Expression of CHL1 and L1 by neurons and glia following sciatic nerve and dorsal root injury

Cell adhesion molecules (CAMs), particularly L1, are important for axonal growth on Schwann cells in vitro. We have used in situ hybridization to study the expression of mRNAs for L1 and its close homologue CHL1, by neurons regenerating their axons in vivo, and have compared CAM expression with that of GAP-43. Adult rat sciatic nerves were crushed (allowing functional regeneration), or cut and ligated to maintain axonal sprouting but prevent reconnection with targets. In other animals lumbar dorsal roots were transected to produce slow regeneration of the central axons of sensory neurons. In unoperated animals L1 and CHL1 mRNAs were expressed at moderate levels by small- to medium-sized sensory neurons and L1 mRNA was expressed at moderate levels by motor neurons. Many large sensory neurons expressed neither L1 nor CHL1 mRNAs and motor neurons expressed little or no CHL1 mRNA. Neither motor nor sensory neurons showed any obvious upregulation of L1 mRNA after axotomy. Increased CHL1 mRNA was found in motor neurons and small- to medium-sized sensory neurons 3 days to 2 weeks following sciatic nerve crush, declining toward control levels by 5 weeks when regeneration was complete. Cut and ligation injuries caused a prolonged upregulation of CHL1 mRNA (and GAP-43 mRNA), indicating that reconnection with target tissues may be required to signal the return to control levels. Large sensory neurons did not upregulate CHL1 mRNA after axotomy and thus regenerated within the sciatic nerve without producing CHL1 or L1. Dorsal root injuries caused a modest, slow upregulation of CHL1 mRNA by some sensory neurons. CHL1 mRNA was also upregulated by many presumptive Schwann cells in injured nerves and by some satellite cells around large sensory neurons after sciatic nerve injuries and was transiently upregulated by some astrocytes in the degenerating dorsal columns after dorsal rhizotomy.     

Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type with cladribine: a phase II study.

PURPOSE: As chemotherapy has not been extensively studied in patients with lymphoma of the mucosa-associated lymphoid tissue (MALT), we initiated a prospective study to evaluate the activity of the nucleoside analog cladribine (2-chlorodeoxyadenosine [2-CdA]) in this disease. PATIENTS AND METHODS: Patients with histologically verified MALT-type lymphoma were enrolled. 2-CdA was administered at a dose of 0.12 mg/kg body weight on 5 consecutive days, as a 2-hour infusion. Cycles were repeated every 4 weeks for a maximum of six cycles. RESULTS: Nineteen patients with gastric and seven patients with extragastric MALT lymphoma were enrolled. All patients were chemotherapy-naive, and two had been locally irradiated before systemic relapse of the lymphoma. A total of 102 cycles was administered to our patients (median number of cycles per patient, four). All 25 assessable patients responded to treatment: 21 patients (84%) achieved complete remission (CR) and four patients achieved partial remission. All patients (100%) with gastric presentation, but only three patients (43%) with extragastric presentation, achieved CR. Toxicities were moderate and mainly hematologic and required dose reduction and/or premature discontinuation of therapy in only three cases. Two patients died from vascular events, one shortly after the first cycle because of myocardial infarction and the other from stroke 3 months after the second course. Three patients relapsed after 13, 18, and 22 months and one patient showed progressive disease after 15 months. At present, 24 patients are alive at a median follow-up time of 32 months. CONCLUSION: Our data demonstrate that 2-CdA is highly effective in inducing CR in 84% of patients with MALT-type lymphoma.     

Comparison of systemic vasodilators: effects on flow in internal mammary and radial arteries

BACKGROUND: Spasm is a major concern with the use of arterial conduits in coronary artery bypass surgery (CABG). We evaluated the effect of systemic vasodilators on in vivo radial artery flow compared with internal mammary artery (IMA) flow. METHODS: Fifty patients undergoing primary CABG with a mean age of 69 +/- 5 years enrolled in this study and were randomized to 1 of 5 groups based on the vasodilating agent administered (nitroglycerin, nitroprusside, dobutamine, milrinone, and normal saline as control group). Radial artery and IMA flows, blood pressure, central venous pressure, and heart rate were measured before and 10 minutes after drug administration. RESULTS: Mean arterial pressure decreased significantly after drug administration in both the nitroglycerin (p = 0.007) and nitroprusside (p < 0.001) groups and increased in the dobutamine group (p < 0.001). There were no significant differences between IMA flow or radial flow among the groups before drug administration. A multivariate general linear model was created and revealed drug (specifically nitroglycerin) as the only predictor to increase flow in the IMA (p < 0.001) or the radial artery (p = 0.009). CONCLUSIONS: We conclude that intravenous nitroglycerin causes in vivo vasodilatation of both the IMA and radial artery and is a good systemic vasodilator to be given when harvesting these two conduits.     

Delayed postoperative paraplegia complicating repair of type A dissection

We describe the very rare event of delayed transient paraplegia after repair of type A dissection of the aorta and discuss therapeutic options. We also suggest insertion of a spinal catheter as soon as there are signs or symptoms of spinal cord injury to drain spinal fluid and maximize the effect of elevated spinal cord perfusion pressure.     

Comparison of myocardial preservation techniques for aortocoronary bypass surgery.

The myocardial properties of three different techniques for cardiac arrest during aortocoronary bypass surgery were analyzed. Ventricular fibrillation and moderate total body hypothermia (30–33°C) (Group I) was found to be an insecure method of preservation. It produced a high incidence of focal irreversible ultrastructural changes (7 of 10 patients), high post-bypass CK-MB levels (mean 85.54 U/liter) indicative of myocardial damage, and impaired clinical and physiologic recovery courses. Six out of ten patients needed inotropic support, three had prolonged stay in ICU, and three patients showed Type III (unacceptable) recovery trajectories, one of whom died of myocardial decompensation four weeks after surgery. This method, which was the most common one used in our institution, was completely abandoned as a result of these studies. Potassium induced cardioplegia combined with methylprednisolone sodium succinate, hypertonic glucose and intermittent moderate topical cooling (25–27°C) of the heart (Group III) offered a generally acceptable form of myocardial protection, as only one patient showed irreversible ultrastructural changes. The mean post-bypass CK-MB level was only moderately elevated (mean 22.32 U/liter), but seven of ten patients needed inotropic support. There were no Type III recovery trajectories and two patients showed an optimal Type I recovery. Only one patient had a prolonged stay in ICU, and another patient exhibited electrocardiographic evidence of a perioperative myocardial injury pattern. Selective intracavitary profound hypothermic arrest (15–18°C) (SIPHA) offered the best myocardial protection as evidenced by remarkably well preserved ultrastructure and significantly (P< 0.005) lower post-bypass CK-MB levels (mean 7.85 U/L). All SIPHA patients had acceptable physiologic recovery trajectories of the Type I or Type II with minimal need for inotropic support (one patient), and none had a Type III recovery.These data also suggest that the major determinant of a successful myocardial preservation is the level of myocardial layer temperature, being best at the lowest temperature (15–18°C), worst at the highest temperature (30–33°C) and intermediate at 25–27°C. Additional injury may also be induced by ventricular fibrillation which by itself increases myocardial metabolic demands.     

The renal handling of polybasic drugs

Naunyn-Schmiedeberg's Archives of Pharmacology -     

Characterization of an antiserum to synaptic glomeruli from rat cerebellum

Rabbit anti-rat cerebellar synaptic glomeruli antiserum when absorbed with non-neural tissues reacts only with neural tissues when tested by indirect immunofluorescence on tissue sections. Further absorption with forebrain results in an antiserum which detectably reacts only with synaptic glomeruli and soma of Purkinje cells of both rat and mouse. The developmental expression of the synaptic glomeruli antigen(s) parallels the formation of synapses between mossy fibers and granule cells. Immature synaptic contacts do not contain recognizable antigent(s), whereas only at postnatal Day 15 glomeruli become antigen-positive. At this stage antigen in Purkinje cells is no longer carried in their dendrites, but becomes confined to the cell soma. Staggerer mutant mice still express the immature pattern of antigen distribution on postnatal Day 18.