Quantitative validation of sensory mapping in persistent postherniorrhaphy inguinal pain patients undergoing triple neurectomy.

PURPOSE: Neurectomy of the inguinal nerves may be considered for selected refractory cases of chronic postherniorrhaphy inguinal pain (CPIP). There is to date a paucity of easily applicable clinical tools to identify neuropathic pain and examine the neurosensory effects of remedial surgery. The present quantitative sensory testing (QST) pilot study evaluates a sensory mapping technique. METHODS: Longitudinal (preoperative, immediate postoperative, and late postoperative) dermatomal sensory mapping and a comprehensive QST protocol were conducted in CPIP patients with unilateral, predominantly neuropathic inguinodynia presenting for triple neurectomy (n = 13). QST was conducted in four areas on the affected, painful side and in one contralateral comparison site. QST variables were compared according to sensory mapping outcomes: (o)/normal sensation, (+)/pain, and (-)/numbness. Diagnostic ability of the sensory mapping outcomes to detect QST-assessed allodynia or hypoesthesia was estimated through calculation of specificity and sensitivity values. RESULTS: Preoperatively, patients exhibited mechanical hypoesthesia and allodynia and pressure allodynia and hyperalgesia in painful areas mapped (+) (p < .05); sensory mapping outcome (+) demonstrated high ability to detect mechanical allodynia [sensitivity 0.74 (95% CI 0.61-0.86), specificity 0.94 (0.84-1.00)] and pressure allodynia [sensitivity 0.96 (0.89-1.00), specificity 1.00 (1.00-1.00)], but not thermal allodynia. Postoperatively, mapped areas of numbness (-) were associated with mechanical and thermal hypoesthesia (p < .05); (-) showed high sensitivity and specificity to detect mechanical and cold hypoesthesia. CONCLUSIONS: Sensory mapping provides an accurate clinical neuropathic assessment with strong correlation to QST findings of preoperative mechanical and pressure allodynia, and postoperative mechanical and thermal hypoesthesia in CPIP patients undergoing neurectomy.

A multi-group confirmatory factor analyses of the LupusPRO between southern California and Filipino samples of patients with systemic lupus erythematosus.

Introduction Systemic lupus erythematosus (SLE) leads to a range of biopsychosocial health outcomes through an unpredictable and complex disease path. The LupusPRO is a comprehensive, self-report measure developed specifically for populations with SLE, which assesses both health-related quality of life and non-health related quality of life. Given its increasingly widespread use, additional research is needed to evaluate the psychometric integrity of the LupusPRO across diverse populations. The objectives of this study were to evaluate the performance of the LupusPRO in two divergent patient samples and the model fit between both samples. Methods Two diverse samples with SLE included 136 patients from an ethnically-diverse, urban region in southern California and 100 from an ethnically-homogenous, rural region in Manila, Philippines. All patients met the ACR classification criteria for SLE. Confirmatory factor analysis (CFAs) were conducted in each sample separately and combined to provide evidence of the factorial integrity of the 12 subscales in the LupusPRO. Results Demographic analyses indicated significant differences in age, disease activity and duration, education, income, insurance, and medication use between groups. Results of the separate CFAs indicated moderate fit to the data for the hypothesized 12-factor model for both the Manila and southern California groups, respectively [χ2 (794) = 1283.32, p < 0.001, Comparative Fit Index (CFI) = 0.793; χ2 (794) =1398.44, p < 0.001, CFI = 0.858]. When the factor structures of the LupusPRO in the southern California and Manila groups were constrained to be equal between the two groups, findings revealed that the factor structures of measured variables fit the two groups reasonably well [χ2 (1697) = 2950.413, df = 1697, p < 0.000; CFI = 0.811]. After removing seven constraints and eight correlations suggested by the Lagrange multiplier test, the model fit improved significantly [χ2 (15) = 147.165, p < 0.000]. Conclusions This research provides significant support for the subscale structure of the LupusPRO in two disparate cultural samples of SLE patients. Despite significant sociodemographic and clinical differences between the two samples, for the most part, the LupusPRO performed similarly in both samples.

Preexisting mild sleep disturbance as a vulnerability factor for inflammation-induced depressed mood: a human experimental study.

Sleep disturbance and depression are common, particularly in females, and sleep disturbance is a well-known risk factor for depression. Systemic inflammation has been suggested as a potential mechanism of this association. This study examined whether preexisting sleep disturbance acted as a vulnerability factor for depressed mood induced by an inflammatory challenge in healthy females vs males. In a randomized double-blind placebo-controlled design, volunteers aged 18-50 (N = 111; 67 females) were assigned to placebo or low-dose endotoxin. Before substance administration, sleep disturbance was assessed using the Pittsburgh Sleep Quality Index and dichotomized using median split (⩾ 3 vs < 3). Self-reported depressed mood (profile of mood states) and circulating proinflammatory cytokines (interleukin-6, tumor necrosis factor-α) were repeatedly assessed over 6 h. Among females, moderation of depressed mood by sleep disturbance was significant even after adjustment for covariates (X(2) = 12.73, df = 6, P < 0.05). There was a robust time-by-condition interaction in females with sleep disturbance (X(2) = 26.22, df = 6, P < 0.001), but not in females without sleep disturbance (X(2) = 8.65, df = 6, P = 0.19). Although cytokines increased equally in all females, the correlations between cytokines and depressed mood were significantly stronger in females with sleep disturbance. Among males, no moderating effect of sleep disturbance was observed. Inflammation-induced depressed mood was considerably more severe among females reporting mild sleep disturbance compared with those reporting no sleep disturbance, suggesting that even mild sleep disturbance may increase vulnerability for inflammation-induced depression in females. Furthermore, sleep disturbance appears to increase the vulnerability to depression by augmenting affective sensitivity to cytokines rather than by enhancing cytokine responses to inflammatory challenge in females.

Sleep depth and fatigue: role of cellular inflammatory activation.

Individuals with underlying inflammation present with a high prevalence of non-specific co-morbid symptoms including sleep disturbance and fatigue. However, the association between cellular expression of proinflammatory cytokines, alterations of sleep depth and daytime fatigue has not been concurrently examined. In healthy adults (24-61 years old), evening levels of monocyte intracellular proinflammatory cytokine production were assessed prior to evaluation of polysomnographic sleep and measures of fatigue the following day. Stimulated monocyte production of interleukin-6 (IL-6), but not tumor necrosis factor α (TNF-α), was negatively associated with slow wave sleep (ΔR²=.17, p=.029). In contrast, stimulated monocyte production of IL-6 was positively associated with rapid-eye movement (REM) sleep duration during the first sleep cycle (ΔR²=.26, p<.01). Moreover, evening stimulated production of IL-6 was associated with fatigue the following day (ΔR²=.17, p=.05). Mediation analyses showed that slow wave sleep, but not REM sleep duration, mediated the relationship between evening levels of IL-6 production and daytime fatigue. These results indicate that increases in stimulated monocyte production of IL-6 may be associated with decreases in slow wave sleep and increases in REM sleep duration. Relative loss of slow wave sleep may be one pathway through which cellular inflammation leads to daytime fatigue.

The nicotine inhaler: clinical pharmacokinetics and comparison with other nicotine treatments.

Nicotine inhaled in smoke is the most rapid form of delivery of the drug. With smoking, arterial boli and high venous blood nicotine concentrations are produced within seconds and minutes, respectively. The potency of nicotine as the primary reinforcement in tobacco addiction is attributed to this rapid rate of delivery. By design, nicotine treatments reduce the rate and extent of drug delivery for weaning from nicotine during smoking cessation. Theoretically, they prevent relapse by reducing withdrawal and craving associated with the abrupt cessation of cigarettes. The nicotine inhaler treats the complexity of smoking through weaning both from the drug and from the sensory/ritual components associated with smoking. The inhaler is 'puffed' but not lit and there is considerable 'puffing' required to achieve slower rising and lower nicotine concentrations. These factors allow it to be used as a nicotine reduction treatment. One inhaler contains 10 mg of nicotine (and 1 mg of menthol) of which 4 mg of nicotine can be extracted and 2mg are systemically available. Shallow or deep 'puffing' results in similar nicotine absorption. Nicotine is delivered mainly to the oral cavity, throat and upper respiratory tract with a minor fraction reaching the lungs. This was confirmed with positron emission tomography and by assessment of arterial concentrations. A single inhaler can be used for one 20-minute period of continuous puffing or periodic use of up to 400 puffs per inhaler. With controlled puffing in laboratory testing, venous plasma nicotine concentrations from a single inhaler puffed 80 times over 20 minutes averaged 8.1 microg/L at 30 minutes. Lower concentrations of 6.4 to 6.9 microg/L have been reported for self-administration under clinical conditions. The time to peak plasma concentrations varies but is always significantly longer than with cigarette delivery. Estimates of nicotine intake from cotinine concentrations were higher than expected (60 to 70% of baseline smoking concentrations). This elevation may be due to the swallowing of nicotine and subsequent first-pass biotransformation to cotinine. In general, venous blood nicotine concentrations are considerably lower than with smoking and are within the range observed for other nicotine reduction therapies. Efficacy trials show consistent superiority of the inhaler over placebo. Despite the 'cigarette-like' appearance of the inhaler and the associated sensory/ritual elements, little treatment dependence or abuse has been reported. This is attributed to the slow rise time and low nicotine blood concentrations. The inhaler is a valuable addition to treatment of tobacco dependence and can be used alone or with other treatments.

Many parallel losses of infA from chloroplast DNA during angiosperm evolution with multiple independent transfers to the nucleus.

We used DNA sequencing and gel blot surveys to assess the integrity of the chloroplast gene infA, which codes for translation initiation factor 1, in >300 diverse angiosperms. Whereas most angiosperms appear to contain an intact chloroplast infA gene, the gene has repeatedly become defunct in approximately 24 separate lineages of angiosperms, including almost all rosid species. In four species in which chloroplast infA is defunct, transferred and expressed copies of the gene were found in the nucleus, complete with putative chloroplast transit peptide sequences. The transit peptide sequences of the nuclear infA genes from soybean and Arabidopsis were shown to be functional by their ability to target green fluorescent protein to chloroplasts in vivo. Phylogenetic analysis of infA sequences and assessment of transit peptide homology indicate that the four nuclear infA genes are probably derived from four independent gene transfers from chloroplast to nuclear DNA during angiosperm evolution. Considering this and the many separate losses of infA from chloroplast DNA, the gene has probably been transferred many more times, making infA by far the most mobile chloroplast gene known in plants.

Disintegration of the scrophulariaceae.

A molecular systematic study of Scrophulariaceae sensu lato using DNA sequences of three plastid genes (rbcL, ndhF, and rps2) revealed at least five distinct monophyletic groups. Thirty-nine genera representing 24 tribes of the Scrophulariaceae s.l. (sensu lato) were analyzed along with representatives of 15 other families of Lamiales. The Scrophulariaceae s.s. (sensu stricto) include part or all of tribes Aptosimeae, Hemimerideae, Leucophylleae, Manuleae, Selagineae, and Verbasceae (= Scrophularieae) and the conventional families Buddlejaceae and Myoporaceae. Veronicaceae includes all or part of tribes Angelonieae, Antirrhineae, Cheloneae, Digitaleae, and Gratioleae and the conventional families Callitrichaceae, Globulariaceae, Hippuridaceae, and Plantaginaceae. The Orobanchaceae include tribes Buchnereae, Rhinantheae, and the conventional Orobanchaceae. All sampled members of Orobanchaceae are parasitic, except Lindenbergia, which is sister to the rest of the family. Family Calceolariaceae Olmstead is newly erected herein to recognize the phylogenetic distinctiveness of tribe Calceolarieae. The Calceolariaceae are close to the base of the Lamiales. The Stilbaceae are expanded by the inclusion of Halleria. Mimulus does not belong in any of these five groups.

Bromocriptine reduces cigarette smoking.

AIMS: Animal studies have shown that nicotine releases dopamine, a neurotransmitter implicated in drug reinforcement. We hypothesized that bromocriptine would decrease smoking behavior in humans. DESIGN: The study was conducted double blind and subjects' order of dose exposure was randomized. PARTICIPANTS: The smoking behavior of 20 heavy smokers was recorded for 5 hours after ingesting placebo or one of two doses of bromocriptine (2.50 mg, 3.75 mg) over three sessions (one dose per session). FINDINGS: There was a significant negative linear trend by dosage indicating shorter total puffing time with increasing bromocriptine dosages (p < 0.02). Other significant negative linear trends by increasing dosage include fewer number of puffs, fewer number of cigarettes smoked and mean latency to smoke after 3 hours (expected CMAX on the drug (all ps < 0.05). There was a negative significant linear trend showing decreased plasma nicotine (p < 0.02) and cotinine (p < 0.005) with increasing dosages of bromocriptine. Shiffman/Jarvik Withdrawal Scale (SJWS) cigarette craving subscale scores decreased significantly across increasing dosages (linear trend p < 0.02). There was a significant negative linear trend (p < 0.05) on the Profile of Mood States (POMS) Vigor and Depression subscales, with subjects reporting decreased vigor and depression with increasing bromocriptine doses. No other mood effects were observed. CONCLUSION: These results support the hypothesis that dopaminergic mechanisms mediate cigarette smoking reinforcement.

Utility of 17 chloroplast genes for inferring the phylogeny of the basal angiosperms.

Sequences from 14 slowly evolving chloroplast genes (including three highly conserved introns) were obtained for representative basal angiosperm and seed-plant taxa, using novel primers described here. These data were combined with published sequences from atpB, rbcL, and newly obtained sequences from ndhF. Combined data from these 17 genes permit sturdy, well-resolved inference of major aspects of basal angiosperm relationships, demonstrating that the new primers are valuable tools for sorting out the deepest events in flowering plant phylogeny. Sequences from the inverted repeat (IR) proved to be particularly reliable (low homoplasy, high retention index). Representatives of Cabomba and Illicium were the first two successive branches of the angiosperms in an initial sampling of 19 exemplar taxa. This result was strongly supported by bootstrap analysis and by two small insertion/deletion events in the slowly evolving introns. Several paleoherb groups (representatives of Piperales) formed a strongly supported clade with taxa representing core woody magnoliids (Laurales, Magnoliales, and Winteraceae). The monophyly of the sampled eudicots and monocots was also well supported. Analyses of three major partitions of the data showed many of the same clades and supported the rooting seen with all the data combined. While Amborella trichopoda was supported as the sister group of the remaining angiosperms when we added Amborella and Nymphaea odorata to the analysis, a strongly conflicting rooting was observed when Amborella alone was added.

Nicotine blood levels and subjective craving for cigarettes.

This study examined cigarette craving and blood nicotine levels in 11 male heavy smokers who were observed during 16 h of tobacco abstinence. Subjects rated their urge to smoke on a new brief 10-item questionnaire, Urge to Smoke (UTS), Schuh and Stitzer's four-item Visual Analog Scale (SSI), and a Strength of Urge to Smoke (SUTS) item. Testing occurred: 1) after 16 h (1700 h the night before to 0900 h the next morning) of abstinence from smoking; 2) after an ad lib smoking period following the 16 h abstinence; 3) every hour during 6 hours of abstinence; 4) and finally, after the 6 h abstinence, another ad lib smoking period. Thus, subjects smoked twice in each session. Blood plasma nicotine levels were measured before, after, and every 2 h during the 6-h abstinence period for a total of six measures. Blood pressure and heart rate were measured prior to each blood draw. There was a significant negative correlation between blood nicotine levels and craving for cigarettes on all craving questionnaires (rs = -0.55 to -0.78; ps < 0.002). Carbon monoxide was shown to correlate highly with nicotine blood levels (rs = 0.83 to 0.98 across subjects; ps < 0.001). Results are consistent with the hypothesis that "urge to smoke" reflects nicotine seeking in continuing smokers.

The phylogeny of the Asteridae sensu lato based on chloroplast ndhF gene sequences.

A phylogenetic study of Asteridae sensu lato was conducted based on chloroplast ndhF gene sequences for 116 ingroup and 13 outgroup species. Prior molecular studies based on rbcL sequences identified terminal groups corresponding to families, but were unable to resolve relationships among them. These results are largely consistent with earlier rbcL studies, but provide much greater resolution and stronger bootstrap support throughout the tree. The parsimony analysis found eight equally parsimonious trees, all of which recognize four major clades with the following relationship: (Cornales (Ericales (Euasterids I, Euasterids II))). Euasterids I includes (Garryales ((Solanales, Boraginaceae) (Gentianales, Lamiales))), although with weak support for relationships among the named clades. Euasterids II includes (Aquifoliales (Asterales (Apiales, Dipsacales))) with strong support for these relationships. Relationships within Ericales are weakly supported and merit further attention.

Evolutionary significance of an unusual chloroplast DNA inversion found in two basal angiosperm lineages.

Two basal lineages of flowering plants possess an intergenic inversion in the chloroplast inverted repeat (IR), a region of the genome from which there have been few previous reports of this class of structural mutation. The size of the inversion (approximately 200 bp) places it in a class not previously seen in the plastid genome. The two lineages with the rearrangement, representatives of the orders Laurales and Nymphaeales, are not closely related and the inversion therefore probably arose independently in each group. The inversion is bordered by short, but highly conserved, inverted repeat motifs that were most likely associated with the inversion process. A stem-loop structure that involves these motifs may play a functional role in mRNA stability. It is seen in all optimal or nearly optimal predicted RNA foldings of the intergenic region.

Molecular systematics of Clerodendrum (Lamiaceae): ITS sequences and total evidence.

Thirty-three species of Clerodendrum s.l. and five outgroup genera were included in a sequence analysis of internal transcribed spacers of the nuclear ribosomal DNA. The results of the cladistic analysis were compared to and combined with cpDNA restriction site data from a previous study. All molecular data identified four major clades within Clerodendrum s.l. and showed the genus to be polyphyletic. Clerodendrum s.s., minus Konocalyx and Cyclonema, is monophyletic and the genus should be restricted to this group. Cyclonema and Konocalyx form a clade distinct from Clerodendrum s.s., which has been recognized as Rotheca Raf.

Early childhood exposure to parental nudity and scenes of parental sexuality ("primal scenes"): an 18-year longitudinal study of outcome.

As part of the UCLA Family Lifestyles Project (FLS), 200 male and female children participated in an 18-year longitudinal outcome study of early childhood exposure to parental nudity and scenes of parental sexuality ("primal scenes"). At age 17-18, participants were assessed for levels of self-acceptance; relations with peers, parents, and other adults; antisocial and criminal behavior; substance use; suicidal ideation; quality of sexual relationships; and problems associated with sexual relations. No harmful "main effect" correlates of the predictor variables were found. A significant crossover Sex of Participant X Primal Scenes interaction was found such that boys exposed to primal scenes before age 6 had reduced risk of STD transmission or having impregnated someone in adolescence. In contrast, girls exposed to primal scenes before age 6 had increased risk of STD transmission or having become pregnant. A number of main effect trends in the data (nonsignificant at p < 0.05, following the Bonferonni correction) linked exposure to nudity and exposure to primal scenes with beneficial outcomes. However, a number of these findings were mediated by sex of participant interactions showing that the effects were attenuated or absent for girls. All effects were independent of family stability, pathology, or child-rearing ideology; sex of participant; SES; and beliefs and attitudes toward sexuality. Limitations of the data and of long-term regression studies in general are discussed, and the sex of participant interactions are interpreted speculatively. It is suggested that pervasive beliefs in the harmfulness of the predictor variables are exaggerated.

Olfactory thresholds for nicotine and menthol in smokers (abstinent and nonabstinent) and nonsmokers.

Nonsmokers and smokers were compared for olfactory sensitivity to two odors associated with cigarettes: nicotine and menthol. Smokers were tested twice--while nonabstinent, and after 16-20 h of smoking abstinence. Smokers showed a higher olfactory threshold for nicotine than did nonsmokers, but the same threshold for menthol. Furthermore, when the smokers were abstinent, they showed a lower olfactory threshold for nicotine than when they were nonabstinent, but again, the same threshold for menthol. These results suggest a nicotine specific olfactory deficit in smokers that is reduced during abstinence.

Evolution of novel morphological and reproductive traits in a clade containing Antirrhinum majus (Scrophulariaceae).

Phylogenetic analysis of DNA sequences of the chloroplast genes rcbL and ndhf revealed a highly supported clade composed of the families Plantaginaceae, Callitrichaceae, and Hippuridaceae in close association with the model organism Antirrhinum majus and other members of family Scrophulariaceae. Plantago has miniature actinomorphic wind-pollinated flowers that have evolved from zygomorphic animal-pollinated precursors. The aquatic Hippuridaceae have reduced windpollinated flowers with one reproductive organ per whorl, and three, rather than four, whorls. In monoecious aquatic Callitrichaceae, further reduction has occurred such that there is only one whorl per flower containing a single stamen or carpel. Optimization of character states showed that these families descended from an ancestor similar to Antirrhinum majus. Recent studies of plant developmental genetics have focused on distantly related species. Differences in the molecular mechanisms controlling floral development between model organisms are difficult to interpret due to phylogenetic distance. In order to understand evolutionary changes in floral morphology in terms of their underlying genetic processes, closely related species exhibiting morphological Variation should be examined. Studies of genes that regulate morphogenesis in the clade described here could aid in the elucidation of a general model tot such fundamental issues as how changes in floral symmetry, organ number, and whorl number are achieved, as well as providing insight on the evolution of dicliny and associated changes in pollination syndrome.

Phylogeny of Poaceae subfamily Pooideae based on chloroplast ndhF gene sequences.

Forty-eight representatives of 12 tribes attributed to the subfamily Pooideae s.l. of grasses (Monocots) have been studied by sequencing the more variable 3' end of the chloroplast ndhF gene. Six representatives from 5 different tribes of Poaceae (Oryzeae, Streptogyneae, Bambuseae, Arundineae, Phareae) and from Joinvilleaceae were used as outgroups. Phylogenetic analyses of the data render a monophyletic Pooideae clade and provide an evolutionary hypothesis for all its tribes (Poeae, Aveneae, Bromeae, Triticeae, Brachypodieae, Meliceae, Stipeae, Lygeae, Nardeae, Diarrheneae, Brachyelytreae, Phaenospermatae). The subfamily is composed of two subsets of tribes, a basal group that includes six old lineages or satellite tribes, in which Brachyelytreae is the first diverging branch followed by the Lygeae/Nardeae clade, and a group of six more recently evolved tribes (Pooideae s.s.), in which the divergence of Diarrheneae antedates that of Brachypodieae, sister group to the "core pooids." The character changes found within the sequenced nucleotide positions of the ndhF gene also have proven to be informative at lower hierarchical levels (genus and species) for some tribes.

Saliva cotinine levels as a function of collection method.

Saliva cotinine is commonly used to estimate nicotine intake but laboratories use different methods of collection. In three small trials, comparisons were made between (1) sugar vs. unstimulated saliva production (n = 29), (2) wax chewing vs. unstimulated production (n = 15) and (3) between two consecutive unstimulated saliva samples (n = 10). Sugar-stimulated saliva cotinine scores were 26% below unstimulated levels (p < 0.001); correlation between measures was high (r = 0.90; p < 0.001). Wax stimulated saliva yielded levels 6% below unstimulated (p < 0.05; correlation: r = 0.98; p < 0.001). No differences were observed between two unstimulated samples taken within a approximately 20-minute period (correlation: r = 0.99; p < 0.001). It is postulated that changes in salivary flow can account for the findings.

Examination of subfamilial phylogeny in Bromeliaceae using comparative sequencing of the plastid locus ndhF.

Parsimony analysis of 31 sequences of the chloroplast locus ndhF was used to address questions of subfamilial phylogeny in Bromeliaceae. Results presented here are congruent with those from chloroplast DNA restriction site analysis in recognizing a clade containing Bromelioideae and Pitcairnioideae, and in resolving Tillandsioideae near the base of the family. Placements of several taxonomically difficult genera (e.g., Glomeropitcairnia and Navia) corroborate those of traditional treatments; however, these data suggest that Brocchinia (Pitcairnioideae) is the sister group to the remainder of Bromeliaceae. Further evidence for the paraphyly of Pitcairnioideae includes the resolution of Puya as the sister group to Bromelioideae. Implications for taxonomic realignment at the subfamily level are considered.