Retinitis sclopeteria associated with airbag inflation.
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Accidents, Traffic↗
Biomedical subjects
P M Sullivan
Publications and source records attributed to P M Sullivan.
Apo E structure determines VLDL clearance and atherosclerosis risk in mice.
We have generated mice expressing the human apo E4 isoform in place of the endogenous murine apo E protein and have compared them with mice expressing the human apo E3 isoform. Plasma lipid and apolipoprotein levels in the mice expressing only the apo E4 isoform (4/4) did not differ significantly from those in mice with the apo E3 isoform (3/3) on chow and were equally elevated in response to increased lipid and cholesterol in their diet. However, on all diets tested, the 4/4 mice had approximately twice the amount of cholesterol, apo E, and apo B-48 in their VLDL as did 3/3 mice. The 4/4 VLDL competed with human LDL for binding to the human LDL receptor slightly better than 3/3 VLDL, but the VLDL clearance rate in 4/4 mice was half that in 3/3 mice. On an atherogenic diet, there was a trend toward greater atherosclerotic plaque size in 4/4 mice compared with 3/3 mice. These data, together with our earlier observations in wild-type and human APOE*2-replacement mice, demonstrate a direct and highly significant correlation between VLDL clearance rate and mean atherosclerotic plaque size. Therefore, differences solely in apo E protein structure are sufficient to cause alterations in VLDL residence time and atherosclerosis risk in mice.
Animals↗
Unicompartmental knee replacement. A minimum 15 year followup study.
One hundred forty Marmor cemented unicompartmental knee replacements were inserted in 103 patients between 1975 and 1982. Fifty-two patients were women and 51 were men. One hundred twenty-five were medial compartment knee replacements and 15 were lateral knee replacements. At minimum 15 year followup 34 patients with 48 knee replacements were living; only four patients with four knee replacements were lost to followup. Average preoperative and final followup Hospital for Special Surgery knee scores were 57 and 82 points, respectively for the knees of living patients. Average preoperative and final followup Knee Society clinical and Knee Society functional scores were 31 and 42, and 85 and 71 points, respectively. For all knees, 10.2% (14 knees) were revised [4.4% (six knees) for tibial loosening, 5.1% (seven knees) for disease progression, and .7% (one knee) for pain]. For patients living 15 years, 12.5% (six knees) were revised [2.1% (one knee) for tibial loosening, and 10.4% (five knees) for disease progression]. Revision for failure of fixation of these unicompartmental replacements was comparable with that reported for fixed bearing total knee replacement. Disease progression (46%; 62 of 136 knees) and tibial subsidence with wear (10.4%; 15 of 136 knees, five of which required revision) were the major long term problems in this group of patients.
Activities of Daily Living↗
Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse Apoe with human Apoe*2.
To study isoform-specific effects of apolipoprotein E (apoE) in vivo, we generated mice with a human APOE*2 allele in place of the mouse Apoe gene via targeted gene replacement in embryonic stem cells. Mice expressing human apoE2 (2/2) have virtually all the characteristics of type III hyperlipoproteinemia. Their plasma cholesterol and triglyceride levels are both twice to three times those in (normolipidemic) mice that are expressing human apoE3 (3/3) made in an identical manner. The 2/2 mice are markedly defective in clearing beta-migrating VLDL particles, and spontaneously develop atherosclerotic plaques, even on a regular diet. An atherogenic diet, high in fat and cholesterol, exacerbates development of atherosclerosis and xanthomas in the 2/2 mice. Thus, comparisons between the 2/2 and 3/3 mice unequivocally demonstrate that a single amino acid difference (Arg158 Cys) in the apoE protein is sufficient to cause type III HLP and spontaneous atherosclerosis in mice.
Animals↗
The association between child maltreatment and disabilities in a hospital-based epidemiological study.
OBJECTIVE: Circumstances of maltreatment and the presence of disabilities. METHOD: An electronic merger of the records of all pediatric patients. RESULTS: Detailed record analysis of circumstances of maltreatment and the presence of disabilities. CONCLUSIONS: Differences between the Hospital and Residential samples, maltreatment and perpetrator characteristics, disability/maltreatment relationships, and their implications for primary health care are discussed.
Adolescent↗
Vitreoretinal surgery after inadvertent globe penetration during local ocular anesthesia.
OBJECTIVE: This study aimed to review visual morbidity resulting from inadvertent globe penetration during administration of local anesthetic and to identify the most appropriate management. DESIGN: The records of 20 consecutive patients referred to a specialist vitreoretinal unit over a 2-year period were reviewed. PARTICIPANTS: Twenty eyes of 20 consecutive patients were included. INTERVENTION: Observations included type of local anesthetic administered (e.g., retrobulbar or peribulbar), level of training of person administering the block, type of needle used for the block, and findings at presentation to the vitreoretinal unit. The authors also observed results of B-scan ultrasound evaluation of the retina, interval between the recognition of the complication and referral, as well as nature and timing of subsequent surgical intervention. MAIN OUTCOME MEASURES: Final visual acuity and retinal status (attached versus detached) were measured. RESULTS: The most common presentation was vitreous hemorrhage observed from the first postoperative day. Ten eyes were found to have an associated retinal detachment on initial assessment in the vitreoretinal unit. These eyes generally had a poor visual outcome despite vitrectomy with long-acting gas or silicone oil tamponade. Seven (70%) of the remaining eyes with attached retina at the time of presentation achieved good visual recovery after vitrectomy. CONCLUSIONS: The authors recommend prompt referral for consideration of early vitrectomy in eyes with dense vitreous hemorrhage after inadvertent globe penetration. This management may improve the overall visual prognosis by preventing subsequent retinal detachment.
Aged↗
The management of dislocated lens material after phacoemulsification.
PURPOSE: To determine the visual outcome, prognostic factors, and effect of timing of surgical intervention in patients with retained lens fragments after phacoemulsification. METHODS: A retrospective review was carried out of the notes of 44 consecutive patients who suffered posterior dislocation of lens fragments during phacoemulsification, of whom 34 underwent vitrectomy. RESULTS: The presence of severe uveitis at presentation was a significant predictor of a final visual acuity of less than 6/60 (p = 0.002). A raised intraocular pressure at presentation (> 29 mmHg) significantly increased the risk of chronic glaucoma (p = 0.0279), but there was no association between glaucoma and delay in vitrectomy. Patients operated on within 1 week of cataract surgery obtained a better visual outcome (64.7%) of patients achieved 6/12 or better visual acuity) than those operated on later than 1 week (41% obtained 6/12), but this difference did not reach statistical significance. CONCLUSIONS: The trend towards a better visual outcome with early vitrectomy was not statistically significant. A large prospective trial is indicated to determine the optimum time for vitrectomy in these patients.
Adult↗
Direct ophthalmoscopy versus slit lamp biomicroscopy in diagnosis of the acute red eye.
The causes of red eye range from trivial to life-threatening, and many general practitioners are uncertain of their ability to diagnose them with the aid of an ophthalmoscope. We tested the hypothesis that, in the assessment of a patient with red eye, a doctor using a slit lamp biomicroscope would not differ in diagnostic accuracy from a doctor using a direct ophthalmoscope. A cross-over study was conducted in 98 patients newly attending an eye casualty department. 71% of diagnoses agreed exactly, and all potentially sight-threatening lesions were either diagnosed correctly or managed appropriately by doctors using an ophthalmoscope. We conclude that the initial diagnosis and management of patients with an acute red eye is not prejudiced by the lack of a slit lamp biomicroscope.
Acute Disease↗
A comparison of sustained-release bupropion and placebo for smoking cessation.
BACKGROUND AND METHODS: Trials of antidepressant medications for smoking cessation have had mixed results. We conducted a double-blind, placebo-controlled trial of a sustained-release form of bupropion for smoking cessation. We excluded smokers with current depression, but not those with a history of major depression. The 615 subjects were randomly assigned to receive placebo or bupropion at a dose of 100, 150, or 300 mg per day for seven weeks. The target quitting date (or "target quit date") was one week after the beginning of treatment. Brief counseling was provided at base line, weekly during treatment, and at 8, 12, 26, and 52 weeks. Self-reported abstinence was confirmed by a carbon monoxide concentration in expired air of 10 ppm or less. RESULTS: At the end of seven weeks of treatment, the rates of smoking cessation as confirmed by carbon monoxide measurements were 19.0 percent in the placebo group, 28.8 percent in the 100-mg group, 38.6 percent in the 150-mg group, and 44.2 percent in the 300-mg group (P<0.001). At one year the respective rates were 12.4 percent, 19.6 percent, 22.9 percent, and 23.1 percent. The rates for the 150-mg group (P=0.02) and the 300-mg group (P=0.01) -- but not the 100-mg group (P=0.09) -- were significantly better than those for the placebo group. Among the subjects who were continuously abstinent through the end of treatment, the mean absolute weight gain was inversely associated with the dose (a gain of 2.9 kg in the placebo group, 2.3 kg in 100-mg and 150-mg groups, and 1.5 kg in the 300-mg group; P= 0.02). No effects of treatment were observed on depression scores as measured serially by the Beck Depression Inventory. Thirty-seven subjects stopped treatment prematurely because of adverse events; the frequency was similar among all groups. CONCLUSIONS: A sustained-release form of bupropion was effective for smoking cessation and was accompanied by reduced weight gain and minimal side effects. Many participants in all groups were smoking at one year.
Adult↗
Targeted replacement of the mouse apolipoprotein E gene with the common human APOE3 allele enhances diet-induced hypercholesterolemia and atherosclerosis.
Apolipoprotein (apo) E, a constituent of several lipoproteins, is a ligand for the low density lipoprotein receptor, and this interaction is important for maintaining cholesterol and triglyceride homeostasis. We have used a gene replacement strategy to generate mice that express the human apoE3 isoform in place of the mouse protein. The levels of apoE mRNA in various tissues are virtually the same in the human apoE3 homozygous (3/3) mice and their littermates having the wild type mouse allele (+/+). Total cholesterol and triglyceride levels in fasted plasma from the 3/3 mice were not different from those in the +/+ mice, when maintained on a normal (low fat) chow diet. We found, however, notable differences in the distribution of plasma lipoproteins and apolipoprotein E between the two groups: beta-migrating lipoproteins and plasma apoB100 levels are decreased in the 3/3 mice, and the apoE distribution is shifted from high density lipoproteins to larger lipoprotein particles. In addition, the fractional catabolic rate of exogenously administered remnant particles without apoE was 6-fold slower in the 3/3 mice compared with the +/+ mice. When the 3/3 and +/+ animals were fed a high fat/high cholesterol diet, the 3/3 animals responded with a dramatic increase (5-fold) in total cholesterol compared with the +/+ mice (1.5-fold), and after 12 weeks on this same diet the 3/3 animals developed significantly (at least 13-fold) larger atherosclerotic plaques in the aortic sinus area than the +/+ animals. Thus the structural differences between human APOE3 and mouse ApoE proteins are sufficient to cause an increased susceptibility to dietary-induced hypercholesterolemia and atherosclerosis in the 3/3 mice.
Alleles↗
Inhibition of inducible nitric oxide synthase ameliorates functional and histological changes of acute lung allograft rejection.
BACKGROUND: We recently demonstrated that inhibition of inducible nitric oxide synthase (iNOS) ameliorated severe acute lung allograft rejection. This study used a rat lung transplant model to determine (1) the time course and cellular localization of iNOS expression during the histological progression of unmodified acute rejection and (2) whether inhibition of iNOS prevented impaired gas exchange function of the allograft lung and/or ameliorated the histological changes of acute rejection. METHODS AND RESULTS: iNOS mRNA and enzyme activity were expressed in allograft lungs during mild, moderate, and severe acute rejection, but not in normal, isograft, or allograft lungs before histological changes of mild acute rejection. iNOS expression in allografts resulted in elevated serum nitrite/nitrate levels, indicative of increased in vivo nitric oxide (NO) production. In situ hybridization demonstrated iNOS mRNA expression in infiltrating inflammatory cells, but not in allograft parenchymal cells. Allografts had significantly impaired gas exchange, which was prevented with the selective iNOS inhibitor aminoguanidine (PaO2 of 566+/-19, 76+/-22, and 504+/-105 mmHg for isograft, allograft, and aminoguanidine-treated allograft, respectively; P<0.0002). Aminoguanidine also significantly improved the histological rejection scores. CONCLUSIONS: (1) iNOS expression and increased NO production occurred during the early stages of acute rejection, persisted throughout the unmodified rejection process, and localized to infiltrating inflammatory cells, but not allograft parenchymal cells; (2) aminoguanidine ameliorated the histological and functional changes of acute rejection; and (3) increased NO production, detected by the presence of iNOS mRNA, protein, or noninvasively by measuring serum nitrite/nitrate levels, may serve as an early marker of acute allograft rejection.
Acute Disease↗
Results of primary retinal reattachment surgery: a prospective audit.
PURPOSE: To define the current success rate of primary retinal detachment repair at one centre. METHODS: One hundred and fifty-three consecutive patients undergoing surgery for primary retinal detachments over a 6 month period were studied prospectively. Data sheets were completed immediately after surgery and at final follow-up. One hundred and twenty-seven patients completed 6 months of follow-up. Follow-up data on the remainder were obtained from the referring unit or directly from the patients by telephone. The term primary success was used to describe persisting retinal reattachment after a single operation. Multiple logistic regression was carried out to establish factors associated with failure. RESULTS: One hundred and twenty-three patients (80%) had persisting retinal reattachment after a single procedure. Of the 30 patients who required further surgery, in 5 the retina remained detached at final follow-up. The final anatomical success rate was 97%. New or missed breaks were the major causes of failure of primary surgery. Failure of primary surgery was associated with the presence of highly elevated breaks (beta = 0.11, p = 0.03). No other pre-operative factors appeared to predict failure to reattach the retina. CONCLUSIONS: Comparison of these results with those of a previous audit carried out at this hospital 23 years ago suggests little improvement in the success rate of primary surgery (75% vs 80%). The improvement in final retinal reattachment has been rather greater (from 88% to 97%). The major impact of recent technical advances in retinal reattachment surgery has been on the success rate of reoperations after failed primary surgery.
Adolescent↗
Overexpression of androgen-binding protein/sex hormone-binding globulin in male transgenic mice: tissue distribution and phenotypic disorders.
The rat androgen-binding protein/sex hormone-binding globulin (ABP/SHBG) gene in transgenic mice was previously shown to be specifically expressed in the testes. This study verifies a Sertoli cell location of ABP and translation of testicular ABP mRNA in the transgenic mice by dihydrotestosterone (DHT)-binding assays and immunohistochemistry. DHT-binding activities in the testis and epididymis of the hemizygous transgenic mice were elevated 20-fold as compared to activity in the wild-type tissues. DHT-binding activities were also elevated in blood plasma at least 25- to 50-fold in the transgenic mice; binding was undetectable in the plasma from control mice. Immunohistochemical analysis revealed that the transgenic testicular ABP was primarily in the cytoplasm of Sertoli cells and lumen of the seminiferous tubules. In some tubules, intense staining also was associated with spermatids. After transport to the epididymis, there were large amounts of immunoreactive ABP internalized in the epithelium of the initial segment and proximal caput. The increased levels of plasma and testicular ABP had no effect on levels of testosterone; there was a 30-fold range of plasma and testicular testosterone levels in the wild-type and transgenic mice. Increased ABP levels in the transgenic mice were associated with structural and functional abnormalities in the testis. Abnormal spermatogenesis resulted in extensive structural changes in the transgenic testis; the degree of the defect varied from near normality to the loss of most germ cells. In the affected mice, seminiferous tubules had smaller diameters and decreased numbers of germ cells, particularly in the spermatid stages of differentiation. Pyknotic nuclei and multinucleated cells were associated with the spermatids in the defective tubules, but not in the wild-type tubules. Consequently, mice with the spermatogenic disorder had reduced epididymal sperm numbers. The variable spermatogenic disorder was associated with variable male fertility. The homozygous transgenic male and female mice also had a serious motor dysfunction affecting their hind limbs. This study demonstrates how the transgenic mouse model can be used to study ABP's function, and the data support several hypotheses on its function in the testis and epididymis.
Androgen-Binding Protein↗
Psychological characteristics of child cochlear implant candidates and children with hearing impairments.
OBJECTIVE: To describe the psychological status of deaf children with hearing parents who were seeking a cochlear implant and to compare them with deaf children with hearing parents who were not seeking a cochlear implant. DESIGN: A sample of children consecutively referred for a cochlear implant at the University of Iowa Hospitals and Clinics was contrasted on a number of standardized psychological measures with a cohort of children from Boys Town National Research Hospital, who had hearing impairments and whose families had not sought a cochlear implant. RESULTS: Although the comparison group evidenced more externalizing and social problems than the implant group, the means of both groups fell well within the normal range. Similarly, although mothers of the implant group rated their child's home as characterized by more positive and supportive interactions than did mothers of the children in the comparison group, both group means were well within the average range. On measures of intelligence, the two groups also did not differ. CONCLUSION: Overall, the study indicated that children with hearing impairments and their families who were seeking cochlear implants are not significantly different from children with hearing impairments whose parents were not seeking a cochlear implant. The results provided no support for the notion that children with hearing impairments from families seeking a cochlear implants for their child evidence more behavioral deviance than children with hearing impairments whose parents have not sought an implant.
Adolescent↗
Inflammatory cell-derived NO modulates cardiac allograft contractile and electrophysiological function.
We previously demonstrated that inhibition of inducible nitric oxide (NO) synthase (iNOS) ameliorated acute cardiac allograft rejection. This study used a rat cardiac transplant model to characterize contractile and electrophysiological dysfunction during early acute rejection, further examine the role of NO and iNOS in this process, and determine which cells expressed iNOS during early rejection. During early acute rejection, before significant myocyte necrosis, allograft papillary muscles had reduced tension development and rates of tension development and decline during beta-adrenergic, adenylate cyclase, and calcium stimulation compared with isograft and normals [e.g., tension of 36 (allograft) vs. 73 (isograft) mN/mm2 during calcium stimulation, P < 0.001]. Allografts had resting membrane potential depolarization and reduced action potential amplitude and upstroke velocity. iNOS mRNA was expressed in infiltrating inflammatory cells but not in allograft myocytes, endothelial cells, or isografts. Corticosteroids attenuated allograft contractile and electrophysiological dysfunction and inhibited iNOS enzyme activity. Direct iNOS inhibition with aminoguanidine inhibited NO production and prevented allograft contractile and electrophysiological dysfunction (e.g., tension of 64 mN/mm2 during calcium stimulation, P < 0.001). We conclude that 1) early allograft rejection caused contractile and electrophysiological dysfunction that was largely mediated by iNOS expression in infiltrating inflammatory cells, 2) corticosteroid-mediated amelioration of allograft contractile and electrophysiological dysfunction may reflect inhibition of iNOS, and 3) iNOS inhibition may offer an alternative in management of immune-mediated myocardial dysfunction.
Action Potentials↗
TNF-alpha causes reversible in vivo systemic vascular barrier dysfunction via NO-dependent and -independent mechanisms.
Tumor necrosis factor (TNF-alpha) and nitric oxide (NO) are important vasoactive mediators of septic shock. This study used a well-characterized quantitative permeation method to examine the effect of TNF-alpha and NO on systemic vascular barrier function in vivo, without confounding endotoxemia, hypotension, or organ damage. Our results showed 1) TNF-alpha reversibly increased albumin permeation in the systemic vasculature (e.g., lung, liver, brain, etc.); 2) TNF-alpha did not affect hemodynamics or blood flow or cause significant tissue injury; 3) pulmonary vascular barrier dysfunction was associated with increased lung water content and impaired oxygenation; 4) TNF-alpha caused inducible nitric oxide synthase (iNOS) mRNA expression in the lung and increased in vivo NO production; 5) selective inhibition of iNOS with aminoguanidine prevented TNF-alpha-induced lung and liver vascular barrier dysfunction; 6) aminoguanidine prevented increased tissue water content in TNF-alpha-treated lungs and improved oxygenation; and 7) nonselective inhibition of NOS with NG-monomethly-L-arginine increased vascular permeation in control lungs and caused severe lung injury in TNF-alpha-treated animals. We conclude that 1) TNF-alpha reversibly impairs vascular barrier integrity through NO-dependent and -independent mechanisms; 2) nonselective NOS inhibition increased vascular barrier dysfunction and caused severe lung injury, whereas selective inhibition of iNOS prevented impaired endothelial barrier integrity and pulmonary dysfunction; and 3) selective inhibition of iNOS may be beneficial in treating increased vascular permeability that complicates endotoxemia and cytokine immunotherapy.
Animals↗
Long-term results of revision total hip arthroplasty with improved cementing technique.
We performed 83 consecutive cemented revision total hip arthroplasties in 77 patients between 1977 and 1983 using improved cementing techniques. One patient (two hips) was lost to follow-up. The remaining 76 patients (81 hips) had an average age at revision of 63.7 years (23 to 89). At the final follow-up 18 hips (22%) had had a reoperation, two (2.5%) for sepsis, three (4%) for dislocation and 13 (16%) for aseptic loosening. The incidence of rerevision for aseptic femoral loosening was 5.4% and for aseptic acetabular loosening 16%. These results confirm that cemented femoral revision is a durable option in revision hip surgery when improved cementing techniques are used, but that cemented acetabular revision is unsatisfactory.
Acetabulum↗
Inducible nitric oxide synthase is expressed during experimental acute lung allograft rejection.
BACKGROUND: We recently demonstrated that inhibition of nitric oxide (NO) production ameliorated acute pulmonary allograft rejection. This study examined whether inducible NO synthase (iNOS) was expressed in the transplanted lung during acute rejection. METHODS: With a rat left lung transplant model, tissue from syngeneic (Fischer 344 to Fischer 344) and allogeneic (Brown Norway to Fischer 344) transplants were harvested on postoperative day 4 and analyzed for iNOS mRNA expression (ribonuclease protection assay), iNOS enzyme activity (conversion of L-[3H]-arginine to NO and L-[3H]-citrulline), and serum nitrite/nitrate levels. RESULTS: The iNOS mRNA was expressed in allograft lungs but was not detected in isografts or controls. The iNOS protein was present in allograft lungs, as demonstrated by high levels of L-[3H]-citrulline production compared with minimal iNOS enzyme activity in isograft and control lungs (10.1 +/- 2.4 vs 0.6 +/- 0.2 and 0.7 +/- 0.2 pmol L-[3H]-citrulline.mg-1.min-1, respectively; n = 6, p < 0.001). Allografts had significantly elevated systemic serum nitrite/nitrate levels compared with isografts and controls (38 +/- 6 vs 18 +/- 2 and 16 +/- 1 mumol/L, respectively; n = 6; p < 0.005). CONCLUSIONS: These results, together with our previous demonstration that iNOS inhibition ameliorated lung allograft rejection, suggest that (1) iNOS expression and increased NO production contributed to acute rejection of the transplanted lung, (2) iNOS inhibition may offer an alternative in management of acute lung allograft rejection, and (3) increased NO production, detected by the presence of iNOS mRNA or protein or noninvasively by measuring serum nitrite/nitrate levels, may serve as an early marker of acute allograft rejection.
Animals↗