FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Recovery of function in adjacent nerve roots after surgery for lumbar disc herniation: use of quantitative sensory testing in the exploration of different populations of nerve fibers

Results from experimental and clinical studies indicate that adjacent nerve roots may be affected in sciatica because of lumbar disc hemiation. This may be caused by proinflammatory mediators in the epidural space being transported into nerve roots at the same or neighboring lumbar segments. The aim of the present study was to investigate the recovery of function of sensory nerve fibers in the adjacent noncompressed nerve roots. Thirty-nine patients undergoing microdiscectomy for monoradiculopathy were investigated with quantitative sensory testing immediately before surgery, and at 6 weeks, 4 months, and 12 months after the operation. Twenty-one healthy volunteers were used as controls. The patients were classified as having a good or a poor result at the 1-year follow-up according to a clinical score. Significant improvement of function in the noncompressed nerve roots were only observed in the 31 patients with a good result. The improvement in small myelinated nerve fibers came within 12 months in the adjacent nerve roots in both the symptomatic as well as the asymptomatic leg. The improvement of function in small unmyelinated fibers also came within 12 months after surgery; however, significant improvement was only observed in the ipsilateral neighboring nerve root. The function in large myelinated fibers did not improve in any of the adjacent nerve roots during the observation period. The observed recovery of function in adjacent noncompressed nerve roots after successful surgical decompression in monoradiculopathy may be because of less production of proinflammatory mediators when the disc herniation is removed.     

Fatigue in patients with systemic lupus erythematosus: the psychosocial aspects

OBJECTIVE: Studies to prove a relationship between fatigue and immunological, inflammatory, or other disease characteristics of systemic lupus erythematosus (SLE) have shown no consistent findings. To further elucidate the basis for fatigue in SLE, we examined the affective states, personality traits, and mental health status in an unselected group of patients with SLE. METHODS: Fifty-seven Caucasian patients with SLE were examined. Fatigue was measured by the Fatigue Severity Scale. Personality traits and psychological function were evaluated by the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), the affective states by Beck Depression Inventory, and mental health status by the General Health Questionnaire version 30 (GHQ-30). RESULTS: Fatigue was closely associated with high scores on subscales Depression (D-2) and Hysteria (Hy-3) on MMPI-2 (R2 = 0.31; p = 0.0002), as well as with high scores on BDI (R2 = 0.22; p = 0.0006) and GHQ (R2 = 0.33; p < 0.0001). CONCLUSION: Fatigue does not seem to be caused by any easily recognizable single or multiple factor(s) of an inflammatory or immunological state. Our results point to fatigue being a multifaceted phenomenon where several psychosocial factors are strongly related, and indicate that fatigue is part of a complex response to chronic disease.     

Autoantibodies against 21-hydroxylase and side-chain cleavage enzyme in autoimmune Addison's disease are mainly immunoglobulin G1

OBJECTIVE: Immunoglobulin G (IgG) antibodies to the steroidogenic enzymes 21-hydroxylase (21OH) and side-chain cleavage enzyme (SCC) are important diagnostic markers for autoimmune Addison's disease and autoimmune polyendocrine syndromes (APS) types I and II. The characterization of autoantibody (IgG) subclasses may reveal information on how tIssue destruction takes place; therefore, IgG subtypes of anti-21OH and anti-SCC antibodies from sera of patients with Addison's disease, APS I and APS II were determined using recombinant 21OH and SCC. METHODS: SCC(51-521) and his-SCC(51-521) were expressed by pET-scc in the Escherichia coli strain BL21 Star (DE3) and inclusion bodies were purified. Full-length, human 21OH fused to an N-terminal 6x histidine affinity tag was expressed in insect cells by using the baculovirus expression system bac-to-bac. Western blots were used to investigate the IgG subtype(s) of the autoantibodies against 21OH and SCC in patients and healthy blood donors. RESULTS: All anti-SCC positive sera (n=10) contained autoantibodies of the IgG1 subclass, while four out of ten also contained IgG3. All anti-21OH positive sera (n=16) had autoantibodies exclusively against IgG1. Sera from 20 healthy subjects did not show any reactivity against 21OH or SCC. CONCLUSIONS: The finding of a predominating IgG1 response against 21OH and SCC may suggest that T helper (Th) cells of the Th1 subclass are involved in destruction of the adrenal cortex in patients with autoimmune Addison's disease.     

Simultaneous defecography and peritoneography in defecation disorders

A number of physiologic and radiologic investigations are used in investigating defecation disorders. Defecography is one important part of these investigations. However, a correct diagnosis of an enterocele is sometimes difficult despite use of contrast media in the rectum, vagina, and small bowel. PURPOSE: This study was undertaken to ascertain if it was technically possible to perform simultaneous defecography and peritoneography in an effort to improve the diagnostic possibilities in patients with defecation disorders. METHODS: Twelve patients with defecation disorders and an unexplained widening of the rectovaginal space at defecography were investigated. Contrast medium was introduced intraperitoneally, after which conventional defecography was performed. RESULTS: All investigations were carried out without complications and demonstrated the peritoneal outline in all patients. Simultaneous defecography and peritoneography differentiated between an enterocele and a pathologically deep pouch of Douglas—a peritoneocele. Three types of peritoneocele were visualized: vaginal peritoneocele, septal peritoneocele, and rectal peritoneocele with or without enterocele. Combinations of the three types were also found. Eight of the 12 patients had rectal intussusception or rectal prolapse. All of these eight patients had a rectal peritoneocele. CONCLUSIONS: Simultaneous defecography and peritoneography can be performed without technical difficulties or complications. Peritoneal outlines and pouches can, therefore, be studied directly during the act of defecation. An unexplained widening of the rectovaginal space at defecography can be clarified as a peritoneocele, with or without an enterocele. Peritoneocele can be of three different types: rectal, septal, or vaginal.Supported by grants from Marianne and Marcus Wallenbergs Stiftelse, Kjell and Märta Beijers Stiftelse, and Karolinska Institutet's research funds.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Orlando, Florida, May 8 to 13, 1994.     

Internal rectal intussusception seldom develops into total rectal prolapse

PURPOSE: This study was designed to analyze how often internal rectal intussusception develops into total rectal prolapse. METHODS: Repeated investigations with defecography were performed in 312 patients because of persisting symptoms. In 79 patients who had a rectal intussusception at the first defecography, results of the second defecography and the patients' records were studied. RESULTS: A total of 38 patients had not undergone any surgical treatment of rectal intussusception or rectal prolapse between the first and second defecographies. One of these patients had a rectal prolapse at the second defecography, and another developed a clinical prolapse after the second defecography. CONCLUSIONS: The present study demonstrates that the risk of developing a rectal prolapse in patients with rectal intussusception is small. This risk should, therefore, not be used as an indication for surgery.     

Defecography

PURPOSE: This study was designed to analyze the frequency of different findings at defecography in patients with defecation disorders and see in what way the evaluation could be improved. METHODS: The reports of investigations in 2,816 patients were analyzed. RESULTS: Twenty-three percent of the investigations were considered normal. Thirty-one percent of the patients had rectal intussusception, 13 percent had rectal prolapse, 27 percent had rectocele, and 19 percent had enterocele. Twenty-one percent of the patients had a combination of two or three of these diagnoses. The combination of rectocele and enterocele was rare. The majority of patients with enterocele had other concomitant findings. Patients with or without abnormal perineal descent had similar frequencies of rectal prolapse, rectal intussusception, and enterocele. Rectocele was more common in patients with abnormal perineal descent. CONCLUSIONS: Defecography is valuable when investigating patients with defecation disorders. Pathologic findings were found in 77 percent of the patients. A standardized protocol should ensure a complete evaluation of defecography.Read in part at the 14th Biennial Congress of University Colon and Rectal Surgeons, Crete, Greece, October 25 to 29, 1992.     

Ileal pouch fistulas after restorative proctocolectomy: management and outcomes

Background

Fistula between an ileal pouch and the vagina, anus, or perineum is an uncommon complication of ileal pouch-anal anastomosis and is a cause of considerable morbidity. Its optimal management has not been determined because of its low incidence. The aim of this study was to review the outcomes of patients who presented with symptomatic ileal pouch-associated fistulas after restorative proctocolectomy (RPC) and to present a diagnostic and treatment algorithm.

Methods

Retrospective review of patients treated for symptomatic ileal pouch-associated fistulas after RPC from 1989 to 2011.

Results

Twenty-five patients (14 men, mean age 40 years) were presented with symptomatic ileal pouch-associated fistulas. Median time to pouch fistula following RPC was 6.9 years (range 1 month–20 years). Fistulas were classified as pouch-anal (n = 12, 48 %), pouch-vaginal (n = 7, 28 %), complex (n = 4, 16 %), and pouch-perineal (n = 2, 8 %). Etiology included Crohn’s disease (n = 15, 60 %), cryptoglandular (n = 6, 24 %), and anastomotic failure (n = 4, 16 %). Each patient underwent an average of 2.8 local procedures or repairs. Overall healing rate was 64 % at a median follow-up of 29 (range 2–108) months. None of the complex fistulas were healed. Postoperative pelvic sepsis, fecal diversion, anti-tumor necrosis factor therapy, and fistula etiology did not significantly impact fistula healing. Three patients required pouch excision with end ileostomy.

Conclusions

Operative treatment of pouch fistulas after RPC resulted in complete healing in 64 % of patients following a stepwise diagnostic and therapeutic approach.     

The nuclear receptors NUR77, NURR1 and NOR1 in obesity and during fat loss

Background:Adipose tissue is critical for systemic metabolic health. Identifying key factors regulating adipose tissue function is a research priority. The NR4A subfamily of nuclear receptors (NRs) (NR4A1/NUR77, NR4A2/NURR1 and NR4A3/NOR1) has emerged as important proteins in different disease states and in the regulation of metabolic tissues, particularly in liver and muscle. However, the expression of the NR4A members in human adipose tissue has not previously been described, and their target genes are largely unknown.Objective:To determine whether the NR4As are differentially expressed in human adipose tissue in obesity, and identify potential NR4A target genes.Design:Prospective analysis of s.c. adipose tissue before and 1 year after fat loss, and during in vitro differentiation of primary human preadipocytes. Case-control comparison of omental (OM) adipose tissue.Subjects:A total of 13 extremely obese patients undergoing biliopancreatic diversion with duodenal switch for fat loss, 12 extremely obese patients undergoing laparoscopic sleeve gastrectomy and 37 lean individuals undergoing hernia repair or laparotomy were included in the study. Measurements were done by quantitative PCR gene expression analysis of the NR4A members and in silico promoter analysis based on microarray data.Results:There was a strong upregulation of the NR4As in extreme obesity and normalization after fat loss. The NR4As were expressed at the highest level in stromal-vascular fraction compared with adipocytes, but were downregulated in both fractions after fat loss. Their expression levels were also significantly higher in OM compared with s.c. adipocytes in obesity. The NR4As were downregulated during differentiation of primary human preadipocytes. Moreover, the NR4As were strongly induced within 30?min of tissue incubation. Finally, promoter analysis revealed potential NR4A target genes involved in stress response, immune response, development and other functions. Our data show altered adipose tissue expression of the NR4As in obesity, suggesting that these stress responsive nuclear receptors may modulate pathogenic potential in humans.     

A retrospective case–control study of gastrostomy use in children undergoing hematopoietic cell transplantation

Background

Maintaining a good nutritional status during the hematopoietic cell transplantation (HCT) procedure is challenging in the pediatric population.

Methods

In a multicentric retrospective study, we compared the outcome of nutritional status and HCT-related parameters in 227 pediatric patients during and after HCT between 2005 and 2015. 112 patients received a gastrostomy before the start of HCT (GS group), and 115 did not receive a gastrostomy (NGS). Data collection was performed at HCT, 3, 6, and 12 months post-HCT.

Results

At time point of HCT the Standard Deviation Score (SDS) of weight was 0.17 in the NGS group, and 0.71 in the GS group (p = .01) Patients in the NGS group lost more weight during the first 3 months after HCT than patients in the GS group. At 12 months, patients in the NGS remained at a lower weight, while patients in the GS group slightly increased their weight. There were no differences between the groups in the incidence of acute graft-versus-host-disease (GvHD), overall survival, and non-relapse mortality. However, the number of febrile episodes requiring intravenous treatment with antibiotics, was higher in the GS group as compared to the NGS group, during the first 3 months post-HCT (p < .001).

Conclusions

Our results indicate that gastrostomy can be utilized in children undergoing HCT without any negative effects on mortality. Therefore, the use of a gastrostomy appears to be a safe option to maintain a good nutritional status during the HCT procedure.