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Biomedical subjects

J Molina

Publications and source records attributed to J Molina.

At least 19 recordsLinked to original sources

The treatment of advanced neuroblastoma. Results of the Spanish Neuroblastoma Study Group (SNSG) studies.

The Spanish Neuroblastoma Study Group has conducted a study on advanced neuroblastoma (N-I-87), which included 33 stage III and 60 stage IV neuroblastoma children more than 1 year of age, enrolled between October 1987 and April 1992. They were staged according to Evans and treated with induction chemotherapy (IC) consisting of 3 courses of cyclophosphamide-doxorubicin alternating with 3 of high-dose cisplatin-teniposide. Evaluation after IC and surgery demonstrated an overall response rate of 88% for stage III and 69% for stage IV. In the latter, complete responses and good partial responses were 33 and 14%, respectively. After surgery, children received maintenance chemotherapy (all stage III except 2 and 30 stage IV) or autologous bone marrow transplantation (ABMT) (11 stage IV), the distribution was not randomised. Probability of survival at 5 years was 0.60 +/- 0.12 for stage III and 0.24 +/- 0.07 for stage IV. A significant difference in survival at 5 years was found between "good responders" and "non-responders" to initial chemotherapy.

Adolescent

Influence of incubation on the chromatin condensation and nuclear stability of human spermatozoa by flow cytometry.

Flow cytometry analysis was used for the accurate and objective evaluation of sperm chromatin condensation and chromatin stability of sperm nuclei. It was also possible to determine the influence of incubation on sperm chromatin. Different types of spermatozoa were studied: unprocessed spermatozoa at 1 and 45 min after ejaculation, after swim-up (migrated), spermatozoa incubated for 6 h in non-capacitating conditions (aged), or in B2 medium (capacitated) or B2 medium followed 1 h later with A23187 (reacted). All types of spermatozoa were analysed before and after treatment with various decondensation agents: sodium dodecyl sulphate (SDS), SDS plus EDTA and SDS plus disulphide-reducing agent [dithiotreitol (DTT)]. Sperm nuclei were enzymatically isolated and stained with propidium iodide. Three flow cytometric parameters were then measured: forward light scatter (cellular size), side light scatter (cellular complexity) and fluorescence (uptake of propidium iodide). Fluorescence was the most suitable parameter to study the degree of condensation and resistance to decondensation of DNA in the spermatozoa. Unprocessed spermatozoa 1 min after ejaculation underwent decondensation by all assessed treatments (anionic detergent, chelating or disulphide-reducing agents). Unprocessed spermatozoa 45 min after ejaculation and migrated spermatozoa did not undergo decondensation with SDS treatment, but decondensation occurred after treatment with SDS+EDTA or SDS+DTT. Spermatozoa incubated for 6 h under both non-capacitating (aged spermatozoa) and capacitating conditions (capacitated spermatozoa) and reacted spermatozoa were decondensed only after treatment with SDS+DTT.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcimycin

Campylobacter infections in HIV-infected patients: clinical and bacteriological features.

OBJECTIVE: To study the clinical and bacteriological features of Campylobacter infections in HIV-infected patients. DESIGN: A retrospective analysis (1989-1992), followed by a prospective analysis (1992-1994). SETTING: Hospital HIV inpatient unit. PATIENTS AND METHODS: All patients with Campylobacter spp. identified by the laboratory of microbiology at Saint-Louis Hospital, Paris were studied, and their clinical features as well as their response to therapy recorded. RESULTS: During the study period, Campylobacter infection was documented in 38 HIV-infected patients, 76% of whom had AIDS. Campylobacter spp. was isolated from stools in 36 cases and from blood cultures in four cases. Species identification yielded C. jejuni (84%) and C. coli (16%). High-level resistance to quinolones was frequently observed (21%), but resistance to erythromycin (3%) and tetracycline (5%) was rare. Diarrhoea, fever and abdominal pain were the main clinical features of infection. Other intestinal pathogens were found in 42% of patients. Most patients had an acute illness with rapid resolution under appropriate antimicrobial therapy. However, eight patients (21%), experienced chronic diarrhoea with persistent isolation of Campylobacter and in vivo selection of resistant strains, requiring multiple courses of antibiotics. CONCLUSIONS: Campylobacter usually cause acute diarrhoea in patients with HIV infection. Antimicrobial therapy should be guided on in vitro susceptibility testing because of the prevalence of antibiotic resistance. Despite appropriate therapy, some patients will present with prolonged diarrhoea and in vivo selection of multiresistant isolates.

AIDS-Related Opportunistic Infections

Thyroid hormones in fibrocystic breast disease.

This study was undertaken to evaluate the role of thyroid hormones in fibrocystic breast disease. The concentrations of thyroid-stimulating hormone (TSH), thyroxine (T4), free T4 and free triiodothyronine (T3) were determined in serum of 50 women with fibrocystic breast disease without macrocysts (cysts of over 3 mm diameter) and in the serum and breast cyst fluid (BCF) of 60 women with fibrocystic breast disease and macrocysts. Possible relationships between thyroid hormones and estradiol, dehydroepiandrosterone sulfate, testosterone, progesterone and 17-hydroxyprogesterone in the BCF also were analyzed. Serum thyroid hormone levels did not differ between the two groups. Free T3 levels were higher in BCF than in serum (p < 0.001), whereas T4, free T4 and TSH concentrations were lower in BCF as compared to serum (p < 0.001). Cysts were divided according to their K+/Na+ ratio because a ratio above 3 represents a predictor of malignant transformation. Free T3 concentrations were higher in BCF than in serum, in both low K+/Na+ cysts and in cysts with a K+/Na+ ratio above 3; those cysts with a high K+/Na+ ratio had the highest free T3 concentration. Free T3 in cysts correlated positively to the K+/Na+ ratio (r = 0.831; p < 0.001). Multiple linear regression analysis demonstrated that the concentration of free T3 in BCF was predicted statistically by the positive regression coefficient for the estradiol concentration. No candidate variable was included in the model to predict concentrations of TSH, free T4 or T4 in BCF. These data suggest an important role of free T3 in the physiology of fibrocystic breast disease.

17-alpha-Hydroxyprogesterone

Coexistence of human immunodeficiency virus infection and systemic lupus erythematosus.

A variety of rheumatic disorders has been reported during the course of human immunodeficiency virus (HIV) infection; however, its association with systemic lupus erythematosus (SLE) is extremely rare. The effect of HIV infection on CD4 lymphocytes may ameliorate SLE activity and spur remission. We observed 2 patients with SLE who later developed HIV infection. Both patients' lupus went into remission, and their course was complicated by aseptic necrosis of the bone. These findings suggest that HIV infection may have an important effect on the natural course of SLE and may also have a pathogenic role in avascular necrosis.

Adult

Intracystic lipidic profile in fibrocystic breast disease.

This study was designed to investigate the lipidic profile of fibrocystic breast disease. The study entailed measuring total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C) and triglyceride levels in the serum of 50 women with fibrocystic breast disease without macrocysts, and in the serum and breast cyst fluid of 60 women with fibrocystic breast disease and macrocysts. The relationships between the lipids analyzed in the cyst fluid and intracystic estradiol, progesterone, dehydroepiandrosterone sulfate, testosterone and 17 alpha-hydroxyprogesterone were studied. No differences were found for serum lipid levels between the two groups of patients. The levels of total cholesterol and HDL-C were found to be significantly higher, and the levels of triglycerides and VLDL-C significantly lower in breast cyst fluid compared to serum. In cysts with high potassium concentrations, we found a higher concentration of cholesterol and HDL-C and a lower concentration of LDL-C than in cysts with a potassium/sodium ratio < 3. No significant differences were found in cystic levels of triglycerides and VLDL-C. Multiple regression analysis showed that the only intracystic variable, which was, in part, positively responsible for the hormone levels measured, was HDL-C. These data suggest that local steroidogenesis in fibrocystic breast disease uses HDL-C as the substrate.

17-alpha-Hydroxyprogesterone

[Microbiologic diagnosis of typhoid fever: report on an outbreak].

BACKGROUND: The incidence of typhoid fever has greatly fallen in Spain although sporadic cases and limited outbreaks may be observed. The usefulness of the serum agglutinin studies for the diagnosis of this disease has been questioned by many authors. However, this diagnosis criteria continues to be used in Spain. The usefulness of blood cultures, stool cultures, urinecultures and serological test is herewith compared. METHODS: Three groups were prospectively studied: 18 patients with typhoid fever from one single outbreak, 50 blood donors, and 24 patients with other infections. Blood, stool culture, urinecultures and serology (agglutination) were carried out in the first group and in the other two groups serological test were used to determine the cut-off points and study cross reactions. RESULTS: Blood culture was found to be the most sensitive technique (94%) followed by stool culture (53%). No positive urineculture of seroconvesrion were observed. The cut off points accepted following the study of the donors were 1/160 or greater for the O antigen and 1/320 or greater for the H antigen. Two false positive for the O antigen and 3 for the H antigen were observed in the 24 patients with other infections. CONCLUSIONS: When suspecting typhoid fever, the combined use of blood culture and stool culture is recommended. The usefulness of serological test in our area lays in the observation of seroconversion associated to a compatible clinical picture. Its performance should not being considered as adequate in unspecific febrile syndromes.

Adolescent

Lack of expression of HLA antigens on immature germ cells from ejaculates with antisperm antibodies.

PROBLEM: The lack of expression of HLA antigen on immature germ cells from ejaculates with antisperm antibodies has been reported. METHOD: The expression of human leukocyte antigens on immature germ cells from ejaculates with antisperm antibodies (ASA) was investigated by indirect immunofluorescence using a panel of monoclonal antibodies (MAb) and automated flow cytometry. Patients were divided into two groups: fertile (prevasectomic; N = 10), and ejaculates with ASA (10 samples with IgG and IgA ASA, and five semen samples with only IgG ASA). ASA were detected on sperm using the direct immunobead test. After centrifuging semen samples on a Ficoll-Hypaque gradient, round cells obtained at the gradient interface were gated by a flow cytometer. The "immature germ cell window" was defined in terms of cellular volume and granularity. RESULTS: The percentage of gated round cells from semen samples that reacted with anti-CD45 was always less than 5%, and with anti-CD44 less than 3%. This lack of reactivity of gated round cells with MAb specific for leukocytes and epithelial cells suggests that they were immature germ cells. Immature germ cells were unreactive with W6/32 and anti-beta-2-microglobulin MAb, which suggests that these cells do not express HLA class I molecules. Similarly, no reactivity of the immature germ cells with the MAb that recognize HLA class II molecules was found. No significant differences were observed in the expression of HLA molecules on immature germ cells between the different semen samples studied: fertile, and ejaculates with ASA. CONCLUSION: The presence of ASA in ejaculate is not associated with abnormal HLA antigen expression on immature germ cells.

Animals

[Alloimmune neonatal neutropenia: flow cytometry study of the 1st patient described in Spain with identification of an anti-NA1].

A strong antibody was found in a mother (first pregnancy) who had a severe neutropenic baby. The father's granulocytes were typed by flow cytometry as NA1+, NA2+, NB1+, ND1+ and the mother as NA1-, NA2+, NB1+ and ND1+. The antibody was identified as anti-NA1 by us, and confirmed later by a reference laboratory. The serum reacted with 54.8% of the 31 donors tested. The same antibody was found in the child's serum 35 days after birth, and the reactivity was stronger than in the mother's serum. The HLA-DR, DQ from the mother was DR3, DR7; DR52, DR53; DQ2. The baby's granulocytes were recovered slowly over a four-month period, but the course was benign without any specific treatment. Five months after birth, with recovery, the child's serum became negative and his granulocytes were confirmed as NA1+. Due to the difficulties in fully diagnosing and working with granulocytes we suspect that there are undetected cases; only one case has been recorded in Spain before.

Female

Immunoprophylactic trial with combined Mycobacterium leprae/BCG vaccine against leprosy: preliminary results.

In an attempt to find a vaccine that gives greater and more consistent protection against leprosy than BCG vaccine, we compared BCG with and without killed Mycobacterium leprae in Venezuela. Close contacts of prevalent leprosy cases were selected as the trial population since they are at greatest risk of leprosy. Since 1983, 29,113 contacts have been randomly allocated vaccination with BCG alone or BCG plus 6 x 10(8) irradiated, autoclaved M leprae purified from the tissues of infected armadillos. We excluded contacts with signs of leprosy at screening and a proportion of those whose skin-test responses to M leprae soluble antigen (MLSA) were 10 mm or more (positive reactions). By July, 1991, 59 postvaccination cases of leprosy had been confirmed in 150,026 person-years of follow-up through annual clinical examinations of the trial population (31 BCG, 28 BCG/M leprae). In the subgroup for which we thought an effect of vaccination was most likely (onset more than a year after vaccination, negative MLSA skin-test response before vaccination), leprosy developed in 11 BCG recipients and 9 BCG/M leprae recipients; there were 18% fewer cases (upper 95% confidence limit [CL] 70%) in the BCG/M leprae than in the BCG alone group. For all cases with onset more than a year after vaccination irrespective of MLSA reaction the relative efficacy was 0% (upper 95% CL 54%; 15 cases in each vaccine group). Retrospective analysis of data on the number of BCG scars found on each contact screened suggested that BCG alone confers substantial protection against leprosy (vaccine efficacy 56%, 95% CL 27-74%) and there was a suggestion that several doses of BCG offered additional protection. There is no evidence in the first 5 years of follow-up of this trial that BCG plus M leprae offers substantially better protection against leprosy than does BCG alone, but the confidence interval on the relative efficacy estimate is wide.

BCG Vaccine

Persistence of hepatitis B virus DNA after reduction of viral replication in serum and liver.

Liver and serum samples from 67 children with hepatitis B chronic infection, whether or not treated with recombinant interferon, were analyzed for the presence of hepatitis B virus DNA. After follow-up, 44/67 (66%) still had serum and liver viral DNA; 23/67 (34%) were negative for serum hepatitis B virus DNA. Of the 23 children in the latter group, liver biopsy was available in 21 and viral DNA was not detected by Southern-blot in 20. In the remaining patient, viral DNA was in an episomal nonreplicative form. Polymerase chain reaction was performed in the 21 serum samples negative for viral DNA by conventional techniques and in the 21 liver samples (20 negative for hepatitis B virus DNA and 1 with episomal nonreplicative form). All liver samples resulted in a positive reaction to viral DNA by this technique. Serum viral DNA by polymerase chain reaction was detected in 15/21 (71%) of these patients. The mean of alanine aminotransferase values was similar in patients with or without hepatitis B virus DNA in serum by polymerase chain reaction. In summary, in the majority of the patients who respond to the therapy, there is a persistence of viral replication detected by polymerase chain reaction. This fact explains the persistence of serum HBsAg in these patients. However, more studies are necessary to determine the meaning of the presence of hepatitis B virus DNA that is only detectable by polymerase chain reaction.

Adolescent

Long-term follow-up of hepatitis B chronic carriers who responded to interferon therapy.

We studied the long-term outcome of patients with chronic hepatitis B virus (HBV) infection who responded to interferon (IFN) therapy. Between 1983 and 1988, 120 patients were included in 5 different protocols; 94 patients were treated with IFN and 26 were controls. Loss of serum HBV-DNA was considered a partial response and occurred in 34 of the treated patients and in 10 of the controls. Only the partial-response patients were followed up for 14-64 months (mean 46 months). HBeAg disappeared in 32/34 of the partial-response treated patients and in 9/10 of the controls. During the follow-up period, 6/34 (18%) treated patients and 1/10 controls suffered a reactivation of the disease with reappearance of HBV-DNA. Only 8/34 (23%) treated patients and 1/10 of the controls lost HBsAg; no statistical differences were observed in baseline characteristics between HBsAg-negative patients and patients who remained HBsAg-positive. Of eight HBsAg-negative treated patients, four were serum HBV-DNA-negative upon polymerase chain reaction and thus formed the HBsAg-negative control cases. Although the frequency of HBsAg loss in treated patients is relatively low, the improvement in liver disease obtained from IFN therapy is sustained over a long period.

Adolescent

Analysis of hepatitis B virus DNA, liver disease and influence of antibody to hepatitis C virus in anti-HBe chronic carriers.

Hepatitis B virus DNA (HBV-DNA) in serum was studied in 67 anti-HBe patients using dot-blot hybridization, a modified technique and polymerase chain reaction (PCR). All patients had abnormal aminotransferase (ALT) levels. Serum HBV-DNA was detected in 14/67 cases by dot-blot and in 39/67 (DNA probe) and 45/67 (RNA probe) using the modified technique. The RNA probe was more sensitive than the DNA probe when they were compared, using serial dilutions of HBV-DNA of known concentration (0.1 pg vs 1 pg, respectively). HBV-DNA was found by PCR in 57/67 patients. Ten patients were negative to serum HBV-DNA. The ALT level was significantly higher in patients with serum HBV-DNA by dot-blot as compared to those who had serum HBV-DNA by the modified technique and PCR. With respect to the presence of anti-HCV, 6/67 had anti-HCV confirmed by RIBA test. These 6 patients had serum HBV-DNA. The route of acquisition of HBV infection in anti-HCV positive patients was by parenteral exposure in 67% of the cases and 15% in HCV negative (p less than 0.05). All patients were negative to nonorganic specific autoantibodies. In summary, most of the anti-HBe patients (85%) had viral replication. HCV superinfection plays a minor role in the activity of liver disease.

Adult

Coronary artery disease risk factors in Yaqui Indians and Mexican Americans.

The prevalence of coronary artery disease risk factors in adults was studied in Yaqui Indians and Mexican Americans. The risk factors studied included hypertension, diabetes, hypercholesterolemia, smoking, and sedentary life-style. Subjects included 94 Mexican Americans, 44 Yaqui Indians, and 12 of mixed or other ancestry. Mexican Americans had higher rates of smoking (21.3% versus 11.4%) and hypercholesterolemia (9.4% versus 4.8%) than did Yaqui Indians although neither comparison was statistically significant. Yaqui Indians had twice the risk of diabetes (40.5% versus 19.8%, P less than .05). When looking at both races combined, men smoked at six times the rate of women (36.4% versus 6.3%, P less than .05). Of all those tested, only 6% had no risk factors, and 88% were classified as having a sedentary life-style. Achieving increased levels of exercise in the population studied would appear to hold the most promise for reducing coronary artery disease risks.

Adult

Prospective, randomized controlled trial of interferon-alpha in children with chronic hepatitis B.

Thirty-six children with chronic hepatitis B were entered into a randomized controlled trial of recombinant human interferon-alpha. All patients had hepatitis B virus DNA and increased levels of aminotransferases in serum for at least 1 yr. Twelve children received 10 MU of interferon-alpha 2b/m2 body surface area three times a week (group I); 12 children received 5 MU/m2 under the same conditions (group II); and 12 children served as controls (group III). During 6 mo of therapy, 12 of 24 (50%) treated patients (7 from group I, 58%, and 5 from group II, 42%) and 2 of 12 (17%) controls lost hepatitis B virus DNA from serum and subsequently remained negative. Comparison of the rate of response in group I vs. controls showed a statistically significant difference (p less than 0.05). Eleven of 12 (92%) treated patients who cleared hepatitis B virus DNA from serum lost HBeAg, seroconverted to anti-HBe and had improvement in liver histological findings with loss of hepatitis B virus DNA from liver. In 10, serum ALT levels became normal. Interferon-alpha was well tolerated and all children finished therapy. These findings indicate that a 6-mo course of interferon-alpha is effective in inducing a serological, biochemical and histological remission of disease in approximately 50% of children with chronic hepatitis B.

Biopsy

[Barrett's esophagus does not revert after medical or surgical therapy for gastroesophageal reflux].

An evaluation was made of 34 patients having Barrett's oesophagus. Medical therapy consisted of antacids, H2 blockers, orthopramides, and postural measures (20 cases, mean follow-up 2.9 years). A Nissen fundoplication was done in 14 cases (mean follow-up 2.5 years). Clinical, endoscopic and histologic evaluation was done in all patients and pH measurements also done in all operated cases. Clinical results have been excellent in 70% of medically treated patients and in 100% of surgically treated ones, pH measurements were between normal limits in all operated patients. However, recovery of the normal epithelium did not occur in any case, except for some partial improvement in one patient treated surgically.

Adolescent

Prevalence of liver disease and infection by hepatitis B, delta virus, and human immunodeficiency virus in two Spanish penitentiaries.

We studied the prevalence of liver disease and the carrier state for hepatitis B (HBV), delta virus (HDV) and HIV-1 infection in two Valencian penitentiaries, one for males and the other for females. Serological results were correlated with history of intravenous drug addiction, alcohol abuse, homosexuality or prostitution (high-risk groups), and duration and number of internments. A high prevalence of increased transaminase levels (52.2%) and serological markers for HBV infection (66.5%) was observed amongst the inmates, figures being higher amongst high-risk individuals and inmates confined for more than 6 months. No signs of HDV or HIV-1 infection were found amongst the prison staff. Anti-HIV-1 positivity was observed most frequently amongst individuals combining both drug abuse and homosexuality/and prostitution.

Acquired Immunodeficiency Syndrome