This study was designed to analyze the prevalence of I405V polymorphism in the cholesteryl ester transfer protein (CETP) gene, the blood CETP concentration, the lipoprotein pattern and certain clinical endpoints in two populations, one of young and another of very old individuals. We recruited 100 healthy young adults (median age 31 years) and 100 very old subjects (median age 89 years) and analyzed their DNA for the presence of variants V and I of the CETP gene. Subjects with the V/V genotype had lower serum concentrations of CETP. The frequency of this genotype in the very old was more than double that in the young population. Young adults with the V/V genotype had a less atherogenic lipoprotein pattern [lower total and LDL cholesterol levels, lower apolipoprotein (Apo) B levels, and a lower Apo B/Apo A-I ratio] than those with the I/V or I/I genotypes. The very old subjects, particularly those with the V/V genotype, had larger LDL than the young adults. The prevalence of clinical endpoints was much lower among the very old subjects with the V/V genotype.
Deep venous thrombosis (DVT) is a serious illness sometimes causing death due to acute pulmonary thromboembolism (PTE). Blood stasis of the pelvic vein is a major etiologic factor for DVT. Occasionally a large myomatous uterus can cause compression of the pelvic venous system leading to DVT. We describe a very rare case of massive pulmonary embolism in a 39-year-old woman with multiple uterine myomas and no other recognized risk factors for PTE and DVT. The patient was successfully treated with thrombolytic and anticoagulation therapy associated with total hysterectomy.
Mixed cryoglobulinemia (MC) and glomerulonephritis are the most important extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. MC is a non-neoplastic B cell lymphoproliferative process induced by HCV in an antigen-driven mechanism. The clinical expression of cryoglobulinemia varies from an indolent course to the development of systemic vasculitis. Glomerulonephritis is predominantly associated with MC, and almost always takes the form of membranoproliferative glomerulonephritis. The renal manifestations may range from isolated proteinuria to overt nephritic or nephrotic syndrome with variable progression towards chronic renal insufficiency. The treatment of these virus-related diseases must be individualized on the basis of the severity of clinical symptoms. Antiviral therapy with interferon alpha and ribavirin (the currently recommended treatment of HCV infection) may be successful in patients with mild-to-moderate disease, but sustained responses are uncommon. In case of severe and rapidly progressive disease, although it is capable of suppressing viremia and cryoglobulinemia, antiviral therapy is not fully effective in controlling the inflammatory and self-perpetuating reaction consequent to the deposition of cryoglobulins in the glomeruli and vessel walls. In such cases, a short course of steroids and cytotoxic drugs (with or without plasmapheresis) may be needed to improve the vascular manifestations and decrease the production of cryoglobulins. Once the acute disease flare has been controlled, antiviral therapy may be administered to eradicate HCV, the causative agent of the cryoglobulinemic syndrome. In patients in whom antiviral therapy is ineffective, contraindicated or not tolerated, rituximab, a monoclonal anti-CD20 antibody, may be an alternative to standard immunosuppression.
Although, in the course of the last 50 years, the achievements in the medical field have been astonishing, at the beginning of the third millennium a number of clinical pictures are still left without a precise nosographic origin. In the past, the delay in scientific communication was the main explanation presented for the lack of understanding of clinical pictures of unknown nosographic origin. The history of medicine provides excellent examples of this dispersion of human capital, even if the history of clinical neurology presents "exceptions" (the pictures that we now call de la Tourette's syndrome and Parkinson's disease) that indicate that major clinical syndromes could be clearly detected and relatively rapidly diffused even in the 19th century. Contrary to the past, the delay in scientific communication no longer seems an obstacle to the sharing of medical knowledge. Nevertheless, the problem of the in-depth comprehension of clinical pictures of unknown nosographic origin still remains dominant, mainly because of the limited spread of ample and flexible online accessible databases of unknown nosographic origin clinical syndromes. The need for interactive electronic archives and other artificial intelligence resources in order to promote progress in clinical knowledge is discussed in this paper.
With an eye to clinical applications, it should be noted that the amount of radiation absorbed by a patient during measurement of coronary calcium by multidetector row computed tomography is about 1.5-5.2 mSv in men and 1.8-6.2 mSv in women, whereas the corresponding amounts during coronary artery angiography are 2.1 and 2.5 mSv2. The highest doses are absorbed during angiography performed with multidetector row computed tomography: 6.7-10.9 mSv for men and 8.1-13.0 mSv for women2. According to the studies available, this method adds little information for patients who can already be stratified as being at high or low risk of future coronary events on the basis of clinical and traditional factors, although it may be of aid in indicating the aggressiveness of strategies needed in patients classified as having an intermediate risk (10-20% risk of events at 10 years). Here again, the key factor remains the demonstration of inducible ischemia, because a high calcium score does not necessarily indicate the presence of significant stenoses in an individual patient and cannot, alone, be used as an indication for an angiographic examination3.
Cardiovascular disease and depression, which is frequently encountered in developed countries, are unexpectedly linked and someway interdependent. Although it has been proven that major depression is a risk factor for cardiovascular disease, it is also true that cardiovascular disease may often cause depression. This article provides epidemiological data regarding this phenomenon and focuses on the mechanisms and causes that link these apparently unrelated pathologies. The diagnosis of depression and the difficulty in recognizing it as such are reviewed and several tests useful for this purpose are presented. Finally, the most common antidepressants particularly suitable for cardiac patients are examined along with any possible interactions between these drugs and those currently used for treatment of cardiovascular disease.
Over the last 20 years, many studies explored how the way information is presented modifies choices. This sort of effect, referred to as "framing effects", typically consists of the inversion of choices when presenting structurally identical decision problems in different ways. It is a common assumption that physicians are unaffected (or less affected) by the surface description of a decision problem, because they are formally trained in medical decision making. However, several studies showed that framing effects occur even in the medical field. The complexity and variability of these effects are remarkable, making it necessary to distinguish among different framing effects, depending on whether the effect is obtained by modifying adjectives (attribute framing), goals of a behavior (goal framing), or the probability of an outcome (risky choice framing). A further reason for the high variability of the framing effects seems to be the domain of the decision problem, with different effects occurring in prevention decisions, disease-detection decisions, and treatment decisions. The present work reviews the studies on framing effects, in order to summarize them and clarify their possible role in medical decision making.
Antibodies against factor VIII occur in about 15-35% of hemophilia A patients and induce refractoriness to factor VIII substitution. In very rare cases, factor VIII inhibitors also develop in association with various autoimmune and chronic inflammatory diseases, hematologic malignancies, solid tumors, certain drugs, dermatologic conditions, and in puerperium. In the majority of cases, the clinical course is characterized by severe hemorrhages. Strategies to treat such inhibitors are controversial. We present the case of a patient with generalized pustular psoriasis who developed severe bleeding complications due to an acquired factor VIII inhibitor, after lymph node and skin biopsy. Initial treatment with high doses of human factor VIII concentrate was unsuccessful. Hemorrhage was partially controlled by the administration of recombinant activated factor VII. Subsequently, the human factor VIII was reinitiated in association with immunosuppressive therapy with prednisone. Within 8 weeks this combined modality achieved a complete remission of bleeding, a normalization of coagulation parameters and a complete disappearance of the inhibitor. Our case illustrates that, although the clinical course in patients with acquired factor VIII inhibitor is not predictable and the inhibitor may disappear spontaneously, combined modality with replacement and immunosuppressive therapy should be considered for patients with severe and refractory hemorrhages.
In this issue of Annali Boddi et al.5 report the case of an 81-year-old male admitted to the hospital with extensive hematomas and prolonged activated partial thromboplastin time, with normal prothrombin time and fibrinogen concentration. An activated partial thromboplastin time mixing study did not show any correction, suggesting a coagulation inhibitor and the presence of lupus anticoagulant and anticardiolipin antibodies was excluded. Extremely low factor VIII and elevated factor VIII inhibitor were found. The patient was treated by red blood cells and i.v. methylprednisolone and after a progressive improvement in clinical conditions and laboratory parameters, the patient was Dipartimento di Area Critica Medico-Chirurgica (Direttore: Prof. Giulio Masotti), Universita degli Studi di Firenze © 2005 CEPI Srl (Ann Ital Med Int 2005; 20: IV-V)
Screening procedures performed in research-setting studies have shown that the prevalence of celiac disease in patients with autoimmune thyroid disease is approximately 4-15 times higher than the general population, thus suggesting that patients with autoimmune thyroid disease should be routinely screened for celiac disease. However, the performance of these screening programs has never been evaluated in everyday, clinical-practice setting. We invited newly diagnosed patients with autoimmune thyroid disease, seen at our Hospital, to participate in a serological screening for celiac disease. Two-hundred and thirty-one patients, female to male ratio 8.89:1, mean age 41.3 +/- 18.1 years, range 7.1-80.5 years were included. The number of diagnosed celiac disease was 0. Our results do not support the usefulness of a screening for celiac disease in patients with autoimmune thyroid disease in daily practice, despite the favorable results obtained in research-setting studies. Since screening is a resource-consuming activity, for both patients and clinicians, we suggest that a careful evaluation of the yield of a screening is always warranted before its adoption in the clinical practice.
Our research is based on the critical evaluation of plasma concentration variation of B-type natriuretic peptide (BNP)--in emergency--in paroxysmal atrial fibrillation, acute pulmonary edema, acute coronary syndrome and dilated cardiomyopathy. The aim of our research was to assess if the BNP concentration variation may be useful in the diagnosis and therapy. Peptide synthesis takes place mainly in the ventricular myocardium. We selected 102 patients: 27 control subjects, and 75 admitted to the emergency and reception department for dyspnea and/or precordialgia and/or palpitations. At the beginning they were considered as one group only, and then they were divided into groups according to the diagnosis: 20 with paroxysmal atrial fibrillation with reversion to sinus rhythm in the first week; 20 with acute pulmonary edema; 22 with acute coronary syndrome without electrocardiographic ST-segment changes; 13 with compensated dilated cardiomyopathy. Our research assessed that the BNP activation and secretion are evident especially in patients with heart failure and remains at the high level until the administration of an effective therapy and then they reach a balance with values higher than the standards, while in the paroxysmal atrial fibrillation and in acute coronary syndrome they rise and come back to the standard levels or even at lower levels after the disease solution. For this reason, BNP reiterated measurements allow to assess treatment efficacy, even at home, and to optimize the therapy. The main limit of BNP diagnostic role is in the need of knowing in advance the specific values for each patient. The BNP concentration evaluation in the acute phase is necessary to differentiate patients with dyspnea due to heart failure from those with pulmonary pathologies, while the BNP assessment in the acute coronary syndrome predicted exitus or heart failure manifestations.
From May 1999 to January 2002 we observed 7 patients (4 females and 3 males, median age 55 years, range 31-81 years) with thrombotic thrombocytopenic purpura (TTP). Six patients has been previously undiagnosed and 1 patient was at second relapse. Trigger factors of TTP were identified in 6 patients: ticlopidine treatment (2 patients); an acute cutaneous infection episode immediately before the features of TTP (1 patient); presence of devices: orthodontic (1 patient) and intrauterine contraceptive (1 patient), Mycoplasma urealyticum vaginal infection (1 patient). In all the 7 patients the clinical status was mainly related to the hemolytic anemia, thrombocytopenia and neurological events. One of these patients presented with hemolytic-uremic syndrome with acute renal failure and macrohematuria at onset, another one showed a systemic exanthema post-infection-like. Six out of 7 patients presented with different neurological events: headache, confusion, focal neurological failure. All the 7 patients were promptly treated with plasma-exchange and cryosupernatant plasma infusion. In addition they received prednisone 25-50 mg/day. All the 7 patients achieved a complete remission after plasma-exchange, one relapsed 3 months later and was treated with plasma-exchange again. All the patients are in complete remission with a median follow-up of 36.3 months (range 20-62 months). From these cases we suggest: 1) clinicians should take in mind the suspicion of TTP in every patient with hemolytic, negative direct Coombs test, anemia, thrombocytopenia, high level of lactate dehydrogenase; 2) the treatment of choice is plasma-exchange; 3) the response of treatment is good if therapy is promptly and aggressively administered; 4) the possible role of a trigger factor for removing it and to prevent relapses.
Immune thrombocytopenic purpura (ITP) occurs in 2-3% of chronic lymphocytic leukemia (CLL) patients, whereas autoimmune thrombocytopenia is very rare before the diagnosis of lymphoma. A 67-year-old patient, was admitted to our Department because of purpura on his inferior limbs. Family history revealed arterial hypertension, a previous presence of hepatitis C virus (HCV) antibodies, with no sign of liver damage. Physical examination showed purpura of inferior limbs. Laboratory analysis revealed: marked thrombocytopenia (platelet count 5000/microL); hypogammaglobulinemia (9%, immunoglobulin-IgG 634 mg/dL); presence of HCV antibody (negative HCV-RNA); low-titer anti-nuclear antibody and anti-smooth muscle antibody (1:80); positive cryoglobulin (polycolonal, IgG-IgM, cryocrit 0.5%). Abdomen ultrasound revealed a mild liver steatosis and bone marrow aspirate megakaryocytic hyperplasia. Platelet kinetics study showed a markedly reduced platelet half-life (<1 day) with evident splenic uptake. The patient was treated with steroids, intravenous Ig and immunosuppressive agent (cyclophosphamide) with only temporary effect; a splenectomy was therefore performed with a subsequent durable increase in the platelet count. Two years later, the patient underwent a prostatectomy for prostate cancer and within the pelvic nodal screening the histological examination unexpectedly revealed features of B-cell non-Hodgkin's lymphoma, type CCL/small lymphocytic lymphoma; a bone marrow aspirate showed a monotypic CD5+, CD19+, CD23+ B-cell proliferation confirming the diagnosis of CLL. Six months later, a computed tomography scan revealed multiple pathological node enlargements (1.5-3 cm), compatible with a malignant lymphoma. The marked thrombocytopenia may have been an early expression of the lymphoproliferative disease. Otherwise, the association between CLL and ITP might reflect the underlying role of HCV infection causing an immune dysregulation responsible for both pathologies.
Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autosomal dominant inherited condition of periodic fever and pain. TRAPS is caused by mutations of the TNFRSF1A gene localized at 12p13. The gene encodes extracellular region of the p55 TNF-alpha receptor, resulting in impaired cleavage and down-regulation of the membrane expressed form of the receptor, a diminished shedding of potentially antagonistic soluble form of the receptor and, as a consequence, an unbalanced TNF-alpha action. Most affected patients are from northern Europe. Fever, sterile peritonitis, pleural pain, arthralgia, myalgia, skin rash, and/or conjunctivitis occur during the syndrome episodes; some patients also develop systemic amyloidosis, with some differences among patients. An acute-phase response occurs during the episodes. We describe a case of a 23-year-old Moldavian woman, living in Italy presenting recurrent fever episodes with abdominal pain and skin rash. A biopsy showed small vessel vasculitis. The genetic analysis showed a TNFRSF1A gene (R92Q) mutation. In this paper we report also a literature review on this rare disease.
Skin and soft tissue infections that usually follow minor traumatic events or surgical procedures are caused by a wide spectrum of bacteria. We describe a soft tissue infection caused by a Mycobacterium chelonae in an immunocompetent patient who underwent liposculpture and lipofilling of the gluteal-trochanteric region, emphasizing the importance of clinical suspicion and effective treatment of infection.
who presented at an A&E department with acute dyspnea and showed that a BNP > 100 pg/mL had a sensitivity of 90% and a specificity of 70% in differentiating dyspnea of cardiac origin from that of other causes. The diagnostic accuracy rose from 74 to 81% when BNP levels were added to clinical criteria7. The diagnostic power of BNP was greater than that of either the Framingham criteria or the National Health and Nutrition Examination Survey (NHANES) criteria, which are two of the most widely used sets of diagnostic criteria for heart failure. The study by Coppola et al.4 does, however, highlight some of the difficulties in using BNP for diagnostic purposes, particularly when concomitant diseases are present. First of all, it is important to remember that the diagnostic cut-off may need to be increased when renal function is impaired, for example from > 100 to > 200 pg/mL in patients with a glomerular filtration rate < 60 mL/min10. Another diagnostically relevant aspect is that BNP, as an expression of wall stress, can also identify patients with heart failure with preserved systolic function. The BNP assay does not, therefore, discriminate patients with systolic dysfunction from those with diastolic dysfunction, although for the same NYHA functional class those with altered systolic function seem to have higher BNP levels8. In their study Coppola et al. highlight that patients at discharge and 30 days postdischarge have significantly lower BNP levels, reflecting the efficacy of treatment. Indeed, one of the developing fields of application of BNP assays is that of patients’ management and optimization of treatment. In a study by Mueller et al.5, 452 patients who presented at the A&E department with acute breathlessness were randomized into two groups. The diagnostic strategy used for one group included a single measurement of BNP, whereas the standard diagnostic strategy – not including BNP assays – was used in the other group. Knowing the BNP level in the A&E department reduced the number of days spent in hospital (8 vs 11 days, p = 0.001), the percentage of admissions (75 vs 85%, p = 0.008), the frequency of admissions to intensive care (15 vs 24%, p = 0.01) and costs (5410 vs 7264 dollars, p = 0.006). S.O.D. Medicina Generale 1 (Responsabile: Dr. Carlo Nozzoli), Azienda Ospedaliero-Universitaria Careggi di Firenze © 2005 CEPI Srl (Ann Ital Med Int 2005; 20: II-III)
Juvenile idiopathic arthritis represents a heterogeneous group of autoimmune diseases. It arises before 16 years of age and lasts more than 6 months. We can distinguish many arthritis sub-types. A serious problem in juvenile idiopathic arthritis is skeletal growth retardation, osteopenia and greater risk of developing fractures. Juvenile idiopathic arthritis diagnosis is an exclusion diagnosis. Many conditions can simulate it. First-choice drugs in juvenile idiopathic arthritis treatment are nonsteroidal anti-inflammatory drugs, analgesic and antipyretic drugs. The second-choice drugs are slow-acting antirheumatic drugs, like methotrexate. The use of glucocorticoids is strongly influenced by their side effects, in particular the inhibition of statural growth and the premature appearance of osteoporosis. Recent findings on the central role of tumor necrosis factor-alpha, in particular damage pathogenesis in the course of juvenile idiopathic arthritis, have permitted the development of new therapeutic strategies (infliximab, etanercept), aimed at blocking this cytokine.
The aim of this study was to describe the characteristics of institutionalized patients, the patterns of admission, hospital stay and discharge and the extent of resource utilization before, during and after hospitalization, in an Acute Division of Internal Medicine of a university hospital. All adult patients admitted to the division were consecutively enrolled during a 3-month study period. Patients underwent a multidimensional assessment and data collection concerning admission and discharge patterns, resource utilization, and discharge diagnosis. Three hundred and eighteen patients, with an average age of 73.8 years, entered in the study; the rate of patients both affected by severe cognitive and functional impairment was high (29.9%); 3-4 comorbidity classes were estimated in 70.8% of patients; the most frequent diagnoses at discharge were gastrointestinal (major diagnostic category 6), liver and pancreas diseases (major diagnostic category 7); despite the high rate of comorbidity and severity of illness, the average diagnosis-related groups was low (1.15 +/- 0.59) and also the levels of nursing and personal care provided in the hospital were low (21 +/- 15 and 19 +/- 16, respectively). Median length of stay was 9 days and 3-4 comorbidity classes significantly prolonged hospitalization (p < 0.01). The main critical aspects concerning hospital admissions were the low rates of general practitioner requests of admission (26.7%), the high rates of unplanned readmissions (17.9%) and inappropriate recovery (12.6%). Concerning discharge, only 18.5% of patients had assisted discharges despite the high rates of patients with functional impairment; difficulties at discharge were estimated in 15.0% of patients. Our data suggest to improve the relation between hospital and primary health services in order to assure appropriateness of patient care and optimal use of a specialistic division.
