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J Ludwig

Publications and source records attributed to J Ludwig.

At least 37 records · Page 2Linked to original sources
PubMed2001

A sequence motif responsible for ER export and surface expression of Kir2.0 inward rectifier K(+) channels.

Integral membrane proteins are sorted via the secretory pathway. It was proposed that this pathway is non-selective provided that the cargo protein is properly assembled and lacks an endoplasmic reticulum (ER) retention signal. However, recent experimental evidence suggests that efficient export of proteins from the ER to the Golgi complex is not simply a default pathway. Here we demonstrate a novel sequence motif (FxYENEV) in the cytoplasmic C-terminus of mammalian inward rectifier potassium (Kir) channels which determines ER export. This motif is found to be both necessary and sufficient for efficient export from the ER that eventually leads to efficient surface expression of Kir2.1 channels.

Amino Acid Motifs↗
PubMed2001

Reciprocal electromechanical properties of rat prestin: the motor molecule from rat outer hair cells.

Cochlear outer hair cells (OHCs) are responsible for the exquisite sensitivity, dynamic range, and frequency-resolving capacity of the mammalian hearing organ. These unique cells respond to an electrical stimulus with a cycle-by-cycle change in cell length that is mediated by molecular motors in the cells' basolateral membrane. Recent work identified prestin, a protein with similarity to pendrin-related anion transporters, as the OHC motor molecule. Here we show that heterologously expressed prestin from rat OHCs (rprestin) exhibits reciprocal electromechanical properties as known for the OHC motor protein. Upon electrical stimulation in the microchamber configuration, rprestin generates mechanical force with constant amplitude and phase up to a stimulus frequency of at least 20 kHz. Mechanical stimulation of rprestin in excised outside-out patches shifts the voltage dependence of the nonlinear capacitance characterizing the electrical properties of the molecule. The results indicate that rprestin is a molecular motor that displays reciprocal electromechanical properties over the entire frequency range relevant for mammalian hearing.

Amino Acid Sequence↗
PubMed2001

Monocytes coexpress endothelial and macrophagocytic lineage markers and form cord-like structures in Matrigel under angiogenic conditions.

OBJECTIVES: It has been shown that circulating human non-adherent CD34+ cells coexpressing vascular endothelial growth factor (VEGF)-R2 and AC133 have the capacity to differentiate into adherent mature endothelial cells. However, prior studies have demonstrated that a much bigger subset of primary adherent mononuclear cells can also form endothelial progenitor cells (EPC). To determine the origin of the latter cell population we tested the hypothesis: do monocytes as a firmly adherent and plastic cell type have the potential to differentiate into an endothelial phenotype. METHODS: CD34-/CD14+ monocytes were isolated from human peripheral blood by adherence separation and magnetic bead selection (purity >90%) and cultured on fibronectin-coated plastic dishes (medium containing VEGF 10 ng/ml, basic fibroblast growth factor (bFGF) 2 ng/ml, insulin like growth factor (IGF-1) 1 ng/ml, 20% fetal calf serum). RESULTS: After 2 weeks of culture, using fluorescence activated cell analysis we observed a new expression of the endothelial markers von Willebrand factor (vWf), VE-cadherin (VE) and ec-NOS in 45.2, 12.4 and 9.8% of the cells, respectively. The proportion of cells expressing these markers further increased after 4 weeks (94.2, 89.7 and 58.8% of these cells, respectively). The proportion of CD45 expressing cells remained unchanged during this period. However, after 14 days the specific macrophage antigen CD68 was newly expressed in 62% of the analysed cells with a further increase to 90% after 28 days of culture. In three-dimensional gel (Matrigel the formation of cord- and tubular-like structures was observed. CONCLUSION: The present data indicate that under angiogenic stimulation macrophages develop an endothelial phenotype with expression of specific surface markers and even form cord- and tubular-like structures in vitro suggesting that this cell population may be recruited for vasculogenesis.

Antigens, CD↗
PubMed2001

Allosteric sensitization of nicotinic receptors by galantamine, a new treatment strategy for Alzheimer's disease.

Cholinesterase inhibitors are the only approved drug treatment for patients with mild to moderately severe Alzheimer's disease. Interestingly, the clinical potency of these drugs does not correlate well with their activity as cholinesterase inhibitors, nor is their action as short lived as would be expected from purely symptomatic treatment. A few cholinesterase inhibitors, including galantamine, produce beneficial effects even after drug treatment has been terminated. These effects assume modes of action other than mere esterase inhibition and are capable of inducing systemic changes. We have recently discovered a mechanism that could account, at least in part, for the above-mentioned unexpected properties of some cholinesterase inhibitors. We have found that a subgroup of cholinesterase inhibitors, including galantamine but excluding tacrine, directly interacts with nicotinic acetylcholine receptors. These compounds, named allosterically potentiating ligands, sensitize nicotinic receptors by increasing the probability of channel opening induced by acetylcholine and nicotinic agonists and by slowing down receptor desensitization. The allosterically potentiating ligand action, which is not necessarily associated with cholinesterase inhibition, has been demonstrated by whole-cell patch-clamp recordings to occur in natural murine and human neurons and in murine and human cell lines expressing various subtypes of neuronal nicotinic acetylcholine receptors.

Allosteric Regulation↗
PubMed2001

Transradial approach for renal artery stenting.

Percutaneous interventional procedures in the renal arteries are usually performed using a femoral or brachial vascular access. The transradial approach, which has been extensively investigated for coronary angiography and intervention, could be an attractive new technique for renal artery angioplasty and stenting. In 18 patients with hemodynamically relevant unilateral renal artery stenosis (mean diameter stenosis, 83% +/- 18%; right, n = 7; left, n = 11), interventional treatment with PTA and stenting was performed using a left (n = 16) or right (n = 2) radial artery access. Indications for the transradial approach were acute aorto-renal angles or severe peripheral arterial obstructions. After engagement of the renal artery ostium with a 6 Fr Multipurpose guiding catheter (length, 125 cm; Cordis) the stenosis was passed with a 0.014" guidewire followed by stent implantation (ACS Multi-Link RX Ultra, Guidant; length, 18 mm; diameter, 5 mm). Direct stenting was successfully performed in 16 cases. Predilatations were required in two cases. In five patients, optimal stent expansion was achieved by additional postdilatations. A primary technical success (residual stenosis < 30%) could be achieved in all cases. There were no periprocedural complications. According to color-coded doppler ultrasound, all access site arteries showed a normal perfusion. Clinically blood pressure control was improved in 11 patients with a significant reduction in systolic and diastolic blood pressure values. Serum creatinine values dropped from 1.81 +/- 0.3 mg/dl to 1.49 +/- 0.3 mg/dl (P < 0.001). Transradial renal artery angioplasty and stenting is technically feasible and safe. Particularly in patients with unfavorable vessel anatomy, this new cranio-caudal approach is an attractive alternative technique.

Aged↗
PubMed2001

Surgical or conservative treatment for chronic rotator cuff calcifying tendinitis--a matched-pair analysis of 100 patients.

Conservative or operative treatment for rotator cuff calcifying tendinitis was investigated in 100 patients in a matched-pair analysis. They were examined clinically and ultrasonographically 35-60 months after the initial visit. The mean Patte score was 91.8 for the patients who underwent surgical treatment and 81 for the ones who received conservative therapy (p < 0.004), while the age-related Constant-score was 103.4 and 95, respectively. Ultrasonography showed 28% calcifications in the surgical group, 18% newly formed and 10% that did not resolve after surgery. In the conservatively treated group, 33% calcifications were seen, of which 67% resolved. The number of rotator cuff ruptures was significantly higher in the conservative group. In the surgical group, 2% of partial tears and in the conservative group 5% of partial and 4% of complete cuff ruptures were found. Conservative treatment for calcifying tendinitis leads to less favourable pain results in the long term than surgical treatment. Surgery shortens the painful period and may reduce the number of future rotator cuff ruptures. Finally, the subjective functional outcome is significantly better after surgery.

Activities of Daily Living↗
PubMed2001

Transcatheter occlusion of a large coronary arterial fistula with new detachable platinum microcoils.

We report a 17 year old boy with a large fistula from the right coronary artery to the right ventricle. The fistula consisted of two major branches. The smaller branch could be embolised with three detachable platinum microcoils without problems. The high flow of blood in the larger branch, however, prevented conventional occlusion using coils. Interventional occlusion of this branch was achieved in a second attempt. Following creation of an arterio-venous wire-loop, we advanced a balloon catheter into the distal end of the fistula. Under temporary occlusion of the fistula, complete closure was achieved by delivery of 7 detachable platinum microcoils. Thus, even large coronary arterial fistulas can be closed safely with these new platinum detachable microcoils. The procedure, however, requires temporary control of the flow of blood by balloon occlusion.

Adolescent↗
PubMed2001

Native tissue second harmonic imaging improves endocardial and epicardial border definition in dobutamine stress echocardiography.

AIMS: Native tissue second harmonic imaging (SHI) implemented in two-dimensional (2D) echocardiography was found to improve left ventricular (LV) endocardial border delineation. Dobutamine stress echocardiography (DSE) depends on the ability to adequately visualize these borders. We analysed whether SHI, compared to fundamental imaging (FI), can improve echogenicity qualitatively and quantitatively, as well as looking at the diagnostic accuracy of the stress test. METHODS AND RESULTS: Fifty consecutive patients with suspected or known coronary artery disease (history of myocardial infarction and/or coronary artery bypass grafting) underwent DSE sequentially by SHI as well as FI 3 days before or after quantitative coronary angiography. Regional mean echogenicity scores (0=uninterpretable; 4=excellent imaging) for SHI and FI at peak dobutamine titration were 1.8 +/- 0.8 and 1.0 +/- 0.6 (P=0.0020) for the anterior region, 2.3 +/- 0.8 and 1.5 +/- 0.7 (P=0.0002) laterally, 2.7 +/- 1.0 and 1.9 +/- 0.8 (P=0.0001) posteriorly, 2.9 +/- 0.8 and 2.2 +/- 0.7 (P<0.0006) inferiorly, 3.0 +/-0.7 and 2.2 +/- 0.7 (P=0.0001) septally, and 3.1 +/- 1.0 and 2.1 +/-0.8 (P=0.0001) anteroseptally, respectively. Medians [upper; lower quartiles] of a global endocardial visualization index (calculated analogously with the wall motion score index based on a 16-segment model recommended by the American Society of Echocardiography) for the harmonic and the fundamental techniques were 2.59 [2.91; 2.22] and 1.87 [2.19; 1.53] (P=0.0001) at rest, 2.62 [2.94; 2.13] and 1.84 [2.19; 1.50] (P=0.0001) at low dose dobutamine, 2.51 [3.00; 2.13] and 1.74 [2.00; 1.44] (P=0.0001) at peak dose dobutamine, and 2.52 [2.94; 2.19] and 1.76 [2.19; 1.38] (P=0.0001) at recovery, respectively. For repeated quantitative LV volumetry in the harmonic and fundamental modality by the same observer, coefficients of variation were 4.4 +/- 0.4 vs. 6.0 +/- 0.5 (P<0.0001) for end-diastolic volume, 7.4 +/- 0.8 vs. 9.2 +/- 1.1 (P<0.0001) for end-systolic volume, and 5.2 +/- 1.1 vs. 8.2 +/- 1.3 (P<0.0001) for ejection fraction, respectively. Sensitivity and specificity related to coronary angiography for both methods were 80% and 60% as well as 90% and 93%, respectively. CONCLUSION: Native tissue SHI enhances LV image quality in all stress stages of DSE in unselected patients. This translates into beneficial effects on not only qualitative but also quantitative testing and diagnostic accuracy. SHI should be recommended as a standard tool in DSE and extends its applicability to difficult-to-image patients previously deemed unsuitable.

Adult↗
PubMed2001

Disease recurrence after living liver transplantation for primary biliary cirrhosis: a clinical and histological follow-up study.

We describe the recurrence of primary biliary cirrhosis (PBC) in recipients of living liver transplants. We are not aware of similar previous reports. Because most donors for living liver transplantation (LLT) are blood relatives with close HLA matches, the recurrence of PBC in transplant recipients might offer additional insights in the pathogenesis of the condition. We studied 6 women (age, 29 to 61 years) with PBC who survived LLT for at least 1 year. Tests for antimitochondrial autoantibody (AMA), antipyruvate dehydrogenase complex-E2, immunoglobulin G (IgG) anti-M2, and IgM anti-M2 had confirmed the diagnosis. Donors were blood relatives in 5 instances, and one donor who was not a blood relative still had multiple HLA matches with the recipient. After LLT, we observed a decrease in AMA titers, but within 1 year, these titers increased again in 5 of the 6 patients to pre-LLT levels or greater. Immunoblotting analysis of the anti-M2 protein profile failed to show loss of bands and showed new bands in 3 of 6 patients. Histologically, strong evidence of recurrent PBC was found in 2 patients, and findings compatible with PBC were present in 1 additional patient. All 6 patients are doing well, without symptoms of recurrent PBC (median time post-LLT, 35.5 months; range, 12 to 50 months).

Adult↗
PubMed2001

High-energy shock wave treatment of femoral head necrosis in adults.

Adults with Stages I to III osteonecrosis of the femoral head present an overall therapeutic challenge. The objective of the current prospective study was to show the effectiveness of high-energy shock wave therapy in treatment of patients with Association Research Circulation Osseous Stage I to Stage III necrosis of the femoral head by assessing clinical and magnetic resonance imaging results. The current study presents the results of 22 patients with femoral head necrosis 1 year after shock wave treatment. The study population consisted of 10 women and 12 men with an average age of 54.9 years (+/- 12.3). The scores achieved on the visual pain analog scale decreased from 8.5 before treatment to 1.2 after 1 year. Simultaneously, the Harris hip score increased from 43.3 to 92 points. Magnetic resonance imaging visualization of a distinct zone of sclerosis around the necrotic area remaining after treatment with extracorporeal shock wave therapy indicated therapeutic failure. The results obtained so far with high-energy shock wave therapy in these patients suggest that this method may offer an alternative to invasive treatment modalities for femoral head necrosis. A noninvasive and moderately priced method then would be available for the treatment of femoral head necrosis in the early stages of the disease process.

Adult↗
PubMed2001

Memantine inhibits efferent cholinergic transmission in the cochlea by blocking nicotinic acetylcholine receptors of outer hair cells.

Memantine is a blocker of Ca(2+)-permeable glutamate and nicotinic acetylcholine receptors (nAChR). We investigated the action of memantine on cholinergic synaptic transmission at cochlear outer hair cells (OHCs). At this inhibitory synapse, hyperpolarization of the postsynaptic cell results from opening of SK-type Ca(2+)-activated K(+) channels via a highly Ca(2+)-permeable nAChR containing the alpha 9 subunit. We show that inhibitory postsynaptic currents recorded from OHCs were reversibly blocked by memantine with an IC(50) value of 16 microM. RT-PCR revealed that a newly cloned nAChR subunit, alpha 10, is expressed in OHCs. In contrast to homomeric expression, coexpression of alpha 9 and alpha 10 subunits in Xenopus laevis oocytes resulted in robust acetylcholine-induced currents, indicating that the OHC nAChR may be an alpha 9/alpha 10 heteromer. Accordingly, nAChR currents evoked by application of the ligand to OHCs and currents through alpha 9/alpha 10 were blocked by memantine with a similar IC(50) value of about 1 microM. Memantine block of alpha 9/alpha 10 was moderately voltage dependent. The lower efficacy of memantine for inhibition of inhibitory postsynaptic currents (IPSCs) most probably results from a blocking rate that is slow with respect to the short open time of the receptor channels during an IPSC. Thus, synaptic transmission in OHCs is inhibited by memantine block of Ca(2+) influx through nAChRs. Importantly, prolonged receptor activation and consequently massive Ca(2+) influx, as might occur under pathological conditions, is blocked at low micromolar concentrations, whereas the fast IPSCs initiated by short receptor activation are only blocked at concentrations above 10 microM.

Animals↗
PubMed2001

Patients with acute coronary syndromes express enhanced CD40 ligand/CD154 on platelets.

OBJECTIVE: To investigate whether CD40L/CD154 on platelets and soluble CD40L/CD154 may play a role in the inflammatory process of acute coronary syndromes. DESIGN AND SETTING: Observational study in a university hospital. PATIENTS: 15 patients with acute myocardial infarction, 25 patients with unstable angina, 15 patients with stable angina, and 12 controls. MAIN OUTCOME MEASURES: CD40L/CD154 on platelets, P-selectin/CD62P on platelets, soluble CD40L/CD154 serum concentrations. RESULTS: Mean (SD) CD40L/CD154 expression on platelets was 6.2 (2.8) MFI (mean fluorescence intensity) in the infarct group, 11 (3.3) MFI in the unstable angina group (p < 0.001 v infarction), 3.6 (0.9) MFI in the stable angina group (p < 0.01 v infarction; p < 0.001 v unstable angina), and 3.2 (1.0) MFI in the controls (p < 0.01 v infarction; p < 0.001 v unstable angina; NS v stable angina). Soluble CD40L/CD154 concentration was 5.2 (1.1) ng/ml in the infarct group, 4.2 (0.7) ng/ml in the unstable angina group (p < 0.001 v infarction), 2.9 (1.0) ng/ml in stable angina group (p < 0.001 v infarction and unstable angina), and 3.0 (0.5) ng/ml in the controls (p < 0.001 v infarction and unstable angina; NS v stable angina). At a six months follow up, there was lower expression of CD40L/CD154 on platelets in patients with unstable angina (12.3 (3.6) v 3.8 (1.2) MFI, p < 0.0001) and acute myocardial infarction (6.2 (2.8) v 3.5 (0.8) MFI, p < 0.01) compared with their admission values six months earlier. Patients with unstable angina who needed redo coronary angioplasty (PTCA) or who had recurrence of angina were characterised by increased CD40L/CD154 expression on platelets compared with the remainder of the study group (recurrence of angina: 12.7 (3.2) v 9.7 (1.6) MFI, p < 0.05; re-do PTCA: 14.3 (4.2) v 10.3 (2.1) MFI, p < 0.05). CONCLUSIONS: Both CD40L/CD154 on platelets and soluble CD40L/CD154 are raised in patients with unstable angina and myocardial infarction. These findings suggest that CD40-CD40L/CD154 interactions may play a pathogenic role in triggering and propagation of acute coronary syndromes.

Aged↗
PubMed2001

Individual dosing of ASA prophylaxis by controlling platelet aggregation.

Acetylsalicylic acid is widely used in the primary and secondary prevention of cardiovascular diseases. In the current study, we used platelet aggregation ex vivo in platelet-rich plasma induced with arachidonic acid as a routine method for the determination of the individual dose of acetylsalicylic acid necessary to inhibit platelet aggregation in 108 patients with cardiovascular diseases. In 40% of all patients studied, a dose of 30 mg/day was sufficient to block the arachidonic acid-induced platelet aggregation nearly completely. In 50% of all patients, a dose of 100 mg/day was necessary. In 10% of all patients, the dose had to be further increased to 300 mg/day or even to 500 mg/day to inhibit platelet aggregation nearly completely. These results demonstrate that platelet aggregation can be used as a simple routine laboratory method to control acetylsalicylic acid treatment in patients with cardiovascular diseases and to determine individual doses of acetylsalicylic acid for a nearly complete inhibition of platelet aggregation. With a standard dose of 100 mg/day, 10% of the patients were nonresponders.

Aged↗
PubMed2001

Pseudoaneurysm formation at the site of external iliac artery stents: percutaneous stent-graft treatment.

PURPOSE: To present a patient who developed an asymptomatic large iliac pseudoaneurysm complicating stent-supported iliac artery recanalization. CASE REPORT: The pseudoaneurysm was detected in an asymptomatic 69-year-old man during routine angiography 6 months after an uncomplicated procedure to implant 3 overlapping Palmaz stents in an occluded external iliac artery. There was no evidence of stent infection. During a second intervention, the pseudoaneurysm was successfully treated by percutaneous implantation of an EndoPro System I stent-graft. Contrast-enhanced spiral computed tomography at 6 and 12 months confirmed the durability of aneurysm exclusion and the patency of the endoprosthesis. CONCLUSIONS: Angioplasty-induced pseudoaneurysm is rare and usually asymptomatic, but elective percutaneous stent-graft repair should be considered as the first treatment option.

Aged↗
PubMed2001

End-tidal carbon dioxide measurements as a prognostic indicator of outcome in cardiac arrest.

PURPOSE: To evaluate the use of end-tidal carbon dioxide values in predicting survival in cardiopulmonary arrest. BACKGROUND: The decision about when to terminate resuscitative efforts for patients with cardiopulmonary arrest is often subjective. End-tidal carbon dioxide values have been suggested as potential objective criteriafor making this decision. METHODS: This study was a cooperative effort of the St Louis chapter of the American Association of Critical-Care Nurses and its members and involved 6 hospitals and an air evacuation service. All adult patients who had a cardiopulmonary arrest were eligiblefor the study. Once a patient with cardiac arrest was intubated, end-tidal carbon dioxide and cardiac rhythms were measured and recorded every 5 minutes for 20 minutes or until resuscitation efforts were terminated. Patients' survival at the time of the arrest, survival 24 hours after the arrest, and discharge status were followed up. RESULTS: A total of 127 patients were enrolled in the study. All but 1 patient with end-tidal carbon dioxide values less than 10 mm Hg died before discharge. End-tidal carbon dioxide values greater than 10 mm Hg were associated with various degrees of survival. Overall survival to discharge was less than 14%, regardless of the end-tidal carbon dioxide value. CONCLUSION: Measurements of end-tidal carbon dioxide can be used to accurately predict nonsurvival of patients with cardiopulmonary arrest. End-tidal carbon dioxide levels should be monitored during cardiopulmonary arrest and should be considered a useful prognostic value for determining the outcome of resuscitative efforts.

Capnography↗
PubMed2000

Treatment of iliac artery aneurysms by percutaneous implantation of stent grafts.

BACKGROUND: Iliac artery aneurysms have traditionally been treated by direct surgical reconstruction. Endovascular stent grafts have been developed to provide an effective but less invasive treatment option for patients with peripheral arterial aneurysms. METHODS AND RESULTS: In 48 patients, a total of 53 endoprostheses (mean length 7. 3 cm, mean diameter 8.1 mm) were implanted into the iliac arteries (common iliac artery n=29, external iliac artery n=19) for percutaneous exclusion of aneurysmal lesions. The technical success of complete exclusion of the aneurysm was achieved in 47 of 48 cases (97.9%). In 1 case, persistent perfusion through a collateral branch was detected; however, this aneurysm thrombosed spontaneously within 2 weeks. In all patients, graft patency was monitored by clinical examination, which included the standardized treadmill test with calculation of the ankle-brachial Doppler index and color-coded duplex ultrasound. Forty-two of the 48 patients (87.5%) underwent follow-up angiography. According to Kaplan-Meier life-table calculations, primary patency rates were 100% after 1 year, 97.9% after 2 years, 94.9% after 3 years, and 87.6% after 4 years. Serial contrast-enhanced spiral CT scans were performed to rule out late procedural failures and to assess growth progression of the lesions. No secondary leaks were observed. Furthermore, the aneurysm diameter had reduced from 24.8+/-8.0 mm to 23.1+/-6.6 mm at the last follow-up (P:=NS). CONCLUSIONS: Stent grafts are a safe and effective treatment option for iliac artery aneurysms and provide good long-term patency of the graft.

Aged↗
PubMed2000

Homicide and suicide rates associated with implementation of the Brady Handgun Violence Prevention Act.

CONTEXT: In February 1994, the Brady Handgun Violence Prevention Act established a nationwide requirement that licensed firearms dealers observe a waiting period and initiate a background check for handgun sales. The effects of this act have not been analyzed. OBJECTIVE: To determine whether implementation of the Brady Act was associated with reductions in homicide and suicide rates. DESIGN AND SETTING: Analysis of vital statistics data in the United States for 1985 through 1997 from the National Center for Health Statistics. MAIN OUTCOME MEASURES: Total and firearm homicide and suicide rates per 100,000 adults (>/=21 years and >/=55 years) and proportion of homicides and suicides resulting from firearms were calculated by state and year. Controlling for population age, race, poverty and income levels, urban residence, and alcohol consumption, the 32 "treatment" states directly affected by the Brady Act requirements were compared with the 18 "control" states and the District of Columbia, which had equivalent legislation already in place. RESULTS: Changes in rates of homicide and suicide for treatment and control states were not significantly different, except for firearm suicides among persons aged 55 years or older (-0.92 per 100,000; 95% confidence interval [CI], -1.43 to -0.42). This reduction in suicides for persons aged 55 years or older was much stronger in states that had instituted both waiting periods and background checks (-1.03 per 100,000; 95% CI, -1.58 to -0.47) than in states that only changed background check requirements (-0.17 per 100,000; 95% CI, -1.09 to 0.75). CONCLUSIONS: Based on the assumption that the greatest reductions in fatal violence would be within states that were required to institute waiting periods and background checks, implementation of the Brady Act appears to have been associated with reductions in the firearm suicide rate for persons aged 55 years or older but not with reductions in homicide rates or overall suicide rates. However, the pattern of implementation of the Brady Act does not permit a reliable analysis of a potential effect of reductions in the flow of guns from treatment-state gun dealers into secondary markets. JAMA. 2000;284:585-591

Adult↗