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Biomedical subjects

E Heineman

Publications and source records attributed to E Heineman.

At least 37 records · Page 2Linked to original sources

Parental occupational exposure to hydrocarbons and risk of acute lymphocytic leukemia in offspring.

Parental exposure to hydrocarbons at work has been suggested to increase the risk of childhood leukemia. Evidence, however, is not entirely consistent. Very few studies have evaluated the potential parental occupational hazards by exposure time windows. The Children's Cancer Group recently completed a large-scale case-control study involving 1842 acute lymphocytic leukemia (ALL) cases and 1986 matched controls. The study examined the association of self-reported occupational exposure to various hydrocarbons among parents with risk of childhood ALL by exposure time window, immunophenotype of ALL, and age at diagnosis. We found that maternal exposure to solvents [odds ratio (OR), 1.8; 95% confidence interval (CI), 1.3-2.5] and paints or thinners (OR, 1.6; 95% CI, 1.2-2.2) during the preconception period (OR, 1.6; 95% CI, 1.1-2.3) and during pregnancy (OR, 1.7; 95% CI, 1.2-2.3) and to plastic materials during the postnatal period (OR, 2.2; 95% CI, 1.0-4.7) were related to an increased risk of childhood ALL. A positive association between ALL and paternal exposure to plastic materials during the preconception period was also found (OR, 1.4; 95% CI, 1.0-1.9). The ALL risk associated with parental exposures to hydrocarbons did not vary greatly with immunophenotype of ALL. These results suggest that the effect of parental occupational exposure to hydrocarbons on offspring may depend on the type of hydrocarbon and the timing of the exposure.

Adolescent↗

Renal arginine metabolism in fasted rats with subacute short bowel syndrome.

1. Arginine can be produced in the kidney from citrulline. An important source of circulating citrulline is the intestinal breakdown of glutamine. Consequently, partial enterectomy leads to decreased plasma citrulline levels. The aim of the present study was to investigate the effect of diminished arterial citrulline levels on renal arginine production and total-body free arginine pools.2. Renal amino acid metabolism was studied 24 h after 75% small bowel resection in rats fasted overnight (16 h) (n=12; total fast 40 h). Sham-operated (n=9) and non-operated 16-h and 40-h fasted controls were studied in parallel (n=8/n=7). During anaesthesia, L-(2, 3-3H)-arginine and para-aminohippuric acid were infused until steady state. Subsequently, arterial and renal venous blood samples were taken. Concentrations of para-aminohippurate and amino acids and specific activity of arginine and citrulline were measured to calculate renal plasma flow, net renal uptake or release, and unidirectional influx or efflux of arginine and citrulline, as well as whole-body arginine turnover.3. Arterial citrulline was decreased in enterectomized rats compared with sham-operated rats (23+/-3 versus 44+/-6 microM). Net renal citrulline uptake and arginine release were almost stoichiometric (-36+/-7 and 38+/-6 nmol.min-1. 100 g-1 body weight respectively in sham-operated rats) and were both diminished by 50% in enterectomized versus sham-operated rats. In all groups, net renal arginine production accounted for less than 10% of whole-body rate of arginine appearance (488 nmol.min-1.100 g-1 body weight in the sham group). Despite decreased net renal citrulline consumption and renal arginine production in enterectomized rats, whole-body rate of arginine appearance and arterial arginine did not change significantly.4. In conclusion, net renal arginine production is reduced 24 h after 75% enterectomy in fasted rats. However, this does not have important effects on whole-body arginine production.

Amino Acids↗

Glutathione S-transferase as predictor of functional outcome in transplantation of machine-preserved non-heart-beating donor kidneys.

Non-heart-beating (NHB) donors are a valuable source of kidneys for transplantation. The organs, however, sustain substantial warm ischemic damage that may jeopardize the transplantability and result in nonfunction of the grafts. Quantification of warm ischemic time (WIT) and prediction of transplant outcome are essential for the use of NHB donor organs. During machine preservation (MP) the viability of NHB donor kidneys was evaluated through calculating intrarenal vascular resistance and determining lactate dehydrogenase and alpha-glutathione S-transferase (alphaGST) in the perfusate. Thirty-seven functioning (F) and nine nonfunctioning kidneys (NF) were compared. WIT was longer in NF; serum creatinine, donor age, and preservation time were not different. WIT correlated well with alphaGST after 4 and 8 hr of MP (r=0.353, P=0.009, and r=0.346, P=0.011, respectively). When compared with F, intrarenal vascular resistance was increased in NF after 4 and 8 hr of perfusion (P<0.05); at all time points, alphaGST levels were elevated in NF (P<0.05). Lactate dehydrogenase activity was not different between the groups, but could identify immediate functioning grafts within the F group. In conclusion, alphaGST levels correlated strongly with WIT and were also able to distinguish NF from F grafts. alphaGST can adequately predict the functional outcome of NHB donor grafts before transplantation; levels of alphaGST can be used to define reliable safety margins for viability. Therefore, MP is useful in evaluating the viability of NHB donor kidneys, and the parameters discussed will help to select nonviable grafts from this valuable pool of kidneys for transplantation.

Adult↗

Effects of different durations of total warm ischemia of the gut on rat mesenteric microcirculation.

BACKGROUND: Gut injury due to ischemia and reperfusion (I/R) plays a pivotal role in many clinical conditions, such as small bowel transplantation, heart or aortic surgery in adults, and necrotizing enterocolitis in neonates. The influence of ischemic events on microcirculatory mechanisms is not well understood. Therefore, we studied, in vivo, local perfusion and leukocyte-vessel wall interactions before and after different periods of total warm ischemia of the whole gut and subsequent reperfusion in mesenteric microvessels. MATERIALS AND METHODS: Groups of pentobarbital-anaesthetized Lewis rats were subjected to 15 (n = 9), 30 (n = 12), or 60 min (n = 5) of total warm gut ischemia and 2 h reperfusion. As control a sham group (n = 10) was included. After ligating the inferior mesenteric artery, total warm ischemia was induced by clamping the superior mesenteric artery. Before and at different time periods after start of reperfusion intravital video microscopic measurements were performed. RESULTS: Rats subjected to 60 min ischemia died during the early reperfusion phase. Fifteen, 30, and 60 min ischemia induced in venules a significant decrease in blood flow, while diameter changes were not observed. This flow decrease was severe in the 15- and 30-min ischemia groups, dropping to 40 and 25% of control, respectively. Following 60 min ischemia blood flow did not exceed 10% of control. The total number of interacting leukocytes, a parameter which includes both leukocyte rolling and adhesion in venules, increased up to 5 or 10 times its control value following 15 or 30 min ischemia, respectively. Leukocyte-vessel wall interactions could not be studied in the 60-min ischemia group, due to the low blood flow. CONCLUSIONS: Even short periods of total warm ischemia of the whole gut induce severe attenuation of venular blood flow with an increase in leukocyte-vessel wall interactions. These changes increase with prolongation of the ischemic period. A 60-min period of total warm ischemia is fatal during the early reperfusion phase.

Animals↗

Total anorectal reconstruction with a double dynamic graciloplasty after abdominoperineal reconstruction for low rectal cancer.

PURPOSE: Total anorectal reconstruction with a double dynamic graciloplasty was performed after abdominoperineal reconstruction (APR) for low rectal cancer. In four patients an additional pouch was constructed to improve neorectal motility and capacity. The aim of this study was to evaluate the results in the first 20 patients and to report on the preliminary results of patients with an additional pouch. METHODS: Twenty patients with a mean age of 52 (range, 25-71) years and a rectal tumor at a mean of 3 (range, 0-5) cm from the anal verge were treated. In 14 patients the Miles resection, colon pull-through, and construction of a neosphincter were performed in one session. Six patients had the double graciloplasty at an average of 4.1 (range, 1.1-8.8) years after APR. In four patients a pouch was constructed with an isolated segment of distal ileum. RESULTS: After a mean follow-up of 24 (range, 1-60) months after APR, none of the patients developed local recurrence, whereas four patients developed distant metastasis. Fifteen of 20 patients were available for evaluation, and 5 patients were still in training. Of these 15 patients, 8 patients were continent (53 percent), 2 patients were incontinent, and in 5 patients the perineal stoma was converted to an abdominal stoma. Failures were attributable to necrosis of the colon stump (n = 2) and incontinence (n = 3). At 26 weeks mean resting pressure was 44 (standard deviation (SD), 28) mmHg, and mean pressure during stimulation was 90 (SD, 46) mmHg at a mean of 3.5 (SD, 1.2) volts at 52 weeks. Mean defecation frequency was three times per day (range, 1-5). Of the eight patients who were continent, six used daily enemas. Mean time to postpone defecation was 11 (range, 0-30) minutes. CONCLUSION: In experienced hands, the double dynamic graciloplasty is an oncologically safe procedure that can have an acceptable functional outcome in a well-selected group of patients. However, to improve the outcome, further modifications will be necessary. So far, the addition of a pouch has not resulted in improved outcome.

Adenocarcinoma↗

Vascular and stimulation delays in dynamic musculoplasty.

BACKGROUND: Dynamic musculoplasty is increasingly being used to replace severely damaged muscle. Electrical stimulation induces a change in muscle composition from type II to type I muscle fibers. The aim of this study was to assess the optimal time to start stimulation and the beneficial effect of a vascular delay. METHODS: Both gracilis muscles in rabbits (n = 3 x 6) were wrapped around a double polyurethane tube, and leads were implanted together with a neurostimulator. Right muscles were electrically stimulated for 11 weeks, and left muscles served as controls. In group 1 the muscle was stimulated immediately after transposition, in group 2 it was stimulated after 6 weeks, and in group 3 a vascular delay was performed and stimulation was started immediately after transposition. RESULTS: During stimulation the percentage of type 1 muscle fibers increased from a mean of 4.6% to 41.9%. In group 1 there was significantly more change in muscle tissue. There were no significant differences in recorded pressures between groups. In group 1 the increase in amplitude during stimulation was significantly elevated (p < 0.05). The fatigue index in group 1, 259 (SE 130) seconds, was significantly lower than that of group 2, 515 (SE 102) seconds (p < 0.05). CONCLUSIONS: Compared with the methods used in groups 2 and 3, immediate stimulation (group 1) gives more change in muscle tissue, demanding a higher increase in amplitude to achieve sufficient contraction. The fatigue index is also impaired. Thus vascular delay, as presently applied, does not improve muscle function.

Animals↗

The non heart-beating donor.

Given the shortage of donor kidneys for transplantation, we have focused on the use of non heart-beating (NHB) donor kidneys since 1982. The major drawback for the use of NHB donor kidneys is the inherent possibility of severe ischaemic damage leading to primary non function. Thus viability assessment of ischaemically damaged kidneys is crucial, and, therefore, a machine perfusion programme was reinstituted in 1993. Machine perfusion (MP) enables viability assessment through analysis of perfusion characteristics and measurement of enzyme release into the perfusate. Of the last 100 consecutive MP NHB donor kidneys, 71 kidneys were transplanted and 29 kidneys were discarded. Nine kidneys started functioning immediately, 51 kidneys showed delayed function and 11 kidneys never functioned. When analysing in retrospect different parameters for viability assessment, only alpha-GST, an enzyme specific for damage of proximal tubular cells within the kidney, could discriminate between functioning and non-functioning kidneys. With this promising viability assessment, the large NHB donor potential and the good transplant results, we recommend the use of these donors.

Adult↗

Use of neonatal intensive care unit as a safe place for neonatal surgery.

AIM: To evaluate the advantages, disadvantages, and short term morbidity and mortality of major surgical interventions performed in the neonatal intensive care unit. METHODS: A retrospective case review of 45 neonates was performed from April 1991 to September 1995. The characteristics of the patients were: gestational age 29 (SD 4) weeks (range 24 to 41 weeks); birth-weight 1305 (870) g (range 540 to 4040 g); presurgical weight 1430 (895) g (range 550 to 4370 g); postconceptional age at surgery 31 (4) weeks (26 to 47 weeks). The indications for surgery were: ligation of patent ductus arteriosus (n = 16); insertion of a subcutaneous ventricular catheter reservoir for hydrocephalus (n = 14); repair of congenital diaphragmatic hernia (n = 2); open lung biopsy (n = 1); and laparotomies (because of necrotising enterocolitis, anorectal malformations, and intestinal obstructions) (n = 12). The management of these neonates at laparotomy was: bowel resection with stomas (n = 8) and stomas (n = 4). No specially designed area was used to perform surgery. RESULTS: Local or systemic infection associated with surgery was not seen and no perioperative mortality was related to the surgical procedure. CONCLUSIONS: The neonatal intensive care unit is suitable for major surgery during the neonatal period and no special area is needed to perform complication free surgery.

Evaluation Studies as Topic↗

Assessment of ischaemia of the distal part of the gracilis muscle during transposition for anal dynamic graciloplasty.

BACKGROUND: Dynamic graciloplasty is used to create a neosphincter in patients with intractable faecal incontinence. When mobilizing the distal gracilis muscle from the upper leg, the minor vascular pedicles have to be ligated. This can interfere with the vascular supply in this part of the muscle. METHODS: The arterial anatomy within the muscle was visualized by means of angiography of 11 postmortem specimens. To quantify potential acute ischaemia, blood flow in the distal gracilis muscle was measured in ten patients with laser Doppler flowmetry during mobilization of the muscle. RESULTS: Angiography showed that the main vascular pedicle and all minor pedicles drain into one and the same arterial system. After clamping of the minor vascular pedicles, blood flow (mean 25.8 (range 6.5-74.3) perfusion units) did not differ from values obtained before clamping (mean 25.4 (range 7.5-68.7) perfusion units). After a mean of 1.8 years, all muscles were vital. No correlation existed between the change in muscle blood flow and either squeeze pressure (r = -0.2) or functional outcome (r = 0.31). CONCLUSION: This study provides direct anatomical and physiological evidence of one arterial system within the gracilis muscle. It is therefore questionable whether ligation of the minor vascular pedicles is the bottleneck in human dynamic graciloplasty. An additional operation for vascular delay may be redundant. A prospective randomized clinical study should be performed to compare the functional outcome in patients with and without a delay procedure.

Adolescent↗

Short-term outcome of kidney transplants from non-heart-beating donors after preservation by machine perfusion.

In this study, the short-term outcome of renal transplants from non-heart-beating donors (NHBD) preserved by machine perfusion (MP) is evaluated and compared to preservation by cold storage (CS). Twenty-two NHBD kidneys were procured during 1993 and 1994 after in situ perfusion with histidine-tryptophan ketoglutarate and preserved by continuous perfusion using University of Wisconsin organ preservation solution for MP as a perfusate. Between 1980 and 1992, 57 NHBD kidneys were procured and preserved by CS. Donors in the MP group sustained increased first warm ischemia times (WIT1) (P < 0.1) and recipients in the MP group suffered longer anastomosis time, worse HLA-DR mismatch, and more initial use of cyclosporin as immunosuppressant; all these factors are known to be deleterious to short-term outcome. Despite these unfavorable conditions, delayed function (DF) rate was decreased in the MP group, although not significantly. However, when considering only kidneys with WIT1 > or = 45 min, short-term outcome was significantly better in the MP group (P < 0.05). We conclude that MP is superior for the preservation of NHBD kidneys, especially after prolonged warm ischemia.

Adult↗

Dynamic graciloplasty. Complications and management.

PURPOSE: Patients with intractable fecal incontinence, in whom all other treatment failed, can be treated by dynamic graciloplasty. Good results have been reported, but this technique involves specific problems. All problems that occurred over an eight-year period are presented, and management is discussed. METHODS: Dynamic graciloplasty was performed in 67 patients with a mean follow-up of 2.7 years. All patients were monitored by physical examination, anal manometry, defecography, and electromyography at fixed intervals. All complications were noted and treated. Continence was defined as being continent to solid and liquid stools. RESULTS: The technique was successful in 52 patients (78 percent), whereas failures occurred in 15 patients (22 percent). Complications resulted from technical problems, problems with infection, and problems attributable to an abnormal physiology of the muscle or an anorectal functional imbalance. In total, 53 complications were identified in 36 patients. Most technical problems, concerning the transposition and stimulation of the gracilis muscle, could be treated. Failures were attributable to a bad contraction of the distal part of the muscle (n = 4) and perforation of the anal canal during stimulation (n = 1). In eight patients, infection of the stimulator and leads required explantation. Three patients did not regain continence after reimplantation. Apart from moderate constipation, physiologic complications were very hard to treat and resulted in failures in five patients because of overflow incontinence, soiling, a nondistending rectum, strong peristalsis, and strong constipation. In two patients, the technique failed despite a well-contracting graciloplasty; no clear reason for the failure was found. CONCLUSION: Complications associated with the technique of dynamic graciloplasty such as loss of contraction, infection, bad contraction in the distal part of the muscle, and constipation can often be prevented or treated. Difficulties related to an impaired sensation and/or motility, attributable to a congenital cause or degeneration, are impossible to treat, and this signifies that a good selection of patients is essential to prevent disappointment.

Adult↗

Ischemia/reperfusion injury in rat mesenteric venules: red blood cell velocity and leukocyte rolling.

The authors determined the effects of 15 (n = 9) and 30 (n = 12) minutes of warm ischemia on the rat mesentery and compared the results with those of a sham-operated group (n = 10). Red blood cell velocity and number of rolling leukocytes were assessed before ischemia as well as 10, 20, 30, 60, 90, and 120 minutes after the start of reperfusion. Leukocyte rolling is considered to be an early step of the inflammatory process. Leukocytes roll along the vessel wall at a velocity that is clearly lower than that of the other blood cells. The preischemic values of red blood cell velocity and number of rolling leukocytes in the 15- and 30-minute ischemia groups did not differ from those of the sham group. In the sham group, no significant changes in red blood cell velocity and number of rolling leukocytes were observed over time. Compared with the sham group, the red blood cell velocity of the 15-minute ischemia group was significantly lower at 30, 60, 90, and 120 minutes after the start of reperfusion the number of rolling leukocytes did not differ significantly. For the 30-minute ischemia group, red blood cell velocity also was significantly lower at 20, 30, 60, 90, and 120 minutes after the start of reperfusion, and the number of rolling leukocytes was higher at 10, 20, and 30 minutes after the start of reperfusion. The results of this study indicate that short periods of total warm ischemia of the rat small bowel and subsequent reperfusion result in a significantly impaired microcirculatory blood flow in the mesentery. However, a prolonged period of ischemia is required to increase leukocyte-vessel wall interactions. In the future, this model will enable us to study the effect of pharmacological interventions during an early stage of the inflammatory response to ischemia/reperfusion in the gut.

Animals↗

Prospective evaluation of faecal fatty acid excretion in short bowel syndrome in newborns.

Short bowel syndrome (SBS) in the newborn results in limited intestinal absorptive capacity, leading especially to fatty acid (FA) malabsorption. It is unknown whether adaptation occurs in time in FA absorption, and whether this adaptation is chain-length dependent. The aid of the present study was to prospectively evaluate FA absorption and excretion during SBS in the newborn. Twenty-one neonates who underwent small bowel resection (of variable length) for various reasons (necrotizing enterocolitis, intestinal atresia, meconium peritonitis, cloacal extrophy, etc) were studied. Eight neonates had SBS, defined as a small bowel remnant of less than 50% of the original small bowel length related to gestational age. The mean remaining small bowel length in the SBS group was 34% (24% to 42%). The non-SBS control group consisted of 13 neonates who had only minor small bowel resections. The mean remaining bowel length for the non-SBS group was 95% (70% to 100%). The results show that the total fractional excretion of FA (FE-FA) at 2 weeks and 1, 2, 3, and 4 months postsurgery was 51% +/- 37%, 33% +/- 24%, 51% +/- 65%, 53% +/- 27%, and 7% +/- 2% in patients with SBS, versus 12% +/- 8%, 24% +/- 10%, 9% +/- 3%, 8% +/- 3% and 17% +/- 14% in the non-SBS controls, respectively (P < .05 by ANOVA). There appeared to be an amelioration in time in FA absorption, especially in the SBS group, after 3 months. FE-FA was chain-length related, being considerably less for C10 and C12 than for C14 and longer amounts. An amelioration of absorption occurred in the SBS patients, especially with the longer-chain FA. On the basis of the study data, the authors conclude that in the initial adaptation phase shorter chain lengths are better absorbed than longer chain lengths; however, in the latter FA group, substantial adaptation occurs with time.

Fatty Acids↗

Supplementation of enteral nutrition with butyrate leads to increased portal efflux of amino acids in growing pigs with short bowel syndrome.

Previously, short-chain fatty acids (SCFAs) infused into the hindgut or administered intravenously have been shown to stimulate intestinal adaptation after massive small bowel resection. To study the effects of enterally supplemented n-butyrate on food digestion and absorption in growing pigs with short bowel syndrome, the authors examined the portal efflux of glucose and amino acids during a meal. In 12 growing pigs, 75% of the small intestine was resected. Five control (CONT) animals underwent transection and reanastomosis of the small bowel. A splenic vein, the aorta, the portal vein, and the stomach were catheterized. Postoperatively, seven enterectomized (ENT) pigs and the CONT pigs were fed by infusion of a liquid diet, without SCFAs, through the gastrostomy catheter. Five enterectomized animals received the same diet, supplemented with butyrate (ENTB) (0.26 g/kg body weight/d). After 3 weeks, the portal efflux of amino acids and glucose was measured after 2 hours of constant feeding. The portal efflux of glucose expressed per kilogram of body weight in the ENT group was 10% of that in the CONT group, and in the ENTB group it was 42%. No significant difference in portal glucose efflux between the ENT and the ENTB groups was found. The portal efflux of amino acids during a meal in the ENT group in relation to the CONT groups was 34%; in the ENTB group it was 63%. These data suggest that enteral supplementation with SCFAs leads to improvement of intestinal food digestion and absorption during short bowel syndrome, possibly related to improved intestinal adaptation.

Amino Acids↗

Anal dynamic graciloplasty in the treatment of intractable fecal incontinence.

BACKGROUND: In patients with intractable fecal incontinence, conventional treatment is not always successful. Dynamic graciloplasty (transposition of the gracilis muscle to the anus with the implantation of stimulating electrodes) was developed to provide such patients with functional neosphincters. We evaluated the clinical results of this new surgical approach and the effects on quality of life. METHODS: We treated 52 patients with dynamic graciloplasty. The clinical results of treatment were evaluated in an interview, by anal manometry, and by enema testing. The degree of continence was scored. To assess quality of life, four questionnaires were administered (parts 1 and 2 of the Nottingham Health Profile, the State-Trait Anxiety Inventory, and the Self-rating Depression scale). RESULTS: Among the 52 patients, 38 (73 percent) were continent after a median follow-up of 2.1 years. At 52 weeks the patients' condition had improved with respect to the median frequency of defecation (from five to two times per 24 hours, P < 0.001), the median time defecation could be postponed (from 9 seconds to 19 minutes, P = 0.012), and the median time an enema could be retained (from 0 to 180 seconds, P = 0.005). Patients in whom the technique was successful became less anxious than those in whom it failed (P = 0.002) and improved with regard to effectiveness in their occupations, ability to perform tasks around the home, personal relationships, sexual function, and social life (P = 0.01). They also became less isolated socially (P = 0.05). CONCLUSIONS: Dynamic graciloplasty is a safe and reliable technique in patients with severe incontinence and may result in a better quality of life.

Adolescent↗