Determinants of early sexual initiation among female adolescents in Bangladesh: evidence from a countrywide cross-sectional survey.

OBJECTIVES: Early sexual initiation (ESI), defined as sexual activity that begins before 15 or 18 years of age, is one of the risky sexual behaviours that has been linked to increased likelihood of adverse consequences, such as sexually transmitted diseases, unintended pregnancies and unsafe abortions. However, to date, there are no studies investigating the prevalence and factors influencing ESI among adolescent females (aged 10-19 years) in Bangladesh. Thus, this study aimed to identify the potential determinants of ESI among adolescent females in Bangladesh based on data that are representative of the country. STUDY DESIGN: This was a cross-sectional study. METHODS: Based on the availability of the data, the analysis included a weighted sample of 2051 adolescent females aged 15-19 years from the Bangladesh Demographic and Health Survey 2017/18. Initial selection of predictor variables was based on the bivariate analysis using the Chi-squared test. Univariate and multivariable logistic regression modelling were performed to measure the crude and adjusted effect of the selected predictor variables on ESI using the odds ratio (OR). The elasticity of the effects was calculated by their 95% confidence intervals (CIs). RESULTS: Approximately 22% and 85% of female adolescents experienced ESI before the age of 15 and 18 years, respectively. Findings revealed that illiteracy (adjusted OR [AOR]: 3.61, 95% CI: 1.82-7.18), primary education (AOR: 2.08, 95% CI: 1.60-2.69), working status (AOR: 1.25, 95% CI: 0.98-1.60), living in Chittagong (AOR: 0.46, 95% CI: 0.27-0.79), living in Sylhet (AOR: 0.21, 95% CI: 0.08-0.56), reading newspapers (AOR: 0.63, 95% CI: 0.40-1.01), earlier marriage preference (AOR: 3.30, 95% CI: 2.31-4.71) and later marriage preference (AOR: 4.10, 95% CI: 3.01-5.59) were significantly linked with ESI before the age of 15 years. ESI before the age of 18 years was significantly association with primary education (AOR: 1.47, 95% CI: 1.01-2.13), religion (AOR: 0.55, 95% CI: 0.32-0.94), female household head (AOR: 1.93, 95% CI: 1.17-3.19), living in Rajshahi (AOR: 1.97, 95% CI: 0.95-4.08), being in the 'poorest' wealth category (AOR: 2.43, 95% CI: 1.45-4.07), being in the 'poorer' wealth category (AOR: 1.70, 95% CI: 1.06-2.72), being in the 'middle' wealth category (AOR: 1.76, 95% CI: 1.12-2.77), being in the 'richer' wealth category (AOR: 1.58, 95% CI: 1.02-2.44), earlier marriage preference (AOR: 15.71, 95% CI: 9.09-27.14), later marriage preference (AOR: 12.62, 95% CI: 8.82-18.06) and heard about family planning (AOR: 0.70, 95% CI: 0.47-1.04). CONCLUSIONS: In Bangladesh, the prevalence of ESI among female adolescents is a public health concern. Due to the detrimental impact of ESI on the well-being of adolescents, it is crucial that policymakers consider the factors influencing ESI that have been identified in this study when designing health strategies. The findings from this study will help the development of evidence-based effective initiatives by policymakers in collaboration with governmental and non-governmental organisations.

Mogamulizumab efficacy is underscored by its associated rash that mimics cutaneous T-cell lymphoma: a retrospective single-centre case series.

BACKGROUND: Mogamulizumab is a humanized antibody against chemokine receptor type 4. It was recently approved by the US Food and Drug Administration for relapsed or refractory mycosis fungoides (MF) and Sézary syndrome (SS). The most commonly reported adverse event in the phase III licensing trial was drug eruption (28%), now termed mogamulizumab-associated rash (MAR). Clinical recommendations about MAR and its treatment differ between the current package insert and postapproval insights reported from two single-centre studies that focused on its characterization, but less so on outcomes and clinicopathological differentiation from cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To describe our experience in the diagnosis of MAR and treatment of patients with CTCL with mogamulizumab. METHODS: This is a single-centre retrospective case series study. RESULTS: We found a higher incidence of MAR in patients with CTCL (17 of 24, 68%) than previously reported. MAR development is associated with complete (11 of 17) or partial (four of 17) responses, with an overall response rate of 88%, compared with 29% (two of seven) in patients without MAR. Diagnosis of MAR may be obscured by its ability to mimic key CTCL features both clinically and histologically, but an absence of T-cell-receptor clonality and relatively decreased CD4 : CD8 ratio compared with baseline lesions strongly favour MAR over recurrent disease. CONCLUSIONS: MAR has the potential to create a significant management problem for patients on mogamulizumab. Misidentification of MAR as recurrent CTCL may detrimentally result in the premature discontinuation of mogamulizumab in patients whose disease is historically hard to treat. Thorough clinicopathological investigation of new lesions during treatment with mogamulizumab is required to inform ideal treatment decisions and achieve better outcomes.

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly.

This protocol presents the use of Lewis acidic multi-role reagents to circumvent kinetic trapping observed during the self-assembly of information-encoded oligomeric strands mediated by paired dynamic covalent interactions in a manner mimicking the thermal cycling commonly employed for the self-assembly of complementary nucleic acid sequences. Primary amine monomers bearing aldehyde and amine pendant moieties are functionalized with orthogonal protecting groups for use as dynamic covalent reactant pairs. Using a modified automated peptide synthesizer, the primary amine monomers are encoded into oligo(peptoid) strands through solid-phase submonomer synthesis. Upon purification by high-performance liquid chromatography (HPLC) and characterization by electrospray ionization mass spectrometry (ESI-MS), sequence-specific oligomers are subjected to high-loading of a Lewis acidic rare-earth metal triflate which both deprotects the aldehyde moieties and affects the reactant pair equilibrium such that strands completely dissociate. Subsequently, a fraction of the Lewis acid is extracted, enabling annealing of complementary sequence-specific strands to form information-encoded molecular ladders characterized by matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). The simple procedure outlined in this report circumvents kinetic traps commonly experienced in the field of dynamic covalent assembly and serves as a platform for the future design of robust, complex architectures.

Associations between ApoE gene and psychological consequences post stroke in a Bahraini cohort.

BACKGROUND: The contribution of genetic factors such as the presence of ApoE allele e4 and its association with psychological consequences post stroke remains unknown within Middle-Eastern regions. This study examined the association of ApoE genotype with cognitive impairment and mood in stroke patients and compare with healthy older adults in Bahrain. METHOD: A prospective sample of n = 62 stroke patients (case group) and n = 53 healthy ageing individuals (control group) were eligible to participate in the study. A neuropsychological battery of cognitive assessments were conducted on all participants, and then stratified by cognitive function: no cognitive impairment, mild cognitive impairment and moderate to severe cognitive impairment. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). RESULTS: Most frequent ApoE genotype was e2/e3 in case (44%) and control groups (63%). ApoE allele e3 had the highest frequency for both groups with all stroke patients presenting with this allele and 86% for the control group (χ2 = 12.14, p < .0001). Stroke patients' non-carriers for ApoE allele e4 performed better on all cognitive measures but differences were not statistically significant (ns). Carriers of ApoE allele e2 in both groups had less mood symptoms compared to non-carriers. DISCUSSION: ApoE genotype e3/e4 and e4/e4 was low in this Bahraini cohort explaining why there may been no significant associations found for this genotype variant with cognitive impairment. Further investigation of cognitive impairment and mood dysregulation with the different variants of the ApoE gene in general ageing and stroke populations is required from different ethno-cultural groups and geographical regions globally.

Association Between Metacognition and Mood Symptoms Poststroke.

INTRODUCTION: The link between metacognition and mood has been well established, particularly in other conditions with psychological comorbidity, however, there is no evidence regarding this association in the area of stroke. AIM: The aim of this study was to examine the association between metacognition, based on the Self-Regulatory Executive Function model, and mood symptoms in the acute phase after stroke. METHODS: One hundred thirty patients were recruited to a prospective stroke study in Bahrain, and n = 64 were assessed for mood and cognition. A neuropsychological battery of cognitive assessments included the following measures: the Mini-Mental State Examination, the Trail Making Test (A+B), and the Metacognition Questionnaire 30 (MCQ-30) for metacognition. The Hospital Anxiety and Depression Scale assessed mood symptoms, and stroke severity was measured using the National Institute of Health Stroke Severity Scale. RESULTS: Total MCQ-30 scores were significantly associated with both anxiety (r = .47, P = .001) and depression (r = .54, P <. 0001). The MCQ-30 subscales' cognitive confidence, cognitive self-consciousness, and uncontrollability/danger were the specific factors to be associated with mood symptoms (P < .01). Global cognition (r =.32, P < .01), but not executive function, was significantly associated with depression only. Metacognition remained a statistically significant correlate with depression (ß = .42, P < .0001) and anxiety (ß = .51, P < .0001) after adjusting for education and global cognition. DISCUSSION: Metacognition is a better determinant of mood symptoms after stroke, especially in regions where illiteracy levels are high in older populations, in comparison to executive function and global cognition.

Can Iron Treatments Aggravate Epistaxis in Some Patients With Hereditary Hemorrhagic Telangiectasia?

OBJECTIVES/HYPOTHESIS: To examine whether there is a rationale for iron treatments precipitating nosebleeds (epistaxis) in a subgroup of patients with hereditary hemorrhagic telangiectasia (HHT). STUDY DESIGN: Survey evaluation of HHT patients, and a randomized control trial in healthy volunteers. METHODS: Nosebleed severity in response to iron treatments and standard investigations were evaluated by unbiased surveys in patients with HHT. Serial blood samples from a randomized controlled trial of 18 healthy volunteers were used to examine responses to a single iron tablet (ferrous sulfate, 200 mg). RESULTS: Iron tablet users were more likely to have daily nosebleeds than non-iron-users as adults, but there was no difference in the proportions reporting childhood or trauma-induced nosebleeds. Although iron and blood transfusions were commonly reported to improve nosebleeds, 35 of 732 (4.8%) iron tablet users, in addition to 17 of 261 (6.5%) iron infusion users, reported that their nosebleeds were exacerbated by the respective treatments. These rates were significantly higher than those reported for control investigations. Serum iron rose sharply in four of the volunteers ingesting ferrous sulfate (by 19.3-33.1 µmol/L in 2 hours), but not in 12 dietary controls (2-hour iron increment ranged from -2.2 to +5.0 µmol/L). High iron absorbers demonstrated greater increments in serum ferritin at 48 hours, but transient rises in circulating endothelial cells, an accepted marker of endothelial damage. CONCLUSIONS: Iron supplementation is essential to treat or prevent iron deficiency, particularly in patients with pathological hemorrhagic iron losses. However, in a small subgroup of individuals, rapid changes in serum iron may provoke endothelial changes and hemorrhage. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2468-2474, 2016.

Reported cardiac phenotypes in hereditary hemorrhagic telangiectasia emphasize burdens from arrhythmias, anemia and its treatments, but suggest reduced rates of myocardial infarction.

INTRODUCTION: Cardiac phenotypes should be pronounced in hereditary hemorrhagic telangiectasia (HHT) due to frequent systemic arteriovenous malformations (AVMs), iron deficiency anemia, hypoxemia, hyperdynamic circulations, venous thromboemboli, and paradoxical emboli through pulmonary AVMs. METHODS/RESULTS: In an international survey, 1025 respondents (median age 55years) met HHT diagnostic criteria: 942 (91.9%) reported nosebleeds, 452 (44.1%) at least daily. AVMs were commonly reported in pulmonary (544, 53%), hepatic (194, 18.9%) and/or cerebral (92, 9.0%) circulations. 770/1025 (75%) had used iron tablets, 256 (25.0%) intravenous iron, and 374 (36.5%) received blood transfusions. Arrhythmias were reported by 113/1025 (11%, including 44 (4.3%) with atrial fibrillation), angina by 36 (3.5%), and cardiac failure by 26 (2.5%). In multivariate logistic regression, these phenotypes were associated with hepatic AVMs/pulmonary hypertension (relatively interchangeable variables), blood transfusions, and intravenous iron. Cardiac insufficiency/failure often provokes intensive anemia treatments, but associations with arrhythmias, particularly with a greater transfusion burden, were less easy to explain. Myocardial infarction (23/1025; 2.2%), and abnormal coronary angiogram (≤31/76, ≤54%) rates appeared low. Provocative preliminary data were obtained including HHT-affected respondents' parents and grandparents in whom HHT could be confidently assigned, or excluded based on autosomal dominant inheritance patterns: in crude and survival analyses, myocardial infarctions were reported less frequently for individuals with HHT, particularly for males (p=0.001). CONCLUSION: Arrhythmias are the most common cardiac phenotype in HHT, and likely to be aggravated by iron deficiency anemia, its treatments, and/or high output states due to AVMs. Myocardial infarction rates may be reduced in this apparently high risk population.

Pattern of migraine headache in a group of Kurdish Iraqi patients.

OBJECTIVE: To study the pattern of migraine, and to show the effect of age and duration of illness on the evolution of migraine symptoms. METHODS: A review of 200 migraine cases (attending the outpatient neurology clinic at Rezgary Teaching Hospital, and Kurdistan Private Neurology Clinic) was carried out during the period between October 2007 to May 2008. Case definition of migraine was according to the International Headache Society (IHS) criteria. RESULTS: The majority (77%) of the studied sample was female. The mean age (+/- SD) at onset was 22.33+/-9.52 years. The most common type of migraine observed was migraine without aura (72%). Different symptoms like phonophobia (92%), nausea (86.5%), photophobia (84%), vertigo (78%), scalp tenderness (75%), attacks of facial pallor (64%), sweating (57%), vomiting (50%), pain in the arms (39%), and pain in the chest (6%) was studied in relation to age at presentation and duration of illness in years. No significant association was found between the duration of illness and age at presentation and evolution of migraine symptoms. No significant association was found between the duration of illness and frequency of the attacks. CONCLUSION: Many migraine symptoms remain the same in each attack no matter the duration of illness and age at presentation, except for bouts of vomiting, which may be less common in younger patients.

Characteristics of pulmonary tuberculosis and extrapulmonary tuberculosis in immunocompetent adults

Objective: While tuberculosis is primarily considered a pulmonary disease, it has the potential to infect almost every organ via lymphohematogenous dissemination during the initial pulmonary infection. The aim of this study was to explore the importance of demographics, clinical characteristics and the various patterns of extrapulmonary tuberculosis among Saudi and non Saudi patients presenting to King Fahd Hospital of the University, Alkhobar, in the Eastern Province of Saudi Arabia. <br>Methods: Prospective study of all adult patients (13 years of age and above) with tuberculosis over a period of 9 years between 1997 and 2005. <br>Results: A total of 390 cases of tuberculosis were diagnosed during the 9-year period. There were 221 Saudis (57%), and 169 non-Saudis (43%). Pulmonary tuberculosis (PTB) was diagnosed in 132 cases (33 %), extrapulmonary tuberculosis (EPTB) in 244 cases (63%), and both pulmonary and extrapulmonary in 14 cases (4%). The proportion of EPTB was similar among Saudi and non Saudi patients. Constitutional symptoms were more common among PTB than EPTB patients. Lymphadenopathy was the most frequent site of involvement. Of the 244 EPTB patients, 113 (45%) had lymphadenopathy and more than half were located in the cervical region. Osteoarticular tuberculosis noted in 41 patients (17%) was the second most frequent involvement. Pleural, peritoneal, miliary, genitourinary, and central nervous system tuberculosis, each accounted for 2%10% of the total number of cases of EPTB. Co-morbidities were found in 56 patients, 12% from EPTB, and 16% from PTB. Human immunodeficiency virus test results were available for 234 patients; all were found to be seronegative. <br>Conclusion: Extrapulmonary tuberculosis remains frequent even in patients lacking risk factors. Dealing with EPTB has been hampered by the absence of a quick and accurate diagnostic tool. Because the clinical presentation of EPTB is extremely variable, a high level of suspicion is required to diagnose and treat EPTB in a timely and health-preserving manner.

Cataract and ocular hypertension in children on inhaled corticosteroid therapy.

PURPOSE: To ascertain the incidence of posterior subcapsular cataract and ocular hypertension in a cohort of children < or = 12 years on inhaled steroid therapy. PATIENTS AND METHODS: In this prospective study, a detailed history regarding corticosteroid therapy was obtained for children attending an asthma clinic. The presence and type of lens changes (cataract) was recorded and intraocular pressure (IOP) was measured. The children underwent another eye examination 2 years later. RESULTS: Ninety-five patients were enrolled in the study. Mean patient age was 7 +/- 3 years, and mean duration of inhaled steroid therapy was 2 +/- 1 years. Thirty-six percent of patients received inhaled steroids exclusively, 61% received inhaled steroids with a short course of oral steroids, and 3% received inhaled steroids with a long course of oral steroids. Only 3 (3%) patients had cortical changes that were not visually significant, and none had posterior subcapsular or nuclear cataract. There was no significant differences between children with cataract and those without cataract with respect to age; duration of asthma; and duration, average daily dose, and cumulative dose of inhaled steroids. IOP ranged from 11 to 20 mm Hg (mean, 16 +/- 3 mm Hg). None of the children had ocular hypertension or glaucoma. Ninety patients underwent eye examination 2 years later; none was found to develop posterior subcapsular cataract or increased IOP. CONCLUSION: This study indicates the use of inhaled steroids in children with asthma is probably safe as far as not inducing posterior subcapsular cataract or ocular hypertension.

Effects of zafirlukast on the function of humanpolymorphonuclear neutrophil leukocytes in asthmatic patients: A prospective, controlled, in vitro study.

BACKGROUND: Reactive oxygen species (ROSS) play an important role in the pathogenesis of asthma, and oxidative stress contributes to the initiation and worsening of inflammatory respiratory disorders (eg, asthma). Thus, antioxidant drugs may have a role in reducing or preventing damage in asthma. OBJECTIVE: The aim of the study was to investigate the antioxidant effect of zafirlukast, a leukotriene receptor antagonist, in asthma. METHODS: This prospective, controlled, in vitro study was conducted at KingKhalid University Hospital, Riyadh, Saudi Arabia. The generation of ROSS by polymorphonuclear neutrophil leukocytes (PMNs) in patients with mild to moderate asthma (forced expiratory volume in 1 second [FEVI], >70% of the predicted value) and healthy volunteers was assessed using chemiluminescence (CL) with phorbol 12-myristate 13-acetate (PMA) and opsonized zymosan (OPZ) in the presence of different concentrations of zafirlukast (1.25-60 µg/mL). The xanthine/xanthine oxidase (X-XOD) reaction was used to test the scavenging effect of the drug. RESULTS: Six asthmatic patients (4 women, 2 men; mean age, 30.8 years; meanFEVI, 82.5% of the predicted value) and 8 healthy volunteers (4 women, 4 men; mean age, 28.8 years) were enrolled. A dose-dependent inhibition of the CL response was observed in both groups. However, patients with asthma required higher concentrations of zafirlukast to achieve an inhibitory effect similar to that in healthy controls. This difference was significant at concentrations of 20 to 60 µg/mL (all, P ≤ 0.05). When PMNs were challenged with OPZ, inhibition was also dose dependent in controls at all concentrations (all, P ≤ 0.05), but the inhibitory effect was not significant in the asthmatic patients at any concentration. The difference in the inhibitory effect between the 2 groups was significant at 30, 40, and 60 µg/mL (P < 0.02, <0.01, and <0.01, respectively). The mean (SEM) viability of the PMNs in the healthy controls was significantly affected only at the highest concentration compared with the control saline dose (86.5% [5.8%] vs 97.0% [8.%]; P < 0.05). No scavenging effect of zafirlukast was found using the X XOD system. Incubating PMA-stimulated cells with zafirlukast (5 and 10 µg/mL) for 10 minutes to 1 hour significantly increased the inhibitory effect of the drug by 15% to 46% (all, P < 0.001). When zafirlukast was tested for reversibility of its inhibitory effect on ROS production, its action was found to be irreversible at a concentration of 30 µg/mL (P < 0.001) and partially reversible at 60 µg/mL compared with the baseline saline control. CONCLUSIONS: Zafirlukast inhibited ROS generation by PMNs in a dose-dependentmanner in asthmatic patients and healthy subjects. However, asthmatic patients required much higher concentrations compared with controls. The incubation of the stimulated cells with zafirlukast increased the inhibitory effect. This finding suggests that the therapeutic effect of zafirlukast in asthma may be in part related to its antioxidant action.

Pattern of pulmonary manifestations in patients with sickle cell disease and Fever.

OBJECTIVES: The objective of this study was to determine the frequency and pattern of pulmonary manifestations in febrile patients with sickle-cell disease (SCD), a condition prevalent in the Eastern Province of Saudi Arabia. DESIGN: The main pulmonary complications in febrile adult SCD patients were studied between January 1986 and December 1990. MATERIAL AND METHODS: The medical records, chest X-rays and microbiological data of all febrile (temperature >38°C) SCD patients >12 years of age admitted to KFHU during the study period were retrospectively reviewed. RESULTS: Of the 164 patient-episodes in 49 male and 19 female SCD patients, chest X-rays were abnormal in 33 (20.1%) episodes. Of these 33, there was consolidation in 17 (52%), pleural effusion in 6 (18%), pleural effusion and consolidation in 4 (12%), consolidation with collapse in 3 (9%), pleural thickening in 2 (6%) and bronchogenic carcinoma in one. CONCLUSION: Pneumonia was the most common complication in Saudi SCD patients with abnormal chest X-rays. Chest X-rays are most useful in SCD patients with symptoms of chest infection, abnormal chest signs, or those with persistent fever during vaso-occlusive crisis.

Axotomy- and autotomy-induced changes in the excitability of rat dorsal root ganglion neurons.

The spontaneous, ectopic activity in sensory nerves that is induced by peripheral nerve injury is thought to contribute to the generation of "neuropathic" pain in humans. To examine the cellular mechanisms that underlie this activity, neurons in rat L(4)-L(5) dorsal root ganglion (DRG) were first grouped as "large," "medium," or "small" on the basis of their size (input capacitance) and action potential (AP) shape. A fourth group of cells that exhibited a pronounced afterdepolarization (ADP) were defined as AD-cells. Whole cell recording was used to compare the properties of control neurons with those dissociated from rats in which the sciatic nerve had been sectioned ("axotomy" group) and with neurons from rats that exhibited self-mutilatory behavior in response to sciatic nerve section ("autotomy" group). Increases in excitability in all types of DRG neuron were seen within 2-7 wk of axotomy. Resting membrane potential (RMP) and the amplitude and duration of the afterhyperpolarization (AHP) that followed the AP were unaffected. Effects of axotomy were greatest in the small, putative nociceptive cells and least in the large cells. Moderate changes were seen in the medium and AD-cells. Compared to control neurons, axotomized neurons exhibited a higher frequency of evoked AP discharge in response to 500-ms depolarizing current injections; i.e., "gain" was increased and accommodation was decreased. The minimum current required to discharge an AP (rheobase) was reduced. There were significant increases in spike width in small cells and significant increases in spike height in small, medium, and AD-cells. The electrophysiological changes promoted by axotomy were intensified in animals that exhibited autotomy; spike height, and spike width were significantly greater than control for all cell types. Under our experimental conditions, spontaneous activity was never encountered in neurons dissociated from animals that exhibited autotomy. Thus changes in the electrical properties of cell bodies alone may not entirely account for injury-induced spontaneous activity in sensory nerves. The onset of autotomy coincided with alterations in the excitability of large, putative nonnociceptive, neurons. Thus large cells from the autotomy group were much more excitable than those from the axotomy group, whereas small cells from the autotomy group were only slightly more excitable. This is consistent with the hypothesis that the onset of autotomy is associated with changes in the properties of myelinated fibers. Changes in Ca2+ and K+ channel conductances that contribute to axotomy- and autotomy-induced changes in excitability are addressed in the accompanying paper.

Axotomy- and autotomy-induced changes in Ca2+ and K+ channel currents of rat dorsal root ganglion neurons.

Sciatic nerve section (axotomy) increases the excitability of rat dorsal root ganglion (DRG) neurons. The changes in Ca2+ currents, K+ currents, Ca2+ sensitive K+ current, and hyperpolarization-activated cation current (I(H)) that may be associated with this effect were examined by whole cell recording. Axotomy affected the same conductances in all types of DRG neuron. In general, the largest changes were seen in "small" cells and the smallest changes were seen in "large" cells. High-voltage-activated Ca2+ channel current (HVA-I(Ba)) was reduced by axotomy. Although currents recorded in axotomized neurons exhibited increased inactivation, this did not account for all of the reduction in HVA-I(Ba). Activation kinetics were unchanged, and experiments with nifedipine and/or omega-conotoxin GVIA showed that there was no change in the percentage contribution of L-type, N-type, or "other" HVA-I(Ba) to the total current after axotomy. T-type (low-voltage-activated) I(Ba) was not affected by axotomy. Ca2+ sensitive K+ conductance (g(K,Ca)) appeared to be reduced, but when voltage protocols were adjusted to elicit similar amounts of Ca2+ influx into control and axotomized cells, I(K,Ca)(s) were unchanged. After axotomy, Cd2+ insensitive, steady-state K+ channel current, which primarily comprised delayed rectifier K+ current (I(K)), was reduced by about 60% in small, medium, and large cells. These data suggest that axotomy-induced increases in excitability are associated with decreases in I(K) and/or decreases in g(K,Ca) that are secondary to decreased Ca2+ influx. Because I(H) was reduced by axotomy, changes in this current do not contribute to increased excitability. The amplitude and inactivation of I(Ba) in all cell types was changed more profoundly in animals that exhibited self-mutilatory behavior (autotomy). The onset of this behavior corresponded with significant reduction in I(Ba) of large neurons. This finding supports the hypothesis that autotomy, that may be related to human neuropathic pain, is associated with changes in the properties of large myelinated sensory neurons.

Effects of substance P on excitability and ionic currents of normal and axotomized rat dorsal root ganglion neurons.

Substance P (SP) may act within dorsal root ganglia (DRG) to modulate the transmission of nociceptive information. Because peripheral nerve injury (axotomy) alters the peptide content of sensory neurons, we used whole-cell recording to examine the effects of sciatic nerve section on the sensitivity of rat lumbar DRG neurons to SP (0.3--1 microM). At 1 microM, SP increased the excitability of 'small', putative nociceptive neurons but had little effect on the excitability of 'large' neurons. Two-four weeks after sciatic nerve section, however, the effect of SP on 'large' axotomized neurons was increased and its effect on 'small' neurons was decreased. SP did not affect Ca(2+) channel currents in control or axotomized neurons. The effects of SP on the current-voltage (I--V) relationship of 77% of neurons involved increased inward current at potentials below -30 mV and suppressed outward current at potentials above -20 mV. The effects of SP on the I--V relationship were similar in control and in axotomized neurons and the altered sensitivity of 'small' and 'large' cells could not be attributed to axotomy-induced changes in input resistance or membrane potential. The possible relevance of alterations in sensitivity, of 'large' DRG neurons to SP, to the generation of neuropathic pain is discussed.

Cellular neurophysiological actions of nociceptin/orphanin FQ.

Cellular actions of nociceptin/orphanin FQ (N/OFQ) resemble those of micro-, delta-, and kappa-opioids, i.e. activation of inwardly rectifying K(+) conductance, inhibition of high-voltage-activated Ca(2+) channel currents, and impediment of neurotransmitter release. Differences in ORL(1) and micro-receptor distribution lead to: 1) more widespread actions of N/OFQ on periaqueductal gray neurons than opioids and 2) differential effects of N/OFQ and opioids in the brainstem. Also, unlike opioids, N/OFQ inhibits T-type Ca(2+) channel current in sensory neurons. Opioids and N/OFQ may modulate glutamate responses in different ways, and certain actions of N/OFQ are potentiated following nerve injury whereas those of micro-opioids are attenuated. Agonists at ORL(1) receptors may therefore be of clinical interest in the management of neuropathic pain.

Methane emissions from domestic waste management facilities in Jordan--applicability of IPCC methodology.

In this paper, methane emissions from municipal wastewater treatment plants and municipal solid waste (MSW) landfills in Jordan for 1994 have been estimated using the methodology developed by the Intergovernmental Panel on Climate Change (IPCC). For this purpose, the 14 domestic wastewater treatment plants in the country were surveyed. Generation rates and characterization of MSW components as well as dumping and landfilling practices were surveyed in order to estimate 1994 CH4 emissions from these sites. Locally available waste statistics were used in cases where those of the IPCC guidelines were not representative of Jordan's statistics. Methane emissions from domestic wastewater in Jordan were estimated at 4.66 gigagrams (Gg). Total 1994 CH4 emissions from MSW management facilities in Jordan are estimated at 371.76 Gg--351.12 Gg (94.45%) from sanitary landfills, 19.83 Gg (5.33%) from MSW open dumps, and 0.81 Gg (0.22%) from raw sewage-water dumping ponds. Uncertainties associated with these estimations are presented.

Neuropeptide Y actions and the distribution of Ca2+-dependent Cl- conductance in rat dorsal root ganglion neurons.

Neuropeptide Y (NPY) increases the excitability of 'small', nociceptive, dorsal root ganglion (DRG) neurons. This effect, which may contribute to the etiology of 'neuropathic' pain, has been attributed to attenuation of Ca2+-sensitive K+ conductance(s) (gK,Ca) following suppression of Ca2+ entry via N-type Ca2+ channels. A problem arises with this conclusion because rat DRG neurons normally contain high intracellular Cl- and some of them express a Ca2+-dependent Cl- conductance (gCl,Ca). In this study, we find that in rat DRG neurons increasing intracellular Cl- does not attenuate the effect of 1 microM NPY because gCl,Ca is not found in 'small' DRG cells and the peptide failed to affect the gCl,Ca found in 'large' cells. Thus, the presence of gCl,Ca in a subpopulation of 'large' DRG neurons does not alter the conclusion that excitatory effects of NPY result from attenuation of gK,Ca.

Nerve injury increases an excitatory action of neuropeptide Y and Y2-agonists on dorsal root ganglion neurons.

Damage to sensory nerves invokes the expression of neuropeptide Y in the cell bodies of sensory neurons in dorsal root ganglia. We therefore compared the action of this peptide on control dorsal root ganglia neurons with its action on neurons from animals in which the sciatic nerve had been cut. Neuropeptide Y (0.1-1.0 microM) increased the excitability of 24% of control neurons and its effect was stronger and more cells (56%) were affected after axotomy. Increased excitability was mediated via a Y2-receptor and resulted from attenuation of Ca2+-sensitive K+-conductance(s) secondary to suppression of N-type Ca2+ channel current. Y1-agonists potentiated L-type Ca2+ channel current in control neurons without altering excitability. This Y1-effect was attenuated whereas effects mediated via Y2-receptors were enhanced after axotomy. No evidence was found for involvement of Y4- or Y5-receptor subtypes in the actions of neuropeptide Y either on control or on axotomized dorsal root ganglion neurons. It is concluded that neuropeptide Y increases the excitability of sensory neurons by interacting with a Y2-receptor and thereby decreasing N-type Ca2+ channel current and Ca2+-sensitive K+-conductance(s). When peripheral nerves are damaged, dorsal root ganglion neurons start to express neuropeptide Y and its excitatory Y2-excitatory effects are enhanced. The peptide may therefore contribute to the generation of aberrant sensory activity and perhaps to the etiology of injury-induced neuropathic pain.