Lack of tissue glucocorticoid reactivation in 11beta -hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) intracellularly regenerates active corticosterone from circulating inert 11-dehydrocorticosterone (11-DHC) in specific tissues. The hippocampus is a brain structure particularly vulnerable to glucocorticoid neurotoxicity with aging. In intact hippocampal cells in culture, 11beta-HSD-1 acts as a functional 11beta-reductase reactivating inert 11-DHC to corticosterone, thereby potentiating kainate neurotoxicity. We examined the functional significance of 11beta-HSD-1 in the central nervous system by using knockout mice. Aged wild-type mice developed elevated plasma corticosterone levels that correlated with learning deficits in the watermaze. In contrast, despite elevated plasma corticosterone levels throughout life, this glucocorticoid-associated learning deficit was ameliorated in aged 11beta-HSD-1 knockout mice, implicating lower intraneuronal corticosterone levels through lack of 11-DHC reactivation. Indeed, aged knockout mice showed significantly lower hippocampal tissue corticosterone levels than wild-type controls. These findings demonstrate that tissue corticosterone levels do not merely reflect plasma levels and appear to play a more important role in hippocampal functions than circulating blood levels. The data emphasize the crucial importance of local enzymes in determining intracellular glucocorticoid activity. Selective 11beta-HSD-1 inhibitors may protect against hippocampal function decline with age.     

Reoperative coronary bypass surgery: effect of patent grafts and retrograde cardioplegia

OBJECTIVE: To determine the effects of patent or diseased aorta-coronary bypass grafts and retrograde cardioplegia on mortality during reoperative coronary bypass surgery. METHODS: We conducted a retrospective review of prospectively gathered data, supplemented by systematic chart review, of all patients (n = 744) undergoing reoperative coronary bypass surgery at our institution between 1990 and 1997. Independent predictors of survival were determined by stepwise logistic regression analysis. RESULTS: At least one patent or stenosed graft to the left anterior descending artery was present in 50% of patients, to the circumflex territory in 27% of patients, and to the right coronary artery territory in 33% of patients. The previous left anterior descending graft was a saphenous vein in 82% and a left internal thoracic artery in 18% of patients. In-hospital mortality occurred in 42 (5.6%) patients. Patent or diseased grafts of any coronary artery territory did not significantly increase the risk of mortality. Retrograde cardioplegia use increased in more recent years, was more frequent in patients with stenosed grafts, and was associated with improved survival. Independent predictors of mortality were as follows (with odds ratios and 95% confidence intervals in parentheses): failure to use retrograde cardioplegia (odds ratio 2.81; 1.28-6.20), New York Heart Association class (odds ratio 2.69; 1.25-5.81), peripheral vascular disease (odds ratio 2.60; 1.25-5.41), and left ventricular grade (2.07; 1.31-3.27). CONCLUSIONS: In this series, patent or stenosed grafts were not associated with an increased risk of mortality during reoperative coronary bypass surgery, possibly because of increased use of retrograde cardioplegia in this patient group. We strongly recommend the routine use of retrograde cardioplegia during redo coronary bypass surgery.     

Transplantation of cryopreserved cardiomyocytes

BACKGROUND: The present study examined the survival and rate of contraction of (1) cardiomyocytes cultured from cryopreserved fetal rat myocardium and (2) cryopreserved cultured cardiomyocytes. In addition, the effects of transplantation of cryopreserved fetal cardiomyocytes were evaluated. METHODS: Segments of fetal rat myocardial tissue (0.2, 2.0, and 6.0 mm(3) mince size) and cultured cardiomyocytes were cryopreserved in liquid nitrogen for 1, 2, and 4 weeks. After cryopreservation, the tissue samples and cultured cardiomyocytes were thawed at 37 degrees C and cultured, and cell proliferation and rate of contraction were determined. Cultured cryopreserved (n = 5) and noncryopreserved (control, n = 5) fetal cardiomyocytes were transplanted into the subcutaneous tissue and into a transmural left ventricular free wall scar of Sprague-Dawley rats (n = 3). The survival and rate of contraction of these transplanted cells were also examined. RESULTS: Cryopreservation of cultured fetal cardiomyocytes resulted in viable and functional cardiomyocytes although the cell number and percentage of beating cells were diminished. Survival of cardiomyocytes isolated from cryopreserved fetal myocardium was a function of tissue size before cryopreservation; the lowest survival was recorded in tissues with the largest mince size (6.0 mm(3)). The subcutaneous transplants contracted spontaneously and regularly with an idioventricular rhythm. In addition, the transplanted cardiomyocytes were elongated and formed a myocardium-like pattern with blood vessels present within the contractile tissue. In the transmural left ventricular scar, both control and experimental fetal cardiomyocyte transplants formed myocardium-like tissue. CONCLUSIONS: The present study uncovers the following key observations: (1) cryopreservation of fetal cardiomyocytes and cardiomyocytes isolated from cryopreserved myocardial tissue results in viable and functional cells, (2) cryopreserved fetal cardiomyocytes can be successfully transplanted into subcutaneous and myocardial scar tissue, and (3) improvements in cryopreservation techniques are required to augment the rates of cardiomyocyte survival observed in the study.     

Accuracy of the oncology patients information system in a regional cancer centre.

This study was designed to evaluate the accuracy of the Oncology Patient Information Systems (OPIS) database for patients with breast cancer and lymphoma. We conducted a detailed individual patient chart review of patients with lymphoma or breast cancer who were seen in consultation by an oncologist between July 1991 and June 1995. Information extracted directly from the patients' clinic charts was compared with information captured in the OPIS database with respect to demographics, staging, histological diagnosis, treatment, relapse status, date of relapse and survival. OPIS database failed to capture 14.4% and 23.4% of lymphoma and breast cancer patients seen over the four-year period. When compared to the clinic charts there were differences in staging in 31.5% and 8.1%, relapse status in 27.6% and 7.2%, and date of relapse in 56.4% and 14.7% of lymphoma and breast cancer patients respectively. The deficiencies and inaccuracies in the OPIS database emphasize the need for caution in basing administrative, policy, or practice decisions on this database.     

Weight to length ratio—a good parameter for determining nutritional status in preterm and full-term newborns

To identify which parameter showed the strongest correlation with neonatal body fat store, when the ratios for assessing both weight-for-length and the mid-arm circumference to head circumference (MAC/HC) were included in the analysis, body anthropometrics and skinfold thickness were measured in 250 full-term and 125 preterm infants. Among the study cases, 66.7% were appropriate for gestational age, 26.7% were small for gestational age and 6.7% were large for gestational age. Sum of the skinfold thickness measured at the midtricepital and subscapular areas correlated well with body anthropometrics, weight/length ratio, body mass index, ponderal index and mid-arm circumference to head circumference ratio. Multiple stepwise regression analysis revealed that the weight/length ratio correlated best with skinfold thickness in both full-term and preterm newborn infants. Therefore, the simple weightllength ratio might be useful for evaluation of the nutritional status of intrauterine growth, and in the prediction of metabolic complications in both full-term and preterm newborns with abnormal intrauterine growth.     

Percutaneous transluminal angioplasty following endarterectomy

Recurrent occlusive disease was found by noninvasive methods and confirmed arteriographically in 7 patients who had undergone endarterectomy for stenosis of one [5] or both iliac arteries [1] or the subclavian artery [1]. Three patients with iliac artery stenosis had percutaneous transluminal angioplasty (PTA) 1 to 5 years after endarterectomy. One patient with stenosis of the external iliac artery had PTA 4 years after endarterectomy, and dilatation was repeated 7 months later because of recurrence. One patient had 2 endarterectomies and 2 PTAs within 8 years for stenosis of the right common iliac artery. One patient had recanalization of the left common iliac artery 6 years after endarterectomy with low-dose streptokinase followed by PTA. Another patient underwent endarterectomy of the left subclavian artery 3 months after PTA and required further dilatation at 5 and 10 months because of recurrence. The authors conclude that endarterectomy does not preclude PTA (or vice versa) in patients with recurrent arterial occlusive disease.     

Tuberculosis of the knee — A long term follow-up

Summary Thirty cases of tuberculosis of the knee followed up for an average of 15 years were reviewed. The majority of patients developed the disease during childhood. All had received standard anti-tuberculous drug treatment. Fifteen were treated conservatively alone, while the other 15 had a debridement type of surgery in addition to drugs. At review, one-third had occasional mild pain, but this was only present in the conservatively treated group. Stiffness, however, was more predominant in the operated and in the late onset groups. Some mild deformity was seen in 17 out of 30 patients and was related not so much to disturbance of epiphyseal growth, but rather, to bone collapse. Interesting X-ray appearances at follow-up were found. The factors which could lead to a good outcome included young age of onset, treatment within six months of onset, and early mobilisation. If the disease is well advanced, surgical treatment will lead to a painless joint, but with greater restriction of joint movement.

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Résumé Etude rétrospective de 30 cas de tuberculose du genou suivis en moyenne pendant 15 ans. Dans la plupart des cas l'affection avait débuté pendant l'enfance. Tous les malades avaient reçu un traitement antituberculeux standard. Quinze d'entre eux n'ont subi qu'un traitement conservateur, tandis que les 15 autres ont bénéficié, en plus du traitement spécifique, d'une intervention de nettoyage. Au moment de la révision un tiers des malades présentaient des douleurs occasionnelles modérées, mais ils faisaient tous partie du groupe soumis au traitement conservateur. La raideur au contraire était observée plus souvent chez ceux qui avaient subi une intervention ou dans le groupe où la maladie était d'apparition tardive. Des désaxations peu sévères ont été retrouvées 17 fois sur 30, plutôt en rapport avec un effondrement osseux qu'avec une perturbation de la croissance épiphysaire. Des aspects radiologiques intéressants ont été notés lors de la révision. Les facteurs pouvant conditionner une évolution favorable sont au nombre de trois: début dans le jeune âge, traitement dans les premiers six mois et mobilisation précoce. Si la maladie est déjà évoluée, le traitement chirurgical apportera l'indolence, mais aussi une importante limitation de la mobilité.

     

Fishbone perforation of the small bowel: laparoscopic diagnosis and laparoscopically assisted management

We report a patient with small bowel perforation caused by a piece of fishbone diagnosed by laparoscopy and treated with laparoscopically assisted surgery through a small incision. This uncommon cause of peritonitis and the role of laparoscopy for this condition are discussed.