Sapling leaf trait responses to light, tree height and soil nutrients for three conifer species of contrasting shade tolerance.

We developed models to describe the responses of four commonly examined leaf traits (mass per area, weight, area and nitrogen (N) concentration) to gradients of light, soil nutrients and tree height in three conifer species of contrasting shade tolerance. Our observational dataset from the sub-boreal spruce forests of British Columbia included subalpine fir (Abies lasioscarpa [Hook.] Nutt; high shade tolerance), interior spruce (Picea glauca × Picea engelmannii [Moench] Voss; intermediate shade tolerance) and lodgepole pine (Pinus contorta Dougl. ex Loud. var. latifolia; low shade tolerance) saplings from 0.18 to 4.87 m tall, in 8-98% of total incident light, from field sites with <17.6 kg ha(-1) to >46.8 kg ha(-1) total dissolved N. Leaf weights and areas showed strong positive responses to light and height, but little or no response to soil nutrients. Parameter estimates indicated that the shape of leaf weight and area responses to light corresponded with shade tolerance ranking for the three species; pine had the most linear response whereas spruce and fir had asymptotic responses. Leaf N concentration responded positively to soil nutrients, negatively to light and idiosyncratically to height. The negative effect of light was only apparent on sites of high soil nutrient availability, and parameter estimates for the shape of the negative response also corresponded to shade tolerance ranking (apine = -0.79, aspruce = -0.15, afir = -0.07). Of the traits we measured, leaf mass per area showed the least response to light, soil nutrient and height gradients. Although it is a common practice in comparisons across many species, characterizing these conifers by mean values of their leaf traits would miss important intraspecific variation across environmental and size gradients. In these forests, parameter estimates representing the intraspecific variability of leaf trait responses can be used to understand relative shade tolerances.

Salmonella and on-farm risk factors in healthy slaughter-age cattle and sheep in eastern Australia.

OBJECTIVE: To examine healthy slaughter-age cattle and sheep on-farm for the excretion of Salmonella serovars in faeces and to identify possible risk factors using a questionnaire. PROCEDURE: The study involved 215 herds and flocks in the four eastern states of Australia, 56 with prior history of salmonellosis. Production systems examined included pasture beef cattle, feedlot beef cattle, dairy cattle, prime lambs and mutton sheep and animals were all at slaughter age. From each herd or flock, 25 animals were sampled and the samples pooled for Salmonella culture. All Salmonella isolated were serotyped and any Salmonella Typhimurium isolates were phage typed. Questionnaires on each production system, prepared in Epi Info 6.04, were designed to identify risk factors associated with Salmonella spp excretion, with separate questionnaires designed for each production system. RESULTS: Salmonellae were identified in all production systems and were more commonly isolated from dairies and beef feedlots than other systems. Statistical analysis revealed that dairy cattle were significantly more likely to shed Salmonella in faeces than pasture beef cattle, mutton sheep and prime lambs (P<0.05). A wide diversity of Salmonella serovars, all of which have been isolated from humans in Australia, was identified in both cattle and sheep. Analysis of the questionnaires showed access to new arrivals was a significant risk factor for Salmonella excretion on dairy properties. For beef feedlots, the presence of large numbers of flies in the feedlot pens or around stored manure were significant risk factors for Salmonella excretion. CONCLUSION: Dairy cattle pose the highest risk of all the slaughter-age animals tested. Some of the identified risk factors can be overcome by improved management practices, especially in relation to hygiene.

Survival benefits select for group living in a social spider despite reproductive costs.

The evolution of cooperation requires benefits of group living to exceed costs. Hence, some components of fitness are expected to increase with increasing group size, whereas others may decrease because of competition among group members. The social spiders provide an excellent system to investigate the costs and benefits of group living: they occur in groups of various sizes and individuals are relatively short-lived, therefore life history traits and Lifetime Reproductive Success (LRS) can be estimated as a function of group size. Sociality in spiders has originated repeatedly in phylogenetically distant families and appears to be accompanied by a transition to a system of continuous intra-colony mating and extreme inbreeding. The benefits of group living in such systems should therefore be substantial. We investigated the effect of group size on fitness components of reproduction and survival in the social spider Stegodyphus dumicola in two populations in Namibia. In both populations, the major benefit of group living was improved survival of colonies and late-instar juveniles with increasing colony size. By contrast, female fecundity, female body size and early juvenile survival decreased with increasing group size. Mean individual fitness, estimated as LRS and calculated from five components of reproduction and survival, was maximized for intermediate- to large-sized colonies. Group living in these spiders thus entails a net reproductive cost, presumably because of an increase in intra-colony competition with group size. This cost is traded off against survival benefits at the colony level, which appear to be the major factor favouring group living. In the field, many colonies occur at smaller size than expected from the fitness curve, suggesting ecological or life history constraints on colony persistence which results in a transient population of relatively small colonies.

Aborted genital herpes simplex virus lesions: findings from a randomised controlled trial with valaciclovir.

OBJECTIVES: In prospective trials, episodic valaciclovir significantly increased the chance of preventing or aborting the development of painful vesicular genital herpes simplex virus (HSV) lesions compared with placebo. We explored the clinical outcome of aborted lesions and its association with early treatment in a study designed to compare 3 and 5 days' treatment with valaciclovir. METHODS: In a randomised controlled trial, valaciclovir 500 mg twice daily for 3 or 5 days was initiated at the first symptoms of a genital herpes outbreak. The primary end point was length of episode with pain, HSV shedding, and aborted lesions secondary end points. The effect of time from symptom recognition to treatment initiation on aborted lesions was assessed in a post hoc analysis. RESULTS: In 531 patients, no differences were observed between 3 and 5 days' treatment in episode duration (median 4.7 v 4.6 days), loss of pain/discomfort (2.8 v 3.0 days), or lesion healing (4.9 v 4.5 days). Vesicular lesions were aborted in 27% of patients treated for 3 days v 21% of patients receiving valaciclovir for 5 days. The odds of achieving an aborted episode were 1.93 (95% CI: 1.28 to 2.90) times higher for those initiating treatment with valaciclovir within 6 hours of first sign or symptom. CONCLUSIONS: There was no difference between 3 and 5 days' treatment in reducing episode duration or lesion abortion. Prompt treatment with valaciclovir can abort genital HSV reactivation episodes, preventing a vesicular outbreak. Maximum treatment benefit depends on prompt therapy after recognition of symptoms.

Validating Livanow: molecular data agree that leeches, Branchiobdellidans, and Acanthobdella peledina form a monophyletic group of oligochaetes.

To investigate the phylogenetic relationships of leeches, branchiobdellidans, and acanthobdellidans, whole nuclear 18S rDNA and over 650 bp of mitochondrial cytochrome c oxidase subunit I were acquired from 101 annelids, including 36 leeches, 18 branchiobdellidans, Acanthobdella peledina, as well as 28 oligochaetes and combined with homologous data for 17 polychaete outgroup taxa. Parsimony analysis of the combined aligned dataset supported monophyly of leeches, branchiobdellidans, and acanthobdellidans in 100% of jackknife replicates. Monophyly of the oligochaete order Lumbriculida with Acanthobdellida, Branchiobdellida, and Hirudinea was supported in 84% of jackknife replicates. These results provide support for the hypotheses that leeches and branchiobdellidans are sister groups, that acanthobdellidans are sister to them, and that together with the family Lumbriculidae they all constitute a clade within Oligochaeta. Results support synonymy of the classes Clitellata and the more commonly used Oligochaeta. Leeches branchiobdellidans, and acanthobdellidans should be regarded as orders equal to their closest relatives, the order Lumbriculida.

Ketamine and its preservative, benzethonium chloride, both inhibit human recombinant alpha7 and alpha4beta2 neuronal nicotinic acetylcholine receptors in Xenopus oocytes.

1. Ketamine is a dissociative anaesthetic that is formulated as Ketalar, which contains the preservative benzethonium chloride (BCl). We have studied the effects of pure racemic ketamine, the preservative BCl and the Ketalar mixture on human neuronal nicotinic acetylcholine receptors (nAChRs) composed of the alpha7 subunit or alpha4 and beta2 subunits expressed in Xenopus laevis oocytes. 2. Ketamine inhibited responses to 1 mM acetylcholine (ACh) in both the human alpha7 and alpha4beta2 nAChRs, with IC(50) values of 20 and 50 microM respectively. Inhibition of the alpha7 nAChRs occurred within a clinically relevant concentration range, while inhibition of the alpha4beta2 nAChR was observed only at higher concentrations. The Ketalar formulation inhibited nAChR function more effectively than was expected given its ketamine concentration. The surprising increased inhibitory potency of Ketalar compared with pure ketamine appeared to be due to the activity of BCl, which inhibited both alpha7 (IC(50) value of 122 nM) and alpha4beta2 (IC(50) value of 49 nM) nAChRs at concentrations present in the clinical formulation of Ketalar. 3. Ketamine is a noncompetitive inhibitor at both the alpha7 and alpha4beta2 nAChR. In contrast, BCl causes a parallel shift in the ACh dose-response curve at the alpha7 nAChR suggesting competitive inhibition. Ketamine causes both voltage-dependent and use-dependent inhibition, only in the alpha4beta2 nAChR. 4. Since alpha7 nAChRs are likely to be inhibited during clinical use of Ketalar, the actions of ketamine and BCl on this receptor subtype may play a role in the profound analgesia, amnesia, immobility and/or autonomic modulation produced by this anaesthetic.

Analysis of surgical complications and patient outcomes in a residency training program.

OBJECTIVES: This study compares surgical complications and patient outcomes between pelvic reconstructive surgery performed by an experienced surgeon (group 1) and those performed by resident physicians with the senior surgeon assisting and teaching (group 2). STUDY DESIGN: During a 5-year interval, 310 consecutive women underwent vaginal prolapse repair. Demographic, historic, and preoperative physical examination variables were compared. Intraoperative and postoperative outcomes were also compared. RESULTS: Patients operated on by the senior surgeon (Bob L. Shull) were thinner (group 1 vs group 2: 25.8 kg/m2 vs 27.1 kg/m2; P =.014), more often had prior prolapse or incontinence procedures (55% vs 33%; P <.001), and required shorter operating times (124 minutes vs 140 minutes; P =.002). The senior surgeon's patients differed from the resident physicians' patients with regard to stage of pelvic organ prolapse. No differences were observed for patient age (P =.51), estimated blood loss (P =.50), urologic complications (P =.59), and hospital stay (P =.25). The durability of the repairs was not different between the groups. CONCLUSIONS: We have demonstrated that in a tertiary referral practice resident surgeons can be taught to perform complex vaginal surgery with the only observed disadvantage being a slightly prolonged operative time.

A new instrument to measure sexual function in women with urinary incontinence or pelvic organ prolapse.

OBJECTIVE: Our aim was to develop a condition-specific, reliable, validated, and self-administered instrument to evaluate sexual function in women with pelvic organ prolapse or urinary incontinence. STUDY DESIGN: The questionnaire was designed after review of the literature and of nonspecific validated instruments. The study was completed in 2 phases. In phase 1 a total of 83 women completed both our questionnaire and the Incontinence Impact Questionnaire-7, with 20 women undergoing test-retest reliability analyses. Item analysis was based on the internal consistency, the correlations with the Incontinence Impact Questionnaire-7, the patient's age and self-rating of satisfaction, and the results of reliability testing. For final validation the questionnaire was administered in phase 2 to 99 women. Factor and item analyses were repeated, results were correlated with the Sexual History Form-12, and comparison was made between patients with high depression scores and those with low depression scores on the Symptom Questionnaire. RESULTS: Factor analysis identified 3 domains, labeled Behavioral/Emotive, Physical, and Partner-Related. Sexual function scores were highly correlated with scores on the Sexual History Form-12 for the questionnaire (r = -0.74; P <.001) and for both the Behavioral/Emotive and the Partner-Related domains (r = -0.79 and -0.5, respectively; P <.001). The Physical domain was correlated with scores on the Incontinence Impact Questionnaire-7 (r = -0.63; P <.001). Women with high depression scores on the Symptom Questionnaire had significantly lower scores on the final questionnaire, in comparison with women without depression (P <.001). CONCLUSION: We developed a condition-specific, validated, and reliable instrument, containing 31 items divided into 3 domains, to evaluate sexual functioning in women with urinary incontinence or pelvic organ prolapse.

Thiopental is a competitive inhibitor at the human alpha7 nicotinic acetylcholine receptor.

UNLABELLED: The nicotinic acetylcholine receptors (nAChRs) in the central nervous system may be a potential target for the anesthetic effects of thiopental. We evaluated the mechanism of action of thiopental on the human alpha7 nAChR by using 2-electrode voltage clamp methodology. Concentration response curves for agonist were prepared in the presence of 25-250 microM of thiopental. Inhibition by the S- and R-thiopental enantiomers was compared with inhibition by racemic thiopental. We found that thiopental acts as a competitive inhibitor at the human alpha7 nAChR. Inhibition is independent of membrane potential and the K(i(apparent)) is 13 microM of thiopental. The clinical 50% effective concentration for thiopental in humans is 25 microM. Thus, with a K(i(apparent)) of 13 microM, inhibition of the human alpha7 nAChR is within a clinically relevant range. The S- and R-enantiomers of thiopental cause inhibition indistinguishable from the inhibition caused by racemic thiopental. This discordance makes it unlikely that the alpha7 nAChR plays a role in loss of righting reflex induced by thiopental in mice, although nicotinic inhibition by thiopental may mediate other anesthetic effects and side effects. IMPLICATIONS: The receptors for nicotine in the brain may be involved in the mechanism of general anesthetics. We have shown that a human receptor for nicotine is inhibited by the anesthetic barbiturate thiopental, at concentrations used clinically. The nicotinic receptor thus may mediate some of the actions of this drug.

A transvaginal approach to repair of apical and other associated sites of pelvic organ prolapse with uterosacral ligaments.

OBJECTIVE: The objectives of this study were (1) to describe a group of women with pelvic organ prolapse associated with apical loss of support through grading with the Baden-Walker halfway system before, during, and after the corrective operation, (2) to describe the operative repair of the support defects, (3) to report the morbidity associated with the operative repair, and (4) to assess the durability of the repair at each site. STUDY DESIGN: Between January 1, 1994, and December 31, 1998, a total of 302 consecutive women with apical and associated other support defects were evaluated before, during, and after the corrective operation by the senior author (Bob L. Shull). All patients underwent transvaginal reconstructive surgery with native tissue. Two hundred eighty-nine patients (96%) returned for at least one postoperative visit, and they constitute the group used for the follow-up data. Perioperative morbidity was considered to include hemorrhage necessitating homologous blood transfusion, visceral injury, neurologic impairment, or death. Durability was assessed by means of life-table analysis for each of 5 sites in the vagina. RESULTS: All patients had preoperative or intraoperative evidence of grade 1 or greater apical loss of support of and at least one other site of pelvic organ prolapse. Two hundred eighty-nine patients (96%) returned for at least one postoperative visit. Two hundred fifty-one patients (group 1, 87%) had optimal anatomic outcomes, with no persistent or recurrent support defects at any site. Thirty-eight patients (group 2, 13%) had one or more sites with at least grade 1 loss of support during the follow-up interval. Twenty-four of these 38 patients had grade 1 defects that were detectable only on careful pelvic examination. Fourteen of these patients (5%) had grade 2 or greater persistent or recurrent support defects. The anterior segment (bladder) was the site with the most persistent or recurrent support defects, which means that it was the site of the least durable repair. The urethra and cuff had the most durable repairs. Morbidity included a 1% transfusion rate, a 1% ureteral injury or ureteral kinking rate, and a 0.3% postoperative death rate. CONCLUSION: Careful preoperative and intraoperative evaluation of pelvic support defects and the use of native connective tissue and uterosacral ligaments are associated with excellent anatomic outcomes. The durability of the surgical correction varies according to the individual site of repair and the duration of postoperative follow-up.

Rapid full-length genomic sequencing of two cytopathically heterogeneous Australian primary HIV-1 isolates.

Two Australian HIV-1 isolates, derived from patient blood (HIV(MBC200)) and cerebrospinal fluid (HIV(MBC925)), were characterized after in vitro culture in peripheral blood mononuclear cells (PBMC). Although virus replication was similar, as measured by cell-free reverse transcriptase activity, only one of the two isolates (HIV-1(MCB200)) consistently induced cell syncytia and depleted the PBMC population of CD4+ cells by cell killing. A novel technique, devised for rapidly obtaining high-quality viral sequence data and the full-length genomic sequence of these two isolates, is presented. Analysis of the predicted sequence of the viral Env proteins provides correlates of the observed phenotypes. Phylogenetic analysis derived using near full-length sequence of these and other HIV-1 subtype B genomic sequences (including two other Australian isolates) shows a star-shaped phylogeny with each member having a similar genetic diversity. These data expand the database of genomic sequence available from well-characterized primary clinical isolates of HIV-1 using a novel rapid technique.

Accuracy of clinical assessment of paravaginal defects in women with anterior vaginal wall prolapse.

OBJECTIVE: The objective of this study was to determine the accuracy of clinical assessment of paravaginal defects in women with anterior vaginal wall prolapse. STUDY DESIGN: A retrospective chart review of all women undergoing surgery for anterior vaginal wall prolapse during the years of 1994 to 1996 identified operative notes that described the surgical assessment of paravaginal support. These surgical findings were compared with the preoperative clinical assessment. Clinical parameters that predicted poor correlation were identified. Statistical analysis used the chi(2) test. RESULTS: One hundred seventeen patients had surgery for anterior vaginal prolapse. Seventy had documentation of an intraoperative paravaginal support evaluation. Of these, 44 patients had vaginal procedures, and 26 had abdominal procedures. All patients had at least stage 2 prolapse before surgery, and all were noted to have excellent pelvic support 4 to 6 weeks after surgery. The prevalence of paravaginal defects at surgery was 47% on the right and 41% on the left. The sensitivity and negative predictive value for the clinical assessment for paravaginal defects were good on both the right and left sides, whereas the specificity and positive predictive values were poor. Stage of prolapse, previous hysterectomy, or previous anterior colporrhaphy did not significantly affect the accuracy of the clinical examination in predicting fascial defects. However, previous retropubic urethropexy did significantly decrease the accuracy of the clinical examination in predicting right paravaginal defects (P <.01) but not left. CONCLUSION: Although preoperative clinical assessment for paravaginal defects is useful, it does not substitute for careful intraoperative evaluation for endopelvic fascial defects.

The value of an evaluation framework for telehealth initiatives.

Healthcare managers and policy makers will, in the immediate and near future, make major decisions about the allocation of scarce healthcare resources for telehealth 'solutions'. In our haste to capitalize on what technology can do we may be obscuring discussion and research about what technology should do. For example, currently much attention is being paid to standardization for technological aspects of telehealth. In contrast few efforts have been made to seek standardization in regards to a broad evaluation framework for telehealth. A body of opinion believes that missing in our rush into the on-line world is a systematic approach to research into the human, social, cultural, economic, and political factors associated with healthcare. As a result we lack the tools and experience necessary to assess the true value and implications of telehealth 'solutions'. Developing general guidelines for an evaluation framework, from needs assessment through integrated research to post-study assessment, would greatly enhance the quality of decision making by healthcare managers and policy makers. We propose a model--the Telehealth Integrated Research Model (TIRM)--as the first step in encouraging discussion and development of an internationally accepted standardized telehealth evaluation framework.

Urinary incontinence and pelvic organ prolapse in nulliparous women.

OBJECTIVE: To determine differences between vaginally parous and nulliparous women presenting with urinary incontinence and pelvic organ prolapse. METHODS: Seven hundred forty eight consecutive referrals with urinary incontinence or pelvic organ prolapse, 62 of whom were nulliparous, were included in the analysis. Five hundred thirty-seven (72%) had urinary incontinence and 235 (31%) had at least stage III pelvic organ prolapse. Each subject had standard history, physical examination, and multichannel urodynamic testing. Differences between parous and nulliparous women were compared using parametric and nonparametric analysis of variance and the chi2 test with Yates correction where appropriate. RESULTS: The only significant demographic difference between the groups was that parous women had more previous continence and prolapse surgery. There were significant differences in distribution of diagnoses according to parity, with the nulliparas much less likely to have pelvic organ prolapse. Among incontinent women without prolapse, nulliparas were significantly more likely to have pure detrusor instability. Of those with pure genuine stress incontinence, nulliparas were older, had less anterior vaginal wall descent, less bladder neck mobility, narrower genital hiatus and perineal body measurements, and lower maximum urethral closure pressures. Of those with pure detrusor instability, the only difference was that nulliparas were significantly younger. For women with stage III pelvic organ prolapse or worse, no significant difference in any measured characteristic was noted. CONCLUSION: Nulliparous women were less likely to present with pelvic organ prolapse and those with urinary incontinence differed little from incontinent parous women.

Urethral prolapse after collagen injection.

A woman who was treated for intrinsic urethral sphincteric deficiency with periurethral injection of glutaraldehyde cross-linked collagen had prolapse of the urethral mucosa and recurrence of incontinence. She subsequently required surgical resection and a fascia lata sling. This is the first known occurrence of this postinjection complication.

Physiologic evaluation of the pelvic floor.

This article has addressed the value, technique, rationale, and limitations of the commonly performed physiologic tests of the pelvic floor. Urodynamics provides a means for evaluation of the lower urinary tract and for assessment of the filling and emptying phases of the bladder. Neurophysiologic tests including EMG and nerve conduction studies offer methods to assess the neuromuscular integrity of the urethral and anal sphincteric mechanisms and the pelvic floor. Anorectal manometry studies provide a means of measuring pressure in the rectum and anal canal, rectal compliance, and anorectal reflexes and sensation in patients with anal incontinence and select patients with constipation. Colonic transit studies permit an assessment of functional constipation and may be helpful in the evaluation of patients in whom standard management of constipation has failed. Any test used in the evaluation of patients with pelvic floor dysfunction should be validated and found to be reliable. Most patients in need of complex physiologic evaluation are identified on the basis of their history and physical examination findings.

Clinical predictors of urinary incontinence in women.

OBJECTIVE: Our purpose was to characterize historic and clinical parameters in incontinent women to determine the predictive value for urodynamic diagnoses. STUDY DESIGN: The analysis includes 535 consecutive women with final diagnoses of genuine stress incontinence, detrusor instability, or both. Evaluations included a standardized history, examination, urinary diary, quantitation test, and urodynamics. The analysis used one-way analysis of variance, chi 2 analysis with Yates' correction, and Fisher's exact test. RESULTS: A total of 351 (66%) women were diagnosed with genuine stress incontinence, 102 (19%) with detrusor instability, and 82 (15%) with both. Half had symptoms of both stress incontinence and urge incontinence, of whom only 21% had both genuine stress incontinence and detrusor instability. Fewer than half of women diagnosed with genuine stress incontinence or detrusor instability had just symptoms of stress incontinence or urge incontinence, respectively. Evaluation of historic, examination, and urinary diary data for their influences on the predictive value of pure stress incontinence or urge incontinence revealed statistical differences for urethral hypermobility, estrogen deficiency, and incontinent episodes, yet they were not clinically practical predictors. CONCLUSIONS: Pure symptoms identify fewer than half of patients with pure genuine stress incontinence or detrusor instability; historic and clinical parameters do not improve the sensitivity of these symptoms.

Diagnosing intrinsic sphincteric deficiency: comparing urethral closure pressure, urethral axis, and Valsalva leak point pressures.

OBJECTIVES: Our purpose was to compare three measures proposed to diagnose intrinsic sphincteric deficiency: maximum urethral closure pressure, Valsalva leak point pressure, and straining urethral axis. STUDY DESIGN: A total of 159 women with pure genuine stress incontinence had the three measures determined in a standardized fashion. Critical cutoff values for the Valsalva leak point pressure (52 cm) and urethral axis (22 degrees) were established by examining relative frequency distribution curves, using closure pressure of 20 as the arbitrary benchmark value for the prevalence of intrinsic sphincteric deficiency. The distribution of cutoff values is described and differences among the measures with respect to risk factors for intrinsic sphincteric deficiency and incontinence severity were determined. RESULTS: Half the subjects fell below at least one cutoff value, but only 10% fell below all three. Sixty-four percent of subjects with either low closure pressure or leak point pressure had low values for the other, whereas 21% had discordance between them. Only 53% of subjects with low closure pressure and 40% with low leak point pressure had an axis < or = 22 degrees. Conversely, a substantial portion (36%) of subjects with pure genuine stress incontinence without urethral hypermobility had neither low urethral or leak point pressures. All three cutoff-values were associated with risk factors for intrinsic sphincteric deficiency, but only low closure and leak point pressures had significant associations with the severity of incontinence. CONCLUSIONS: Intrinsic sphincteric deficiency should be diagnosed by a composite of historic, urodynamic, anatomic, and clinical severity criteria. We would include a maximum urethral closure pressure < or = 20, a Valsalva leak point pressure < or = 50, and a stress urethral axis < or = 20 in this composite.

Uroflowmetry in women with urinary incontinence and pelvic organ prolapse.

OBJECTIVE: To characterize uroflowmetry parameters in women with pelvic organ prolapse (POP) and urinary incontinence (UI) and to assess the effects of clinical and urodynamic variables on these parameters. PATIENTS AND METHODS: The study comprised 655 consecutive women who presented with UI or POP and who had interpretable uroflowmetry values. Normal uroflowmetry values were defined as a maximum flow (Q(max)) > or = 15 mL/s, a mean flow (Q(mean)) > or = 10 mL/s, a post-void residual volume (PVR) < or = 100 mL and a continuous, single-peak waveform. Parametric and non-parametric analysis of variance and chi-square analysis were used to compare differences between diagnostic groups. Multiple linear regression models were developed to evaluate factors considered to influence uroflowmetry. RESULTS: Of the 655 patients, 471 (72%) had UI of whom 16% had pure detrusor instability (DI), 69% pure genuine stress incontinence (GSI) and 15% with both, and 184 (28%) had POP, 26% of whom also had DI. Of all patients, 72% had normal uroflowmetry patterns, 13% had multiple peaks and 15% had patterns with interrupted flow; 56% had completely normal uroflowmetry. There were significant differences in uroflowmetry values between the POP and UI groups, with the former having a lower Q(max) and Q(mean) (P < 0.001), larger PVRs (P < 0.001) and a lower percentage of totally normal uroflowmetry (33% and 64%, respectively, P < 0.001). Of patients with POP, 30% had a PVR > 100 mL. Because of the differences, the POP and UI groups were evaluated separately in the regression analysis. In both groups, the most important determinants of flow rate were the volume voided and pressure transmission ratio (PTR). However, when several factors (including age, voided volume, PTR and maximum detrusor pressure with flow and at Q(max)) were included in the model, they accounted for only 23-26% of the variability of flow in the patients with UI and 36-39% of the variability in patients with POP. The subsets of patients with pure DI in both the UI and POP groups had higher PVR volumes than the other subsets. CONCLUSIONS: These results show that the positive correlation between flow rate and voided volume described in normal populations is also observed in women with UI and POP. However, most of the variability in urine flow was not attributable to factors such as age, voided volume and PTR, confirming the complexity of the micturition mechanism. Women with POP had more objective evidence of emptying-phase dysfunction than women with UI, although most emptied their bladders efficiently. Finally, the results suggest that women with DI exhibit dysfunction of both inhibitory and facilitory detrusor control.

Protein kinase C-mediated phosphorylation of HIV-I nef in human cell lines.

Stable human cell lines expressing the human immunodeficiency virus type I (HIV-I) Nef protein from inducible promoters were used to analyze the phosphorylation status of Nef in vivo. Nef phosphorylation in both HeLa and Jurkat cells was stimulated by phorbol ester treatment. Phosphoamino acid analysis revealed a predominance of phosphoserine with a small proportion of phosphothreonine. Treatment of cells with selective protein kinase inhibitors revealed that Nef phosphorylation was markedly reduced by bisindolylmaleimide, an inhibitor of protein kinase C, but was unaffected by inhibitors of mitogen-activated protein kinase kinase or cAMP-dependent kinase. These data implicate protein kinase C in Nef phosphorylation in vivo, and thus confirm and extend earlier in vitro data. Phosphorylation of a nonmyristoylated Nef mutant was impaired, suggesting that membrane targeting of Nef was required for phosphorylation. This was expected given that activated protein kinase C translocates from the cytosol to the plasma membrane. However, analysis of the subcellular localization of phosphorylated wild-type Nef revealed that both the cytosolic and membrane-associated pools of Nef were phosphorylated to an equivalent extent. Thus the significance of myristoylation for Nef function may be in influencing protein conformation, although these data could be explained by a transient and dynamic interaction between myristoylated Nef and the plasma membrane.