Challenges and opportunities to prevent tuberculosis in people living with HIV in low-income countries.

People living with the human immunodeficiency virus (HIV) (PLHIV) are at high risk for tuberculosis (TB), and TB is a major cause of death in PLHIV. Preventing TB in PLHIV is therefore a key priority. Early initiation of antiretroviral therapy (ART) in asymptomatic PLHIV has a potent TB preventive effect, with even more benefits in those with advanced immunodeficiency. Applying the most recent World Health Organization recommendations that all PLHIV initiate ART regardless of clinical stage or CD4 cell count could provide a considerable TB preventive benefit at the population level in high HIV prevalence settings. Preventive therapy can treat tuberculous infection and prevent new infections during the course of treatment. It is now established that isoniazid preventive therapy (IPT) combined with ART among PLHIV significantly reduces the risk of TB and mortality compared with ART alone, and therefore has huge potential benefits for millions of sufferers. However, despite the evidence, this intervention is not implemented in most low-income countries with high burdens of HIV-associated TB. HIV and TB programme commitment, integration of services, appropriate screening procedures for excluding active TB, reliable drug supplies, patient-centred support to ensure adherence and well-organised follow-up and monitoring that includes drug safety are needed for successful implementation of IPT, and these features would also be needed for future shorter preventive regimens. A holistic approach to TB prevention in PLHIV should also include other important preventive measures, such as the detection and treatment of active TB, particularly among contacts of PLHIV, and control measures for tuberculous infection in health facilities, the homes of index patients and congregate settings.

Gatifloxacin for short, effective treatment of multidrug-resistant tuberculosis.

The 9-month regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) piloted in Bangladesh and used, with modifications, in Cameroon and Niger, has achieved treatment success in a very large proportion of patients; gatifloxacin (GFX) is likely to have played a critical role in this success. Two months after the publication of a study reporting that GFX and not moxifloxacin (MFX) was associated with dysglycaemia, the manufacturer announced the withdrawal of GFX from the market. The findings of that study may have less significance for the majority of MDR-TB patients living in high-incidence countries who are much younger, have a lower risk of dysglycaemia and suffer from a highly fatal condition. The problem of dysglycaemia is not limited to GFX use and may occur with other fluoroquinolones; furthermore, GFX-associated dysglycemia was manageable among those MDR-TB patients in Bangladesh and Niger in whom it occurred. GFX has now become unavailable in Bangladesh, Cameroon, Niger and other countries piloting the shorter MDR-TB regimens, depriving resource-poor countries of an efficacious, effective and inexpensive drug with a demonstrated good safety profile for the given indication. There is little reason not to make GFX available for MDR-TB treatment as long as the superiority of non-GFX-based MDR-TB regimens is not demonstrated.

Does enhanced diabetes management reduce the risk and improve the outcome of tuberculosis?

SETTING: The Bureau of National Health Insurance (NHI) has implemented a pay-for-performance (p4p) programme for diabetes mellitus (DM) in Taiwan. OBJECTIVE: To investigate whether patients with DM enrolled in the p4p programme (DM-p4p) are less likely to develop tuberculosis (TB) and whether they have a better outcome than patients with DM not enrolled in the p4p programme (DM-non-p4p) if they do develop TB. DESIGN: A random sample of 79,471 DM-p4p, 100,000 DM-non-p4p and 100,000 non-diabetic patients (non-DM) was obtained from the 2008-2009 NHI database, and the patients were matched with the National TB Registry to determine whether they had developed TB by the end of 2010. RESULTS: The average annual incidence of TB was respectively 259.9 (95%CI 230.2-293.4), 137.5 (95%CI 116.4-162.5) and 74.1 (95%CI 59.0-93.0) per 100,000 population among DM-non-p4p, DM-p4p and non-DM patients. The relative risk of death over treatment success was 1.79 (95%CI 1.05-3.04) among DM-non-p4p and 1.69 (95%CI 0.84-3.40) among non-DM patients, relative to DM-p4p patients. CONCLUSIONS: Enhanced case management of DM reduced risk and improved outcomes of TB among patients with DM.

Caring stress, suicidal attitude and suicide care ability among family caregivers of suicidal individuals: a path analysis.

ACCESSIBLE SUMMARY: What is known on the subject? Suicide is a global mental health issue. Taking care of suicidal individuals is a substantial challenge. Most studies emphasize the suicidal individual. Few studies have emphasized the family caregivers of suicidal individuals. No study has explored the relationship between family caregivers' caring stress with suicidal attitudes and suicide care ability. What this paper adds to existing knowledge? The main results indicated that the older family caregivers tended to have a more negative attitude towards suicidal individuals. Female family caregivers' stress was higher than that of male family caregivers. A mild level of caring stress would help family caregivers have a more positive attitude towards suicidal individuals. Furthermore, a positive attitude would help family caregivers improve their caring ability. What are the implications for practice? Mental health nurses could help family caregivers, especially female family caregivers, reduce their holistic caring burden by looking for support resources and enhancing their coping strategies. Mental health nurses could help family caregivers promote positive attitudes towards suicidal relatives by understanding suicidal individuals' suffering. INTRODUCTION: Suicide is a global mental health issue. Family caregivers play a key role in preventing suicide attempts. AIMS: The aim of this study was to examine the relationship among stress due to the family caregiver's role, suicidal attitude of the family caregiver and suicide care ability among family caregivers. Additionally, instruments of caring stress, attitudes towards suicidal relatives and caring abilities used in the study were tested to measure construct validity. METHODS: A cross-sectional correlational study was conducted with 164 family caregivers of people who are suicidal. The following three questionnaires were used: the Caring Stress Scale, the Suicidal Attitudes Scale and the Suicidal Caring Ability Scale. Structural equation modelling was performed using SPSS AMOS 19.0 to examine the path relationships among variables. RESULTS: Bivariate analyses showed that age was negatively correlated with suicidal attitude. In the final path model, caring stress had a positive effect on suicidal attitudes. Suicidal attitude and suicide care ability were highly positively correlated. Gender had a direct effect on caring stress, which indicated that female family caregivers experienced more stress from their role. IMPLICATIONS FOR PRACTICE: Mental health nurses could help family caregivers become aware of the emotional pain that suicidal people experience and then promote their positive attitudes towards their suicidal relatives. Furthermore, family caregivers could increase their ability to care for their suicidal relatives, which could reduce the numbers of suicides.

The effects of diallyl sulfide upon Porphyromonas gingivalis lipopolysaccharide stimulated proinflammatory cytokine expressions and nuclear factor-kappa B activation in human gingival fibroblasts.

BACKGROUND AND OBJECTIVE: Diallyl sulfide (DAS), a flavor compound from garlic, has varied potential therapeutic activities. Periodontitis is a disease that develops because of host-mediated inflammation to periodontal pathogens. In this study, the effects of DAS on the common proinflammatory cytokines and nuclear factor-kappa B (NF-κB) in human gingival fibroblasts (HGFs) being stimulated with lipopolysaccharide from Porphyromonas gingivalis, a potent periodontal pathogen, were evaluated. MATERIAL AND METHODS: Cytotoxicities of DAS and lipopolysaccharide on HGFs were measured with MTS assay. The mRNA and protein expressions of proinflammatory cytokines, including interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α, from the HGFs treated with lipopolysaccharide with and without DAS were examined with reverse transcription-polymerase chain reaction and immunocytochemistry, respectively. In addition, the activation and nuclear translocation of NF-κB with and without DAS were compared. RESULTS: DAS and lipopolysaccharide treatments within 3 mm and 10 µg/mL, respectively, did not affect the survival rate of HGFs. Lipopolysaccharide (1 µg/mL) significantly increased the mRNA expressions of IL-1ß, IL-6 and TNF-α; however, DAS (1 mm) inhibited these expressions. The protein expressions of TNF-α, IL-1ß, as well as the NF-κB nuclear translocation were increased after lipopolysaccharide treatment, but decreased when there was a DAS pretreatment. CONCLUSION: DAS diminished P. gingivalis lipopolysaccharide-stimulated cytokine expression and NF-κB activation in HGFs; we therefore suggest DAS may be beneficial on periodontal inflammation.

Central α-adrenoceptors contribute to mustard oil-induced central sensitization in the rat medullary dorsal horn.

Our previous studies have demonstrated that application of the inflammatory irritant mustard oil (MO) to the tooth pulp produces trigeminal central sensitization that includes increases in mechanoreceptive field size and responses to noxious stimuli and decrease in activation threshold in brainstem nociceptive neurons of trigeminal subnucleus caudalis (the medullary dorsal horn, MDH). The aim of the present study was to test if central noradrenergic processes are involved in the central sensitization of MDH neurons and if α1-adrenoceptors or α2-adrenoceptors or both are involved. In urethane/α-chloralose-anesthetized rats, the activity of extracellularly recorded and functionally identified single nociceptive neurons in the MDH was studied. Continuous intrathecal (i.t.) superfusion of the adrenergic modulator guanethidine and α-adrenoceptor blocker phentolamine or selective α1-adrenoceptor antagonist prazosin over the medulla strongly attenuated all three MO-induced parameters of central sensitization in the MDH nociceptive neurons, compared to phosphate-buffered saline (as vehicle control). In contrast, i.t. superfusion of the selective α2-adrenoceptor antagonist yohimbine had little effect on the mechanoreceptive field expansion and the decreased mechanical activation threshold, and indeed facilitated responses to noxious stimuli of sensitized nociceptive neurons. Superfusion of each of the four chemicals alone did not affect baseline nociceptive neuronal properties. These findings provide the first documentation of the involvement of central noradrenergic processes in MDH in the development of the central sensitization, and that α1- and α2-adrenoceptors may be differentially involved.

Involvement of ATP in noxious stimulus-evoked release of glutamate in rat medullary dorsal horn: a microdialysis study.

Our electrophysiological studies have shown that both purinergic and glutamatergic receptors are involved in central sensitization of nociceptive neurons in the medullary dorsal horn (MDH). Here we assessed the effects of intrathecal administration of apyrase (a nucleotide degrading enzyme of endogenous adenosine 5-triphosphate [ATP]), a combination of apyrase and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, an adenosine A1 receptor antagonist), or 2,3-O-2,4,6-trinitrophenyl-adenosine triphosphate (TNP-ATP, a P2X1, P2X3, P2X2/3 receptor antagonist) on the release of glutamate in the rat MDH evoked by application of mustard oil (MO) to the molar tooth pulp. In vivo microdialysis was used to dialyse the MDH every 5 min, and included 3 basal samples, 6 samples after drug treatment and 12 samples following application of MO. Tooth pulp application of MO induced a significant increase in glutamate release in the MDH. Superfusion of apyrase or TNP-ATP alone significantly reduced the MO-induced glutamate release in the MDH, as compared to vehicle. Furthermore, the suppressive effects of apyrase on glutamate release were reduced by combining it with DPCPX. This study demonstrates that application of an inflammatory irritant to the tooth pulp induces glutamate release in the rat MDH in vivo that may be reduced by processes involving endogenous ATP and adenosine.

Systemic pregabalin attenuates sensorimotor responses and medullary glutamate release in inflammatory tooth pain model.

Our previous studies have demonstrated that application of inflammatory irritant mustard oil (MO) to the tooth pulp induces medullary glutamate release and central sensitization in the rat medullary dorsal horn (MDH), as well as nociceptive sensorimotor responses in craniofacial muscles in rats. There is recent evidence that anticonvulsant drugs such as pregabalin that influence glutamatergic neurotransmission are effective in several pain states. The aim of this study was to examine whether systemic administration of pregabalin attenuated glutamate release in the medulla as well as these nociceptive effects reflected in increased electromyographic (EMG) activity induced by MO application to the tooth pulp. Male adult rats were anesthetized with isofluorane (1.0-1.2%), and jaw and tongue muscle EMG activities were recorded by needle electrodes inserted bilaterally into masseter and anterior digastric muscles and into the genioglossus muscle, and also the medullary release of glutamate was assessed by in vivo microdialysis. Pregabalin or vehicle control (isotonic saline) was administered 30 min before the pulpal application of MO or vehicle control (mineral oil). Application of mineral oil to the maxillary first molar tooth pulp produced no change in baseline EMG activity and glutamate release. However, application of MO to the pulp significantly increased both the medullary release of glutamate and EMG activity in the jaw and tongue muscles for several minutes. In contrast, pre-medication with pregabalin, but not vehicle control, significantly and dose-dependently attenuated the medullary glutamate release and EMG activity in these muscles after MO application to the tooth pulp (analysis of variance (ANOVA), p<0.05). These results suggest that pregabalin may attenuate the medullary release of glutamate and associated nociceptive sensorimotor responses in this acute inflammatory pulpal pain model, and that it may prove useful for the treatment of orofacial inflammatory pain states.

Xpert® MTB/RIF for national tuberculosis programmes in low-income countries: when, where and how?

Xpert ® MTB/RIF offers new and important possibilities for the diagnosis of sputum smear-negative tuberculosis (TB) and/or rifampicin (RMP) resistance, and many are encouraging rapid and widespread implementation. This simple test can be implemented almost everywhere, and it provides results within a few hours. In low-income countries (LICs), however, its cost, environmental limitations (stable and regular electricity, adequate room temperature) and difficulties involved in supply and maintenance are major obstacles. While it may be suitable for major reference hospitals, operational research is needed to evaluate the test and its additional yield above high-quality smear microscopy and clinical algorithms before its use at the peripheral level. In the meantime, direct microscopy should remain the initial diagnostic test for TB suspects. In most LICs, the prevalence of RMP resistance among new TB patients is very low; an Xpert MTB/RIF result indicating RMP resistance will thus always need confirmation by another test. In a population at high risk of RMP resistance (> 15%), however, the positive predictive value for RMP resistance by Xpert MTB/RIF is high, and identification of RMP resistance is an excellent proxy for multidrug-resistant TB (MDR-TB). The assay should be widely used for this purpose if, and only if, excellent MDR-TB management is available, both for ethical reasons and to reduce the risk of extensively drug-resistant TB.

Inconsistent dosing of anti-tuberculosis drugs in Taipei, Taiwan.

SETTING: Taipei City, Taiwan. OBJECTIVES: To evaluate prescribing practices for anti-tuberculosis drugs in the treatment of tuberculosis (TB). METHOD: Medical audit of the medical charts of all patients notified and treated for TB in Taiwan in 2003 to determine the treatment regimens prescribed and to compare these with recommended dosages. RESULTS: A total of 24 different anti-tuberculosis regimens were prescribed. Of 1700 patients notified, 1096 (64.5%) had their body weight recorded. Of 506 patients prescribed a three-drug fixed-dose combination (FDC), the dosage was adequate in 374 (73.9%), too low in 100 (19.8%) and too high in 32 (6.3%). Of 75 patients prescribed a two-drug FDC, the dosage was adequate in 57 (76.0%), too low in 15 (20.0%) and too high in 3 (4.0%). Of 481 patients prescribed rifampicin, the dosage was adequate in 302 (62.8%), too low in 152 (31.6%) and too high in 27 (5.6%). Of 451 patients prescribed isoniazid, the dosage was adequate in 396 (87.8%), too low in 29 (6.4%) and too high in 26 (5.8%). CONCLUSION: The prescribing practices for anti-tuberculosis drugs were substandard and need improvement. These findings imply that the National TB Programme needs strengthening.

Central sensitization in thalamic nociceptive neurons induced by mustard oil application to rat molar tooth pulp.

We have recently demonstrated that application of mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces central sensitization that is reflected in changes in spontaneous activity, mechanoreceptive field (RF) size, mechanical activation threshold, and responses to graded mechanical stimuli applied to the neuronal RF in trigeminal brainstem subnucleus caudalis and subnucleus oralis. The aim of this study was to test whether central sensitization can be induced in nociceptive neurons of the posterior thalamus by MO application to the pulp. Single unit neuronal activity was recorded in the ventroposterior medial nucleus (VPM) or posterior nuclear group (PO) of the thalamus in anesthetized rats, and nociceptive neurons were classified as wide dynamic range (WDR) or nociceptive-specific (NS). MO application to the pulp was studied in 47 thalamic nociceptive neurons and found to excite over 50% of the 35 VPM neurons tested and to produce significant long-lasting (over 40 min) increases in spontaneous activity, cutaneous pinch RF size and responses to graded mechanical stimuli, and a decrease in threshold in the 29 NS neurons tested; a smaller but statistically significant increase in mean spontaneous firing rate and decrease in activation threshold occurred following MO in the six WDR neurons tested. Vehicle application to the pulp did not produce any significant changes in six VPM NS neurons tested. MO application to the pulp produced pronounced increases in spontaneous activity, pinch RF size, and responses to mechanical stimuli, and a decrease in threshold in three of the six PO neurons. In conclusion, application of the inflammatory irritant MO to the tooth pulp results in central sensitization of thalamic nociceptive neurons and this neuronal hyperexcitability likely contributes to the behavioral consequences of peripheral inflammation manifesting as pain referral, hyperalgesia and allodynia.

Patient and health system delays in the diagnosis and treatment of tuberculosis in Southern Taiwan.

SETTING: Tainan city, Tainan county and 13 townships of Kaohsiung county, Southern Taiwan. OBJECTIVE: To measure delays in the diagnosis and treatment of sputum-positive tuberculosis (TB) and to determine factors associated with delays in seeking health care (patient delay) and in starting anti-tuberculosis treatment (health system delay). DESIGN: A population-based patient interview study. RESULTS: Median patient delay was 7 days (range 0-730). Median health system delay was 23 days (range 0-489), 13 for smear-positive patients and 37 for smear-negative patients (P < 0.005). Median total delay was 44 days (range 0-730). Age <65 years was associated with longer patient delay. Negative smear, absence of haemoptysis, not having a chest radiograph at the first medical consultation and visiting clinics for first consultation were associated with a longer health system delay. Age <65 years, negative smear and cough as the only presenting symptom were associated with longer total delay. CONCLUSION: Patient delay was substantially shorter than health system delay. To reduce health system delay, clinics need to be involved and the referral mechanism must be strengthened. Physicians should maintain high alert for TB and perform prompt sputum smear examinations.

Endogenous ATP involvement in mustard-oil-induced central sensitization in trigeminal subnucleus caudalis (medullary dorsal horn).

Central sensitization represents a sustained hypersensitive state of dorsal horn nociceptive neurons that can be evoked by peripheral inflammation or injury to nerves and tissues. It reflects neuroplastic changes such as increases in neuronal spontaneous activity, receptive field size, and responses to suprathreshold stimuli and a decrease in activation threshold. We recently demonstrated that purinergic receptor mechanisms in trigeminal subnucleus caudalis (Vc; medullary dorsal horn) are also involved in the initiation and maintenance of central sensitization in brain stem nociceptive neurons of trigeminal subnucleus oralis. The aim of the present study was to investigate whether endogenous ATP is involved in the development of central sensitization in Vc itself. The experiments were carried out on urethan/alpha-chloralose anesthetized and immobilized rats. Single neurons were recorded and identified as nociceptive-specific (NS) in the deep laminae of Vc. During continuous saline superfusion (0.6 ml/h it) over the caudal medulla, Vc neuronal central sensitization was readily induced by mustard oil application to the tooth pulp. However, this mustard-oil-induced central sensitization could be completely blocked by continuous intrathecal superfusion of the wide-spectrum P2X receptor antagonist pyridoxal-phosphate-6-azophenyl-2, 4-disulphonic acid tetra-sodium (33-100 microM) and by apyrase (an ectonucleotidase enzyme, 30 units/ml). Superfusion of the selective P2X1, P2X3 and P2X(2/3) receptor antagonist 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate (6-638 microM) partially blocked the Vc central sensitization. The two P2X receptor antagonists did not significantly affect the baseline nociceptive properties of the Vc neurons. These findings implicate endogenous ATP as an important mediator contributing to the development of central sensitization in nociceptive neurons of the deep laminae of the dorsal horn.

Neuroplasticity induced by tooth pulp stimulation in trigeminal subnucleus oralis involves NMDA receptor mechanisms.

We have recently demonstrated that application of the mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces significant increases in jaw muscle electromyographic (EMG) activity and neuroplastic changes in trigeminal (V) subnucleus caudalis. Since subnucleus oralis (Vo) as well as caudalis receives projections from molar pulp afferents and is also an integral brain stem relay of afferent input from orofacial structures, we tested whether MO application to the exposed pulp induces neuroplastic changes in oralis neurons and whether microinjection of MK-801, a noncompetitive NMDA antagonist, into the Vo influences the pulp/MO-induced neuroplastic changes in chloralose/urethan-anesthetized rats. Single neuronal activity was recorded in Vo, and neurons classified as low-threshold mechanoreceptive (LTM), wide dynamic range (WDR), nociceptive-specific (NS), deep (D), or skin/mucosa and deep (S + D). The spontaneous activity, mechanoreceptive field (RF) size, mechanical threshold, and response to suprathreshold mechanical stimuli applied to the neuronal RF were assessed prior to and throughout a 40- to 60-min period after MO application to the maxillary molar pulp. In animals pretreated with saline microinjection (0.3 microl) into the Vo, MO application to the pulp produced a significant increase in spontaneous activity, expansion of the pinch or deep RF, decrease in the mechanical threshold, and increase in response to suprathreshold mechanical stimuli of the nociceptive (WDR, NS, and S + D) neurons except for those nociceptive neurons having their RF only in the intraoral region. The pulpal application of MO did not produce any significant neuroplastic changes in LTM neurons. Furthermore, in animals pretreated with MK-801 microinjection (3 microg/0.3 microl) into the Vo, MO application to the pulp did not produce any significant changes in the RF and response properties of nociceptive neurons. In other animals pretreated with saline (0.3 microl) or MK-801 (3 microg/0.3 microl) microinjected into the Vo, mineral oil application to the pulp did not produce any significant changes in RF and response properties of nociceptive neurons. These findings indicate that the application of MO to the tooth pulp can induce significant neuroplastic changes in oralis nociceptive neurons and that central NMDA receptor mechanisms may be involved in these neuroplastic changes.

Involvement of trigeminal subnucleus caudalis (medullary dorsal horn) in craniofacial nociceptive reflex activity.

We have previously shown that an increase in electromyographic (EMG) activity of digastric (DIG) and masseter (MASS) muscles can be reflexly evoked by injection into the rat's temporomandibular joint (TMJ) region of the small-fibre excitant and inflammatory irritant mustard oil (MO). Since the trigeminal (V) subnucleus caudalis (Vc, i.e. medullary dorsal horn) has traditionally been viewed as an essential brainstem relay site of nociceptive information from craniofacial tissues, an EMG study was carried out in 45 anaesthetized rats to determine if Vc is involved in the MO-evoked increases in jaw muscle EMG activity. The effects of histologically confirmed surgical or chemical lesions of Vc on this evoked EMG activity were tested in different groups of rats. MO injection into the left TMJ region of intact rats evoked bilateral increases in EMG activity of DIG and MASS which could be significantly reduced by surgical transection of the left caudal brainstem at the obex level; MO injection into the right TMJ region in these same rats still readily evoked increases in EMG activity. A sagittal section medial to Vc or transection at the level of the second cervical spinal segment did not produce any significant reduction in the reflexly evoked EMG activity. Neurones in Vc, as opposed to fibres of passage, appear to be important for the MO-evoked EMG activity, since injection into Vc of the neurotoxic chemical ibotenic acid significantly reduced the mustard oil-evoked EMG activity. The Vc also appears to play a role in the activation of contralateral V motoneurons, as evidenced by the activation of the contralateral DIG and MASS muscles by the injection of MO into the left TMJ region of intact rats and by the reduction of this evoked EMG activity in the contralateral DIG and MASS of rats with a surgical transection or ibotenic acid lesion of the left Vc. These findings suggest that Vc may be a critical element in the neural pathways underlying the reflex responses evoked bilaterally in DIG and MASS muscles by noxious stimulation of the TMJ region.

NMDA receptor mechanisms contribute to neuroplasticity induced in caudalis nociceptive neurons by tooth pulp stimulation.

We recently demonstrated that application of mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces significant and prolonged increases in jaw muscle electromyographic (EMG) activity that are suggestive of central neuroplasticity. Because small-fiber afferents, including pulp afferents, access nociceptive neurons in trigeminal (V) subnucleus caudalis, this study examined whether pulpal application of MO induces neuroplastic changes in caudalis nociceptive neurons (wide dynamic range and nociceptive specific) and whether central N-methyl--aspartate (NMDA) receptor mechanisms are involved in these MO-induced neuroplastic changes. After pretreatment with vehicle (saline, 10 microliter i.t.) to the surface of the medulla, the pulpal application of MO to the maxillary molar tooth pulp produced a significant increase in neuronal spontaneous activity, a significant expansion of the pinch and/or tactile mechanoreceptive field (RF), a significant decrease in mechanical threshold, and significant increases in neuronal responses to graded pinch stimuli. Compared with vehicle-treated rats, pretreatment with the NMDA receptor antagonist MK-801 (10 microgram/10 microliter i.t.) followed by MO application to the pulp in another group of rats significantly reduced or abolished these MO-induced neuroplastic changes in nociceptive neurons. In another group of rats pretreated with saline (intrathecally), mineral oil application to the pulp did not show any significant changes in spontaneous activity or RF properties over the 40-min observation period. The pulpal application of MO in other rats (pretreated with saline, intrathecally) did not produce any significant neuroplastic changes in caudalis low-threshold mechanoreceptive neurons. These results indicate that the MO-induced activation of molar pulpal afferents can produce profound NMDA receptor-related neuroplastic changes in caudalis nociceptive neurons. Such neuroplastic changes may contribute to the hyperalgesia and spread of pain that can be associated with pulpal inflammation.

NMDA receptor involvement in neuroplastic changes induced by neonatal capsaicin treatment in trigeminal nociceptive neurons.

NMDA receptor involvement in neuroplastic changes induced by neonatal capsaicin treatment in trigeminal nociceptive neurons. J. Neurophysiol. 78: 2799-2803, 1997. This study examines whether 1) the neonatal loss of C-fiber afferents results in neuroplastic changes in the mechanoreceptive field (RF) properties and spontaneous activity of nociceptive neurons in trigeminal subnucleus caudalis (medullary dorsal horn) of adult rats, and that 2) N-methyl--aspartic acid (NMDA) receptor mechanisms are involved in these neuroplastic changes. Compared with vehicle-treated (i.e., control, CON) rats, capsaicin-treated (CAP) rats showed a marked increase in neuronal spontaneous activity and RF size per se, but these neuroplastic changes could be significantly reduced by MK-801 (1 mg/kg, iv), a noncompetitive NMDA receptor antagonist; RF size and spontaneous activity remained unchanged in CON rats after MK-801 administration and in CAP rats after vehicle (saline, iv). Administration of 7-chlorokynurenic acid intrathecally (5 microgram/10 microliter), an antagonist of strychnine-insensitive glycine bindin sites on the NMDA receptor, also significantly reduced neuronal RF size and spontaneous activity in CAP rats, but not in CON rats. These data provide evidence that C-fiber afferents play a role in shaping the properties of nociceptive neurons and that the neuroplastic changes involve NMDA receptor mechanisms.

Treatment of multidrug-resistant tuberculosis in Taiwan.

Eighty-seven patients with multidrug-resistant tuberculosis (MDR-TB) diagnosed between 1988 and 1990 were treated with isoniazid and at least three other effective second-line drugs based on in vitro susceptibility tests. Of these patients, 10% failed to adhere to the regimen and 43% remained sputum positive after 6 months of treatment. Only 47% showed sputum conversion within 6 months of treatment and 12% of them relapsed during the first year of follow-up. From September 1987 to July 1989, 36 patients with MDR-TB were treated with a regimen containing rifabutin, isoniazid and at least three other susceptible drugs. Only 47% achieved a sustained sputum conversion. Four died during treatment due to disease progression. From March 1992 to July 1993, 17 cases of MDR-TB were treated with an ofloxacin-containing anti-TB regimen for 12-24 months. Two failed to adhere to the regimen for more than 1 month during the first 6 months of therapy. Among the remaining 15, 26% failed to achieve sputum conversion, 73% achieved bacterial conversion, 9 within 1 month and the other 2 within 2 months. No significant adverse effect was associated with ofloxacin use. We concluded that ofloxacin is a better choice among the more toxic and less potent second-line drugs, and should be used along with other anti-TB drugs in treating patients with MDR-TB.

Postpartum worries: an exploration of Taiwanese primiparas who participate in the Chinese ritual of tso-yueh-tzu.

PROBLEM: To explore worries of postpartum mothers who participate in Tso-Yueh-Tzu. SUBJECTS: Primiparas (N = 21) with a mean age of 30 years, a mean educational level of 15 years. Seventeen (81%) were working. The mean number of postpartum days was 14. METHODS: Focus groups, each group session lasted approximately 2 hours and was audiotaped. FINDINGS: Four themes regarding worries emerged: searching process to integrate the self into the rituals of Tso-Yueh-Tzu, understanding that the newborn's care influences evaluation of the self as a "good mother," decision-making process of the self to arrange the best baby care for a career women, and reconciling the need for self-fulfillment with the demand to be a "family-mother." CONCLUSIONS & IMPLICATIONS FOR NURSING: Nurses can help a mother work through her worries. Although the women expressed their worries in different content, all focused on the need for "the integration of the self" while they went through Tso-Yueh-Tzu.

The afferent and efferent connections of the nucleus submedius in the rat.

The afferent and efferent connections of the nucleus submedius (Sm) in the medial thalamus of the rat were examined. Injections of wheat-germ agglutinin conjugated horseradish peroxidase (WGA-HRP) into the Sm resulted in dense terminal labeling in the middle layers of the ipsilateral ventrolateral orbital cortex (VLO). Less dense labeling was also observed in the superficial and deep layers of VLO and in the medial part of the lateral orbital cortex (LO) and in the contralateral VLO. Retrogradely labeled neurons were observed primarily in the deep layers of VLO and the dorsal peduncular cortex (DP). Labeled neurons were also observed bilaterally, in the nucleus of the horizontal limb of the diagonal band, the lateral hypothalamus, the thalamic reticular nucleus (Rt), medial parabrachial nucleus (MPB), and the laterodorsal tegmental nucleus (LDT). Many labeled neurons were also observed in the trigeminal brain-stem complex. Injections of Fluoro-Gold (FG) into Sm resulted in a very similar distribution of retrogradely labeled neurons. Injections of WGA-HRP and FG in the orbital cortex confirmed the ipsilateral Sm projection to VLO and suggested that the middle and deep layers of VLO receive a specific ipsilateral projection from the dorsal Sm and that the superficial layers receive a projection primarily from the ventral Sm. Injections of WGA-HRP into the lateral hypothalamus, LDT, and MPB confirmed the retrograde labeling findings; the lateral hypothalamus was found to send a projection to the medial Sm, the LDT region to the ventromedial Sm and the MPB to the medial and dorsal Sm. These findings confirm and extend the results of previous studies in cat and rat indicating that Sm has a major and specific reciprocal connection with VLO. This finding, in conjunction with previous studies showing direct spinal and trigeminal inputs and the existence of nociceptive neurons in Sm and VLO, provides further support for a role of Sm in nociception.