In a current publications, it has been suggested that hypoxia-triggered "good angiogenesis" involving hypoxic up-regulation of vascular endothelial growth factor (VEGF) molecules, genes, and receptors is likely responsible in a major way for the remarkable gut and patient salvage experience associated with use of the "patch, drain, and wait" (PD&W) surgical approach to perforated necrotizing enterocolitis and midgut volvulus (MGV) with extensive ischemia/necrosis. We report a case in which extensive ischemia/necrosis in a newborn with gastroschisis (likely MGV-induced) was managed successfully by PD&W with an associated marked (24-fold) elevation of VEGF in drainage fluid at 7 days post-initiation of PDW.

The traditional and most frequently employed surgical approach to perforated necrotizing enterocolitis (NEC), laparotomy and bowel resection with enterostomy creation, has been associated with an unacceptably high mortality and major morbidity (sepsis, short-gut syndrome, strictures, long-term total parenteral nutrition (TPN), prolonged and costly hospitalizations with multiple operations, the inevitable open-and-close procedure for “hopeless” extensive gut ischemia in approximately 10% of laparotomy cases, etc.). The use of the laparotomy “patch, drain, and wait” (PD&W) approach to this serious of NEC complication has provided a simple, direct, and effective means of dealing with this problem. The basic principle is to resect no gut and do no enterostomies. The details are presented here as well as the multiple types of “patching” and the importance of use of extensive direct-vision draining with bilateral small Penrose drains from the undersurfaces of both diaphragms into the pelvis with exit sites in both lower quadrants. Proper and effective patching and draining cannot be done blindly, but requires direct vision (laparotomy or laparoscopy). The critical components and timing of the “waiting” are emphasized, including the vital importance of strict avoidance of early post-drainage laparotomy in the 7- to 14-day post-drainage period (whether the drainage is percutaneous, laparotomy PD&W, or laparoscopy PD&W) due to the early, life-threatening-ending hypervascularity that occurs at this time and if left unmolested will function beneficially as life- and gut-saving “good angiogenesis”. The bilateral Penrose drains capture fecal fistulas and function quite well as de-facto enterostomies as the peritoneal cavity is rapidly obliterated by adhesions and massive, florid hypervascularity/gut hypoxia triggered “good angiogenesis” (no peritoneal cavity, no peritonitis). Broad-spectrum triple antibiotics and the routine use of TPN contribute to favorable results. The lessons/experiments of nature encountered in newborns with midgut atresia(s) and remarkable levels of gut survival, in the occasional case with only meconium peritonitis and no obstruction (“auto-anastomosis”) are pertinent here as the TPN of PD&W is provided in atresia(s) by the maternal-placental circulation and the sterile peritoneal cavity of atresia(s) is simulated by the combination of antibiotics and peritoneal-cavity obliteration. Life- and gut-saving “good angiogenesis” is common to both situations. A 15-year personal experience with the PD&W laparotomy approach to perforated NEC in 23 cases is reported here with no mortality in the initial 60 postoperative days, no major morbidity, and no second operation required in 70% (spontaneous “auto-anastomosis”) of cases. All infants with extensive gut ischemia/necrosis (NEC totalis) who would otherwise be classified as “hopeless” and managed by open-and-close only were managed in this experience successfully by PD&W with preservation of both life and an adequate amount of gut, although a second operation was required in these cases to re-establish intestinal continuity. A particularly striking observation was the rapid transition of these infants from profound illness to near-normalcy in a matter of hours after the initiation of PD&W – much like the rapid clinical changes accompanying the lancing of a boil or an abscess. An involvement of hypoxia-induced “good angiogenesis” with marked hypervascularity and involving molecules, genes, and receptors of the vascular endothelial growth factor family of hypoxia-induced angiogenesis molecules is speculated upon, and clinical studies to document these speculations are suggested as well as studies evaluating the potential of laparoscopic PD&W. The usefulness of Argyle chest-tube “venting” and “stenting” by trans-anal passage above colonic “patched” areas as seen in 2 cases is worthy of further study and use.

Twelve consecutive cases of gastrochisis seen during the past 3 years are reported. Four were managed by elective pre-term and pre-labor cesarean section as soon as lung maturity was established by biochemical means and 8 by delivery after the onset of labor, 4 by vaginal delivery and 4 by cesarean section. There was no intestinal thickening or “peel” in any of the 4 infants born by elective pre-term and pre-labor section. All were quickly and easily repaired (the last 3 with umbilicus preservation) with no associated atresias or stenosis and with minimal length of hospitalization. The 8 cases delivered after the onset of labor all had marked instestinal thickening, 2 (25%) had severe and extensive intestinal necrosis or atresias (“apple-peel”), and 1 died (12.5%). All had prolonged and complicated hospital stays with multiple operations. The routine use of elective pre-term and pre-labor section in all cases of gastroschisis diagnosed prenatally by α-fetoprotein (AFP) screening and ultrasound is strongly recommended, as are routine AFP screening and ultrasound studies during pregnancy.

A 3-year-old boy with a history of recurrent episodes of abdominal pain and vomiting, a prior history of intra-abdominal sepsis (amoebiasis), and marked retroperitoneal mesenteric lymphadenopathy on ultrasound was admitted to the hospital because of severe abdominal pain of 2 days' duration associated with fever, nausea, and vomiting. His abdomen was distended and tender and a plain X-ray film revealed a large, dumb-bell-shaped double bubble in the mid-upper abdomen. A barium enema showed non-rotation of the colon with the cecum in the left upper quadrant. At operation, a large, dumbbell-shaped right paraduodenal hernia filled with air and pus was found, but no intestine. The body of the duodenum crossed the hernia and gave it its dumb-bell shape. The hernia/abscess was opened and drained. Penrose drains were left in the abscessed area and the margin of the hernia sac that contained the superior mesenteric artery was closed around the drains with care. The postoperative course was uneventful with no recurrence of symptoms.

In vitro systems have provided increasing evidence of significant lymphocyte transmembrane signalling by plasma membrane receptors which utilize antigen and other ligand activation of the inositol phosphate dual second messenger system of intracellular signalling. Elevation of intracellular Ca2+ and activation of protein kinase C are important products of these signals and appear to provide a complete set of mitogenic signals for both T and B cells. Calcium inophore and phorbol ester have been found to mimic these events in vitro and are here employed in vitro to study their effects on lymphocyte traffic and efferent lymph flow through primary peripheral lymph nodes of sheep and on the output into efferent lymph of the arachidonic acid metabolite, thromboxane B2. Calcium ionophore and phorbol ester were given alone or in combination to popliteal lymph nodes of sheep by drainage area injection or by acute infusion into cannulated afferent lympatics of study popliteal lymph nodes whose efferent lymphatic was chronically cannulated for study. The findings resembled those of drainage area immunization with an early increase in efferent lymph flow and prompt and marked depressions in the output into efferent lymph of both small recirculating and blast lymphocytes ('shutdown', 'recruitment'), followed by a marked increase in the output into efferent lymph of both small recirculating and blast lymphocytes. The greatest elevation in both small recirculating and blast lymphocyte outputs was at 24 and 48 h following phorbol ester and calcium ionophore administration. Acute phorbol ester and calcium ionophore administration was associated with a prompt and marked elevation in efferent lymph levels of thromboxane B2 which were of short duration. The findings observed here with lymph node drainage area infusion/injection of both phorbol ester and calcium ionophore are quite similar to those encountered in this sheep lymphocyte traffic model following popliteal lymph node drainage area immunization with killed Salmonella muenchen antigen.

There are receptors on lymphocytes for substance P which are found both on small recirculating and on blast lymphocytes. The principal effect of substance P on lymphocytes appears to be a stimulating one, both in vitro and in vivo. The in vivo administration of substance P to sheep by acute infusion into cannulated afferent lymphatics of peripheral lymph nodes has been found to stimulate efferent lymph flow and the output into efferent lymph of both small recirculating and blast lymphocytes. We here report that substance P both enhances and prolongs the enhancement of the output of T4 (CD4) lymphocytes from lymph nodes of sheep in vivo. This output-stimulating effect appears to be specific to T4 (CD4) lymphocytes and is associated with a depressant effect on the output of T8 (CD8) and B lymphocytes. The output-stimulating effect on small T4 (CD4) lymphocytes is quite prolonged, lasting in excess of 96 h after a single 50 μg acute infusion. A brief post-infusion depression in T4 (CD4) lymphocyte output is associated with an equally brief, but marked, elevation in the output into efferent lymph of the arachidonic acid metabolite, thromboxane B2. The output-stimulating effect of substance P on blast T lymphocytes is confined to the T4 (CD4) blast lymphocytes. Substance P or a similar molecule may be of value when a specific T4 (CD4) lymphocyte output stimulant effect is desired. A single prior (6 days) acute infusion of substance P into a popliteal lymph node via its cannulated afferent lymphatic produced profound changes in the response to nodal drainage area immunization with killed S. muenchen bacteria. The latent period prior to increased antibody production was abolished, as was the standard post-immunization ‘shutdown’ period of decreased output of lymphocytes into efferent lymph. These changes were accompanied by a marked and progressive increase in antibody production. The findings reported here suggest substance P-induced long-term potentiation (LTP) of the immune response and raise the question of an involment of substance P as a major mediator of immunological memory.

Annals of the New York Academy of SciencesVolume 594, Issue 1 p. 403-407 Neurovascular Immunology. Vasoactive Neurotransmitters and Cellular Immunitya THOMAS C. MOORE, Corresponding Author THOMAS C. MOORE Department of Surgery, UCLA Laboratory for Surgical Research in Molecular Immunology Harbor-UCLA Medical Center Torrance, California 90509Thomas C. Moore, M.D., Ph.D. (Cantab.), Professor of Surgery, Harbor-UCLA Medical Center, 1000 W. Carson St., Torrance, CA 90509.Search for more papers by this authorJOSE L. LAMI, JOSE L. LAMI Department of Surgery, UCLA Laboratory for Surgical Research in Molecular Immunology Harbor-UCLA Medical Center Torrance, California 90509Search for more papers by this authorGREGORY A. WHITLEY, GREGORY A. WHITLEY Department of Surgery, UCLA Laboratory for Surgical Research in Molecular Immunology Harbor-UCLA Medical Center Torrance, California 90509Search for more papers by this authorAZMY GHALY, AZMY GHALY Department of Surgery, UCLA Laboratory for Surgical Research in Molecular Immunology Harbor-UCLA Medical Center Torrance, California 90509Search for more papers by this authorSAMI I. SAID, SAMI I. SAID Department of Medicine University of Illinois College of Medicine at Chicago Chicago, Illinois 60612Search for more papers by this author THOMAS C. MOORE, Corresponding Author THOMAS C. MOORE Department of Surgery, UCLA Laboratory for Surgical Research in Molecular Immunology Harbor-UCLA Medical Center Torrance, California 90509Thomas C. Moore, M.D., Ph.D. (Cantab.), Professor of Surgery, Harbor-UCLA Medical Center, 1000 W. Carson St., Torrance, CA 90509.Search for more papers by this authorJOSE L. LAMI, JOSE L. LAMI Department of Surgery, UCLA Laboratory for Surgical Research in Molecular Immunology Harbor-UCLA Medical Center Torrance, California 90509Search for more papers by this authorGREGORY A. WHITLEY, GREGORY A. WHITLEY Department of Surgery, UCLA Laboratory for Surgical Research in Molecular Immunology Harbor-UCLA Medical Center Torrance, California 90509Search for more papers by this authorAZMY GHALY, AZMY GHALY Department of Surgery, UCLA Laboratory for Surgical Research in Molecular Immunology Harbor-UCLA Medical Center Torrance, California 90509Search for more papers by this authorSAMI I. SAID, SAMI I. SAID Department of Medicine University of Illinois College of Medicine at Chicago Chicago, Illinois 60612Search for more papers by this author First published: June 1990 https://doi.org/10.1111/j.1749-6632.1990.tb40510.xCitations: 4 a This work supported in part by grants from the Joseph Drown Foundation and the National Institutes of Health (DK-37895 and HL-30450). AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume594, Issue1Neuropeptides and Immunopeptides: Messengers in a Neuroinunune AxisJune 1990Pages 403-407 RelatedInformation

The development of the posterior sagittal anorectoplasty approach has been a major recent advance in the repair of imperforate anus. It has been found that sagittal anoplasty can easily and preferably be carried out in the newborn period without the need for colostomy or “tapering”. It is suggested that the perineal sagittal approach be attempted first, with the infant positioned so that the abdominal part of the abdominoperineal approach can be used if necessary—this seldom may be required. Neonatal closure of urinary tract fistulas in boys is an added attractive feature of this approach. The importance of optical magnification (microsurgery) and excellent, intense lighting of the perineal area with a headlamp is stressed for this approach in the newborn, particularly for the management of high pouches and high fistulas. This operation at birth relieves alimentary tract obstruction at birth, eliminates urinary tract contamination (when it exists) at birth, establishes anorectal continuity and maximum potential for “normal” defecation reflexes at birth, and achieves all of this in one rather than three operations.

Glass shrapnel from explosions of "dry ice bombs," created by thrusting dry ice into glass soft-drink bottles and occluding the opening of the bottles, has produced serious and multiple lacerating injuries in three children, which required major operative intervention. We found no previous reports of this grave hazard.

During a recent 4 1/2-year period, an increasing number of young children aged 13 years and younger (230 consecutive patients) came to our institution with signs, symptoms, and findings of acute appendicitis, which was perforated in nearly half of the cases (47%). This was accompanied by a marked increase in the number of very young children aged 6 years and younger (32% of our 230 patients). A prompt response to broad preoperative antibiotic coverage and definitive operative intervention (appendectomy in all cases) was found, with no mortality and essentially no major morbidity (less than 1%). The rapid transition from serious illness to near normalcy in the matter of a few hours with a standardized approach to treatment stimulated this review of appendicitis in this pediatric age group in an effort to define factors influencing these findings.

Malignant hyperthermia (MH) is a seemingly rare genetic myopathy. Hypermetabolic crisis accompanied by a rise in body temperature to as high as 44 degrees C, is its hallmark. Malignant hyperthermia is usually triggered by potent inhalation anesthetics and/or depolarizing muscle relaxants. Because of the extraordinary incidence of death in patients who are at risk, pediatric surgeons may be reluctant to operate on these patients. Eight such patients were referred to the Pediatric Surgery Service and the UCLA Malignant Hyperthermia Center following pediatric surgical procedures aborted for first episodes of malignant hyperthermia (five) or for a strong family history of malignant hyperthermia (three). They were anesthetized with nitrous oxide, barbiturates, opiates, tranquilizers, and nondepolarizing muscle relaxants. The patients were not treated prophylactically with dantrolene. Cardiac monitoring, end-tidal PCO2, and rectal temperatures were monitored. After completion of their pediatric surgical procedures, all eight patients had a vastus lateralis muscle biopsy performed and subsequent caffeine/halothane contracture studies completed. The contracture study result was positive in all patients studied. No anesthetic or surgical complications were encountered. This study shows that patients at risk for developing MH crisis can have pediatric surgical procedures performed safely with appropriately selected general anesthesia.

Substance P, an 11 amino acid residue vasoactive neurotransmitter peptide, has been found on acute infusion (50 micrograms) into cannulated afferent lymphatics of popliteal lymph nodes of sheep to produce marked elevations in both efferent lymph flow and in the outputs of both blast and small recirculating lymphocytes into popliteal node efferent lymph (chronically cannulated). These elevations were characterized by a delay in the onset of major elevations, a marked prolongation of the elevations and a substantially greater stimulative effect on the output of blast lymphocytes. It is suggested that the number and types of substance P receptors on lymphocytes and in sheep peripheral lymph nodes may be responsible for these observations. Infusion of substance P, known for involvement in pain impulse transmission, was able to briefly overcome anaesthesia-induced depression in lymphocyte traffic. The substance P-induced alterations in lymph flow and lymphocyte traffic in vivo were demonstrated to be due to local rather than systemic effects of substance P.

The Department of Surgery UCLA School of Medicine The Pediatric Surgical Service Harbor- UCLA Medical Center Torrance, California 90509

A case of necrotizing amebic pancolitis in a 6-year-old boy with asplenia, partial situs inversus, and cyanotic congenital heart disease is reported and the literature is reviewed briefly. Our patient was managed successfully by prompt colectomy, ileostomy, a Stamm gastrostomy, and extensive drainage of the peritoneal cavity with administration of metronidazole postoperatively and prolonged jugular vein Broviac catheter hyperalimentation. This child may be the first survivor of total colonic amebic necrosis in childhood. Necrotizing amebic colitis appears to be more hazardous in infancy and childhood than in adult years. Malnutrition and additional illnesses and malformations may produce greater immunocompromise in the very young, placing them at greater risk for the ultimate of amebic intestinal complications, total colonic necrosis and disintegration.

In the past decade, the main interest in the involvement of prostaglandin E2 (PGE2) in the immune response has been concerned with its role in immunomodulation (suppression) both in vitro and in vivo. Comparatively little attention has been devoted to its immunostimulatory role. It has been suggested that PGE2, like histamine, may function as a ‘double agent’, initially triggering, facilitating and augmenting a stimulatory immune response and later modulating, limiting and contributing to the turning off of this response. We here report an early (within minutes) immunostimulatory involvement of PGE2 (and thromboxane A2) in the sheep, with prompt elevations in levels of PGE2 and thromboxane B2 in popliteal lymph node efferent lymph following drainage area immunization with killed Salmonella muenchen bacteria. These elevations were associated with an increase in efferent lymph flow and an equally prompt but limited depression of lymphocyte outputs into efferent lymph (‘shutdown’, ‘recruitment’). Local increases in blood flow and vascular permeability probably play important roles in these events.

Vasoactive intestinal peptide (VIP) is a 28 amino acid-residue neurovascular and gut peptide with a number of important biological activities. Recent in vitro studies suggest an immunomodulatory (depressant) role for VIP. In the present in vivo studies, employing the Hall and Morris sheep lymphocyte traffic model, acute infusions of VIP into cannulated afferent lymphatics of popliteal lymph nodes produced prompt and marked depressions in the output of both small recirculating and blast lymphocytes into popliteal efferent lymph, with a selective effect on T4 (CD4) lymphocytes. It has been suggested that the HIV (AIDS) virus may employ VIP or VIP-like receptors on brain cells and lymphocytes for intracellular access.

Core pentapeptides and an octapeptide (Peptide T) computer deduced from amino acid sequences from vasoactive intestinal peptide (VIP) and the 120 gp external envelope of the HIV (AIDS) virus and synthesized have been reported to have important in vitro and in vivo activity including inhibition of HIV binding to CD4 surface antigens of brain cells and lymphocytes and limitation of HIV infectivity. Two of these core pentapeptides, peptide TTNYT (Peptide T [4–8]) and peptide TDNYT (VIP[7–11]), are reported here, on acute infusion into cannulated afferent popliteal lymphatics of sheep, to produce prompt and marked depressions in the output of both small recirculating and blast lymphocytes into popliteal lymph node efferent lymph. As with a prior VIP infusion study, there appeared to be a selective effect on T4 (CD4) lymphocytes, with a marked predominance of T4 (CD4) lymphocytes in the lymphocyte depleted efferent lymph.

For the first time in some 36 years of experience with gastroschisis. the author has encountered in short order both his first and second cases of gastroschisis without any thickening of the eviscerated intestine. Both infants, whose gastroschisis had been detected by maternal alphafetoprotein and ultrasound studies, were delivered by elective preterm cesarean section and were repaired easily with closure of the abdomen in layers. It is suggested that the bowel thickening and rigidity in gastroschisis may result from the trauma of labor and delivery and that elective preterm section, as soon as lung maturity can be demonstrated, may substantially improve the ease of primary repair in gastroschisis.

A case of massive acquired omental cyst in a 13-year-old girl as a complication of ventriculo-peritoneal (VP) shunting is reported. This is the first such case to be reported. Most complications of VP shunting involve shunt blockade, infection, or both. The absence of shunt blockade, infection or inflammation, and associated symptoms in this case permitted the acquired omental cyst to reach a massive size before detection; the cyst was managed successfully by simple resection of a large part of its thin wall.