Radionuclides in the lichen-caribou-human food chain near uranium mining operations in northern Saskatchewan, Canada.

The richest uranium ore bodies ever discovered (Cigar Lake and McArthur River) are presently under development in northeastern Saskatchewan. This subarctic region is also home to several operating uranium mines and aboriginal communities, partly dependent upon caribou for subsistence. Because of concerns over mining impacts and the efficient transfer of airborne radionuclides through the lichen-caribou-human food chain, radionuclides were analyzed in tissues from 18 barren-ground caribou (Rangifer tarandus groenlandicus). Radionuclides included uranium (U), radium (226Ra), lead (210Pb), and polonium (210Po) from the uranium decay series; the fission product (137Cs) from fallout; and naturally occurring potassium (40K). Natural background radiation doses average 2-4 mSv/year from cosmic rays, external gamma rays, radon inhalation, and ingestion of food items. The ingestion of 210Po and 137Cs when caribou are consumed adds to these background doses. The dose increment was 0.85 mSv/year for adults who consumed 100 g of caribou meat per day and up to 1.7 mSv/year if one liver and 10 kidneys per year were also consumed. We discuss the cancer risk from these doses. Concentration ratios (CRs), relating caribou tissues to lichens or rumen (stomach) contents, were calculated to estimate food chain transfer. The CRs for caribou muscle ranged from 1 to 16% for U, 6 to 25% for 226Ra, 1 to 2% for 210Pb, 6 to 26% for 210Po, 260 to 370% for 137Cs, and 76 to 130% for 40K, with 137Cs biomagnifying by a factor of 3-4. These CRs are useful in predicting caribou meat concentrations from the lichens, measured in monitoring programs, for the future evaluation of uranium mining impacts on this critical food chain.     

Presurgical assessment and surgical treatment for epilepsy

In the last ten years, dramatic advances in surgical treatment options and techniques have allowed surgical intervention for patients who would otherwise not have been considered as surgical candidates. In this article, a multidisciplinary, logical decision algorithm for a rational approach to surgical treatments is outlined. A carefully considered hierarchy is presented that provides for maximized seizure improvement outcomes. Topics presented include temporal lobectomy, detailed discussion of dominant temporal lobectomy and speech-sparing techniques, neocortical resection, the use of subdural electrode array, depth electrodes, and strip electrodes, multiple subpinal transection, vagus nerve stimulation, and corpus callosotomy. The application of these various techniques to maximize surgical outcome are discussed.     

Routine EEG vs. intensive monitoring in the evaluation of intractable epilepsy

Appropriate treatment of patients with intractable seizures requires precise identification of the type (or types) of seizure the patient experiences and correlation of this information with data from electroencephalography localizing the focus of the seizure in the brain. For such patients, the technique of "intensive monitoring" has gained rapid acceptance in the past several years as the investigative method of choice.Intensive monitoring usually entails prolonged electroencephalographic recording with simultaneous videotaping of the patient. Another common technique is prolonged monitoring of the patient's electroencephalogram (EEG) by radiotelemetry, during which time the patient is closely observed by trained personnel for suspected seizures.To compare the quality of information obtained from intensive monitoring with that from careful routine electroencephalography, the authors reviewed the medical records of 100 consecutive patients who had received both kinds of study after being referred for treatment in the special Epilepsy Treatment Unit of the University of Minnesota's Comprehensive Epilepsy Program (CEP).Success of each method was defined by ability to record an actual seizure. The routine EEG examination recorded actual seizures in 7 percent of patients in the study. With video EEG, following careful withdrawal of anticonvulsant drugs, seizures were recorded in 70 percent of patients. Telemetered EEG recorded seizure activity in 50 percent of those patients for whom the other two methods had failed to detect seizures.Intensive monitoring revealed that 60 percent of patients for whom the routine EEG study had recorded only one seizure type actually suffered from two or more types. Clinical diagnosis was changed in 84 percent of the patients. In this study, intensive monitoring was found to be far superior to the routine EEG examination as an aid to precise diagnosis of intractable seizure disorders.     

KP544, a nerve growth factor amplifier: Pharmacokinetics,safety, and efficacy in the rat

In cultured cells, KP544 [2‐amino‐5‐(4‐chlorophenylethynyl)‐4‐(4‐trans‐hydroxycyclohexyl amino) pyrimidine] amplifies differentiation initiated by nerve growth factor (NGF) or cAMP. This report describes the pharmacokinetics, safety, and neuroprotective efficacy of KP544 in rats. After an oral dose of 10 mg/kg KP544 was 25% bioavailable with a plasma half‐life of 1.3 h and brain levels 6‐fold higher than plasma levels at 4 and 8 h post‐dose. In a safety study, daily oral dosing for 30 days at 10 and 100 mg/kg was well tolerated. The favorable pharmacokinetic and safety profiles, together with its amplification of NGF in vitro, prompted evaluation of KP544 in two models involving NGF deficiencies. In the first model, brains were lesioned with intrastriatal injections of quinolinic acid. KP544 at oral doses of 0.02 to 1.0 mg/kg/day almost completely prevented the resulting learning deficits as evaluated using a radial‐arm‐water maze. At the lowest dose, there was a slower onset of functional improvement. These effects were accompanied by reductions (16–34%) in the striatal lesion size that were greatest at the highest dose and comparable to those seen with NGF therapy. The second model involved a peripheral neuropathy induced by taxol that is associated with decreases in NGF. KP544 at oral doses of 0.1–10 mg/kg/day decreased the severity of the neuropathy as measured by caudal nerve conduction velocities (30–70% return to control values). In both models, KP544 had a large therapeutic index suggesting its potential as a new approach for treating clinical disorders involving deficiencies in NGF. Drug Dev. Res. 62:60–70, 2004. © 2004 Wiley‐Liss, Inc.     

Concepts and Controversies in Cancer Screening

Screening for cancer is a common and expected part of primary care medicine. However, the known effects of lead time, length, and selection bias confound our ability to objectively evaluate screening tests, and often result in an overestimation of the benefits of screening. Because of these biases, the randomized controlled trial remains the only reliable way to measure the true effects of a screening program. Significant controversy remains for many screening tests, because most common screening procedures have come into widespread use without the benefit of definitive trials. These concepts are illustrated by exploring current controversies in screening for cancer of the lung, colon, breast and prostate, which together account for more than 50% of US cancer deaths. In the face of ongoing controversy and uncertainty about the value of screening tests, physicians are advised to engage patients in a process of shared decision making and informed consent.     

Nonoperative management of bile leaks following liver transplantation

The biliary anastomosis has been called ‘the Achilles heel’ of liver transplantation (Rabkin JM, Orloff SL, Reed MH . Transplantation 1998: 65 [2]: 193; Davidson BR, Rai R, Kurzawinski TR . Br J Surg 1999: 86 [4]: 447). Biliary complications after liver transplantation reportedly occur at an incidence of 20–30%, 10–15% as bile leaks. The management of bile leaks, especially early bile leaks, is controversial. In the present study, we report our experience with the management of bile leaks after liver transplantation.
In this retrospective study, we reviewed 85 liver transplants over a 3‐yr period. In 79, the biliary anastomosis was choledochocholedochostomy (CDCD) over a small‐caliber T‐tube, while choledochojejunostomy (CDJ) was used in 7. Over a mean follow up period of 13.5 months (median 10 months), 10 patients (12%) experienced a clinically significant bile leak within the first 3 months after liver transplantation.
The early leaks, occurring within 1 month of transplant, were successfully managed by observation (Davidson BR, Rai R, Kurzawinski TR . Br J Surg 1999: 86 [4]: 447) or endoscopic retrograde cholangiopancreatography (ERCP) and the placement of a biliary stent for a duration of 6–12 wk (Randall HB, Wachs ME, Somberg KA . Transplantation 1996: 61 [2]: 258). One of these resulted from accidental dislodgement of the T‐tube on postoperative day 1; one resulted from necrosis at the CDCD anastomosis and required CDJ; the remaining four resulted from leaks along the T‐tube track.
One of the late leaks occurred following the planned removal of the T‐tube at 3 months after liver transplantation; the other two were leaks along the T‐tube track. All were successfully treated by ERCP and stent placement, though in one case, ERCP was initially unsuccessful because of the inability to advance a guidewire, necessitating a fluoroscopically aided guide wire placement during a mini laparotomy. ERCP was then successfully performed with the placement of a stent. Table 1 Conclusions: Our experience indicates that most bile leaks after liver transplantation, including early leaks, can be successfully managed nonoperatively. Most will require intervention, but ERCP and stent placement are usually sufficient.

Nintendo® Wii Fit based sleepiness tester detects impairment of postural steadiness due to 24 h of wakefulness

A field-usable sleepiness tester could reduce sleepiness related accidents. 15 subjects’ postural steadiness was measured with a Nintendo^® Wii Fit balance board every hour for 24 h. Body sway was quantified with complexity index, C_I, and the correlation between C_I and alertness predicted by a three-process model of sleepiness was calculated. The C_I group average was 8.9 ± 1.3 for alert and 7.9 ± 1.4 for sleep deprived subjects (p < 0.001, ρ = 0.94). The Wii Fit board detects the impairment of postural steadiness. This may allow large scale sleepiness testing outside the laboratory setting.     

Air Transport of Patients with Unstable Aortic Aneurysms Directly into Operating Rooms

Objective. The purpose of this study was to describe an air transport service's protocol for direct transport of patients with abdominal aortic aneurysm leak (AAAL) into receiving hospital operating rooms (ORs). Methods. This retrospective consecutive-case analysis examined AAAL patients undergoing nurse-paramedic Boston MedFlight (BMF) transport during 1999–2004, who were taken directly into ORs at four academic centers. BMF uses a rotating roster system to assign receiving hospitals when referring physicians have no preidentified receiving facility, but this practice may prolong patient transport or be associated with less diagnostic certainty, andthus more delay, at receiving hospitals. Thus, the study compared “Roster” versus “Non-roster” patients' time andoutcome end points. Continuous nonparametric data (e.g., time intervals) were described with median andinterquartile range (IQR). Chi-square andKruskal-Wallis tests were used for univariate comparisons; regression analysis assessed dependent variables while adjusting for covariates (e.g., transport mileage). Results. There were 29 direct-to-OR transports, with median distance of 30 miles. All patients had AAAL diagnosis confirmed; 51.7% survived. System performance for end points was similar as assessed between Roster versus Non-roster patients. Conclusions. Interfacility direct-to-OR transport of AAAL patients is feasible. Use of a roster system allows for timely transport facilitation for patients needing specialized care; roster patients achieve similar end points as did patients who had already-identified receiving hospitals upon air medical transport request.