HP 818: A centrally acting analgesic with neuroleptic properties

HP 818 (1-benzoyl-6-fluoro-3-(1-methyl-4-piperidinyl)-1H-indazole) exhibits the profile of a potent nonnarcotic analgesic with neuroleptic properties. HP 818 blocks the effects of chemical (phenylquinone), pressure (tail clip), and radiant heat (tail flick) painful stimuli in mice (ED₅₀ values of 0.3, 1.2, and 4.1 mg/kg s.c., respectively). This compound displays antinociceptive activity by the subcutaneous, oral, and intravenous routes of administration. It is also effective in the shock titration assay in squirrel monkeys and in a model of surgically induced pain. The rank order of potency of HP 818 and several other standard compounds in these tests for analgesia was Innovar > fentanyl > HP 818 > codeine > droperidol. In addition to its antinociceptive effects, HP 818 possesses neuroleptic properties. It is active in the climbing mouse, pole climb avoidance, and intracranial self-stimulation assays (ED₅₀ values of 1.8, 1.7, and 2.5 mg/kg i.p., respectively). Moreover, HP 818 inhibits amphetamine- and apomorphine-induced stereotypy, indicative of D₂-dopaminergic blocking properties. HP 818, unlike typical neuroleptic agents, does not induce supersensitivity to the effects of apomorphine when administered chronically in mice. In contrast to the clinical standard neuroleptanalgesic Innovar, HP 818 (1.0–3.0 mg/kg i.v.) produces no significant cardiovascular or respiratory changes in the anesthetized dog. Thus, HP 818 is potentially an effective presurgical medication due to its nonnarcotic analgesic activity and sedative neuroleptic effects, along with its lack of limiting cardiorespiratory side effects.     

Dysphagia due to cervical osteophytes

Summary Five patients are described who had cervical fusion for dysphagia. A prospective study showed that this symptom was rare in those presenting with cervical spondylosis. Excision of the osteophytes together with an anterior fusion is required.

---

Résumé Cinq malades, dont le symptôme principal était une dysphagie, ont du subir une arthrodèse du rachis cervical. Une étude rétrospective a montré que ce symptôme était rare chez les malades atteints d'arthrose du rachis cervical. L'ablation des ostéophytes, associée à une fusion vertébrale antérieure, paraît le meilleur traitement.

     

Interobserver variability in neonatal cranial ultrasonography

The reliability of cranial ultrasound diagnosis in the premature neonate was examined using data from an ongoing multicentre study of the epidemiology and long-term consequences of neonatal brain haemorrhage. First week ultrasound films (obtained at 4 hours, 24 hours and 7 days) from 60 study subjects were randomly selected for independent review by two groups of experienced interpreters, and results were recorded separately for observations (i.e. presence or absence of an abnormal echodense area on a film) and interpretations (i.e. presence or absence of haemorrhage or ventricular dilatation) in each hemisphere. Because of deaths in the first week of life, the total number of films examined was 138. Concordance on the presence or absence of an abnormal echodensity was examined for each individual film for three areas of interest: the germinal matrix, the ventricles and the parenchyma. Concordance on the presence or absence of haemorrhage or ventricular dilatation was examined only for the seventh-day film, or the final film prior to death. Finally, concordance was analysed with the diagnostic interpretations grouped into categories thought to differ prognostically for long-term outcome. In general, concordance was poorest for germinal matrix lesions and best for parenchymal lesions. Concordance was lower for observations made on each individual film than it was for interpretation of the final film in each case. Fifty-five of 60 cases (92%) were assigned to the same major prognostic category by both readers. Ultrasound review conferences were held periodically and there was evidence that concordance in ultrasound reading and interpretation improved during the course of the study.     

Health assessment of environmental pollutants: proliferative and degenerative diseases

In order to achieve a balanced approach to risk assessment between carcinogenic and non-carcinogenic health effects one must examine the risk of disease or death in the general population exposed to a particular air pollutant that can be related quantitatively to intensity and duration of exposures (National Academy of Sciences, 1983). Such risk assessment should be based upon careful evaluation of scientific findings of dose-response relationships in the chronically exposed population. Quantitative assessment of environmentally produced disease in man has proven to be complex and demanding. A variety of factors play important roles in this task. As an example, there are induction-latency periods for chronic diseases, including cancer, which may range from five to twenty-five years. The diseases themselves, whether proliferative or degenerative, may follow several stages of progression. There is only sparse epidemiological data on serious health effects that may be due to environmental as compared to occupational exposures. Exposures to chemical or radiological air contaminants do not occur singly but to a multiplicity of agents, and disease processes are frequently markedly affected by the interaction of a variety of factors, particularly that of cigarette smoking. There is growing recognition of potentially sensitive subpopulations, including the elderly and the very young, but adequate techniques for assessing the magnitude of increased risks to these groups have not yet been developed.     

Office-based surgery and anesthesia: Where are we now?

At the time of publication of this journal, the Center for Urinary Control in Memphis, Tennessee, has performed eight office-based surgical procedures using anesthesia. Patients were aged between 56 and 80 years, and all were ASA I–III class. The procedures involved either cystoscopy with collagen injection into the bladder neck or cystoscopy with indigo laser treatment of the prostate. All patients were prepared by the anesthesiologist prior to the day of surgery, and appropriate laboratory tests were ordered and evaluated. All patients did very well, the surgical field was quiet, and each procedure went very smoothly. Each patient tolerated anesthesia without any adverse effect, was recovered in an adjacent examination room, and was extremely satisfied upon discharge from the office. Anesthesia was induced with Propofol (Diprivan) and sublimaze, maintained with a Propofol infusion and oxygen. The surgeon performed a periprostatic block on the patient having the Indigo laser treatment.     

Respiratory syncytial virus infection and meningococcal disease.

Although viral respiratory tract infections may predispose to meningococcal disease, strong evidence that they do so exists only for influenza. Data on laboratory reported cases of respiratory syncytial virus (RSV) infections and meningococcal disease in England and Wales from mid-1989 to mid-1994 were analysed. Although the rise in RSV cases preceded the rise in meningococcal disease cases each winter, the interval between the rise and fall of the two diseases was inconsistent, no association was found between time series after removal of the seasonal component, and there was no evidence that more cases of meningococcal disease occurred in winters with more RSV disease. RSV may have less effect on the two most likely mechanisms whereby influenza predisposes to meningococcal disease, namely lowered immunity and impaired pharyngeal defences.