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Biomedical subjects

M Gonzalez

Publications and source records attributed to M Gonzalez.

At least 235 records · Page 13Linked to original sources

Fetoacinar pancreatic protein in the developing human pancreas.

The distribution of the 110-kilodalton fetoacinar pancreatic (FAP) protein was examined in 56 pancreases obtained from human embryos and fetuses (ranging 6 from weeks of gestation to full term) and 10 normal adult pancreases. This recently discovered protein is a concanavalin-A-binding glycoprotein that is specific for acinar cells of the pancreas. Using a murine monoclonal antibody for either immunoperoxidase or immunofluorescence procedures, FAP-protein expression was not found in embryos at less than 9 weeks of gestation. At 9-10 weeks, a clear staining was observed in the terminal portions of dilated buds in primitive pancreatic tubular structures (i.e., the site of the first development of the future acinus). At 11-12 weeks, acinar structuration began, and FAP-protein expression increased as shown by the higher number of stained acini and the greater staining intensity. Maximal expression occurred at 15-22 weeks and then gradually decreased; from 28 to 32 weeks until full term, the pancreas was almost negative for this protein. In the adult pancreases, the protein was either absent or only present in acinar cells surrounding the islets of Langerhans. The pancreatic ducts and endocrine cells remained negative throughout gestation and in adults. FAP-protein thus appears to be a marker of acinar-cell differentiation. Its function remains unknown at present. Its close association with the growth and development of the pancreas together with the fact that, in a previous study, it was found to be re-expressed in pancreatitis and in cancer, suggest that it may play a role in developmental regenerative and neoplastic processes in the pancreas.

Adult↗

Prevention of deep venous thrombosis in patients with acute spinal cord injuries: use of rotating treatment tables.

A randomized clinical trial of 15 patients with acute spinal cord injuries was performed to test the hypothesis that rotating treatment tables prevent deep venous thrombosis in this population. Four of 5 control (nonrotated) patients developed distal and proximal thrombi, assessed by 125I fibrinogen leg scans and impedance plethysmography. In comparison, only 1 of 10 treated (rotated) patients developed both distal and proximal thrombosis (P = 0.007). These results suggest but do not prove that rotating treatment tables prevent the development of proximal deep venous thrombosis in spinal cord-injured patients. Larger clinical trials are needed to confirm this heretofore undocumented benefit of rotating treatment tables.

Beds↗

Spinal cord substrate of the turning behavior induced by unilateral lesion of the entopeduncular nucleus.

The neural pathways in the spinal cord mediating circling behavior in animals with unilateral kainic acid lesion of the entopeduncular nucleus were studied in rats. The circling activity toward the lesioned side was indiced by i.p. administration of apomorphine (3 mg/kg). Section of the lateral funiculus ipsilateral to the lesioned entopeduncular nucleus, reduced significantly the rate of drug induced rotations. The above was a common lesion of ventrolateral and dorsolateral transections of the cervical spinal cord. However, the latter transection was more effective than the former to block the circling. On the other hand, lesion of the contralateral spinal cord fails to modify turning behavior. These findings suggest that crossed fibers descending in the dorsolateral quadrant directly from the basal ganglia or mediating synaptic relay in the lower brainstem may be the anatomical substrate of the circling produced by striatal stimulation.

Animals↗

Abnormalities in the regulation of sympathetic activity in human hypertension.

Various biochemical, pharmacologic, and physiologic techniques were used to evaluate the sympathetic tone and reactivity in labile and sustained hypertension in humans. The results of these studies suggest the existence of an important subgroup of hypertensive patients characterized by increased basal sympathetic tone and reactivity to standing. Such abnormalities could be the result of various dysfunctions, involving the activity of central and peripheral cardiovascular sympathetic fibers, the presynaptic modulation of sympathetic fibers (including the interaction with the parasympathetic system), the inactivation of circulating norepinephrine, and the sensitivity of the efferent cells. The increase in circulating norepinephrine in a group of hypertensive patients seems to reflect a functional increase in the sympathetic tone as shown by the presence of hyperkinetic cardiac functions in hyperadrenergic patients (elevated catecholamine levels), while cardiac functions are normal in normoadrenergic patients (catecholamine levels within normal range). Moreover, the better hypotensive response, combined with normalization of the basal and reactive circulating norepinephrine levels following beta-blockade in hyperadrenergic hypertensive patients, strongly supports the participation of the sympathetic system in the maintenance of hypertension in those patients. The identification and characterization of this subpopulation of patients may be helpful in the development of more rational therapeutic approaches and could eventually permit us to devise better predictors of outcome in hypertension.

Blood Pressure↗

Thrombotic thrombocytopenic purpura subsequent to acute myelogenous leukemia chemotherapy.

A woman in complete remission from acute myeloblastic leukemia developed thrombotic thrombocytopenic purpura (TTP) subsequent to the third intensive consolidation cycle of cytosine arabinoside and daunorubicin chemotherapy. The constellation of clinical manifestations indicative of TTP were recognized only in retrospect, as they were initially attributed to more usual complications of bone marrow-ablative chemotherapy. The manifestations, probably fueled by numerous red cell and platelet transfusions, increased at the time of recovery of hematopoiesis. At postmortem examination, characteristic microvascular lesions were found in most organs. Similar thrombotic microangiopathy has been described with mitomycin-based chemotherapy regimens and with the combination of cisplatin, vinblastine, and bleomycin. Successful management of this serious complication of chemotherapy requires increased awareness and earlier recognition.

Antineoplastic Agents↗

Monostotic fibrous dysplasia of the ethmoid. Surgical treatment using a combined endocranial and transfacial approach.

Two cases of monostotic fibrous dysplasia of the ethmoid are presented. This condition is of interest to the rhinologist because of the difficulty of differential diagnosis, its location, and the frequent tendency to local recurrence. The two patients presented in this paper were aged fifteen and seven respectively, with almost identical lesions and with very similar x-rays. A clinical picture of each patient is given, following a brief description of fibrous dysplasia. Special emphasis has been placed on the treatment which is necessarily surgical. In both cases extensive radical surgery of the lesion was performed using a combined craniofacial approach. Finally, a brief evaluation is made of these two cases.

Adolescent↗

Surface marker analysis in acute myeloid leukaemia and correlation with FAB classification.

The immunological phenotype of blast cells in 102 patients with acute myeloid leukaemia (AML) was analysed with a panel of 20 monoclonal antibodies and the enzyme terminal transferase, and correlated with the FAB classification. Although a partial correlation between these two approaches could be observed, almost every morphological group contained patients from more than one immunological phenotype. The M1 and M5a leukaemias showed the most undifferentiated phenotype, often lacking in specific myelomonocytic antigens. The M3 formed a uniform group defined as My7+, Ia-, FMC8+, a phenotype which was also observed in two cases of the microgranular variant. The granulocytic (CDw15) and monocytic (CDw14) antibodies crossreacted with some M5b and M2 leukaemias, respectively. Compared with M5a, the M5b leukaemias showed a large increase in the expression of CDw14 antigen, confirming the validity of the morphological differentiation. Glycophorin-A was present in four out of five M6 leukaemias. TdT activity was demonstrated in 10% of AML cases, with a higher incidence among the monocytic variants: M4 and M5-. Eleven AML were considered as unclassifiable according to the FAB criteria and in seven of them a megakaryoblastic cell population (GP IIb/IIIa+, GPIb+) was demonstrated; this confirms the need to include the subgroup of megakaryoblastic leukaemias within the AML. Finally, a possible immunological classification for AML is proposed.

Adult↗

Immunological phenotype of neoplasms involving the B cell in the last step of differentiation.

The immunological phenotype of diseases involving the last step of B cell differentiation--multiple myeloma (MM, 38 patients) and Waldenström's macroglobulinaemia (WM, 12 patients)--was analysed with a panel of monoclonal antibodies (McAb) as well as conventional markers. Most of the bone marrow plasma cells (80%) from MM patients reacted with the McAb OKT10, FMC8 and FMC48. Plasma cells were consistently negative with FMC7, Leu-1 and mouse rosettes. Ia, B1 and SIg were expressed in a minority of plasma cells (less than 30%) in half of the cases. The circulating neoplastic cells from five MM patients showed a more immature phenotype, with a higher reactivity for OKIa, B1 and increased SIg and a lower expression of CIg, than bone marrow plasma cells. The malignant cells of WM patients differed from those of MM in the reactivity with FMC7, being positive in 10 out of 11 cases, and in their high expression of B1, Ia and SIg with a predominant mu+ phenotype. Mouse rosettes and Leu-1 were positive in one case; OKT10 was positive in three out of five WM patients studied. This phenotype indicates that WM cells correspond to an earlier stage of B cell differentiation than MM plasma cells. The McAb J5 was positive in three out of six MM and two out of four WM analysed. The antigenic differences observed in MM and WM patients support the notion that the cells of the neoplastic clone are able to undergo a certain degree of differentiation.

Antibodies, Monoclonal↗

Influence of dialysis membranes on the convective transport of middle molecules.

Ultrafiltrates from 10 patients in chronic maintenance hemodialysis (7 males and 3 females) were obtained simultaneously using three different membranes: cuprophan, polyacrilonitrile and polysulfone. Middle molecules (MM) chromatographic profiles and total MM amount were determined by gel chromatography and high performance liquid chromatography. The convective transport of MM was similar and not membrane related. Hemofiltration, a predominantly convective solute transfer procedure using high flux membranes such as polyacrilonitrile and polysulfone, in which large amounts of fluids have to be ultrafiltered, is an effective form of MM removal.

Acrylic Resins↗

T-cell subpopulations in patients with monoclonal gammopathies: essential monoclonal gammopathy, multiple myeloma, and Waldenstrom macroglobulinemia.

T-cell subsets defined by monoclonal antibodies (OKT3, OKT4, and OKT8) were analyzed in 117 patients with monoclonal gammopathies--69 multiple myeloma (MM) (30 untreated and 39 treated), 14 Waldenström's macroglobulinaemia (WM), and 34 essential monoclonal gammopathy (EMG) patients. The percentage and absolute numbers of total T-lymphocytes (E+, OKT3+ cells) were within the normal range in all groups except for the treated MM patients, in which a decrease in the absolute number could be observed. The percentages of OKT4+ cells were significantly lower in MM (35 +/- 1.7) than in EMG patients (43 +/- 2) and controls (50 +/- 2). In contrast, OKT8 cells correspondingly increased in MM (38 +/- 1.6) compared with EMG patients (29 +/- 1) and controls (27 +/- 1). The OKT4/OKT8 ratio was lower in MM than that in EMG patients and controls (p less than 0.01) and was shown to be one of the four most significant variables in a linear discriminant analysis used to distinguish between MM and EMG groups. The MM patients in clinical stage III as well as Bence-Jones myeloma patients showed a more pronounced OKT4/OKT8 imbalance. The treatment did not influence the percent distribution of T-cell subpopulations. The patients with WM exhibit an alteration in the distribution of the T-cell subsets similar to the MM patients with a T4/T8 ratio of 1.1 +/- 0.1. This imbalance was more pronounced in WM patients with monoclonal B-lymphocytes in peripheral blood (leukaemic phase of WM). The functional significance of the altered T-cell subsets in MM and WM patients remains to be established, though it is probable that such an imbalance plays an important role in regulating these B-cell proliferations.

Adult↗

Hemodynamic effects of intravenous flecainide in acute noncomplicated myocardial infarction.

Hemodynamic and ECG effects of intravenous flecainide were assessed in 10 patients with acute myocardial infarction and no symptoms or signs of heart failure. The dose was 2 mg/kg injected over a 15-minute period. R-R interval did not change, but PR interval and QRS increased significantly, 28% (p less than 0.0005) and 20% (p less than 0.05), respectively. Duration of P wave also increased significantly, 15% (p less than 0.02). Pulmonary wedge pressure increased 29% (p less than 0.005) and cardiac index and left ventricular stroke work index decreased 9% (p less than 0.05) and 20% (p less than 0.05), respectively. No significant change in mean aortic pressure and systemic vascular resistance occurred. Thus, intravenous flecainide has a mild and transient negative inotropic effect in patients with noncomplicated acute myocardial infarction. It did not induce ventricular failure in this group of patients but should be administered cautiously to patients with overt heart failure or severe conduction defects.

Adult↗

Sulindac and indomethacin suppress the diuretic action of furosemide in patients with cirrhosis and ascites: evidence that sulindac affects renal prostaglandins.

Nonsteroidal anti-inflammatory drugs (NSAID) suppress prostaglandin-dependent renal blood flow and furosemide-induced diuresis in patients with cirrhosis and ascites. Since sulindac may selectively spare inhibition of renal prostaglandins, we evaluated the interactions of acute administration of sulindac or indomethacin with furosemide in 15 patients with cirrhosis and ascites. Prior to furosemide, indomethacin reduced creatinine clearance (by 55%), urinary volume (by 82%), sodium (by 93%), and prostaglandin E2 (by 87%) (all P less than 0.05), whereas sulindac had no effect. However, both drugs reduced furosemide-induced diuresis. Indomethacin appeared slightly more potent in reducing the diuresis (55% v 38%), natriuresis (67% v 52%), and prostaglandin E2 (PGE2) release (81% v 74%). In a similar protocol in healthy subjects, furosemide-induced diuresis and natriuresis were also blunted by both drugs. Thus, under conditions of enhanced prostaglandin activity from furosemide, sulindac does affect renal function. These data suggest that renal function should be monitored in patients with cirrhosis and ascites who receive sulindac as well as other NSAID.

Anti-Inflammatory Agents↗