Tifluadom, a kappa-opiate agonist, acts as a peripheral cholecystokinin receptor antagonist

Tifluadom, a benzodiazepine kappa-opiate agonist, stereoselectively inhibited the binding of 125I-CCK to pancreatic membranes (IC50 = 47 nM). Several other opiate agonists were ineffective. Scatchard analysis indicated the inhibition of CCK binding by tifluadom was competitive in nature. Tifluadom (1 microM) did not displace 125I-CCK binding to brain tissue or 125I-gastrin binding to fundic glands. In the isolated guinea pig gallbladder, tifluadom antagonized CCK-8 induced contractions with an estimated pA2 of 6.8. These data demonstrate that tifluadom is a peripherally selective CCK antagonist. This unique action could contribute to its reported analgesic and appetite stimulatory properties.     

The development ofAmblyomma americanum andDermacentor variabilis (Acari: Ixodidae) fed on rabbits immunized with tick hemolymph

The possibility of interfering with the normal function of tick hemolymph using antihemolymph antibodies taken in with the bloodmeal, was investigated. Cell free hemolymph from repleteAmblyomma americanum andDermacentor variabilis ticks was used to immunize rabbits. Immunized rabbits developed high antihemolymph antibody titers (ca. 10⁵) and had no ill side effects. Rabbits were simultaneously infested with larvae, nymphs, and adult ticks. The biological performance of ticks fed on immunized rabbits was virtually identical to that of ticks fed on nonimmunized rabbits. Usually, the mean engorgement weights of nymphs and females and the weights of the egg masses of both species were slightly higher for ticks fed on the nonimmunized rabbits but differences were not significant (P>0.05) due to a large standard deviation. The possibility of deactivating a single hemolymph component with specific antibodies is discussed.Journal article 4979 of the Agricultural Experiment Station, Oklahoma State University, Stillwater, OK, USA     

Atmungserregung und zentrale Erregbarkeit bei Ventilationsstörungen der Lunge und bei respiratorischer Acidose

Zusammenfassung Atemphysiologische Untersuchungen an 19 Patienten mit Ventilationsstörungen der Lunge mit dem Atmungsanalepticum Micoren ergeben eine Ventilationssteigerung um 60% des Ausgangswertes, eine Abnahme der arteriellen CO₂-Spannung und eine Zunahme des Blut-p_H, somit eine ventilationsbedingte Verschiebung der Blutgase in Richtung einer relativen respiratorischen Alkalose. Im Mittelpunkt der Untersuchung steht die Frage einer über die Atmungserregung hinaus bei der respiratorischen Acidose und Atemdepression erzielbaren Erregbarkeitsänderung der Zentren. Im Gegensatz zu Patienten ohne respiratorische Acidose läßt sich bei Kranken mit respiratorischer Acidose eine Steigerung der Erregbarkeit auf CO₂-Reiz und eine wahrscheinlich begrenzte Verzögerung der unter O₂-Atmung drohenden zentralen Depression nachweisen. Indikationen und klinische Gesichtspunkte einer medikamentösen Atmungserregung werden unter besonderer Berücksichtigung der respiratorischen Acidose besprochen.Mit freundlicher Unterstützung der Deutschen Forschungsgemeinschaft.     

Coordinated Strategy for a Model-Based Decision Support Tool for Coronavirus Disease,Utah, USA

The coronavirus disease pandemic has highlighted the key role epidemiologic models play in supporting public health decision-making. In particular, these models provide estimates of outbreak potential when data are scarce and decision-making is critical and urgent. We document the integrated modeling response used in the US state of Utah early in the coronavirus disease pandemic, which brought together a diverse set of technical experts and public health and healthcare officials and led to an evidence-based response to the pandemic. We describe how we adapted a standard epidemiologic model; harmonized the outputs across modeling groups; and maintained a constant dialogue with policymakers at multiple levels of government to produce timely, evidence-based, and coordinated public health recommendations and interventions during the first wave of the pandemic. This framework continues to support the state’s response to ongoing outbreaks and can be applied in other settings to address unique public health challenges.     

The use of intravenous lidocaine for postoperative pain and recovery: international consensus statement on efficacy and safety

Intravenous lidocaine is used widely for its effect on postoperative pain and recovery but it can be, and has been, fatal when used inappropriately and incorrectly. The risk-benefit ratio of i.v. lidocaine varies with type of surgery and with patient factors such as comorbidity (including pre-existing chronic pain). This consensus statement aims to address three questions. First, does i.v. lidocaine effectively reduce postoperative pain and facilitate recovery? Second, is i.v. lidocaine safe? Third, does the fact that i.v. lidocaine is not licensed for this indication affect its use? We suggest that i.v. lidocaine should be regarded as a ‘high-risk’ medicine. Individual anaesthetists may feel that, in selected patients, i.v. lidocaine may be beneficial as part of a multimodal peri-operative pain management strategy. This approach should be approved by hospital medication governance systems, and the individual clinical decision should be made with properly informed consent from the patient concerned. If i.v. lidocaine is used, we recommend an initial dose of no more than 1.5 mg.kg^-1, calculated using the patient’s ideal body weight and given as an infusion over 10 min. Thereafter, an infusion of no more than 1.5 mg.kg^-1.h^-1 for no longer than 24 h is recommended, subject to review and re-assessment. Intravenous lidocaine should not be used at the same time as, or within the period of action of, other local anaesthetic interventions. This includes not starting i.v. lidocaine within 4 h after any nerve block, and not performing any nerve block until 4 h after discontinuing an i.v. lidocaine infusion.     

Identification of natural antibodies to interleukin-18 in the sera of normal humans and three nonhuman primate species

Natural antibodies to cytokines can be found in the sera of normal healthy individuals in the absence of specific immunostimulation. However, the function, impact, and purpose of natural antibody development have yet to be fully elucidated. Interleukin (IL)-18 is a cytokine that exerts proinflammatory activities and induces natural killer (NK) cell activity. Recombinant human IL-18 (rHuIL-18) is currently in development as a cancer immunotherapy. In this study, the presence of natural antibodies to IL-18 in the sera of normal humans and three nonhuman primate species was evaluated by electrochemiluminescence immunoassay (ECLIA). Of the human sera tested, 6 of 47 samples were positive for natural antibodies to IL-18. Of the nonhuman primate sera tested, 22 of 80 cynomolgus monkey samples, 4 of 31 rhesus monkey samples, and 2 of 20 chimpanzee samples were positive for natural antibodies to IL-18. Natural anti-IL-18 antibodies were neutralizing in 5 of 22 cynomolgus and 2 of 4 rhesus sera. None of the chimpanzee or human sera were able to neutralize IL-18 induction of interferon (IFN)-gamma in vitro. In vivo activity of rHuIL-18 was compared in IL-18 natural antibody-positive and -negative cynomolgus monkeys. The presence of natural antibodies to IL-18 did not alter rHuIL-18 systemic exposure levels, induction of neopterin, or induction of treatment-induced antibodies following intravenous administration of rHuIL-18. In conclusion, our data indicate that, as has been found with other cytokines, natural anti-IL-18 antibodies are relatively common. Moreover, natural anti-IL-18 antibodies do not appear to influence rHuIL-18 activity in vivo and are not predictive of a heightened immune response, suggesting that natural anti-IL-18 antibodies do not impact IL-18 therapy. Finally, our data suggest that the ability to detect natural anti-cytokine antibodies may be a useful measure of the adequacy of an assay for deployment in clinical trials.     

Clinical aspects of vasospasm

In summary, clinically significant vasospasm is characterized by several relatively consistent features. Those patients most at risk are adults, of either sex, who have had a subarachnoid hemorrhage about 4 to 9 days previously; who had a poor clinical grade on admission; and in whom a CT scan taken 24 to 48 hours after the ictus showed a thick layer of blood surrounding one or more of the major cerebral vessels. Initially afebrile, affected patients later develop a steady low-grade fever and may have an elevated WBC count, but no infectious source of fever can be found. Patients complain of worsening headache, but not as bad as the one a few days ago; the neck may feel a little more stiff. The pulse is slightly faster than usual, the blood pressure perhaps a bit higher; however, the ECG shows only "cerebral T waves." An antifibrinolytic agent may have been used. The serum sodium concentration has dropped significantly. Such patients need a more thorough examination than usual, directed toward more subtle neurologic signs, and a few extra checks during the day by both physician and nurses, so that we can apply what remedies we have when the patients are just "a little more confused," rather than later, when they are exhibiting decerebrate posturing and coma.     

Accessing an understudied population in behavioral HIV/AIDS research: low income African American women

Most HIV/AIDS behavior research involving African American women has focused on traditional high risk populations, such as those in drug treatment centers, STD clinics, and hospitals. Few studies have examined the health needs and behaviors of African American women in the general population (i.e., working mothers and homemakers). The Parent Health Project examined beliefs and concepts of illness, including AIDS, of low income African American mothers of young children. We used a variety of methods of community outreach and recruitment strategies to gain access and trust from these African American women, including (1) recruitment of women who had children in a related research project, (2) subject reimbursement, and (3) culturally sensitive community based outreach. Of approximately 200 women contacted, 147 (74%) agreed to participate in a two-hour face-to-face interview about concepts of health and illness. Through our efforts, we were able to gain access to a population generally not studies in HIV/AIDS research. We were also exposed to a number of issues, concerns and behaviors faced by women not classified as high risk, yet who are at risk as a result of their own and/or their sexual partner's(s) risk behaviors.     

Human rabies postexposure prophylaxis during a raccoon rabies epizootic in New York, 1993 and 1994.

We describe the epidemiology of human rabies postexposure prophylaxis (PEP) in four upstate New York counties during the 1st and 2nd year of a raccoon rabies epizootic. We obtained data from records of 1,173 persons whose rabies PEP was reported to local health departments in 1993 and 1994. Mean annual PEP incidence rates were highest in rural counties, in summer, and in patients 10 to 14 and 35 to 44 years of age. PEP given after bites was primarily associated with unvaccinated dogs and cats, but most (70%) was not attributable to bites. Although pet vaccination and stray animal control, which target direct exposure, remain the cornerstones of human rabies prevention, the risk for rabies by the nonbite route (e. g., raccoon saliva on pet dogs' and cats' fur) should also be considered.     

Odontogenic myxoma

The odontogenic myxoma is an uncommon tumor that has the potential for extensive bony destruction, extension into surrounding structures, and a relatively high recurrence rate. Treatment often requires bone resection. The bland histologic features of a monotonous proliferation of a loose, mesenchymal fibrous tissue that lacks atypia may easily lead to a misdiagnosis. The primitive dental pulp, the dental papilla, and the tooth follicle are histologically similar to myxoma. These soft tissue fragments often separate from extracted developing teeth that are submitted to the pathologist and may easily be misinterpreted as an odontogenic myxoma. The pathologist must have good clinical and radiographic correlation to avoid a misdiagnosis and to prevent unnecessary additional surgery.