ROLE OF NITRIC OXIDE IN THE CONTROL OF THE RENAL MEDULLARY CIRCULATION

1. Nitric oxide (NO) has been implicated as an important controller in the short- and long-term regulation of arterial pressure. Studies performed in our laboratory have demonstrated that chronic intravenous administration of the NO synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME) selectively decreases renal medullary blood flow, causes sodium and water retention and leads to hypertension. 2. To determine the importance of the renal medullary effects in this model of hypertension, further studies were conducted to examine the influence of selective stimulation or inhibition of renal medullary NO on whole kidney function and cardiovascular homeostasis. With the use of a unique catheter to directly infuse into the renal medullary interstitial space, stimulation (bradykinin or acetylcholine) or inhibition (L-NAME) of renal medullary NO selectively increased or decreased renal medullary blood flow. 3. The changes in medullary flow in these experiments were associated with parallel changes in sodium and water excretion independent of alterations in renal cortical blood flow or glomerular filtration rate. 4. Studies were then undertaken to examine the long-term effects of selective NO inhibition in the renal medulla on cardiovascular homeostasis. Chronic infusion of L-NAME directly into the renal medullary interstitial space of uninephrectomized Sprague-Dawley rats led to a selective decrease in renal medullary blood flow that was sustained throughout the 5 day L-NAME infusion period. The decrease in medullary blood flow was associated with retention of sodium and the development of hypertension and the effects were reversible. 5. The data reviewed indicate that NO in the renal medulla has a powerful influence on fluid and electrolyte homeostasis and the control of blood pressure.     

Definition of An Optimal First-line Chemotherapy in Metastatic Breast Cancer

Single-agent chemotherapy of metastatic breast cancer is the treatment of choice in patients with slow tumor progression and asymptomatic disease. In this patient group, the choice of drugs is based more on good tolerability than on efficacy. By contrast, symptomatic or rapidly progressing disease requires the use of highly active regimens where more weight is put on reliable antitumor activity. While anthraycline-based combination regimens have set the standard of effective treatment, the addition of docetaxel (and to a lesser extent paclitaxel) has improved tumor response, but failed to induce a consistent prolongation of survival. Based on retrospective analyses, it is hypothesised that the combined use of anthracyclines and taxanes in first-line therapy may be most beneficial in defined subgroups: after adjuvant chemotherapy, in patients with HER-2 gene amplification, possibly also in patients with rapidly progressing visceral disease.     

ACTIVIT OF HUMAN PLACENTAL GAMMA GLOBULININ BLOCKING IMMUNE FUNCTIONS IN VITRO AND IN ABROGATING THE XENOGENEIC, LOCAL GRAFT-VERSUS-HOST-REEACTEON

In order to understand the mechanism of immunosuppression caused by infusion of placental gamma globulin (PGG) in patients with renal allografts, rheumatoid arthritis, and graft – versus –host disease (GCHD) following bone marrow transplantation (BMT) ,we have examined the effect of PGG in vitro and in a model of the xenogeneic , local graft –ver- sus – host reaction (LGVHR) .PGG inhibited lymphocyte proliferation in mixed lymphocyte cultures (MLC) (P<0.005) and depressed interleukin -2 (IL-2) levels in such cultures at 72 hours (P<0.01) . In contrast phytohemagglutinin (PHA) –and pokeweed mitogen (PWM) –induced T and B lymphocyte blastogenesis was not affected by such PGG treatment .PGG treatment .PGG neither decreased the [3H] TdR pulse incorporation in unstimulated lymphocytes nor affected cell viability .Cell cycle analysis by flow cytometry showed that PGG reduced the percentage of cells in S and G2, M phases during the MLC, but did not alter cell cycling during PWM-stimulated proliferation . An immunosuppressive effect of PGG on the LGCHR was tested in a model of intracutaneous transplantation of PGG –treat human lymphocytes into cyclophosphamide – immunosuppressed rats. Lymphoprep – separated human tonsillar lymphocytes were incubated with RPMI-1640 buffer containing：（1）PGG,4mg/ml,(2) human plasma albumin,4mg/ml,(3)mitomycin-C,25ug/ml, or (4) no additive. Cell of each preparation (3x107cells in 0.1ml) were injected intracutaneously into cyclophosphamide-treated male rats at separate abdominal locations. A fifth site received only the buffer solution. Five days after injection of cells ,each rat received [125 I]IUdR (10uCi) intraperitoneally and was killed after 5 hours. For each site of injection, the diameters of induration were measured and 125 I was counted . There was no difference between buffer – treated and a ibumin – treated groups either in the diameter of the area of induration (t=0.66;P>0.5)or in radioactive counts(t=0.22;P>0.05).In the PGG –treated group, the induration and radioactivity measurements were significantly less than in control groups (t=3.72 and P<0.1;t=2.62 and P<0.02,respectively ) Cytophilic antibodies in PGG were thought to inhibit an early phase of T cell activation, and not to be cytotoxicity .In the LGVHR, the immune response might be abrogated either by immuno- regulatory suppression of T cell function or by toxicity to the infused lymphoid cells. For some clinical purposes, immuno- modulating, human antibodies might be preferred to murine, monoclonal antibodies.     

Antegrade interlocking nailing of humeral shaft fractures

The results of 39 humeral shaft fractures (37 patients) treated with antegrade locked nailing using a Russell–Taylor nail were reviewed. There were 30 acute fractures, 6 fractures malaligned in a hanging cast or brace, and 3 pathological fractures. Patient age ranged from 26 to 80 years (average, 59.7 years) and average follow-up was 25.7 months (range, 6–48 months). Fracture union was achieved in 92.3% of our cases, while shoulder function was excellent or good in 87.2% of cases. Antegrade locked nailing offers a dependable solution for the treatment of humeral shaft fractures, especially in polytrauma patients and cases of segmental or pathological fractures. Far less satisfactory results were obtained in comminuted fractures of the proximal third in the humerus, especially in osteoporotic patients, and we therefore advocate caution with the use of intramedullary nailing in this type of fracture. Certain technical aspects such as avoiding nailing the fracture in distraction, properly countersinking the tip of the nail, and achieving adequate fixation stability have been found to be of paramount importance to reduce the incidence of delayed union/non-union rate and to obtain better functional results from the shoulder joint.     

Biliopancreatic diversion with duodenal switch vs. gastric bypass for severe obesity

Conclusion In the year 2003 there is no “one best bariatric operation” for every severely obese patient. The choice of operation must be tailored to each individual patient’s needs and wishes. For the superobese patient, the patient diagnosed with intestinal metaplasia of the stomach, and for those patients who do not wish to undergo the severe dietary restrictions imposed by the RNY-GB, the BPD-DS is a valuable surgical option.