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Biomedical subjects

F Arellano

Publications and source records attributed to F Arellano.

At least 19 recordsLinked to original sources
PubMed2000

Are schizophrenia or antipsychotic drugs a risk factor for cataracts?

Lens changes and ocular disturbances have been reported in conjunction with the use of antipsychotic drugs. We estimated the incidence rate of a clinical diagnosis of cataract in patients with a psychotic disorder, schizophrenia, and compared it with the rate in the general population. Among the schizophrenic patients, we also examined the role of dose and duration of antipsychotic drugs on the risk of cataract development. We followed up two cohorts of patients 30-85 years of age who were included in the United Kingdom General Practice Research Database. Patients in one group had a diagnosis of schizophrenia (N = 4,209). The other group was an age- and sex-matched cohort of 10,000 patients sampled from the source population. The incidence of cataracts was 4.5 per 1,000 person-years among the general population and 3.5 in the schizophrenia population. Overall, antipsychotic drug use was not associated with the occurrence of cataracts. Nevertheless, among long-term users of chlorpromazine at daily doses of 300 mg or greater, and among users of prochlorperazine, the relative risks were 8.8 (95% confidence interval = 3.1-25.1) and 4.0 (95% confidence interval = 0.8-20.7), respectively. There is no indication that schizophrenia per se is associated with an increased risk of developing cataracts.

Adult↗
PubMed1998

Reducing clozapine-related morbidity and mortality: 5 years of experience with the Clozaril National Registry.

UNLABELLED: The Clozaril National Registry (CNR) was created to help protect patients from developing potentially fatal agranulocytosis secondary to treatment with the antipsychotic medicine clozapine. The CNR, designed and maintained by the manufacturer of the branded Clozaril (clozapine), has the principal goals of (1) prophylaxis-preventing inappropriate retreatment, and (2) quality assurance-overseeing adherence to a "no blood, no drug" policy. This article reviews the estimated impact of the CNR on clozapine-related morbidity and mortality over the first 5 years of commercial experience in the United States. METHOD: Complete data on leukopenia and agranulocytosis, gathered from the CNR database for the period of 1990-1994, were reviewed and compared with data from the pre-CNR period. RESULTS: Use of clozapine in 99,502 patients according to package labeling requirements (distribution of the medicine linked to mandated white blood cell count testing) was associated with a total of 382 cases of agranulocytosis (0.38%) versus an expected cumulative total of 995 cases (based on the pre-CNR rate of 1% to 2%). Based on the expected agranulocytosis rate, up to 149 deaths might have been anticipated. Instead, there were only 12 deaths attributed to complications of agranulocytosis. CONCLUSION: The CNR provides for universal rechallenge protection as well as controlled dispensing of clozapine. It also serves as an early warning system to promote the safe and effective use of clozapine. The CNR includes quality assurance mechanisms designed to enhance compliance. Despite the added logistic requirements this system places upon physician, pharmacist, and manufacturer, the CNR has helped to reduce substantially potential fatal outcomes. The CNR reinforces both patient and treatment system compliance. Based on this favorable experience concerning agranulocytosis and associated fatalities, the Neuropsychopharmacology Advisory Committee to the U.S. Food and Drug Administration has unanimously recommended a reduction in frequency of the white blood cell count testing requirement after 6 months to every 14 days, instead of weekly. Finally, the CNR database containing white blood cell count and demographic data on every patient in the United States who has received the medicine has served as a unique epidemiologic database.

Adverse Drug Reaction Reporting Systems↗
PubMed1997

Mortality in current and former users of clozapine.

Clozapine (Clozaril), a tricyclic dibenzodiazepine, causes fewer extrapyramidal side effects than do other antipsychotic drugs. Because it can induce agranulocytosis, however, clozapine is indicated only for schizophrenia that is not responsive to other therapies. To describe the drug's effects on mortality, we compared rates of various causes of death in 67,072 current and former clozapine users. We linked data from a national registry of clozapine recipients to the National Death Index and Social Security Administration Death Master Files, obtained death certificates, and calculated mortality rates for underlying causes of death using standardization to adjust for age, sex, and race. During 1991-1993, there were 396 deaths in 85,399 person-years for patients ages 10-54 years. Mortality was lower during current clozapine use than during periods of non-use. Mortality from suicide was decreased in current clozapine users by comparison with past users [rate ratio (RR) = 0.17; 95% confidence interval (CI) = 0.10-0.30]. During clozapine use, there were elevations in mortality rates for less common causes of death, including pulmonary embolism (RR for current exposure compared with past clozapine use = 5.2) and respiratory disorders (RR = 2.9). Clozapine appears to reduce mortality in severe schizophrenics, mostly by decreasing suicide rates.

Adolescent↗
PubMed1993

Allopurinol hypersensitivity syndrome: a review.

OBJECTIVE: To review the pathophysiology, pathology, and clinical findings of allopurinol hypersensitivity syndrome (AHS), an infrequent but life-threatening adverse effect of allopurinol therapy. DATA SOURCES: A MEDLINE search (key terms hepatitis, interstitial nephritis, severe hypersensitivity, severe toxicity, vasculitis, toxic epidermal necrolysis, Lyell's syndrome, erythema multiforme, and Stevens-Johnson syndrome) was used to identify cases reported in the literature through the end of 1990. STUDY SELECTION: All cases evaluated met Singer and Wallace's diagnostic criteria for AHS. DATA EXTRACTION: We extracted data from 101 cases of AHS reported in the literature. The following information, when available, was analyzed: (1) patient data (age, gender, medical history), (2) treatment data (daily dosage of allopurinol, duration of treatment, indications, concomitant medications, and (3) adverse-event data. DATA SYNTHESIS: Patients were mostly middle-aged men with hypertension and/or renal failure receiving excessive doses of allopurinol primarily for asymptomatic hyperuricemia. Cutaneous rash and fever were the most common clinical findings. CONCLUSIONS: Although the pathophysiologic pathway leading to the development of AHS is unknown, it probably involves an immunologic mechanism following allopurinol accumulation in patients with poor renal function. Our findings suggest that the accepted diagnostic criteria for AHS may be too broad, and we recommend the application of more restrictive criteria. There is no effective treatment for AHS. The use of allopurinol only for accepted indications and in dosages adjusted for a patient's renal function may be the only means of minimizing the incidence of AHS.

Adult↗
PubMed1993

Malignancies in rheumatoid arthritis patients treated with cyclosporin A.

More than a thousand RA patients have been treated with cyclosporin A (CyA) in clinical trials. In seventeen of them, tumours developed after treatment with the drug. An indirect approach used to calculate the relative risk associated with the use of CyA in clinical trials suggested that: (i) RA itself increases the risk of cancer development; (ii) the use of CyA further increases the risk by approximately the same degree as DMARDs; and (iii) neither the pattern of malignancies nor the risk associated with CyA seems to be different from that observed with conventional DMARDs. Nevertheless, patients treated with CyA should be carefully monitored while more experience is gathered.

Aged↗
PubMed1992

Bacterial ice nucleation activity after T4 bacteriophage infection.

The changes in ice nucleation activity of transformed Ina+ Escherichia coli K12 after infection with T4D bacteriophage have been examined. Within 2 min after infection class A nucleation activity (measured at -4 degrees C) fell about 100-1000-fold whilst class B (measured at -5.5 degrees C) and class C (measured at -9 degrees C) nucleation activities increased 50-100-fold and then rapidly decreased. These changes also occurred after interaction with T4D ghost particles or T4D 11-/12- particles. Since ghost particles lack DNA and 11-/12- particles lack short tail fibres, the T4D particles appear to be exerting their effect by the attachment of the phage long tail fibres to the cell. The changes were not influenced by the addition of chloramphenicol.

Escherichia coli↗
PubMed1991

Components of ice nucleation structures of bacteria.

Nonprotein components attached to the known protein product of the inaZ gene of Pseudomonas syringae have been identified and shown to be necessary for the most efficient ice nucleation of supercooled H2O. Previous studies have shown that cultures of Ina+ bacteria have cells with three major classes of ice-nucleating structures with readily differentiated activities. Further, some cells in the culture have nucleating activities intermediate between those of the different classes and presumably have structures that are biosynthetic intermediates between those of the different classes. Since these structures cannot be readily isolated and analyzed, their components have been identified by the use of specific enzymes or chemical probes, by direct incorporation of labeled precursors, and by stimulation of the formation of specific classes of freezing structures by selective additions to the growth medium. From these preliminary studies it appears that the most active ice nucleation structure (class A) contains the ice nucleation protein linked to phosphatidylinositol and mannose, probably as a complex mannan, and possibly glucosamine. These nonprotein components are characteristic of those used to anchor external proteins to cell membranes of eucaryotic cells and suggest that a similar but not identical anchoring mechanism is required for efficient ice nucleation structure. The class B structure has been found to contain protein presumably linked to the mannan and glucosamine moieties but definitely not to the phosphatidylinositol. The class C structure, which has the poorest ice nucleation activity, appears to be the ice nucleation protein linked to a few mannose residues and to be partially imbedded in the outer cell membrane.

Bacterial Outer Membrane Proteins↗
PubMed1991

Formation of bacterial membrane ice-nucleating lipoglycoprotein complexes.

The preliminary finding that nonprotein additions to the protein product of the ice-nucleating gene of Pseudomonas syringae or Erwinia herbicola are essential for ice nucleation at the warmest temperatures has led to experiments aimed at identifying possible linkages between the ice protein and the other components. It appears that the protein is coupled to various sugars through N- and O-glycan linkages. Mannose residues are apparently bound via an N-glycan bond to the amide nitrogen of one or more of the three essential asparagine residues in the unique amino-terminal portion of the protein. In turn, these mannose residues are involved in the subsequent attachment of phosphatidylinositol to the nucleation structure. This phosphatidylinositol-mannose-protein structure is the critical element in the class A nucleating structure. In addition to sugars attached to the asparagine residues, additional sugar residues appear to be attached by O-glycan linkages to serine and threonine residues in the primary repeating octapeptide, which makes up 70% of the total ice protein. These additional sugar residues include galactose and glucosamine and most likely additional mannose residues. These conclusions were based on (i) the changes in ice-nucleating activity due to the action of N- and O-glycanases, alpha- and beta-mannosidoses, and beta-galactosidase; (ii) immunoblot analyses of ice proteins in cell extracts after enzyme treatments; and (iii) the properties of transformed Ice+ Escherichia coli cells containing plasmids with defined amino-terminal and carboxyl-terminal deletions in the ice gene. Finally, evidence is presented that these sugar residues may play a role in aggregating the ice gene lipoglycoprotein compound into larger aggregates, which are the most effective ice nucleation structures.

Bacterial Outer Membrane Proteins↗
PubMed1991

Phosphatidylinositol, a phospholipid of ice-nucleating bacteria.

The nature of the phospholipids of the various bacteria that have ice nucleation activity in supercooled water has been determined. The seven bacteria studied included Pseudomonas syringae, Erwinia herbicola, three Escherichia coli K-12 strains that are phenotypically Ice+ because they contain plasmids with different amounts of either P. syringae or E. herbicola cloned DNA, and two E. coli K-12 strains without cloned ice gene DNA. All five Ice+ bacterial strains contained small amounts (0.1 to 1.0% of the total phospholipids) of phosphatidylinositol (PI), a phospholipid not previously detected in E. coli, Pseudomonas, or Erwinia species. The Ice- E. coli strains also contained trace level of PI that amounted to 2 to 30% of the level found in the Ice+ E. coli strains. Extracts of Ice+ strains contained low but measurable activities of PI synthase, while the activities in Ice- strains amounted to only 8 to 12% or less of that found in extracts of Ice+ bacteria. The functioning of the ice gene apparently increased both the PI synthase activity and the PI content of Ice+ strains from low endogenous levels. The relative ice nucleation activity at -4 degrees C or above (class A nucleation activity) of all Ice+ strains was found to be proportional to their PI content. The addition of myo-inositol (5 x 10(-4) M) to synthetic culture media increased the class A nucleation activity of both Ice+ E. coli strains and P. syringae up to sevenfold but had no stimulating effect on ice nucleation at lower temperatures (class B and class C nucleation activities). If these cells after fusion with PI vesicles were incubated with an energy source, the class A nucleation activity increased 70-fold over that present before fusion. These results indicate that PI plays an important role in ice nucleation at warm temperatures and is a likely precursor or component of the class A structure.

CDP-Diacylglycerol-Inositol 3-Phosphatidyltransfer↗
PubMed1990

Metamizole: reassessment of its therapeutic role.

The use of metamizole is controversial, as reflected in the very different national regulations affecting it. The striking disparities between policies for metamizole made us try to determine if there were reasons to ban, limit or liberalize its utilization. After reviewing the literature, it was concluded that metamizole should not be withdrawn from the countries where its use is still relatively free. However, metamizole causes life-threatening adverse events that are usually unpredictable and can only be prevented by better prescribing habits, so it is suggested that its use as a first-line agent should be restricted to the treatment of the pain of acute colic and circumstances in which parenteral administration of a non-narcotic agent is mandatory. Studies are needed to determine the role of second-line oral analgesics in terms of their overall toxicity and efficacy. In the meantime it is proposed that oral metamizole should be used only when other analgesics (e.g. paracetamol) have failed.

Aminopyrine↗