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Biomedical subjects

J Serrano

Publications and source records attributed to J Serrano.

At least 109 records · Page 6Linked to original sources

Autologous reconstitution with BCR-ABL-negative haematopoiesis after T cell-depleted allogeneic BMT for CML.

We report a patient with Ph chromosome-positive CML who underwent an HLA-identical T cell-depleted BMT from a sibling donor. DNA polymorphism analysis showed complete donor chimaerism after BMT, followed by mixed chimaerism of granulocytes, natural killer cells and B lymphocytes, with T lymphocytes host-derived at day +120 post BMT. From month +20 haematopoiesis was exclusively of host origin in all cell lineages. RT-PCR was used in order to detect residual disease, but at the time, analysis did not show BCR-ABL transcripts. This case is unusual in that non-malignant stem cells of recipient origin survived the transplant and reconstituted haematopoiesis after BMT. Two years post transplant, no molecular or haematological relapse was documented. The observation that subsequent recipient recovery without molecular relapse implies that, at least in this case, the GVL effect can occur in the absence of donor T cells.

Bone Marrow Purging↗

Iron absorption in patients with Zollinger-Ellison syndrome treated with long-term gastric acid antisecretory therapy.

BACKGROUND: Gastric acid secretion is important for absorption of dietary non-haem iron, and iron deficiency is common in gastric hyposecretory states such as after gastric resection. It is not known if prolonged, continuous treatment with potent acid suppressants such as omeprazole will lead to iron deficiency or lower body iron stores. AIM: To assess iron stores and the occurrence of iron deficiency anaemia in patients with Zollinger-Ellison syndrome (ZES) treated long-term with gastric antisecretory drugs. METHODS: One hundred and nine patients with ZES but without previous gastric resections were studied. All patients underwent assessment of acid control on antisecretory agents, determination of tumour extent, evaluation of haematological parameters (Hct, haemoglobin, WBC, MCV, MCHC), and determination of serum iron parameters (iron, ferritin, transferrin, iron/ transferrin ratio). Acid control values for the last 4 years were reviewed, the presence or absence of acid hyposecretion determined using three different criteria and this result correlated with haematological and iron parameters. RESULTS: Eighty-nine patients were taking omeprazole, nine patients were taking histamine H2-antagonists and 11 patients were taking no drugs following curative resection. The mean duration of omeprazole treatment was 5.7 years (range 0.7-12.5 years) and total duration of any treatment was 10.1 years (range 0.7-21 years). Acid hyposecretion was present by at least one criterion in 45% of patients. There were no significant differences between patients with or without acid hyposecretion, taking or not taking omeprazole, having different durations of omeprazole treatment or different durations of total time receiving any antisecretory treatment, for any serum iron parameter, haematological parameter, or for the frequency of iron deficiency. Males and females did not differ in percentage with low ferritin levels or percentage with iron deficiency. CONCLUSIONS: Continuous treatment with omeprazole for 6 years or continuous treatment with any gastric antisecretory drug for 10 years does not cause decreased body iron stores or iron deficiency. These results suggest that, in contrast to recent results which show yearly monitoring of vitamin B12 in such patients is needed, such monitoring for iron parameters is not necessary.

Adolescent↗

Mitochondrial DNA variability in the Canary Islands honeybees (Apis mellifera L.).

The mitochondrial DNA (mtDNA) of individuals from 79 colonies of Apis mellifera from five Canary Islands was studied using the DraI test based on the restriction of PCR products of the tRNA(leu)-COII intergenic region. Five haplotypes of the African (A) lineage and one of the west European (C) lineage were found. The haplotypes A14 and A15 are described for the first time. These haplotypes have a new P sequence named P1. The wide distribution and high frequency of haplotype A15 suggest that it is characteristic of the Canarian Archipelago. Sources of haplotype variability of honeybee mtDNA in the Canary Islands (waves of colonization from Africa, queen importations, habitat diversification) are discussed.

Animals↗

Prospective study of somatostatin receptor scintigraphy and its effect on operative outcome in patients with Zollinger-Ellison syndrome.

OBJECTIVE: To determine the relative abilities of somatostatin receptor scintigraphy (SRS) and conventional imaging studies (computed tomography, magnetic resonance imaging, ultrasound, angiography) to localize gastrinomas before surgery in patients with Zollinger-Ellison syndrome (ZES) subsequently found at surgery, and to determine the effect of SRS on the disease-free rate. SUMMARY BACKGROUND DATA: Recent studies demonstrate that SRS is the most sensitive imaging modality for localizing neuroendocrine tumors such as gastrinomas. Because of conflicting results in small series, it is unclear in ZES whether SRS will alter the disease-free rate, which gastrinomas are not detected, what factors contribute to failure to detect a gastrinoma, or whether the SRS result should be used to determine operability in patients without hepatic metastases, as recently recommended by some investigators. METHODS: Thirty-five consecutive patients with ZES undergoing 37 exploratory laparotomies for possible cure were prospectively studied. All had SRS and conventional imaging studies before surgery. Imaging results were determined by an independent investigator depending on surgical findings. All patients underwent an identical surgical protocol (palpation after an extensive Kocher maneuver, ultrasound during surgery, duodenal transillumination, and 3 cm duodenotomy) and postoperative assessment of disease status (fasting gastrin, secretin test imaging within 2 weeks, at 3 to 6 months, and yearly), as used in pre-SRS studies previously. RESULTS: Gastrinomas were detected in all patients at each surgery. Seventy-four gastrinomas were found: 22 duodenal, 8 pancreatic, 3 primaries in other sites, and 41 lymph node metastases. The relative detection order on a per-patient or per-lesion basis was SRS > angiography, magnetic resonance imaging, computed tomography > ultrasound. On a per-lesion basis, SRS had greater sensitivity than all conventional studies combined. SRS missed one third of all lesions found at surgery. SRS detected 30% of gastrinomas < or =1.1 cm, 64% of those 1.1 to 2 cm, and 96% of those >2 cm and missed primarily small duodenal tumors. Tumor size correlated closely with SRS rate of detection. SRS did not increase the disease-free rate immediately after surgery or at 2 years mean follow-up. CONCLUSIONS: SRS is the most sensitive preoperative imaging study for extrahepatic gastrinomas in patients with ZES and should replace conventional imaging studies as the preoperative study of choice. Negative results of SRS for localizing extrahepatic gastrinomas should not be used to decide operability, because a surgical procedure will detect 33% more gastrinomas than SRS. SRS does not increase the disease-free rate. In the future, more sensitive methods to detect small gastrinomas, especially in the duodenum and in periduodenal lymph nodes, or more extensive surgery will be needed to improve the postoperative disease-free rate in ZES.

Adult↗

Bone metastases in patients with gastrinomas: a prospective study of bone scanning, somatostatin receptor scanning, and magnetic resonance image in their detection, frequency, location, and effect of their detection on management.

PURPOSE: To determine whether bone scan, magnetic resonance imaging (MRI), or somatostatin receptor scintigraphy (SRS) is best for identifying bone metastases in patients with gastrinomas, as well as their frequency and location, whether their detection affects management, and what patient subgroups should be examined. MATERIALS AND METHODS: One hundred fifteen patients with gastrinoma were prospectively studied. Patients were examined yearly and those with liver metastases were reexamined every 3 months. Based on clinical history, histology, growth pattern, and development of new bone lesions, possible bone metastases were classified as to whether they were or were not bone metastases. Imaging results were correlated at different times in the disease course and with disease extent. RESULTS: Bone scan was positive in 52 patients, MRI in seven, and SRS in six. Eight patients (7%) were determined to have bone metastases and MRI was correctly positive in seven, SRS in six, and bone scan in five. SRS or MRI was positive in all patients with bone metastases. Bone scan had significantly lower specificity and sensitivity, and a higher rate (P < .02) of false-negative results than MRI or SRS. Bone metastases occurred in 31% of patients with liver metastases and 0% with only lymph node metastases. The initial bone metastases were in the spine or sacrum (75%) followed in descending order by the pelvis or sacroiliac joints (38%), scapula or shoulder, and ribs. In all cases, detection of bone metastases changed the management. CONCLUSION: SRS and MRI, because of high sensitivity and specificity, are recommended over bone scanning to screen for bone metastases in patients with gastrinomas. However, because bone metastases can occur initially outside the axial skeleton, SRS is the recommended initial localization method of choice. Bone metastases occur in 7% of all patients and 31% of patients with liver metastases, only occur in patients with liver metastases, are usually in the axial skeleton initially, and their detection changes management in all cases. Patients with pancreatic endocrine tumors with liver metastases should undergo SRS every 6 months to 1 year to detect bone metastases.

Adolescent↗

Influence of the human immunodeficiency virus in the incidence of tuberculosis in a cohort of intravenous drug users: effectiveness of anti-tuberculosis chemoprophylaxis.

SETTING: A residential program in Barcelona for drug addicts (therapeutic community) admitted between November 1988 and March 1992, and followed until September 1994. OBJECTIVE: To study the incidence of tuberculosis as related to the presence of tuberculosis infection and/or human immunodeficiency virus (HIV) infection, and to evaluate the protective effect of chemoprophylaxis with isoniazid. DESIGN: Prospective cohort study. Incidence rates were compared using the Chi-square test for cohort studies. The effectiveness of chemoprophylaxis was evaluated by the Kaplan-Meier method at the univariate level, and by logistic regression models and proportional risks analysis at the multivariate level. RESULTS: During the study of 361 individuals without previous known tuberculosis or history of anti-tuberculosis chemoprophylaxis, 25 developed tuberculosis, an overall incidence rate of 1.79/100 person-years. For HIV-positive persons, the incidence rate was 3.25/100 person-years, compared with 0.30/100 in those who were HIV-negative (P < 0.05). The highest incidence rates occurred among HIV-positive persons who did not receive chemoprophylaxis and who were either anergic (HIV-positive, purified protein derivative [PPD]-negative, Multitest-negative) or who were infected with Mycobacterium tuberculosis (PPD+), 10.0/100 person-years and 4.64/100 person-years, respectively. Of the 53 persons who received chemoprophylaxis, three developed tuberculosis, an incidence rate of 1.4/100 person-years. In comparison, in the group of 51 patients who were designated to receive chemoprophylaxis but where none was actually taken, 17 developed tuberculosis, an incidence rate of 5.7/100 person-years (P = 0.03). CONCLUSION: HIV-infected intravenous drug users, particularly those who are anergic or who are PPD positive, are at increased risk of developing tuberculosis. Anti-tuberculosis chemoprophylaxis proved effective in this population.

AIDS-Related Opportunistic Infections↗

[Reversible hyperparathyroid metabolic osteopathy secondary to parathyroid carcinoma].

Parathyroid carcinoma is a rare cause of hyperparathyroidism and metabolic osteopathy. The authors report a patient with parathyroid carcinoma who underwent 99mTc-Sestamibi parathyroid and 99mTc-MDP bone scanning. These techniques showed the parathyroid lesion and typical features of severe metabolic osteopathy respectively. The bone scan performed at only four months after surgery showed near complete resolution.

Bone Diseases, Metabolic↗

Preferential oxidation of cardiac mitochondrial DNA following acute intoxication with doxorubicin.

The purpose of this investigation was to determine whether acute doxorubicin intoxication causes a preferential accumulation of 8-hydroxydeoxyguanosine (8OHdG) adducts to mitochondrial DNA (mtDNA) as opposed to nuclear DNA (nDNA), particularly in cardiac tissue. Adult male rats received a single i.p. bolus of doxorubicin (15 mg/kg) and were killed 1-14 days later. Acute intoxication with doxorubicin caused a 2-fold greater increase in 8OHdG adducts to mtDNA compared to nDNA, the concentration of adducts to both nDNA and mtDNA being 20%-40% greater for heart as opposed to liver. For both tissues, the relative abundance of adducts was highest at the earliest time-point examined (24 h) and decreased to control values by 2 weeks. The temporal dilution of 8OHdG adducts was not the result of cell hyperplasia and was only partially due to amplification of the mitochondrial genome, most probably via an increase in DNA copy number rather than a stimulation of mitochondrial biogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

Absence of detectable PML-RAR alpha fusion transcripts in long-term remission patients after BMT for acute promyelocytic leukemia.

Twenty patients with APL in long-term remission after BMT were analyzed for the presence of the PML-RAR alpha fusion gene by RT-PCR. Ten patients had undergone autologous BMT (six of them peripheral blood stem cell transplantation) and 10 allogeneic BMT. A total of 60 samples were examined by two different protocols. Of the eight patients studied just before conditioning, five showed PML-RAR alpha transcript prior to transplantation. Three of them were in CR and became PCR negative early post-transplantation. The other two patients, that were not in CR before transplant, remained PCR positive, relapsed early post-transplant and died. In the remaining patients no PML-RAR alpha transcripts were visible throughout their post-BMT courses. Our data show that long-term remission after BMT in APL patients is associated with eradication of cells carrying the PML-RAR alpha transcript, and that continued positivity of this test predicts subsequent relapse. The fact of the disappearance of PML-RAR alpha transcript early after BMT in patients previously positive suggest that transplant is capable of curing APL mainly through antileukemic action of the conditioning regimen and therefore, transplantation must be indicated in CR patients if a positive RT-PCR remains after treatment with ATRA plus chemotherapy.

Bone Marrow Transplantation↗

Long-term follow-up of immunosuppressive treatment for obstructive airways disease after allogeneic bone marrow transplantation.

To describe clinical outcome with first line immunosuppression therapy for obstructive airways disease (OAD) after allogeneic BMT, we have retrospectively examined 20 long-term survivors affected by OAD. All patients had normal pulmonary function test (PFTs) before BMT. OAD was defined as FEV1 less than 80%, FER less than 80%, maximum midexpiratory flow rate of 50% vital capacity (MMFR) less than 65%, or residual volume greater than 120. Prednisone (n = 4), CsA (n = 8) and azathioprine (n = 8) have been used as first-line immunosuppression agents. Mean follow-up was 65 months (range 15-142). We identified three categories of patients according to response to treatment: complete (n = 6, 30%), partial (n = 6, 30%) or no response (n = 8, 40%). Age, FEV1, time of onset after BMT, Karnofsky index or immunosuppression modality do not seem to be related to subsequent response. However, patients with low values of MMFR and high values of RV at the beginning of therapy are likely to show poor response. In the complete response group, normalisation of PFTs is achieved within the first months of treatment (median 6 months ranging from 3 to 9 months), suggesting that prolonged therapy is not advantageous and could increase morbidity and mortality if there are no other signs of CGVHD.

Adolescent↗

Myeloperoxidase gene expression in acute lymphoblastic leukaemia.

The FAB classification of acute leukaemias is based on the light microscopic detection of myeloperoxidase (MPO) activity in blast cells. Cases with MPO activity in > or = 3% of blasts are classified as acute myeloid leukaemia. We describe two cases of acute leukaemia in which the blast cells had lymphoid morphology, ultrastructure, immunophenotype and molecular rearrangements, but expressed significant levels of the MPO gene (MPO mRNA) by reverse transcription polymerase chain reaction (RT-PCR), in the absence of translation to protein. Both cases presented a short remission duration. We discuss the incidence, features and outcome of MPO mRNA positive acute lymphoblastic leukaemia (ALL).

Adolescent↗

Bronchial mucoepidermoid carcinoma after allogeneic bone marrow transplantation.

A 16 year old man underwent an allogeneic bone marrow transplantation (BMT) from an HLA identical sibling donor for acute lymphoblastic leukaemia in 1984. He developed chronic graft versus host disease involving the skin and kidneys. At day 400 after BMT his condition was complicated by obstructive airways disease, which was partially responsive to azathioprine and steroids. Five years after withdrawal of immunosuppressive treatment he developed dyspnoea and decreased pulmonary function test results, and steroid treatment was resumed. Fibrobronchoscopy revealed the presence of a mucoepidermoid carcinoma in the left main bronchus. After surgical laser resection, there was gradual clinical and functional improvement. There was no evidence of recurrence one year after surgery.

Adolescent↗