Private industry and public health join forces: an occupational health program for workers at a construction site in rural Alabama.
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Biomedical subjects
Publications and source records attributed to K D Newman.
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Malignant liver tumors in children are uncommon but have a high mortality. Survival rates have improved with advances in chemotherapy, imaging, tumor biology, and supportive care. However, complete surgical resection is the cornerstone of successful management. Important determinants of outcome are stage, histology, and resectability. A multidisciplinary team approach to the care of pediatric patients with liver tumors using the latest guidelines from clinical trials provides the best opportunity for care.
We have achieved in vivo expression of recombinant low-density-lipoprotein (LDL) receptors in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model for the human disease familial hypercholesterolemia. A retroviral vector was constructed containing the human LDL receptor cDNA and was used to stably transduce primary skin fibroblasts from WHHL rabbits. The integrity and function of the introduced LDL receptor was established by immunoprecipitation, by a fluorescent LDL binding assay, and by the ability of the transduced cells to suppress 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase activity in response to exogenous cholesterol. Autologous transduced fibroblasts were reimplanted into donor rabbits; in vivo LDL receptor expression and the survival of the transduced cells were analyzed by immunohistochemistry and by LDL binding assays performed on cells recovered from the implants. LDL receptor-bearing cells could be identified on tissue sections and recovered from implants for up to four weeks. Total and LDL cholesterol levels decreased significantly after implantation of the transduced cells; however, control experiments indicated that the decreases were not mediated through the recombinant LDL receptor. While in vivo stable expression of recombinant LDL receptors in Watanabe rabbits is possible, consequent changes in lipid levels must be interpreted with caution. This system of site-specific in vivo expression of recombinant LDL receptors permits further evaluation of the role of LDL receptor-gene replacement in the therapy of hypercholesterolemia.
Laparoscopic cholecystectomy has gained increasing application as an operative approach for adults with gallbladder disease. We assessed the safety and feasibility of this technique in five pediatric patients with symptomatic cholelithiasis, two of whom had sickle cell disease. With several technical modifications, we found that laparoscopic cholecystectomy was safe and effective in children. This technique permitted early discharge with expedient return to full activity.
The incidence of alkaline gastroesophageal reflux (GER) was examined in 111 consecutive children referred for evaluation of GER during a 1-year period. The results of 24-hour pH monitoring studies and the medical records were retrospectively evaluated. Acid reflux was defined as occurring whenever the pH was less than 4 and alkaline reflux was defined whenever the pH was greater than 7. The percentage of time that reflux occurred, the number of reflux episodes, the number of episodes greater than 5 minutes, and the longest episode were all recorded. Based on these data, four categories of patients were identified as compared with normal values as determined by Pellegrini et al. When using criteria based on the percentage of time that reflux occurred, the largest group of children with GER was found to reflux acid (50%). However, 27 children (24%) had combined acid and alkaline reflux. Eighteen (16%) had predominantly alkaline reflux. Previously, these 18 children would have been considered as having a low likelihood of reflux by pH criteria. Endoscopic examination showed that pathological evidence of esophagitis occurred in four of the children with pure alkaline reflux. This review shows that symptomatic GER in infants and children may be due to acid or alkaline secretions or a mixture of both. A previously unrecognized cohort exists of children who demonstrate primary alkaline reflux. These patients need to be recognized and may benefit from a therapeutic program specifically designed to control alkaline reflux.
Current methods for the evaluation of retention of endothelial cells seeded on vascular grafts are limited by the inability to specifically identify and quantitate seeded cells on a long-term basis. To address this problem we developed a method of quantification of graft surface coverage using genetic labeling of endothelial cells combined with computer-assisted image analysis. Rabbit aortic endothelial cells were transduced with a marker gene (lac-Z) and seeded on polytetrafluoroethylene grafts. After histochemical staining in which the genetically labeled cells turn blue, computer-assisted image analysis was used to measure the percentage of graft surface covered by the seeded cells. The utility of the method was evaluated by using it to assess the effect on graft coverage of seeded cell density and by precoating with fibronectin. Quantification of surface area coverage was automated and reproducible both between scans and between observers. Use of this method allowed the determination of a linear correlation between cell density in the seeding suspension and graft coverage (r2 = 0.93, p less than 0.0001). The method also permitted confirmation of the positive contribution of fibronectin coating to graft coverage by seeded cells: 73% coverage coated versus 8% coverage uncoated (p less than 0.0001). The ability of this method to specifically identify genetically marked endothelial cells and their progeny makes it attractive for use in studies targeted at optimization of graft coverage in vivo.
We have noted a complex of common injuries in children wearing lap-styled safety belts during vehicular accidents. Sixty-one children who were restrained passengers in motor vehicle crashes had linear ecchymosis across the abdomen and had CT for abdominal trauma. Thirteen children (21%) had a lumbar spine injury, and 14 children (23%) injured a hollow viscus (bowel, 12; bladder, two); five children (8%) had both spine and hollow viscus injuries. Abnormal findings on abdominal CT were recognized retrospectively in three of 13 children with lumbar spinal injury. Lateral radiographs of the spine showed lumbar spinal injury in all cases. Free intraperitoneal air was noted in on three (25%) of 12 children with bowel injury. In eight of those children, CT showed large, unexplained collections of peritoneal fluid. The presence of lap-belt ecchymosis should prompt a careful search for spine, bowel, and bladder injury. Recognition of the limitations of CT diagnosis of these injuries is important to reduce errors in interpretation.
The clinical course of the papillary-cystic neoplasm of the pancreas is contrasted with that of the pancreatic ductal adenocarcinoma. The former occurs predominantly in young women, has a low malignant potential, and is highly curable with surgical treatment. Three cases are reported that illustrate the typical clinical features and the indolent nature of the tumor. One case was discovered after blunt abdominal trauma resulted in rupture of the tumor and hemoperitoneum. All cases were treated by pancreatic resection with preservation of the spleen, an important consideration in younger patients. All patients were free of disease at long-term follow-up. Increasing awareness of this tumor has resulted in the reclassification of several tumors and should lead to better recognition by surgeons caring for patients with pancreatic diseases.
Mortality in infants with congenital diaphragmatic hernia (CDH) remains high despite improvements in neonatal and surgical care because many infants develop persistent pulmonary hypertension of the newborn (PPHN) following repair. Since 1984, extracorporeal membrane oxygenation (ECMO) has been used as rescue therapy in all infants (n = 25) with PPHN following CDH repair when conventional management failed, with an overall survival of 60%. Repair was performed in this hospital on 12 infants and in other hospitals in 13 infants transferred for consideration of ECMO after repair. Mortality was the same in the group repaired here and those transferred for ECMO. Although complications were frequent in the surviving group, they were successfully managed with nonoperative or operative therapy. Selective use of ECMO has been advocated in CDH patients based on various predictors of high mortality such as "best" PO2 postrepair less than 100 mm Hg, oxygenation index greater than 40, and ventilation index greater than 1,000 with PCO2 greater than 40. Seven surviving infants following ECMO would have been classified as unsalvageable by at least one parameter if selection criteria based on these parameters had been used. We conclude from this series that current predictors of high mortality in CDH patients are unreliable when ECMO is used. Surgeons caring for infants with CDH should consider the use of ECMO in all infants.
This study was undertaken to assess the significance of thoracic trauma as a marker of morbidity and mortality in children. During a 34-month period, 2,086 children younger than 15 years old were consecutively admitted to a Level I pediatric trauma center with blunt or penetrating trauma. For each child we prospectively recorded Trauma Score (TS), Injury Severity Score, (ISS), medical, and etiologic data. One hundred four children (4.4%) presented with thoracic trauma. The most common mechanisms of injury were pedestrian injury (36%), motor vehicle crashes (32%), and armed assault (12%). The most common injuries were pulmonary contusion (48%), pneumothorax, hemothorax, or pneumohemothorax (39%), and rib fractures (32%). Multisystem injury was present in 82% of the children. The mean TS and ISS were 11 and 27, respectively, significantly worse than scores for children without thoracic injury (15 and 7; P less than .0001). Seventy-one percent of the children were admitted to the intensive care unit, where they stayed an average of 6 days; 20% required surgery. The mortality rate was 26%. Injuries to the heart or great vessels had the highest mortality rate (75%), followed by hemothorax (53%), lung laceration (43%), and rib fracture (42%). Mortality for children with isolated chest injury was 5%, compared with rates of 20% for abdominal and chest trauma, 35% for head and chest trauma, and 39% for trauma to the head, chest, and abdomen. Less than 5% of the admissions to a pediatric trauma center incurred thoracic injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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Trauma is the leading cause of death for children over 1 year of age. This study was undertaken to identify the patterns of injury among children admitted to a regional pediatric trauma center. During a 34-month period, 3,472 injured children were consecutively admitted to a regional pediatric trauma center. Data were collected on medical, etiological, and financial aspects of injury. Eight subgroups were defined by mechanism of injury: motor-vehicle crash occupants, pedestrian and cycle injuries, falls, child abuse, gunshot and stab wounds, burns, poisonings, and foreign body ingestions or aspirations. Analysis of variance, Duncan's multiple range test, and contingency table analysis were used to determine differences among subgroups of children. Blunt and penetrating trauma accounted for 64.3% of all admissions. The mean age of injured children was 5.5 years; 64% of the children were boys. Sixty-seven percent of the children were admitted directly from the scene of injury. One-way analysis of variance yielded significant differences in mean age, mean hospital length of stay (LOS), mean intensive care LOS, mean trauma score, mean injury severity, and mean hospital charges by mechanism of injury (P less than .01). The overall mortality rate was 2.4%. Child abuse, gunshot/stab wounds, and drowning had the highest mortality rates, but injuries to motor-vehicle crash occupants and pedestrians accounted for the greatest number of deaths.
To determine the effect of extracorporeal membrane oxygenation (ECMO) on the survival of infants with congenital diaphragmatic hernia, we undertook a retrospective review of 31 infants with congenital diaphragmatic hernia treated at Children's National Medical Center. Infants were categorized by means of the Bohn quadrant analysis to determine the impact of ECMO on infants with congenital diaphragmatic hernia and a "poor prognosis." All infants assigned to the Bohn 100% mortality quadrant required ECMO. The survival rate in this group was 86% (6/7) when assessed preoperatively and 67% (6/9) when assessed postoperatively. Comparison of the change occurring in ventilation index and arterial carbon dioxide pressure demonstrated that after repair the clinical condition of 48% of infants deteriorated, 40% improved, and 12% remained unchanged. Of the 12 infants whose condition was worse after surgery, 11 eventually required ECMO. Our review demonstrates that ECMO improved survival significantly in infants with congenital diaphragmatic hernia who had a "poor prognosis" by the criteria of Bohn et al. We recommend consideration of ECMO for all infants with congenital diaphragmatic hernia for whom maximal medical therapy has failed.
Polycystic liver disease (PLD) associated with autosomal dominant polycystic kidney disease is usually well tolerated. However there is a small subset of patients who become incapacitated by massive liver enlargement and for whom effective nonsurgical therapy is limited. Recent surgical advances in the treatment of PLD have raised uncertainties regarding proper management of these highly symptomatic patients. We have reviewed our recent experience with a combined hepatic resection-fenestration procedure to assess its efficacy in nine patients. All patients underwent resection of two or more liver segments and extensive fenestration of residual cysts in the remnant liver. Symptomatic relief and reduction in abdominal girth were obtained in eight surviving patients, persisting for an average follow-up period of 17 months. No progression of cystic disease has been observed clinically or by computed tomography and hepatic function was preserved. Three patients had no complications. Five patients had complications including transient right pleural effusion (3) and thrombosis of an arteriovenous fistula (2). One patient who had a previous hepatic cyst fenestration and a cadaveric renal transplantation died after operation of an intracerebral hemorrhage after experiencing coagulopathy, hyperbilirubinemia, and sepsis. Our results suggest (1) some highly symptomatic patients with massive PLD may benefit from combined hepatic resection and fenestration with acceptable risk, and (2) previous liver surgery and immunosuppressive therapy may increase the risk of such surgery. Longer follow-up is needed in a larger number of patients to determine the duration of benefit from the combined resection-fenestration procedure for highly symptomatic PLD.
The WHHL rabbit serves as an animal model for the human genetic disease, familial hypercholesterolemia. In initial studies aimed at the development of a genetic therapy for familial hypercholesterolemia (i.e., introduction of a normal LDL receptor gene), WHHL rabbit skin fibroblasts were transduced with a retroviral vector expressing a normal human LDL receptor. Correction of the WHHL rabbit genetic defect in vitro was confirmed. Autologous fibroblasts expressing LDL receptors were reimplanted in donor rabbits and were found to survive and express the recombinant receptor in vivo for up to 4 weeks. In vivo LDL receptor expression by autologous cells stably transduced with functioning LDL receptors is possible. Transduction of greater numbers of cells along with increased cell survival in vivo may eventually lead to a specific and effective genetic therapy for familial hypercholesterolemia.
The "seatbelt syndrome" describes intestinal and spinal injury caused by lap-style automotive restraints. More than 2,600 children were admitted to Children's National Medical Center with blunt injury in 3 years; 395 were involved in a motor vehicle crash. Ninety-five of the crash occupants (24%) were known to be wearing safety belts. Ten children sustained a "lap belt injury": five with lumbar spine injury, four with combined lumbar spine and intestinal injuries, and one child with intestinal injury. All ten children presented with a characteristic transverse abdominal ecchymosis. The CT scan was unreliable in evaluation of both spinal and intestinal injury. Lateral radiographs were required for definitive diagnosis in eight of nine children with lumbar spinal injury. CT scan was clearly diagnostic in only one of five children with intestinal injury. Children wearing lap belts are at risk of a "lap belt complex." Lateral spine X-rays, peritoneal lavage, and early laparotomy are recommended to establish an accurate diagnosis and to decrease morbidity.
This report describes a 4-month-old female infant with complex congenital heart disease and prolonged nasogastric intubation who developed an aberrant subclavian artery-esophageal fistula that was successfully managed in a two-staged procedure. To our knowledge, this is the first patient to survive correction of this problem after massive hemorrhage.
Four children, aged 5 to 13 years, were treated for malignant mesenchymoma of the liver. Two survived longer than 5 years with complete resection and adjuvant chemotherapy. Two children who had incomplete resection with microscopic residual mesenchymoma both had tumor recurrence and died of disease progression despite radiation therapy and chemotherapy. Although previous reports emphasize a poor prognosis for children with this tumor, our experience would indicate that long-term survival can be achieved using complete surgical extirpation and adjuvant chemotherapy.