Value of scintigraphic localization of obscure gastrointestinal bleeding.

A total of 51 technetium-99m (99mTc)-labelled autologous red cell (LRC) scans performed on 49 patients for the localization of obscure gastrointestinal bleeding over a 5-year period was reviewed. The sensitivity for LRC scanning was 72.7% with a positive predictive value of 84.2%. Forty patients underwent both LRC scanning and visceral angiography during the same admission; angiography had a sensitivity of 38.9% compared with 66.7% for LRC scanning and the positive predictive values were 77.8% and 85.7%, respectively. Overall, the site of bleeding was located in 22 (45%) of 49 patients, but LRC scanning alone was successful in identifying the lesion in 16 (33%) cases. In patients who continue to bleed to the point of requiring operation, a combination of scintigraphy and angiography will localize a source in 70% of patients.     

DNA polymerase beta mutations in human colorectal cancer.

Increasing numbers of alterations have been found in protooncogenes (e.g., ras, myc), as well as tumor suppressor genes (e.g., p53, Rb) in various types of tumors. The multiple mutations cannot be explained by the spontaneous mutation rate. It has been suggested that mutator phenotypes leading to the accumulation of these mutations may be required in the early stages of tumorigenesis. To test this hypothesis, the entire coding region of DNA polymerase beta, a repair enzyme, mRNA from colorectal tumors, and corresponding normal mucosa were amplified by polymerase chain reaction, cloned, and sequenced. Mutations in the catalytic domain of DNA polymerase beta were detected in colorectal tumor specimens compared to the normal colorectal mucosa, placenta, and blood samples. Since these mutations changed the structure of polymerase beta, it is expected that the efficiency of the DNA repair system would be impaired and thus may account for the high mutation rate observed in colorectal carcinomas.     

Non-linkage of the islet amyloid polypeptide gene with Type 2 (non-insulin-dependent) diabetes mellitus

Summary Type 2 (non-insulin-dependent) diabetes is associated with the deposition of islet amyloid. The major formative peptide, islet amyloid polypeptide, has recently been characterised and an abnormality of the structure or expression of this gene is a possible candidate for the inherited component of Type 2 diabetes. A restriction fragment length polymorphism of the gene has been identified with Pvu II. To study the relationship between the islet amyloid polypeptide gene and Type 2 diabetes, two distinct genetic approaches have been undertaken. Firstly, non-linkage has been demonstrated in four pedigrees, with four normoglycaemic first degree relatives having an allele associated with diabetes in other family members, and one affected relative not having the putatively associated allele. The LOD score taking age-related penetrance into account was –1.68, making linkage unlikely (p=0.02). Secondly, in a population-based restriction fragment length polymorphism survey, no linkage disequilibrium of the alleles was found between a population of unrelated Caucasian subjects with Type 2 diabetes and a normal population. A mutation in or near the islet amyloid polypeptide gene is thus unlikely to be a common cause of Type 2 diabetes.     

Physicians and DRGs. Hospital management alternatives.

Rising health care costs in general and hospital costs in particular have placed significant financial strain on federal programs such as Medicare. It was with this in mind that the Reagan administration in 1983 initiated Medicare's new prospective payment system based on diagnostic-related groups (DRGs) to reduce the growth rate of Medicare expenditures. The introduction of DRGs has generated significant controversy in the health care community. The DRG system may necessitate consideration of four new management alternatives by hospital administrators: increased monitoring and regulation of physicians, profit-loss sharing arrangements between physicians and hospital management, development of collective protocols among physicians, and bedside budget balancing. This study examines the opinions of a random sample of 838 physicians from the West North-Central region regarding these management alternatives. The findings suggest that physicians have strong negative opinions about these management alternatives and believe that they will have a negative impact on the health care system. The development of collective protocols emerges as the most likely acceptable alternative among physicians, but even collective protocols as an alternative promise limited success.     

Early mobilisation after percutaneous cardiac catheterisation using collagen plug (VasoSeal) haemostasis.

OBJECTIVE--To assess the efficacy and safety of a haemostatic bovine collagen plug (VasoSeal) in reducing patient immobilisation after cardiac catheterisation from a percutaneous femoral arterial approach. DESIGN--A non-randomised, prospective analysis of a new biodegradable haemostatic agent on an intention to treat basis. SETTING--The catheterisation suite of a regional cardiothoracic unit. PATIENTS--A series of 63 patients having various diagnostic investigations and therapeutic interventions agreed to participate in this study. INTERVENTIONS--Cardiac catheterisation was performed from a percutaneous femoral artery approach. Patients taking aspirin and those who required formal anticoagulation were not excluded. Patients were measured for the appropriate sized collagen delivery system at the beginning of the procedure. At the end of the procedure two bovine collagen plugs were applied to the surface of the femoral artery through the channel created by the application device. MAIN OUTCOME MEASURES--Incidence of successful delivery, insertion time, immediate outcome, inpatient complications, success of mobilisation of the patient at one and two hours after the procedure, and whether these variables relate to individual patient characteristics. RESULTS--Successful placement of the device was achieved in 57 of 63 consecutive patients (90.5%). The mean (SD) insertion time was 86 (24) seconds. Six (9.5%) patients did not receive the haemostat because of femoral artery perforation by the tissue dilator (n = 3), inability to compress the femoral artery proximal to the site of delivery (n = 1), pre-existing haematoma (n = 1), or patient withdrawal from the study (n = 1). Uncomplicated mobilisation within two hours of investigation was possible in 54 of 57 (94.7%) patients receiving this device. A sizeable haematoma (> 5 x 5 cm) prevented early mobilisation in the remaining three patients. Mobilisation was uncomplicated in 32 of 34 (94.1%) patients mobilised at two hours and 22 of 23 (95.6%) at one hour (NS). One patient who was mobilised early without complication later developed evidence of claudication in the treated leg. Femoral arteriography showed a smooth intraluminal filling defect attached to the wall of the femoral artery at the puncture site. This obstruction, presumed to be a collagen plug, was treated successfully with angioplasty. Sheath size, arterial pressure, the use of aspirin, heparin or warfarin, and body mass index did not influence patient outcome. The pattern of complications did not relate to a learning curve experience. CONCLUSIONS--The bovine collagen haemostat is a relatively safe and effective device that allows far earlier patient mobilisation than conventional haemostasis after diagnostic and therapeutic interventions from a percutaneous femoral artery approach. These results have important implications for patients undergoing investigation in mobile x ray units or in hospital based day case units.     

Factors influencing calcitriol metabolism in renal failure

Metabolic clearance rate (MCR) and production rate (PR) of calcitriol is decreased in experimental renal failure. In this experiment, we studied uremia and secondary hyperparathyroidism as possible causes of the abnormal calcitriol metabolism. Normal rats were made uremic by infusing phosphorus-free urine for 24 hours. Both the MCR (0.22 +/- 0.01 ml/min/kg, N = 6 P less than 0.001) and the PR (16.6 +/- 1.97 ng/kg/day, P less than 0.01) of calcitriol were significantly suppressed in normal rats following urine infusion when compared to saline infused rats (MCR, 0.30 +/- 0.01; PR, 32.9 +/- 4.1, N = 6). Different levels of protein intake by rats with renal failure produced by subtotal nephrectomy also alter the PR but not the MCR of calcitriol. Thus, the synthesis of calcitriol was significantly lower in rats with renal failure fed a high protein (50% protein) diet (17.6 +/- 0.7 ng/kg/day, N = 8, P less than 0.001) than in rats with renal failure fed a normal protein (20% protein) diet (22.2 +/- 1.4, N = 7). Thyroparathyroidectomy (TPTX) did not alter the MCR of calcitriol in renal failure, even though parathyroid hormone, which may suppress the degradation enzyme, could be elevated in this model of renal failure. The MCR of TPTXed rats with renal failure (0.15 +/- 0.01 ml/min/kg, N = 7) remained lower than that of the TPTXed control rats (0.19 +/- 0.01, N = 7, P less than 0.001), and chronic infusion of PTH to TPTXed rats with renal failure did not change the MCR of calcitriol (0.15 +/- 0.01, vs. control, 0.24 +/- 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

T lymphocyte subsets and antilymphocyte antibodies in lupus nephritis

T lymphocyte subsets were determined in 12 patients with untreated systemic lupus erythematosus (SLE) and in 14 healthy controls. Six out of 8 (75%) patients with lupus nephritis had reduction in the percentage of T helper cells and low helper: suppressor cell ratios compared with controls. None of the 4 patients without nephritis had low ratios. Cold-reactive anti-lymphocyte antibodies cytotoxic to both the helper and the suppressor cells were detected in 7 of the 8 patients who had nephritis. Low T helper: suppressor cell ratio in SLE seems to correlate with the presence of active nephritis.     

Beneficial Effects of Short-term Vasopressin Infusion during Severe Septic Shock

Background: Septic shock is associated with vasopressin deficiency and a hypersensitivity to its exogenous administration. The goal of the current study was to determine whether short-term vasopressin infusion in patients experiencing severe septic shock has a vasopressor sparing effect while maintaining hemodynamic stability and adequate end-organ perfusion.

Methods: Patients experiencing septic shock that required high-dose vasopressor support were randomized to a double-blinded 4-h infusion of either norepinephrine (n = 11) or vasopressin (n = 13), and open-label vasopressors were titrated to maintain blood pressure. To assess end-organ perfusion, urine output and creatinine clearance, gastric mucosal carbon dioxide tension, and electrocardiogram ST segment position were measured.

Results: Patients randomized to norepinephrine went from a median prestudy norepinephrine infusion of 20.0 [mu]g/min to a blinded infusion of 17.0 [mu]g/min at 4 h, whereas those randomized to vasopressin went from a median prestudy norepinephrine infusion of 25.0 [mu]g/min to 5.3 [mu]g/min at 4 h (P < 0.001). Mean arterial pressure and cardiac index were maintained in both groups. Urine output did not change in the norepinephrine group (median, 25 to 15 ml/h) but increased substantially in the vasopressin group (median, 32.5 to 65 ml/h;P < 0.05). Similarly, creatinine clearance did not change in the norepinephrine group but increased by 75% in the vasopressin group (P < 0.05). Gastric mucosal carbon dioxide tension and electrocardiogram ST segments did not change significantly in either group.     

Chronic lithium treatment increases the phosphorylation of a 64-kDa protein in rat brains

Despite the wide clinical use of lithium in the treatment of manic depressive illness there is no adequate explanation for its mechanism of action. In the light of lithium's suggestive effects on the second messenger system in the brain, we studied the effects of chronic dietary lithium treatment (achieving blood levels in the therapeutic range) on protein phosphorylation in different areas of rat brain. An increase in the phosphorylation of a 64-kDa membrane-associated protein was evident in the lithium-treated rats compared to controls. This increase was observed only under basal phosphorylating conditions and was abolished when the phosphorylation was performed in the presence of Ca²⁺ or Ca²⁺ and calmodulin. The possibility that this 64-kDa protein affected by lithium is the beta-subunit of the calmodulin-dependent protein kinase or a different protein which co-migrates with it is discussed.