A postbiotic from Aspergillus oryzae attenuates the impact of heat stress in ectothermic and endothermic organisms.

Heat stress is detrimental to food-producing animals and animal productivity remains suboptimal despite the use of heat abatement strategies during summer. Global warming and the increase of frequency and intensity of heatwaves are likely to continue and, thus, exacerbate the problem of heat stress. Heat stress leads to the impairment of physiological and cellular functions of ectothermic and endothermic animals. Therefore, it is critical to conceive ways of protecting animals against the pathological effects of heat stress. In experiments with endothermic animals highly sensitive to heat (Bos taurus), we have previously reported that heat-induced systemic inflammation can be ameliorated in part by nutritional interventions. The experiments conducted in this report described molecular and physiological adaptations to heat stress using Drosophila melanogaster and dairy cow models. In this report, we expand previous work by first demonstrating that the addition of a postbiotic from Aspergillus oryzae (AO) into the culture medium of ectothermic animals (Drosophila melanogaster) improved survival to heat stress from 30 to 58%. This response was associated with downregulation of genes involved in the modulation of oxidative stress and immunity, most notably metallothionein B, C, and D. In line with these results, we subsequently showed that the supplementation with the AO postbiotic to lactating dairy cows experiencing heat stress decreased plasma concentrations of serum amyloid A and lipopolysaccharide-binding protein, and the expression of interleukin-6 in white blood cells. These alterations were paralleled by increased synthesis of energy-corrected milk and milk components, suggesting enhanced nutrient partitioning to lactogenesis and increased metabolic efficiency. In summary, this work provides evidence that a postbiotic from AO enhances thermal tolerance likely through a mechanism that entails reduced inflammation.

Methyl donor supplementation suppresses the progression of liver lipid accumulation while modifying the plasma triacylglycerol lipidome in periparturient Holstein dairy cows.

Co-supplementation of methyl donors may lower hepatic lipid content in transition cows. To define the ability of methyl donor supplementation (MDS) to reduce hepatic lipid content and modify the plasma lipidome, 30 multiparous Holstein cows (2.04 ± 0.69 lactations; 689 ± 58 kg of body weight; 3.48 ± 0.10 units of body condition score) were fed a ration with or without rumen-protected methyl donors (22 g/d of Met, 10 g/d of choline chloride, 3 g/d of betaine, 96 mg/d of riboflavin, and 1.4 mg/d of vitamin B12) from d -28 before expected calving through d 14 postpartum. Cows were randomly enrolled based on predefined selection criteria (body condition score and parity). Base diets without MDS were formulated for gestation (15.4% crude protein with a predicted Lys-to-Met ratio of 3.25; 1.44 Mcal of net energy for lactation/kg of dry matter) and lactation (16.6% crude protein with a predicted Lys-to-Met ratio of 3.36; 1.64 Mcal of net energy for lactation/kg of dry matter). Blood sampling occurred from d -28 relative to expected calving through d 14 postpartum. Liver tissue was biopsied at d -28 relative to expected calving and on d 5 and 14 postpartum. In addition to routine analyses, serum AA concentrations on d 10 and 12 were quantified using mass spectrometry. Plasma triacylglycerol (TAG) and cholesteryl esters (CE) were qualitatively measured using time-of-flight mass spectrometry. Data were analyzed using a mixed model with repeated measures. Dry matter intake and milk yield were not modified by MDS. The transition from d -28 relative to expected parturition to d 14 postpartum was characterized by increased plasma fatty acid (0.15 to 0.71 mmol/L) and ß-hydroxybutyrate (0.34 to 0.43 mmol/L) levels and liver lipid content (3.91 to 9.16%). Methyl donor supplementation increased the serum Met level by 26% and decreased the serum Lys-to-Met ratio by 21% on d 10 and 12, respectively. Moreover, the increase in hepatic lipid content from d 5 through 14 postpartum was suppressed with MDS relative to control (3.57 vs. -0.29%). Dietary MDS modified the TAG and CE lipidome. For example, MDS increased plasma TAG 46:3 (carbon number:double bond) by 116% relative to control cows on d 5 postpartum. Moreover, MDS tended to increase plasma CE 34:6. In contrast, MDS lowered plasma TAG 54:8 by 39% relative to control cows on d 5 postpartum. We concluded that in the absence of gains in dry matter intake and milk and milk protein yields, dietary MDS slows the progression of hepatic lipid accumulation and modifies the plasma TAG lipidome in transition cows.

Treatment of Refractory Gastrointestinal Bleeding in Patients With Portal Hypertension: A Case Series and Treatment Algorithm.

In patients with portal hypertension, ectopic varices can develop at any site along the gastrointestinal tract outside the classically described gastroesophageal location. Like esophageal variceal hemorrhage, bleeding from ectopic varices can be life-threatening. Diagnosis and treatment of ectopic varices can be challenging; to date, no effective treatment algorithm has been described. A systematic teamwork approach to diagnosing and treatment of ectopic varices is required to successfully manage hemorrhage from ectopic varices.

Local excision of rectal cancer followed by radical surgery because of poor prognostic features does not compromise the long term oncologic outcome.

AIM: The outcome of patients undergoing full-thickness local excision (LE) of rectal cancers may be compromised if poor prognostic features are found in the LE specimen. Our aim was to evaluate the long-term results of radical surgery performed after LE because poor prognostic factors are identified. METHOD: Patients with biopsy-proven rectal cancer who had undergone full-thickness LE followed by radical surgery because of a positive margin, T stage ≥3, lymphovascular invasion, poor differentiation or mucinous histology were identified from a prospective database. Their records were retrospectively reviewed and follow up was updated. RESULTS: Between 1995 and 2003, 17 patients underwent LE followed by radical surgery because of poor prognostic features. Combined chemotherapy and radiotherapy was given to 11 (65%) patients before radical surgery. Patients underwent radical surgery after a median of 14 (range: 0-40) weeks from LE. Nine underwent a low anterior resection and eight an abdominoperineal resection. At the time of radical surgery, residual disease was found in six (35%) patients (in lymph nodes in three; intramural in two; and both lymph nodes and intramural in one). Four of the patients with residual disease had undergone neoadjuvant therapy before radical surgery. The mean follow up was 110 (95% CI: 92-129) months. Recurrence-free survival at 10 years was 88%. There was no case of local recurrence, and two patients died of metastatic disease. CONCLUSION: In this series patients who underwent early radical surgery because of poor prognostic features found at LE had good overall and cancer-specific long-term survival. Even after neoadjuvant therapy, more than a third of patients had residual disease at the time of radical surgery. We therefore recommend radical surgery with neoadjuvant therapy when poor prognostic features are found at LE.

Non-consultant career grade doctors in genitourinary medicine - are they up to the job? National survey 2007.

Non-consultant career grade doctors in genitourinary (GU) medicine have been called 'a reliable silent backbone of the specialty' and 'a spare pair of hands' [Hiscock E. Non-consultant career grade staff in GU medicine; a reliable backbone or, a spare pair of hands? Int J STD AIDS 1996;7:375-7]. But are they adequate pairs of hands? This survey, conducted in July 2007, examined the work, qualifications and experience of these doctors. A summary of the 154 (19%) responses is presented. Respondents contributed 773 sessions per week, including 164 special interest sessions; 30 (19.5%) were doing regular HIV work. Non-clinical work was described by 134 (87%), especially teaching (132 [86%]) and management roles (26 [17%]). Postgraduate qualifications were cited by 148 (96%), including DipGUM or Dip Ven (51 [33%]), contraception qualifications such as DFFP, MFFP or FFFP (110 [71%]), MRCGP (43 [8%]) and qualifications in psychosexual medicine/therapy (10 [6.5%]). Over half were trained in general practice. Certificate of completion of specialist training or equivalent was held by 55 (36%), including two in GU medicine. These doctors are well qualified, and an asset to the specialty.

Safety and efficacy of dynamic graciloplasty for fecal incontinence: report of a prospective, multicenter trial. Dynamic Graciloplasty Therapy Study Group.

PURPOSE: Dynamic graciloplasty has been used for intractable fecal incontinence, and good results have been reported. The aim of this study was to assess prospectively the safety and efficacy of dynamic graciloplasty for intractable fecal incontinence in a prospective, multicenter trial. METHODS: A total of 123 adults were treated with dynamic graciloplasty at 20 institutions. Continence was assessed preoperatively and postoperatively by use of 14-day diaries. RESULTS: There was one treatment-related death. One hundred eighty-nine adverse events occurred in 91 patients (74 percent). Forty-nine patients (40 percent) required one or more operations to treat complications. One hundred seventy (90 percent) events were resolved. Sixty-three percent of patients without pre-existing stomas recorded a 50 percent or greater decrease in incontinent events 12 months after dynamic graciloplasty, and an additional 11 percent experienced lesser degrees of improvement. Twenty-six percent were not improved, worsened, or exited. In patients with pre-existing stomas, 33 percent achieved successful outcomes at 12 months. This number increased to 60 percent at 18 months. Seventy-eight percent of patients had increased enema retention time, and mean anal canal pressures improved significantly at 12 months. Significant changes in quality of life were also observed. CONCLUSIONS: Objective improvement can be demonstrated in the majority of patients with end-stage fecal incontinence treated with dynamic graciloplasty. Reduction in incontinence episodes can be correlated with improved quality of life. Adverse events are frequently encountered, but most resolve with treatment.

Single-layer continuous colon and rectal anastomosis using monofilament absorbable suture (Maxon): study of 500 cases.

PURPOSE: The study purpose was to evaluate the results of continuous, single-layer colon and rectal anastomoses using a monofilament absorbable suture material (Maxon). METHODS: Four hundred ninety-two consecutive patients undergoing five hundred colon and rectal anastomoses with the above technique were evaluated for outcome, including anastomotic leakage, stricture, and other complications, by means of chart review. RESULTS: Three patients (0.6 percent) died after surgery and 7 (1.4 percent) developed clinical evidence of anastomotic leakage. Twenty-four percent developed some postoperative complications, most of which were minor. CONCLUSIONS: Continuous, single-layer colorectal anastomosis using monofilament absorbable suture can be performed safely, quickly, and with a favorable cost ratio. Handsewn anastomoses should still be part of the armamentarium of the well-trained surgeon.

Incidence of small-bowel obstruction and adhesiolysis after open colorectal and general surgery.

PURPOSE: The study contained herein was undertaken to establish the incidence of small-bowel obstruction, adhesiolysis for obstruction, and additional abdominal surgery after open colorectal and general surgery. METHODS: A retrospective cohort study was performed using patient-specific Health Care Financing Administration data to evaluate a random 5 percent sample of all Medicare patients who underwent surgery in 1993. Of these, 18,912 patients had an index abdominal procedure. Two-year follow-up data documented outcomes of hospitalizations with obstruction, adhesiolysis for obstruction, and/or additional open colorectal or general surgery. RESULTS: Within two years of incision, excision, and anastomosis of intestine (International Classification of Dis eases (ICD)-9 code 45), 14.3 percent of patients had obstructions, 2.6 percent required adhesiolysis for obstructions, and 12.9 percent underwent additional open colorectal or general surgery. After other operations of intestine (ICD code 46), 17 percent of patients had obstructions, 3.1 percent required adhesiolysis for obstructions, and 20.2 percent underwent additional open colorectal or general surgery. After operations of rectum, rectosigmoid, and perirectal tissue (ICD code 48), 15.3 percent of patients had obstructions, 5.1 percent required adhesiolysis for obstructions, and 16.4 percent underwent additional open colorectal or general surgery. After other operations on the abdominal region (ICD code 54), 12.4 percent of patients had obstructions, 2.3 percent required adhesiolysis for obstructions, and 8.8 percent underwent additional open colorectal or general surgery. CONCLUSIONS: In this retrospective study of Medicare patients, we learned that bowel obstruction, adhesiolysis for obstructions, and additional abdominal surgery occurred more often after abdominal surgery than was previously published.

Development of invasive adenocarcinoma in a long-standing Kock continent ileostomy: report of a case.

The first case of adenocarcinoma developing in a continent ileostomy is reported. A healthy, 39-year-old man with a continent ileostomy for 17 years developed subacute obstructive symptoms and was found on endoscopy to have a large adenocarcinoma involving the intussusception valve. At operation, he was found to have a large tumor originating in the valve, extending through the reservoir, and involving the afferent ileal limb. A number of metastatic lymph nodes were identified in the mesentery of the small bowel. He underwent excision of the pouch and formation of an end ileostomy. He is currently undergoing adjuvant chemotherapy. Biochemical and morphologic changes in the ileal pouch, both in the pelvis and the continent ileostomy, are discussed. The implications of this apparent de novo cancer arising in an ileal pouch are discussed.

Enhancement of melphalan toxicity by octanol in ovarian adenocarcinoma cell lines: effects of altered cell-cell communication, glutathione levels, and plasma membrane fluidity.

A2780 and COLO-316 ovarian adenocarcinoma cell lines were exposed to 1.0 mM 1-octanol for 12 hr in order to evaluate the potential effects of inhibition of gap junction-mediated intercellular communication (GJIC) on cellular responses to the chemotherapeutic drug melphalan. Other cellular endpoints relevant to drug-resistance mechanisms which were monitored after treatments included cellular glutathione levels, glutathione S-transferase activity, mitochondrial membrane potential, and plasma membrane lipid mobility. In cells which were sensitive to melphalan, octanol enhanced melphalan toxicity in the GJIC-competent (A2780/S) but not GJIC-incompetent (COLO-316/S) sensitive cells. Although octanol increases plasma membrane lipid mobility in A2780/S and COLO-316/S, it appears that enhancement of A2780/S sensitivity to melphalan may be due to inhibition of GJIC. In melphalan-resistant cells (A2780/R and COLO-316/R), 1.0 mM octanol treatment for 12 hr combined with melphalan reversed the resistance of the cells to the drug. Therefore, alterations in cellular glutathione metabolism and effects on the plasma membrane in addition to uncoupling of GJIC may be involved in sensitizing communication-competent and communication-incompetent resistant cells because COLO-316/R lacks gap junction-mediated intercellular communication. Further, analysis of mitochondrial membrane potential provided an index of acquired drug resistance and the efficacy of melphalan and combined octanol/melphalan toxicity.

Development of mucinous adenocarcinoma in chronic Crohn's disease fistulae without luminal involvement.

SUMMARY: A patient with Crohn's disease who developed mucinous adenocarcinoma in chronic fistulae is reported. Malignancy may complicate chronic nonhealing Crohn's sinus tracts and fistulae, even with no mucosal involvement by carcinoma. Persistent non-remitting perianal induration and pain should alert the physician to the possibility of underlying malignancy. Prompt examination under anesthesia and biopsy or fine-needle aspiration may facilitate diagnosis and therapy of the carcinoma at an early stage.

Ambulatory surgical hemorrhoidectomy--a solution to postoperative urinary retention?

PURPOSE: The most frequent complication of surgical hemorrhoidectomy is urinary retention. This study evaluates the incidence of urinary retention in a series of patients undergoing surgical hemorrhoidectomy in an ambulatory setting. METHODS: The records of all patients undergoing anorectal surgical operative procedures during the calendar year 1990 were reviewed, with particular emphasis on urinary retention and other postoperative complications. RESULTS: Of 201 patients undergoing full surgical hemorrhoidectomy by Colon and Rectal Clinic, 91 percent had operations performed on an ambulatory basis (discharge less than four hours following surgery). Of these 190 patients, only 1 (0.53 percent) required urinary catheterization during the postoperative period. CONCLUSIONS: The ambulatory setting, when combined with careful patient education and perioperative fluid restriction, allows surgical hemorrhoidectomy to be performed with a very low incidence of urinary retention to the benefit of both patient and surgeon.

Aggressive surgical management for advanced colorectal endometriosis.

PURPOSE: The aim of this study was to evaluate the results of aggressive surgical management in patients with advanced colorectal endometriosis. METHODS: The medical records of 130 women who had undergone aggressive surgical management of advanced colorectal endometriosis were reviewed. They were then interviewed a mean of 60 months following surgery and asked to rank relief of their symptoms. RESULTS: The most common symptoms before surgery were pelvic pain, dyspareunia, rectal pain, change in bowel habit, and cyclic rectal bleeding. Colorectal operations included low anterior resection, sigmoid resection, disc excision of the rectal wall, right colectomy, appendectomy, and small bowel resection. At follow-up symptom relief was high, ranging from 100 percent in cyclic bleeding to 91 percent for rectal pain. Mortality and clinical leakage rates were 0 percent, small bowel obstruction 3 percent, and abscess 1 percent. The crude pregnancy rate following surgery was 49 percent. CONCLUSIONS: These findings strongly support the use of aggressive surgical extirpation of all visible colorectal endometriosis for patients with advanced disease.

Autonomic dysreflexia resulting from prolapsed hemorrhoids. Report of a case.

PURPOSE: This article reports a case of autonomic dysreflexia associated with hemorrhoidal disease in a patient with high spinal cord lesions and successful treatment by surgical hemorrhoidectomy. METHODS: Following an unsuccessful attempt at conservative treatment which included bulk agents and warm compresses, the patient subsequently underwent three-column, closed surgical hemorrhoidectomy. RESULTS: The patient was symptom free and had normal bowel activity six weeks postoperatively, and five-year follow-up showed no recurrence of the hemorrhoidal prolapse or dysreflexia. CONCLUSION: Carefully controlled hemorrhoidectomy, when conservative measures fail, may be effective in managing autonomic dysreflexia in high spinal cord transection patients when prolapse serves as the stimulus.

Local excision of carcinoma of the rectum for cure.

During the past 10 years, we have treated 63 patients with invasive adenocarcinoma of the rectum by full-thickness local excision. Rigid criteria were employed in patient selection. None of the tumors was pedunculated or in situ carcinoma. Of the 63 lesions, 53 were confined to the bowel wall and constitute the basis for this report. Thirty-five lesions penetrated only the submucosa and 18 invaded the muscularis propria. Twenty-four patients underwent full-dose postoperative radiotherapy with minimal complications. Follow-up ranged from 12 to 130 months, with a median of 44 months. Four tumors recurred locally (8%). Of these, two patients apparently have been salvaged by reexcision. One patient died 32 months after abdominoperineal resection of brain metastases (without local tumor). One patient who did not receive close follow-up died of local recurrence. Seven have died of unrelated causes. The 5-year corrected disease-free survival is 90%. Local excision combined with radiotherapy for selected rectal cancers yields a high rate of cure with minimal morbidity and is now our preferred mode of treatment for all patients whose tumors meet our rigid criteria.

Results of 1,000 single-layer continuous polypropylene intestinal anastomoses.

Between 1979 and 1988, we created intestinal anastomoses in 1,000 patients using a single-layer, continuous suturing technique and a polypropylene suture. The technique is easily learned, flexible in its application, and incurs less cost than most other techniques. The anastomoses involved all levels of the colon and the upper (intraperitoneal and extraperitoneal) rectum. All patients were followed for a minimum of 1 year. The clinically suspected anastomotic leak rate was 1%. Other morbidity included would complications (2%), obstruction of the small intestine (2%), anastomotic stricture (1%), and death (1%). No death was due to anastomotic complications. These rates of complications are comparable with, and in many instances lower than, those reported with other techniques of intestinal anastomosis.

Surgical treatment of symptomatic colorectal endometriosis.

The approach to the treatment of bowel endometriosis has varied greatly. In this paper we present 77 consecutive patients with deep colorectal endometriosis treated with a full-thickness resection. Gynecologic procedures included conservative laparotomies for preserving fertility (39 patients); hysterectomy with bilateral salpingo-oophorectomy (29 patients); bilateral salpingo-oophorectomy (2 patients); left salpingo-oophorectomy (1 patient) and resection of pelvic endometriosis in patients with previous ablative surgery (6 patients). A low anterior bowel resection was performed in 68 patients (88.3%); a disc excision of the anterior rectal wall in 5 (6.5%); sigmoid resection in 3 (3.9%), and partial cecal resection in 1 (1.3%). The postoperative febrile morbidity was 10.4%, with no apparent anastomotic leaks. Of 33 patients who attempted to conceive postoperatively, 13 achieved a term pregnancy (39.4%). Complete relief of pelvic symptoms was obtained in 38 patients (49.4%); improvement in 30 (39%); no improvement in 8 (10.4%); and worsening of symptoms in 1 (1.2%). There has been no recurrence of symptomatic bowel endometriosis during 1 to 9 years of follow-up. Full-thickness resection of the colon for the treatment of deep bowel endometriosis is a safe procedure with low morbidity, good postoperative relief of symptoms, and favorable pregnancy rates.

The single-layer continuous polypropylene colon anastomosis. A prospective assessment using water-soluble contrast enemas.

Fifty consecutive unselected patients with anastomoses to the left side of the colon were studied. Each patient had an anastomosis constructed with a single layer of continuous 4-0 polypropylene. On the seventh postoperative day, or sooner, a water-soluble contrast enema was obtained to evaluate the integrity of the anastomosis. Two patients developed radiographic and clinical evidence of anastomotic leakage, and one patient developed a late pelvic abscess and colocutaneous fistula. The documented leak rate of 6 percent attests to the safety of this method of colonic anastomosis.