Intrarectal Foley catheter-assisted high-intensity focused ultrasound ablation for benign uterine diseases beyond the treatment region.

OBJECTIVE: To evaluate the feasibility of using an intrarectal Foley catheter during ultrasound-guided high-intensity focused ultrasound (US-HIFU) in patients with benign uterine diseases of the posterior wall beyond the HIFU therapeutic range. METHODS: Patients were treated with US-HIFU and lesion changes were monitored using contrast-enhanced MRI from June 2020 to September 2021. A Foley catheter was inserted into the rectum to facilitate a successful US-HIFU ablation. Complications and lesion responses were recorded during the treatment and follow-up. RESULTS: Thirteen patients with 14 lesions beyond the device's treatable area were enrolled. The average placement time and insertion depth of the intrarectal Foley catheter was 7.6 ± 2.7 min and 23.2 ± 7.6 cm, respectively. A median of 50 mL degassed water was injected into the Foley catheter balloon. All 14 lesions were successfully pushed into a treatable area and subjected to HIFU. The average treatment time, irradiation time, and total therapeutic energy of HIFU were 44.2 ± 17.3 min, 394.4 ± 295.7 s, and 73.3 ± 46.6 kJ, respectively. The mean non-perfusion volume (NPV) in all treated lesions was 23.2 ± 19.2 cm3, and the mean NPV ratio was 57.8 ± 16.9%. Major complications were not observed. CONCLUSION: Intrarectal Foley catheter-assisted US-HIFU is effective and safe. Its clinical application could benefit patients with benign uterine diseases outside the HIFU therapeutic range.

Intrarectal Administration of Adelmidrol plus Hyaluronic Acid Gel Ameliorates Experimental Colitis in Mice and Inhibits Pro-Inflammatory Response in Ex Vivo Cultured Biopsies Derived from Ulcerative Colitis-Affected Patients.

Improving clinical outcomes and delaying disease recrudescence in Ulcerative Colitis (UC) patients is crucial for clinicians. In addition to traditional and new pharmacological therapies that utilize biological drugs, the development of medical devices that can ameliorate UC and facilitate the remission phase should not be overlooked. Drug-based therapy requires time to be personalized and to evaluate the benefit/risk ratio. However, the increasing number of diagnosed UC cases worldwide necessitates the exploration of new strategies to enhance clinical outcomes. By incorporating medical devices alongside pharmacological treatments, clinicians can provide additional support to UC patients, potentially improving their condition and slowing down the recurrence of symptoms. Chemically identified as an azelaic acid derivative and palmitoylethanolamide (PEA) analog, adelmidrol is a potent anti-inflammatory and antioxidant compound. In this study, we aimed to evaluate the effect of an intrarectal administration of 2% adelmidrol (Ade) and 0.1% hyaluronic acid (HA) gel formulation in both the acute and resolution phase of a mouse model of colitis induced via DNBS enema. We also investigated its activity in cultured human colon biopsies isolated from UC patients in the remission phase at follow-up when exposed in vitro to a cytomix challenge. Simultaneously, with its capacity to effectively alleviate chronic painful inflammatory cystitis when administered intravesically to urological patients such as Vessilen, the intrarectal administration of Ade/HA gel has shown remarkable potential in improving the course of colitis. This treatment approach has demonstrated a reduction in the histological damage score and an increase in the expression of ZO-1 and occludin tight junctions in both in vivo studies and human specimens. By acting independently on endogenous PEA levels and without any noticeable systemic absorption, the effectiveness of Ade/HA gel is reliant on a local antioxidant mechanism that functions as a "barrier effect" in the inflamed gut. Building on the findings of this preliminary study, we are confident that the Ade/HA gel medical device holds promise as a valuable adjunct in supporting traditional anti-UC therapies.

Intrarectal diazepam following pelvic reconstructive surgery: a double-blind, randomized placebo-controlled trial.

BACKGROUND: Patients undergoing vaginal hysterectomy with native tissue pelvic reconstruction typically have low pain levels overall in the postoperative period. Notwithstanding, pain control immediately after surgery may be more challenging and a barrier to same-day discharge. Intrarectal diazepam has been used for acute and chronic pelvic pain and has a pharmacokinetic profile ideal for intermittent use. However, its use has not been investigated after the surgical intervention. OBJECTIVE: This study aimed to evaluate the effect of diazepam rectal suppositories on early postoperative pain after hysterectomy and vaginal reconstruction for pelvic organ prolapse. STUDY DESIGN: This was a double-blind, randomized, placebo-controlled trial comparing postoperative pain scores after vaginal hysterectomy with native tissue prolapse repairs. Patients were randomized to receive either an intrarectal 10-mg diazepam suppository or an identical placebo. Moreover, the participants completed the questionnaires at baseline, the morning of postoperative day 1, and 2 weeks after the operation. Surveys included visual analog scales for pain, a validated Surgical Satisfaction Questionnaire, and queries regarding medication side effects and postoperative recovery. The primary outcome was pain scores based on a visual analog scale approximately 3 hours after surgery. The secondary outcomes included total morphine equivalents after surgery, patient satisfaction with pain control, same-day discharge outcome, and overall satisfaction. The chi-square, Fisher exact, and Mann-Whitney tests were used. Based on a 10-mm difference in postoperative vaginal pain using the visual analog scale, sample size was calculated to be 55 patients in each arm to achieve 80% power with an alpha of.05. RESULTS: From February 2020 to August 2021, 130 participants were randomized. Of those participants, 7 withdrew, and 123 were analyzed: 60 in the diazepam group and 63 in the placebo group. The median age was 65 years (interquartile range, 27-80), the median body mass index was 27.9 kg/m2 (interquartile range, 18.70-45.90), and 119 of 123 participants (96.7%) were White. There was no difference in the baseline characteristics, prolapse stage, or types of procedures performed between groups. Most participants had concurrent uterosacral ligament suspension with anterior and posterior repairs. Of note, 50 of 123 participants (41%) had midurethral slings. Moreover, 61 of 123 participants (50%) were discharged on the day of surgery. There was no difference in the primary outcome of vaginal pain 3.5 to 6.0 hours postoperatively (25 vs 21 mm; P=.285). In addition, the amount of rescue narcotics used in the immediate postoperative period (19.0 vs 17.0 MME; P=.202) did not differ between groups. At 2-weeks postoperatively, patients in the placebo group reported higher satisfaction with pain control in the hospital (31 vs 43 mm; P=.006) and pain control at home (31 vs 42 mm; P=.022). No difference was noted between same-day discharges and those who were admitted overnight. CONCLUSION: The placement of a 10-mg diazepam rectal suppository immediately after pelvic reconstructive surgery did not improve pain or narcotic usage in the early postoperative period. Although the placebo group reported slightly higher satisfaction with pain control 2 weeks after surgery, overall pain levels were low. Therefore, we do not believe that the addition of diazepam to the postoperative regimen is warranted.

Once-Weekly Oral Dosing of MK-8591 Protects Male Rhesus Macaques From Intrarectal Challenge With SHIV109CP3.

BACKGROUND: MK-8591 (4'-ethynyl-2-fluoro-2'-deoxyadenosine [EFdA]) is a novel reverse transcriptase-translocation inhibitor. METHODS: We assessed MK-8591 as preexposure prophylaxis in the rhesus macaque model of intrarectal challenge with simian/human immunodeficiency virus (SHIV). In study 1, 8 rhesus macaques received 3.9 mg/kg of MK-8591 orally on day 0 and once weekly for the next 14 weeks. Eight controls were treated with vehicle. All rhesus macaques were challenged with SHIV109CP3 on day 6 and weekly for up to 12 challenges or until infection was confirmed. The dose of MK-8591 was reduced to 1.3 and 0.43 mg/kg/week in study 2 and further to 0.1 and 0.025 mg/kg/week in study 3. In studies 2 and 3, each dose was given up to 6 times once weekly, and animals were challenged 4 times once weekly with SHIV109CP3. RESULTS: Control macaques were infected after a median of 1 challenge (range, 1-4 challenges). All treated animals in studies 1 and 2 were protected, consistent with a 41.5-fold lower risk of infection (P < .0001, by the log-rank test). In study 3, at a 0.1-mg/kg dose, 2 rhesus macaques became infected, consistent with a 7.2-fold lower risk of infection (P = .0003, by the log-rank test). The 0.025-mg/kg dose offered no protection. CONCLUSIONS: These data support MK-8591's potential as a preexposure prophylaxis agent.

Periprostatic nerve block alone versus combined with perineal pudendal nerve block or intrarectal local anesthesia during transrectal ultrasound-guided prostate biopsy: A prospective randomized controlled trial.

OBJECTIVES: To compare the efficacy, safety and cost of combinations of perineal pudendal nerve block + periprostatic nerve block and intrarectal local anesthesia + periprostatic nerve block with the standard technique (periprostatic nerve block). METHODS: The study was designed as a randomized prospective controlled trial. Patients with elevated serum prostate-specific antigen values (prostate-specific antigen ≥4 ng/mL) and/or abnormal digital rectal examination findings were included in the study. Patients with anorectal diseases, chronic prostatitis, previous history of prostate biopsy and anorectal surgery were excluded from the study. A total of 148 patients (group 1 [periprostatic nerve block], n = 48; group 2 [intrarectal local anesthesia + periprostatic nerve block], n = 51; group 3 [perineal pudendal nerve block + periprostatic nerve block], n = 49) were included in the final analysis. Pain during insertion and manipulation of the transrectal ultrasound probe was recorded as visual analog scale 1, pain during penetration of the biopsy needle into the prostate and sampling was recorded as visual analog scale 2, and pain during the entire procedure recorded as visual analog scale 3. RESULTS: The mean visual analog scale 1 score was significantly lower in group 3, when compared with group 1 and group 2 (P < 0.001). There was no significant difference between the groups in terms of the mean visual analog scale 2 score. The mean visual analog scale 3 score was significantly lower in group 3 when compared with other groups (P < 0.001). The total cost for transrectal ultrasound-guided biopsy in the intrarectal local anesthesia + periprostatic nerve block group was significantly higher than the other two groups. CONCLUSIONS: The combination of perineal pudendal nerve block and periprostatic nerve block provides more effective pain control than intrarectal local anesthesia plus periprostatic nerve block and periprostatic nerve block alone, with similar complication rates and without increasing cost.

Innervation asymmetry of the external anal sphincter in aging characterized from high-density intra-rectal surface EMG recordings.

AIMS: The innervation zone asymmetry of the external anal sphincter (EAS) has been investigated as a risk factor for the development of fecal incontinence (FI). This study aims to utilize an intra-rectal high-density surface electromyogram (HD-sEMG) recording and advanced HD-sEMG decomposition technique to characterize the effects of aging on the asymmetry of EAS functional innervation. METHODS: HD-sEMG signals were recorded intra-rectally from six healthy young and seven healthy elderly women during voluntary contractions of the EAS. EMG signals were decomposed into constituent motor unit action potentials (MUAPs) and the innervation zone of each decomposed motor unit was identified. Asymmetry index (AI) was defined and calculated for all subjects. The maximum squeezing pressures of the EAS were also measured for all subjects as a comparison. RESULTS: The HD-sEMG decomposition and AI calculation were successfully performed from EMG data acquired from all the subjects. The AI values were 28.7 ± 17.0% for the young group and 55.6 ± 18.8% for the elderly group. The AI and EAS contraction strength were found to be negatively correlated (P < 0.05). A two-tailed student's t-test demonstrated a significant increase in AI with age by comparison between two groups (P < 0.05). CONCLUSIONS: Our work demonstrates, for the first time, that EAS functional innervation tends to become increasingly asymmetrical with advancing age, and this increase is associated with a compromised anorectal function. Results suggest that the intra-rectal HD-sEMG will serve as an advanced tool for assessing and monitoring the anorectal neuromuscular function minimally invasively under different pathophysiological conditions.

Combined intrarectal lidocaine gel and periprostatic nerve block: A 'balanced' anaesthesia for transrectal ultrasound-guided prostate biopsy?

BACKGROUND AND AIM: Periprostatic nerve block (PNB) which appears to be the gold standard for pain relief during transrectal ultrasound-guided prostate (TrusP) biopsy has been proven to be lacking in providing satisfactory anaesthesia during transrectal ultrasound (Trus) probe insertion into the anorectum necessitating the addition of another technique to produce a 'balanced' anaesthesia. The aim of this study was to determine whether combined intrarectal lidocaine gel and periprostatic nerve block (cGPNB) will provide adequate anaesthesia at all stages of TrusP compared with caudal block (CB). PATIENTS AND METHODS: Data were prospectively collected from patients with indications for TrusP who were randomly assigned to either cGPNB (Group A) or CB (Group B). Comparative analysis of the numerical rating pain score (NRS) between two groups was done after administration of anaesthesia, Trus probe insertion, biopsy needle puncture of the prostate and 1 h after biopsy. RESULTS: There were 56 patients in Group A and 53 in Group B. There was no significant difference in NRS grouping between the two arms of the study after administration of anaesthesia (P = 0.93), biopsy needle puncture of the prostate (P = 0.28) and 1 h after the procedure (P = 0.39). There was no statistically significant difference in the number of patients with no/mild pain between the two arms of the study during probe insertion (P = 0.65). None of the patients in both arms of the study had severe pain. Across Group A and B, 35 (62.5%) versus 40 (75.5%), 20 (35.7%) versus 11 (20.8%) and 1 (1.8%) versus 2 (3.8%) adjudged the procedure as very tolerable, fairly tolerable and intolerable respectively (P = 0.20). All the patients in Group A versus 49 (92.5%) in Group B will choose the same anaesthesia for subsequent biopsies (P = 0.11). CONCLUSIONS: cGPNB provides balanced anaesthesia at all stages of TrusP with excellent patient tolerability.

[Intrarectal local anesthesia versus periprostatic nerve block in transrectal prostate biopsy for patients with different prostate volumes: A prospective randomized controlled trial].

OBJECTIVE: To evaluate the analgesic effect of intrarectal local anesthesia (IRLA) versus that of periprostatic nerve block anesthesia (PPNB) in initial transrectal ultrasound-guided prostate biopsy (TRUS-PB) for patients with different prostate volumes (PV). METHODS: A total of 253 patients undergoing initial TRUS-PB in our hospital from January 2014 to November 2017 were divided into three PV groups (<50 ml, 50－100 ml, and >100 ml), each again randomized into three subgroups (control, IRLA, and PPNB) with the random number table method. The pain during the procedure was assessed based on the Visual Analogue Scale (VAS) scores and the blind method was used by the biopsy operator, VAS valuator and data analyst. RESULTS: Among the patients with PV <50 ml, the VAS scores in the blank control, IRLA, and PPNB subgroups were 4.39±0.87, 3.51±0.84 and 3.43±1.07, respectively, remarkably higher in the control than in the IRLA and PPNB groups (P<0.05), but with no statistically significant differences between the latter two (P>0.05). Among those with PV of 50－100 ml, the VAS scores in the three subgroups were 4.50±1.05, 4.38±1.13 and 3.38±1.44, respectively, markedly higher in the control and IRLA than in the PPNB group (P<0.05), but with no statistically significant differences between the former two groups (P>0.05). Among those with PV >100 ml, the VAS scores in the three subgroups were 5.19±1.05, 5.00±1.25 and 4.19±0.91, respectively, remarkably higher in the former two groups than in the latter (P<0.05), but with no statistically significant differences between the former two groups (P>0.05). CONCLUSIONS: Either IRLA or PPNB can be recommended for initial TRUS-PB in patients with PV <50 ml, PPNB for those with PV of 50－100 ml, and PPNB with other painkillers for those with PV >100 ml.

High Infection Rates for Adult Macaques after Intravaginal or Intrarectal Inoculation with Zika Virus.

Unprotected sexual intercourse between persons residing in or traveling from regions with Zika virus transmission is a risk factor for infection. To model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with Zika virus by intravaginal or intrarectal routes. In macaques inoculated intravaginally, we detected viremia and virus RNA in 50% of macaques, followed by seroconversion. In macaques inoculated intrarectally, we detected viremia, virus RNA, or both, in 100% of both species, followed by seroconversion. The magnitude and duration of infectious virus in the blood of macaques suggest humans infected with Zika virus through sexual transmission will likely generate viremias sufficient to infect competent mosquito vectors. Our results indicate that transmission of Zika virus by sexual intercourse might serve as a virus maintenance mechanism in the absence of mosquito-to-human transmission and could increase the probability of establishment and spread of Zika virus in regions where this virus is not present.

Continuous recording of intrarectal pressures during the second phase of labour: correlations with postpartum pelvic floor complaints. A biomechanical-clinical study.

INTRODUCTION AND HYPOTHESIS: We correlated intrarectal pressure parameter recordings during the second phase of labour in primiparous women with postpartum pelvic floor (PF) complaints to try to define a critical pressure threshold for the occurrence of permanent PF injury. METHODS: Using a microsystem device, the duration of bearing-down efforts, the area under the pressure curve and the peak pressure during bearing-down efforts were continuously recorded in 43 women with spontaneous delivery (group one) and in 17 women with forceps-assisted delivery (group two). PF complaints were assessed using ICS-validated questionnaires established before delivery and 14 ± 6 months after delivery. RESULTS: Postpartum PF complaints were not significantly different between the groups. The first and second phases of labour were longer in women of group two. The three parameters measured were not correlated with the baby's weight or mode of delivery. The duration of bearing-down efforts was correlated with difficulty voiding and lower abdominal discomfort in women of group one only. The area under the pressure curve was correlated with feeling of urgency to void, urge incontinence, drops escape, decreased frequency of orgasm and difficulties in reaching orgasm in women of group two only. Peak pressure values were not correlated with any PF dysfunction. CONCLUSIONS: Intrarectal pressure parameters during second phase of labour show no significant correlations with obstetric parameters, but were significantly correlated with some urinary and sexual PF complaints 14 months after spontaneous and forceps-assisted delivery with a higher incidence of significant correlations in women of group two with forceps-assisted delivery, probably because of the longer first and second phases of labour.

The Efficiency and Safety of Intrarectal Topical Anesthesia for Transrectal Ultrasound-Guided Prostate Biopsy: A Systematic Review and Meta-Analysis.

OBJECTIVE: The study aims to review the current evidence to determine the efficiency and safety of intrarectal topical anesthesia (ITA) for transrectal ultrasound-guided prostate biopsy. MATERIALS AND METHODS: A comprehensive search of the literature was performed using Medline, Embase and Cochrane central register of controlled trials. All randomized controlled trials (RCTs) comparing the efficacy and safety of periprostatic nerve block (PNB), ITA, and PNB combined with ITA were included. The mean pain scores after the biopsy procedure, the mean pain scores after the probe insertion and adverse events were evaluated. RESULTS: Thirty-2 RCTs were identified in the meta-analysis. ITA could significantly reduce pain during probe insertion compared to control and placebo. The PNB group had less pain after the prostate biopsy than the ITA group. PNB combined with ITA could significantly reduce pain during the biopsy procedure compared to ITA alone. No significant differences were found in adverse events in ITA versus control, ITA versus placebo, and ITA versus PNB. CONCLUSIONS: ITA could reduce pain after probe insertion and pain after biopsy although it was inferior to PNB in reducing pain during prostate biopsy. ITA combined with PNB was more effective than ITA alone. In addition, it was safe to perform ITA for prostate biopsy.

The critical roles of tumor-initiating cells and the lymph node stromal microenvironment in human colorectal cancer extranodal metastasis using a unique humanized orthotopic mouse model.

Colorectal cancer (CRC) is the second-most common cause of cancer-related mortality. The most important prognostic factors are lymph node (LN) involvement and extranodal metastasis. Our objective is to investigate the interactions between CD133(+)CXCR4(+) (CXC receptor 4) colorectal cancer tumor-initiating cells (Co-TICs) and the LN stromal microenvironment in human CRC extranodal metastasis. We established a unique humanized orthotopic xenograft model. Luciferase-tagged CRC cell lines and human cancer cells were injected intrarectally into nonobese diabetic/SCID mice. Mesenteric LN stromal cells, stromal cell line HK, or CXCL12 knockdown HK (HK-KD-A3) cells were coinoculated with CRC cells. Tumor growth and metastasis were monitored by bioluminescent imaging and immunohistochemistry. We found that this model mimics the human CRC metastatic pattern with CRC cell lines or patient specimens. Adding LN stromal cells promotes CRC tumor growth and extranodal metastasis (P < 0.001). Knocking down CXCL12 impaired HK cell support of CRC tumor formation and extranodal metastasis. When HK cells were added, sorted CD133(+)CXCR4(+) Co-TICs showed increased tumor formation and extranodal metastasis capacities compared to unseparated and non-Co-TIC populations. In conclusion, both Co-TIC and LN stromal factors play crucial roles in CRC metastasis through the CXCL12/CXCR4 axis. Blocking Co-TIC/LN-stromal interactions may lead to effective therapy to prevent extranodal metastasis.

Health worker and policy-maker perspectives on use of intramuscular artesunate for pre-referral and definitive treatment of severe malaria at health posts in Ethiopia.

BACKGROUND: The World Health Organization (WHO) recommends injectable artesunate given either intravenously or by the intramuscular route for definitive treatment for severe malaria and recommends a single intramuscular dose of intramuscular artesunate or intramuscular artemether or intramuscular quinine, in that order of preference as pre-referral treatment when definitive treatment is not possible. Where intramuscular injections are not available, children under 6 years may be administered a single dose of rectal artesunate. Although the current malaria treatment guidelines in Ethiopia recommend intra-rectal artesunate or alternatively intramuscular artemether or intramuscular quinine as pre-referral treatment for severe malaria at the health posts, there are currently no WHO prequalified suppliers of intra-rectal artesunate and when available, its use is limited to children under 6 years of age leaving a gap for the older age groups. Intramuscular artesunate is not part of the drugs recommended for pre-referral treatment in Ethiopia. This study assessed the perspectives of health workers, and policy-makers on the use of intramuscular artesunate as a pre-referral and definitive treatment for severe malaria at the health post level. METHODS: In-depth interviews were held with 101 individuals including health workers, malaria focal persons, and Regional Health Bureaus from Oromia and southern nations, nationalities, and peoples' region, as well as participants from the Federal Ministry of Health and development partners. An interview guide was used in the data collection and thematic content analysis was employed for analysis. RESULTS: Key findings from this study are: (1) provision of intramuscular artesunate as pre-referral and definitive treatment for severe malaria at health posts could be lifesaving; (2) with adequate training, and provision of facilities including beds, health posts can provide definitive treatment for severe malaria using intramuscular artesunate where referral is delayed or not possible; (3) health workers at health centres and hospitals frequently use the intravenous route because it allows for co-administration of other drugs, but they find the intramuscular route easier to use at the health post level; (4) the reasons commonly cited against the management of severe malaria using intramuscular artesunate at health post level were: lack of capacity to manage complications and fear of irrational drug use; (5) use of intramuscular artesunate at health post level will require evidence on safety and feasibility before policy shift. CONCLUSION: From the perspective of health workers, use of intramuscular artesunate as pre-referral treatment of severe malaria cases at the health post is possible but dependent on training and availability of skilled workers. Use of intramuscular artesunate as definitive treatment at health posts was not supported, however, operational research to establish its feasibility, safety and efficacy was recommended to guide any implementation of such an intervention.

Functional mapping of the pelvic floor and sphincter muscles from high-density surface EMG recordings.

INTRODUCTION AND HYPOTHESIS: Knowledge of the innervation of pelvic floor and sphincter muscles is of great importance to understanding the pathophysiology of female pelvic floor dysfunctions. This report presents our high-density intravaginal and intrarectal electromyography (EMG) probes and a comprehensive innervation zone (IZ) imaging technique based on high-density EMG readings to characterize the IZ distribution. METHODS: Both intravaginal and intrarectal probes are covered with a high-density surface electromyography electrode grid (8 × 8). Surface EMG signals were acquired in ten healthy women performing maximum voluntary contractions of their pelvic floor. EMG decomposition was performed to separate motor-unit action potentials (MUAPs) and then localize their IZs. RESULTS: High-density surface EMG signals were successfully acquired over the vaginal and rectal surfaces. The propagation patterns of muscle activity were clearly visualized for multiple muscle groups of the pelvic floor and anal sphincter. During each contraction, up to 218 and 456 repetitions of motor units were detected by the vaginal and rectal probes, respectively. MUAPs were separated with their IZs identified at various orientations and depths. CONCLUSIONS: The proposed probes are capable of providing a comprehensive mapping of IZs of the pelvic floor and sphincter muscles. They can be employed as diagnostic and preventative tools in clinical practices.

B subunits of cholera toxin and thermolabile enterotoxin of Escherichia coli have similar adjuvant effect as whole molecules on rotavirus 2/6-VLP specific antibody responses and induce a Th17-like response after intrarectal immunization.

The purpose of this study was to evaluate the adjuvant effect of the B subunits of cholera toxin (CT) and the thermolabile enterotoxin of Escherichia coli (LT) by the intrarectal route of immunization and compare them to the whole molecules CT and LT-R192G, a non toxic mutant of LT, using 2/6-VLP as an antigen, in mice. All molecules induced similar antigen specific antibody titers in serum and feces, whereas different T cell profiles were observed. CTB and LTB, conversely to CT and LT-R192G, did not induce detectable production of IL-2 by antigen specific T cells. Moreover, CTB, conversely to LT-R192G, CT and LTB, did not induce antigen specific CD4+CD25+Foxp3- and Foxp3+ T cells, thus showing different effects between the B subunits themselves. However, all molecules induced an antigen specific Th17 response. In conclusion, B subunits are potent adjuvants on B cell responses by the intrarectal route. Although their impact on T cell responses are different, all molecules induce a 2/6-VLP-specific Th17 T cell response that may play a major role in helping B cell responses and thus in adjuvanticity and protection.

Tetrodotoxin/Saxitoxin Accumulation Profile in the Euryhaline Marine Pufferfish Chelonodontops patoca.

Marine Takifugu pufferfish, which naturally possess tetrodotoxins (TTXs), selectively take up and accumulate TTXs, whereas freshwater Pao pufferfish, which naturally possess saxitoxins (STXs), selectively take up and accumulate STXs. To further clarify the TTXs/STXs selectivity in pufferfish, we conducted a TTX/STX administration experiment using Chelonodontops patoca, a euryhaline marine pufferfish possessing both TTXs and STXs. Forty nontoxic cultured individuals of C. patoca were divided into a seawater group (SW, acclimated/reared at 33‱ salinity; n = 20) and a brackish water group (BW, acclimated/reared at 8‱ salinity; n = 20). An aqueous TTX/STX mixture was intrarectally administered (both at 7.5 nmol/fish), and five individuals/group were analyzed after 1-48 h. Instrumental toxin analyses revealed that both TTX and STX were taken up, transferred, and retained, but more STX than TTX was retained in both groups. TTX gradually decreased and eventually became almost undetectable in the intestinal tissue, while STX was retained at ~5-10% of the dose level, and only STX showed transient transfer in the liver. The BW group showed a faster decrease/disappearance of TTX, greater STX retention in the intestine, and greater STX transient transfer to the liver. Thus, C. patoca appears to more easily accumulate STXs than TTXs, especially under hypoosmotic conditions.

A Comparison of the Intrarectal and Intramuscular Effects of a Dexmedetomidine, Ketamine and Midazolam Mixture on Tear Production in Cats: A Randomized Controlled Trial.

Cats are often easily stressed and uncooperative. The use of sedative agents in the feline species is widely used to perform even minor clinical and diagnostic procedures. The aim of this study is to assess the impact on tear film production of the intrarectal route (IR) administration of a mixture of dexmedetomidine, ketamine and midazolam in comparison with the intramuscular (IM) one. A group of twenty cats were involved in a randomized and blinded clinical trial. A clinical and ophthalmological examination was conducted on the cats. The IR group received dexmedetomidine 0.003 mg kg-1, ketamine 4 mg kg-1 and midazolam 0.4 mg kg-1; the IM group received dexmedetomidine 0.003 mg kg-1, ketamine 2 mg kg-1 and midazolam 0.2 mg kg-1. A Shirmer tear test I (STT- I) was conducted 1 h before sedation and 2', 10', 20', 30', 40', and 80' post drug administration. The reaction to STT-I administration was also evaluated. The IM group has a lower mean tear production than the IR group for all time points evaluated. Cats in the IM group showed less reaction to STT-I administration. This study may suggest that the effect of sedative agents administered by the IR route has a lower incidence on tear production than the IM one. The use of eye lubricant is recommended in any case.

The Patient Hides the Truth, but the Computer Tomography Examination Restores It!

In this article, we present the case of a patient who hid the real reason for which he came to the emergency room. This patient in this case is a 61-year-old man, who presented to the emergency department for symptoms relevant to respiratory disease. However, the initial diagnosis turned out to be only the "tip of the iceberg" in the evolution and treatment of this patient. Fournier gangrene is a fulminant form of infectious necrotizing fasciitis of the perineal, genital, or perianal regions, which frequently affects men, but can also occur in women and children. It is a rare but life-threatening disease. Due to potential complications, it is important to diagnose Fournier gangrene as early as possible. Although antibiotics and aggressive debridement have been widely accepted as standard treatment, the mortality rate remains high. In many cases, the doctor's mission is much more difficult than it first seems. The challenges to which the doctor is subjected, especially in the emergency room, are immense. In establishing a diagnosis and emergency treatment, all parties involved-medical staff, on the one hand, and patients and relatives, on the other hand-must collaborate so that the outcome is a positive one. The overall conclusion of the medical team was that Fournier gangrene in the patient was the consequence of both the presence of an intrarectal foreign body, as well as excessive alcohol consumption. The case of our patient with Fournier gangrene and an intrarectal foreign body had a positive outcome due to quick, aggressive, and adequate medical and surgical management, as well as the fact that the patient had no other associated pathologies beyond alcohol "passion." Our patient's case is an example of the exceptional situations we sometimes encounter in medical practice.

Comparison of Certain Intrarectal versus Intramuscular Pharmacodynamic Effects of Ketamine, Dexmedetomidine and Midazolam in Cats.

The aim of this clinical trial was to evaluate the impacts of administration via the intrarectal route (IR) in cats on their heart and respiratory rates, blood pressure, body temperature, and sedation quality compared to the intramuscular route (IM). The intramuscular group (IMG) received 0.003 mg kg−1 dexmedetomidine, 2 mg kg−1 ketamine, and 0.2 mg kg−1 midazolam while the intrarectal group (IRG) protocol was 0.003 mg kg−1 dexmedetomidine, 4 mg kg−1 ketamine, and 0.4 mg kg−1 midazolam. Cardiorespiratory values, temperature, and sedation score were measured 2 min after administration and then every 5 min up to the 40th minute. Cats belonging to IRG reacted less strongly to the drug, as opposed to those receiving intramuscular administration (2/10 in IRG vs. 8/10 in IMG). Average time between drug administration and standing position was 44.9 ± 5.79 in IRG and 57 ± 9.88 min in IMG. In IRG, maintenance of SpO2 values is >95% at each time point. Median and range peak of sedation {7 (5)} in IMG occurs at 20th, 25th, and 30th minutes post drug administration while was lower in IRG. Cardiorespiratory values were slightly lower in IMG than in IRG, but always constant in both treatments. Temperature did not differ between groups. At this dosage, although sedation score was higher in IMG, intrarectal route could be efficacious for performing minimally invasive clinical and diagnostic procedures in cats.