Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

BACKGROUND: We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine. METHODS: Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period. Subjects were asked to self-treat at moderate or severe pain, or after 20 minutes of mild pain. RESULTS: Of 30 enrolled patients (25 females, five males, median age 39), two treated no attacks, and one treated aura only, leaving a Full Analysis Set of 27 treating 80 attacks with pain. An adverse event was reported in 13 patients, notably: neck twitching (n = 1), raspy voice (n = 1) and redness at the device site (n = 1). No unanticipated, serious or severe adverse events were reported. The pain-free rate at two hours was four of 19 (21%) for the first treated attack with a moderate or severe headache at baseline. For all moderate or severe attacks at baseline, the pain-free rate was 12/54 (22%). CONCLUSIONS: nVNS may be an effective and well-tolerated acute treatment for migraine in certain patients.

A comparison of the environmental impact of Jersey compared with Holstein milk for cheese production.

The objective of this study was to compare the environmental impact of Jersey or Holstein milk production sufficient to yield 500,000 t of cheese (equivalent cheese yield) both with and without recombinant bovine somatotropin use. The deterministic model used 2009 DairyMetrics (Dairy Records Management Systems, Raleigh, NC) population data for milk yield and composition (Jersey: 20.9 kg/d, 4.8% fat, 3.7% protein; Holstein: 29.1 kg/d, 3.8% fat, 3.1% protein), age at first calving, calving interval, and culling rate. Each population contained lactating and dry cows, bulls, and herd replacements for which rations were formulated according to DairyPro (Agricultural Modeling and Training Systems, Cornell, Ithaca, NY) at breed-appropriate body weights (BW), with mature cows weighing 454 kg (Jersey) or 680 kg (Holstein). Resource inputs included feedstuffs, water, land, fertilizers, and fossil fuels. Waste outputs included manure and greenhouse gas emissions. Cheese yield (kg) was calculated according to the Van Slyke equation. A yield of 500,000 t of cheese required 4.94 billion kg of Holstein milk compared with 3.99 billion kg of Jersey milk-a direct consequence of differences in milk nutrient density (fat and protein contents) between the 2 populations. The reduced daily milk yield of Jersey cows increased the population size required to supply sufficient milk for the required cheese yield, but the differential in BW between the Jersey and Holstein breeds reduced the body mass of the Jersey population by 125×10(3) t. Consequently, the population energy requirement was reduced by 7,177×10(6) MJ, water use by 252×10(9) L, and cropland use by 97.5×10(3) ha per 500,000 t of cheese yield. Nitrogen and phosphorus excretion were reduced by 17,234 and 1,492 t, respectively, through the use of Jersey milk to yield 500,000 t of Cheddar cheese. The carbon footprint was reduced by 1,662×10(3) t of CO(2)-equivalents per 500,000 t of cheese in Jersey cows compared with Holsteins. Use of recombinant bovine somatotropin reduced resource use and waste output in supplemented populations, with decreases in carbon footprint equivalent to 10.0% (Jersey) and 7.5% (Holstein) compared with nonsupplemented populations. The interaction between milk nutrient density and BW demonstrated by the Jersey population overcame the reduced daily milk yield, thus reducing resource use and environmental impact. This reduction was achieved through 2 mechanisms: diluting population maintenance overhead through improved milk nutrient density and reducing maintenance overhead through a reduction in productive and nonproductive body mass within the population.

Effect of recombinant bovine somatotropin and a shortened or no dry period on the performance of lactating dairy cows.

The objective of this study was to determine the effects of altering dry period length in multiparous dairy cows (n = 341) on milk production for a full lactation (294 d). The study used 3 commercial herds in the western United States. Cows producing greater than 8,400 kg of mature-equivalent milk were assigned to treatments 60 d before their due dates. The 4 treatments were 1) 60-d dry period, label use of recombinant bovine somatotropin (rbST; 60d-L); 2) 32-d dry period, label use of rbST (32d-L); 3) 0-d dry period, label use of rbST (0d-L); and 4) 0-d dry period, continuous use of rbST (0d-C). Cows with shortened dry periods produced 625, 1,000, and 1,042 kg of milk during the prepartum period for treatments 2 to 4, respectively. During the postpartum period, cows on the 32d-L treatment produced similar amounts of milk compared with the 60d-L treatment (11,490 vs. 11,968 kg, respectively). However, cows on the 0d-L (10,316 kg) and 0d-C (10,195 kg) treatments produced significantly lower amounts of milk during the postpartum period compared with the 60d-L treatment. Total milk production from the prepartum and postpartum periods was not altered significantly and was 11,974, 12,112, 11,310, and 11,230 kg for treatments 1 to 4, respectively. The concentrations of beta-hydroxybutyrate and nonesterified fatty acids in serum after calving were decreased for cows on the 32d-L, 0d-L, and 0d-C treatments compared with cows on the 60d-L treatment, which may indicate improved metabolic status.

Determination of diffusion coefficients and diffusion characteristics for chlorferon and diethylthiophosphate in Ca-alginate gel beads.

Diffusion characteristics of chlorferon and diethylthiophosphate (DETP) in Ca-alginate gel beads were studied to assist in designing and operating bioreactor systems. Diffusion coefficients for chlorferon and DETP in Ca-alginate gel beads determined at conditions suitable for biodegradation studies were 2.70 x 10(-11) m(2)/s and 4.28 x 10(-11) m(2)/s, respectively. Diffusivities of chlorferon and DETP were influenced by several factors, including viscosity of the bulk solution, agitation speed, and the concentrations of diffusing substrate and immobilized cells. Diffusion coefficients increased with increasing agitation speed, probably due to poor mixing at low speed and some attrition of beads at high speeds. Diffusion coefficients also increased with decreasing substrate concentration. Increased cell concentration in the gel beads caused lower diffusivity. Theoretical models to predict diffusivities as a function of cell weight fraction overestimated the effective diffusivities for both chlorferon and DETP, but linear relations between effective diffusivity and cell weight fraction were derived from experimental data. Calcium-alginate gel beads with radii of 1.65-1.70 mm used in this study were not subject to diffusional limitations: external mass transfer resistances were negligible based on Biot number calculations and effectiveness factors indicated that internal mass transfer resistance was negligible. Therefore, the degradation rates of chlorferon and DETP inside Ca-alginate gel beads were reaction-limited.

Treatment satisfaction and efficacy of the rapid release formulation of sumatriptan 100 mg tablets utilising an early intervention paradigm in patients previously unsatisfied with sumatriptan.

AIMS: To evaluate treatment satisfaction, efficacy and functional ability of the rapid release formulation of sumatriptan 100 mg tablets (sumatriptan RT 100 mg) in an early intervention paradigm in patients who were dissatisfied with low-dose sumatriptan and not completely satisfied with their current migraine regimen. METHODS: Experienced migraineurs who reported a mild migraine pain phase, dissatisfaction with the previous sumatriptan treatment and some dissatisfaction with their current treatment regimen had no experience with sumatriptan at the 100 mg dose were enrolled in an open-label, single group study. Subjects were instructed to treat four migraine attacks within 30 min of the onset of mild pain. Treatment satisfaction was measured with the Patient Perception of Migraine Questionnaire Revised version (PPMQ-R) questionnaire. RESULTS: More than half of the subjects were either very satisfied or satisfied with the efficacy of early intervention sumatriptan RT 100 mg after each attack and at the follow-up study visit. The mean total PPMQ-R score was 75.2 out of 100. Between 63% and 73% of subjects were pain-free within 4 h of dosing. Between 79% and 90% of subjects reported an ability to function normally within 4 h of taking the study medication. CONCLUSION: Subjects who were previously unsatisfied with lower doses of sumatriptan and less than very satisfied with their current treatment regimen were more likely to be satisfied or very satisfied with sumatriptan RT 100 mg in an early intervention paradigm. Results were consistent across four migraine attacks and at a follow-up visit. The treatment satisfaction results corresponded with positive results on efficacy measures and a functional status measure.

Biodegradation of chlorferon and diethylthiophosphate by consortia enriched from waste cattle dip solution.

Chlorferon and diethylthiophosphate (DETP) are the hydrolysis products of coumaphos, an organophosphate pesticide. In this research, two consortia of bacterial cultures, one responsible for degrading chlorferon and the other for degrading DETP, were selectively enriched from waste cattle dip solution. The enriched cultures were used as inocula to grow biomass for biodegradation studies. For chlorferon degradation, the optimum biomass concentration was found to be 80g/L, and pH 7.5 was selected as the optimal operating pH. Chlorferon degradation was characterized by substrate inhibition kinetics with parameter values estimated to be V(m)=0.062+/-0.011mg/(g-biomass)h, K(m)=21+/-7mg/L, and K(Si)=118+/-45mg/L. For DETP degradation, the optimum biomass concentration was found to be 60g/L, and the optimum pH was in the range of 7.5-8. DETP degradation was characterized by Michaelis-Menten kinetics with parameter values estimated to be V(m)=1.52+/-0.10mg/(g-biomass)h and K(m)=610+/-106mg/L.

Sumatriptan injection reduces productivity loss during a migraine attack: results of a double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the impact of sumatriptan succinate injection compared with placebo on productivity loss during a migraine attack in the workplace. DESIGN: Randomized, double-blind, placebo-controlled, parallel-group clinical trial. SETTING: Fifteen clinical centers in the United States. PATIENTS: One hundred thirty-five patients 18 years and older diagnosed as having migraine according to International Headache Society criteria. INTERVENTIONS: Patients self-administered sumatriptan injection (6 mg) or matching placebo to treat a moderate or severe migraine occurring within the first 4 hours of a minimum 8-hour work shift. MAIN OUTCOME MEASURES: Mean productivity loss 2 hours after dosing and across the work shift; percentages of patients returning to normal work performance within 2 hours after dosing and across the work shift; percentages of patients experiencing headache relief (reduction of moderate or severe predose pain to mild or no pain) 1 and 2 hours after dosing. RESULTS: Mean productivity loss was significantly (P< or =.002) lower in the sumatriptan group compared with the placebo group both during the 2-hour postdose period (sumatriptan, 39 minutes; placebo, 54 minutes) and across the work shift (sumatriptan, 86 minutes; placebo, 168 minutes). Significantly (P<.001) greater percentages of patients in the sumatriptan group compared with the placebo group returned to normal work performance by 2 hours after dosing (sumatriptan, 52%; placebo, 9%) and across the work shift (sumatriptan, 66%; placebo, 18%). Significantly (P< or =.001) greater percentages of patients in the sumatriptan group compared with the placebo group experienced headache relief 1 hour after dosing (sumatriptan, 69%; placebo, 18%) and 2 hours after dosing (sumatriptan, 79%; placebo, 32%). CONCLUSION: Sumatriptan reduced migraine-associated productivity loss during a minimum 8-hour work shift by approximately 50% compared with placebo and alleviated headache in more than three fourths of patients.

Efficacy of subcutaneous sumatriptan in repeated episodes of migraine.

This double-blind, placebo-controlled, multicenter, crossover study investigated the efficacy and tolerability of sumatriptan administered for up to three separate migraine attacks. One hundred twenty adults received sumatriptan (SC, 6 mg; three attacks) and placebo (one attack). Patients completed questionnaires assessing the impact of migraine on their lives and the performance of sumatriptan relative to their usual acute therapies. Sumatriptan statistically outperformed placebo on all efficacy measures, including pain severity; presence/absence of nausea, vomiting, phonophobia, and photophobia; rescue medication use; and clinical disability. Efficacy was consistently maintained with repeated administration. For all attacks, pain relief 90 minutes postdose occurred in 86% to 90% of sumatriptan-treated patients, compared with 9% to 38% of placebo-treated patients. Sumatriptan was well tolerated, and the frequency and severity of adverse events did not change with repeated administration. Patients' perceptions of sumatriptan were consistent with clinical data demonstrating the drug's high degree of efficacy and tolerability.

Diagnostic lessons from the spectrum study.

Article abstract Migraine is a heterogeneous condition that causes symptoms that vary both among individuals and within individuals from attack to attack. We examined and reviewed several important lessons on the diagnosis of migraine learned from the distribution of headache types and patterns of treatment response in the Spectrum Study, including recruitment and diagnostic issues. The accuracy of an initial diagnosis, assigned by a clinician in the context of a clinical trial, was compared with the results of a final diagnosis, assigned by a neurologist, reviewing the initial evaluation as well as headache diaries for up to 10 attacks. Several lessons can be learned from the Spectrum Study. Recruitment difficulties teach us that disabling tension-type headache is difficult to find, suggesting that it is rare. Examination of the final diagnosis given after diary evaluations suggests that a diagnosis of migraine can usually be confirmed for patients with disabling headache. After reclassification of the final sample of 432 subjects, 24/75 (32%) patients initially clinically classified as having disabling episodic tension-type headache proved to have migraine or migrainous headache after a diary review. Among study participants, 90% of subjects with disabling headache (HIMQ score >250) had a migraine-related disorder. Treatment response suggests that, in migraineurs, tension-type headaches may have a pathophysiology similar to that of migraine. The diary data show that mild headaches in patients with disabling migraine often evolve into full-blown migraine. The Spectrum Study supports the view that, for patients with disabling episodic headache, migraine is often the correct diagnosis. In clinical practice, the suspicion of migraine should be high for patients experiencing episodic disabling headache. Assessment of headache-related disability may assist practitioners in making a diagnosis of migraine.

Clinical efficacy and tolerability of 2.5 mg zolmitriptan for the acute treatment of migraine. The 042 Clinical Trial Study Group.

Previous studies demonstrated that zolmitriptan at doses of 1 to 25 mg was highly effective in treating acute migraine attacks. The 2.5-mg dose had a favorable therapeutic effect with high efficacy and good tolerability. The objective of this study was to further evaluate the efficacy of a single 2.5-mg dose of zolmitriptan (Zomig, formerly known as 311C90) for acute treatment of a single moderate or severe migraine attack. The study was a randomized, double-blind, placebo-controlled clinical trial. Female and male patients, 12 to 65 years old, with migraine (with or without aura) for > or = 1 year, one to six migraines per month, and age at onset < 50 years were included; 327 patients were screened and randomized to receive either zolmitriptan (n = 219) or placebo (n = 108). Patients treated a single moderate or severe migraine headache with 2.5 mg zolmitriptan or placebo and recorded clinical efficacy and adverse events on a diary form. Headache response at 2 hours was 62% for zolmitriptan compared with 36% for placebo (p < 0.001); at 4 hours, headache response was 70% with zolmitriptan and 37% with placebo (p < 0.001). Headache recurrence in patients treated with 2.5 mg zolmitriptan was 22% (versus placebo 30%). The headache response at 4 hours, pain-free rate, and response rate of nonheadache symptoms favored zolmitriptan over placebo. No serious adverse events were associated with zolmitriptan treatment. A 2.5-mg dose of zolmitriptan is clinically effective and well tolerated for the acute treatment of migraine.

Cost-effectiveness and cost-benefit of sumatriptan in patients with migraine.

OBJECTIVE: To investigate the cost-effectiveness and cost-benefit of initiating sumatriptan therapy in patients with acute migraine who were previously taking nontriptan drugs. PATIENTS AND METHODS: This is an economic analysis of a prospective, pretest-posttest, observational 6-month outcomes study of 178 patients with a physician diagnosis of migraine who received their first prescription for sumatriptan between October 1994 and August 1996 and were members of a mixed-model managed care organization in western Pennsylvania. Migraine-related resource use data were obtained from the managed care organization's medical and pharmacy claims databases. The primary outcome measure for this economic analysis was the total disability time that patients experienced because of migraine. Patients reported time missed from work and usual nonwork activities because of migraine on self-administered questionnaires at baseline and at 3 and 6 months after initiation of sumatriptan. RESULTS: Initiation of sumatriptan resulted in a decrease of 662 migraine-disability-days for work and 1236 migraine-disability-days for nonwork activities during the 6 months of the study (decrease from 27.8 to 17.2 days per person), totaling 1898 migraine-disability-days averted with sumatriptan therapy. Migraine-related medical costs were lower after sumatriptan was initiated ($18,351 vs $26,192), whereas migraine-related pharmacy costs were lower with prior nontriptan drug therapy ($22,209 vs $74,861). The overall net cost savings after sumatriptan was initiated in these patients was $222,332 ($1249 per patient) with a benefit-to-cost ratio of $5.67 gained for each health care dollar spent from a societal perspective. The incremental cost-effectiveness ratio was $25 for each additional migraine-disability-day averted by using sumatriptan vs nontriptan drug therapy. Sensitivity analysis showed that changes in medical costs had little effect on the ratios and that sumatriptan remained cost-beneficial across a wide range of patient wages. CONCLUSION: This study showed that initiation of sumatriptan in patients previously receiving nontriptan therapy was cost-effective and had an economic benefit for patients, employers, and society. Sumatriptan also helped patients and physicians achieve goals recommended by the US Headache Consortium by reducing patients' disability and thus improving their ability to function at work and nonwork activities.

Effectiveness of sumatriptan in reducing productivity loss due to migraine: results of a randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: To determine the effect of sumatriptan on migraine-related workplace productivity loss. PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled, parallel-group trial, adult migraineurs self-injected 6 mg of sumatriptan or matching placebo to treat a moderate or severe migraine within the first 4 hours of a minimum of an 8-hour work shift. Outcome measures included productivity loss and number of patients returning to normal work performance 2 hours after injection and across the work shift, time to return to normal work performance, and time to headache relief. RESULTS: A total of 206 patients underwent screening, 140 (safety population) of whom returned for clinic treatment. Of these 140 patients, 119 received migraine treatment in the workplace (intent-to-treat population), 116 of whom comprised the study population. Of these 116 patients, 76 self-administered sumatriptan, and 40 self-administered placebo. Sumatriptan treatment tended to reduce median productivity loss 2 hours after injection compared with placebo (25.2 vs 29.9 minutes, respectively; P = .14). Significant reductions in productivity loss were obtained across the work shift after sumatriptan treatment compared with placebo (36.8 vs 72.6 minutes, respectively; P = .001). Significantly more sumatriptan-treated patients vs placebo-treated patients experienced shorter return to normal work performance at 2 hours (53/76 [70%] vs 12/40 [30%], respectively) and across the work shift (64/76 [84%] vs 23/40 [58%], respectively; P < .001). Significantly more sumatriptan-treated patients experienced headache relief 1 hour after injection compared with placebo-treated patients (48/76 [63%] vs 13/40 [33%], respectively; P = .004). CONCLUSION: Across an 8-hour work shift, sumatriptan was superior to placebo in reducing productivity loss due to migraine.

Efficacy and tolerability of subcutaneous sumatriptan administered using the IMITREX STATdose System.

The efficacy and tolerability of subcutaneous (SC) sumatriptan administered with the IMITREX (sumatriptan succinate) STATdose System, which circumvents the need for patients or health care professionals to handle a syringe, were evaluated in two randomized, double-masked, parallel-group, placebo-controlled, multicenter studies. In the clinic, 158 adults with migraine diagnosed according to International Headache Society criteria received SC sumatriptan (6 mg) or placebo delivered with the IMITREX STATdose System for treatment of a migraine attack. By 120 minutes after SC dosing, 73% and 79% of sumatriptan-treated patients, compared with 28% and 37% of placebo-treated patients in studies 1 and 2, respectively, experienced headache relief (a statistically significant difference). Clinical disability scores 120 minutes after dosing showed that 75% and 85% of sumatriptan-treated patients, compared with 30% and 42% of placebo-treated patients, were normal or only mildly impaired (a statistically significant difference). Similar efficacy rates were observed for nausea, phonophobia, and photophobia. No serious or unusual adverse events occurred, and no clinically relevant abnormalities in laboratory test values were reported. Based on these results, we concluded that SC sumatriptan (6 mg) administered using the IMITREX STATdose System is effective for the treatment of migraine. The efficacy and tolerability profiles of SC sumatriptan administered with this device are similar to those reported for SC sumatriptan administered with a conventional syringe.

Economic implications of early treatment of migraine with sumatriptan tablets.

BACKGROUND: Early treatment of migraine with sumatriptan 50 mg and 100 mg, while pain is mild, has been reported to enhance pain-free response 2 hours and 4 hours postdose and sustained pain-free response 2 to 24 hours postdose compared with treatment when pain has become moderate to severe. Early treatment with sumatriptan 50 mg and 100 mg also resulted in less redosing, which translated to a reduction in the mean number of doses used per migraine episode. OBJECTIVE: We examined the economic implications of early treatment with sumatriptan 50 mg and 100 mg while pain is mild versus treatment when pain has become moderate to severe. METHODS: Using data from retrospective analyses of a dose-ranging clinical trial of sumatriptan (protocol S2CM09) involving 1003 patients, we estimated the mean cost per treatment success for a hypothetical population of 1000 migraine patients who received treatment with sumatriptan 50-mg or 100-mg tablets early while pain was mild versus treatment when pain had become moderate to severe. RESULTS: With a conservative estimate of migraine frequency of 1.5 episodes per month, the total cost of early migraine treatment with sumatriptan 50 mg and 100 mg was reduced by $31.68 and $20.16, respectively, per patient per year. The average cost per pain-free treatment success was reduced by 32% to 57% with sumatriptan 50 mg and 100 mg if migraines were treated while pain was mild in intensity versus when pain had become moderate to severe. CONCLUSIONS: Treatment of migraine with sumatriptan 50-mg and 100-mg tablets is effective regardless of whether pain is mild, moderate, or severe. However, initiating treatment while pain is mild may be more cost-effective than delaying treatment until pain has become moderate to severe.

Effect of early intervention with sumatriptan on migraine pain: retrospective analyses of data from three clinical trials.

OBJECTIVE: This study assessed the efficacy of sumatriptan 50- and 100-mg tablets in the treatment of migraine attacks while the pain is mild rather than moderate/severe. BACKGROUND: Results from The Spectrum Study suggested that early treatment of migraine attacks with sumatriptan 50-mg tablets while the pain is mild might enhance pain-free response and reduce headache recurrence. METHODS: Retrospective analyses of headaches treated during mild pain were performed using data from 3 studies of sumatriptan tablets (protocols S2CM09, S2BT25, and S2BT26). Our primary interest was pain-free response 2 and 4 hours after dosing; secondary interests were use of a second dose of medication, clinical disability (as measured on a 4-point disability scale), migraine-associated symptoms, meaningful pain relief (patient defined), time to meaningful relief, sustained pain-free response, and proportion of attacks in which pain had worsened 2 and 4 hours after dosing, all of which were compared in headaches treated during mild versus moderate/severe pain. RESULTS: In S2CM09, 92 patients treated 118 headaches during mild pain. Rates of pain-free response were higher 2 hours after dosing with sumatriptan 50 mg (51%) or 100 mg (67%; P < 0.05) compared with placebo (28%), and were higher with early treatment of mild pain compared with treatment of moderate/severe pain at 2 hours (sumatriptan 50 mg: mild pain, 51%; moderate/severe pain, 31%; P < 0.05; sumatriptan 100 mg: mild pain, 67%; moderate/severe pain, 36%) and 4 hours (50 mg: 75% vs 56%; 100 mg: 90% vs 61%; P < 0.05). Early intervention also resulted in less redosing than when moderate/severe pain was treated (50 mg: 21% vs 32%; 100 mg: 20% vs 29%). More attacks treated early with sumatriptan 50 or 100 mg were associated with normal function 4 hours after dosing compared with placebo (70% and 93% vs 46%, respectively). Sustained pain-free response rates 2 to 24 hours after early dosing with sumatriptan 50 or 100 mg were also higher (34% and 53%, respectively) compared with treatment of moderate/severe pain (19% and 24%, respectively). Early treatment with sumatriptan 100 mg produced significantly higher pain-free rates at 2 hours after dosing (P < 0.001) than did ergotamine plus caffeine (S2BT25: 69% vs 34%, respectively) or aspirin plus metoclopramide (S2BT26: 73% vs 25%, respectively). CONCLUSIONS: Sumatriptan 50- and 100-mg tablets are effective whether pain is mild or moderate/severe. However, treatment with sumatriptan while pain is mild provides high pain-free response rates while reducing the need for redosing, benefits not seen with ergotamine plus caffeine or aspirin plus metoclopramide.

Enhanced-rate biodegradation of organophosphate neurotoxins by immobilized nongrowing bacteria.

Pesticide wastes generated from livestock dipping operations containing the organophosphate (OP) insecticide coumaphos (CP) are well suited for disposal by biodegradation since they are highly concentrated (approximately 1 g/L), generally contained, and lack additional toxic components. In this study, a significantly enhanced efficiency of degrading CP in cattle dip waste (CDW) is reported using a dense, nongrowing cell population that functions without the addition of nutrients required for growing cell cultures. A recombinant strain of Escherichia coli containing the opd gene for organophosphate hydrolase (OPH), which is capable of active hydrolysis of OP neurotoxins including CP, was cultivated in a rich medium containing all essential nutrients. Cells were harvested and utilized in lab scale experiments in the form of either freely suspended cells or cells immobilized within a macroporous gel matrix, poly(vinyl alcohol) (PVA) cryogel. Significantly higher degradation rates were achieved with either suspended or immobilized OPH(+) cells compared to rates with the microbial consortium naturally present in CDW. Of the two nongrowing cell systems, the detoxification rate with immobilized cells was approximately twice that of freely suspended cells, and kinetic studies demonstrated that a higher maximum reaction rate was achieved with the immobilized cell system. A comparative study using both the CDW and pure CP substrates with free cells indicated that the CDW contained one or more factors that reduced the bioavailability of CP. The immobilized cells retained their activity over a 4-month period of use and storage, demonstrating both sustained catalytic activity and long-term mechanical stability.

Workplace productivity. A review of the impact of migraine and its treatment.

Migraine is a common disorder characterised by recurrent episodes of disability. Despite the high prevalence of migraine, data have been lacking on its impact in a working population. The advent of new therapies has stimulated interest in this area, and evidence is now available that documents the substantial impact of migraine on workplace productivity and the likelihood of untreated migraine leading to unemployment or underemployment for the patient. This paper reviews current findings of both observational and interventional studies about the impact of migraine on productivity and employment. When considered in the light of migraine demographics, the high prevalence of migraine, and its low consultation and treatment rates, this evidence indicates that improved screening and treatment for this common condition could have a substantial impact on worker productivity and on patient well-being.

Inhibition of diacylglycerol:CDPcholine cholinephosphotransferase activity by dimethylaminoethyl p-chlorophenoxyacetate.

Cholinephosphotransferase [EC 2.7.8.2] activity of rat liver microsomes, with 1,2-di-0-[3H]acyl glycerol or 1-0-hexadecanoyl [U-14C]ethanediol as substrate, was inhibited by N,N-dimethylaminoethyl p-chlorophenoxyacetate (centrophenoxine). Inhibition progressed in a linear fashion with increasing drug levels and was complete at 30 mM concentration. It appears that the microsomal enzyme was largely affected by the drug itself because the hydrolysis products of centrophenoxine, viz., N,N-dimethylaminoethanol and p-chlorophenoxyacetic acid, were less inhibitory.

"Cold" bone scans in acute osteomyelitis.

The diagnosis of acute osteomyelitis is often very difficult during the first 24 to 48 hours. Bone scanning has been a useful adjunct in this diagnosis by demonstrating increased uptake in the area or areas of involvement. Occasionally the pathological area is "cold" on scanning, which may lead to a misdiagnosis. This paper presents three cases demonstrating this unusual finding.

Diagnosis and treatment of migraine.

Migraine is one of the most common and misunderstood disease encountered in general medical practice. An estimated 23 million Americans suffer disabling migraines, yet only a minority are diagnosed (1,2). An even smaller percentage receive optimal care. Migraine extracts a significant personal, psychologic, social, and economic toll from migraineurs and their families. An estimated 150 million workdays are lost annually due to headache at an estimated cost of $6 to $17 billion (3,4). Recent advances in understanding of the pathophysiology and acute therapy provide the potential to markedly reduce the impact of migraine. Available abortive medications have efficacy rates as high as 80%, but only a minority of afflicted patients currently receive these therapies. While reducing headache pain, they also restore function, enabling an individual to return to work, family, and personal commitments (5). Future progress in migraine management resides in early identification and optimization of migraine treatment. This article focuses on diagnosis and treatment.