Study of arterial and autonomic effects of cyclosporine in humans

Altered sympathetic activity and peripheral vascular function are suspected as a mechanism of the development of arterial hypertension in organ transplantation recipients treated with cyclosporine. We assessed whether cyclosporine might alter peripheral vascular properties or autonomic modulation of the sinus node and the vasculature during rest and standing. We examined 17 orthotopic heart transplantation recipients, 8 solid organ transplantation recipients, 17 patients with essential hypertension, and 42 normotensive control subjects. All except the normotensive control subjects were treated with a long-acting dihydropyridine calcium entry blocker; transplantation recipients also received cyclosporine-based immunosuppression. Radial artery compliance was reduced in patients with essential hypertension and in patients with heart and solid organ transplantation as compared with normotensive control subjects, with this reduction being more marked in heart transplantation recipients. At rest, R-R variance was lowest in heart transplantation recipients, denoting denervation. The spectral profile of both R-R and systolic blood pressure variability as well as the index of baroreflex gain was normal at rest in patients with solid organ transplantation. On standing, both transplantation groups demonstrated reduced responsiveness in markers of autonomic modulation. The decrease in arterial compliance in cyclosporine-induced hypertension seems to imply a degree of ventricular vascular uncoupling more apparent in heart transplantation recipients. These changes are associated with alterations in autonomic modulation that are evidenced by an orthostatic stimulus.     

CHF: "compressive" heart failure? A clinical review of metastatic cardiac tumors

Nearly 10% of patients with malignant neoplasms are found to have cardiac metastasis. Metastatic disease is much more common than primary cardiac tumors and is also associated with a worse prognosis. The authors describe a case of mitral inflow obstruction due to metastatic malignancy to the left atrium which led to "compressive" heart failure. They further provide a clinical review of malignant metastatic heart disease.     

Do atrial tachyarrhythmias beget ventricular tachyarrhythmias in defibrillator recipients?

OBJECTIVES: This study was designed to analyze the incidence of "dual tachycardia"-ventricular tachycardia (VT) or ventricular fibrillation (VF) preceded by paroxysmal atrial tachycardia (AT) or atrial fibrillation (AF)-in patients receiving dual-chamber implantable cardioverter defibrillators (ICDs). BACKGROUND: Paroxysmal AT/AF occurs commonly in patients who receive ICDs for the treatment of life-threatening VT/VF. Although AF is associated with an adverse prognosis in the setting of structural heart disease, the relationship between AT/AF and VT/VF is unclear. METHODS: We followed 537 patients undergoing implantation of the Jewel AF ICD (Model 7250, Medtronic, Minneapolis, Minnesota) for 11.4 +/- 8.2 months. These included 398 patients with a history of at least two episodes of AT or AF during the preceding year as well as 139 patients enrolled because of VT/VF alone. RESULTS: There were 233 dual tachycardia episodes in 45 patients during follow-up. Overall, 8.9% of episodes detected as VT/VF were dual tachycardias, and 20.3% of patients with VT/VF had at least one dual tachycardia episode. The median duration of AT/AF preceding the first VT/VF detection was 1.09 h (25% to 75% quartile 0.24 to 33.4 h). When AT/AF continued between two consecutive VT/VF detections, the median interdetection interval was 11 min. When AT/AF terminated either because of a ventricular therapy or spontaneously, the median interdetection interval was prolonged to 71 h (p < 0.001). CONCLUSIONS: Dual tachycardia is common in ICD recipients with a history of AT/AF. The duration of AT/AF preceding the first VT/VF detection is < or =1 h about 50% of the time. Termination of the AT/AF significantly delays the time to the next VT/VF detection.     

Human leukocyte antigen class I supertypes influence susceptibility and severity of tuberculosis

Although both differential susceptibility to Mycobacterium tuberculosis infection and disease pathogenesis depend on a multitude of factors, elucidation of specific host genetic markers, particularly those in the human major histocompatibility complex, is important. The present study is an attempt to delineate human leukocyte antigen (HLA) class I association in tuberculosis (TB) on the basis of a shared sequence motif in peptide-binding pockets of HLA molecules. In patients with pulmonary TB and miliary/disseminated TB, we observed significantly increased frequencies of A3-like supertypes and decreased frequencies of A1-like supertypes. These 2 positively and negatively associated supertypes (allele groups) share a similar peptide-binding motif, except for residues in pocket F of the HLA class I molecules. In addition, the HLA-Cw specificities that are major ligands for killer cell immunoglobulin-like (inhibitory) receptors (KIRs), particularly KIR2DL1 (Cw2, Cw4, and CW5) and KIR2DL2 (Cw1, Cw3, and Cw7), were found more frequently among patients with TB, which suggests a possible inhibition of natural killer cell activity against the infected target cells. The results of the present study suggest that the frequent occurrence of HLA class I specificities comprising an A3-like peptide-binding motif and the increased occurrence of ligands for KIR2DL in TB together may influence the outcome of TB.     

Psoriatic arthritis. Follow-up study.

227 patients with psoriasis and various forms of arthritis have been kept under review. Psoriasis and inflammatory arthropathy was present in 168 patients, of whom 94 have been followed up for more than 10 years. An arthritis indistinguishable from rheumatoid disease was present in 78%, distal joint arthritis in 16-6%, and deforming arthritis in 4-8%. There was a female predominance in the sex ratio of patients, although males predominated in the distal joint group (male:female 1-5:1). The peak age of onset was between 36 and 45 years, although in the deforming group the arthritis began before the age of 20 three times as commonly as it did in the indistinguishable group. Onset was acute in nearly half of the patients. At onset the distal joints were affected in one-third of the distal joint group. A synchronous onset of skin and joint changes was uncommon. Skin lesions usually preceded the arthritis but occurred after onset in 16%. Apart from in the deforming group, the arthritis was mild, judged by the number of admissions to hospital for treatment of the joint disease, and the time off work. Deterioration clinically and radiographically occurred in only a small portion of the distal joint and indistinguishable groups. Antimalarial drugs have been used in 7 patients, with deterioration of the skin condition in 4. Uveitis occurred particularly in the men of all three groups, but was most frequent in those with deforming arthritis. A family history of psoriasis was obtained in 26% of first-degree relatives and 13% of second-degree relatives. A history of polyarthritis was most common in patients in the deforming group. The sheep cell agglutination test was negative in the majority, but was positive in 16% of the indistinguishable group, fluctuating in a further 10%. A small number of joints only deteriorated radiographically (10% of the distal and indistinguishable groups). The men in the distal group showed greater radiographic changes and more deterioration in the terminal interphalangeal joints of the fingers than the women. Similarly they showed more deterioration of the metatarsophalangeal joints than the women. 18 patients died, one with gastric haemorrhage resulting from treatment of exfoliative psoriasis with immunosuppressive therapy, and 2 from bronchopneumonia thought to be related to immobility caused by the arthritis.     

Maxillary sinusitis of odontogenic origin

Odontogenic etiology accounts for 10% to 12% of cases of maxillary sinusitis. Although uncommon, direct spread of dental infections into the maxillary sinus is possible due to the close relationship of the maxillary posterior teeth to the maxillary sinus. If a periapical dental infection or dental/oral surgery procedure violates the schneiderian membrane integrity, infection will likely spread into the sinus, leading to sinusitis. An odontogenic source should be considered in individuals with symptoms of maxillary sinusitis and a history of dental or jaw pain; dental infection; oral, periodontal, or endodontic surgery; and in those people resistant to conventional sinusitis therapy. An odontogenic infection is a polymicrobial aerobic-anaerobic infection, with anaerobes outnumbering the aerobes. Diagnosis requires a thorough dental and clinical evaluation including radiographs. Management of sinus disease of odontogenic origin often requires medical treatment with appropriate antibiotics, surgical drainage when indicated, and treatment to remove the offending dental etiology.     

Heart Failure Association,Heart Failure Society of America,and Japanese Heart Failure Society Position Statement on Endomyocardial Biopsy

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumors. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples has significantly improved the diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (1) an overview of the practical approach to EMB, (2) an update on indications for EMB, (3) a revised plan for heart transplant rejection surveillance, (4) the impact of multimodality imaging on EMB, and (5) the current clinical practice in the worldwide use of EMB.     

Intrapericardial therapeutics: a pharmacodynamic and pharmacokinetic comparison between pericardial and intravenous procainamide delivery

INTRODUCTION: Procainamide delivery into the pericardial space may produce a greater and more prolonged electrophysiologic effect, particularly in thin superficial atrial tissue, compared with intravenous delivery. METHODS AND RESULTS: Swine were randomized to sequential procainamide doses delivered intravenously (n = 6) or into the pericardial space (n = 7). The cumulative pericardial doses were 0.5, 1.5, and 3.5 mg/kg, and the intravenous doses were 2, 10, and 26 mg/kg. Pericardial procainamide prolonged right atrial effective refractory period from baseline by 22% (P < 0.01) but only at the 3.5 mg/kg cumulative dose. This dose slowed interatrial conduction time by 14% (P < 0.05) and raised atrial fibrillation threshold by 70 mA (P < 0.05). Pericardial procainamide had minimal effect on ventricular electrophysiology. Similar results occurred with a single 2 mg/kg pericardial dose in a closed chest model. Intravenous 10 and 26 mg/kg cumulative doses prolonged atrial effective refractory period from baseline by 24% and 18% (P < 0.01), respectively. The 26 mg/kg cumulative intravenous dose slowed interatrial and atrial-ventricular conduction times by 27% and 17%, respectively (P < 0.05), raised atrial fibrillation threshold, and slowed ventricular conduction time by 29% (P < 0.05). Pericardial procainamide produced pericardial fluid concentrations ranging from 250 to 1,500 microg/mL, but plasma concentrations were <1 microg/mL. Intravenous procainamide doses produced pericardial fluid concentrations similar to plasma trough concentrations 0 to 12 microg/mL. CONCLUSION: The single 2 mg/kg and 3.5 mg/kg cumulative pericardial procainamide doses prolonged atrial refractoriness and raised atrial fibrillation threshold similar to the 26 mg/kg cumulative intravenous dose, but the duration of effect was similar between delivery methods. Pericardial procainamide did not affect global or endocardial ventricular electrophysiology nor was it associated with ventricular proarrhythmia.     

Quantitative analysis of the high-frequency components of the signal-averaged QRS complex in patients with acute myocardial infarction: a prospective study

We performed a prospective study of the high-frequency components of the terminal portion of the QRS complex in 50 patients with acute myocardial infarction (AMI) (mean age 63 +/- 10 years) within 3.25 +/- 2.45 days of the acute event. Signal averaging (400 beats) at a filter setting of 80 to 300 Hz was performed and the duration of the low-amplitude signals of less than 40 microV in the terminal portion of the QRS, the root-mean-square (RMS) voltage of the terminal 40 msec of the QRS complex, and the total duration of the signal-averaged QRS vector complex were measured. The low-amplitude signals were abnormally prolonged in 22 of 50 patients (44%); the RMS-V was abnormal (less than 20 microV) in 21 of 50 patients (58%), and the signal-averaged vector complex was abnormal (greater than 120 msec) in 15 of 46 patients (33%) without bundle branch block. There was no significant correlation between any of the signal-averaged parameters and site of AMI or total creatine kinase (CK) and CK-MB values. On the basis of the occurrence of spontaneous ventricular tachycardia in the acute and postcoronary care phase of AMI, the patients were divided into two groups. Group I consisted of 31 patients (62%) who had no documented ventricular tachycardia and group II consisted of 19 patients (38%) who had one or more runs of ventricular tachycardia. Fourteen of the 19 patients in group II (73.6%) had nonsustained ventricular tachycardia and five patients (26.3%) suffered sustained ventricular tachycardia/ventricular fibrillation or sudden death.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phase II study of a high-dose ifosfamide-based chemotherapy regimen with growth factor rescue in recurrent aggressive NHL. High response rates and limited toxicity, but limited impact on long-term survival

The purpose of the study was to evaluate in patients with recurrent intermediate-grade NHL, the tolerance to and efficacy of an intensive salvage regimen consisting of high doses of ifosfamide, etoposide and mitoxantrone with G-CSF support, followed by autologous stem cell transplantation and to identify prognostic factors for survival in patients with recurrent aggressive lymphoma. Patients with recurrent intermediate-grade NHL under the age of 60 years were eligible. Induction consisted of ifosfamide 10 g/m(2) and etoposide 900 mg/m(2) with G-CSF 5 microg/kg twice a day. Upon recovery, patients underwent stem cell apheresis. Patients achieving complete remission (CR) underwent autologous stem cell transplantation using BEAM conditioning. Those with partial remission (PR) received treatment with ifosfamide 10 g/m(2), mitoxantrone 20 mg/m(2) and G-CSF 5 microg/kg. Those with CR received BEAM, those with PR received cyclophosphamide 4.5 g/m(2), etoposide 1200 mg/m(2) and cisplatin 135 mg/m(2) with stem cell rescue followed by BEAM. Antibiotic prophylaxis was given with all treatment cycles. The results were compared with those obtained in a prior study that used MINE-ESHAP salvage. Forty-four patients with recurrent intermediate-grade NHL were enrolled between March 1994 and September 1996. Median age was 50 years (24-61). Eleven patients had transformed lymphoma and seven had a T cell phenotype. Response rate to the high-dose ifosfamide regimen was 77% +/- 12% after two cycles and the complete response rate was 41% +/- 14%. Myelosuppression was profound but short. Median nadir ANC was 0 and the median duration of ANC <0.5 x 10(9)/l was 6 days (range 3-12). No severe infections occurred; 55% of the patients required blood transfusion and 42% required platelet transfusions. Myelosuppression and transfusion requirements were similar after the first and second cycles. Thirty-five of the 44 patients proceeded to autologous stem cell transplantation and one transplant-related death occurred. With a median follow-up of 52 months, progression-free survival at 2 years is 38% +/- 14% and survival is 52% +/- 15%. Data from these 44 patients were pooled with data on 53 patients who had received salvage treatment with MINE-ESHAP, for a multivariate analysis of prognostic factors. In multivariate analysis, serum LDH was strongly associated with survival. The use of a more intensive salvage regimen, did not result in a significant increase in long-term outcome, despite a high response rate. In conclusion, duration of treatment, response rates, treatment-related mortality and survival compare favorably with previous salvage regimens, but recurrence remains a major problem. Long-term survival in recurrent large cell lymphoma is influenced more by disease characteristics than by the type of salvage regimen used.