The link between maltreatment and juvenile firesetting: correlates and underlying mechanisms.

OBJECTIVE: Despite the widely held belief that abuse is a risk factor for childhood firesetting, the role of maltreatment in firesetting is largely unexplored. This study reports on a sample of children and adolescents referred to a brief assessment and intervention program for juvenile firesetters. Firesetting histories of maltreated youth were compared to a group of firesetting youth with no maltreatment history. METHODS: Participants included 205 children and youth aged 4-17 years and their caregivers. Assessments were completed with a standardized protocol. Forty-eight percent of the sample had a history of maltreatment as reported by caregivers; 26% of the sample had experienced more than one type of maltreatment. RESULTS: When compared to the non-maltreated group, children with histories of maltreatment demonstrated more frequent fire involvement, more versatility regarding ignition sources and targets, and a greater likelihood of an immediate family stressor as a motive for firesetting (all p<.05). Maltreated children were more likely to become involved with fire out of anger (p=.001), and there was also a trend towards higher rates of recidivism (p=.07). Children's externalizing behavior partially mediated the influence of maltreatment on specific fire-related outcomes of children (OR=1.10; 95% CI=1.04-1.17; p=.001). CONCLUSIONS: Within a juvenile firesetting population, the presence of maltreatment is a risk factor for a more severe course of firesetting. The findings also suggest that the link between maltreatment and firesetting is operating partially through heightened emotional and behavioral difficulties. PRACTICE IMPLICATIONS: This study demonstrates that maltreatment is a risk factor that contributes to a more severe course of juvenile fire involvement, and that the link between maltreatment and firesetting operates largely through heightened behavioral and emotional difficulties. These findings highlight the need for mental health clinicians to (a) be aware that these two serious clinical issues frequently co-occur, (b) screen for fire-related behaviors and maltreatment during general assessments, and (c) consider maltreatment status when thinking about the risk of firesetting.

A feedback-controlled dynamic linear actuator to test foot withdrawal thresholds in rat.

We describe a method for evaluating the threshold for cutaneous mechanical sensation in rodents, based on a stimulator that drives a probe against the plantar surface of the foot. The stimulator applies loads that can be either constant or linearly increased. We describe withdrawal responses, including forms of movement that precede foot withdrawals. With constant stimuli, response latency declines in a nonlinear fashion as stimulus magnitude is increased. With ramped stimuli the effect of loading rate is complex, reflecting both the rate of change of the stimulus and the animal's reaction time. We demonstrate the utility of using ramped stimuli in experiments that show that thresholds vary spatially across the foot and experiments that show that intradermal capsaicin injections cause allodynia but not hyperalgesia.

Alternative therapy of earth elements increases the chondroprotective effects of chondroitin sulfate in mice.

The administration of mineral sulphur water is an alternative experimental approach for the treatment of rheumatic diseases, such as osteoarthritis (OA), that cause the degeneration of bone and cartilage and sufferance to the patients. Chondroitin sulfate (CS) is a symptomatic slow acting nutropeucital agent currently used in molecular therapy of OA. Therefore, we have studied the role and efficacy of the selective soil paste from the mineral sulphur enriched spring (mud)-therapy alone or in combination with CS in the treatment of OA. The study was performed on 40 C57 Black 6N mice, an experimental model which spontaneously develop an osteoarthritic process. The animals were divided in 4 groups and were treated with the single agents or with the combination. After 30 days of treatment all the mice were sacrificed and right knees and blood were collected. It was found that CS determined a reduction of radiological and histological features of chondrodegeneration and that mud-therapy increased the effects of CS in the animal group treated with the combination. However, the effects of thermal therapy alone were not statistically significant. Since OA is characterized by an increase of the production of nitric oxide (NO) by chondrocytes in extracellular matrix with its consequent elevation in serum and synovial fluid, we have evaluated the effects of the treatments on serum NO levels. CS alone induced a statistically significant reduction of NO serum levels (90+/-13 micromM vs 219+/-60 microM of control group, P<0.05) while mud-therapy alone induced a not statistically significant reduction of serum NO (170+/-62 microM, P>0.05). However, the latter strongly potentiated the decrease of serum NO induced by CS (31+/-1.5 microM) with a high statistical significance if compared to both the control group (P<0.01) and the CS-treated group (P<0.05). In conclusion, this study demonstrates that mud-therapy with sulphur mineral water could represent an important phase of the therapeutic strategy of OA. This experimental strategy could integrate and potentiate the standard pharmacological tools. Moreover, we have set a valid experimental in vivo model for the study of the thermal effects on the development of OA.

The trigeminal nerve and augmentation of regional cerebral blood flow during experimental bacterial meningitis.

We investigated whether trigeminal nerve fibers contribute to enhanced regional cerebral blood flow (rCBF) in a rat model of experimental bacterial meningitis. rCBF was measured continuously for 6 h by laser Doppler flowmetry through thinned bone over the frontal cortex. Meningitis was induced with pneumococcal cell wall components and confirmed by a significant increase of (a) leukocytes within the cerebrospinal fluid, (b) brain water content, (c) intracranial pressure and (d) rCBF. The increase of rCBF was significantly attenuated (p < 0.05) at 3, 4, 5, and 6 h in animals after a chronic (200 +/- 21% versus 138 +/- 13% at 6 h on the intact and denervated sides, respectively) but not after an acute section of the nasociliary branch of the trigeminal nerve. We conclude that elevations in blood flow during the early phase of bacterial meningitis are mediated in part by the trigeminal nerve, probably by local perivascular release of neuropeptides from afferent axons innervating the meninges.

Rat peripheral nerve components release calcitonin gene-related peptide and prostaglandin E2 in response to noxious stimuli: evidence that nervi nervorum are nociceptors.

The presence of an intrinsic afferent innervation of nerves and their connective tissues (nervi nervorum) suggests that these neural elements participate in sensation and pathological processes affecting nerves. Primary afferent nociceptors contain and release neuropeptides including calcitonin gene-related peptide, implicated in inflammatory vasodilatation. We sought to evaluate the ability of different peripheral nerve components, in vitro, to release calcitonin gene-related peptide and prostaglandin E2 in response to electrical and noxious chemical stimuli, using sensitive enzyme immunoassays. We observed significant increases in both calcitonin gene-related peptide and prostaglandin E2 in response to a mixture of inflammatory mediators (bradykinin, histamine, and serotonin; 10(-5) M) applied to the intact nerves (+37% and +700%, respectively) and isolated sheaths (35% and 430%, respectively), but not when this mixture was applied to isolated axons. Proximal (antidromic) but not distal (orthodromic) electrical stimulation also evoked a comparable release of calcitonin gene-related peptide (+30%) from intact nerves. These results suggest that nervi nervorum nociceptors participate in neural inflammation. Capsaicin (10(-6) M) elicited a very large release of calcitonin gene-related peptide when applied to either the intact nerve (+400%), isolated sheaths (+500%), or isolated axons (1400%). The latter effect was substantially but not completely blocked by Ruthenium Red and capsazepine, and was completely blocked using a calcium-free bathing solution. The results support the presence of capsaicin receptors in peripheral nerves that can effect calcitonin gene-related peptide release from axons as well as from terminals.

The efficacy and safety of imipenem/cilastatin in the treatment of severe bacterial infections.

We have assessed the efficacy and safety of imipenem/cilastatin in a non-comparative study of 27 immunocompromised patients suffering from severe bacterial infections. Moreover in two groups of 14 patients the efficacy of imipenem/cilastatin versus a standard broad spectrum antibiotic therapy has also been compared. Clinical and microbiological efficacy and side effects have been evaluated.

[Complications of acupuncture: viral hepatitis]. / Complicanze in agopuntura: l'epatite virale

Complications arising in association with acupuncture are frequently reported. Some are strictly technical, others--including viral hepatitis--are the result of hygienic problems. A statistical assessment of the frequency of HB antigen in out-patients treated during 1975 is reported.

Family physicians, chiropractors, and back pain.

In this article, major aspects of back care provided to patients by family physicians and chiropractors are reviewed, and the recent guidelines on spinal manipulation therapy are discussed. These guidelines should be useful for family physicians wishing to refer patients to chiropractors.

[Therapeutic manipulation of episodic tension type headache. A randomized, controlled clinical trial]. / Manipulationsbehandling af episodisk spaendings-type-hovedpine. En randomiseret, kontrolleret klinisk undersøgelse.

In a randomized controlled clinical trial, 75 subjects fulfilling the IHS criteria for episodic tension-type headache were treated for four weeks. One group received spinal manipulation plus soft tissue therapy in the neck, the other received soft tissue therapy plus low-power laser therapy to the same region. In the three month follow-up period both groups showed significant improvement, but there were no differences between the groups. Thus, spinal manipulation had no effect on episodic tension-type headache, in contrast to the significant effect of spinal manipulation which has previously been demonstrated in cases of cervicogenic headache. These two headaches should therefore be diagnostically differentiated in the future.

Spinal manipulation in the treatment of episodic tension-type headache: a randomized controlled trial.

CONTEXT: Episodic tension-type headache is common and is often treated using manual therapies. Few data exist for the efficacy of these interventions. OBJECTIVE: To determine the effects of spinal manipulation therapy on adults with episodic tension-type headache. DESIGN: Randomized controlled trial lasting 19 weeks. SETTING: Outpatient facility of a National Health Service-funded chiropractic research institution in Denmark. PARTICIPANTS: Volunteer sample of 26 men and 49 women aged 20 to 59 years who met the diagnostic criteria for episodic tension-type headache as defined by the International Headache Society. INTERVENTION: Participants were randomized into 2 groups, 1 receiving soft tissue therapy and spinal manipulation (the manipulation group), and the other receiving soft tissue therapy and a placebo laser treatment (the control group). All participants received 8 treatments over 4 weeks; all treatments were performed by the same chiropractor. MAIN OUTCOME MEASURES: Daily hours of headache, pain intensity per episode, and daily analgesic use, as recorded in diaries. RESULTS: Based on intent-to-treat analysis, no significant differences between the manipulation and control groups were observed in any of the 3 outcome measures. However, by week 7, each group experienced significant reductions in mean daily headache hours (manipulation group, reduction from 2.8 to 1.5 hours; control group, reduction from 3.4 to 1.9 hours) and mean number of analgesics per day (manipulation group, reduction from 0.66 to 0.38; control group, reduction from 0.82 to 0.59). These changes were maintained through the observation period. Headache pain intensity was unchanged for the duration of the trial. CONCLUSION: As an isolated intervention, spinal manipulation does not seem to have a positive effect on episodic tension-type headache.

Primary afferent neurons innervating guinea pig dura.

We made recordings from filaments of guinea pig nasociliary nerve to study response properties of afferent axons innervating the anterior superior sagittal sinus and surrounding dura mater. We analyzed 38 units in 14 experiments. Units were initially located with the use of mechanical stimuli, and were then characterized by their conduction velocity and sensitivities to mechanical, thermal, and chemical stimuli. Single-unit recordings revealed innervation of dura and superior sagittal sinus by slowly conducting axons, mostly in the unmyelinated range. The receptive fields were 1-30 mm2, and typically had one to three punctate spots of highest sensitivity. All units tested responded to topical application of chemical agents. Ninety-seven percent of units responded to 10(-5) M capsaicin, 79% responded to a mixture of inflammatory mediators, and 37% responded to an acidic buffer (pH 5). These data underline the importance of chemical sensitivity in intracranial sensation. Heat and cold stimuli evoked responses in 56 and 41% of units tested, respectively. Although the response patterns during heating were typical of polymodal nociceptors innervating other tissues, the thresholds were lower than for other tissues (32.3-42 degrees C). Cooling led to a phasic discharge, with thresholds between 25 and 32 degrees C. Although units had different combinations of responses to mechanical, chemical, and thermal stimuli, when grouped by their sensitivities the groups did not differ regarding mechanical thresholds or presence of ongoing activity. This suggests that meningeal primary afferents are relatively homogeneous. Sensitivities of these units are in general consistent with nociceptors, although the thermal thresholds differ. These data provide the first detailed report of response properties of intracranial primary afferent units, likely to be involved in transmission of nociception and possibly mediation of intracranial pain.

Unmyelinated nociceptors of rat paraspinal tissues.

1. We made recordings from rat dorsal root filaments to study unmyelinated afferent units (conduction velocity < or = 1.5 m/s) associated with deep paraspinal tissues of the dorsal sacrum and proximal tail. Data from 57 unmyelinated units were analyzed in 47 experiments. Receptive fields were identified in intact animals and then surgically isolated using microdissection. Units were characterized using mechanical, noxious chemical, and thermal stimuli. 2. These recordings revealed innervation of the nerve sheaths and surrounding connective tissue, muscles, tendons, and tissue apposed to the undersurface of the skin. No units were found with receptive fields directly on joint capsular tissue. The receptive fields of the units were often multiple and located in more than one tissue; 31 of 57 units showed convergence from different tissues. 3. The units with receptive fields on neurovascular bundles shared sensitivities with other deep tissue units described in this and other reports. These units may have clinical importance in pain due to peripheral neuropathies. 4. The units initially responded to strong mechanical stimulation of the intact animal and often to noxious stretch of the tail. Once surgically isolated, an individual unit's threshold to mechanical stimuli appeared lower. 5. Capsaicin (0.001%-0.1%) elicited responses in 81% (17 of 21) of the units tested. Bradykinin (20 micrograms/ml) elicited responses in 45% (10 of 22) of the units tested. Noxious cold (4-10 degrees C) and hot (55 degrees C) stimulation elicited discharges from 33% (5 of 15) and 25% (5 of 20) of the units tested, respectively. 6. The unmyelinated units had similar mechanical, chemical, and thermal sensitivities. These similarities and the observed convergence only allowed separation of units by the tissue in which the ending was found, and did not allow further classification. 7. The prevalence of background discharge suggested that many units were sensitized during the experiments. 8. The sensitivities of these paraspinal units were similar to those reported for other tissues. Because of the anatomic similarity of the paraspinal tissues of the proximal tail and the lumbar spine, the conclusions of the present study can be related to the lumbar spine. These afferent units are thought to participate in nociception from the deep paraspinal tissues.

Calcitonin gene-related peptide and peripherin immunoreactivity in nerve sheaths.

The intrinsic innervation of rat sciatic nerve sheaths was studied by means of immunohistochemical labeling for calcitonin gene-related peptide (CGRP) and peripherin. CGRP immunoreactivity (CGRP-IR) and peripherin immunoreactivity (peripherin-IR) were found in fine nerve fibers independent of nerve sheath vasculature. These findings suggest that a subset of the nervi nervorum may have nociceptive functions, and that this subset is distinct from nerve fibers that innervate the blood vessels of the nerve sheaths.

Pressure pain threshold and pain tolerance in episodic tension-type headache do not depend on the presence of headache.

Pressure pain thresholds and responses to painful mechanical stimuli were obtained from 20 subjects with episodic tension-type headaches (TTH). Tender points in the temporalis and trapezius muscles were studied, along with two nontender points, one in the temporalis and one on the Achilles tendon. Two examinations were performed, one during and one without a headache, and results were compared. No significant differences were found in either variable for any tested points. The data demonstrate that the sensitivity level of these points does not differ based on the presence or absence of TTH. This suggests that the muscle sensitivity in TTH is constant. The observation that the sensitivity levels of both tender and nontender points did not vary suggests that the underlying mechanism or effect of TTH is not restricted to tender muscles.

Noxious heat-induced CGRP release from rat sciatic nerve axons in vitro.

Noxious heat may act as an endogenous activator of the ionotropic capsaicin receptor (VR1) and of its recently found homologue VRL1, expressed in rat dorsal root ganglion cells and present along their nerve fibres. We have previously reported that capsaicin induces receptor-mediated and Ca++-dependent calcitonin gene-related peptide (CGRP) release from axons of the isolated rat sciatic nerve. Here we extended the investigation to noxious heat stimulation and the transduction mechanisms involved. Heat stimulation augmented the CGRP release from desheathed sciatic nerves in a log-linear manner with a Q10 of approximately 15 and a threshold between 40 and 42 degrees C. The increases were 1.75-fold at 42 degrees C, 3.8-fold at 45 degrees C and 29.1-fold at 52 degrees C; in Ca++-free solution these heat responses were abolished or reduced by 71 and 92%, respectively. Capsazepine (10 microm) and Ruthenium Red (1 microm) used as capsaicin receptor/channel antagonists did not significantly inhibit the heat-induced release. Pretreatment of the nerves with capsaicin (100 microm for 30 min) caused complete desensitization to 1 microm capsaicin, but a significant heat response remained, indicating that heat sensitivity is not restricted to capsaicin-sensitive fibres. The sciatic nerve axons responded to heat, potassium and capsaicin stimulation with a Ca++-dependent CGRP release. Blockade of the capsaicin receptor/channels had little effect on the heat-induced neuropeptide release. We conclude therefore that other heat-activated ion channels than VR1 and VRL1 in capsaicin-sensitive and -insensitive nerve fibres may cause excitation, axonal Ca++ influx and subsequent CGRP release.

Effects of triiodothyronine on rat-liver mitochondrial transcription process.

1. In order to demonstrate that triiodothyronine affects mitochondrial RNA synthesis by acting on the enzyme component of the DNA. RNA polymerase complex, mitochondrial RNA polymerase from thyroidectomized and hormone-treated rats was purified up to a stage in which activity was dependent on the addition of exogenous template. In these conditions and using different DNAs as templates, the enzyme from hormone-treated animals displayed an activity about double that of the activity of thyroidectomized animals. 2. Measurements of stability of mitochondrial RNA synthesized in vitro suggest, however, that the hormone can act also at the template level in mitochondrial transcription: the RNA population synthesized in vitro from hormone-treated rats is indeed much more enriched in unstable, probably messenger, RNA species. 3. The turnover of mitochondrial messenger RNA is higher after hormone treatment. 4. Adenosine cyclic 3':5'-monophosphate (cAMP) and its dibutyryl derivative added in vitro to mitochondria from thyroidectomized animals do not affect the incorporation of labeled precursor into mitochondrial RNA, suggesting that the level of the cyclic nucleotide in mitochondria is probably not involved in the hormone action. 5. It is concluded from these and previous studies that the thyroid hormone affects more than one parameter in the mitochondrial transcription process. The interrelationship between these events at molecular level remains, however, to be clarified.