The human Ab repertoire exhibits restrictions during fetal life characterized by biases of variable gene segment usage and lack of junctional diversity. We tested the hypotheses that Ab repertoire ...restriction persists in the early postnatal period and contributes to the observed poor quality of specific Ab responses made by neonates to viruses and vaccines. We analyzed the molecular determinants of B cell responses in humans to respiratory syncytial virus (RSV). Analysis of the variable gene segment usage of adult RSV-specific B cells revealed a repertoire profile in these cells similar to that seen in randomly selected B cells, which was VH3-dominant. Four gene segments (VH3–23, VH3–30, VH3–33 and VH4–04) accounted for almost half of the VH genes used. In contrast, very young infant RSV-specific antibodies exhibited a biased repertoire characterized by comparable use of the VH1, VH3, and VH4 families, and less common use of the four immunodominant gene segments. Infants and children older than three months used an antibody repertoire similar to that of adults. Mutational analysis revealed that the antibody variable genes of infants under three months of age also possessed significantly fewer somatic mutations in both framework and complementarity-determining region (CDR) regions than those of adults, even in a child with recurrent RSV infection. These data suggest that neonates use a biased antibody gene repertoire that is less VH3-focused and that possesses a dramatically lower frequency of somatic mutations. These biased features of the RSV-specific repertoire likely contribute to the poor functional Ab response in very young infants.
the purpose of this integrative review was to explore mentor-mentee relationships and benefits from the perspective of the mentor rather than that of the mentee.
all nursing and case management ...settings.
: Research studies related to the concept of mentoring were selected after a search of the CINAHL and the OVID databases for the years 1979 to 2009. Nonresearch articles were also utilized to obtain additional background information on the concepts of mentoring and case management.
an analysis of the research identified four different areas of focus: the mentoring relationship, mentor attributes, barriers to mentoring, and mentor benefits. Researchers focused on perceptions of the nurse mentoring relationship and identified that mentees and mentors have similar experiences and perceptions. Personal attributes, professional skills and abilities, and communication skills were three themes associated with the qualities of mentors. The barriers to nurse mentoring that were identified included difficulties developing relationships and lack of time. Positive impact on person or practice, personal satisfaction, professional success, and organizational and professional contributions were identified as benefits of being a nurse mentor.
nurses entering a specialty field may not have the necessary skill set for competent practice in that specialty and should be viewed as novice and advanced beginner specialty nurses until their level of proficiency is established. Novice case managers could benefit from mentorship for guidance through Benner's stages of clinical proficiency and development.
A SARS-CoV-2 serosurvey among first responder/healthcare personnel showed that loss of taste/smell was most predictive of seropositivity; percent seropositivity increased with number of COVID-19 ...symptoms. However, 22.9% with nine symptoms were seronegative, and 8.3% with no symptoms were seropositive. These findings demonstrate limitations of symptom-based surveillance and importance of testing.
The mechanism whereby cyclooxygenase-2 and its prostaglandin (PG) products are involved in colonic carcinogenesis is not fully understood. Prostacyclin (PGI(2)) is a major PG with antiapoptotic ...activity and is produced in the gastrointestinal tract. We reported previously that a human colorectal cancer (CRC) cell line, HCA-7, produces significant levels of PGE(2), PGD(2), thromboxane, and PGF(2alpha), but not PGI(2). We now report that human colonic fibroblast cell lines produce significant amounts of PGI(2) and that fibroblast lines derived from normal-appearing colonic mucosa of hereditary nonpolyposis CRC individuals produce 50-fold more PGI(2) than normal fibroblast lines derived from individuals with nonhereditary CRC. Coculture of HCA-7 cells with hereditary nonpolyposis CRC fibroblasts, but not normal fibroblasts, markedly reduced butyrate-induced apoptosis of HCA-7 cells. This antiapoptotic effect was inhibited by the cyclooxygenase-2 inhibitor rofecoxib and was restored by the stable PGI(2) analogue carbaprostacyclin. PGI(2) binds either G protein-coupled cell surface PGI(2) receptor or the nuclear peroxisome proliferator-activated receptor (PPAR) delta. PPAR delta likely mediates this antiapoptotic effect because HCA-7 cells express this receptor, and another PPAR delta agonist, docosahexaenoic acid, mimics the effect. We propose a novel mechanism by which stromal production of PGI(2) promotes survival of colonocytes through PPAR delta activation. This mechanism may have relevance to maintenance of cells in the normal crypt and to clonal expansion of mutant colonocytes during tumorigenesis.
The formulation of sulfite-containing propofol (SCP) has not been thoroughly investigated in patients with the extensive smoking history for the effects on the total respiratory system resistance ...after tracheal intubation. However adverse effects, including acute asthma and bronchospasm, have been reported with several other parenteral formulations of drugs containing sulfite as preservative. Therefore, the aim of this prospective randomized and double blind study was to investigate the effects of EDTA-containing propofol (ECP) and SCP on total respiratory system resistance (Rrs) in patients with the prolonged smoking history and undergoing propofol-based total intravenous anesthesia with tracheal intubation.
40 patients scheduled for general anesthesia were enrolled into the study. Anesthesia was induced with either 2 mg/kg ECP, or 2 mg/kg SCP followed by vecuronium (0.1 mg/kg) to ensure complete neuromuscular relaxation for the time of the study. Maintenance anesthesia was continued with propofol infusion at 0.15 mg/kg/min for the first 15 min after intubation. Total respiratory system resistance (Rrs), was measured continuously for 10 min postintubation.
The analysis of repeated Rrs measurements taken every minute for 10 min postintubation revealed trend consisting of higher Rrs in the SCP group when compared to the ECP group. The statistical analysis of the data performed using repeated measures analysis of covariance demonstrated statistically significant effect (P < 0.05) of the treatment group factor (SCP vs. ECP) and the time factor (time after intubation) on the postintubation Rrs.
The total respiratory system resistance measured repeatedly for 10 min after tracheal intubation in patients with smoking history is significantly elevated after induction with SCP than after induction with ECP. The preservative used for propofol formulation may alter the effects of propofol on the total respiratory system resistance in smokers.
Herpes zoster (HZ) is a frequent complication of advanced human immunodeficiency virus (HIV) infection. We determined the effect of highly active antiretroviral therapy (HAART) on reconstitution of ...varicella-zoster virus (VZV)—specific cell-mediated immunity (VZV-CMI) in 56 VZV- and HIV-infected children. VZV-CMI did not change over thecourse of ⩽3 years of observation, despite a reduction inHIV load. VZV-CMI correlated with lower HIV load but not with CD4 cell percentage. The incidence of HZ was unaffectedby HAART. None of 5 patients who developed HZ during the study had VZV-CMI before developing HZ. After developing HZ, only the 2 HAART-compliant patients developed VZV-CMI. Thus, VZV-specific immune reconstitution in HIV infection may require antigenic reexposure, in addition to control of HIV replication.
Determining which patients are at risk for prostatic urethral involvement of urothelial carcinoma may alter assessment of the prostatic urethra before radical cystectomy and ultimately influence the ...choice of urinary diversion. We determined risk factors predictive of prostatic urethral involvement using preoperative bladder tumor characteristics in male patients who underwent radical cystoprostatectomy due to urothelial carcinoma of the bladder.
We reviewed 192 consecutive radical cystectomy specimens from men with transitional cell carcinoma from June 1995 to June 2000. The prostatic urethra in each specimen was analyzed and urethral involvement was characterized as carcinoma in situ, intraductal invasion or prostatic stromal invasion. We then examined which clinical bladder tumor characteristics correlated with the incidence and extent of prostatic urethral involvement by performing multiple variable analysis.
Prostatic urethral involvement was evident in 30 of the 192 patients (15.6%). Of the 80 patients with carcinoma in situ in the bladder 25 (31.3%) had concomitant prostatic urethral involvement with carcinoma, whereas only 5 (4.5%) of the 112 with no evidence of carcinoma in situ had prostatic urethral involvement. Likewise 25 of the 72 patients (34.7%) with multifocal tumors had concomitant prostatic urethral involvement with carcinoma, whereas only 5 (4.2%) of the 120 with no evidence of multifocality had prostatic urethral involvement. In the multiple variable logistic regression model the odds of prostatic urethral involvement were 12 and 15-fold greater when carcinoma in situ and tumor multifocality were present, respectively.
Carcinoma in situ and/or tumor multifocality are valuable prognostic indicators of prostatic urethral involvement. However, in their absence prostatic urethral involvement was rare. Ultimately the extent of prostatic urethral involvement may influence decisions, such as the choice of urinary diversion and need for urethrectomy, in men undergoing radical cystectomy.
Mandatory minute ventilation (MMV) is a novel ventilator mode that combines synchronized intermittent mandatory ventilation (SIMV) breaths with pressure-supported spontaneous breaths to maintain a ...desired minute volume. The SIMV rate is automatically adjusted to maintain minute ventilation.
To evaluate MMV in a cohort of infants without parenchymal lung disease alternately ventilated by MMV and SIMV.
Neonates >33 weeks' gestational age and electively intubated for medical or surgical procedures were enrolled. Exclusionary criteria included: nonintact respiratory drive or active pulmonary disease. Infants were randomized to receive 2 hours of either SIMV or MMV and then crossed over to the other mode for 2 hours. Ventilator parameters and end-tidal CO(2) (etCO(2)) were measured via inline, mainstream monitoring and recorded every minute.
In total, 20 infants were evaluated. No statistically significant differences were found for overall means between etCO(2), minute volumes, peak inspiratory pressure (PIP), or positive end expiratory pressure (PEEP). However, there was a significant difference in the type of ventilator breaths given and in the mean airway pressure. Additionally, there was a statistically significant negative trend in MMV over time compared to SIMV, although this was subtle and could have been due to extreme cases.
Neonates with an intact respiratory drive can be successfully managed with MMV without an increase in etCO(2). While this mode generates similar PIP and PEEP, the decrease in mechanical breaths and the mean airway pressure generated with MMV may reduce the risk of some of the long-term complications associated with mechanical ventilation.
Increasingly, laparoscopy is being employed in the treatment of urologic malignancies. This is most apparent in kidney cancer, where laparoscopic radical nephrectomy is now considered to be a gold ...standard. Herein, we compared early postoperative morbidity in a contemporary series of open and laparoscopic radical nephrectomies. We reviewed all patients that underwent a radical nephrectomy between October 1999 and May 2001 at our institution. We then compared open radical nephrectomy patients to those undergoing laparoscopic approaches with specific attention to early complications. A total of 74 radical nephrectomies were performed: 41 open, 18 hand-assisted and 15 pure laparoscopic nephrectomies. Overall, complication rates between the open, hand-assist and pure laparoscopic groups were similar (10%, 17% and 12%, respectively,
P = 0.133). There was no statistically significant difference in ASA score (
P = 0.144), pre-operative hematocrit (
P = 0.575) or intra-operative blood loss (
P = 0.364). The open nephrectomy group had a statistically larger average tumor size (7.4 cm vs. 4.6 cm;
P = 0.005) and younger average age (57 vs. 63;
P = 0.019) than the laparoscopic group. Length of hospital stay was significantly shorter in the laparoscopic group (3.6 days vs. 1.7 days;
P < 0.0001). Laparoscopic radical nephrectomy has an acceptably low complication rate and compares favorably to open radical nephrectomy. The low rate of complications combined with the advantages of laparoscopic surgery favor a laparoscopic approach for the majority of patients with stage T1 and T2 tumors.
Background Individuals with adjustable gastric bands experience plateaus in weight loss. Patients commonly attribute this to a “loosening” of their band with time. We sought to elucidate a ...physiologic mechanism for this pattern in patient behavior and describe the feasibility of a pressure-based adjustment algorithm for adjustable gastric bands. Methods Following IRB protocol, 100 consecutive patients undergoing placement of the Lap-Band (Inamed) were enrolled and followed prospectively for 12 months. Intraband pressure measurements at band volumes 0 to 4 mL were recorded intraoperatively and at each subsequent band adjustment. Band adjustments were made using the currently accepted volume-based postoperative protocol. Results Seventy-nine patients were included in analysis. Mean percent excess weight loss for the study cohort was 36 ± 17% at a median followup of 347 days. During the time between adjustments, there was a statistically significant decrease (p < 0.001) in intraband pressure without a corresponding decrease in band volume. This was a result of a substantial change in the pressure−volume relationship of the Lap-Band. As time progressed, the Lap-Band developed less intraband pressure per unit volume. This change was not a result of changes in the elastic properties of the band material itself. Conclusions Between adjustments, Lap-Band patients experience gradual loss of satiety and a loosening of their band, despite stable band volume. Their experience is substantiated by degradation in their intraband pressures with time. We have demonstrated that intraband pressures correlate with the patient's clinical history and have thereby established the foundation for a pressure-based adjustment protocol.
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