Phenotypic and genetic associations between gray matter covariation and tool use skill in chimpanzees (Pan troglodytes): Repeatability in two genetically isolated populations.

Humans and chimpanzees both exhibit a diverse set of tool use skills which suggests selection for tool manufacture and use occurred in the common ancestors of the two species. Our group has previously reported phenotypic and genetic associations between tool use skill and gray matter covariation, as quantified by source-based morphometry (SBM), in chimpanzees. As a follow up study, here we evaluated repeatability in heritability in SBM components and their phenotypic association with tool use skill in two genetically independent chimpanzee cohorts. Within the two independent cohorts of chimpanzees, we identified 8 and 16 SBM components, respectively. Significant heritability was evident for multiple SBM components within both cohorts. Further, phenotypic associations between tool use performance and the SBM components were largely consistent between the two cohorts; the most consistent finding being an association between tool use performance and an SBM component including the posterior superior temporal sulcus (STS) and superior temporal gyrus (STG), and the interior and superior parietal regions (p < 0.05). These findings indicate that the STS, STG, and parietal cortices are phenotypically and genetically implicated in chimpanzee tool use abilities.

Age- and sex-related differences in baboon (Papio anubis) gray matter covariation.

Age-related changes in cognition, brain morphology, and behavior are exhibited in several primate species. Baboons, like humans, naturally develop Alzheimer's disease-like pathology and cognitive declines with age and are an underutilized model for studies of aging. To determine age-related differences in gray matter covariation of 89 olive baboons (Papio anubis), we used source-based morphometry (SBM) to analyze data from magnetic resonance images. We hypothesized that we would find significant age effects in one or more SBM components, particularly those which include regions influenced by age in humans and other nonhuman primates (NHPs). A multivariate analysis of variance revealed that individual weighted gray matter covariation scores differed across the age classes. Elderly baboons contributed significantly less to gray matter covariation components including the brainstem, superior parietal cortex, thalamus, and pallidum compared to juveniles, and middle and superior frontal cortex compared to juveniles and young adults (p < 0.05). Future studies should examine the relationship between the changes in gray matter covariation reported here and age-related cognitive decline.

Ghrelin contributes to derangements of glucose metabolism induced by rapamycin in mice.

AIMS/HYPOTHESIS: Rapamycin impairs glucose tolerance and insulin sensitivity. Our previous study demonstrated that rapamycin significantly increases the production of gastric ghrelin, which is critical in the regulation of glucose metabolism. Here, we investigated whether ghrelin contributes to derangements of glucose metabolism induced by rapamycin. METHODS: The effects of rapamycin on glucose metabolism were examined in mice receiving ghrelin receptor antagonist or with Ghsr1a gene knockout. Changes in GLUT4, c-Jun N-terminal kinase (JNK) and phosphorylated ribosomal protein S6 (pS6) were investigated by immunofluorescent staining or western blotting. Related hormones were detected by radioimmunoassay kits. RESULTS: Rapamycin impaired glucose metabolism and insulin sensitivity not only in normal C57BL/6J mice but also in both obese mice induced by a high fat diet and db/db mice. This was accompanied by elevation of plasma acylated ghrelin. Rapamycin significantly increased the levels of plasma acylated ghrelin in normal C57BL/6J mice, high-fat-diet-induced obese mice and db/db mice. Elevation in plasma acylated ghrelin and derangements of glucose metabolism upon administration of rapamycin were significantly correlated. The deterioration in glucose homeostasis induced by rapamycin was blocked by D: -Lys3-GHRP-6, a ghrelin receptor antagonist, or by deletion of the Ghsr1a gene. Ghrelin receptor antagonism and Ghsr1a knockout blocked the upregulation of JNK activity and downregulation of GLUT4 levels and translocation in the gastrocnemius muscle induced by rapamycin. CONCLUSIONS/INTERPRETATION: The current study demonstrates that ghrelin contributes to derangements of glucose metabolism induced by rapamycin via altering the content and translocation of GLUT4 in muscles.

Performance of a constructed wetland for treating farm-yard dirty water.

Constructed wetlands (CWs) have been used to treat agricultural effluents with varying success especially with respect to their operational efficiency in winter and ability to retain phosphorus. Dirty water (DW) from dairy farms is a mixture of manure contaminated runoff and milk parlour washings with a highly polluting biochemical oxygen demand (BOD) < or =3000 mg/L. The initial performance a CW of a 1.2 ha horizontal flow CW consisting of five ponds in series designed to treat DW from a dairy unit was assessed over four years. Ponds were earth-lined and shallow (0.3 m) with a water residence time of 100 days and planted with five species of emergent macrophytes. In comparison to CW inflow, annual reductions were as follows: BOD 99%, P 95% and N 92.8%. Coliforms were reduced by a 10(-5) factor to natural levels. From May to October there was little CW discharge due to evaporative losses. Final effluent quality was poorest in February but remained within a regulatory effluent standard for BOD of 40 mg/L. If the CW had only four ponds (25% less surface area) effluent would have failed the BOD standard in three years.

Do research papers provide enough information on design and material used in ankle foot orthoses for children with cerebral palsy? A systematic review.

OBJECTIVES: The purpose of this article is to determine how many of the current peer-reviewed studies of ankle foot or-thoses (AFOs) on children with cerebral palsy (CP) have included adequate details of the design and material of the AFO, to enable the study to be reproduced and outcomes clearly understood. METHODS: A thorough search of studies published in English was conducted in March 2015, with no restriction on dates, within all major databases using relevant phrases. These searches were then supplemented by tracking all key references from the appropriate articles identified. STUDY SELECTION: The inclusion criteria were as follows: (1) population - children with CP; (2) intervention - AFOs; and (3) outcome measure. One reviewer extracted data regarding the characteristics of the included studies, with the extracted data checked for accuracy and completeness by a second reviewer. None of the studies reviewed gave adequate details of the AFOs. Only 3.6% (n = 2) of papers tested the stiffness. Many studies (54.5%) did not describe the material used nor the material thickness (72.7 %). None of them gave any clinical justification for the chosen design of AFO. CONCLUSIONS: There is a clear paucity of detail regarding the design and material used in AFOs on studies involving children with CP. Such a lack of detail has the potential to affect the validity of the reported outcomes, the ability to reproduce the studies and may misinform clinical practice.

The nitrogen physiology of the marine N2-fixing cyanobacteria Trichodesmium spp.

Trichodesmium spp. have proved to be enigmatic organisms, and their ecology and physiology are unusual among diazotrophs. Recent research shows that they can simultaneously fix N2 and take up combined nitrogen. The co-occurrence of these two processes is thought to be incompatible, but they could be obligatory in Trichodesmium spp. if only a small fraction of cells within a colony or along a filament are capable of N2 fixation. Combined nitrogen is released from cells during periods of active growth and N2 fixation, and concomitantly taken up by Trichodesmium spp. or cells living in association with colonies. Although the nitrogenase of Trichodesmium spp. is affected by high concentrations of combined nitrogen, it might be relatively less sensitive to low concentrations of combined nitrogen typical of the oligotrophic ocean and culture conditions. Nitrogenase activity and synthesis exhibits an endogenous rhythm in Trichodesmium spp. cultures, which is affected by the addition of nitrogen.

Classification of chondroitin sulfate A, chondroitin sulfate C, glucosamine hydrochloride and glucosamine 6 sulfate using chemometric techniques.

Chondroitin sulfate A, chondroitin sulfate C, glucosamine hydrochloride and glucosamine sulfate are natural products that are becoming increasingly popular in the treatment of arthritis. They belong to a class of compounds known as glycosaminoglycans (GAGs). They are available over the counter as nutritional supplements. However, increasing use has led to increasing scrutiny of the quality of products on the market. There is also interest in the pharmacological properties of these compounds. To facilitate this, there is a need for better qualitative and quantitative methods of analysis. This paper describes methods for achieving the qualitative identification of chondroitin sulfate A, chondroitin sulfate C, glucosamine hydrochloride or glucosamine sulfate. Fourier transform infrared spectroscopy coupled with a variety of chemometric methods successfully classified these compounds. Using soft independent modeling of class analogies (SIMCA), hierarchical cluster analysis (HCA) and principal components analysis (PCA) samples were classified as either chondroitin sulfate A, chondroitin sulfate C, glucosamine hydrochloride or glucosamine sulfate. This work also examined the discriminating ability of different sections of the spectrum. It was found that for the classification of these compounds that using the finger print region of the spectrum (below 2000 cm(-1)) gave the best discrimination.

Potassium channel conductance: a mechanism affecting hair growth both in vitro and in vivo.

The opening of intracellular potassium channels has been suggested as a mechanism regulating hair growth. Enhancing the flux of potassium ions is a mechanism shared by several structurally diverse antihypertensive agents including minoxidil sulfate (the active metabolite of minoxidil), pinacidil, P-1075 (a potent pinacidil analog), RP-49,356, diazoxide, cromakalim, and nicorandil. Of these drugs, minoxidil, pinacidil, and diazoxide have been reported to elicit hypertrichosis in humans. This potassium channel hypothesis was examined by testing these drugs for effects on hair growth both in vitro and in vivo. For the in vitro studies, mouse vibrissae follicles were cultured for 3 d with drug and the effects on hair growth were measured by metabolic labeling. All drugs, except diazoxide, enhanced cysteine incorporation into the hair shafts of the cultured vibrissae. Diazoxide was poorly soluble and thus was tested only at low doses. Minoxidil, P-1075, cromakalim, and RP-49,356 were also evaluated in vivo by measuring hair growth effects in balding stumptail macaque monkeys. The drugs were administered topically to defined sites on balding scalps once per day for 4-5 months and the amount of hair grown was determined by monthly measurements of shaved hair weight. Three of the drugs produced significant increases in hair weight whereas, the RP-49,356 had no effect. These studies provide correlative evidence that the opening of potassium channels is an important regulatory mechanism for hair growth. This provides the impetus for further studies on this potentially important mechanism affecting hair biology.

Proliferation of gastric endocrine cells after vagotomy in the rat.

The effects of truncal vagotomy on gastrin cell and somatostatin cell populations and circulating hormone levels were studied in rats. Truncal vagotomy produced significant gastrin cell hyperplasia, with the largest increase in gastrin cell density observed 2 weeks postvagotomy. Gastrin cell hyperplasia was sustained up to 6 months. Both antral somatostatin cell and corpus somatostatin cell numbers demonstrated significant and sustained increases after vagotomy; the largest increases were observed 2 weeks after operation. Early elevation of circulating gastrin to 3 times the baseline level was followed by sustained, lower level hypergastrinemia. Plasma somatostatin levels were decreased 2 days after vagotomy, with a return to control values 2 weeks after operation. Gastrin cells and somatostatin cells are dynamic populations, capable of changes in both number and secretory function after truncal vagotomy.

Relationship of antral gastrin cells and serum gastrin to thyroid function in the rat.

Using a quantitative immunocytochemical technique, antral gastrin cell populations in the rat were studied in various states of thyroid function. Simultaneous determinations of circulating serum gastrin were made by RIA. Rats made hypothyroid by ingestion of methimazole (0.01% solution in drinking water for 30 days) demonstrated a significant 32% decrease in gastrin cell density (306 +/- 9/cm vs. 207 +/- 11/cm for controls) associated with a significant 50% decrease in serum gastrin (143 +/- 12 vs. 307 +/- 20 pg/ml for controls). Induction of hypothyroidism and hypoparathyroidism by surgical thyroparathyroidectomy resulted in similarly significant decreases in gastrin cell numbers (229 +/- 12/cm) and serum gastrin (169 +/- 14 pg/ml). Animals that underwent thyroparathyroidectomy followed by T4 replacement (2.5 micrograms/100 g X day, ip) for 30 days had a mean gastrin cell density that was not significantly different from that of controls; serum gastrin was decreased to 207 +/- 11 pg/ml. The administration of excess T4 (200 micrograms/100 g X day, ip) for either 15 or 30 days was associated with a significant increase in gastrin cell numbers (413 +/- 23/cm at 15 days; 352 +/- 21/cm at 30 days). Mean serum gastrin was increased by 82% after 15 days of T4 administration (558 +/- 51 pg/ml) and by 65% at 30 days (506 +/- 36 pg/ml). We conclude that T4 is trophic for gastrin cells in the rat.

Inhibition of pancreatic exocrine secretion in the rat by calcitonin gene-related peptide: involvement of circulating somatostatin.

Calcitonin gene-related peptide (CGRP), a 37-amino acid peptide, has been shown to be a potent inhibitor of pancreatic exocrine secretion when administered exogenously The present study was performed to determine if this inhibitory effect is due to the direct actions of exogenous CGRP on the exocrine pancreas or to the effects of another inhibitor released by CGRP. To this end, we first confirmed the inhibitory effects of the peptide on exocrine function by infusing the peptide into conscious rats previously prepared with bile-pancreatic fistulas and measuring cholecystokinin-stimulated amylase and protein outputs. CGRP produced a dose-dependent inhibition of both protein and amylase outputs in vivo. In marked contrast, CGRP in vitro had no direct inhibitory effect on amylase output from either the isolated buffer-perfused pancreas or dispersed acinar cells. Thus, the inhibitory effects of exogenous CGRP on pancreatic exocrine function appear to be indirect. In an attempt to determine the mediator of the inhibitory effects of CGRP, we assessed the ability of similar doses of CGRP to stimulate the release of a potential endogenous inhibitor of pancreatic exocrine function, circulating somatostatin. In conscious rats, iv CGRP dose-dependently increased circulating plasma somatostatin-like immunoreactivity from 35 +/- 5 to 86 +/- 7 fmol/ml. To determine if these increments in circulating somatostatin were sufficient to impair exocrine function, the isolated pancreas was exposed in vitro to a similar concentration of somatostatin. Somatostatin perfusion resulted in a significant inhibition of pancreatic amylase output (73%). Overall, these results support the hypothesis that 1) the inhibitory effect of exogenous CGRP on pancreatic exocrine function is indirect; 2) exogenous CGRP stimulates the release of endogenous somatostatin into the systemic circulation; and 3) the concentration of circulating somatostatin is sufficient to mediate the effect of exogenous CGRP on the exocrine pancreas.

Hair growth effects of oral administration of finasteride, a steroid 5 alpha-reductase inhibitor, alone and in combination with topical minoxidil in the balding stumptail macaque.

A 5 alpha-reductase inhibitor, finasteride, was administered orally at 0.5 mg/day, alone or in combination with topical 2% minoxidil, for 20 weeks to determine the effects on scalp hair growth in balding adult male stumptail macaque monkeys. A 7-day dose-finding study showed that both 0.5- and 2.0-mg doses of the drug produced a similar diminution in serum dihydrotestosterone (DHT) in male stumptails. Hair growth was evaluated by shaving and weighing scalp hair at baseline and at 4-week intervals during treatment to obtain cumulative delta hair weight (sum of the 4-week changes in hair weight from baseline) for the 20-week study. The activity of the 5 alpha-reductase enzyme was assessed by RIA of serum testosterone (T) and DHT at 4-week intervals. The combination of finasteride and minoxidil generated significant augmentation of hair weight (additive effect) compared to either drug alone. Finasteride increased hair weight in four of five monkeys. When the data of the one nonresponsive monkey were excluded, finasteride elicited a significant elevation in hair weight compared to topical vehicle alone. Minoxidil also evoked a significant increase in hair weight compared to vehicle alone. Serum T was unchanged, whereas serum DHT was significantly depressed in monkeys that received either finasteride or the combination of finasteride and minoxidil. These data suggest that inhibition of the conversion of T to DHT by this 5 alpha-reductase inhibitor reverses the balding process and enhances hair regrowth by topical minoxidil in the male balding stumptail macaque.

Lysophosphatidic acid stimulates calcium transients in enteric glia.

The enteric nervous system plays an integral role in the gastrointestinal tract. Within this intricate network, enteric glia are crucial in the maintenance of normal bowel function, yet their signaling mechanisms are poorly understood. Enteric glia, and not enteric neurons, selectively responded to lysophosphatidic acid (LPA), a product of phosphatidylcholine metabolism, with dose-dependent calcium (Ca(2+)) signaling over a range from 100 pM to 10 microM. The elicited calcium transients involved both the mobilization of intracellular Ca(2+) stores and the influx of extracellular Ca(2+) as LPA signals were obliterated following the depletion of intracellular Ca(2+) and attenuated by the removal of Ca(2+) from the perfusion buffer. Pretreatment with pertussis toxin (100 ng/ml) reduced the magnitude of LPA Ca(2+) transients (95+/-20 nM vs 168+/-17 nM for controls). Repetitive exposure yielded diminished responsiveness, with a 25% reduction in [Ca(2+)](i) between first and second exposures. Inhibition of the inositol 1,4,5-trisphosphate (IP(3)) receptor with 200 microM 2-aminoethoxydiphenylborate (2APB) abolished LPA signals. RT-PCR analysis demonstrated the presence of two LPA-coupled endothelial differentiation gene (EDG) receptor mRNAs (EDG-2 and EDG-7) in myenteric plexus primary cultures. EDG-2 expression in glial cells of the ENS was confirmed immunocytochemically.

Effectiveness of double bolus alteplase in the treatment of acute myocardial infarction.

Fifty-nine consecutive patients presenting within 6 hours of the onset of symptoms of an acute myocardial infarction were treated with 150 mg of soluble aspirin orally, and either 70 or 100 mg of alteplase divided into 2 intravenous bolus injections separated by 30 minutes. Dosage regimens were either 20 followed by 50 mg (group A), 50 followed by 20 mg (group B), or 50 followed by 50 mg (group C). Coronary angiography 60 minutes after the first bolus showed infarct-related coronary artery patency (Thrombolysis in Myocardial Infarction score 2 or 3) in 13 of 16 (81%) patients in group A, 12 of 17 (71%) in group B, and 10 of 11 (91%) in group C (overall patency rate at 60 minutes: 35 of 44 [80%] patients; 95% confidence interval 68 to 91%). At 90 minutes, patency rates were 15 of 20 (75%) patients in both groups A and B, and 18 of 19 (95%) in group C (overall patency rate 48 of 59 [81%] patients; 95% confidence interval 72 to 91%). Residual thrombus was identified with the 90-minute angiogram in 7 patients in group A, 5 in group B, and 3 in group C. Although there was no statistically significant difference in patency between the 3 dosage regimens at either 60 or 90 minutes there was a trend toward increased patency and more complete thrombolysis at 90 minutes in group C. No episodes of bradyarrhythmia, hypotension or cerebrovascular bleeding were observed after double bolus therapy. There were 7 episodes (12%) of reocclusion, and 3 deaths (5%) within 1-month follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Proximal diverting jejunostomy for compromised small bowel.

The use of a totally diverting proximal jejunostomy in the surgical therapy of five cases of compromised small bowel is reported. In each case a diverting end-on jejunostomy was constructed 30 to 100 cm beyond the ligament of Treitz. The oversewn distal end of bowel was anchored intraperitoneally at the jejunum, and a tube was introduced into the distal intestine for subsequent radiologic study. In three of five cases small bowel leaks were demonstrated after operation by x-ray examination. The leaks caused no clinical problems. The jejunostomy remained in place for 4 to 13 weeks. The mean daily stoma output ranged from 200 to 2800 ml/day. Fluid and electrolyte losses were replaced and total parenteral nutrition was supplied. No stomal complications occurred. Intestinal continuity was restored when contrast medium passed through the intestine without leak or obstruction. Reanastomosis of the intestinal tract was accomplished with minimal dissection through a small peristomal incision because the distal closed end of the divided bowel had been fixed to the stoma base. Each of the patients recovered gastrointestinal function without further complication and was discharged from the hospital on a general diet. With parenteral nutritional support, a high jejunostomy is well tolerated. Proximal intestinal diversion can salvage an otherwise hopeless situation.

Physiology and pathophysiology of gastrin: a review.

Recent advances in understanding the physiology and pathophysiology of the gastrointestinal hormone, gastrin, are reviewed. Details of gastrin biosynthesis, secretion, and cellular actions may have broad implications for other peptide hormones. Potentially useful antigastrin drugs are described. Areas of future development are suggested.

Neuroligands evoke calcium signaling in cultured myenteric neurons.

BACKGROUND: Myenteric neurons, which control gut motility and absorption, are heterogeneous in structure, electrophysiology, and neuropeptide content. We hypothesized that myenteric neurons would display heterogeneous responses to neuroligands found in enteric tissue. We examined increases in intracellular calcium ([Ca2+]i), an important second messenger, evoked by selected neuroligands in cultured myenteric neurons. METHODS: Primary cultures of guinea pig myenteric neurons were characterized by using a standard immunocytochemical stain for microtubule-associated protein (MAP2). Increases in [Ca2+]i were measured by digital imaging microscopy. Results expressed as mean +/- SEM, Student's t test. RESULTS: Cultured myenteric neurons examined with phase contrast and Nomarsky optics extend processes and stain positively with the neuron-selective stain MAP2. Histamine did not evoke calcium mobilization in cultured neurons, although progressive increases in [Ca2+]i were seen with bradykinin, glutamate, serotonin, cholecystokinin, bombesin, adenosine triphosphate (ATP), substance P, and acetylcholine. Enteric neurons differed from one another in the ability to respond to one, two, or three of the agonist combinations tested. Time in culture did not alter the percentage of neurons responding to ATP, substance P, or acetylcholine. ATP evoked equivalent [Ca2+]i increases in neurons examined at the three time points, whereas significant decrements in neuronal calcium mobilization were seen after 8 days in culture with substance P or acetylcholine (p < 0.05 versus 1 day in vitro). CONCLUSIONS: Cultured myenteric neurons extend processes and retain expression of neuron-specific antigens. Selected neuroligands found in enteric tissue increase [Ca2+]i, as a second messenger in subsets of myenteric neurons. Heterogeneity exists among cultured neurons in their ability to respond to ligand combinations. Changes in [Ca2+]i induced by neuroligands in myenteric neurons may be altered with time in vitro.

Pituitary adenylate cyclase-activating peptide stimulates amylase release and cyclic adenosine monophosphate production in pancreatic acinar cells.

BACKGROUND: Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide member of the secretin/glucagon family of peptides, which also includes vasoactive intestinal peptide (VIP). This study was designed to examine the effects of PACAP-38 on pancreatic exocrine function in vitro. METHODS: Amylase release and signal transduction pathways were examined by using dispersed guinea pig acinar cells. RESULTS: PACAP-38 produced dose-dependent increases in amylase release. Coincubation of PACAP-38 (1 nmol/L) additively augmented amylase release stimulated by cholecystokinin, carbachol, or bombesin. Coexposure with PACAP-38 did not affect amylase release in response to maximally stimulatory concentrations of VIP (1 nmol/L). The VIP antagonist, [N-Ac-Tyr1,D-Phe2]-GRF(1-29)-NH2, abolished amylase release in response to either PACAP-38 or VIP. Dose-dependent increases in cyclic adenosine monophosphate production were noted on exposure to PACAP-38, with a 70-fold increment relative to the control value at 1 nmol/L PACAP-38. Inositol phosphate turnover and intracellular Ca2+ levels were not affected by PACAP-38 exposure. CONCLUSIONS: In guinea pig pancreatic acini, VIP preferring receptors for PACAP-38 are functionally linked to adenylate cyclase.

Galanin inhibition of enteric cholinergic neurotransmission: guanosine triphosphate-binding protein interactions with adenylate cyclase.

BACKGROUND: The ability of galanin, a unique 29 amino acid peptide, to affect cholinergic neurotransmission was examined in the guinea pig myenteric plexus. METHODS: The effects of galanin on tritiated acetylcholine ([3H]ACh) release were studied with cultured guinea pig myenteric plexus neurons. Functional correlations were made with longitudinal strips of ileal smooth muscle with attached myenteric plexus for examination of isometric contraction. RESULTS: Galanin abolished potassium-stimulated [3H]ACh release (170% +/- 18% of basal vs 109% +/- 16%). Galanin inhibited [3H]ACh release stimulated by forskolin or cholera toxin. [3H]ACh release stimulated by cholecystokin octapeptide, calcitonin gene-related peptide, substance P, or vasoactive intestinal peptide was also suppressed by galanin (10(-8) mol/L). Inhibitory effects were reversed by pertussis toxin preexposure, indicating involvement of guanosine triphosphate-binding proteins. Galanin inhibited contractility of longitudinal smooth muscle strips exposed to cholecystokinin-8 (EC50 7.0 X 10(-9) mol/L for cholecystokinin alone vs 1.3 X 10(-8) mol/L for cholecystokinin-8 plus galanin) and abolished contractile responses to calcitonin gene-related peptide. CONCLUSIONS: Galanin inhibits cholinergic neurotransmission in myenteric plexus neurons. Inhibitory effects involve guanosine triphosphate-binding protein mediation.

Gastrointestinal complications of chronic granulomatous disease: surgical implications.

Eleven of 20 patients with chronic granulomatous disease (55%) developed serious gastrointestinal complications requiring surgical consultation or operation over a 10-year period with an average of 2.2 complications per patient. The mean age of onset of symptoms was 12 years (range 2.5 months to 25 years), and 91% of the patients were male. Admission for gastrointestinal complications constituted 18% of all admissions for these patients; the mean hospitalization time was 27.8 +/- 3.5 (SEM) days. Hepatic abscess, the most common complication, occurred in 16 instances. Perirectal abscess developed in three patients and gastric outlet obstruction developed in two patients. Other complications included appendicitis, acalculous cholecystitis, and Salmonella enteritis. Open hepatic debridement and external drainage combined with long-term intravenous antibiotics (mean 25.2 +/- 4.8 days) were curative in every case, but operative morbidity was frequent and severe. Twelve major complications accompanied open hepatic drainage in 14 cases including wound disruption, prolonged febrile course, subhepatic abscess, and recurrent hepatic abscess. Five secondary operations were required for treatment of these complications. Gastric outlet obstruction, by contrast, was successfully managed nonoperatively. Staphylococcus aureus was an etiologic agent in 66% of the cases, but many other aerobic gram-positive and gram-negative organisms were isolated. Anaerobic bacteria were unusual. Bacteremia occurred only once.