotides ATP, ATPgammaS, ADP and ADPbetaS were about equally potent. UTP, UDP and alpha,beta-methylene ATP had no effect. ATP, ADPbetaS but not alpha,beta-methylene ATP activated MAPK42/44. ATP induced MAPK42/44 activation, and [3H]-thymidine uptake was abolished in the presence of the MAPK inhibitor PD 98059 (100 micromol/L). mRNA for P2X4,5,6,7 and P2Y1,2,4,6,11 were detected in human vGEC by RT-PCR. CONCLUSIONS: In human renal cortex, adrenergic stimulation releases ATP from neuronal and non-neuronal sources. ATP has mitogenic effects in vGEC and therefore the potential to contribute to progression in chronic renal disease. The pattern of purinoceptor agonist effects on DNA synthesis together with the mRNA expression suggests a major contribution of a P2Y1-like receptor.     

Bone scintigraphy in nonsurgically treated Ewing's sarcoma at diagnosis and follow-up: Prognostic information of the primary tumor site

In order to detect skeletal metastases in patients with Ewing's sarcoma, bone scanning is commonly used. However, little information is available about the scintigraphic aspects of the primary Ewing's sarcoma during non-surgical treatment and follow-up. We studied retrospectively the significance of bone scintigraphic findings at the primary tumor site of 58 patients with a Ewing's sarcoma. These patients had chemotherapy and radiotherapy. At presentation 53/58 patients showed an increased tracer uptake at the primary tumor site while 5 patients with a pelvic or sacral bone localization had a normal scan. Bone scans made during treatment and more than 2 years thereafter in the 32 eligible patients demonstrated three patterns. In 16 patients the hot spot disappeared and no local tumor recurrence was encountered. In the other 16 patients the high uptake at the primary tumor site either persisted or diminished first to a normal uptake after a median period of 18 months (range 12-36 months) and returned again to a high uptake within 6-12 months. In these patients local Ewing's sarcoma was still present in 13, while in the other 3 cases a benign disorder (fracture, ectopic bone formation) was the underlying cause. These findings suggest that in non-surgically treated Ewing's sarcoma persisting increased tracer uptake or its recurrence is highly suspicious for the presence of Ewing's sarcoma, while bone scans becoming negative and remaining so for more than 12 months suggest the absence of local tumor. © 1994 Wiley-Liss, Inc.     

Valved jugular vein segments for right ventricular outflow tract reconstruction in young sheep

OBJECTIVE: This study was undertaken to investigate the degeneration and calcification of valved bovine jugular vein segments for right ventricular outflow tract reconstruction in juvenile sheep. METHODS: Seven valved bovine jugular vein conduits (Contegra model 220; VenPro Corporation, Irvine, Calif) and 3 control conduits (MH100; Medtronic, Inc, Minneapolis, Minn) were implanted in the pulmonary artery in young sheep. After 20 weeks the conduits were explanted and qualitatively analyzed by epicardial echocardiography, gross examination, x-ray analysis, light microscopy, and transmission electron microscopy. Calcification was determined quantitatively by flame atomic absorption spectrometry. RESULTS: Two Contegra conduits could not be analyzed because of endocarditis. All other Contegra conduits functioned well, with preserved structure and minimal calcification. The control MH100 conduits exhibited extensive fibrous sheathing, with calcification of the aortic wall portion and the commissural part of the Hancock valve. CONCLUSIONS: The Contegra conduit's performance was clearly superior to that of the control MH100 conduit when implanted in the pulmonary artery position in juvenile sheep for 5 months.     

Benign familial infantile convulsions: a clinical study of seven Dutch families.

Benign familial infantile convulsions (BFIC) is a recently identified partial epilepsy syndrome with onset between 3 and 12 months of age. We describe the clinical characteristics and outcome of 43 patients with BFIC from six Dutch families and one Dutch-Canadian family and the encountered difficulties in classifying the syndrome. Four families had a pure BFIC phenotype; in two families BFIC was accompanied by paroxysmal kinesigenic dyskinesias; in one family BFIC was associated with later onset focal epilepsy in older generations. Onset of seizures was between 6 weeks and 10 months, and seizures remitted before the age of 3 years in all patients with BFIC. In all, 29 (67%) of the 43 patients had been treated with anti-epileptic drugs for a certain period of time. BFIC is often not recognized as (hereditary) epilepsy by the treating physician. Seizures often remit shortly after the start of anti-epileptic drugs but, because of the benign course of the syndrome and the spontaneous remission of seizures, patients with low seizure frequency do not necessarily have to be treated. If prescribed, anti-epileptic drugs can probably be withdrawn after 1 or 2 years of seizure freedom.     

Diagnosis of ectopic pregnancy after in vitro fertilization and embryo transfer

Objective: The combination of transvaginal sonography and serum hCG measurement is reliable in the diagnosis of ectopic pregnancy (EP) in spontaneous pregnancies. In patients who became pregnant through IVF-ET, transfer of multiple embryos after IVF could be responsible for the different performance of these tests. We evaluated the discriminative capacity of transvaginal sonography in combination with hCG measurement in the diagnosis of EP after IVF-ET.

Design: Prospective cohort study.

Setting and Patient(s): Consecutive patients, pregnant through IVF-ET, who presented with clinically suspected EP.

Intervention(s): Transvaginal sonography, serum hCG measurement at 6, 9, and 15 days after ET and after a negative transvaginal sonography.

Main Outcome Measure(s): Ectopic pregnancy confirmed at laparoscopy.

Result(s): Between September 1993 and May 1996, 86 women were included in the study, of whom 24 had an EP. Transvaginal sonography identified 46 intrauterine pregnancies and 5 EPs, but serum hCG could not diagnose EPs in patients in whom transvaginal sonography did not show a gestational sac. Serum hCG measurement 9 days after ET could identify pregnancy failure with 100% specificity at a cut-off value of 18 IU/L, but it could not identify patients with EP with enough certainty to justify immediate treatment.

Conclusion(s): We recommend single serum hCG measurement 9 days after ET to discriminate between viable and nonviable pregnancies. Transvaginal sonography can be postponed until 5 weeks after ET, except for patients with abdominal pain and/or vaginal bleeding, or patients with a serum hCG level of <18 IU/L.     

Longitudinal relationship between pain and depression in older adults: sex, age and physical disability

Objective Better understanding of the relationship between pain and depression in older adults in the community is of particular importance considering the high prevalence of both conditions in these adults. In the present study, the longitudinal relationship between pain and depression in older adults was examined, thereby taking into account the role of physical disability and the possibly modifying effect of sex and age. Methods The study is based on a sample which at the outset consisted of 325 non-depressed and 327 depressed persons (55–85) drawn from a larger random community-based sample in the Netherlands. Depression (CES-D) and pain (subscale of the Nottingham Health Profile) were measured at eight successive waves over 3 years. Results Pain was very persistent over time as was to a lesser extent depression. The prognosis of comorbid pain and depression was poor. In longitudinal analyses (Generalized Estimating Equations), pain and depression were strongly associated. At the symptom level, the pain-depression relationship was found to be stronger in men than in women. There was no effect of age on the pain-depression relationship. No support was found for the hypothesis that the pain-depression relationship is mediated by disability. Conclusion The persistent nature of pain and to a lesser extent depression and the intimate and probably reciprocal association between them stress the need for adequate treatment strategies. Accepted: 30 October 2001