Calosphaeria Canker of Sweet Cherry Caused by Calosphaeria pulchella in California and South Australia.

California is the second largest sweet cherry producer in the United States with annual revenues up to $200 million. The South Australian cherry industry generates about 10% of Australia's overall production with approximately 1,500 metric tons of cherries produced yearly. In California, perennial canker diseases and subsequent branch dieback are responsible for extensive damage throughout sweet cherry orchards, reducing annual yields and tree longevity. Surveys of cherry orchards and isolation work were conducted in California to identify the main canker-causing agents. Calosphaeria pulchella was the main fungus isolated from cankers, followed by Eutypa lata and Leucostoma persoonii, respectively. Preliminary surveys in cherry orchards in South Australia documented C. pulchella and L. persoonii in cankers. The pathogenicity of C. pulchella in sweet cherry was confirmed following field inoculations of 2- to 3-year-old branches. C. pulchella was able to infect healthy wood and produce cankers with as much virulence as E. lata or L. persoonii. Spore trapping studies were conducted in two sweet cherry orchards in California to investigate the seasonal abundance of C. pulchella spores. Experiments showed that rain and sprinkler irrigation were important factors for aerial dissemination. Finally, this study illustrates the symptoms and signs of the new disease Calosphaeria canker.

Omega-3 enriched egg production: the effect of α -linolenic ω -3 fatty acid sources on laying hen performance and yolk lipid content and fatty acid composition.

1. Diets high in total lipids, saturated fatty acids, trans fatty acids, and having high ω-6:ω-3 fatty acid ratios, have been shown to be related to increased instances of coronary heart disease, while diets high in ω-3 fatty acids have been shown to decrease the risk. 2. Feeding ω-3 fatty acid diets to laying hens has been shown to improve the quality of eggs produced in terms of saturation and ω-3 content. 3. A study was undertaken to determine if the ω-3 fatty acid source, when fed to hens, influences the amount transferred to eggs. 4. Flaxseed and flaxseed oil, along with chia seed and chia seed oil, were the two main sources of ω-3 fatty acid examined during the 84 d trial. 5. All α-linolenic enriched treatments yielded significantly higher ω-3 fatty acid contents per g of yolk and per yolk, than the non-α-linolenic enriched diets. Chia oil and chia seed yielded 54·5 and 63·5% more mg of ω-3 fatty acid per g of yolk for the 56 d test period, and 13·4 and 66·2% more for the 84 d test period, than flaxseed oil and flaxseed, respectively. 6. The differences in omega-3 content were significant, except for the chia oil compared with the flax oil, at the end of the trial. 7. This trial has shown that differences in conversion exist among ω-3 fatty acid sources, at least when fed to hens, and indicates that chia may hold a significant potential as a source of ω-3 fatty acid for enriching foods, thereby making these foods a healthier choice for consumers.

First Report of Calosphaeria pulchella Associated with Branch Dieback of Sweet Cherry Trees in California.

California is the second largest sweet cherry producer in the United States with approximately 10,800 ha and an average annual crop value of approximately $150 million. Perennial canker diseases constitute major threats to the cherry industry productivity by reducing tree health, longevity, and yields. During the course of summer 2006, we observed severe limb and branch dieback of sweet cherry (Prunus avium L.) in San Joaquin, San Benito, Contra Costa, and Stanislaus counties of California. Isolation from diseased branches repeatedly yielded the fungus Calosphaeria pulchella (Pers.: Fr.) J. Schröt. (1,2). Cankers and vascular necroses had developed in tree limbs and branches, generally initiating from the heart wood and later spreading into the sapwood. External symptoms of disease may be unapparent throughout the early stages of infection, particularly in large diameter shoots. Older infections often appeared as wilted leaves. Branches and trunks affected with cankers from which C. pulchella was isolated also generally bore perithecia of C. pulchella beneath the periderm. Perithecia were nonstromatic and arranged in dense, circinate groups, with elongated necks converging radially and fissuring the periderm. Asci were unitunicate, clavate, and 45 to 55 × 5 to 5.5 µm. Ascospores were allantoid to suballantoid, hyaline, and 5 to 6 × 1 µm. Colonies on potato dextrose agar (PDA) were dark pink to red in their center with a white margin. Conidia were hyaline, allantoid to oblong-ellipsoidal, and (3-) 4 to 6 (-9) × 1.5 to 2 (-2.5) µm. Identification of C. pulchella isolates also was confirmed by sequence comparison in GenBank database using the internal transcribed spacer region (ITS1-5.8S-ITS2) of the rDNA. Sequences of California isolates shared 100% similarity with C. pulchella reference isolate CBS 115999 (EU367451) (2). ITS sequences of the California isolates used in this study were deposited into GenBank (Nos. HM237297 to HM237300). Pathogenicity of four isolates recovered from the margin of active cankers was determined by branch inoculations. In December 2006, 2- to 4-year-old twigs of P. avium cv. Bing were inoculated with a 5-mm cork borer to remove bark and by placing an agar plug from the growing margin of 8-day-old colonies directly into the fresh wound, mycelium side down. Ten branches per isolate were inoculated. Ten control shoots were inoculated with noncolonized agar plugs. Inoculations were covered with vaseline and wrapped with Parafilm to retain moisture. Branches were harvested in July 2007 and taken to the laboratory to be examined for canker development, and the extent of vascular discoloration in each branch was assessed. Isolations from the edge of discolored tissue were conducted to fulfill Koch's postulates. After 8 months, C. pulchella was reisolated from 100% of the inoculated branches. Length of vascular discoloration averaged 62.5 mm in branches inoculated with the four C. pulchella isolates and 16.5 mm in the control twigs. No fungi were reisolated from the slightly discolored tissue of the controls. To our knowledge, this study constitutes the first report of C. pulchella as a pathogen of sweet cherry trees in California. References: (1) M. E. Barr. Mycologia 77:549, 1985. (2) U. Damm et al. Persoonia 20:39, 2008.

Chia (Salvia hispanica L.) seed as an n-3 fatty acid source for finishing pigs: effects on fatty acid composition and fat stability of the meat and internal fat, growth performance, and meat sensory characteristics.

Coronary heart disease is caused by arteriosclerosis, which is triggered by an unbalanced fatty acid profile in the body. Today, Western diets are typically low in n-3 fatty acids and high in SFA and n-6 fatty acids; consequently, healthier foods are needed. Chia seed (Salvia hispanica L.), which contains the greatest known plant source of n-3 alpha-linolenic acid, was fed at the rate of 10 and 20% to finishing pigs, with the goal to determine if this new crop would increase the n-3 content of the meat as has been reported for other n-3 fatty acid-rich crops. The effects of chia on fatty acid composition of the meat, internal fats, growth performance, and meat sensory characteristics were determined. Productive performance was unaffected by dietary treatment. Chia seed modified the fatty acid composition of the meat fat, but not of the internal fat. Significantly (P < 0.05) less palmitic, stearic, and arachidic acids were found with both chia treatments. This is different than trials in which flaxseed, another plant based source of omega-3 fatty acid, has been fed. Alpha-linolenic acid content increased with increasing chia content of the diet; however, only the effect of the 20% ration was significantly (P < 0.05) different from that of the control. Chia seed increased panel member preferences for aroma and flavor of the meat. This study tends to show that chia seems to be a viable feed that can produce healthier pork for human consumption.

Dietary levels of chia: influence on hen weight, egg production and sensory quality, for two strains of hens.

1. Laying hens, 225 white and 225 brown, were fed for 90 d to compare a control diet with diets containing 70, 140, 210 and 280 g/kg chia (Salvia hispanica L.) seed. 2. Hen weight was not significantly affected by diet; however, manure production was less for the hens fed on chia. 3. Egg weight and production, yolk weight, and yolk percentage were determined at d 0, 30, 43, 58, 72 and 90. 4. A sensory evaluation was conducted on eggs produced during the last week of the trial. 5. No significant differences in egg production were found among treatments for the brown hens. 6. With the 280 g/kg chia diet, the white hens produced fewer and lighter eggs than did the hens fed on the control diet. 7. No significant differences were detected in yolk weight until d 90. 8. On this date the yolks produced by the white hens fed on the 70 g/kg chia diet were significantly lighter in weight, whereas the brown hens produced significantly heavier yolks, compared with the hens fed on the control diet. 9. Yolk weight as a percentage of egg weight was lower for white hens throughout the trial except on d 58 with the 140 g/kg chia diet. Significant differences, however, were detected only with the 70 g/ kg chia diet on d 90 and with the 210 g/kg chia diet on d 58, 72 and 90. 10. No significant differences in taste preference or flavour were found among any of the chia treatments and the control.

Chia seed (Salvia hispanica L.) as an omega-3 fatty acid source for broilers: influence on fatty acid composition, cholesterol and fat content of white and dark meats, growth performance, and sensory characteristics.

Five thousand four hundred, 1-d-old, male, Ross 308, broiler chicks were fed for 49 d to compare diets containing 10 and 20% chia (Salvia hispanica L.) seed to a control diet. Cholesterol content, total fat content, and fatty acid composition of white and dark meats were determined at the end of the trial. A taste panel assessed meat flavor and preference. Cholesterol content was not significantly different among treatments; however, the 10% chia diet produced a lower fat content in the dark meat than did the control diet. Palmitic fatty acid content was less in both meat types when chia was fed, with differences being significant (P < 0.05), except for the white meat and the 20% chia diet. alpha-Linolenic fatty acid was significantly higher (P < 0.05) in the white and dark meats with the chia diets. Chia significantly lowered the saturated fatty acid content as well as the saturated:polyunsaturated fatty acid and omega-6:omega-3 ratios of the white and dark meats compared to the control diet. No significant differences in flavor or preference ratings were detected among diets. Body weight and feed conversion were significantly lower with the chia diets than with the control, with weight reductions up to 6.2% recorded with the 20% chia diet.

The emergency medicine subinternship--a standard experience for medical students?

OBJECTIVE: To determine whether emergency medicine (EM)-bound and non-EM-bound senior medical students on the EM subinternship have a uniform experience with respect to number and acuity of patients seen and procedures performed. METHODS: Prospective observational analysis of patient diagnosis and procedures recorded in logs by students at a public teaching hospital over 12 consecutive months. Logs were reviewed blindly and assigned an acuity level based on predetermined criteria. Preselected procedures were categorized as general or surgical and tallied. Identity, specialty choice, gender, and month of rotation for each student were identified. RESULTS: Seventy of 74 students completed logs. On average, 34 EM-bound students saw 59.82 patients (95% CI = 55.19 to 64.45) and performed 10.58 procedures (95% CI = 8.62 to 12.56); 36 non-EM-bound students saw 51.17 patients (95% CI = 47.41 to 54.90) and performed 8.33 procedures (95% CI = 6.81 to 9.84). Univariate analysis showed EM-bound students saw more patients than non-EM-bound students, performed more surgical procedures, and saw higher-acuity patients (p = 0.004; 0.009; 0.016). Multivariate analyses controlled for EM specialty, gender, and month. Significant effects for EM specialty were found (ordinary least squares) for number of patients, procedures, and surgical procedures (p = 0.013; 0.048; 0.011). Logistic regression explaining acuity level showed EM specialty and gender were significant (p = 0.010; 0.038). CONCLUSIONS: In an EM subinternship, experience was variable between EM-bound and non-EM-bound students. Male students saw lower-acuity patients. The EM-bound students saw more patients, higher-acuity patients, and performed more procedures than non-EM-bound cohorts. Emergency medicine educators responsible for medical education should be aware of these differences.

Dietary levels of chia: influence on yolk cholesterol, lipid content and fatty acid composition for two strains of hens.

Four hundred fifty H&N laying hens, half white and half brown, were fed for 90 d to compare a control diet to diets containing 7, 14, 21, and 28% chia (Salvia hispanica L.) seed. Cholesterol content, total fat content, and fatty acid composition of the yolks were determined 30, 43, 58, 72, and 90 d from the start of the trial. Significantly less cholesterol was found in the egg yolks produced by the hens fed the diets with 14, 21, and 28% chia compared with the control, except at Day 90. Palmitic fatty acid content and total saturated fatty acid content decreased as chia percentage increased and as the trial progressed. Total omega-3 fatty acid content was significantly greater (P < 0.05) for both strains for all chia diets compared with the control diet. Total polyunsaturated fatty acid (PUFA) content of the yolks from the chia diets was significantly greater (P < 0.05) than from the control diet. Generally, total PUFA content tended to be highest in the yolks of the white hens.

Undergraduate curriculum. SAEM Undergraduate Education Committee, Society for Academic Emergency Medicine.

The specialty of emergency medicine (EM) is becoming more and more involved in medical school education. The previous article discusses the integration of EM in medical school curricula. This outline was developed by the SAEM Undergraduate Education Committee to offer specific goals and objectives as well as suggestions for implementation of EM concepts into medical school curricula.

The health care experience of patients with low literacy.

OBJECTIVES: To understand the difficulties that patients with poor reading ability have interacting with the health care system and to identify the coping mechanisms they use to deal with these problems. DESIGN: Focus groups and individual interviews with patients who are illiterate and patients with low literacy. SETTING: Two large, urban public hospitals. PARTICIPANTS: Sixty patients with marginal to poor reading abilities as measured by the Rapid Estimate of Adult Literacy in Medicine were interviewed in focus groups or individual interviews. MEASUREMENTS AND MAIN RESULTS: Patients with low literacy harbor a deep sense of shame, which is reinforced by hospital staff who become frustrated or angry when someone cannot complete a form or read instructions. Seeking medical care is intimidating for patients with low literacy because they cannot understand signs and registration forms. Many patients recounted serious medication errors resulting from their inability to read labels. To cope with these problems, the patients with low literacy rely heavily on oral explanations, visual clues, and demonstrations of tasks to learn new material. Most also use a friend or family member as a surrogate reader. CONCLUSIONS: Patients with poor reading ability have important problems accessing the health care system, understanding recommended treatments, and following the instructions of providers. Because of their shame, patients with low literacy may be unwilling to disclose their problem to health care providers, and screening tests of reading ability may be necessary to identify those who need special assistance. Patients' coping mechanisms give insight into possible interventions that may improve their interactions with the health care system.

Use and effectiveness of interpreters in an emergency department.

OBJECTIVE: To determine how often interpreters were used for Spanish- speaking patients, patients' perceived need for an interpreter, and the impact of interpreter use on patients' subjective and objective knowledge of their diagnosis and treatment. DESIGN: Cross-sectional survey. SETTING: Public hospital emergency department. PATIENTS: A total of 467 native Spanish-speaking and 63 English-speaking Latino patients presenting with nonurgent medical problems. MAIN OUTCOME MEASURES: Patients' report of whether an interpreter was used, whether one was needed, self-perceived understanding of diagnosis and treatment, and objective knowledge of discharge instructions. RESULTS: An interpreter was used for 26% of Spanish-speaking patients. For 52%, and interpreter was not used but was not thought to be necessary by the patient. A total of 22% said an interpreter was not used but should have been used. When both the patient's English and the examiner's Spanish were poor, an interpreter was not called 34% of the time, and 87% of the patients who did not have an interpreter thought one should have been used. Nurses and physicians interpreted most frequently (49%), and professional interpreters were used for only 12% of patients. Patients who said an interpreter was not necessary rated their understanding of their disease as good to excellent 67% of the time, compared with 57% of those who used an interpreter and 38% of those who thought an interpreter should have been used (P<.001). For understanding of treatment, the figures were 86%, 82%, and 58%, respectively (P<.001). However, when objective measures of understanding diagnosis and treatment were used, the differences between these groups were smaller and generally not statistically significant. There were no differences between English-speaking Latinos and native Spanish-speakers who said they did not need an interpreter. CONCLUSIONS: Interpreters are often not used despite a perceived need by patients, and the interpreters who are used usually lack formal training in this skill. Language concordance and interpreter use greatly affected patients' perceived understanding of their disease, but a high proportion of patients in all groups had poor knowledge of their diagnosis and recommended treatment.

New-onset atrial fibrillation: when is admission medically justified?

OBJECTIVE: To determine 1) the percentage of patients with new-onset atrial fibrillation for whom admission is medically justified and 2) whether those patients for whom hospitalization is medically justified can be reliably identified in the ED. METHODS: A retrospective, descriptive cohort analysis was performed using consecutive adult patients with new-onset atrial fibrillation seen in an urban, county hospital ED from 1987 through 1992. Admissions were categorized as medically justified if patients were hypotensive (systolic blood pressure < 90 mm Hg), had a diagnosis other than new-onset atrial fibrillation that warranted admission, or had a significant complication during the ED stay or during the subsequent hospitalization. The need for admission was considered to have been apparent during the ED evaluation if the patient fulfilled the above criteria for a medically justified admission while in the ED. RESULTS: Admission was medically justified for 143 of the 216 patients (66%; 95% CI 60-71%) admitted to our institution. For those patients whose admissions were medically justified, the most common concurrent conditions were congestive heart failure and chest pain suggestive of myocardial ischemia. The need for admission was apparent during the ED evaluation for 140 of the 143 patients (98%; 95% CI 94-100%) whose admissions were categorized as medically justified. CONCLUSION: Approximately one third of patients with new-onset atrial fibrillation may not require admission to the hospital. Most patients (98%) for whom admission is medically justified can be reliably identified during the ED evaluation.

Inadequate functional health literacy among patients at two public hospitals.

OBJECTIVE: To determine the ability of patients to complete successfully basic reading and numeracy tasks required to function adequately in the health care setting. DESIGN: Cross-sectional survey. SETTING: Two urban, public hospitals. PATIENTS: A total of 2659 predominantly indigent and minority patients, 1892 English-speaking and 767 Spanish-speaking, presenting for acute care. MAIN OUTCOME MEASURE: Functional health literacy as measured by the Test of Functional Health Literacy in Adults (TOFHLA), an instrument that measures ability to read and understand medical instructions and health care information presented in prose passages and passages containing numerical information (eg, prescription bottle labels and appointment slips). RESULTS: A high proportion of patients were unable to read and understand written basic medical instructions. Of 2659 patients, 1106 (41.6%) were unable to comprehend directions for taking medication on an empty stomach, 691 (26%) were unable to understand information regarding when a next appointment is scheduled, and 1582 (59.5%) could not understand a standard informed consent document. A total of 665 (35.1%) of 1892 English-speaking patients and 473 (61.7%) of 767 Spanish-speaking patients had inadequate or marginal functional health literacy. The prevalence of inadequate or marginal functional health literacy among the elderly (age > or = 60 years) was 81.3% (187/230) for English-speaking patients and 82.6% (57/69) for Spanish-speaking patients, and was significantly higher (P < .001) than in younger patients. CONCLUSIONS: Many patients at our institutions cannot perform the basic reading tasks required to function in the health care environment. Inadequate health literacy may be an important barrier to patients' understanding of their diagnoses and treatments, and to receiving high-quality care.

Pulmonary effects of type V cyclic GMP specific phosphodiesterase inhibition in the anaesthetized guinea-pig.

1. We have investigated the bronchodilator potential of type V phosphodiesterase (PDE V) inhibitors in anaesthetized ventilated guinea-pigs using the potent and selective PDE V inhibitor, SK&F 96231. We have compared its activity to that of salbutamol, the PDE III inhibitors, siguazodan and SK&F 95654 and to the PDE IV inhibitor rolipram. 2. Administered as an i.v. infusion SK&F 96231 (0.6 and 1 mg kg-1 min-1, i.v.) caused a slowly developing inhibition of histamine (100 nmol kg-1, i.v.)-induced bronchoconstriction and elevated tracheal cyclic GMP levels in the anaesthetized guinea-pig. SK&F 96231 (0.1 and 0.3 mg kg-1 min-1, i.v.) was without effect on histamine-induced bronchoconstriction. In the presence of a sub-threshold infusion of SNP (0.1 mumol kg-1 min-1, i.v.) there was a marked enhancement of SK&F 96231-induced inhibition of histamine responses such that at infusion rates that were ineffective alone, SK&F 96231 caused a > 50% inhibition of histamine responses. The stimulation of tracheal cyclic GMP accumulation by SK&F 96231 was also potentiated. 3. Administered directly into the airway, SK&F 96231 (300 micrograms in 5 mg lactose carrier) was largely without effect on histamine-induced bronchoconstriction (4.9 +/- 1.9% inhibition). In the presence of SNP (0.1 mumol kg-1 min-1, i.v.) or isosorbide dinitrate (200 micrograms administered by insufflation into the trachea) there was a marked potentiation of the inhibitory activity of SK&F 96231 (40 +/- 4% and 62 +/- 1.8% respectively). 4. Salbutamol and rolipram (3-300 microg by insufflation) caused a dose-related inhibition of histamine responses with a maximum of 91 +/- 2% and 59 +/- 10% respectively. The PDE III inhibitor, siguazodan,was without effect on histamine responses but they were reduced (27.7 +/- 4.8% at 300 microg) by SK&F95654. There was a marked enhancement of the inhibitory activity of rolipram in the presence of SK&F 95654.5. We conclude that SK&F 96231 has weak anti-spasmogenic activity in the guinea-pig in vivo, we suggest that this is primarily a consequence of a low endogenous guanylate cyclase activity in the airway. The potentiation of the anti-spasmogenic activity of SK&F 96231 by SNP suggests that a combination of PDE V inhibitor and guanylate cyclase agonist might provide significant bronchodilator activity.6. We have established that PDE IV inhibitors are bronchodilators when administered directly into the airway of anaesthetized guinea-pigs but that PDE III inhibitors are only weakly active. The marked enhancement of the inhibitory activity of rolipram by the PDE III inhibitor, SK&F 95654, indicates that inhibitors of both PDE III and PDE IV might offer greater potential as bronchodilators than inhibitors of either isoenzyme alone.

Cyclic nucleotide phosphodiesterase inhibition by imidazopyridines: analogues of sulmazole and isomazole as inhibitors of the cGMP specific phosphodiesterase.

The synthesis and phosphodiesterase (PDE) inhibitory profile of a series of imidazopyridines, including sulmazole and isomazole, on separated PDE isoenzymes are described. The results show that both sulmazole and isomazole are weak inhibitors of PDE III, and their inotropic activity is unlikely to be due to PDE III inhibition alone. Surprisingly, both compounds were found to be significant inhibitors of the cGMP specific isoenzyme, PDE V, and a series of simple 2-substituted phenylimidazo[4,5-b]pyridines have been made to investigate the SAR of PDE activity. This has been shown to be sensitive to chain length, polarity, and the nature of the heteroatom linking group. Potent PDE V inhibitors, many of which are also significant inhibitors of PDE IV, have been identified.

The effect of SK&F 95654, a novel phosphodiesterase inhibitor, on cardiovascular, respiratory and platelet function.

1. SK&F 95654 inhibited the guanosine 3':5'-cyclic monophosphate (cyclic GMP)-inhibited phosphodiesterase (cGI-PDE) with an IC50 value of 0.7 microM. The IC50 values were greater than 100 microM for the other four phosphodiesterase isoenzymes tested. The R-enantiomer of SK&F 95654 (IC50 = 0.35 microM) was a more potent inhibitor of cGI-PDE than was the S-enantiomer (IC50 = 5.3 microM). 2. In the guinea-pig working heart, SK&F 95654 produced a positive inotropic response without altering heart rate. 3. Oral administration of SK&F 95654 to conscious dogs caused dose-dependent increases in left ventricular dp/dtmax in the range 10-50 micrograms kg-1. These positive inotropic responses were maintained for 3 h without simultaneous changes in heart rate or blood pressure. The peak effects on left ventricular dp/dtmax were similar for orally and intravenously administered compound, indicating good oral bioavailability. 4. SK&F 95654 caused a potent inhibition of U46619-induced aggregation in both a human washed platelet suspension (WPS) (IC50 = 70 nM) and in human platelet-rich plasma (PRP) (IC50 = 60 nM), indicating that the compound shows negligible plasma binding. 5. The R-enantiomer of SK&F 95654 was twenty fold more potent as an inhibitor of platelet aggregation than was the S-enantiomer. The similarity of this ratio to that obtained on the cGI-PDE suggests that SK&F 95654 inhibits platelet aggregation via its effects on cGI-PDE. This was also indicated by studies which showed that SK&F 95654 increased adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels and activated cyclic AMP-dependent protein kinase in human platelets. 6. Collagen-induced aggregation of rat PRP was also inhibited by SK&F 95654 (ICso = 65 nM). The effects of SK&F 95654, administered intravenously, on ex vivo platelet aggregation were studied in the conscious rat. At 1 mg kg-', SK&F 95654 inhibited aggregation for at least 4 h post dose and was more potent than the two other cGI-PDE inhibitors studied (siguazodan and SK&F 94120).7. In contrast to its potent effects on heart and platelets, SK&F 95654 caused only a modest relaxation of histamine- or U46619-induced bronchoconstriction in the anaesthetized, ventilated guinea-pig.8. Taken together, these results indicate that SK&F 95654 may be a suitable agent for the treatment of congestive heart failure.

Flumazenil for the reversal of refractory benzodiazepine-induced shock.

Benzodiazepines are known to cause central nervous system and centrally mediated cardiovascular depression. The benzodiazepine antagonist flumazenil has been shown to antagonize benzodiazepine-induced central nervous system depression. We report a case in which cardiovascular depression secondary to benzodiazepine use was reversed by this agent.

1,4-bis(3-oxo-2,3-dihydropyridazin-6-yl)benzene analogues: potent phosphodiesterase inhibitors and inodilators.

1,4-Bis(3-oxo-2,3-dihydropyridazin-6-yl)benzene and a series of related bis(azinone) compounds were synthesized. These novel compounds were evaluated for inhibition of the low Km, cAMP-selective, cGMP-inhibited phosphodiesterase (PDE III) derived from cat heart and hemodynamic activity in the ganglion- and beta-blocked anesthetized cat. The most potent PDE III inhibitor of the series was 6-[4-(5-methyl-3-oxo-2,3,4,5-tetrahydropyridazin-6-yl)-phenyl]p yridazin- 3(2H)-one (IC50 = 0.07 microM), which also retained the greatest inotrope and vasodilator (inodilator) potency (ED50 for first derivative of left ventricular pressure (dLVP/dt(max)) = 0.02 mumol/kg, ED15 for 15% fall in perfusion pressure = 0.01 mumol/kg). The structure-activity relationships observed within the bis(azinone) series were consistent with those reported for formally analogous 6-(4-substituted-phenyl)pyridazin-3(2H)-one-based PDE III-inhibiting inodilators with less-extended phenyl substituents (see e.g. Sircar et al. J. Med. Chem. 1987, 30, 1955, Moos et al. J. Med. Chem. 1987, 30, 1963). PDE III inhibitory potency is associated with overall planar topology of the phenylpyridazinone moiety and the presence of two critically separated electronegative centers. A methyl group at the 5-position of a dihydropyridazinone ring leads to enhanced potency. However, the generally higher levels of PDE III inhibitory potency shown by compounds in the bis(azinone) series relative to earlier 6-(4-substituted-phenyl)pyridazin-3(2H)-one derivatives appears to derive from a closer to optimal separation of two interacting points in the inhibitor molecule achieved through the more extended bis(azinone) structure. Correlation between the pharmacological and PDE III inhibitory activities of compounds in the bis(azinone) series provides additional evidence for PDE III being an important mediator of inodilator action.

Trauma and the full moon: a waning theory.

There exists a popular belief in the causal relationship between the moon's phase and the incidence of major trauma. In this retrospective study we reviewed 1,444 trauma victims admitted to the hospital during one calendar year. Full moons were defined as three-day periods in the 29.531-day lunar cycle, with the middle day being described in the world almanac as the full moon. Victims of violence included those patients sustaining blunt assault, gunshot wounds, and stabbings. There was no statistical difference in number of trauma admissions between the full moon, 129 patients per 36 days (mean, 3.58), and nonfull moon days, 1,315 patients per 330 days (mean, 3.98). Mortality rate, 5.4% versus 10.3%; mean Injury Severity Score, 13 versus 15; and mean length of stay, ten versus 12 days, were not significantly different during the full moon and nonfull moon days. Victims of violence were admitted at a similar frequency on full moon, 16 patients per 36 days (mean, 0.444), and nonfull moon days, 183 patients per 330 days (mean, 0.555). We conclude that the belief in the deleterious effects of the full moon on major trauma is statistically unfounded.