Acute hemodynamic effects of biventricular DDD pacing in patients with end-stage heart failure

OBJECTIVES: The aim of this study was to assess the potential acute benefit of multisite cardiac pacing with optimized atrioventricular synchrony and simultaneous biventricular pacing in patients with drug-refractory congestive heart failure (CHF). BACKGROUND: Prognosis and quality of life in severe CHF are poor. Various nonpharmacological therapies have been evaluated but are restricted in their effectiveness and applications. In the early 1990s, dual chamber pacing (DDD) pacing was proposed as primary treatment of refractory CHF but results were controversial. Recently, tests to evaluate the effect of simultaneous pacing of both ventricles have elicited a significant improvement of cardiac performance. METHODS: Acute hemodynamic study was conducted in 18 patients with severe CHF (New York Heart Association class III and IV) and major intraventricular conduction block (IVCB) (QRS duration = 170+/-37 ms). Using a Swan-Ganz catheter, pulmonary artery pressure, pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were measured in different pacing configurations: atrial pacing (AAI) mode, used as reference, single-site right ventricular DDD pacing and biventricular pacing with the right ventricular lead placed either at the apex or at the outflow tract. RESULTS: The CI was significantly increased by biventricular pacing in comparison with AAI or right ventricular (RV). DDD pacing (2.7+/-0.7 vs. 2+/-0.5 and 2.4+/-0.6 l/min/m2, p < 0.001). The PCWP also decreased significantly during biventricular pacing, compared with AAI (22+/-8 vs. 27+/-9 mm Hg; p < 0.001). CONCLUSIONS: This acute hemodynamic study demonstrated that biventricular DDD pacing may significantly improve cardiac performance in patients with IVCB and with severe heart failure, in comparison with intrinsic conduction and single-site RV DDD pacing.     

Variations in response of four lines of ring-necked pheasants to infection with marble spleen disease virus

This study evaluated the response and susceptibility of four lines of ring-necked pheasants to infection with marble spleen disease (MSD) virus. Fifteen birds of the following lines were used: the standard ring-necked gamebird, the highly inbred jumbo white, the Sichuan, and the first-generation cross of the Sichuan and the standard gamebird. Baseline immune responses were assessed at 6 weeks of age by lymphoblastogenesis assays. All birds were orally challenged at 7 weeks of age with cell -culture-propagated MSD virus. Eight birds of each group were necropsied at 6-7 days post-inoculation (PI), and gross splenic lesions were recorded. Appropriate tissue sections were collected, fixed in 10% buffered formalin, and routinely processed for microscopic evaluation. The remaining birds were bled weekly from week 2 through week 8 Pl. Serum was tested for antibodies to MSD virus using a commercial enzyme-linked immunosorbent assay kit. Results of the lymphoblastogenesis assays and the gross and microscopic lesion incidences indicated that variations did exist between several lines evaluated. The jumbo white pheasant had significantly higher lymphoblastogenesis stimulation index and was more resistant to developing gross and histologic lesions than was the standard ring-necked gamebird.     

Prevalence of attenuated wavy fibers in myocardium of dogs with dilated cardiomyopathy

OBJECTIVE: To determine the prevalence of attenuated wavy fibers in the myocardium of dogs with and without dilated cardiomyopathy (DCM). DESIGN: Prevalence survey. ANIMALS: 70 dogs clinically suspected to have DCM (ie, fractional shortening < 25%, absence of echocardiographic lesions other than chamber dilatation, and radiographic or postmortem evidence of congestive heart failure) and 147 dogs with chronic valvular disease (n = 60), congenital heart disease (49), myocardial infarcts (23), myocarditis (8), or endocarditis (7). PROCEDURE: Echocardiography and electrocardiography were performed, and thoracic radiographs were obtained with dogs in left lateral recumbency. Necropsy specimens were examined for attenuated wavy fibers (ie, myocardial cells < 6 microns in diameter with a wavy appearance). RESULTS: 65 of 70 dogs clinically suspected to have DCM were confirmed to have the disease on postmortem examination, and 64 of 65 had attenuated wavy fibers. The remaining 5 dogs were found during postmortem examination to have heart disease other than DCM, and none had attenuated wavy fibers. Only 1 of 147 dogs with heart disease other than DCM had attenuated wavy fibers. CLINICAL IMPLICATIONS: Findings suggest that histologic examination for attenuated wavy fibers may be a useful postmortem test for DCM in dogs. The diagnosis was confirmed in 65 of 70 dogs suspected to have DCM on the basis of standard clinical criteria.     

Hemorrhagic ascites due to congestive heart failure

Ascites due to congestive heart failure (CHF) is characteristically serous in gross appearance. Although hemorrhage into ascites commonly indicates a malignant or inflammatory cause, cirrhosis of the liver is a well known cause of bloody ascites. We report a case of hemorrhagic ascites due to biventricular congestive heart failure in which workup for other causes was negative and hemorrhage cleared after 4 months. In as much as the mechanism of ascites is similar in both cirrhosis and CHF, we propose that a similar mechanism could cause bleeding into ascites in CHF.     

Evidence for cardiomyopathy in familial diabetes mellitus

Recent epidemiologic studies have suggested that cardiac disease in common in diabetics and may often have a noncoronary basis. To examine the status of the left ventricle, 17 adult-onset diabetics of familial type without hypertension or obesity underwent hemodynamic study and were compared to 9 controls of similar age. Of the 17, 12 subjects had no significant occlusive lesions by coronary angiography. From this group eight without heart failure had a modest, but significant, elevation of left ventricular end-diastolic pressure. End-diastolic and stroke volumes were reduced, but ejection fraction and mean rate of fiber shortening were within normal limits. The left ventricular end-diastolic pressure/volume ratio was significantly higher than controls. Afterload increments effected a significant increase of filling pressure compared to normals without a stroke volume response, consistent with a preclinical cardiomyopathy. Four patients with prior heart failure had similar but more extensive abnormalities. None had local dyskinesia by angiography, and lactate production was not observed during pacing-induced tachycardia. Left ventricular biopsy in two patients without ventricular decompensation showed interstitial collagen deposition with relatively normal muscle cells. These findings suggest a myopathic process without ischemia. Postmortem studies were performed in 11 uncomplicated diabetics. Nine were without significant obstructive disease of the proximal coronary arteries, and the majority succumbed with cardiac failure. On left ventricular sections, none had evident luminal narrowing of the intramural vessels. All nine exhibited periodic acid-Schiff-positive material in the interstitium. Collagen accumulation was present in perivascular loci, between myofibers, or as replacement fibrosis. Multiple samples of left ventricle and septum revealed enhanced triglyceride and cholesterol concentrations, as compared to controls. Thus, a diffuse extravascular abnormality may be a basis for cardiomyopathic features in diabetes.     

Coronary artery bypass grafting in cases with poor left ventricular function

From January 1987 through June 1992, 18 patients with poor left ventricular function (left ventricular ejection fraction [LVEF] less than 0.3) underwent elective isolated primary coronary artery bypass surgery. The mean age was 56.4 years (range, 46 to 72 years), and 15 were males and 3 were females. Mean pre-operative LVEF measured by ventriculography was 0.26 +/- 0.03 (range, 0.19 to 0.30). Sixteen patients (88.9%) had a prior myocardial infarction and 9 (50%) had a history of congestive heart failure. Complete revascularization was the goal for all patients, and the mean number of bypass grafts was 3.0 +/- 0.8 per patient. The left anterior descending coronary artery (LAD) was revascularized in all patients. There were no operative deaths. Post-operative LVEF improved significantly from 0.26 +/- 0.03 to 0.42 +/- 0.11 (p = 0.0002), and the regional left ventricular wall motion improved in the diaphragmatic and posterobasal regions (p < 0.01). The patency of the grafts was 93.9% in all, and 100% for LAD. The mean follow-up period was 77 months, and the overall actuarial survival rate was 88.9% at 10 years. During follow-up periods, two patients died of congestive heart failure (CHF), and two required three rehospitalizations because of CHF. The overall cardiac event free rate was 75.8% at 10 years. In patients with poor left ventricular function, surgical revascularization can be performed safely, but congestive heart failure sometimes occurs during follow-up periods and may be the cause of death. Therefore alternate forms of therapy such as cardiac transplantation and/or TMLR should be considered in selected patients.     

Exacerbation of congestive heart failure after administration of polyethylene glycol-electrolyte lavage solution

OBJECTIVE: To report a patient with exacerbation of congestive heart failure after administration of polyethylene glycol-electrolyte lavage solution (PEG-ELS). METHODS: A MEDLINE search was performed, using the terms congestive heart failure (CHF), gastric lavage, colonoscopy, irrigation, and gastroparesis, of English-language articles published from January 1980 through January 1995, as well as review of pertinent articles' bibliographies. CASE SUMMARY: A 45-year-old white woman with left ventricular systolic dysfunction and diabetic gastroparesis received 4 L of a PEG-ELS as preparation for colonoscopy. Within 24 hours she presented to the emergency department with shortness of breath and increased bilateral lower extremity edema. She was admitted and treated with intravenous furosemide therapy. After aggressive diuresis her symptoms returned to baseline and she was discharged. DISCUSSION: The literature search revealed no report of a patient requiring hospitalization as a result of sodium and water retention after bowel preparation with PEG-ELS. CHF is not considered a contraindication to the use of this solution; however, most studies that included patients with heart failure did not describe the degree of left ventricular dysfunction. Our patient's severe CHF, in combination with chronic renal insufficiency, resulted in significant retention of sodium and water. CONCLUSIONS: Patients with severe left ventricular dysfunction and chronic renal insufficiency who are being considered for procedures that necessitate bowel cleansing with PEG-ELS may be at risk for sodium and water retention and exacerbation of CHF.     

Right ventricular aneurysm associated with advanced hypertrophic cardiomyopathy

A previously undescribed case of right ventricular aneurysm (RVA) associated with hypertrophic cardiomyopathy in an advanced stage is reported. The diagnosis was established by noninvasive (cardiac two-dimensional echocardiogram and nuclear MRI) and invasive (cardiac catheterization, angiography, and biventricular endomyocardial biopsy) cardiac examinations, which documented hypertrophied, dilated and hypokinetic biventricular chambers associated with typical histologic findings (histologic hypertrophic cardiomyopathy index of 66%). A prominent narrowing of myocardial arterioles, extended to the right ventricular myocardium, has been identified and has been hypothesized as being responsible for RVA formation.     

Atrial fibrillation and coronary disease

OBJECTIVE: To study the incidence of atrial fibrillation in patients (pts) with angiographic coronary artery disease and its relation with clinical and angiographic parameters. DESIGN: Retrospective study. SETTING: Six hundreds consecutive pts, submitted to diagnostic coronary angiography, performed in Hemodynamic Laboratory of Santa Marta Hospital (from 88/04/03 to 90/05/04). MATERIAL AND METHODS: From six hundreds pts were excluded 43 because they had also valvular heart disease and/or minimal coronary artery lesions. Two groups were considered: Group I-pts with atrial fibrillation (n = 7) and Group II-pts in sinus rhythm (n = 549). We evaluated the following parameters: age, sex, clinical history, basal ECG, cardiac enlargement in chest X-ray, angiographic score of LVF, left ventricular diastolic pressure (LVDP), ventricular aneurysm, mitral regurgitation and number of vessels disease. RESULTS: We only found significant statistically differences between the two groups concerning the following parameters: a) age-mean age was superior in group I (Group I-64.2 +/- 8.2 versus 56.3 +/- 9.6), the number of pts older than 60 years in group I was 75% vs 33.8% in group II (p < 0.02); b) heart failure-the incidence was superior in group I, 37.5% vs 9% in group II (p < 0.03); c) cardiac enlargement in chest X-ray-75% pts of group I vs 22% of group II (p < 0.002); d) moderate to severe mitral regurgitation-25% of pts in group I vs 5% of pts of group II (p < 0.05). CONCLUSIONS: Atrial fibrillation is an unusual rhythm in pts with angiographic coronary artery disease. Its presence is related with age, clinical evidence of heart failure, cardiac enlargement and moderate to severe mitral regurgitation.     

Incidence of primary malignancies other than breast cancer among women treated with radiation therapy for benign breast disease

In addition to left ventricular pump failure and low cardiac output, structural and metabolic alterations of skeletal muscle are thought to contribute to exercise intolerance seen in patients with CHF. Studies using cardiac myocytes have implicated nitric oxide elaborated by inducible nitric oxide synthase (iNOS) as a potential agent associated with the genesis of dilated cardiomyopathy. The present study was designed to locate iNOS in the working skeletal muscle of patients with congestive heart failure. Specific antibodies were used to detect iNOS by immunohistochemistry in skeletal muscle biopsies (m. vastus lateralis) of 37 patients with left ventricular pump failure and 8 normal controls. The expression was restricted to skeletal muscle myocytes and was increased five- to ninefold in patients with chronic heart failure. There was no statistically significant difference in iNOS expression between patients with dilated cardiomyopathy and those with ischemic cardiomyopathy. The finding of a locally increased expression of iNOS and the experimental evidence that NO attenuates the contractile performance of the skeletal muscle suggest that the expression of iNOS may be responsible for the exercise intolerance seen in patients with chronic heart failure.     

Investigation of the selenium status of aborted calves with cardiac failure and myocardial necrosis

Lesions of heart failure, specifically cardiac dilation or hypertrophy along with a nodular liver (chronic passive congestion) and ascites, have been found in 4-5% of aborted bovine fetuses. In this study, a group of 22 such fetuses was compared with groups of aborted fetuses without lesions of heart failure and with nonaborted fetuses obtained from a slaughterhouse. The fetuses were necropsied, tissues were taken for histopathology, and samples were collected for routine bacteriologic and virologic examinations. Liver and kidney tissue was saved for selenium analysis. Histopathologic examinations of myocardium of fetuses with cardiac failure revealed myocardial necrosis and mineralization in 7 fetuses, lymphocytic myocarditis in 5 fetuses, myocardial fibrosis in 5 fetuses, or no microscopic lesions in 5 fetuses. Mean liver selenium levels were 5.5 mumol/kg in the fetuses with heart lesions, 6.5 mumol/kg in the fetuses without heart lesions and 7.5 mumol/kg in fetuses from the slaughterhouse; these differences were statistically significant. The results suggest that selenium deficiency in bovine fetuses may cause myocardial necrosis and heart failure. This study also provides data on normal liver and kidney selenium levels in bovine fetuses from the analyses of 19 nonaborted fetuses.     

Congestive heart failure and ischaemic heart disease treated with trandolapril and verapamil. DAVIT Study Group. Danish Verapamil Infarction Trial

CLINICAL TRIALS WITH VERAPAMIL AND TRANDOLAPRIL: In the Danish Verapamil Infarction Trial II, verapamil improved survival in patients without heart failure but had no effect in patients with heart failure who were receiving diuretic treatment. In the Acute Infarction Ramipril Efficacy study ramipril improved survival in patients receiving diuretic treatment but had no effect in patients not receiving diuretics. COMBINATION WITH THERAPY WITH VERAPAMIL AND TRANDOLAPRIL: By combining verapamil with trandolapril we hypothesized that we could obtain an improvement in left ventricular function and prevent cardiac events. In an open study of 14 patients with angina pectoris and left ventricular ejection fraction below 40%, treatment with trandolapril-verapamil significantly improved left ventricular function. In a double-blind randomized study of 100 postinfarct patients with congestive heart failure the cardiac event rate was significantly lower in verapamil-trandolapril-treated than in the trandolapril-treated patients. These results indicate that the combined treatment with verapamil and trandolapril might be beneficial in patients with ischaemic heart disease and congestive heart failure.     

Differences in the stimulation of NO synthesis during heat shock in genetically different rats]

OBJECTIVES: In certain younger patients with congestive heart failure (CHF), Doppler/echocardiography has identified a "restrictive" pattern of early diastolic ventricular filling characterized by very rapid early filling and a steep deceleration slope. We asked whether a similar restrictive pattern can be identified in very old patients with CHF, and if so, what are its clinical correlates and prognostic implications. DESIGN: Retrospective cohort with prospective follow-up. SETTING: Academic long-term care facility. PARTICIPANTS: Thirty-nine residents with clinical CHF (age 89 +/- 5 (SD) years) MEASUREMENTS: Transmitral Doppler flow, clinical characteristics, recurrent CHF episodes, hospitalizations, and mortality were measured. RESULTS: Fifteen (38%) of the subjects had restrictive filling patterns, characterized by a ratio of early to late flow (E/A) > 1.00 and 24 (62%) had nonrestrictive patterns. The restrictive pattern was associated with a longer duration of CHF, more angina, and higher rate of symptomatic recurrences of CHF. CONCLUSION: A restrictive diastolic filling pattern may represent a late stage in the evolution of congestive heart failure when left ventricular filling pressure is markedly increased. The treatment of CHF in older patients may need to account for different patterns of diastolic filling.     

Selective ETA receptor blockade prevents left ventricular remodeling and deterioration of cardiac function in experimental heart failure

BACKGROUND: Left ventricular (LV) dilation, which is a predictor of survival in humans with chronic heart failure (CHF), is limited by a mixed endothelin ETA-ETB antagonist. Whether selective ETA receptor blockade influences LV dilation is unknown. We determined, in a rat model of CHF, the effects of the ETA receptor blocker LU 135,252 on LV remodeling. METHODS AND RESULTS: Rats were subjected to coronary artery ligation and treated for ten weeks with placebo or LU 135,252 (LU), at a dose of 10 or 30 mg kg-1 day-1. Systolic blood pressure and heart rate (plethysmography) were determined in conscious animals before and after four and ten weeks of treatment. At these time points, cardiac output and LV dimensions were measured in anesthetized rats by transthoracic echocardiography. LV hemodynamics were determined in anesthetized rats after ten weeks. Pressor responses to ET-1 (1 nmol/kg, i.v.) and sarafotoxin S6c (0.3 ng/kg, i.v.) were measured, to assess the efficacy of ET receptor antagonism and the lack of blockade of ETB receptor blockade, respectively. The pressor response to ET-1 was significantly reduced by LU (% change in systolic blood pressure: sham: 9 +/- 1; CHF: 5 +/- 1; CHF LU: 0 +/- 3 and -4 +/- 2% for the low and high dose, respectively). LU did not affect the response to sarafotoxin (CHF: -37 +/- 3; CHF LU: -29 +/- 3 and -28 +/- 2% for the low and high dose, respectively). Both doses of LU decreased systolic blood pressure, but only the high dose of LU reduced heart rate. Furthermore, LU restored cardiac output dose-dependently throughout the study. Both doses of LU limited LV dilatation and deterioration of LV fractional shortening to the same extent. After ten weeks, LU normalized LV end-diastolic- and central venous pressures, but did not affect LV dP/dtmax or dP/dtmin. LU did not prevent the development of cardiac hypertrophy, but reduced LV collagen density. CONCLUSIONS: In this rat model, the selective ETA receptor blocker LU, at the dose of 30 mg kg-1 day-1, reduced blood pressure and heart rate, limited progressive left ventricular remodeling and improved cardiac hemodynamics and function. These effects of LU might have important clinical relevance in the treatment of heart failure.     

Further studies of the relationships among strains classified as taxon 15, taxon 18, taxon 20, (Pasteurella) granulomatis or the (Pasteurella) haemolytica-complex in ruminants using quantitative evaluation of phenotypic data

Congestive heart failure (CHF) patients share several similar features, such as reduced cardiac contractility and neurohumoral activation to compensate the impaired cardiac function. In CHF patients, the cardiac renin-angitensin (RA) system, receptors, GTP-binding proteins, and their effector molecules are inevitably exposed to chronically elevated neurohumoral stimulation. A widely recognized concept is that a chronic increase in such stimulation can desensitize target cell receptors and the post-receptor signal transducing pathway. Recently, reports of several studies have indicated that the inhibitory GTP-binding protein (Gi) can be increased in CHF patients and animal models. Although direct evidence for a change in catalytic protein of adenylyl cyclase has not been found, limited information has suggested a reduced catalytic activity in terminally failing hearts. In this paper, we have assessed the changes in beta AR, GTP-binding protein, catalytic protein and beta ARK. We also examined angiotensinogen mRNA expression in failing heart. It was detected not only in the liver, but also in both the atrial and ventricular heart tissues, suggesting that angiotensinogen is synthesized in the human heart. Immunohistochemical studies revealed a stronger reaction in the endocardial layer of the human left ventricle than in the epicardial layer, and intense immunoreactivity in the conduction system and right atrium. Our experiments revealed a widespread immunopositive reaction for angiotensinogen in the left ventricle of diseased hearts. In the non-diseased heart, ACE and AT1 receptor RNA are present in ventricular muscles. Renin and Ao mRNA could not be detected in the subendocardium of non-diseased left ventricle, but both were present in the left ventricle of diseased hearts. These data indicate that the cardiac RA system plays an important role in the deterioration of cardiac function.     

Determinants of clinical results of mechanical circulatory support for ventricular failure after cardiotomy

To clarify determinants of clinical results of circulatory support for ventricular failure after cardiotomy, we examined 53 patients (33 men and 20 women) who underwent circulatory support for post operative heart failure from 1984 to October 1995. Their ages ranged from 22 to 74 years (mean, 51 years). In 53 patients, 32 had valvular, 19 had ischemic, and 2 had congenital heart disease. After operation, 21 patients underwent venoarterial bypass, 20 underwent biventricular bypass, and 8 underwent left ventricular bypass. The remaining 4 patients received a pulsatile left ventricular assist device. Weaning and discharge rates of the patients by type of support were 52.4% and 28.6% with venoarterial bypass, 75.0% and 55.0% with biventricular bypass, 87.5% and 37.5% with left ventricular bypass, and 75.0% and 50.0% with left ventricular assist device, respectively. The results of this series (67.9% weaning rate and 41.5% discharge rate) were acceptable. Peri-operative variables before and during circulatory support were analyzed multivariately by logistic regression analysis. Selected independent determinants (odds ratio) of significant difference (p < .05) were type of support (7.547) for non weaning and pre support cardiogenic shock (17.246), and type of support (8.780) and support duration (1.487) for mortality. These results suggest that early application before profound shock and appropriate selection of type of support might be key factors in successful circulatory support for ventricular failure occurring after cardiotomy.     

Patellar tendon rupture in five deer

Acute unilateral or bilateral rupture of the patellar tendon was diagnosed in 5 aged obese female Pere David's deer housed at a zoological park. Rupture occurred after an episode of sudden exertion in 4 of 5 deer. Fragmentation, degeneration, necrosis, and mineralization of ruptured patellar tendon fibers were found on histologic examination. Similar changes were often seen in intact contralateral tendons that did not have gross lesions. Patellar tendon rupture in humans is associated with concurrent systemic disease, such as systemic lupus erythematosus, rheumatoid arthritis, or chronic renal failure. Without evidence of underlying systemic disease, spontaneous patellar tendon rupture in deer can be considered a sequela to age-related tendinous degeneration compounded by sudden exertion and chronic overload attributable to obesity.     

An outbreak of Pacheco's parrot disease in psittacine birds recently imported to Campania, Italy: isolation of psittacid herpesvirus 2

The authors describe an outbreak of Pacheco's Parrot Disease (PPD) which occurred in Italy in recently imported psittacine birds and was caused by Psittacid Herpesvirus type 2 (PsiHV2). The authors stress the different susceptibility to the disease in the species involved. This outbreak showed the failure of the vaccine prophylaxis that had been administered to the birds with ordinary commercial preparations containing Psittacid Herpesvirus type 1. The authors emphasize the necessity of producing a vaccine containing inactivated viruses of all known serotypes.     

US case of the day. Diffuse large B-cell lymphoma (posttransplant lymphoproliferative disorder [PTLD])

OBJECTIVE: We describe two new CT findings of congestive heart failure (CHF): enlarged mediastinal lymph nodes and hazy heterogeneous mediastinal fat. MATERIALS AND METHODS: Forty-six patients were retrospectively identified who had major and minor clinical signs of congestive heart failure and had undergone chest CT during their symptomatic period. Two radiologists reviewed the CT studies and by consensus documented the presence or absence of imaging findings of CHF, including interstitial abnormalities, vascular redistribution, axial thickening, pleural effusions, cardiac enlargement, and mediastinal abnormalities. RESULTS: Smooth septal thickening, bilateral pleural effusions, vascular redistribution, and cardiac enlargement were the most common CT findings in patients with CHF. Enlarged mediastinal lymph nodes and hazy mediastinal fat were seen in 55% and 33% of cases, respectively. In a cohort of 17 patients with elevated pressures in the pulmonary capillary wedge documented within 24 hr of CT, CT scans revealed lymphadenopathy in 14 patients (82%) and inhomogeneous fat in 10 patients (59%). CONCLUSION: Enlarged mediastinal lymph nodes and hazy mediastinal fat occur in patients with CHF and are revealed by CT. Lymphadenopathy in patients with CHF does not necessarily indicate malignancy or an infectious process.