Search PubMed⌕ Search

Biomedical subjects

F Medina

Publications and source records attributed to F Medina.

At least 37 records · Page 2Linked to original sources

Regulatory role of CD95 ligation on human B cells induced in vivo capable of spontaneous and high-rate Ig secretion.

CD95 ligation elicits apoptotic signals in many cell systems. This study analyzes the effect of anti-CD95 mAb on human cells capable of spontaneous and high-rate Ig secretion. Such cells have been induced in vivo and represent a highly mature B cell stage. Addition of the anti-CD95 monoclonal antibody (mAb) CH11 to tonsil B cells inhibited 50-60% of their spontaneous Ig secretion. The effect was exerted early in the culture and could be reversed by a pre-treatment with a neutralizing mAb. N-acetyl-D-sphingosine (C2-ceramide), although not a close analog, also reduced Ig secretion to a similar extent. The inclusion of a tetrapeptide inhibitor for certain interleukin-1beta-converting enzyme proteases prevented the inhibitory effect of CH11 mAb on tonsil B cells. B cells capable of spontaneous Ab secretion obtained from blood of recently-immunized volunteers were also inhibited by CH11 mAb and C2-ceramide. In contrast, bone marrow (BM) B cells capable of spontaneous Ig secretion were unaffected by these agents. This CD95 ligation-mediated inhibition of tonsil and blood Ig-secreting B cells could not be reversed by cytokines with demonstrated activity on these B cells. Human mature B cells induced in vivo are identifiable as CD38hi cells. Flow cytometric analysis revealed that a fraction of tonsil CD38hi cells expressed low levels of CD95. Moreover, about 20% of these cells exhibited basal apoptosis, as defined by annexin V binding. This phenomenon was markedly increased by CD95 ligation. On the other hand, BM CD38hi cells showed neither CD95 expression nor CD95-induced annexin V binding. These data suggest that CD95 ligation might play a role in the control of human humoral responses by inducing apoptosis in susceptible mature B cells.

ADP-ribosyl Cyclase↗

Acute abdomen in systemic lupus erythematosus: the importance of early laparotomy.

BACKGROUND: Acute abdomen (AA) in systemic lupus erythematosus (SLE) is a challenging diagnostic and therapeutic problem. Most patients are on steroid and/or immunosuppressive treatment and mortality is high. METHODS: We assessed the relationship between the causes of AA in SLE and the SLE disease activity index (SLEDAI). RESULTS: Of 51 patients with SLE and AA, 36 had active disease (Group 1) and 15 inactive disease (Group 2). Group 1 included 19 patients with vasculitis (mean SLEDAI 15.4, range 13 to 24). Three patients with intraabdominal thrombosis and high titers of anticardiolipin antibodies (mean SLEDAI 18.3) and 14 patients with non-SLE-related AA (SLEDAI 8.2, range 5 to 11). Group 2 consisted of 15 inactive SLE patients (mean SLEDAI 1.7, range 0 to 4). Mortality was high in the active group (14 patients) compared with inactive SLE (2 cases). A delay in surgical exploration (39.3 vs 178.6 hours) had a negative influence on the prognosis. CONCLUSIONS: In SLE patients with AA, a SLEDAI score below 5 is indicative of non-SLE-related AA. Elevated aCL were found in patients with intraabdominal thrombosis. AA in inactive SLE is non-SLE-related and has low mortality, provided an appropriate surgical treatment is given. Early laparotomy influences positively the prognosis of SLE patients with AA.

Abdomen, Acute↗

Efficacy of permethrin-impregnated uniforms in the prevention of malaria and leishmaniasis in Colombian soldiers.

We determined the efficacy of the use of permethrin-impregnated uniforms for prevention of malaria and leishmaniasis in a double-blind, randomized study of Colombian soldiers on patrol. In the study of malaria, soldiers were issued impregnated uniforms (i.e., a shirt, an undershirt, pants, socks, and a hat) or uniforms washed in water; the soldiers wore the uniforms day and night for a mean of 4.2 weeks and were observed for an additional 4 weeks. Three (3%) of 86 soldiers wearing impregnated uniforms contracted malaria, whereas 12 (14%) of 86 soldiers wearing control uniforms contracted malaria (P = .015). In the study of leishmaniasis (soldiers were in the area of endemicity for 6.6 weeks and were observed for 12 weeks thereafter), 4 (3%) of 143 soldiers wearing impregnated uniforms and 18 (12%) of 143 soldiers wearing control uniforms acquired disease (P = .002). In the leishmaniasis study, and presumably in the malaria study, breakthrough infections in the treated group were primarily due to bites in unclothed regions of the body (face and hands). Permethrin-treated uniforms were virtually nontoxic (there were only two cases of mild skin irritation among 229 subjects), and impregnation is quick and inexpensive. Impregnation of clothing with permethrin is suggested for nonimmune populations who are likely to be exposed to malaria or leishmaniasis over a period of 1-2 months.

Colombia↗

Salmonella pyomyositis in patients with the human immunodeficiency virus.

Pyomyositis is a common disease in the tropics, mostly due to Staphylococcus aureus. We report two patients infected with the human immunodeficiency virus (HIV) who presented with fever and unilateral limb swelling and in whom pyomyositis was diagnosed in quadriceps and gluteus major, respectively. Salmonella enteritidis was isolated in both, with recurrent episodes of muscle involvement and secondary osteomyelitis in one case. Non-typhi Salmonella pyomyositis may occur in HIV + patients with a relapsing and aggressive clinical course in some cases.

Adult↗

Danazol for systemic lupus erythematosus with refractory autoimmune thrombocytopenia or Evans' syndrome.

OBJECTIVE: To determine the efficacy of danazol for refractory autoimmune thrombocytopenia or Evans' syndrome complicating systemic lupus erythematosus (SLE). METHODS: We studied 16 consecutive patients with SLE and corticosteroid refractory autoimmune thrombocytopenia; 3 patients had coexisting autoimmune hemolysis (Evans' syndrome). Five patients had undergone splenectomy. Danazol was commenced at 200 mg/day, and increased stepwise (maximum 1200 mg/day) until benefit or toxicity was observed. After remission the danazol dose was gradually reduced to 200-400 mg/day. RESULTS: All 16 patients achieved a complete remission (platelet count >100 x 10(9)/l, hematocrit >39%) 2 months after starting danazol (range 6 weeks-8 months). Remission persisted during continued danazol therapy (mean followup 18.2 months, range 2-49 months). One patient with Evans' syndrome required discontinuation of danazol because of jaundice and biopsy proven minimal hepatic necrosis: hemolysis recurred after discontinuation of danazol. CONCLUSION: Danazol is effective for the treatment of autoimmune thrombocytopenia or Evans' syndrome complicating SLE irrespective of splenectomy status. Longer followup will be needed to determine whether the remission persists after withdrawal of danazol.

Adult↗

Renal biopsy in systemic lupus erythematosus: significance of glomerular thrombosis. Analysis of 108 cases.

We investigated the frequency and distribution of glomerular thrombosis (GT) in 108 renal biopsies of lupus patients and correlated this finding with the presence of anticardiolipin antibodies (ACLA). GT was present mainly in the diffuse proliferative form. The activity index was higher in those patients with GT (12.9 +/- 4.7 vs 5.4 +/- 4.1, P < 0.01). The more severe histologic features, necrosis and extracapillary proliferation were also related with GT. In 18 cases with repeated biopsy the best predictors for the subsequent development of glomerular sclerosis were fibrinoid necrosis (P < 0.01), glomerular infiltration (P < 0.01) and an activity index of 10 or more (P < 0.05). GT also showed to be an important prognostic factor for sclerosis, although no statistically significant. ACLA were investigated in 36 patients at the time of renal biopsy. There were nine positive cases and in three of them this finding was related to GT. We can conclude that GT is a relevant feature showing active lupus nephritis and that it is not related to the presence of ACLA.

Adult↗

Clinical pharmacology and economics of recombinant human erythropoietin in end-stage renal disease: the case for subcutaneous administration.

The clinical pharmacology of human recombinant erythropoietin (epoetin) was studied in order to compare the effectiveness of various routes and dosing schedules in dialysis patients. Thirty-six patients received epoetin beta three times a week i.v. for at least 12 wk. The mean dose needed to achieve target hemoglobin was 225 +/- 36 U/kg per week (median dose, 180 U/kg per week). Twenty-eight of 36 patients who were converted to a once-a-week i.v. schedule increased their requirements to 429 +/- 50 U/kg per week in order to maintain a target hematocrit of 33 to 40 vol%. Twelve of 28 patients could maintain their target hematocrit when dosed once a week s.c. at 84 +/- 10 U/kg. The other 16 patients required 137 +/- 15 U/kg per week divided into two doses. In the entire group of 28 patients, the weekly requirement for epoetin was reduced by 50% when the s.c. route was used two or three times a week. Pharmacokinetic studies performed during chronic therapy indicated rapid clearance of erythropoietin (t1/2 of 6.8 +/- 0.3 h). Single i.v. doses greater than 150 U/kg were required to increase basal erythropoietin by 30 mU/mL at 44 h postdosing. With s.c. dosing, such increments in erythropoietin levels frequently persisted beyond 60 h because of prolonged and slow absorption. Pharmacokinetic simulations in conjunction with clinical correlation of the erythropoietic response suggest that the duration that the erythropoietin levels are maintained, and not the absolute peaks, is the primary determinant of efficacy. This may result from nonlinearity in the dose response. Pharmacokinetic simulation also indicated that i.v. dosing could not maintain adequate interdialytic erythropoietin levels, whereas s.c. dosing could. Cost analysis indicated that the use of s.c. dosing two or three times a week at an average total weekly dose of 110 to 120 U/kg is effective treatment of anemia in most dialysis patients.

Adolescent↗

Blast trauma in a child.

In 1986, we cared for a four-year-old boy who was injured in the explosion of an illegal firecracker equivalent to one-third of a stick of dynamite. Although little has been reported on the injuries children sustain in an explosion, we found that this child's injuries were similar to those encountered in adults. This case is presented as illustrative of blast trauma in childhood, and as a review of blast injury.

Blast Injuries↗

Equilibrium oxygen binding to human hemoglobin cross-linked between the alpha chains by bis(3,5-dibromosalicyl) fumarate.

Oxygen equilibrium curves of human hemoglobin Ao (HbAo) and human hemoglobin cross-linked between the alpha chains (alpha alpha Hb) by bis(3,5-dibromosalicyl) fumarate were measured as a function of pH and chloride or organic phosphate concentration. Compared to HbAo, the oxygen affinity of alpha alpha Hb was lower, cooperativity was maintained, although slightly reduced, and all heterotropic effects were diminished. The major effect of alpha alpha-cross-linking appears to be a reduction of the oxygen affinity of R-state hemoglobin under all conditions. However, while the oxygen affinity of T-state alpha alpha Hb was slightly reduced at physiologic chloride concentration and in the absence of organic phosphates, KT was the same for both hemoglobins in the presence of 2,3-diphosphoglycerate (or high salt) and higher for alpha alpha Hb in the presence of inositol hexaphosphate. The reduced O2 affinity arises from smaller binding constants for both T- and R-state alpha alpha Hb rather than through stabilization of the low affinity conformation. All four Adair constants could be determined for alpha alpha Hb under most conditions, but a3 could not be resolved for HbAo without constraining a4, suggesting that the cross-link stabilizes triply ligated intermediates of hemoglobin.

2,3-Diphosphoglycerate↗

A critical examination of the reaction of pyridoxal 5-phosphate with human hemoglobin Ao.

Pyridoxylated normal adult human hemoglobin (HbAo) has been prepared using both oxygenated and deoxygenated HbAo at pH 6.8 and room temperature without the addition of Tris to produce a mixture with P50 of 30 +/- 2 torr and a Hill coefficient of 2.3 +/- 0.1 similar to that of the isolated adult human hemoglobin from the red blood cell. Reduction of the pyridoxylated HbAo in the oxygen-ligated form by sodium borohydride gives unacceptable levels of methemoglobin (i.e., greater than 10%). Excessive foaming and methemoglobin formation can be partially avoided using deoxyHbAo. Reduction with sodium cyanoborohydride is much gentler and gives solutions with less than 5% methemoglobin. Both reducing agents give products with multiple components as shown by analytical chromatography. Radioautography on the isoelectric focusing gels of HbAo treated with 14C pyridoxal 5-phosphate (PLP) shows three major bands for the cyanoborohydride-reduced derivatives and a much more complex mixture of labeled molecules after the sodium borohydride reduction. When pyridoxylated hemoglobin is prepared without reduction, the preparation, after passage through a mixed-bed resin, contains 0.4 equivalents of PLP per heme, and has a P50 of 30 +/- 2 torr and an n value of 2.3 similar to the values found after reduction. Upon anion exchange resin chromatography, the PLP is removed, indicating that the reaction forms a reversible Schiff base. On standing at 4 degrees C for one month, this preparation produces a mixture of HbAo and pyridoxylated HbAo with the original P50. Methemoglobin increased to 3% during this incubation. After four months in the cold, the yield of a single chromatographic species is 70% with 20% methemoglobin. This fraction appears to be stable and can be passed through an anion exchange column without release of the PLP. Separation of the individual chains by reverse-phase chromatography indicates that the addition of PLP to HbAo is directed solely to the beta-chains. This is also the case for the cyanoborohydride reduced derivatives. When NaBH4 is used for the reduction, radioactively labeled PLP is found on both the alpha- and beta-chains.

Hemoglobin A↗

Salmonella septic arthritis in systemic lupus erythematosus. The importance of chronic carrier state.

Salmonella bacteremia is more frequently seen in hospitalized patients with systemic lupus erythematosus (SLE) than in hospitalized patients with other diseases. In our experience. Salmonella enteritidis septic arthritis is more common in SLE than in patients with others connective tissue diseases. We report that 4 of 7 patients with SLE with glomerulonephritis and history of Salmonella enteritidis septic arthritis were chronic carriers of this bacteria, since positive cultures were obtained from feces, bone marrow and bile fluid from 20 84 months after Salmonella arthritis developed. In contrast, none of 24 patients with SLE without a history of Salmonella arthritis were chronic carriers and only one of 12 patients with rheumatoid arthritis had positive bile culture to S. typhi while otherwise being asymptomatic. From our study we conclude that patients with active SLE who have gomerulonephritis are at increased risk of becoming chronic carriers of Salmonella enteritidis and of developing Salmonella arthritis once combined prednisone cyclophosphamide treatment has begun. A chronic Salmonella carrier state must be ruled out in patients with active SLE living in endemic zones, before initiating immunosuppressive therapy.

Adult↗

Preparation of human hemoglobin Ao for possible use as a blood substitute.

A procedure is presented for the preparation of a purified fraction of adult human hemoglobin (HbAo) from one unit of outdated blood. The entire process requires less than 16 h and gives a sterile, endotoxin-free solution of HbAo (approximately 30 g) in a yield of 50%. The solutions are isoionic with a conductivity of less than 15 mu mhos and less than 2 mmol total phosphorus per mol heme. The methemoglobin content is less than 1% and on storage at 4 degrees C rises less than 1% per month.

Adult↗

Removal of bacteria from blood by charcoal hemoperfusion.

E. coli bacteria were successfully removed from contaminated RBC/plasma by using a special matrix of micro-encapsulated albumin activated charcoal (ACAC). Efficacy of removing the bacteria was directly related to the amount of time the contaminated blood was in contact with the charcoal. The data indicated that the bacteria adhered to the ACAC, but that the charcoal was not bactericidal.

Albumins↗