Multiple pulmonary neoplasia positive for thyroglobulin

We present, for the first time, a case of carcinoid metastatic pulmonary tumor positive for thyroglobulin. A 73-yr-old woman diagnosed with metastases of probable thyroid carcinoma, manifested by a mediastinic mass and multiple pulmonary nodules positive for radioiodine (I131). Histological analysis showed typical findings of carcinoid tumor with positive immunohistochemistry for neuron-specific enolase, synaptophysin and thyroglobulin, and negative for chromogranin and calcitonin. We underline the exceptional finding of positive reaction for thyroglobulin, and discuss difficulties in differential diagnosis between metastatic differentiated thyroid and carcinoid neoplasms.     

Prophylactic tocainide or lidocaine in acute myocardial infarction

Twenty-nine patients with acute myocardial infarction (AMI) were studied in a randomized double-blind trial of intravenous lidocaine and tocainide, followed by either oral tocainide or placebo without regard to previous therapy, for the prophylaxis of arrhythmias associated with acute infarction. No patient had symptomatic ventricular tachycardia or fibrillation, although 1 patient taking lidocaine was withdrawn from therapy because of breakthrough arrhythmias. One patient in each group died from mechanical complications of AMI. Tocainide was administered to 16 patients and lidocaine to 13. Seven of the 13 patients receiving lidocaine had ventricular tachycardia or accelerated idioventricular rhythm, compared with 2 of 16 receiving tocainide (p less than 0.05). Adverse effects were noted in 11 of the 13 patients receiving lidocaine and 6 of the 16 patients receiving tocainide. The infusions used provided therapeutic levels of lidocaine or tocainide and the transition to oral tocainide was accomplished safely with maintenance of therapeutic antiarrhythmic levels. Thus, tocainide appears to be at least as efficacious and may be safer than lidocaine for the prophylaxis of ventricular arrhythmias associated with AMI. The transition to oral tocainide is well tolerated and can be accomplished with minimal difficulty.     

Assessment of hematologic progenitor engraftment by complete reticulocyte maturation parameters after autologous and allogeneic hematopoietic stem cell transplantation

BACKGROUND AND OBJECTIVES: Hematopoietic restoration after marrow ablation is initiated by the erythroid compartment. However, the absolute microscope counts or corrected percentage of reticulocytes have proven to be poor markers of hematopoietic engraftment. Some reports have highlighted the usefulness of automatic flow cytometry methods to determine highly fluorescent reticulocytes, or mean fluorescence index. In this series of 60 hematopoietic stem cell transplants, we sought the normal kinetics throughout the post-transplant period of the following reticulocyte maturing parameters: highly fluorescent reticulocytes (RETH), immature reticulocyte fraction (IRF), mean fluorescence index (MFI) and also mean reticulocyte volume (MRV). DESIGN AND METHODS: Sixty consecutive patients undergoing allogeneic bone marrow (30 cases) and autologous mobilized stem cell transplantation (30 cases) were studied. Parameters of reticulocyte maturation were measured every other day from the beginning of the conditioning regimen until myeloid engraftment. RESULTS: Nadir values for the analyzed reticulocyte parameters were found between days +4 and +7 and thereafter, increases in these reticulocyte parameters appeared earlier than the rise in neutrophils. We considered erythroid engraftment to have occurred on the day when RETH reached 3%, IRF 10%, MFI 10 and MRV 110 fL. These cut-offs were assigned considering the 25% quartile for each parameter on the day that the myeloid engraftment occurred. The median engraftment days for RETH were +9 and +16, for IRF +9 and +13, for MFI +9 and +13 and for MRV +11 and +13 in autologous and allogeneic procedures, respectively. When compared to standard neutrophil engraftment, IRF and MFI engraftment occurred significantly earlier in all patients. Remarkably, we found a statistical correlation between the day a reticulocyte parameter reached its cut-off and the subsequent day of absolute neutrophil count (ANC) recovery for MFI after allogeneic transplants and for MRV after autologous procedures (p < 0.001 and p= 0.02, respectively). Of all the clinical parameters tested, only the number of infused CD34 cells showed a statistical influence on erythroid engraftment in autologous transplant. INTERPRETATION AND CONCLUSIONS: Early reticulocytes appear sooner than neutrophils after both autologous and allogeneic transplants, and any determined reticulocyte parameter can reliably measure this fraction. Nevertheless, our results show that MRV and MFI cut-offs are useful for determining subsequent myeloid engraftment. These findings could be relevant to decision-making in those patients with primary graft failure heralded by an absence of increasing values of MFI and MRV, indicating very low production of reticulocytes from the graft, who could, therefore, benefit from earlier rescue therapy.     

The 47-kD protein increased in neutrophil actin dysfunction with 47- and 89-kD protein abnormalities is lymphocyte-specific protein

A male child born of related parents suffered recurrent infections because of neutrophil actin dysfunction with increased amounts of a 47- kD protein and decreased amounts of an 89-kD protein (NAD 47/89). The patient and family members were studied to define the nature of the abnormal proteins and to examine their role in the functional defects of neutrophil actin dysfunction (NAD) 47/89 polymorphonuclear neutrophils (PMNs). NAD 47/89 PMNs are defective in motility, microfilamentous cytoskeletal structure, and formyl peptide-induced actin polymerization and express increased amounts of a 47-kD protein and decreased amounts of an 89-kD proteins intermediate abnormality in amount of 47-kD and 89-kD proteins in PMNs from parents and a female sibling suggest the disease is an autosomal recessive disorder. Immunoblots with monoclonal antibody (MoAb1) and polyclonal antibody raised to 47-kD protein showed the 89-kD protein is antigenically distinct from the 47-kD protein and the 89-kD protein is not gelsolin. 125I-actin binding to one-dimensional (1 D) and 2 D gels of PMN proteins from NAD 47/89 proband, family members, and controls showed the 47-kD protein binds actin, is acidic (pl = 4.5 to 4.7), is recognized by the MoAb1, exists on 2-D gels as three distinct actin binding species (MWapp 52 kD, 47-kD, and 44-kD), and is present in control PMNs in lesser amount than in PMNs of NAD 47/89 proband or parents. Immunoaffinity purification of the 47 kD actin binding protein on MoAb1 matrix yielded a multimolecular complex with proteins of MWapp 180 kD, 71 kD, 47 kD and actin. Cloning, sequencing, and expression of a 1.58-kb cDNA selected for MoAb1 reactivity from a HL60 expression library and microsequence of native PMNs, 47-kD actin binding protein showed the overexpressed 47-kD protein is lymphocyte-specific protein 1 (LSP1), which is a known actin binding protein. The results show LSP1 is expressed in PMNs and suggest overexpression of LSP1 is related to the motility and cytoskeletal abnormalities in NAD 47/89 PMNs.     

Genes and kidney disease. Candidate genes

Molecular biology techniques have provided important advances in the search for causal relationships in complex diseases supporting traditional epidemiologic studies. Genetic epidemiology allows us to detect genetic variants that could be related to the onset and progression of different diseases. In cardiovascular and renal diseases, this approach linking traditional risk factors to new described ones and those allelic variants, which contribute to the development of these manifestations permits a better understanding of individual disease susceptibility. This is usually afforded through case-control studies evaluating allelic variants of candidate genes previously associated with the disease. Even in this candidate gene search, association-based methods are more powerful than linkage studies in complex traits if we assume that some of the typed polymorphisms are causative although with subtle phenotypic effects. Some brief examples may illustrate the progress in the understanding of renal and cardiovascular diseases.     

Valsalva maneuver in chagasic patients with documented past medical history of acute chagasic myocarditis

BACKGROUND: We studied the heart rate responses to the Valsalva maneuver in eight patients with documented past medical history of acute Chagas' disease. METHODS: Four patients were studied 8-21 months after the acute episode and four, 58-68 months thereafter (age 25+/-8.65 years M+/-S.D.). Seventeen healthy subjects of similar age were included as controls (age 27+/-7.5 years, P=NS). RESULTS: Baseline heart rate was higher in chagasic patients (88+/-15 beats/min) compared to controls (69.8+/-9.8, P=0.001). Maximum heart rate at phase II of the maneuver was also higher (114+/-16.3 vs. 101.5+/-9.9, P=0.02). Minimum heart rate at phase IV was, however, not different (57.4+/-10.4 vs. 63.3+/-7.3 P=NS). The magnitude of the absolute negative change at phase IV was larger in the chagasic patients, although, not different (-50.8+/-13.8 vs. -44+/-13.8, P=NS). The Valsalva index was 1.81+/-0.26 in the chagasic patients and 1.82+/-0.42 in the controls (P=NS). Minimum heart rate at phase IV correlated neither with the baseline heart rate (r=-0.28, P=NS) nor with the Valsalva index (r=-0.40, P=NS). The magnitude of the absolute negative change during phase IV correlated with, both, the baseline heart rate (r=-0.80, P<0.01) and the Valsalva index (r=-0.95, P<0.0001). The higher baseline high rate influenced the magnitude of the negative heart rate change, but not the minimum heart rate reached at phase IV. CONCLUSIONS: Chagasic patients with proven past medical history of acute Chagas' disease had unimpaired heart responses to the Valsalva maneuver.