Findings of universal cystoscopy at incontinence surgery and their sequelae.

OBJECTIVE: The purpose of this study was to report the frequency of abnormal cystoscopy at incontinence surgery and to identify risk factors and sequelae of injury. STUDY DESIGN: Findings of cystoscopy were collected prospectively in 3 multicenter surgical trials. Clinical, demographic, and procedure characteristics and surgeon experience were analyzed for association with iatrogenic injury and noninjury abnormalities. Impact of abnormalities on continence outcomes and adverse events during 12 months after the procedure were assessed. RESULTS: Abnormal findings in the bladder or urethra were identified in 95 of 1830 women (5.2%). Most injuries (75.8%) were iatrogenic. Lower urinary tract (LUT) injury was most common at retropubic urethropexy and retropubic midurethral sling (MUS) procedures (6.4% each), followed by autologous pubovaginal sling procedures (1.7%) and transobturator MUS (0.4%). Increasing age (56.9 vs 51.9 years; P = .04), vaginal deliveries (3.2 vs 2.6; P = .04), and blood loss (393 vs 218 mL; P = .01) were associated with LUT injury during retropubic urethropexy; however, only age (62.9 vs 51.4 years; P = .02) and smoking history (P = .04) were associated for pubovaginal sling procedures. No factors correlated with increased risk of injury at retropubic and transobturator MUS. Notably, previous incontinence surgery, concomitant procedures, anesthesia type, and trainee participation did not increase LUT injury frequency. Although discharge with an indwelling catheter was more common after trocar perforation compared with the noninjury group (55.6% vs 18.5%; P < .001), they did not differ in overall success, voiding dysfunction, recurrent urinary tract infections, or urge urinary incontinence. CONCLUSION: Universal cystoscopy at incontinence surgery detects abnormalities in 1 in 20 women. Urinary trocar perforations that are addressed intraoperatively have no long-term adverse sequelae.

Obesity and Native Tissue Repairs: A Secondary Analysis of the OPTIMAL Trial.

IMPORTANCE: The Operations and Pelvic Muscle Training in the Management of Apical Support Loss (OPTIMAL) Trial compared sacrospinous ligament fixation (SSLF) and uterosacral ligament suspension (ULS) surgical outcomes. Increasing body mass index (BMI) is associated with an increased risk of pelvic organ prolapse, and the prevalence of obesity is increasing worldwide. OBJECTIVE: The purpose of this study was to better understand the effect of obesity on the results of native tissue vaginal apical suspension procedures. STUDY DESIGN: This was a secondary analysis of the OPTIMAL Trial data set. Subgroup analysis was performed to compare surgical failure rates between SSLF and ULS across BMI subgroups after 2 years. RESULTS: There were 75, 120, 63, and 39 patients in the normal, overweight, class 1 obesity, and class 2 obesity or greater BMI subgroups, respectively. There were no statistically significant differences in surgical failure rates between SSLF and ULS within BMI subgroups; however, failure rates increased in the ULS group between the nonobese and obese groups (normal, 35.9% SSLF vs 30.6% ULS [P = 0.81]; overweight, 38.6% vs 30.2% [P = 0.44]; class 1 obesity, 38.7% vs 40.6% [P = 0.92]; class 2 obesity or greater, 21.1% vs 45% [P = 0.21]). CONCLUSIONS: The risk of surgical failure between SSLF and ULS was not significant across BMI subgroups. Additional investigation is required to further elucidate whether SSLF or ULS is a more reliable option for obese patients.

Sacral neuromodulation effects on periurethral sensation and urethral sphincter activity.

AIMS: To characterize the effect of sacral neuromodulation (SNM) on urethral neuromuscular function. METHODS: Following IRB approval, women with refractory overactive bladder (OAB) underwent standardized urethral testing prior to and after Stage 1 SNM implantation. Periurethral sensation was measured using current perception thresholds (CPT). Striated urethral sphincter activity was quantified using concentric needle electromyography (CNE) and Multi-Motor Unit Action Potential (MUP) analysis software. Nonparametric analyses were used to characterize pre/post changes with intervention. Baseline CPT and CNE findings were compared between SNM responders and non-responders. RESULTS: Twenty-seven women were enrolled in this pilot study with a mean age of 61 ± 13 years. Twenty of 26 women (76.9%) responded to SNM and went to Stage 2 permanent implantation. Four (14.8%) withdrew after Stage 1 implantation; three of the four withdrawals had not had therapeutic responses to SNM. CPT and CNE parameters did not significantly differ from baseline 2 weeks after SNM. Pre-SNM urethral sensation was not significantly different between responders and non-responders. However, responders had larger amplitude, longer duration and more turns and phases at baseline approaching significance, reflecting more successful urethral reinnervation, than non-responders. CONCLUSIONS: SNM does not alter urethral neuromuscular function 2 weeks post Stage 1 implantation.

Technical and operational users' opinions of a handheld device to detect directed energy.

INTRODUCTION: Lasers, a form of directed energy (DE), are a threat to pilots and Air Force personnel. In light of this threat, a handheld medical device called the "Tricorder" is under development to improve situational awareness of DE. Current operational procedures do not include methods for recording or handling new information regarding DE. The purpose of this study was to understand Air Force personnel opinions and beliefs about desired features and operational use to enhance user acceptance of the Tricorder. METHOD: Q-methodology was implemented to study opinions and beliefs related to DE. Two groups were approached, medical personnel in the Illinois Air National Guard and four active duty members of an Air Force Rescue Squadron. Both groups completed the same Q-sort of both operational and equipment concerns. RESULTS: Six opinion sets regarding operational concerns described 61% of the total variation in perceptions among participants. The factors were: concern over health effects, implications to individuals, combat/tactical concerns, force health protection, and theater/tactical concerns. Five opinion sets described 68% of the variation in the equipment functions perceived as most important. The participants indicated that ideally the device should measure exposure, enhance laser detection/response, support night vision and ease of use, detect threats, and enhance combat medicine. CONCLUSION: This survey revealed the complexity of equipment and the operational implications of detecting DE. Q-methodology is a unique strategy to both evaluate technology and explore users' concerns.

Qualitative assessment of the emotional and behavioural responses of haemophilia A carriers to negative experiences in their medical care.

Previous discussions with haemophilia A (HA) carriers suggested that carriers may experience inappropriate care, resulting in poor relationships with healthcare providers (HCPs; principally physicians and nurses), and unfortunate and extreme emotional and behavioural responses. This was a qualitative study to explore medical experiences of HA carriers and their emotional and behavioural responses. Eleven HA carriers and five Haemophilia Treatment Centre nurses were interviewed. Themes were identified using QSR NVivo 8.0. Carriers and nurses reported HA-related bleeding symptoms in carriers, including life-threatening haemorrhage following injury or medical intervention. Menorrhagia was common and distressing. Negative carrier experiences were related in the determination of genotypic and phenotypic status, management, precautions and HCP attitude, including dismissing carriers' symptoms, concerns or requests for care. Carriers responded with mistrust, lost confidence, disappointment, fear, anxiety, doubt of self or child, discussing experiences, avoidance of healthcare and self-treatment. Dismissive HCP attitudes, ignorance about bleeding disorders in women and unique aspects of the carrier population appear to make errors more likely. This study indicates that carriers experience inappropriate care and encounter dismissive attitudes, and respond emotionally and behaviourally. Our model suggests that systematic medical errors aggravate a negative feedback loop leading to negative emotional and behavioural responses and worsening carrier care. Improved carrier care policies and increased awareness of women's bleeding disorders may improve this situation. Further research is needed to determine whether the themes identified in this study accurately reflect the experiences of carriers in general.

Factors impacting quality of life in women with fecal incontinence.

PURPOSE: The aim of this study was to characterize differences in health-related quality of life among women presenting for treatment of fecal incontinence. METHODS: Among 155 women presenting for treatment of fecal incontinence in a specialty clinic, validated questionnaires measured impact on quality of life (Modified Manchester Health Questionnaire) and severity (the Fecal Incontinence Severity Index). Bowel symptoms, including frequency, urgency, and stool consistency, were ascertained. Comorbid diseases were self-reported. Linear regression models were constructed from significant univariate variables to examine differences observed in quality of life scores. RESULTS: The average age was 58.7 +/- 11.5 years, with no differences found in quality of life scores according to race, body mass index, or number of vaginal deliveries (P > .05). Younger age, increased urinary incontinence symptoms, prior cholecystectomy, prior hysterectomy, and severity of bowel symptoms correlated with a negative impact on quality of life in univariate analysis (P < .05). Average severity scores were 30.5 +/- 13.7, with moderate correlation seen with increasing severity and quality of life scores (R2 = 0.60). After controlling for severity, women had increased quality of life scores with more bowel urgency (15 points; 95% CI, 8.1-21.2), harder stool consistency (10 points; 95% CI, 3.8-16.3), and prior hysterectomy (9 points; 95% CI, 2.7-15.4). CONCLUSION: Bowel symptoms and having undergone a hysterectomy had the greatest negative impact on quality of life in women seeking treatment for fecal incontinence. Targeting individualized treatments to improve bowel symptoms may improve quality of life for women with fecal incontinence.

The ELFIN Mission.

The Electron Loss and Fields Investigation with a Spatio-Temporal Ambiguity-Resolving option (ELFIN-STAR, or heretoforth simply: ELFIN) mission comprises two identical 3-Unit (3U) CubeSats on a polar (∼93∘ inclination), nearly circular, low-Earth (∼450 km altitude) orbit. Launched on September 15, 2018, ELFIN is expected to have a >2.5 year lifetime. Its primary science objective is to resolve the mechanism of storm-time relativistic electron precipitation, for which electromagnetic ion cyclotron (EMIC) waves are a prime candidate. From its ionospheric vantage point, ELFIN uses its unique pitch-angle-resolving capability to determine whether measured relativistic electron pitch-angle and energy spectra within the loss cone bear the characteristic signatures of scattering by EMIC waves or whether such scattering may be due to other processes. Pairing identical ELFIN satellites with slowly-variable along-track separation allows disambiguation of spatial and temporal evolution of the precipitation over minutes-to-tens-of-minutes timescales, faster than the orbit period of a single low-altitude satellite (Torbit ∼ 90 min). Each satellite carries an energetic particle detector for electrons (EPDE) that measures 50 keV to 5 MeV electrons with Δ E/E < 40% and a fluxgate magnetometer (FGM) on a ∼72 cm boom that measures magnetic field waves (e.g., EMIC waves) in the range from DC to 5 Hz Nyquist (nominally) with <0.3 nT/sqrt(Hz) noise at 1 Hz. The spinning satellites (Tspin ∼ 3 s) are equipped with magnetorquers (air coils) that permit spin-up or -down and reorientation maneuvers. Using those, the spin axis is placed normal to the orbit plane (nominally), allowing full pitch-angle resolution twice per spin. An energetic particle detector for ions (EPDI) measures 250 keV - 5 MeV ions, addressing secondary science. Funded initially by CalSpace and the University Nanosat Program, ELFIN was selected for flight with joint support from NSF and NASA between 2014 and 2018 and launched by the ELaNa XVIII program on a Delta II rocket (with IceSatII as the primary). Mission operations are currently funded by NASA. Working under experienced UCLA mentors, with advice from The Aerospace Corporation and NASA personnel, more than 250 undergraduates have matured the ELFIN implementation strategy; developed the instruments, satellite, and ground systems and operate the two satellites. ELFIN's already high potential for cutting-edge science return is compounded by concurrent equatorial Heliophysics missions (THEMIS, Arase, Van Allen Probes, MMS) and ground stations. ELFIN's integrated data analysis approach, rapid dissemination strategies via the SPace Environment Data Analysis System (SPEDAS), and data coordination with the Heliophysics/Geospace System Observatory (H/GSO) optimize science yield, enabling the widest community benefits. Several storm-time events have already been captured and are presented herein to demonstrate ELFIN's data analysis methods and potential. These form the basis of on-going studies to resolve the primary mission science objective. Broad energy precipitation events, precipitation bands, and microbursts, clearly seen both at dawn and dusk, extend from tens of keV to >1 MeV. This broad energy range of precipitation indicates that multiple waves are providing scattering concurrently. Many observed events show significant backscattered fluxes, which in the past were hard to resolve by equatorial spacecraft or non-pitch-angle-resolving ionospheric missions. These observations suggest that the ionosphere plays a significant role in modifying magnetospheric electron fluxes and wave-particle interactions. Routine data captures starting in February 2020 and lasting for at least another year, approximately the remainder of the mission lifetime, are expected to provide a very rich dataset to address questions even beyond the primary mission science objective.

Securing ePHI--can clinicians and IT ever agree?

The Health Insurance Portability and Accountability Act (HIPAA) affects patients, IT professionals and providers. Implementation requires cooperation among clinical and staff, presuming an equal understanding of the law and its implementation. Two Q-sort sessions with different Conditions of Instruction (COI) were attended by each study participant: one COI focused on a personal perspective about the effectiveness of security standards in preventing or mitigating security problems with EPHI. The second COI examined the participant's perception of how a co-worker would see aspects of security problems. The first Q-sort resulted in four distinct factors, two of which, administratively minded and patient centric, suggest divergence in opinion. The second sort's results reveal the inability of participants to forecast what their co-workers will perceive as salient to a security situation. Results suggest that people might adapt to changes required by security applications if the changes in workflow are described in role-based situations.

Predictors of success with postoperative voiding trials after a mid urethral sling procedure.

PURPOSE: We identified predictors of passing a voiding trial after incontinence surgery with a mid urethral sling and examined if successful performance on a voiding trial was maintained. MATERIALS AND METHODS: A total of 89 women scheduled for incontinence surgery were enrolled from July 2005 until April 2006. Voiding trials were performed the day of discharge from the hospital, with a two-thirds volume void after a 300 ml fill considered passing. Those who passed underwent a second voiding trial 3 hours later. RESULTS: Of the participants 60 (67.4%) underwent tension-free vaginal tape surgery, 29 underwent transobturator tape (32.6%) and 64 (71.9%) underwent concurrent vaginal repairs. A total of 59 (67.0%) participants passed the first voiding trial. Univariate analysis identified 12 potential predicting variables for passing the first voiding trial. From these 12, model building via backward stepwise logistic regression found maximum flow on preoperative uroflowmetry to be the only significant predictive variable (p = 0.0002). Of the 59 women who passed the initial voiding trial 9 (16.4%) failed the second voiding trial. None of the 11 participants who had maximal flow rates greater than 30 cc per second failed the first or second voiding trial, whereas 17 of 22 subjects (77.3%) who had maximal flow rates less than 15 cc per second failed either of these trials. CONCLUSIONS: Maximum flow rates on preoperative uroflowmetry were the best predictor of passing an initial voiding trial after undergoing a mid urethral sling procedure for incontinence. However, the ability to maintain performance on a second voiding trial, even only 3 hours after passing an initial trial, is not assured.

Obesity and pelvic floor disorders: a systematic review.

OBJECTIVE: To review the current literature and summarize the effect of obesity on outcomes of surgical treatment of pelvic floor disorders as well as the effect of weight loss on pelvic floor disorder symptoms. DATA SOURCES: Relevant sources were identified by a MEDLINE search from 1966 to 2007 using the key words obesity, pelvic floor disorders, urinary incontinence (UI), fecal incontinence, and pelvic organ prolapse (POP). References of relevant studies were hand searched. METHODS OF STUDY SELECTION: Relevant human observational studies, randomized trials, and review articles were included. A total of 246 articles were identified; 20 were used in reporting and analyzing the data. Meta-analyses were performed for topics meeting the appropriate criteria. TABULATION, INTEGRATION, AND RESULTS: There is good evidence that surgery for stress UI in obese women is as safe as in their nonobese counterparts, but cure rates may be lower in the obese patient. Meta-analysis revealed cure rates of 81% and 85% for the obese and nonobese groups, respectively (P<.001; odds ratio [OR] 0.576, 95% confidence interval [CI] 0.426-0.779). Combined bladder perforation rates were 1.2% in the obese and 6.6% in the nonobese (P=.015; OR 0.277, 95% CI 0.098-0.782). There is little evidence on which to base clinical decisions regarding the treatment of fecal incontinence and POP in obese women, because few comparative studies were identified addressing the outcomes of prolapse surgery in obese patients compared with healthy-weight patients. Weight loss studies indicate that both bariatric and nonsurgical weight loss lead to significant improvements in pelvic floor disorder symptoms. CONCLUSION: Surgery for UI in obese women is safe, but more trials are needed to evaluate its long-term effectiveness as well as treatments for both fecal incontinence and POP. Weight loss, both surgical and nonsurgical, should be considered in the treatment of pelvic floor disorders in the obese woman.

ARED: human AU-rich element-containing mRNA database reveals an unexpectedly diverse functional repertoire of encoded proteins.

The adenylate uridylate-rich elements (AREs) mediate the rapid turnover of mRNAs encoding proteins that regulate cellular growth and body response to exogenous agents such as microbes, inflammatory and environmental stimuli. However, the full repertoire of ARE-containing mRNAs is unknown. Here, we explore the distribution of AREs in human mRNA sequences. Computational derivation of a 13-bp ARE pattern was performed using multiple expectation maximization for motif elicitations (MEME) and consensus analyses. This pattern was statistically validated for the specificity towards the 3'-untranslated region and not coding region. The computationally derived ARE pattern is the basis of a database which contains non-redundant full-length ARE-mRNAs. The ARE-mRNA database (ARED; http://rc.kfshrc.edu.sa/ared) reveals that ARE-mRNAs encode a wide repertoire of functionally diverse proteins that belong to different biological processes and are important in several disease states. Cluster analysis was performed using the ARE sequences to demonstrate potential relationships between the type and number of ARE motifs, and the functional characteristics of the proteins.

MDR1 C3435T polymorphisms correlate with cyclosporine levels in de novo renal recipients.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the multidrug resistance (MDR1) gene correlate with the intestinal function of P-glycoprotein (PGP). PGP serves as a hydrophobic export pump that extrudes cyclosporine (CsA) across the luminal membrane thus preventing CsA absorption. These genetic variants may predict CsA exposure levels in the early posttransplantation period. METHODS: CsA absorption profiles were established in 75 renal transplant patients using total daily dose and body weight adjusted 4-hour area under the time-concentration curve, AUC(0-4)/mg dose/kg body weight, on posttransplant day 3. These patients were subsequently genotyped for C3435T and G2677T polymorphisms using real-time polymerase chain reaction. An analysis was conducted to assess the independent impact of C3435T and G2677T SNPs on CsA bioavailability. RESULTS: C3435T polymorphisms were found to be an independent predictor of CsA AUC(0-4)/mg dose/kg levels on postoperative day 3. An inverse correlation was found between the number of T alleles and AUC values such that every T allele was associated with an approximate 15% decrement in AUC(0-4)/mg dose/kg (P = .034). A similar nonsignificant trend was observed for G2677T polymorphisms. CONCLUSIONS: MDR1 SNPs are correlated with CsA exposure in the early post-transplant period. Polymorphisms, in conjunction with other criteria, may become a useful tool to optimize initial drug dosing in renal transplantation.

Increase in intracellular Na+: transmembrane signal for rejoining of DNA strand breaks in proliferating lymphocytes.

Two early events in the mitogen-induced entry of murine splenocytes into proliferation are (a) a rapid rise in influx of Na+, causing its total internal concentration to increase by 42 +/- 7% within 2 h of culture with concanavalin A (Con A), and (b) rejoining of some 3000 DNA strand breaks per diploid genome within the same period. Con A did not induce rejoining in low Na+ (less than 9 mM) medium, but the process began directly when Na+ was added, at its usual concentration, to the growth medium. Incubation of cells with ouabain, an inhibitor of the Na+K+-ATPase, or monensin, a Na+ ionophore, caused an increase in the internal Na+ concentration in normal, but not in low, Na+ medium. In the former (but not in the latter) medium, both ouabain and monensin caused rejoining of the DNA strand breaks to occur in resting lymphocytes, i.e., in the absence of mitogen. Stimulation of splenocytes with Con A also resulted in a rapid but transient increase in the level of intracellular free Ca2+. This effect was also observed in the absence of extracellular Na+; however, deprivation of extracellular Ca2+ completely abolished this effect. Moreover, the intracellular free Ca2+ level was significantly higher in cells suspended in Na+-free buffer or medium. Since the Con A-induced rejoining of DNA strand breaks occurred in the absence of extracellular Ca2+ and removal of extracellular Na+ had no inhibitory effect on the Con A-induced increase in the level of intracellular free Ca2+, the Con A-stimulated repair could not have been mediated by the initial increase in Ca2+ influx. The early mitogen-induced increase in the internal Na+ concentration is a necessary and sufficient signal for the rejoining of breaks, an event that must occur before the proliferating lymphocytes can replicate their DNA.

Geographical distribution of congenital heart defects in Saudi Arabia.

BACKGROUND: Congenital heart defects (CHD), which are caused by abnormalities early in fetal life, encompass over 50 diagnoses. Since the detailed etiology is unknown, the geographical distribution of defects might suggest likely risk factors. METHODS: The geographical distribution of 5 865 Saudi Arabian nationals with CHD was studied by cross-matching their residential provinces and towns with a geographical information system provided by the General Directorate for Military Survey. Population data were obtained from the 1413H census. RESULTS: CHD cases were mostly distributed across the provinces in proportion to their total population but due to their size and inhomogeneity, province-based thematic maps were found to be misleading. City-based maps were preferable and showed similar geographic distributions for cases registered in successive years. Thematic maps of the distribution of the CHD burden highlighted the southwestern provinces, nearthe border with Yemen, and the northeast section of the Eastern Province. CONCLUSIONS: Patterns of disease in Saudi Arabia are best studied at the level of individual towns and villages. The CHD registry has already attained good national coverage and can therefore support nationwide epidemiological studies. Southwestern Saudi Arabia and the northern part of the Eastern Province appear to exhibit a higher burden of CHD.

Medication effects on periurethral sensation and urethral sphincter activity.

AIM: The aim of this study was to characterize urethral neuromuscular function before and 2 weeks after medication therapy. METHODS: Premenopausal women without lower urinary tract symptoms were randomly allocated to 1 of the 6 medications for 2 weeks (pseudoephedrine ER of 120 mg, imipramine of 25 mg, cyclobenzaprine of 10 mg, tamsulosin of 0.4 mg, solifenacin of 5 mg, or placebo). At baseline and after medication, participants underwent testing: quantitative concentric needle electromyography (CNE) of the urethral sphincter using automated multimotor unit action potential software, current perception threshold (CPT) testing to measure periurethral sensation, and standard urodynamic pressure flow studies (PFS). Nonparametric tests were used to compare pre-post differences. RESULTS: Fifty-six women had baseline testing, 48 (85.7%) completed follow-up CNE, and 49 (87.5%) completed follow-up CPT and PFS testing. Demographics showed no significant differences among medication groups with respect to age (mean, 34.3; SD, 10.1), body mass index (mean, 31.8; SD, 7.5), parity (median, 1; range, 0-7), or race (14% Caucasian, 80% African American). The PFS parameters were not significantly different within medication groups. No significant pre-post changes in CNE values were noted; however, trends in amplitudes were in a direction consistent with the expected physiologic effect of the medications. With CPT testing, a trend toward increased urethral sensation at the 5-Hz stimulation level was observed after treatment with pseudoephedrine (0.15-0.09 mA at 5 Hz, P = 0.03). CONCLUSIONS: In women without lower urinary tract symptoms, pseudoephedrine improved urethral sensation but not urethral neuromuscular function on CNE or PFS. Imipramine, cyclobenzaprine, tamsulosin, solifenacin, and placebo did not change urethral sensation or neuromuscular function.

Nasopharyngeal carcinoma in Saudi Arabia: a retrospective study of 166 cases treated with curative intent.

A retrospective review was performed of the medical records of 166 adult patients with biopsy-proven carcinomas of the nasopharynx treated with curative intent at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. All patients were treated between June 1975 and December 1985 using megavoltage therapy equipment. Most patients presented with advanced nodal disease: 23 patients (13.9%) were N0, 16 patients (9.6%) were N1, 29 patients (17.5%) were N2, and 98 patients (59%) were N3. The overwhelming majority of patients had nonkeratinizing lesions (158/166). At the time of analysis, mean follow-up time was 24.2 months (range 2-108). Actuarial curves are presented for local/regional control as a function of T-stage and N-stage and for survival and time to development of distant metastases as a function of N-stage. At 4 years local/regional control was 70% for T1 lesions, 59% for T2 lesions, 30% for T3 lesions, and 35% for T4 lesions. There was little correlation between local/regional control and N-stage being about 50% at 4 years for all nodal subgroups. Only six patients exhibited an isolated first failure in the regional nodes alone, whereas 60 patients failed initially at the primary site (either alone or in conjunction with a simultaneous nodal failure). The development of distant metastases correlated to some extent with nodal disease ranging from 20% at 4 years for T1/T2 N0 patients to 70% for patients who initially presented with N3 disease. Survival data was more difficult to obtain due to cultural biases in a medically unsophisticated patient population. True survival curves are bounded by calculating actuarial curves in two ways: death as the failure endpoint and death plus lost-with-active-disease as failure endpoints. In terms of the latter curves, at 4 years "survival" ranged from 39% for patients with T1/T2 N0 lesions to 23% for patients with N3 lesions.

Immunogenicity of a new Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) (PedvaxHIB).

Haemophilus influenzae type b is responsible for an estimated 15,000 to 20,000 cases of meningitis per year in the United States, mainly in children 2 months to 5 years old. The mortality rate from meningitis due to H influenzae type b infections ranges from 5% to 10%. Despite antibiotic treatment, up to 35% of survivors have permanent neurologic sequelae. In addition to meningitis, H. influenzae type b is responsible for other invasive infections, including epiglottitis, septicemia, cellulitis, septic arthritis, osteomyelitis, pneumonia, pericarditis, and otitis media; approximately 30,000 cases H influenzae diseases occur annually in the United States. The diseases peak in incidence between 6 and 12 months of age, with almost one half of the cases occurring before 1 year of age. About 75% of disease caused by H influenzae type b occurs in children younger than 24 months old. The incidence of disease is higher in children of certain groups, including blacks, Hispanics, Eskimos and Native Americans, young children attending day-care facilities, patients with asplenia or antibody-deficiency syndromes, and children of lower socioeconomic status. There is considerable evidence that antibody to the capsular polysaccharide (polyribosylribitol-phosphate [PRP] of H influenzae type b is protective.(ABSTRACT TRUNCATED AT 250 WORDS)

Chicken mucin-cross-reactive antigen.

We have previously described a chicken heterophile antigenic determinant (CHAD-1) shared by Mycobacterium smegmatis and chicken tissues. We then demonstrated that CHAD-1 is present on several chicken glycoproteins and that its immunoreactive domains are highly branched asparagine-linked oligosaccharides terminating in N-acetylglucosamine residues. In the present study, we have shown that CHAD-1 is also expressed by mucin purified to homogeneity from a soluble mucus of chicken intestine. Another antigen found on chicken mucin is a chicken mucin-cross-reactive antigen (CMCRA). Antisera to this antigen were produced by immunization of rabbits with an enriched preparation of CHAD-1 isolated from the bursa of Fabricius. These antisera were absorbed with Mycobacterium smegmatis (to block the anti-CHAD-1 antibody) and with chicken serum, and then used for immunoperoxidase staining of chicken tissue sections for CMCRA. The latter antigen was detected in most medullary cells of the bursa, in epithelial cells and Hassal's corpuscles of the thymus, and in mucus-producing cells of the intestine, esophagus, trachea, and bronchi. Using Western immunoblot analysis, we demonstrated that CMCRA is expressed by a number of polypeptides extracted from bursal lymphoid cells. These polypeptides could not be detected in extracts of thymus, spleen, peripheral blood or bone marrow mononuclear cells.

Neurological mapping using an electron microscope/microprocessor data acquisition system.

Quantitative electron microscopy is used widely in many neurobiological laboratories but can be greatly enhanced by the computer storage, display and analysis of features or boundaries observed under the microscope. An interactive system is described, in which a microprocessor and microcomputer combination controls the data acquisition and display; more detailed analysis can be carried out on a mainframe computer. The performance of this system is examined and it is shown to be a cheap and effective solution, capable of expansion in many directions.

Genetic analysis of familial myelodysplastic syndrome: absence of linkage to chromosomes 5q31 and 7q22.

Myelodysplastic syndrome (MDS) is a hematological disorder that occurs primarily in the elderly as an acquired, sporadic disease. Familial cases of MDS are rare. We have identified a kindred with three affected individuals, with early age of onset, suggesting a possible inherited predisposition to this disease. Using a molecular genetic approach, we examined whether bands 5q31 or 7q22 or both, the chromosomal regions most frequently associated with sporadic MDS, are involved in familial expression of MDS in this pedigree. Linkage analysis using polymorphic microsatellite DNA markers demonstrated that neither 5q31 nor 7q22 cosegregated with MDS in this family. There was no history of common environmental or occupational exposure among family members with MDS. In addition, analysis of polymorphisms at two loci [glutathione S-transferase T1 and M1 (GSTT1 and GSTM1)] involved in carcinogen detoxification and associated with cancer susceptibility, including increased risk for MDS, showed no evidence for enhanced sensitivity to environmental carcinogens in affected family members. Taken together, our findings suggest that (1) there is an inherited predisposition to MDS in this kindred; and (2) genes at 5q31 and 7q22, the regions most commonly associated with sporadic MDS, are excluded from a causal role in this family's disease.