Circular polarization in the optical afterglow of GRB 121024A.

Gamma-ray bursts (GRBs) are most probably powered by collimated relativistic outflows (jets) from accreting black holes at cosmological distances. Bright afterglows are produced when the outflow collides with the ambient medium. Afterglow polarization directly probes the magnetic properties of the jet when measured minutes after the burst, and it probes the geometric properties of the jet and the ambient medium when measured hours to days after the burst. High values of optical polarization detected minutes after the burst of GRB 120308A indicate the presence of large-scale ordered magnetic fields originating from the central engine (the power source of the GRB). Theoretical models predict low degrees of linear polarization and no circular polarization at late times, when the energy in the original ejecta is quickly transferred to the ambient medium and propagates farther into the medium as a blast wave. Here we report the detection of circularly polarized light in the afterglow of GRB 121024A, measured 0.15 days after the burst. We show that the circular polarization is intrinsic to the afterglow and unlikely to be produced by dust scattering or plasma propagation effects. A possible explanation is to invoke anisotropic (rather than the commonly assumed isotropic) electron pitch-angle distributions, and we suggest that new models are required to produce the complex microphysics of realistic shocks in relativistic jets.

Three-dimensional assessment of postural tremor during goal-directed aiming.

The performance of fine motor tasks which require a degree of precision can be negatively affected by physiological tremor. This study examined the effect of different aiming positions on anterior-posterior (AP), medial-lateral (ML) and vertical (VT) postural tremor. Participants were required to aim a mock handgun at a target located in front of them at eye level. Changes in AP, ML and VT tremor from the forearm and gun barrel were assessed as a function of limb (i.e., whether one or both arms were used) and upper arm position (elbow bent or extended). Tremor was recorded using triaxial accelerometers. Results showed that, across all tasks, the ML and VT tremor for any point was characterized by two frequency peaks (between 1-4 and 8-12 Hz) with amplitude increasing from proximal (forearm) to distal (gun barrel). Interestingly, irrespective of the posture adopted, ML accelerations were of greater amplitude than VT oscillations. AP oscillations were markedly smaller compared to VT and ML tremor, did not display consistent frequency peaks, and were not altered by the arm conditions. Altering the aiming posture resulted in changes in VT and ML tremor amplitude, with oscillations being greater when using a single arm as compared to when two arms were used together. Similarly, tremor amplitude was reduced when the task was performed with the elbow bent compared to the straight arm condition. Overall, these results highlight that ML oscillations make as significant a contribution to the overall tremor dynamics as those observed in the VT direction. However, the origin of ML tremor is not simply the product of voluntary adjustments to maintain aim on the target, but also exhibits features similar to the neural generated 8-12-Hz tremor seen under postural conditions.

Bracing of the trunk and neck has a differential effect on head control during gait.

During gait, the trunk and neck are believed to play an important role in dissipating the transmission of forces from the ground to the head. This attenuation process is important to ensure head control is maintained. The aim of the present study was to assess the impact of externally restricting the motion of the trunk and/or neck segments on acceleration patterns of the upper body and head and related trunk muscle activity. Twelve healthy adults performed three walking trials on a flat, straight 65-m walkway, under four different bracing conditions: 1) control-no brace; 2) neck-braced; 3) trunk-braced; and 4) neck-trunk braced. Three-dimensional acceleration from the head, neck (C7) and lower trunk (L3) were collected, as was muscle activity from trunk. Results revealed that, when the neck and/or trunk were singularly braced, an overall decrease in the ability of the trunk to attenuate gait-related oscillations was observed, which led to increases in the amplitude of vertical acceleration for all segments. However, when the trunk and neck were braced together, acceleration amplitude across all segments decreased in line with increased attenuation from the neck to the head. Bracing was also reflected by increased activity in erector spinae, decreased abdominal muscle activity and lower trunk muscle coactivation. Overall, it would appear that the neuromuscular system of young, healthy individuals was able to maintain a consistent pattern of head acceleration, irrespective of the level of bracing, and that priority was placed over the control of vertical head accelerations during these gait tasks.

Receptor editing in self-reactive bone marrow B cells.

A central paradigm of immunology is clonal selection: lymphocytes displaying clonally distributed antigen receptors are generated and subsequently selected by antigen for growth or elimination. Here we show that in mice transgenic for anti-H-2Kk,b antibody genes, in which a homogeneous clone of developing B cells can be analyzed for the outcome of autoantigen encounter, surface immunoglobulin M+/idiotype+ immature B cells binding to self-antigens in the bone marrow are induced to alter the specificity of their antigen receptors. Transgenic bone marrow B cells encountering membrane-bound Kb or Kk proteins modify their receptors by expressing the V(D)J recombinase activator genes and assembling endogenously encoded immunoglobulin light chain variable genes. This (auto)antigen-directed change in the specificity of newly generated lymphocytes is termed receptor editing.

Efficient peripheral clonal elimination of B lymphocytes in MRL/lpr mice bearing autoantibody transgenes.

Peripheral B cell tolerance was studied in mice of the autoimmune-prone, Fas-deficient MRL/ lpr.H-2(d) genetic background by introducing a transgene that directs expression of membrane-bound H-2Kb antigen to liver and kidney (MT-Kb) and a second transgene encoding antibody reactive with this antigen (3-83mu delta, anti-Kk,b). Control immunoglobulin transgenic (Ig-Tg) MRL/lpr.H-2(d) mice lacking the Kb antigen had large numbers of splenic and lymph node B cells bearing the transgene-encoded specificity, whereas B cells of the double transgenic (Dbl-Tg) MRL/lpr.H-2(d) mice were deleted as efficiently as in Dbl-Tg mice of a nonautoimmune B10.D2 genetic background. In spite of the severely restricted peripheral B cell repertoire of the Ig-Tg MRL/lpr.H-2(d) mice, and notwithstanding deletion of the autospecific B cell population in the Dbl-Tg MRL/lpr.H-2(d) mice, both types of mice developed lymphoproliferation and exhibited elevated levels of IgG anti-chromatin autoantibodies. Interestingly, Dbl-Tg MRL/lpr.H-2(d) mice had a shorter lifespan than Ig-Tg MRL/lpr.H-2(d) mice, apparently as an indirect result of their relative B cell lymphopenia. These data suggest that in MRL/lpr mice peripheral B cell tolerance is not globally defective, but that certain B cells with receptors specific for nuclear antigens are regulated differently than are cells reactive to membrane autoantigens.

Evidence-based guide to perioperative medicine.

The discipline of perioperative medicine is assuming greater importance as increasing numbers of older patients with medical comorbidity undergo complex surgical procedures. If patient outcomes and use of limited hospital resources are to be optimized, physicians with skills and interest in perioperative risk assessment and therapeutic intervention are needed. This systematic review attempts to provide an evidence-based update in several key areas in the management of the perioperative patient.

Vitamin D deficiency in general medical inpatients in summer and winter.

BACKGROUND: Vitamin D deficiency is common in various populations worldwide. Adverse effects of vitamin D deficiency are the development of bone disorders; however, other diseases such as multiple sclerosis, type 1 diabetes, rheumatoid arthritis and certain cancers have also been linked to vitamin D deficiency. The general medical inpatient population is a group at increased risk of vitamin D deficiency. These patients often have coexistent risk factors for its consequences. This study aims to document a point prevalence of vitamin D deficiency in this population. METHODS: Two cross-sectional audits of patients admitted to general medicine units were carried out--the first in mid-November at the end of winter and the second in mid-April and May at the end of summer. Information regarding patients' comorbidities, medication usage, previous falls and fractures was obtained and serum 25-hydroxyvitamin D, parathyroid hormone and calcium levels were measured. RESULTS: A total of 129 patients was studied (65 in winter and 64 in summer). Ninety-four patients (74%) had 25-hydroxyvitamin D levels < or = 50 nmol/L. Seven patients had severe deficiency (levels < or = 12.5 nmol/L). Average vitamin D levels were lower at the end of winter (35 vs 43 nmol/L, P = 0.007). Of the 37 patients receiving vitamin D supplements, 20 (54%) had 25-hydroxyvitamin D levels < or = 50 nmol/L. CONCLUSION: Low vitamin D levels were common in this general medical inpatient population. The average vitamin D level was lower in the patient group tested in November following winter. Supplementation of vitamin D did not uniformly prevent deficiency.

Upper body accelerations during walking are altered in adults with ACL reconstruction.

This study was designed to assess and compare the pattern of acceleration from the lower trunk, neck and head regions for individuals with reconstructed ACL compared to healthy controls during walking. Participants with unilateral ACL reconstruction and matched control persons participated in the study. Accelerations were collected using three triaxial accelerometers attached to the head, neck, and lower trunk. Measures of amplitude and signal regularity of the acceleration data were performed. Similarities were seen between both groups with regards to the general acceleration patterns in all three axes. However, the results also revealed that the individuals with ACL reconstruction had significantly greater peak power in the AP direction at higher frequencies, indicating a reduced ability to attenuate frequency signals. Further, the ACL group had a reduced ability to control head motion during gait, as indicated by reduced regularity in VT. Both groups demonstrated a similar pattern of gait-related oscillations across the head, neck and trunk segments. However, adults with a reconstructed ACL demonstrated a reduced capacity to compensate for the higher frequency components of the gait signal, which may have led to a decline in head control. Overall, these findings indicate that previous damage to the ACL is not simply localized to the knee joint, but influences upper body control, too.

Enhancement of 1,25-dihydroxyvitamin D3-mediated antitumor activity with dexamethasone.

BACKGROUND: The active metabolite of vitamin D, i.e., 1,25-dihydroxycholecalciferol (1,25-D3), inhibits the growth of murine SCCVII/SF squamous cell carcinoma cells, both in vitro and in vivo. However, in vivo use of 1,25-D3 is hampered as a result of hypercalcemia (i.e., elevated levels of calcium in the blood). Glucocorticoids, such as dexamethasone, affect calcium absorption and modulate vitamin D receptor binding and have been used to treat hypercalcemia. In this study, we examined the effect of dexamethasone on tumor growth inhibition by 1,25-D3. METHODS: The effects of 1,25-D3 and dexamethasone, alone and in combination, on the growth of SCCVII/SF cells in in vitro culture or in vivo in female C3H/HeJ mice were determined by clonogenic tumor cell assay and/or by actual changes in tumor volume. Vitamin D receptor-ligand-binding activities in whole-cell extracts from cells (in culture), tumors, and normal tissues were assayed by single-point saturation analysis and equilibrium binding. RESULTS: Treatment of cultured SCCVII/SF cells with 500 nM dexamethasone for 24 hours before addition of 1,25-D3 reduced their survival. The growth of SCCVII/SF tumors was inhibited in mice treated simultaneously with dexamethasone and 1,25-D3 (as compared with no treatment or single-agent treatment); hypercalcemia was also reduced. Total vitamin D receptor content in SCCVII/SF cells was increased after treatment with dexamethasone. Treatment of tumor-bearing animals with dexamethasone (9 microg/day) for 7 days led to increased vitamin D receptor-ligand-binding activities in whole-cell extracts from tumor or kidneys and decreased activity in intestinal mucosa. CONCLUSIONS: Dexamethasone may enhance the antitumor effect of 1,25-D3 by increasing vitamin D receptor-ligand-binding activity.

Interleukin 1 alpha and gamma-interferon induction of nitric oxide production from murine tumor-derived endothelial cells.

The role of nitric oxide (NO) in vascular function, host tumoricidal activity, and antiinflammatory effects is well documented. A number of cytokines induce NO from a variety of cell types. We have demonstrated in murine models that interleukin 1 alpha (IL-1 alpha) induces acute hemorrhagic necrosis, microvascular injury, and enhanced clonogenic tumor cell kill. Effects on the vasculature are observed only in tumor and not in normal tissues. Using methods established previously in our laboratory, murine tumor-derived and normal endothelial cells were cultured with IL-1 alpha, IFN-gamma, or IL-1 alpha/IFN-gamma at various doses with NO production quantitated through the measurement of nitrite by the Griess reaction. In tumor-derived endothelial cells, we demonstrated that neither cytokine alone was capable of inducing nitrite but that the combination of IL-1 alpha/IFN-gamma induced dose-dependent nitrite, with peak levels observed after 4 days incubation. When tumor-derived, normal yolk sac, mouse brain, or mouse aortic endothelial cells were treated with IL-1 alpha (100 units/ml)/IFN-gamma (10 units/ml), tumor-derived endothelial cells produced significantly more nitrite when compared to the normal endothelial cells. Nitrite production from IL-1 alpha/IFN-gamma was sensitive to the nitric oxide synthase inhibitors, NG-methyl-L-arginine or NG-nitro-L-arginine in a dose-dependent manner. In addition, dexamethasone significantly inhibited nitrite production from IL-1 alpha/IFN-gamma-treated, tumor-derived endothelial cells. These studies suggest that the antitumor activity of IL-1 alpha may be mediated through the production of NO from tumor-derived endothelial cells.

Potentiation of cisplatin antitumor activity using a vitamin D analogue in a murine squamous cell carcinoma model system.

In a murine squamous cell carcinoma (SCC) model, we have demonstrated that both 1,25-dihydroxycholecalciferol (1,25-D3) and the analogue 1,25-dihydroxy-16-ene-23-yne-cholecalciferol (Ro23-7553) have significant in vitro and in vivo antitumor activity. We have examined here the cell cycle effect of 1,25-D3 and Ro23-7553 on SCCVII/SF tumor cells by quantitating nuclear DNA using a detergent-trypsin method via flow cytometry analysis. Both 1,25-D3 and Ro23-7553 resulted in a significant increase of cells in G0-G1, with an accompanying decrease of cells in S phase. The ability to arrest cells in G0-G1 has been exploited by combining Ro23-7553 with the cytotoxic agent cisplatin (cis-diamminodichloroplatinum; cDDP). Using the in vitro clonogenic assay, pretreatment with Ro23-7553 for 24-48 h significantly enhanced cDDP-mediated tumor cell kill as compared to concurrent treatment with Ro23-7553 and cDDP or cDDP alone. To examine the effect of Ro23-7553 and cDDP in vivo, C3H/HeJ mice with 9-14-day SCC tumors were treated either for 3 days with varying i.p. doses of Ro23-7553 or for 7 days continuously through the use of Alzet pumps, and on the last day of Ro23-7553 treatment, cDDP (1-6 mg/kg) was administered. Using the in vivo excision tumor cell clonogenic assay, in which tumors were removed from animals 24 h after cDDP treatment and plated in a clonogenic assay, pretreatment with Ro23-7553 markedly enhanced cDDP-mediated clonogenic tumor cell kill, even at low doses of cDDP as compared to cDDP treatment alone. Similarly, a significant decrease in fractional tumor volume and increase in tumor regrowth delay was observed when animals were pretreated before cDDP with Ro23-7553 as compared to either agent alone. These results demonstrate a significant enhanced antitumor effect with Ro23-7553 pretreatment before cDDP both in vitro and in vivo and suggest that Ro23-7553 may potentiate cDDP cytotoxicity through effects on cell cycle progression.

Effects of total parenteral nutrition and chemotherapy on the metabolic derangements in small cell lung cancer.

Changes in energy metabolism, substrate use, and hormone profiles were prospectively studied in 31 patients with small cell lung cancer receiving chemotherapy. Patients were randomized to receive either 4 weeks of total parenteral nutrition (n = 15) or to continue self-regulated p.o. diet (control group; n = 16). The initial actual resting energy expenditure measured by indirect calorimetry was 31% higher than the predicted resting energy expenditure determined by the Harris-Benedict formula. The p.o. calorie intake was inappropriately low for these hypermetabolic patients. Total parenteral nutrition resulted in a significant positive net energy balance, but in follow-up was associated with prolonged anorexia and a negative energy balance. Complete response to therapy reduced resting energy expenditure and increased calorie intake, whereas the contrary was true in nonresponders. Elevated plasma-free fatty acids (800 +/- 62 microM; S.E.) and a low respiratory quotient (0.74 +/- 0.02) indicate that the dominant energy source in patients with small cell lung cancer is fat, and that increased fat oxidation continues despite tumor response. Elevated fasting plasma catecholamines and insulin resistance may contribute to continued fat mobilization. Initially, there was a significant increase in blood lactate (1118 +/- 95 microM) suggesting either increased tumor or tumor-mediated glycolytic activity. Response to therapy was associated with a fall in blood lactate levels. The most effective way of improving the metabolic derangements in patients with small cell lung cancer was to achieve tumor response to therapy.

Delayed gastric emptying and improvement with domperidone in a patient with anorexia nervosa.

A woman with anorexia nervosa who displayed severe bloating after eating was treated with domperidone, a novel compound with prokinetic properties. Both subjective ratings of satiety and assessment of gastric emptying documented improvement.

Skeletal muscle function in malnutrition.

Skeletal muscle function was studied in 10 malnourished patients with various gastrointestinal disorders and in 22 normal subjects. The function of the adductor pollicis muscle was assessed by electrical stimulation of the ulnar nerve. The objective parameters of muscle function measured were: 1) Force of contraction expressed as a percentage of the maximal force obtained with electrical stimulation at 10, 20, 30, 50 and 100 Hz. 2) Maximal relaxation rate expressed as percentage force loss/!10 ms. 3) Endurance expressed as percentage force loss/30 s. The force of contraction at 10 Hz was higher in malnourished patients compared with normal subjects, with a mean +/- SEM (n) of 43.0 +/- 4.2% (n = 10) and 28.8 +/- 1.2% (n = 22), respectively, (p less than 0.001). The maximal relaxation rate was slower in patients compared with normals with a mean +/- SEM (n) of 7.2 +/- 0.4% (n = 9) ad 9.6 +/- 0.2% (n = 22), respectively, (p less than 0.001). Muscle endurance testing showed an increased force loss with prolonged tetanic stimulation in patients compared with normals, with a mean +/- SEM (n) of 29.1 +/- 4.0% (n = 7) and 3.5 +/- 0.8% (n = 22), respectively, (p less than 0.001). Four patients were restudied after a 4-wk period of total parenteral nutrition, with a significant improvement in muscle function parameters. Malnutrition results in both increased muscle fatiguability and an altered pattern of muscle contraction and relaxation which are reversible by nutritional supplementation. This technique promises to be valuable in assessing the functional effects of malnutrition and the response to nutritional support.

Skeletal muscle function during hypocaloric diets and fasting: a comparison with standard nutritional assessment parameters.

Skeletal muscle function and standard nutritional assessment parameters were measured in six obese patients. Base-line measurements were made on a weight-maintaining diet, and further measurements after 2 wk of a 400-cal diet, followed by 2 wk of fasting and then after 2 wk of refeeding. The function of the adductor pollicis muscle was assessed by electrical stimulation of the ulnar nerve. The objective parameters of muscle function measured were: 1) force of contraction expressed as a percentage of the maximal force obtained with electrical stimulation at 10, 20, 30, 50, and 100 Hz. 2) Maximal relaxation rate expressed as percentage force loss/10 ms. 3) Endurance expressed as percentage force loss/30 s. Standard nutritional assessment parameters (serum albumin and transferrin, creatinine height index, anthropometry and total body nitrogen and potassium) were also measured. There was a significant increase in the force of contraction at 10 Hz from a base-line of 29.6 +/- 1.0% to 49.0 +/- 2.8% (mean +/- SEM) after 2 wk of a 400-cal diet (p less than 0.01). These was a significant slowing of the maximal relaxation rate from a base-line of 9.8 +/- 0.03% force loss/10 ms to 8.2 +/0 0.3% force loss/10 ms (mean +/- SEM) (p less than 0.01) after 2 wk of a 400-cal diet. After a further 2 wk of fasting these abnormalities in muscle function persisted. There was a significant increase in muscle force loss from a base-line of 3.9 +/- 0.8% force loss/30 s to 13.7 +/- 3.4% force loss/30 s (mean +/- SEM) after fasting (P less than 0.01). After 2 wk of refeeding all aspects of muscle function measured were normal. During the study the standard nutritional assessment parameters did not change significantly.

A comparison between muscle function and body composition in anorexia nervosa: the effect of refeeding.

Skeletal muscle function, body composition (total body nitrogen and total body potassium) and standard parameters of nutritional assessment were measured in six severely depleted patients with primary anorexia nervosa, both on admission and during oral refeeding. The function of the adductor pollicis muscle was assessed by electrical stimulation of the ulnar nerve. On admission muscle function was markedly abnormal in the patients with anorexia nervosa (n = 6) compared with normal subjects (n = 22), with a significant increase in the force of contraction at 10 Hz, with a mean +/- SEM of 48.0 +/- 3.7% and 28.8 +/- 1.2%, respectively (p less than 0.001). There was slowing of the maximal relaxation rate, 6.6 +/- 0.6% and 9.6 +/- 0.2%, respectively (p less than 0.001) and increased muscle fatigue 18.6 +/- 5.9% and 3.5 +/- 0.8%, respectively (p less than 0.01). Initially, the mean serum albumin was normal (4.0 +/- 0.1 g/dl), although there was evidence of severe depletion of somatic protein stores, with a low total body nitrogen and creatinine-height index. Within 4 wk of oral refeeding, maximal relaxation rate and muscle fatigability were restored to normal, and within 8 wk all parameters of muscle function were normal. During the study total body nitrogen increased by only 13% and was still 19.4% below the predicted normal total body nitrogen, whereas total body potassium increased by 32% and body fat by 46%. Normalization of muscle function may be related to restoration of muscle electrolytes rather than repletion of body nitrogen.

Metabolic and structural changes in skeletal muscle during hypocaloric dieting.

Hypocaloric dieting and fasting alter the contraction-relaxation characteristics of skeletal muscle and result in low frequency fatigue. We report the metabolic and structural changes in skeletal muscle in five morbidly obese female subjects who had biopsies of the gastrocnemius muscle on a base-line diet (2500 kcal/day) followed by a repeat biopsy after 2 wk of a 400-kcal/day carbohydrate diet. Hypocaloric dieting resulted in a significant increase in the intracellular muscle calcium content (p less than 0.05), which may account for the observed changes in muscle function. There were no significant changes in muscle glycogen, lactate, pyruvate, or free energy stores. There was a significant decrease in muscle enzymes [phosphofructokinase (p less than 0.05), succinate dehydrogenase (p less than 0.02)] and some muscle amino acid levels [glutamine (p less than 0.025), glycine (p less than 0.01), and alanine (p less than 0.02)], while muscle histochemistry showed type II fiber atrophy (p less than 0.025). However, these changes reflect a generalized response to hypocaloric dieting and probably do not explain the specific functional changes. Change in the muscle calcium content is probably an important mediator of the adverse functional effects of malnutrition.

Episodic confusion and tremor associated with extrahepatic portacaval shunting in cirrhotic liver disease.

In an elderly male patient with alcohol-related liver disease, who developed episodic confusion and tremor, we found a large extrahepatic portacaval shunt. He had no clinical or laboratory evidence of liver dysfunction except for an elevated serum ammonia level that increased further in response to an ammonium chloride challenge test. Extrahepatic portacaval shunting causing episodic confusion and tremor may occur with alcoholic liver disease without overt liver failure and may require abdominal angiography or a transhepatic portogram to demonstrate the shunt.

Catheter sepsis during parenteral nutrition: the safety of long-term OpSite dressings.

A prospective controlled study of the safety of various catheter dressing protocols was carried out in 168 patients receiving parenteral nutrition via an infraclavicular central venous catheter. Four protocols were compared: 36 patients received gauze dressings changed three times per week; 31 received OpSite dressings changed every 7th day (OpS-7), 32 received OpSite changed every 10th day (OpS-10), and 69 received OpSite changed twice weekly (OpS-ICU). Mean duration of parenteral nutrition was approximately 2 weeks and all groups were well matched except that OpS-ICU patients suffered more frequently from an acute illness. Catheter-related sepsis was identified by clinical signs of systemic sepsis, positive peripheral venous blood and catheter-tip cultures and/or defervescence of fever after catheter removal. Catheter-related sepsis rates were low in all groups: 1/36 for Gauze, 0/31 for OpS-7, 1/32 for OpS-10, and 2/69 for OpS-ICU. Septicemia attributable to causes apart from catheter sepsis occurred in two, two, three, and four patients, respectively. Bacterial colonization of skin beneath OpSite was no more common in the OpS-10 than in the other groups. Signs of inflammation at catheter insertion sites were common in all groups but did not relate closely to skin colonization. OpSite can be safely applied to central venous catheters inserted under strict aseptic conditions, even in patients with open septic drainage. Dressings can be left in place for 7 days with a margin of safety lasting to 10 days, thus saving on cost of materials and nursing time.

Activities associated with drownings in Imperial County, CA, 1980-90: implications for prevention.

Statewide surveillance in California determined that the highest drowning rate from 1980 through 1989 was for the rural, desert county of Imperial (21.9 drownings per 100,000 population). To identify activities associated with drowning in this county, the authors abstracted data from the county sheriff-coroner's reports. From 1980 through 1990, there were 317 unintentional drownings; 85 percent occurred in irrigation canals. The activity prior to drowning was known for 262 persons (83 percent), and the most common activity was illegal entry into the United States. Overall, 140 persons (53 percent) were illegal entrants. Ninety-three percent of illegal entrants drowned in the All American Canal; the monthly drowning rate increased as the monthly average water velocity in the canal increased (r = 0.36; P < 0.001). Forty-eight persons (18 percent) drowned while riding in or on a land vehicle (automobile, pick-up truck, motorcycle, dune buggy, or tractor), the second most common activity associated with drowning. Seventy percent of the 23 drivers had an alcohol concentration of 100 milligrams per deciliter or more, California's limit for intoxication. To reduce drownings in Imperial County, prevention strategies should target persons engaged in at-risk activities near bodies of water. These strategies should include the identification and use of effective canal safety devices.