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Biomedical subjects

F Costello

Publications and source records attributed to F Costello.

10 recordsLinked to original sources

First admissions for depression: is the 'no-treatment interval' a critical predictor of time to remission?

BACKGROUND: This study aimed to replicate findings that length of episode prior to adequate antidepressant treatment (the 'no-treatment interval') and premorbid neuroticism predict time to remission from the institution of adequate treatment for depression. METHODS: Eighty-three inpatients meeting ICD-10 criteria for a depressive illness were entered into an 18-month prospective follow-up study of illness course. Subjects were assessed using the Schedules for Clinical Assessment in Neuropsychiatry, Maudsley Personality Inventory (MPI) and the Hamilton Rating Scale for Depression (HRSD). Remission was defined as an HRSD score of < 8 for 2 consecutive weeks. RESULTS: Twenty-two patients (27%) remained depressed 12 months after the onset of adequate treatment. Significantly longer times to remission were predicted by a longer no-treatment interval and higher premorbid neuroticism scores. LIMITATIONS: Adequate antidepressant treatment was commenced prior to admission in half the cases, requiring a retrospective assessment of illness course prior to study entry. Twenty-four patients (29%) had not remitted at the time of completion of the MPI. CONCLUSIONS: These results replicate previous findings identifying a longer time to treatment and higher neuroticism scores as predictors of chronicity in depression.

Adolescent↗

Epitope mapping of Aleutian mink disease parvovirus virion protein VP1 and 2.

Six overlapping fragments of the Aleutian Mink Disease parvoVirus (AMDV) virion protein VP1 and 2 (VP1/2) gene were inserted into the expression vector pMAL-c2. Four of the clones carried large overlapping fragments covering the entire VP1/2 gene. The remaining two clones covered specifically chosen regions within the VP1/2 gene. Using a Western blotting detection system, sera from AMDV-infected mink were tested against the recombinant polypeptides. These studies showed reactions primarily directed against the two AMDV polypeptides ranging from amino acids 297 to 518. Weaker reactions against other regions of the VP1/2 were also observed. The small fusion protein designed to cover the presumed AMDV VP1/2 loop 4 was purified by affinity chromatography and used to develop solid-phase immunoassays. Twelve small synthetic peptides were constructed and used as inhibitors. A peptide covering amino acids S428 to T448 was shown to block the reactivity of a pool of positive mink sera, indicating the presence of one dominant linear epitope.

Aleutian Mink Disease↗

Expression of Aleutian mink disease parvovirus capsid proteins in defined segments: localization of immunoreactive sites and neutralizing epitopes to specific regions.

The capsid proteins of the ADV-G isolate of Aleutian mink disease parvovirus (ADV) were expressed in 10 nonoverlapping segments as fusions with maltose-binding protein in pMAL-C2 (pVP1, pVP2a through pVP2i). The constructs were designed to capture the VP1 unique sequence and the portions analogous to the four variable surface loops of canine parvovirus (CPV) in individual fragments (pVP2b, pVP2d, pVP2e, and pVP2g, respectively). The panel of fusion proteins was immunoblotted with sera from mink infected with ADV. Seropositive mink infected with either ADV-TR, ADV-Utah, or ADV-Pullman reacted preferentially against certain segments, regardless of mink genotype or virus inoculum. The most consistently immunoreactive regions were pVP2g, pVP2e, and pVP2f, the segments that encompassed the analogs of CPV surface loops 3 and 4. The VP1 unique region was also consistently immunoreactive. These findings indicated that infected mink recognize linear epitopes that localized to certain regions of the capsid protein sequence. The segment containing the hypervariable region (pVP2d), corresponding to CPV loop 2, was also expressed from ADV-Utah. An anti-ADV-G monoclonal antibody and a rabbit anti-ADV-G capsid antibody reacted exclusively with the ADV-G pVP2d segment but not with the corresponding segment from ADV-Utah. Mink infected with ADV-TR or ADV-Utah also preferentially reacted with the pVP2d sequence characteristic of that virus. These results suggested that the loop 2 region may contain a type-specific linear epitope and that the epitope may also be specifically recognized by infected mink. Heterologous antisera were prepared against the VP1 unique region and the four segments capturing the variable surface loops of CPV. The antisera against the proteins containing loop 3 or loop 4, as well as the anticapsid antibody, neutralized ADV-G infectivity in vitro and bound to capsids in immune electron microscopy. These results suggested that regions of the ADV capsid proteins corresponding to surface loops 3 and 4 of CPV contain linear epitopes that are located on the external surface of the ADV capsid. Furthermore, these linear epitopes contain neutralizing determinants. Computer comparisons with the CPV crystal structure suggest that these sequences may be adjacent to the threefold axis of symmetry of the viral particle.

Aleutian Mink Disease Virus↗

The relationship between capsid protein (VP2) sequence and pathogenicity of Aleutian mink disease parvovirus (ADV): a possible role for raccoons in the transmission of ADV infections.

Aleutian mink disease parvovirus (ADV) DNA was identified by PCR in samples from mink and raccoons on commercial ranches during an outbreak of Aleutian disease (AD). Comparison of DNA sequences of the hypervariable portion of VP2, the major capsid protein of ADV, indicated that both mink and raccoons were infected by a new isolate of ADV, designated ADV-TR. Because the capsid proteins of other parvoviruses play a prominent role in the determination of viral pathogenicity and host range, we decided to examine the relationship between the capsid protein sequences and pathogenicity of ADV. Comparison of the ADV-TR hypervariable region sequence with sequences of other isolates of ADV revealed that ADV-TR was 94 to 100% related to the nonpathogenic type 1 ADV-G at both the DNA and amino acid levels but less than 90% related to other pathogenic ADVs like the type 2 ADV-Utah, the type 3 ADV-ZK8, or ADV-Pullman. This finding indicated that a virus with a type 1 hypervariable region could be pathogenic. To perform a more comprehensive analysis, the complete VP2 sequence of ADV-TR was obtained and compared with that of the 647-amino-acid VP2 of ADV-G and the corresponding VP2 sequences of the pathogenic ADV-Utah, ADV-Pullman, and ADV-ZK8. Although the hypervariable region amino acid sequence of ADV-TR was identical to that of ADV-G, there were 12 amino acid differences between ADV-G and ADV-TR. Each of these differences was at a position where other pathogenic isolates also differed from ADV-G. Thus, although ADV-TR had the hypervariable sequence of the nonpathogenic type 1 ADV-G, the remainder of the VP2 sequence resembled sequences of other pathogenic ADVs. Under experimental conditions, ADV-TR and ADV-Utah were highly pathogenic and induced typical AD in trios of both Aleutian and non-Aleutian mink, whereas ADV-Pullman was pathogenic only for Aleutian mink and ADV-G was noninfectious. Trios of raccoons experimentally inoculated with ADV-TR and ADV-Utah all became infected with ADV, but only a single ADV-Pullman-inoculated raccoon showed evidence of infection. Furthermore, none of the ADV isolates induced pathological findings of AD in raccoons. Finally, when a preparation of ADV-TR prepared from infected raccoon lymph nodes was inoculated into mink and raccoons, typical AD was induced in Aleutian and non-Aleutian mink, but raccoons failed to show serological or pathological evidence of infection. These results indicated that raccoons can become infected with ADV and may have a role in the transmission of virus to mink but that raccoon-to-raccoon transmission of ADV is unlikely.

Aleutian Mink Disease↗

Subcellular localization of Aleutian mink disease parvovirus proteins and DNA during permissive infection of Crandell feline kidney cells.

Confocal microscopy allowed us to localize viral nonstructural (NS) and capsid (VP) proteins and DNA simultaneously in cells permissively infected with Aleutian mink disease parvovirus (ADV). Early after infection, NS proteins colocalized with viral DNA to form intranuclear inclusions, whereas VP proteins formed hollow intranuclear shells around the inclusions. Later, nuclei had irregular outlines and were virtually free of ADV products. In these cells, inclusions of viral DNA with or without associated NS protein were embedded in cytoplasmic VP protein. These findings implied that ADV replication within an infected cell is regulated spatially as well as temporally.

Aleutian Mink Disease Virus↗

The efficacy and tolerability of controlled-release dihydrocodeine tablets and combination dextropropoxyphene/paracetamol tablets in patients with severe osteoarthritis of the hips.

A double-blind, parallel group study was undertaken in general practice to compare the efficacy of and tolerability to controlled-release (CR) dihydrocodeine tablets and combination dextropropoxyphene/paracetamol tablets in patients with severe osteoarthritis of the hip(s). Eighty-six patients were randomly allocated to receive either CR dihydrocodeine (60 mg) tablets (1 tablet twice daily to 2 tablets daily) or combination dextropropoxyphene (32.5 mg)/paracetamol (325 mg) tablets (2 tablets 3-times daily to 2 tablets 4-times daily) for a period of 2 weeks. Patients recorded in a diary card 4 times a day the severity of their pain and each morning whether or not they woke during the night due to pain in their hip(s). On entry to the study, after the first week's treatment and at the final visit another week later, the investigator assessed the patient's severity of pain on passive movement of the hip and also noted the severity of any volunteered symptoms or side-effects. After 2-weeks' treatment, pain on passive movement of the hip joint was statistically significantly less severe on CR dihydrocodeine than on dextropropoxyphene/paracetamol (p = 0.02). Nausea and vomiting were more pronounced in the dihydrocodeine than in the dextropropoxyphene/paracetamol group after the first week's treatment but by the end of the study there was no significant treatment difference in any of the volunteered side-effects. Patients on CR dihydrocodeine developed some constipation as expected and the dextropropoxyphene/paracetamol patients suffered from impaired concentration. More patients withdrew on CR dihydrocodeine than on dextropropoxyphene/paracetamol but these withdrawals tended to occur early in the trial just after initiating therapy. Tolerance in terms of withdrawals or side-effect profile did not appear to the dosage of each preparation administered. It is concluded that after 2-weeks' treatment CR dihydrocodeine provided superior analgesia to dextropropoxyphene/paracetamol with no difference in side-effects. Furthermore, CR dihydrocodeine has the advantage of twice rather than 3 or 4-times daily dosing.

Acetaminophen↗

A clinical and flow cytometric analysis of patients with nasopharyngeal cancer.

Abnormal cellular DNA content, a hallmark of malignancy, is known to be an important prognostic factor in many human solid tumors; however, no data have been published on whether cellular DNA content carries prognostic significance for patients with nasopharyngeal cancer (NPC). Archival, formalin-fixed, paraffin-embedded pathology specimens representing pretreatment tissue biopsies from 55 patients (41 men and 14 women) with NPC were analyzed for cellular DNA content in a retrospective fashion from 1968 to 1988. Individual tumors were classified as either lymphoepithelioma, squamous cell, or anaplastic carcinoma, and were staged according to International Union Against Cancer (UICC) criteria. All patients were treated with curative intent using a 4 to 6 MeV linear accelerator to total doses ranging from 50 to 60 Gy in 4 to 6 weeks. The overall 5-year actuarial survival for all 55 patients was 44.4% (men, 41%; women, 52%). Survival by T stage was as follows: T1, 65%; T2, 51%; T3, 36%; and T4, 27%. Similarly, the 5-year survival rate declined as the bulk of nodal metastases increased: N0, 62%; N2, 50%; N3, 37%; and N1, 25%. Patients who had anaplastic carcinoma had a 5-year survival of 73%, those with lymphoepithelioma had a 60% survival, and those with squamous cell cancer (SCC) had a 30% survival. There was a statistically significant difference in 5-year survival between patients with SCC and those with nonkeratinizing histologies (P less than 0.05). In addition, there was a significant association between patients older than 40 years of age with SCC and patients younger than 40 years of age with nonkeratinizing malignancies (P less than 0.01). Of the 55 tumors successfully analyzed, 22 (40%) were diploid and 33 (60%) were aneuploid. The mean coefficient of variation (CV) of all 55 samples was 6.17%. There was no significant difference in 5-year survival between patients with diploid and those with aneuploid tumors (48% versus 42%). Furthermore, there was no statistically significant survival difference between aneuploid and diploid tumors within any one histologic subgroup. There was also no significant survival difference related to the DNA index. The results indicate that the extent of local tumor spread is still the most important prognostic factor for patients treated with radiotherapy for NPC. The data support the conclusion that patients with lymphoepithelioma and anaplastic carcinomas have a superior survival to patients with squamous cell carcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗

Head injuries to children riding bicycles.

This article examines the characteristics of 150 children who were admitted to Brisbane hospitals with head injuries that were caused by bicycle riding. These children constitute over 20% of all the children with head injuries who were admitted to hospital; accidents involving bicycle riding are the second largest single cause of head injury in these children, after falls. There was one death in the group, and three children were moderately disabled nine months after the injury. These four children all had Glasgow coma scores of less than 9 on their admission to hospital. Only two of the 150 children wore helmets. A survey of a random subgroup of children who had sustained head injuries confirmed our opinion that many children owned helmets but did not wear them for fear of peer derision. It is suggested that this refusal can be overcome by a combination of legislative enforcement, helmet design and promotion.

Australia↗

Remission onset and relapse in depression. An 18-month prospective study of course for 100 first admission patients.

BACKGROUND: Few prospective studies of course for first admission depressives are reported. METHODS: One hundred consecutive depressed inpatients were followed prospectively over 18 months. Course was defined operationally using the Hamilton Depression scale and ICD-10 criteria. Results were analysed using life-tables. RESULTS: The cumulative probabilities of remission onset by 3 and 18 months were 0.67 (95% C.I.=0.57-0.77) and 0.82 (95% C.I.=0.74-0.90). The cumulative probability of relapse was 0.25 (95% C.I.=0.15-0.35); 53% of those relapsing did so in the first 2 months. Younger age at onset, longer illness length, higher depression and anxiety ratings, predicted delayed remission onset. ICD-10 episode severity predicted relapse. CONCLUSIONS: The chances of remission onset at 3 months and relapse were increased relative to other studies; risk of chronicity was similar. Predictors of outcome to emerge were similar to other studies. CLINICAL IMPLICATIONS: Adoption of these remission onset criteria may identify earlier (at 3 months), subjects at high risk of chronicity. After remission onset, subjects with severe illnesses warrant careful follow-up to detect relapse, particularly during the first 2 months. LIMITATIONS: The operational criteria used were different to other prospective studies. Relatively few psychosocial variables were included in the analysis.

Adolescent↗