The future of pain management in managed care.

Pain management has made great strides in clinical practice and education, and in research documenting its effectiveness on pain relief, functional improvement, and cost. The profile of pain in managed care settings has recently been raised, notably because of the trend toward replacing inexpensive generic drugs with new and expensive drugs for pain treatment. Managed care organizations have greater motivation to focus on pain care because of recent regulatory initiatives, new accreditation standards, and legal precedents. In order for pain programs to improve the quality of pain care in MCOs, they must balance the complex needs of patients with pain with the financial constraints of the managed care setting.

[Is headache a women's disease?]. / Er hodepine en kvinnesykdom?

Headache is experienced by the majority of people in the population. The prevalence of migraine in women is greater than in men, and there are indications that this is also the case for non-migrainous headache. We reviewed available literature on headache epidemiology for documented knowledge on the prevalence of non-migrainous headache in men and women and severity of the disease. In this article we present a summary of 13 studies of the general population where prevalence of the common headache in men and women could be expressed as a gender ratio. The studies covered the period 1977-96, and included a total number of 75,000 people. The review confirms that non-migrainous headache is a women's disease, in that a female dominated gender ratio was found consistently throughout the studies. However, female dominance is not as great as for migraine. Varying definitions of headache resulted in a great variation in prevalence across the studies, but this did not influence the gender ratio. From the literature available no conclusions can be drawn on gender differences related to severity or frequency of the non-migrainous headache. These areas need to be explored further in order to provide adequate health care for men and women suffering from headache.

Prevention of suicides in Penal Institutions in The Netherlands.

As in other countries, suicides are a matter of great concern in The Netherlands. This article addresses suicide-prevention measures in prisons in The Netherlands. It focuses primarily on screening, monitoring, incapacitation, psychological support, and transferal to specialized institutions. In addition, it asks which practices are common, which can be improved, and the limitations of certain strategies. Relatively speaking, The Netherlands does not appear to be doing too badly in terms of preventive measures, although there is room for improvement.

Long-term impact of perinatal bereavement. Comparison of grief reactions after intrauterine versus neonatal death.

OBJECTIVE: To investigate possible differences in emotional impact on parents following either a deliberate intrauterine death or a neonatal death in extremely preterm growth retarded infants. DESIGN: Retrospectively matched study by audiotaped semi-structured interview, 3-9 years after the perinatal loss. RESULTS: Nineteen couples (ten in the intrauterine death group and nine in the neonatal death group) consented to participate. More than 50% of the intrauterine death group couples could not share or discuss their emotions. Most partners in this group did not feel the loss of their own child. Discongruent grieving between partners was more pronounced in the intrauterine death group and could be identified as a risk factor for prolonged and abnormal grief reactions. Four couples (three in the intrauterine death group and one in the neonatal death group) developed long-term emotional disturbance and psychosocial problems. Long-term follow-up in both groups was failing remarkably. CONCLUSION: Assimilating a non-intervention policy followed by fetal death requires different skills and is more complicated than grief support around an early neonatal death. Follow-up is essential to identify the couple 'at risk' and to mobilize extra support.

Hypericum treatment of mild depressions with somatic symptoms.

In a randomized, placebo-controlled, double-blind study, 39 patients with depression with somatic symptoms were treated with hypericum extract LI 160. The therapy lasted for 4 weeks; the dosage was 300 mg three times daily. At the onset of the study as well as after 2 and 4 weeks, the following criteria were analyzed: HAMD, B-L, CGI, and vegetative symptoms. The results show a significant improvement in the active treatment group at the 5% level as compared to placebo. Seventy percent of the patients treated with LI 160 were free of symptoms after 4 weeks. Typical symptoms of the depression such as lack of activity, tiredness, fatigue, and disturbed sleep, were especially responsive. In no case were any undesirable side effects observed.

Multiple domains of botulinum neurotoxin contribute to its inhibition of transmitter release in Aplysia neurons.

The binding, internalization, and inhibition of transmitter release by botulinum neurotoxin (BoNT) was investigated using the intact toxin, its heavy (HC) or light (LC) chains, and a proteolytic fragment thereof. In Aplysia neurons, blockade of acetylcholine release upon external application of BoNT types A or E was prevented by reducing the temperature to 10 degrees C, due to arresting intoxication at the membrane binding step. At this low temperature, type A HC, H2 (comprised of the N-terminal of HC), or H2L (H2 disulfide-linked to LC) antagonized the neuroparalytic action of BoNT A or E, indicating that the latter bind saturably to common ecto-acceptor via the H2 region. In contrast, H2L was unable to counteract BoNT-induced paralysis at the murine neuromuscular junction. In accordance with this species difference, unlike native BoNT, saturable binding of 125I-labeled H2L could not be detected in mammalian peripheral or central nerve terminals. Possibly, more stringent structural requirements form the basis of the toxin's greater effectiveness in inhibiting neurotransmission at mouse nerve muscle synapses than Aplysia nerve terminals. In further identification of functional domains in the toxin, an unprocessed single-chain form of BoNT type E was found to be ineffective when applied extra- or intracellularly to Aplysia neurons. Notably, bath application of the latter to a neuron preinjected with HC, but not H2L or LC, resulted in a blockade of release. This shows that the single-chain species can become internalized and requires, not only LC, but also processed HC for its inhibitory action; consistently, the proteolyzed form of BoNT E was active.

Effects of botulinum neurotoxin and Lambert-Eaton myasthenic syndrome IgG at mouse nerve terminals.

The interaction between two presynaptically acting agents, Lambert-Eaton myasthenic syndrome (LEMS) immunoglobulin G (IgG) and purified botulinum neurotoxin (BoNT) type A, was studied. Intracellular microelectrode recordings were carried out on mouse muscles after injection with LEMS IgG. BoNT was either injected before recordings were made or applied in vitro. The time course of the in vitro actions of BoNT on miniature end-plate potential and end-plate potential parameters were not affected by pretreatment with LEMS IgG. After in vivo injection of BoNT, end-plate potential quantal content was reduced to less than 2% of control values, whether or not LEMS IgG had also been previously given. Quantitative electron-microscope autoradiographical analysis showed that neither the binding of 125I-BoNT to acceptors on the nerve terminal membrane nor the pattern of its internalisation were affected by pretreatment with LEMS IgG. We conclude that the effects of BoNT are not affected by LEMS IgG, suggesting different presynaptic binding sites for the two agents.

High-performance displacement chromatography of melanotropins and their derivatives.

Mixtures containing derivatives of the biological active peptide alpha-melanocyte stimulating hormone (alpha-MSH) or beta-melanocyte stimulating hormone (beta-MSH) were purified by using reversed-phase chromatography in the displacement mode. On a 250 x 4.6 mm octadecyl silica column and with instrumentation used in analytical high-performance liquid chromatography about 30 mg of the peptide mixture were separated by using an aqueous solution of benzyldimethyldodecylamonium bromide as the displacer in a single chromatographic run. The results demonstrate the advantages of displacement over elution in preparative chromatography of peptides on the scale of tens of milligrams that is typical for physiological tissue extracts and in solid-phase peptide synthesis.

The effects of in vitro application of purified botulinum neurotoxin at mouse motor nerve terminals.

1. Purified botulinum neurotoxin type A (10 nM) was applied in vitro to mouse diaphragm muscles. Intracellular micro-electrode recordings were made continuously in single fibres. 2. This treatment reduced end-plate potential (e.p.p.) amplitudes with a time to half-maximal effect of about 75 min at 22-25 degrees C. E.p.p. rise-times remained fast and unaffected by the toxin. 3. Miniature end-plate potential (m.e.p.p.) frequency was reduced by the toxin to less than 5% of control frequency, and followed a similar time course to the block of e.p.p. amplitudes. The m.e.p.p. rise-time and coefficient of variation (c.v.) of m.e.p.p. amplitude distributions both increased, but the time course of these increases lagged significantly behind the change in frequency. 4. A population of slow rise-time m.e.p.p.s was present in controls at low frequency. This population was found to be unaffected by the toxin. 5. The above-detailed in vitro changes could be explained by the toxin acting by a single common mechanism to inhibit the release process underlying both fast rise-time m.e.p.p.s and e.p.p.s. A distinct release process, which leads to slow rise-time m.e.p.p.s, was unaffected by the toxin.

Differentiation between classically conditioned and cognitively based neurotic fears: two pilot studies.

The ability of clinical trainees to learn to distinguish between classically conditioned and cognitively based neurotic fears was examined in two small-scale studies. The first study showed that they readily learned to make the distinction on the basis of transcripts of key excerpts of actual patient sessions, and that ability to do so increased with training. The second study showed a high degree of inter-rater reliability among assessor ratings of fear type on the basis of independent interviews of phobic patients.

Assay of melanotropic peptides in an in vitro mammalian system.

A reproducible and sensitive assay for melanotropic agents is described employing mouse melanoma cells in culture and measuring tyrosinase activity in terms of production of tritiated water from L-(ring-3,5-3H)-tyrosine. Molar concentrations of peptides inducing one-half maximal stimulation of tyrosinase activity were: beta-MSH, 1 +/- 2 x 10(-9); alpha-MSH and Beta h-LPH, 1 +/- 2 x 10(-8); ACTHp, 1 +/- 2 x 10(-7). Beta p 9-18-MSH and melanotropin potentiating factor, beta s 88-91-LPH exhibited no activity at concentrations as high as 10(-5)M.

An interresponse time analysis of variable-ratio punishment.

An interresponse time analysis was used to study the effects of variable-ratio punishment schedules on the temporal pattern of reinforced responding. Twelve pigeons responded on a baseline variable-interval schedule of food reinforcement. A variable-ratio ten schedule of electric shock punishment was then introduced. The shock intensity was systematically increased to the highest intensity at which responding could be maintained. At this intensity, the mean variable-ratio value was increased and then decreased. Variable-ratio punishment resulted in an increased relative frequency of very short unreinforced interresponse times (response bursting). Increased response bursting accounted for instances of response rate facilitation. In addition, shock was followed by interresponse times of decreasing mean length over the first several responses after shock.

Measurement of atmospheric vinyl chloride.

Methods for atmospheric vinyl chloride measurement have been reviewed. The lowest detection limits and most specific measurement are achieved by scrubbing atmospheric samples with activated charcoal, desorbing the vinyl chloride, and assaying it by gas chromatography (GC). NIOSH currently recommends collecting samples using tubes packed with 150 mg of coconut shell charcoal, desorbing with carbon disulfide, and analyzing by GC equipped with flame-ionization detection (FID); the method is capable of detecting less than 1 ppm vinyl chloride and has an apparent recovery of abo the ppb level with no loss of accuracy or precision. Some field methods, such as infrared analysis and conductivity measurement, are capable of detecting 1 ppm or lower but are subject to interferences by other contaminants; th-y could be useful for evaluating sources of vinyl chloride leaks and for continuous monitoring. Permeation tubes are superior to gravimetric or volumetric methods for generating atmospheres of known vinyl chloride concentration.