Minactivin expression in human monocyte and macrophage populations

Adherent monolayer cultures of human blood monocytes, peritoneal macrophages, bone marrow macrophages, and colonic mucosa macrophages were examined for their ability to produce and secrete minactivin, a specific inactivator of urokinase-type plasminogen activator. All except colonic mucosa macrophages produced and secreted appreciable amounts of minactivin, but only blood monocytes were stimulated by muramyl dipeptide (adjuvant peptide) to increase production. The minactivin from each of these populations could be shown to preferentially inhibit urokinase-type plasminogen activator and not trypsin, plasmin, or "tissue"-type plasminogen activator (HPA66). A plasminogen-activating enzyme present in monocyte cultures appeared unaffected by the presence of minactivin and could be shown to be regulated independently by dexamethasone.     

Meobentine sulfate: antiarrhythmic and electrophysiologic effects assessed by programmed electrical stimulation and ambulatory monitoring in patients with complex ventricular tachyarrhythmia. Report of a multicenter evaluation

Five cardiology centers conducted open-label prospective trials of meobentine sulfate, an intravenously and orally available analog of bethanidine, to assess its potential for treatment of recurrent, drug refractory ventricular tachycardia (VT) or fibrillation (VF), and complex ventricular arrhythmias. The study population comprised 26 patients (mean age, 61 years); 18 were men. Coronary artery disease was present in 15, cardiomyopathy in six, and valvular heart disease in three. Patients presented with both VT and VF (seven), sustained VT alone (12), or frequent ventricular ectopy (PVCs) and nonsustained VT (seven). Of the 26 patients, 5 were enrolled in antiarrhythmic studies (chronic PVC suppression) and 21 were enrolled in programmed electrical stimulation (PES) studies. Two of five in the chronic PVC study showed greater than 75% arrhythmia suppression. Among 21 patients in PES studies, there were eight intravenous (16 mg/kg) and 19 oral trials (400 to 1000 mg every 6 hours, 3 days/dose interval). Five of 22 patients showed efficacy at repeat PES study (neither VT nor VF), one showed partial efficacy, and four were not restudied because of clinical arrhythmia (three) and/or adverse effects (two). Overall, three patients (12%) were continued on the drug for an extended period of time. Adverse experience included hypotension in 50% and gastrointestinal effects (nausea, vomiting, or diarrhea) in 56% (oral trials only). Adverse reactions led to drug discontinuation in six and dosage reduction in eight patients. Thus, meobentine may prevent induction of VT or VF or reduce frequency of complex PVCs in selected patients refractory to other antiarrhythmic agents, but the response rate is relatively low. Symptomatic hypotension or gastrointestinal adverse effects are common and may limit utility of meobentine as a chronic oral antiarrhythmic agent.     

Current thinking on chronic renal allograft rejection: issues, concerns, and recommendations from a 1997 roundtable discussion

Chronic rejection accounts for most renal allograft losses after the first year posttransplantation. On March 24 and 25, 1997, a roundtable of five transplant surgeons, two nephrologists, and one pathologist assembled in Dallas, Texas, to review critical issues surrounding chronic renal allograft rejection. This article summarizes the presentations and relevant discussions of this meeting regarding the cause of chronic rejection, clinical diagnoses, risk factors, future prospects for intervention strategies, and general recommendations for the transplant community. Growing evidence indicates that chronic rejection is the aggregate sum of irreversible immunologic and nonimmunologic injuries to the renal graft over time. A history of acute rejection episodes and inadequate immunosuppression, likely attributable to inconsistent cyclosporine exposure or poor patient compliance, are among the most recognizable immunologic risk factors for chronic rejection. Donor organ quality, delayed graft function, and other donor and recipient variables leading to reduced nephron mass are nonimmunologic factors that contribute to the progressive deterioration of renal graft function. Clinical management of renal transplant recipients should incorporate both immunologic- and nonimmunologic-based intervention strategies aimed at minimizing risk factors to thwart the progression of chronic rejection and improve long-term allograft and patient survival.     

Active surveillance of small renal masses offers short‐term oncological efficacy equivalent to radical and partial nephrectomy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Active surveillance of small renal masses has traditionally been reserved for elderly patients deemed unfit for surgery or ablation. There is increasing evidence showing the safety of active surveillance in the management of small renal masses. In this retrospective study we compared outcomes for patients with small renal masses managed with active surveillance, radical nephrectomy and partial nephrectomy. We showed that active surveillance was safe and appeared as effective as immediate surgery in the management of small renal tumours.

OBJECTIVE

• ? To compare the oncological outcomes of active surveillance (AS), radical nephrectomy (RN) and partial nephrectomy (PN) in the management of T1a small renal masses (SRMs).

PATIENTS AND METHODS

• ? At present AS is used in the treatment of SRMs in elderly patients with multiple co‐morbidities or in those who decline surgery.
• ? We identified all patients with T1a SRMs managed with RN, PN or AS.
• ? Retrospective data were collected from patient case records with survival data and cause of death cross‐referenced with the Oxford Cancer Intelligence Unit.

RESULTS

• ? A total of 202 patients with 234 T1a SRMs (solid or Bosniak IV) were identified; 71 patients were managed with AS, 41 with an RN and 90 by PN.
• ? Over a median follow‐up of 34 months the mean growth rate on AS was 0.21 cm/year with 53% of SRMs managed with AS showing negative or zero growth.
• ? No statistically significant difference was observed in overall (OS) and cancer‐specific (CSS) survival for AS, RN and PN (AS‐CSS 98.6%, AS‐OS 83%; RN‐CSS 92.6%, RN‐OS 80.4%; PN‐CSS 96.6%, PN‐OS 90.0%).

CONCLUSIONS

• ? Active surveillance of SRMs offers oncological efficacy equivalent to surgery in the short/intermediate term.
• ? The results of this study support a multicentre prospective randomized controlled trial designed to compare the oncological efficacy of AS and surgery.

     

Are vitamin B12 and folate deficiency clinically important after roux-en-Y gastric bypass?

Although iron, vltamm B₁₂, and folate deficiency have been well documented after gastric bypass operations performed for morbid obesity, there is surprisingly little information on either the natural course or the treatment of these deficiencies in Roux-en-Y gastric bypass (RYGB) patients Durmg a l0-year period, a complete blood count and serum levels of iron, total iron-binding capacity, vltamin B₁₂, and folate were obtained in 348 patients preoperatively and postoperatively at 6-month intervals for the first 2 years, then annually thereafter The principal objectives of this study were to determine how readily patients who developed metabolic deficiencies after Roux-en-Y gastric bypass responded to postoperative supplements of the deficient micronutrient and to learn whether the risk of developmg these deficiencies decreases over time Hemoglobin and hematocrit levels were slgnificantly decreased at all postoperative intervals in comparison to preoperative values Moreover, at each successive interval through 5 years, hemoglobin and hematocrit were decreased signifiantly compared to the preceding interval Folate levels were significantly increased compared to preoperative levels at all time intervals Iron and vltamin B₁₂ levels were lower than preoperative measurements and remained relatively stable postoperatively Half of the low hemoglobin levels were not associated with iron deficiency Taking multivltamin supplements resulted in a lower incidence of folate deficiency but did not prevent iron or vitamin B₁₂ deficiency Oral supplementation of iron and vitamin B₁₂ corrected defiaencies in 43% and 81% of cases, respectively Folate deficiency was almost always corrected with multivitamins alone No patient had symptoms that could be attributed to either vitamin B₁₂ or folate deficiency Conversely, many patients had symptoms of iron deficiency and anenua Lack of symptoms of vitamin B₁₂ and folate deficiency suggests that these deficiencies are not clinically important after RYGB Conversely, iron deficiency and anemia are potentially serious problems after RYGB, particularly in younger women Hence we recommend prophylactic oral iron supplements to premenopausal women who undergo RYGB     

Preoperative beta-blocker use: impact of national guidelines on clinical practice

STUDY OBJECTIVE: To determine if recommendations regarding perioperative beta-blocker therapy were followed by an increase in the number of eligible presurgical patients receiving beta-blockers and the number achieving the recommended heart rate (HR <60 beats per minute [bpm]). DESIGN: Retrospective, observational study. SETTING: Tertiary-care teaching hospital. MEASUREMENTS: The records of all 718 patients who underwent elective vascular surgery or coronary artery bypass grafting between January 2001 and March 2002 (pre-guideline) and those who did so between April 2002 and September 2003 (post-guideline) were reviewed. Percentage of eligible patients who received beta-blockers preoperatively and the target HR achieved in pre-guideline versus post-guideline patients were recorded. Differences were assessed using the unpaired t test and chi2 analysis. A P value of less than 0.05 is reported. MAIN RESULTS: Fifty percent of the post-guideline patients in the vascular surgery group were receiving beta-blockers at the time of preanesthetic evaluation versus 48% of pre-guideline patients (P = nonsignificant [NS]). Mean HR in the vascular surgery post-guideline beta-blocker group (70 +/- 14 bpm) was higher than in the pre-guideline beta-blocker group (65 +/- 11 bpm) (P < 0.01). Only 22% of those vascular surgery patients in the post-guideline group who were taking beta-blockers achieved the target HR of less than 60 bpm versus 29% of the vascular surgery patients taking beta-blockers in the pre-guideline group (P = NS). In the coronary artery bypass grafting group, 80% of post-guideline patients received beta-blocker before anesthesia assessment versus 75% of pre-guideline patients (P = NS). Mean HR in the post-guideline beta-blocker group (67 +/- 15 bpm) was similar to the pre-guideline beta-blocker group (64 +/- 13 bpm) (P = NS). Only 28% of the post-guideline patients who were receiving beta-blockers achieved the target HR of less than 60 bpm, which was not significantly different from the 17% achieved in the pre-guideline group (P = NS). CONCLUSION: At our institution, preoperative beta-blocker use was not significantly changed by publication of the recommendations.     

Wolf-Hirschhorn syndrome

Chromosomal abnormalities are important cause of mental retardation and congenital anomalies. We report a case of a rare chromosomal disorder, Wolf-Hirschhorn syndrome, caused by deletion of short arm of chromosome 4. It was characterized by well-described facial appearance, seizures, microcephaly and midline closure defects along with growth and mental retardation.