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Biomedical subjects

D Guerra

Publications and source records attributed to D Guerra.

At least 19 recordsLinked to original sources

Fatty acid production in Schizochytrium sp.: Involvement of a polyunsaturated fatty acid synthase and a type I fatty acid synthase.

Schizochytrium sp. is a marine microalga that has been developed as a commercial source for docosahexaenoic acid (DHA, C22:6 (omega-3), enriched biomass, and oil. Previous work suggested that the DHA, as well as docosapentaenoic acid (DPA, C22:5 omega-6), that accumulate in Schizochytrium are products of a multi-subunit polyunsaturated fatty acid (PUFA) synthase (1). Here we show data to support this view and also provide information on other aspects of fatty acid synthesis in this organism. Three genes encoding subunits of the PUFA synthase were isolated from genomic DNA and expressed in E. coli along with an essential accessory gene encoding a phosphopantetheinyl transferase (PPTase). The resulting transformants accumulated both DHA and DPA. The ratio of DHA to DPA was approximately the same as that observed in Schizochytrium. Treatment of Schizochytrium cells with certain levels of cerulenin resulted in inhibition of 14C acetate incorporation into short chain fatty acids without affecting labeling of PUFAs, indicating distinct biosynthetic pathways. A single large gene encoding the presumed short chain fatty acid synthase (FAS) was cloned and sequenced. Based on sequence homology and domain organization, the Schizochytrium FAS resembles a fusion of fungal FAS beta and alpha subunits.

Amino Acid Sequence↗

Nurses as providers of emotional support to patients with MDR-TB.

AIM: To identify the forms and means of emotional support that nurses provide to patients living with multidrug-resistant tuberculosis (MTR-TB) in Lima, Peru. BACKGROUND: A fundamental role of nurses is to provide emotional support, defined as all the strategies that a health team employs to assure the psychosocial well-being of the patient. However, neither the forms of emotional support nor the means used by nurses in resource-poor settings have been much written about. This paper describes a qualitative study of a team of seven nurses working in a programme that provides individualized MDR-TB treatment to patients in Lima, Peru. It describes the various forms of support that facilitated the ability of patients to adhere to treatment despite socio-economic difficulties, social stigma, drug side effects, problems related to different stages of treatment and concurrent illnesses/special situations. METHODS: Qualitative study methods were employed over the course of 8 years to observe nurses and patients in an MDR-TB treatment programme. These included participant observation, structured observation sessions of nurses with their patients and focus groups with seven nurses. CONCLUSION: Through theme and content analyses of qualitative data, ten situations related to MDR-TB treatment were found. These ten issues served as an analytical framework used to identify and discuss the various types of emotional support provided by both formal and informal means. This type of support focused on problems related to different stages of treatment, social stigma of the illness, treatment adherence, side effects, socio-economic difficulties, death and concurrent illnesses/special situations. PRACTICE IMPLICATIONS: The essential role of the nurse as a provider of emotional support in the development or implementation of similar programmes with MDR-TB should, in future, be taken into account.

Adaptation, Psychological↗

Psychiatric issues in the management of patients with multidrug-resistant tuberculosis.

INTRODUCTION: Psychiatric issues present a challenge in the treatment of patients with multidrug-resistant tuberculosis (MDR-TB). Both baseline psychiatric disorders and development of psychiatric complications related to anti-tuberculosis drugs and psychosocial factors require aggressive management. SETTING: A community-based non-governmental health organization in Lima, Peru. OBJECTIVE: To review the literature for psychiatric complications associated with anti-tuberculosis medications, to describe the incidence and prevalence of depression, anxiety and psychosis among individuals receiving MDR-TB therapy, and to detail the management approach used in this cohort. METHODS: A retrospective case series was performed among the first 75 patients to receive individualized MDR-TB therapy in Lima, Peru, between 1996 and 1999. RESULTS: Baseline depression and baseline anxiety were observed in respectively 52.2% and 8.7% of this cohort. Most individuals with baseline depression experienced improvement of depressive symptoms during the course of TB therapy. The incidence of depression, anxiety and psychosis during MDR-TB treatment was 13.3%, 12.0% and 12.0%, respectively. While the majority of individuals with depression, anxiety and psychosis required psychiatric pharmacotherapy, cycloserine was successfully continued in all but one case. CONCLUSION: Psychiatric comorbidities are not a contra-indication to MDR-TB therapy. Management of psychiatric complications is possible without compromising anti-tuberculosis treatment.

Adult↗

The role of the nurse in the community-based treatment of multidrug-resistant tuberculosis (MDR-TB).

SETTING: A community-based treatment program for multidrug-resistant tuberculosis (MDR-TB) in Lima, Peru. OBJECTIVES: To describe the activities carried out by the nurses working with the program. DESIGN: A qualitative study using a variety of ethnographic methods, including participant observation, focus groups, and key informant interviews over a 5-year period. RESULTS: Nurses were responsible for carrying out a wide variety of activities within the program. These included patient-focused activities such as identifying patients, evaluating patients prior to starting and during therapy, and managing emergencies; educational activities for both patients and health professionals managing MDR-TB; and coordination activities, including over-seeing health workers and communicating between team members. CONCLUSION: Nurses play a key role in the community-based management of MDR-TB.

Antitubercular Agents↗

Clinical and programmatic considerations in the treatment of MDR-TB in children: a series of 16 patients from Lima, Peru.

SETTING: Since 2000, the directly observed treatment, short-course (DOTS) strategy has been expanded in several countries to include treatment of multidrug-resistant tuberculosis (MDR-TB). This strategy is known as DOTS-Plus. Tuberculosis is a common cause of morbidity and mortality for children throughout the developing world. Children may also be infected with MDR-TB, yet most developing countries do not specifically address pediatric MDR-TB. OBJECTIVE: To present the intermediate outcomes of the first 16 children enrolled in the Peruvian DOTS-Plus program and to demonstrate the tolerability of second-line anti-tuberculosis drugs. RESULTS: Three children completed therapy and are cured, one child had bacteriologic and clinical failure after 12 months of therapy and died of respiratory insufficiency, and 12 have intermediate outcomes demonstrating favorable clinical, bacteriologic, and radiographic evidence of improvement after 9-19 months of therapy. CONCLUSIONS: Of the 16 pediatric DOTS-Plus patients, 15 have tolerated therapy well and have had favorable clinical evolution. However, the diagnosis of pediatric MDR-TB is often extremely delayed due to reliance on the adult case definition and should be changed to prevent progressive, chronic illness in such children. Programmatic changes could facilitate earlier diagnosis and treatment of pediatric MDR-TB in Peru and in other DOTS-Plus programs.

Adolescent↗

The European study of assisted reproduction families: the transition to adolescence.

BACKGROUND: Findings are presented of the second phase of a European longitudinal study of families created by assisted reproduction. The present investigation reports on data obtained during the child's transition to adolescence. METHODS: A total of 102 IVF families, 94 donor insemination (DI) families, 102 adoptive families, and 102 families with a naturally conceived child were compared on standardized interview and questionnaire measures of parenting and children's psychological well-being. RESULTS: The assisted reproduction families were similar to the adoptive and natural conception families for many of the measures of the quality of parent-child relationships. To the extent that differences were found between the assisted reproduction families and the other family types, these reflected mainly more positive functioning among the assisted reproduction families, with the possible exception of the overinvolvement with their children of a small proportion of assisted reproduction mothers and fathers. The assisted reproduction children were functioning well and did not differ from the adoptive or naturally conceived children on any of the measures of psychological adjustment. However, only 8.6% had been told about their genetic origins. CONCLUSIONS: IVF and DI families with an early adolescent child appear to be functioning well.

Adaptation, Psychological↗

Tuberculosis in Spain: epidemiological pattern and clinical practice.

SETTING: Thirteen Autonomous Regions in Spain. OBJECTIVE: To study the incidence of all forms of tuberculosis (TB) and investigate clinical practice in TB. DESIGN: Cases of all forms of tuberculosis diagnosed in the study setting from May 1986 to April 1997 were identified though active search of different databases. Clinical and epidemiological information on cases was collected from clinical records or by interview with physicians. RESULTS: The overall incidence of all forms of tuberculosis was 38.5/100,000 and the incidence of smear-positive disease was 13.83/100,000. Most cases (97.1%) were Spanish nationals, with rates higher in men than in women (52.7/100,000 vs. 24.87/100,000) and in groups aged 25-34 and 75 years and over (61.35/100,000 and 59.35/100,000, respectively). Disseminated forms were frequent (6.6%), and the most common risk factor was human immunodeficiency virus (HIV) infection (17.7% of cases). Hospitalisation was common (71.6%). Microbiological confirmation of diagnosis was sought for 87.7% of the cases (91.8% of pulmonary vs. 75.5% of extra-pulmonary cases), and 65.2% were culture-positive (73.8% of pulmonary vs. 39.7% of extra-pulmonary cases). HIV-infected patients were treated in almost equal proportions with three or four drugs (49.7% and 48.2%, respectively), while HIV-negative cases or those whose HIV status was unknown were usually treated with three drugs. CONCLUSION: The epidemiological pattern of TB in Spain is different to other industrialised countries in the age distribution of cases and the proportions of foreigners and cases with HIV infection. Microbiological confirmation of diagnosis is more common in pulmonary than in extra-pulmonary disease, and treatment with four drugs more frequent in HIV-positive cases.

Adolescent↗

Morphological analysis of articular cartilage biopsies from a randomized, clinical study comparing the effects of 500-730 kDa sodium hyaluronate (Hyalgan) and methylprednisolone acetate on primary osteoarthritis of the knee.

OBJECTIVE: Histomorphometric study on cartilage samples taken from osteoarthritic human knees before and 6 months after intraarticular injections of a specific fraction (500-730 kDa) of hyaluronan. The results obtained with hyaluronan were compared with the results of methylprednisolone acetate treatment. METHODS: Twenty-four subjects with primary osteoarthritis (OA) of the knee were considered. Eleven patients were treated with Hyaluronan (Hyalgan), 20 mg/2 ml once a week for 5 weeks) and 13 with methylprednisolone (Depo-Medrol, 40 mg/1 ml once a week for 3 weeks). At the time of baseline and after 6 months from the start of treatment, biopsies of cartilage were taken and processed for electron microscopy. Articular surface morphology, territorial matrix, chondrocyte number and ultrastructure were characterized by a set of morphometric parameters. Samples from 19 informed patients showing no arthroscopic sign of OA were also used for comparison. RESULTS: Six months after hyaluronan treatment a significant reconstitution of the superficial layer were observed together with an improvement in chondrocyte density and territorial matrix appearance. Furthermore, chondrocytes appeared significantly improved in their metabolism, as indicated by the increased extension of the synthetic structures and mitochondria with respect to the organelles having catabolic or storage functions. Hyaluronan treatment produced results that were significantly superior to those delivered with Methylprednisolone in almost all the morphometric estimators. CONCLUSIONS: These results cannot be explained simply by temporary restoration of the synovial fluid viscoelasticity, and provide further evidence that the specific fraction of hyaluronan used in this study is a useful tool in OA treatment, with a potential structure-modifying activity.

Adjuvants, Immunologic↗

Morphological analysis of knee synovial membrane biopsies from a randomized controlled clinical study comparing the effects of sodium hyaluronate (Hyalgan) and methylprednisolone acetate (Depomedrol) in osteoarthritis.

OBJECTIVE: The study was part of a randomized open-label clinical trial designed to evaluate the effects of intra-articular injections of hyaluronan (Hyalgan) (HY) in osteoarthritis (OA) of the human knee. Data were compared with those obtained after treatment with methylprednisolone acetate (Depomedrol) (MP). METHODS: Synovial membranes from patients with OA of the knee, primary or secondary to a traumatic event and classified according to the American College of Rheumatology criteria, were examined by arthroscopy and by light and electron microscopy before and 6 months after local injection of HY (2 ml of 500-730 000 MW hyaluronan, 10 mg/ml in saline, one injection per week for 5 weeks) or MP (1 ml of methylprednisolone acetate, 40 mg/ml, one injection per week for 3 weeks). RESULTS: Arthroscopy revealed a significant decrease in inflammatory score after both treatments. Histology showed that HY treatment was effective (P< or =0.05) in reducing the number and aggregation of lining synoviocytes, as well as the number and calibre of the vessels. MP treatment significantly reduced the number of mast cells in primary OA. Both treatments tended to decrease the number of hypertrophic and to increase the number of fibroblast-like lining cells, to decrease the numbers of macrophages, lymphocytes, mast cells and adipocytes, and to decrease oedema, especially in primary OA, and to increase the number of fibroblasts and the amount of collagen. These phenomena were evident throughout the thickness of the synovial tissue. CONCLUSION: At least in the medium term, both HY and MP modified a number of structural variables of the synovial membrane of the osteoarthritic human knee towards the appearance of that of normal synovium. The effect was more evident in primary OA than in OA secondary to a traumatic event. This is the first evidence that local hyaluronan injections modify the structural organization of the human knee synovium in OA.

Adjuvants, Immunologic↗

[Trisomy 21. Report of 2 cases with unusual karyotypes].

We report two patients with trisomy 21 whose karyotypes revealed unusual translocations. In the first case there was a tandem translocation with two chromosomes 21 attached to the long arm of chromosome 10 (45,XX + tan(10:21;21). In the second case there was an inverted tandem translocation between two chromosomes 21 attached through their long arms (46,XY + dic(21q:21q). The clinical picture in both patients was not different from the usually found in trisomy 21. Since the parent's karyotypes were normal in both cases, it is assumed that both translocations arose "de novo". The need for karyotyping all cases of Down syndrome is emphasized.

Chromosome Inversion↗

[The hemangioma-sternum bifidum malformation syndrome. Report of a patient].

We present a male patient with a facial haemangioma extending from the lower left lid to the malar region and the upper left lip. The patient also presents a 1 cm round cutaneous notch on the upper third of the sternum. There are not other physical anomalies. The characteristics of the clinical picture suggest the diagnosis of sternal cleft-haemangiomas malformative spectrum (OMIM 140850).

Abnormalities, Multiple↗

Cell behaviour of Drosophila fat cadherin mutations in wing development.

We have studied several cell behaviour parameters of mutant alleles of fat (ft) in Drosophila imaginal wing disc development. Mutant imaginal discs continue growing in larvae delayed in pupariation and can reach sizes of several times those of wild-type. Their growth is, however, basically allometric. Homozygous ft cells grow faster than their twin cells in clones and generate larger territories, albeit delimited by normal clonal restrictions. Moreover, ft cells in clones tend to grow towards wing proximal regions. These behaviours can be related with failures in cell adhesiveness and cell recognition. Double mutant combinations with alleles of other genes, e.g. of the Epidermal growth factor receptor (DER) pathway, modify ft clonal phenotypes, indicating that adhesiveness is modulated by intercellular signalling. Mutant ft cells show, in addition, smaller cell sizes during proliferation and abnormal cuticular differentiation, which reflect cell membrane and cytoskeleton anomalies, which are not modulated by the DER pathway.

Alleles↗

[Achondroplasia and Down syndrome in the same patient. Report of a case].

Achondroplasia and trisomy 21 are, within their respective categories, conditions the most frequent genetic diseases found in newborns. The simultaneous presence of both conditions in the same patient, has been however, reported only once in the world literature. In this paper we present a patient affected by both entities (Achondroplasia and Trisomy 21). The clinical findings and the reasons for the rare reported frequency of these cases are discussed.

Achondroplasia↗

Screening of larval/pupal P-element induced lethals on the second chromosome in Drosophila melanogaster: clonal analysis and morphology of imaginal discs.

We have carried out screens for lethal mutations on the second chromosome of Drosophila melanogaster that are associated with abnormal imaginal disc morphologies, particularly in the wing disc. From a collection of 164 P element-induced mutations with a late larva/pupa lethal phase we have identified 56 new loci whose gene products are required for normal wing disc development and for normal morphology of other larval organs. Genetic mosaics of these 56 mutant lines show clonal mutant phenotypes for 23 cell-viable mutations. These phenotypes result from altered cell parameters. Causal relationships between disc and clonal phenotypes are discussed.

Animals↗

Psychiatric morbidity in couples attending a fertility service.

The structured clinical interview for diagnosis (axis 1) according to the Diagnostic and Statistical Manual for Mental Disorders (DSM-III-R) was used to assess psychiatric morbidity in 110 infertile patients. They were divided into two groups according to whether referral to the service of psychosomatic medicine was deemed advisable by the physician in charge. Psychiatric disorders were diagnosed in 39 of 56 (69.6%) patients in the referred group and in 13 of 54 (24.1%) in the non-referred group. Psychiatric morbidity was found in 61.1% of females and 21% of males. Adjustment disorders were found in 59.6% (31/52) of all patients, in 59% (24/39) of patients among the referred group and in 61.5% (8/13) of patients among the non-referred group. Fourteen (67%) of 21 women in the referred group with adjustment disorders suffered from anxiety. In addition, 33.3% of patients in the non-referred group showed important psychological dysfunction, although DSM-III-R criteria were not met. Psychiatric morbidity was significantly associated with the number of treatment cycles and female gender in the whole study population, as well as with the type and length of infertility in the non-referred group. Psychological services in an infertility clinic help to identify at an early stage those individuals who are more likely to be vulnerable. This would enable psychological interventions to be targeted towards those in greater need.

Female↗

Developmental constraints in the Drosophila wing.

Selection experiments for shortening the four longitudinal veins in a wild population of Drosophila melanogaster have been performed to evaluate how a local change is integrated in the wing development. Our results show that, though many units of selection seem to exist within a given organ, these are strongly constrained within the developmental programme, in such a way that only some predictable forms are expected. The results are discussed in terms of the 'Entelechia' model proposed by Garcia-Bellido in which the intercalarity of positional values promoted by 'martial' genes in a given organ is the driving force for controlled cell proliferation.

Animals↗

Developmental constraints and wing shape variation in natural populations of Drosophila melanogaster.

The body sizes and shapes of poikilothermic animals generally show clinal variation with latitude. Among the environmental factors responsible for the cline, temperature seems to be the most probable candidate. In the present work we analysed natural populations of Drosophila melanogaster collected at different geographical localities to determine whether the same selective forces acting on wing development in the laboratory are also at work in the wild. We show that the temperature selection acting on wing development in the laboratory is only one of the selective forces operating in the wild. The size differences between natural populations seem to depend exclusively on cell number whereas they depend on cell area in the laboratory. The two wing compartments behave as distinct units of selection subjected to different genetic control, confirming our previous observations on laboratory populations. In addition, subunits of development defined as regions of cell proliferation centres restricted within longitudinal veins can, in turn, be considered as subunits of selection. Their interaction during development and continuous natural selection around an optimum could explain the high wing shape stability generally found in natural populations.

Animals↗

Two male siblings with cavum septum pellucidum, cavum vergae, macrocephaly, seizures and mental retardation. A new hereditary syndrome?

We report two brothers from non-consanguineous parents who share a particular constellation of clinical and radiographic findings, including macrocephaly, mental retardation and seizures as well as megalencephaly, cavum septum pellucidum and persistence of cavum vergae. The similar characteristics of these two brothers suggest a hereditary syndrome.

Abnormalities, Multiple↗