Cerebral lipid deposition in aged apolipoprotein-E-deficient mice.

To assess the influence of age and diet on cerebral pathology in mice lacking apolipoprotein E (apoE), four male apoE knockout mice (epsilon -/-), and five male wild-type (epsilon +/+) littermate controls were placed on a high-fat/high-cholesterol diet for 7 weeks beginning at 17 months of age. All four aged knockout mice developed xanthomatous lesions in the brain consisting mostly of crystalline cholesterol clefts, lipid globules, and foam cells. Smaller xanthomas were confined mainly to the choroid plexus and ventral fornix in the roof of the third ventricle, occasionally extending subpially along the choroidal fissure and into the adjacent parenchyma. More advanced xanthomas disrupted adjoining neural tissue in the fornix, hippocampus, and dorsal diencephalon; in one case, over 60% of one telencephalic hemisphere, including nearly the entire neocortex, was obliterated by the lesion. No xanthomas were observed in aged wild-type controls fed the high-fat/high-cholesterol diet. Brains from 42 additional animals, fed only conventional chow, were examined; 3 of 15 aged (15- to 23-month-old) apoE knockout mice developed small choroidal xanthomas. In contrast, no lesions were observed in five young (2- to 4-month-old) apoE knockout mice or in any wild-type controls between the ages of 2 and 23 months. Our findings indicate that disorders of lipid metabolism can induce significant pathological changes in the central nervous system of aged apoE knockout mice, particularly those on a high-fat/high-cholesterol diet. It may be fruitful to seek potential interactions between genetic factors and diet in modulating the risk of Alzheimer's disease and other neurodegenerative disorders in aged humans.     

Evaluating the Effectiveness of Premarital Prevention Programs: A Meta‐Analytic Review of Outcome Research

We present a comprehensive, meta‐analytic review and critical evaluation of outcome research pertaining to the effectiveness of premarital prevention programs. Results revealed that the mean effect size for premarital programs was .80, which means that the average person who participated in a premarital prevention program was significantly better off afterwards than 79% of people who did not participate. Stated differently, the average participant in a premarital program tends to experience about a 30% increase in measures of outcome success. Our findings suggest that premarital prevention programs are generally effective in producing immediate and short‐term gains in interpersonal skills and overall relationship quality and that these improvements are significantly better than nonintervention couples in these areas. However, because of a lack of extended follow‐up research, conclusions about long‐term effectiveness remain elusive. We propose implications for future research, education, and policy.     

Technetium-99m methoxy isobutyl isonitrile (MIBI) imaging of the parathyroid glands in patients with renal failure

Background. Technetium-99m methoxy isobutyl isonitrile (Tc-99m MIBI) scintigraphy has been reported to be at least as reliable as thallium-technetium subtraction imaging in the preoperative localization of hyperplastic parathyroid glands in patients with renal failure. Reports have suggested that 50% of glands can be identified correctly by this method. The aim of this study was to improve on previous results and demonstrate that Tc-99m MIBI imaging has an important place in the preoperative work-up of these patients. Methods. Eighteen patients on renal replacement therapy were studied. All had tertiary hyperparathyroidism and had Tc-99m MIBI imaging prior to parathyroidectomy. A refined reporting method was employed. The imaging results were compared to the subsequent surgical and histological findings. Results. In the 12 patients in whom serum parathyroid hormone levels fell postoperatively to within or below the normal range, 38 of 46 glands (82.6%) were correctly identified and located in the correct quadrant of the thyroid gland. There were two false positive results where the imaging predicted glands not subsequently found by the surgeon. In the patients who had post-operative hyperparathyroidism, repeat Tc-99m MIBI imaging was able to locate accurately the site of the residual parathyroid tissue. Conclusion. Tc-99m MIBI imaging is able to identify more than 80% of hyperplastic parathyroid glands in renal failure patients if this reporting process is used, and locate them in the correct quadrant of the thyroid gland. Tc-99m MIBI imaging is of particular value when re-exploration of the neck is required for post-parathyroidectomy hyperparathyroidism. These results represent a significant improvement on the sensitivity of this imaging technique when compared to previous published data.     

Risk factors for spinal surgical-site infections in a community hospital: a case-control study.

OBJECTIVE: To characterize risk factors for surgical-site infection after spinal surgery. DESIGN: A case-control study. SETTING: A 113-bed community hospital. METHOD: From January 1998 through June 2000, the incidence of surgical-site infection in patients undergoing laminectomy, spinal fusion surgery, or both increased at community hospital A. We compared 13 patients who acquired surgical-site infections after laminectomy, spinal fusion surgery, or both with 47 patients who were operated on during the same time period but did not acquire a surgical-site infection. Information collected included demographics, risk factors, personnel involved in the operations, length of hospital stay, and hospital costs. RESULTS: Of 13 case-patients, 9 (69%) were obese, 9 (69%) had spinal compression, 5 (38.5%) had a history of tobacco use, and 4 (31%) had diabetes. Oxacillin-sensitive Staphylococcus aureus (6 of 13; 46%) was the most common organism isolated. Significant risk factors for postoperative spinal surgical-site infection were dural tear during the surgical procedure and the use of glue to cement the dural patch (3 of 13 [23%] vs 1 of 47 [2.1%]; P = .02) and American Society of Anesthesiologists risk class of 3 or more (6 of 13 [46.2%] vs 7 of 47 [15%]; P = .02). Case-patients were more likely to have prolonged length of stay (median, 16 vs 4 days; P< .001). The average excess length of stay was 11 days and the excess cost per case was $12,477. CONCLUSION: Dural tear and the use of glue should be evaluated as potential risk factors for spinal surgical-site infection. Systematic observation for potential lapses in sterile technique and surgical processes that may increase the risk of infection may help prevent spinal surgical-site infection.     

Myocardial stiffness and reparative fibrosis following coronary embolisation in the rat

The structural nature of fibrillar collagen involved in the replacement fibrosis which accompanies discrete areas of cell necrosis remains uncertain, as does its influence on the diastolic and systolic stiffness of the intact myocardium. This study, using 15 micron diameter microsphere embolisation of the rat myocardium, was undertaken to address these issues. Collagen volume fraction (trichrome), fibrillar collagens (picrosirius-polarisation technique), and the stress-strain relations of the intact myocardium (isolated hearts) were determined 30 d after the infusion of microspheres into the left ventricle. Significant differences from controls included: (a) the presence of hypertension secondary to renovascular embolisation; (b) a greater volume fraction of collagen that included not only a meshwork of short, taut appearing, thick and thin collagen fibres, interposed between muscle in areas of cell loss, but also a perivascular fibrosis involving intramyocardial coronary arteries; (c) elevated active stiffness, and (d) a more exponential diastolic stress-strain relation with increased stiffness at strains of 5% or more. These findings suggest that the replacement fibrosis accompanying myocyte necrosis has distinguishing morphological features involving fibrillar collagen and which because of its structure, alignment, and location relative to muscle leads to enhanced myocardial stiffness, including a more exponential rise in the diastolic stress-strain relation. The perivascular accumulation of collagen suggests that additional factors other than microsphere induced necrosis were responsible for this reactive fibrosis.     

The nucleophosmin-anaplastic lymphoma kinase fusion protein induces c-Myc expression in pediatric anaplastic large cell lymphomas

The majority of pediatric anaplastic large cell lymphomas (ALCLs) carry the t(2;5)(p23;q35) chromosomal translocation that juxtaposes the dimerization domain of nucleophosmin with anaplastic lymphoma kinase (ALK). The nucleophosmin-ALK fusion induces constitutive, ligand-independent activation of the ALK tyrosine kinase leading to aberrant activation of cellular signaling pathways. To study the early consequences of ectopic ALK activation, a GyrB-ALK fusion was constructed that allowed regulated dimerization with the addition of coumermycin. Expression of the fusion protein caused a coumermycin-dependent increase in cellular tyrosine phosphorylation and c-Myc immunoreactivity, which was paralleled by a rise in c-myc RNA. To assess the clinical relevance of this observation, c-Myc expression was determined in pediatric ALK-positive and -negative lymphomas. Co-expression of c-Myc and ALK was seen in tumor cells in 15 of 15 (100%) ALK-positive ALCL samples, whereas no expression of either ALK or c-Myc was seen in six of six cases of ALK-negative T-cell lymphoma. C-Myc may be a downstream target of ALK signaling and its expression a defining characteristic of ALK-positive ALCLs.     

Effects of arousal and natural baroreceptor activation on the human muscle stretch reflex

The nociceptive flexion reflex is inhibited during systole; this inhibition may be due to increased baroreceptor stimulation. It is yet to be determined whether other spinal reflexes are similarly modulated across the cardiac cycle. There is also evidence that stretch and tendon reflexes are facilitated by increased arousal. This study investigated the effects of phase of the cardiac cycle and arousal on the muscle stretch reflex components M1, M2, and M3. Stretch reflexes were elicited in leg muscles at six intervals across the cardiac cycle during rest, number repetition, and mental arithmetic. Mental arithmetic provoked increased cardiovascular arousal and facilitated both M1 and M2 compared to rest and number repetition. The stretch reflex did not vary with the phase of the cardiac cycle. While the stretch reflex is susceptible to arousal, natural baroreceptor-mediated modulation across the cardiac cycle may be specific to nociception.     

Incidence of cervical dyskaryosis in Ireland: report of a five-year audit

The implementation of a national cervical screening programme in Ireland will require agreement on achievable standards in reporting cervical cytology similar to those published by the NHS cervical screening programme. Due to the opportunistic nature of screening in the Republic of Ireland, national incidence figures for uterine cervical disease are not available. An audit of our practice was performed to find the incidence of human papilloma virus related cervical disease in our population. Our laboratory reported 158,066 cases from 1996-2000. The overall rate of dyskaryosis increased from 3.6% to 7.9%, mostly due to increased low grade dyskaryosis (up from 2.3% to 6.0%). High grade dyskaryosis also increased (from 1.3% to 1.9%), particularly in the under-25 year age group who account for a growing proportion of high grade dyskaryosis (from 15.4% of all high grade diagnoses in 1996 to 23.0% in 2000). The positive predictive value of a diagnosis of high grade dyskaryosis remained stable between 76.0 and 79.5%. While opportunistic screening data may not be directly applicable to the entire screening population it is hoped that these data may form a foundation on which to estimate national incidence figures and define achievable standards for cervical screening cytology in Ireland.