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Biomedical subjects

R Roca

Publications and source records attributed to R Roca.

At least 19 recordsLinked to original sources

Predictive value of (99m)Tc sestamibi scintigraphy in the evaluation of doxorubicin based chemotherapy response in patients with advanced breast cancer.

Resistance to doxorubicin based chemotherapy is a major therapeutic problem limiting advanced breast cancer treatment. 99mTc hexakis-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been reported to be extruded from tumour cells by the P-glycoprotein and multidrug resistance protein encoded by MDR1 and MRP1 genes, respectively. These proteins are involved in the cellular efflux of several chemotherapeutic agents including doxorubicin. The aim of this study was to investigate the clinical value of a standard (99m)Tc-MIBI scintimammography technique in the prediction of response to chemotherapy in advanced breast cancer patients. Fifty-six lesions from 33 female patients with locally advanced (n=27) or recurrent breast cancer (n=6) were included in the study. MIBI scintigraphy was performed 2-8 days prior to chemotherapy (FAC regimen). Images were acquired 10 min and 1 h post-injection of 740-1110 MBq of (99m)Tc-MIBI. Tumour-to-normal background tissue uptake ratios were calculated on each lesion in the early (T/B(e)) and delayed phase of the study (T/B(d)). Both T/B(e) and T/B(d) ratios were significantly higher (P<0.0001) in responders (n=43) than nonresponders (n=13). Diagnostic values of (99m)Tc-MIBI in the prediction of chemotherapy response were evaluated using the arbitrary cut-off values of 1.5 for T/B(e) and 1.4 forT/B(d). Sensitivity, specificity, positive and negative predictive values were 88.4%, 92.3%, 97.4%, 70.6%; and 90.7%, 100.0%, 100.0%, 76.6%, for T/B(e) and T/B(d), respectively. We conclude that (99m)Tc-MIBI scintigraphy may be a clinically valuable tool for guiding chemotherapy in advanced breast cancer patients.

Adult↗

Structural model of the catalytic core of carnitine palmitoyltransferase I and carnitine octanoyltransferase (COT): mutation of CPT I histidine 473 and alanine 381 and COT alanine 238 impairs the catalytic activity.

Carnitine palmitoyltransferase I (CPT I) and carnitine octanoyltransferase (COT) catalyze the conversion of long- and medium-chain acyl-CoA to acylcarnitines in the presence of carnitine. We propose a common three-dimensional structural model for the catalytic domain of both, based on fold identification for 200 amino acids surrounding the active site through a threading approach. The model is based on the three-dimensional structure of the rat enoyl-CoA hydratase, established by x-ray diffraction analysis. The study shows that the structural model of 200 amino acids of the catalytic site is practically identical in CPT I and COT with identical distribution of 4 beta-sheets and 6 alpha-helices. Functional analysis of the model was done by site-directed mutagenesis. When the critical histidine residue 473 in CPT I (327 in COT), localized in the acyl-CoA pocket in the model, was mutated to alanine, the catalytic activity was abolished. Mutation of the conserved alanine residue to aspartic acid, A381D (in CPT I) and A238D (in COT), which are 92/89 amino acids far from the catalytic histidine, respectively (but very close to the acyl-CoA pocket in the structural model), decreased the activity by 86 and 80%, respectively. The K(m) for acyl-CoA increased 6-8-fold, whereas the K(m) for carnitine hardly changed. The inhibition of the mutant CPT I by malonyl-CoA was not altered. The structural model explains the loss of activity reported for the CPT I mutations R451A, W452A, D454G, W391A, del R395, P479L, and L484P, all of which occur in or near the modeled catalytic domain.

Alanine↗

Heteromeric amino acid transporters: biochemistry, genetics, and physiology.

The heteromeric amino acid transporters (HATs) are composed of two polypeptides: a heavy subunit (HSHAT) and a light subunit (LSHAT) linked by a disulfide bridge. HSHATs are N-glycosylated type II membrane glycoproteins, whereas LSHATs are nonglycosylated polytopic membrane proteins. The HSHATs have been known since 1992, and the LSHATs have been described in the last three years. HATs represent several of the classic mammalian amino acid transport systems (e.g., L isoforms, y(+)L isoforms, asc, x(c)(-), and b(0,+)). Members of the HAT family are the molecular bases of inherited primary aminoacidurias cystinuria and lysinuric protein intolerance. In addition to the role in amino acid transport, one HSHAT [the heavy subunit of the cell-surface antigen 4F2 (also named CD98)] is involved in other cell functions that might be related to integrin activation. This review covers the biochemistry, human genetics, and cell physiology of HATs, including the multifunctional character of CD98.

Amino Acid Sequence↗

Effectiveness of a nurse-based outreach program for identifying and treating psychiatric illness in the elderly.

CONTEXT: Elderly persons with psychiatric disorders are less likely than younger adults to be diagnosed as having a mental disorder and receive needed mental health treatment. Lack of access to care is 1 possible cause of this disparity. OBJECTIVE: To determine whether a nurse-based mobile outreach program to seriously mentally ill elderly persons is more effective than usual care in diminishing levels of depression, psychiatric symptoms, and undesirable moves (eg, nursing home placement, eviction, board and care placement). DESIGN: Prospective randomized trial conducted between March 1993 and April 1996 to assess the effectiveness of the Psychogeriatric Assessment and Treatment in City Housing (PATCH) program. SETTING: Six urban public housing sites for elderly persons in Baltimore, Md. PARTICIPANTS: A total of 945 (83%) of 1195 residents in the 6 sites underwent screening for psychiatric illness. Among those screened, 342 screened positive and 603 screened negative. All screen-positive subjects aged 60 years and older (n=310) and a 10% random sample of screen-negative subjects aged 60 years and older (n=61) were selected for a structured psychiatric interview. Eleven subjects moved or died; 245 (82%) of those who screened positive and 53 (88%) of those who screened negative were evaluated to determine who had a psychiatric disorder. Data were weighted to estimate the prevalence of psychiatric disorders at the 6 sites. INTERVENTION: Among the 6 sites, residents in 3 buildings were randomized to receive the PATCH model intervention, which included educating building staff to be case finders, performing assessment in residents' apartments, and providing care when indicated; and residents in the remaining 3 buildings were randomized to receive usual care (comparison group). MAIN OUTCOME MEASURES: Number of undesirable moves and scores on the Montgomery-Asberg Depression Rating Scale (MADRS), a measure of depressive symptoms, and the Brief Psychiatric Rating Scale (BPRS), a measure of psychiatric symptoms and behavioral disorder, in intervention vs comparison sites. RESULTS: Based on weighted data, at 26 months of follow-up, psychiatric cases at the intervention sites had significantly lower (F(1)=31.18; P<.001) MADRS scores (9.1 vs 15.2) and significantly lower (F(1)=17.35; P<.001) BPRS scores (27.4 vs 33.9) than those at the nontreatment comparison sites. There was no significant difference between the groups in undesirable moves (relative risk, 0.97; 95% confidence interval, 0. 44-2.17). CONCLUSIONS: These results indicate that the PATCH intervention was more effective than usual care in reducing psychiatric symptoms in persons with psychiatric disorders and those with elevated levels of psychiatric symptoms. JAMA. 2000;283:2802-2809

Aged↗

TM20, a gene coding for a new class of transmembrane proteins expressed in the meristematic tissues of maize.

In the course of the analysis of lachrima, a recessive, defective kernel, embryo-lethal mutation in Zea mays that alters embryo and endosperm development, a gene coding for a new class of transmembrane proteins was isolated. The mutant was produced by Ac transposon tagging, and a gene located in the insertion region of the transposon was isolated as well as the corresponding cDNA. The predicted protein contains twenty hydrophobic segments that can be grouped in five repeats formed by four segments that fulfill the criteria for membrane spanning domains, and for this reason the gene has been named TM20. The sequences of the domains in each position of each group can be aligned, indicating that TM20 is formed by a four-domain structure duplicated five times. During embryogenesis in wild-type embryos and in the growing plant, TM20 gene expression is associated with meristems.

Amino Acid Sequence↗

Characterization of the sequence coding for the clathrin coat assembly protein AP17 (sigma2) associated with the plasma membrane from Zea mays and constitutive expression of its gene.

The cDNA and genomic sequences coding for the clathrin coat assembly protein AP17 (sigma2) from maize and its corresponding mRNA accumulation have been analyzed. This protein in yeast and mammals has been shown to be part of the associated protein (AP) complex of clathrin in the plasma membrane. The availability of this sequence as well as a previous AP19 in a plant allows one to propose that specific AP complexes exist in plants in the Golgi complex and in the plasma membrane. The AP17 protein is encoded in maize by a single gene, and its mRNA accumulates in all the organs studied. In the immature embryo, it displays a pattern of expression typical of constitutively expressed genes.

Adaptor Protein Complex 1↗

Use of formal and informal sources of mental health care among older African-American public-housing residents.

BACKGROUND: Elderly residents of public housing have high rates of psychiatric disorders, but most of those in need of care do not use any mental health service. This study examines the use of formal and alternative informal sources of mental health care in a sample of elderly African-American public-housing residents. METHOD: Data from an epidemiological survey of six Baltimore public-housing developments for the elderly (weighted N = 818) were analysed to examine the utilization of mental health services by older African-American residents. Logistic regression analyses were used to determine correlates of using formal and informal sources by those needing mental health care. RESULTS: Thirty-five per cent of subjects needed mental health care. Less than half (47%) of those in need received any mental health care in the previous 6 months. Residents in need were more likely to use formal (38.5%) than informal sources (18.6%) for care. The strongest correlates of using formal providers were substance use disorder (OR = 15.62), Medicare insurance (OR = 10.31) and psychological distress (OR = 10.27). The strongest correlates of using informal sources were perceiving little or no support from religious/spiritual beliefs (OR = 21.65), cognitive disorder (OR = 19.71) and having a confidant (OR = 15.07). CONCLUSIONS: Contrary to elderly African-Americans in general, those in public housing rely more on formal than informal sources for mental health problems. Nevertheless, both sources fail to fill the gap between need and met need. Interventions to increase identification, referral and treatment of elderly public-housing residents in need should target general medical providers and clergy and include assertive outreach by mental health specialists.

Black or African American↗

Detection of recurrent malignant melanoma with 99mTc-MIBI scintigraphy.

Initial reports suggest that 99mTc-methoxyisobutylisonitrile (MIBI) scanning may be of clinical value in staging patients with malignant melanoma. We carried out a study to evaluate the potential of this technique in the detection of recurrent disease. Whole-body 99mTC-MIBI scans were performed in 81 patients with a history of a surgically excised MM: 28 with known recurrent lesions and 53 during follow-up without evidence of disease. Images started 10 min post-injection, using a dose of 740 MBq. Diagnoses were confirmed by cytological/histological examination or at least one conventional imaging modality. Blinded interpretations of the MIBI scans were performed. Whole-body MIBI scanning correctly detected 68 (92%) of 74 metastatic lesions in the following sites: regional lymph nodes (n=23), non-regional lymph nodes (n=10), skin (n=16), brain/cerebellum (n=6), lung (n=8), bone (n=4) and breast (n=1). The technique failed to detect three subcutaneous regressive lesions (< 1 cm), one liver metastasis, one spleen metastasis and a case of multiple small lesions of the duodenal mucous membrane. In 14 patients the procedure detected previously unknown metastatic lesions. These results suggest that 99mTc-MIBI scanning is an effective imaging modality for whole-body screening of metastatic disease in malignant melanoma patients with the potential to influence treatment planning.

Adult↗

Characteristics of elderly inpatients at high risk of needing supportive social and health care services.

A two-stage cross-sectional study was conducted in a 951-bed acute-care hospital: a first survey designed to determine the profile of patients aged > or = 64 years needing supportive social/health care services, in which 38 patients discharged between June and July, 1992 (group 1) with social/health care problems that accounted for inappropriate hospitalization days participated, and a second survey designed to identify patients aged > or = 65 years at high risk and thus facilitating the early intervention of social workers, in which 153 patients selected at random and interviewed between August and September, 1992 (group 2) participated. A significantly higher percentage of group 1 patients had no medical insurance, were admitted to hospital for treatment, lived alone, had been readmitted in the previous 6 months, suffered from dementia and/or cognitive impairment, presented with associated chronic illnesses, and showed lower Barthel index scores as compared to group 2 patients. In patients in group 2, hospital discharge was delayed due to the need of supportive social and health care services in only 27 patients. The percentage of agreement in the suitability of the resource provided was higher after (92.6%) than before the intervention (71.1%). The mean number of inappropriate hospitalization days was 3.5 days for patients in group 1 and 1.9 days for those in group 2 (p = 0.013). The early identification of elderly inpatients at high risk of needing additional supportive social and health care would help patients to find the most appropriate resource according to their individuals needs.

Activities of Daily Living↗

Need and unmet need for mental health care among elderly public housing residents.

Epidemiologic survey data from elderly residents of six public housing developments were used to determine the prevalence of need and unmet need for mental health care. Thirty-seven percent of this predominantly African American sample needed mental health services, and 58% of those who needed care had unmet needs. Logistic regression analyses showed that males, older residents, those with no Medicare insurance, and those with more Activities of Daily Living (ADL) impairments were at greater risk of both needing mental health care and receiving no mental health care services. Findings suggest the need for targeted interventions that would increase service utilization and potentially reduce the likelihood of eviction or placement in more restrictive settings.

Black or African American↗

Helical preferences of alanine, glycine, and aminoisobutyric homopeptides.

The stability between helical conformations of homopeptides of alanine, glycine, and aminoisobutyric acid has been studied by means of quantum-mechanical methods. The influence of peptide length on the relative stability between helical conformations has also been analyzed by means of systematic studies for peptides of size up to 11 residues. Finally, the influence of the solvent has been examined by using self-consistent reaction field methods. The results provide a detailed picture of the modulation exerted by these factors on the helical preferences of these peptides.

Alanine↗

The prevalence of psychiatric disorders in elderly residents of public housing.

BACKGROUND: This study estimates lifetime and one-month prevalence of psychiatric disorders among elderly public housing residents. METHOD: Nine hundred forty-five residents of six public housing developments for the elderly were administered the General Health Questionnaire (GHQ), the Mini-Mental State Examination (MMSE), and the CAGE by lay interviewers. Residents screening positive and a 10% random sample of screen negatives were administered the Structured Clinical Interview for DSM-III-R (SCID) and a DSM-III-R derived algorithm for dementia and delirium. Prevalence rates were estimated based on weighted data from 298 subjects. RESULTS: Thirty-six percent of participants screened positive on at least one instrument. Based on the case identification interview, estimated lifetime prevalence of psychiatric disorders was 57.6%, and one-month prevalence was 27.9%. Cognitive disorder (10.5%), mood disorder (8.0%), psychotic disorder (4.6%), and substance abuse/dependence (4.4%) were the most common current disorders. Mood disorders (26.6%) and substance abuse/dependence (23.0%) were the most prevalent lifetime disorders. Compared to data from the Epidemiologic Catchment Area, public housing residents have higher current rates of mood disorder, schizophrenia, and substance use disorder. CONCLUSIONS: Elderly residents of public housing suffer higher rates of psychiatric morbidity than older people living independently in the community. The high prevalence of psychiatric disorders in this growing population of low-income elderly presents a challenge to the delivery of mental health service.

Aged↗

Psychosocial aspects of surgical care in the elderly patient.

Delirium, dementia, and depression often complicate the care of elderly surgical patients. Simple screening procedures performed preoperatively and postoperatively facilitate the early detection of these conditions and enable the physician to promptly institute appropriate treatment. Although the evaluation and management of these disorders are often within the range of the surgical treatment team, psychiatric consultation should be obtained when uncertainty exists about diagnosis or therapy.

Aged↗

Glomus tumour of the trachea: report of a case with microscopic, ultrastructural and immunohistochemical examination and review of the literature.

A case of glomus tumour of the trachea is reported. The patient, a 58-year-old man, complained of dyspnoea, cough and occasional haemoptysis for many years and had been misdiagnosed as having chronic bronchitis. The diagnosis of glomus tumour in a tissue sample taken by bronchoscopy was useful in planning adequate surgery. Light and electromicroscopy of the excised tumour confirmed the preoperative diagnosis. Immunohistochemical examination showed vimentin and actin in the tumour cells, and negativity for high and low molecular weight keratins, desmin, neurofilaments, and factor VIII-related antigen, findings similar to glomus tumours of other sites.

Actins↗

Conservative and bronchoplastic resection for bronchial carcinoid tumours.

From January 1974 to December 1987, 45 cases of bronchial carcinoid were surgically managed at our Unit, 44 of which were evaluated. All patients but 2 were submitted to fiberoptic bronchoscopy prior to surgery. A standard resection was performed in 19 cases (13 lobectomies, 4 bilobectomies and 2 pneumonectomies). In 11 cases, pulmonary resection was complemented with a bronchoplastic technique (6 lobectomies, 2 bilobectomies, 2 pneumonectomies, 1 segmentectomy). Four cases were managed by minimal resections (2 segmental, 1 wedge, 1 enucleation) and 8 others by bronchotomy and local resection without the sacrifice of lung tissue. There were two major postoperative complications and no operative mortality. Mean follow-up has been 53 months and no local bronchial recurrence has been observed although 2 patients have developed distant metastases, with 1 death. The absence of local recurrence in a series in which more than 50% of patients were treated with some form of conservative surgery seems to indicate that resection of lung tissue should be avoided whenever possible.

Adult↗

Instruments for screening for depression and dementia in a long-term care facility.

The high prevalence of mental disorders such as depression and dementia in institutionalized elderly patients warrants screening for psychiatric diagnosis in patients newly admitted to long-term care facilities. The diagnostic accuracy of the Mini-Mental State Examination (MMSE) and the Geriatric Depression Scale (GDS) was evaluated against a standardized psychiatric interview. The MMSE was found to be 81% sensitive and 83% specific in screening for dementia using a previously established cutpoint of less than 24/30 points. Adjusting MMSE scores for physical disabilities precluding completion of specific tasks on the MMSE did not significantly change the diagnostic accuracy of the test. The GDS was 47% sensitive and 75% specific in screening for depression using the suggested cutpoint of greater than 13/30 points. The MMSE was significantly correlated with functional status (r = 0.48, P = .0001), but not with the scores on the GDS or the clinical diagnosis of depression. The GDS did not correlate with functional status. In summary, the MMSE is a good screening test for dementia in institutionalized elderly, but the GDS is not sensitive for depression in this population.

Activities of Daily Living↗