Therapeutic potential of allogeneic mesenchymal stromal cells transplantation for lupus nephritis.

Animal and human studies have suggested the potential of mesenchymal stromal cells (MSCs) to treat systemic lupus erythematosus (SLE). Here, we present the results of compassionate MSC treatments for three SLE patients to provide the proof of concept for a randomized and controlled clinical trial. Three patients of different ethnicities who suffer from chronic SLE, and who presented with class IV active proliferative nephritis confirmed by biopsy, were treated with allogeneic MSCs from healthy donors. Ninety million cells were infused intravenously into each patient during high and very high activity disease flare-ups and follow-up was continued for 9 months. Multi-organic affectation was quantified by the SLE disease activity index (SLEDAI), and indicators of lupus nephritis activity, such as proteinuria, as well as lymphocyte and monocyte antigens and anti-HLA antibodies were measured at 1, 3, 6, and 9 months after treatment. Proteinuria levels improved dramatically during the 1st month after treatment and the ameliorations were sustained throughout the follow-up period. SLEDAI scores revealed early, durable, and substantial remissions that were complete for two patients and partial for the third patient and that permitted medication doses to be reduced 50-90%. These favourable outcomes support completion of the randomized and controlled MSC trial for SLE.

Postprandial cholecystokinin response in patients with chronic pancreatitis in treatment with oral substitutive pancreatic enzymes.

Cholecystokinin (CCK) response to a test meal should be increased in patients with pancreatic insufficiency, as trypsin is absent from the duodenum. If pancreatic enzymes are added, a restoration of the inhibitory feedback should result in lower levels of CCK. Ten patients with chronic pancreatitis and steatorrhea were studied. CCK basal and postprandial levels were evaluated the day before and 45 and 90 days after treatment with oral pancreatin. Twelve healthy volunteers were included as reference group. CCK basal levels did not vary. CCK response to a test meal was increased in patients before treatment and diminished when oral enzymes were maintained for months even after three days of therapy withdrawal. We conclude that long-term therapy with oral enzymes induces changes in CCK response that do not regress after three days of treatment suspension.

[Preoperative coronary angiography in valve patients. Criteria for indication in a determined population]. / Coronariografía preoperatoria en pacientes valvulares. Criterios de indicación en una determinada población.

BACKGROUND AND PURPOSE: The indication for preoperative coronary angiography in patients with valvular heart disease depends on the prevalence of coronary disease in these patients, which differs among different geographical areas. Our aim was to determine the indication criteria for preoperative coronary angiography in our population. METHODS: We studied retrospectively the prevalence of significant coronary disease in 511 consecutive patients with valvular disease diagnosed by non-invasive methods, who underwent preoperative coronary angiography from August/1991 to July/1996. We analyzed in each patient: demographic data, symptoms and presence of risk factors for coronary artery disease. We considered that preoperative coronary angiography had to be performed on patients who had a coronary artery disease prevalence > or = 5%. RESULTS: Mean age was 64 +/- 10 years (51% male). There was mitral valvulopathy in 135 patients, aortic in 234 and combined mitro-aortic in 142. Angina was present in 30% of patients, and risk factors for coronary artery disease in 52%. The prevalence of significant coronary disease was 20.3%. It was significantly higher in patients with angina (35.3% versus 13.8% in patients without angina) and in those with risk factors (28% versus 12.2% in patients without risk factors); no differences between valvulopathies were found. Age was significantly higher in patients with coronary disease (69 +/- 8 versus 63 +/- 10 years). Multivariate analysis showed three independent predictors for significant coronary disease: 1) age; 2) previous angina, and 3) risk factors. Regarding the prevalence of significant coronary disease in patients neither angina nor risk factors was < 5% in males who were under 60 years old (1 man; 3.3%) and in females under 65 years old (2 women; 3.5%). CONCLUSIONS: In our reference population and in others with a similar cardiovascular profile, preoperative coronary angiography is indicated in males who are > or = 60 years old and in females who are > or = 65 years old, and in younger patients who present angina or risk factors, regardless of the valvulopathy present.

Postprandial glucose-dependent insulinotropic polypeptide and insulin responses in patients with chronic pancreatitis with and without secondary diabetes.

OBJECTIVE: To study GIP and insulin release after a test meal in patients with chronic pancreatitis with and without secondary diabetes mellitus. METHODS: 28 patients with chronic pancreatitis were classified in groups I and II according to the presence or absence of secondary diabetes mellitus. Twelve healthy subjects were included as controls. After a test meal plasma GIP levels and serum insulin levels were determined at 0, 30, 60, 120 and 180 min. RESULTS: A significant diminished GIP response was found in the groups of patients with respect to the control group. No association could be detected with severity of pancreatic insufficiency. Higher values of GIP were demonstrated at 60 and 120 min in patients without diabetes than in patients with it. CONCLUSIONS: An abnormal GIP response is present in cases of chronic pancreatitis irrespective of the presence or severity of pancreatic insufficiency. This response is further affected if secondary diabetes mellitus is present.

[Influence of the degree of aortic valve calcification on the estimate of valvular area using planimetry with transesophageal echocardiography]. / Influencia del grado de calcificación de la válvula aórtica en el cálculo del área valvular mediante planimetría con ecocardiografía transesofágica.

BACKGROUND AND PURPOSE: Continuity equation to measure aortic valve area is limited by poor acoustic window or difficulty in obtaining acceptable Doppler signal. Our aim has been to analyze the accuracy of planimetry by transesophageal echocardiography to calculate aortic valve area and the impact of calcification on results. METHODS: Planimetry of aortic valve area by transesophageal echocardiography has been compared to continuity equation by transthoracic approach and the Gorlin formula in 26 consecutive patients with aortic stenosis. Degree of calcification was qualitatively estimated by the 3 methods and 2 groups were distinguished: group A (mild or moderate calcification) and group B (severe calcification). RESULTS: An excellent agreement between continuity equation and the Gorlin formula was found (mean difference: 0.03 +/- 0.15 cm2). Agreement between transesophageal planimetry and the Gorlin formula was poor (mean difference: 0.14 +/- 0.25 cm2). Planimetry and the Gorlin formula demonstrated an excellent agreement in group A (mean difference: -0.03 +/- 0.17 cm2). By contrast, agreement in group B was not acceptable (mean difference: 0.27 +/- 0.22 cm2). CONCLUSIONS: 1) continuity equation by transthoracic echocardiography is useful in calculating aortic valve area. 2) aortic planimetry by transesophageal echocardiography is an excellent method in noncalcified aortic valves, and must not be used on severely calcified valves.

A case of chronic neutrophilic leukemia with original chromosomal abnormalities.

We report a new case of the unusual myeloproliferative syndrome chronic neutrophilic leukemia (CNL) that met all the criteria generally required for the diagnosis of this entity. The patient presented abnormalities in platelet function not previously reported that may explain the bleeding tendency observed in these patients. The study of neutrophil function suggested also defective mobility and intracellular bactericidal activity. The chromosomal study revealed original abnormalities consisting of multiple chromosomal ruptures and figures. The disease was controlled with busulfan. After 20 months, the patient died of sepsis. An autopsy was performed confirming the diagnosis and ruling out the existence of a cause of a leukemoid reaction, such as cancer or granulomatous disease.

Cardiac size and function in Paget's disease of bone.

We performed non-invasive assessment of cardiac size and function by clinical criteria, standard electrocardiography, chest X-ray, systolic time intervals and echo-cardiography in 27 patients with Paget's disease of bone and in 20 control subjects. The patients were divided into two groups on the basis of the degree of skeletal involvement (less than 15% in Group I and greater than 15% in Group II). No differences in heart size parameters of left ventricular performance were noted between Group I and controls. Cardiomegaly, increased left ventricular diastolic dimension and increased left ventricular mass indicative of ventricular hypertrophy were found in Group II compared to control subjects. In addition, patients with more extensive skeletal involvement had signs of depressed myocardial contractility, increased left ventricular volumes in diastole and systole and enlarged stroke volume, with no differences in echographic cardiac output compared to Group I and controls. The findings show an above normal incidence of cardiac enlargement and disturbed left ventricular performance in patients with Paget's disease and osseous lesions in greater than 15% of skeleton. The clinical implications of the altered cardiac function in patients with Paget's disease are briefly discussed.

[Comparative study between HBsAg positive and HBsAg negative panarteritis nodosa in a series of 25 cases (author's transl)]. / Estudio comparativo entre panarteritis nodosa HBsAg positivo y negativo, en una serie de 23 casos.

Clinical symptoms, biochemical analyses, immunologic status and angiographic findings corresponding to seven HBsAg positive patients with panarteritis nodosa and to 16 HBsAg negative patients with panarteritis nodosa have been compared. HBsAg positive cases showed a statistical significant higher incidences of Raynaud's phenomenon (p less than 0.05) and cardiopathies (p les than 0.05), as well as high occurrence of blood hypertension, artropathy, liver involvement and peripheral neuropathy. Significant differences in relation to cell immunity were not found. Humoral immune disturbances were more common among HBsAg positive patients, being hypergammaglobulinemia (p less than 0.01), IgM increase and decrease of complement factors (C3, C4 and C3PA) the most frequent abnormalities recorded. Angiographic studies revealed a high incidence of microaneurisms for the HBsAg positive group.