Fits, faints, or fatal fantasy? Fabricated seizures and child abuse.
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Biomedical subjects
Publications and source records attributed to P M Davis.
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CD178 (CD95-ligand) is expressed on several tumor cells and likely influences the interaction of the tumor with the host immune system. However, little is known about the mechanisms that regulate its expression on the cell surface. We have evaluated the ability of various compounds and cytokines to regulate cell surface expression and release of soluble CD178 in various carcinoma cell lines. Vitamin E succinate (VES) and retinoic acid (RA) were found to reduce CD178 surface expression, whereas interferon-gamma stimulated a slight upregulation. At 48 h, the regulation of surface CD178 by VES and RA arose from a small decrease in CD178 mRNA and to a greater extent due to an increase in the release of soluble CD178; the latter was blocked by addition of a metalloproteinase inhibitor. Accordingly, VES and RA treatment diminished the ability of tumor cells to kill CD95-sensitive cells and this effect was markedly reduced by the presence of a metalloproteinase inhibitor. Our results indicate that, in vitro, CD178 expression on the cell surface of tumor cells can be regulated by agents that alter both expression and release of the ligand. In vivo, such treatments may play an important role in the outcome of tumor sensitivity or resistance to host immune mechanisms.
The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalyses the rate limiting step in cholesterol biosynthesis and is markedly inhibited by the statin family of drugs. The effect of statins on lipid lowering is clearly defined, but the ability of the drugs to directly regulate inflammatory functions has not been well explored. In this report, we show that there are differences among the statins in their capacity to induce proinflammatory responses both in human monocytes in vitro, and in leukocytes in mice in vivo. Treatment of human monocytes with lipophilic statins alone stimulated the production of MCP-1, IL-8, TNF-alpha and IL-1 beta and markedly sensitized the cells to subsequent challenge with inflammatory agents. Lipophilic statins also increased the production of reactive oxygen species in monocytes. In contrast, pretreatment of cells with the hydrophilic pravastatin did not induce these heightened inflammatory responses. Furthermore, treatment of mice with lipophilic statins caused a markedly higher influx of leukocytes into the inflamed peritoneal cavity following challenge with thioglycollate. Overall, these results demonstrate that the lipophilic statins influence a regulatory pathway in monocytes that controls cytokine production and that the statins induce different pro-inflammatory responses both in vitro and in vivo.
The Indian meal moth, Plodia interpunctella (Hübner), and Angoumois grain moth, Sitotroga cerealella (Olivier), are two globally distributed stored-grain pests. Laboratory experiments were conducted to examine the impact that corn (Zea mays L.) kernels (i.e., grain) of some Bacillus thuringiensis Berliner (Bt) corn hybrids containing CrylAb Bt delta-endotoxin have on life history attributes of Indian meal moth and Angoumois grain moth. Stored grain is at risk to damage from Indian meal moth and Angoumois grain moth; therefore, Bt corn may provide a means of protecting this commodity from damage. Thus, the objective of this research was to quantify the effects of transgenic corn seed containing CrylAb delta-endotoxin on Indian meal moth and Angoumois grain moth survival, fecundity, and duration of development. Experiments with Bt grain, non-Bt isolines, and non-Bt grain were conducted in environmental chambers at 27 +/- 1 degrees C and > or = 60% RH in continuous dark. Fifty eggs were placed in ventilated pint jars containing 170 g of cracked or whole corn for the Indian meal moth and Angoumois grain moth, respectively. Emergence and fecundity were observed for 5 wk. Emergence and fecundity of Indian meal moth and emergence of Angoumois grain moth were significantly lower for individuals reared on P33V08 and N6800Bt, MON 810 and Bt-11 transformed hybrids, respectively, than on their non-Bt transformed isolines. Longer developmental times were observed for Indian meal moth reared on P33V08 and N6800Bt than their non-Bt-transformed isolines. These results indicate that MON 810 and Bt-11 CrylAb delta-endotoxin-containing kernels reduce laboratory populations of Indian meal moth and Angoumois grain moth. Thus, storing Bt-transformed grain is a management tactic that warrants bin scale testing and may effectively reduce Indian meal moth and Angoumois grain moth populations in grain without application of synthetic chemicals or pesticides.
Dispersal of neonate European corn borers, Ostrinia nubilalis (Hübner), in seed mixtures of transgenic corn expressing Cry1Ab protein (Bt+) and nontransgenic corn (Bt-) was evaluated in a 2-yr field study. The main objective was to determine if larval dispersal limits the effectiveness of seed mixtures as a resistance management strategy. Mixtures evaluated included (1) all Bt+ plants, (2) every fifth plant Bt- with remaining plants Bt+, (3) every fifth plant Bt+ with remaining plants Bt-, and (4) all Bt- plants. The transformation events MON 802 (B73 BC1F2 x Mol7) and MON 810 (B73 BC1F1 x Mo17), which express the Cry1Ab endotoxin isolated from Bacillus thuringiensis subsp. kurstaki, were used as the sources of Bt+ seed in 1994 and 1995, respectively (YieldGard, Monsanto, St. Louis, MO). At corn growth stage V6-V8, subplots within each mixture (15-20 plants each) were infested so that every fifth plant in mixtures 1 and 4, every Bt- plant in mixture 2, and every Bt+ plant in mixture 3 received two egg masses. Larval sampling over a 21-d period indicated increased neonate dispersal off of Bt+ plants, reduced survival of larvae that dispersed from Bt+ plants to Bt- plants, and a low incidence of late-instar movement from Bt- plants to Bt+ plants. Computer simulations based on mortality and dispersal estimates from this study indicate that seed mixtures will delay the evolution of resistant European corn borer populations compared with uniform planting of transgenic corn. However, resistant European corn borer populations likely will develop faster in seed mixes compared with separate plantings of Bt and non-Bt corn.
BACKGROUND: Treatment of aortic graft infection with graft excision and axillofemoral bypass may carry an increased risk of limb loss, aortic stump blowout, and pelvic ischemia. A review of patients with aortic graft infection treated with in situ prosthetic graft replacement was undertaken to determine if mortality, limb loss, and reinfection rates were improved with this technique. METHODS: The clinical data of 25 patients, 19 males and 6 females, with a mean age of 68 years (range 35 to 83), with aortic graft infection, treated between January 1, 1989, and December 31, 1998, by in situ prosthetic graft replacement were reviewed. Follow-up was complete in the 23 surviving patients and averaged 36 months (range 4 to 103). RESULTS: Twenty aortofemoral, 3 aortoiliac, and 2 straight aortic graft infections were treated with excision and in situ replacement with standard polyester grafts in 16 patients (64%), or with rifampin-soaked collagen or gelatin-impregnated polyester grafts in 9 patients (36%). Fifteen patients (60%) had aortic graft enteric fistulas, 8 patients (32%) had abscesses or draining sinuses, and 2 patients (8%) had bacterial biofilm infections. Thirty-day mortality was 8% (2 of 25). There were no early graft occlusions or amputations. There was one late graft occlusion. There were no late amputations. The reinfection rate was 22% (5 grafts). All reinfections occurred in patients operated upon for occlusive disease. Only one reinfection occurred in the rifampin-soaked graft group (11% versus 29%, P = NS). Reinfection tended to be lower in patients with aortoenteric fistulas and without abscess. Autogenous tissue coverage provided statistically significant protection against reinfection. There were no late deaths related to in situ graft infection. CONCLUSIONS: Patients treated with in situ graft replacement had an 8% mortality and 100% limb salvage rate. Reinfection rates were similar to those of extra-anatomic bypass, but a trend of lower reinfection rates with rifampin-impregnated grafts was apparent. Patients with aortoenteric fistula and without abscess appear to be well treated by the technique of in situ prosthetic grafting and autogenous tissue coverage.
BACKGROUND: To determine optimal management of major abdominal arteriovenous fistulae and define factors affecting outcome. METHODS: We reviewed clinical data of 18 patients, 16 males and 2 females, who underwent repair of major abdominal arteriovenous fistulae between 1970 and 1997. RESULTS: Sixteen patients had primary fistula, caused by rupture of an atherosclerotic aortic or aortoiliac aneurysm into the inferior vena cava (IVC), iliac, or left renal vein. Two had secondary, iatrogenic arteriovenous fistulae. Seventeen patients (94%) were symptomatic, 11 (62%) had acute presentation. Fistula was diagnosed preoperatively in 8 (44%). Fistula closure (direct suture 16, patch 1, iliac vein ligation 1) was followed by aortoiliac reconstruction in all patients. Caval clip was placed in 3 patients. Early mortality was 6%; 7 patients had major complications. During follow-up (mean 6.1 years) 2 patients died of causes related to fistula closure. CONCLUSIONS: Rupture of aortoiliac aneurysms into the iliac veins or IVC carries a better prognosis than intraperitoneal, retroperitoneal, or enteric rupture. Although preoperative diagnosis is ideal, a high index of suspicion, careful repair avoiding pulmonary embolization, and blood salvage were all helpful in keeping morbidity and mortality low. Our data suggest that IVC interruption is seldom warranted.
This article reviews the legal aspects of head injuries resulting from a variety of athletic activities, focusing primarily on head and brain injuries resulting from the playing of football, boxing, horseback riding, winter sports (hockey and skiing), and soccer. Part 1 give a general overview of the occurrence of head injuries in athletics and the potential for litigation. Part 2 reviews the history of and increase in sports injury litigation, as well as resulting changes in the law. In Part 3, the current status of athletic head injury litigation, the parties involved, types of claims brought, and viable defenses are discussed. Finally, Part 4 reviews different ways to reduce athletic head injury litigation through better equipment design and adequate warning and instructions for users and coaches.
Approximately 10,000 Americans suffer catastrophic cervical spinal cord injuries each year. Most are caused by automobile accidents; however, many of these crippling injuries are related to participation in sports. This article evaluates the legal aspects of neck injury resulting from participation in a number of athletic events, including football, wrestling, gymnastics, snow skiing, ice hockey, diving, and surfing.
Hyperplastic polyps represent 75 to 90% of gastric polypoid lesions. The manifestations of these unique gastric neoplasms vary, including abdominal pain, nausea, and vomiting or gastrointestinal bleeding. The vast majority of these lesions are small, asymptomatic, and found incidentally on radiologic evaluation or endoscopic examination of the upper gastrointestinal tract. Herein we describe a large, benign, pedunculated hyperplastic polyp that led to progressive gastric outlet obstruction. In addition, we provide an overview of gastric polyps and a review of the literature. Excision of gastric polyps by endoscopic or surgical means is recommended as prudent treatment to eliminate occurrence of malignant foci.
The typical presentation of acute appendicitis is well known. A few patients, however, have had an atypical clinical course suggestive of recurrent appendiceal inflammation, which has been confirmed by appendectomy. Therefore, in the evaluation of a patient with abdominal pain, a history of similar episodes should not preclude a diagnosis of appendicitis.
Human monocytes express both Fas and Fas ligand (FasL) on the cell surface, and the interaction of these molecules induces spontaneous apoptosis. In this report we present a study of monocytic cells by FACS and confocal microscopy using anti-FasL Abs that reveals high levels of preformed FasL within the intracellular compartment. Further analysis by immunoblotting of cell cytoplasmic proteins confirmed the presence of a 37-kDa protein recognized by anti-FasL Abs. Stimulation of the monocytic cells with immune complexes, PHA, or superantigen gave rise to the rapid release of soluble FasL from within the cells. The presence of high levels of FasL within human monocytes suggests that, upon stimulation, the cells can rapidly translocate intracellular FasL to the cell surface and release it into the extracellular milieu. These findings indicate a novel mechanism for monocytes to respond rapidly to environmental changes, resulting in the release of active, soluble FasL.
Human monocytes undergo spontaneous apoptosis upon culture in vitro; removal of serum from the media dramatically increases the rate of this process. Monocyte apoptosis can be significantly abrogated by the addition of growth factors or proinflammatory mediators. We have evaluated the role of the endogenous Fas-Fas ligand (FasL) interaction in the induction of this spontaneous apoptosis and found that a Fas-immunoglobulin (Ig) fusion protein, an antagonistic anti-Fas monoclonal antibody and a rabbit anti-FasL antibody all greatly reduced the onset of apoptosis. The results indicate that spontaneous death of monocytes is mediated via an autocrine or paracrine pathway. Treatment of the cells with growth factors or cytokines that prevented spontaneous apoptosis had no major effects on the expression of Fas or FasL. Additionally, monocyte-derived macrophages were found to express both Fas and FasL but did not undergo spontaneous apoptosis and were not sensitive to stimulation by an agonistic anti-Fas IgM. These results indicate that protective mechanisms in these cells exist at a site downstream of the receptor-ligand interaction.
OBJECTIVES: This study was undertaken to determine (1) the prevalence of gastrointestinal symptoms including abdominal pain in a community-based population of adolescents, (2) whether a subgroup of these subjects have symptoms resembling Irritable bowel syndrome (IBS), and (3) whether anxiety and depression are more commonly found in adolescents with IBS-type symptoms compared with unaffected adolescents. METHODS: We collected data by administration of a gastrointestinal symptoms questionnaire, State-Trait Anxiety Inventory, and Children's Depression Inventory to middle school and high school students. RESULTS: A total of 507 subjects participated (mean age of middle school students 12.6 years; mean age of high school students 15.6 years). Abdominal pain was noted by 75% of all students. The pain occurred weekly in 13% to 17% of the subjects and was severe enough to affect activities in approximately 21%. Irritable bowel syndrome-type symptoms were noted by 17% of high school students and 8% of middle school students (p <0.01) who reported abdominal pain (n = 381), representing 14% and 6% of all high school and middle school students (p <0.005), respectively. Anxiety and depression scores were significantly higher for students with IBS-type symptoms compared with those without symptoms. Eight percent of all students had seen a physician for abdominal pain in the previous year. These visits were correlated with abdominal pain severity, frequency, duration, and disruption of normal activities but not with anxiety, depression, gender, family structure, or ethnicity. CONCLUSION: Recurrent abdominal pain and symptoms of IBS are commonly noted in a community-based adolescent population and frequently result in use of health care resources. Health care providers who work with this age group need to be able to recognize the symptom complex associated with IBS, as well as the possible relationship to anxiety and depression.
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A two year prospective study was performed to determine the epidemiology of Munchausen syndrome by proxy, non-accidental poisoning, and non-accidental suffocation in the UK and the Republic of Ireland. Cases were notified to the British Paediatric Association Surveillance Unit from September 1992 to August 1994 if a formal case conference had been held for the first time during that period to discuss any of the above conditions. A total of 128 cases were identified: 55 suffered Munchausen syndrome by proxy alone, 15 poisoning, and 15 suffocation; 43 suffered more than one type of abuse. The majority of children were aged under 5 years, the median age being 20 months. On 85% of occasions the perpetrator was the child's mother. In 42% of families with more than one child, a sibling had previously suffered some form of abuse. Eighty five per cent of notifying paediatricians considered the probability of their diagnosis as virtually certain before a case conference was convened. The commonest drugs used to poison were anticonvulsants; opiates were the second commonest. Sixty eight children suffered severe illness of whom eight died. The combined annual incidence of these conditions in children aged under 16 years is at least 0.5/100,000, and for children aged under 1, at least 2.8/100,000.
OBJECTIVE: To investigate the reasons for poor uptake of immunisation (non-immunisation) and the possible side effects of measles, mumps, and rubella vaccine in a catch up immunisation campaign during a community outbreak of measles. DESIGN: Descriptive study of reasons for non-immunisation and retrospective cohort study of side effects of the vaccine. SETTING: Secondary schools in South Glamorgan. SUBJECTS: Random cluster sample of the parents of 500 children targeted but not immunised and a randomised sample of 2866 of the children targeted. MAIN OUTCOME MEASURES: Reasons for non-immunisation; symptoms among immunised and non-immunised children. RESULTS: Immunisation coverage of the campaign was only 43.4% (7633/17,595). The practical problems experienced included non-return of consent forms (6698/17,595), refusal of immunisation (2061/10,897 forms returned), and absence from school on day of immunisation (1203/8836 children with consent for immunisation). The most common reasons cited for non-immunisation were previous measles infection (145/232), previous immunisation against measles (78/232), and concern about side effects (55/232). Symptoms were equally common among immunised and non-immunised subjects. However, significantly more immunised boys than non-immunised boys reported fever (relative risk 2.31 (95% confidence interval 1.36 to 3.93)), rash (2.00 (1.10 to 3.64), joint symptoms (1.58; 1.05 to 2.38), and headache (1.31 (1.04 to 1.65)). CONCLUSIONS: Many of the objections raised by parents could be overcome by emphasising that primary immunisation does not necessarily confer immunity and that diagnosis of measles is unreliable. Measles, mumps, and rubella vaccine is safe in children aged 11-15.
PURPOSE: Emergency surgery for fulminant colitis is often complicated by high-dose steroid therapy, poor nutrition, and psychologic maladjustment. Cyclosporine is effective for fulminant ulcerative colitis in adults, resulting in avoidance of immediate surgery in 75 percent of patients and a 55 percent long-term remission rate. Over the last five years, we studied the effectiveness of cyclosporine in children with fulminant colitis. METHODS: Fourteen patients with ulcerative colitis (age, 7-20 years) received cyclosporine after satisfying the following criteria: 1) greater than five bloody diarrheal stools per day; 2) severe abdominal pain; 3) no improvement after ten days of bowel rest, 4) intravenous methylprednisolone (1-2 mg/kg/day); and 5) parenteral nutrition. Treatment was begun with oral cyclosporine (4.6-9.6 mg/kg/day), and the dose was adjusted to achieve whole blood trough levels measured with a monoclonal radioimmunoassay between 150 and 300 ng/ml. If improved, patients were discharged on oral cyclosporine, prednisone, and a regular diet. RESULTS: Eleven of 14 patients (78 percent) responded within two to nine days and were able to consume a normal diet, had three or less soft stools per day, and had no pain. One did not respond after ten days and underwent an ileal pouch-anal anastomosis procedure. Two patients elected surgery after 20 days of therapy and a partial response. Of 11 patients who left the hospital, 4 had recurrent symptoms after 2 to 11 months of taking therapeutic doses of cyclosporine and 3 flare ups while weaning from cyclosporine after 4 to 8 months. Three patients have been weaned from cyclosporine after 8 to 13 months and have remained in remission from six months to five years. One patient is about to complete a six-month course of cyclosporine. Overall ten (72 percent) have undergone surgery, including 7 of 11 who responded initially to cyclosporine and left the hospital. Weight (P < 0.001), albumin (P < 0.01), erythrocyte sedimentation rate (P > 0.05), and prednisone dose (P < 0.001) improved significantly in the seven patients on cyclosporine who responded initially, left the hospital, and subsequently underwent surgery. CONCLUSIONS: Cyclosporine is effective in achieving clinical remission in 80 percent of children with refractory fulminant colitis; however, within one year, most initial responders will require colectomy because of a flare up of the disease. In a majority of patients, the role of cyclosporine therapy is to rapidly ameliorate symptoms and prevent precipitous colectomy, improve nutrition and psychologic adaptation, and reduce the steroid dose leading to surgery in a well-prepared patient.