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1.
Biopreserv Biobank ; 19(2): 136-142, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33567235

ABSTRACT

Dry blood spots (DBS) offer many advantages over other blood banking protocols due to the reduction of time and equipment needed for collection and the ease of processing, storage, and shipment. In addition, the sample size makes it a very attractive method when considering the banking of small pediatric samples. On that note, the Centers for Disease Control and Prevention (CDC) preanalytical standards for DBS are commonly used in the worldwide mass spectrometry-based inborn errors of metabolism screening programs. However, these guidelines may not apply for analytes and protocols not included in these programs. In fact, the availability of leftover samples and the ongoing interest in protocols outside this scenario are providing us with new DBS biobanking insights. Herein, we review the literature for indicators that should be considered in the design of prospective fit for purpose DBS biobanks, especially for those focused mostly on pediatric and OMIC platforms.


Subject(s)
Biological Specimen Banks , Dried Blood Spot Testing , Humans , Mass Spectrometry , Prospective Studies , United States
2.
Gynecol Oncol ; 158(1): 47-53, 2020 07.
Article in English | MEDLINE | ID: mdl-32381362

ABSTRACT

OBJECTIVES: To determine the impact of chemotherapy dose reductions and dose delays on progression-free survival (PFS) in women with ovarian cancer receiving first line chemotherapy in a real world prospective cohort study. METHODS: Patients with newly diagnosed epithelial ovarian (or peritoneal, fallopian tube) cancer enrolled in a national Australian prospective study, OPAL, who commenced three-weekly carboplatin (AUC 5 or 6) and paclitaxel 175 mg/m2 (CP) or carboplatin (AUC 5 or 6) and dose-dense weekly paclitaxel 80 mg/m2 (DD-CP) were eligible. Primary endpoint was PFS. RESULTS: 634 evaluable patients, 309 commenced CP and 325 DD-CP. Patient's age was similar in the two groups (median 62 years, range 21-79). All planned chemotherapy doses were completed by 66% vs 40% (p < 0.001) in the CP and DD-CP groups respectively. There was at least one treatment delay in 28% vs 58% (p < 0.001) in the CP and DD-CP groups, respectively, and 29% vs 49% (p < 0.001), respectively, required at least a 15% dose reduction for either carboplatin or paclitaxel. Median PFS was 29.2 [22.9, 43.8] and 21.5 [19.4, 23.1] months in the CP and DD-CP groups respectively. Adjusting for age, histology and FIGO stage PFS did not differ between treatment groups. Median PFS was similar in patients irrespective of dose reduction or dose delay. CONCLUSION: Patients receiving DD-CP required more dose reductions and delays due to haematological toxicities and lower completion rates than CP without significant difference in median PFS between CP and DD-CP. Median PFS was similar in patients irrespective of dose reduction or dose delay.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Ovarian Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma, Ovarian Epithelial/surgery , Chemotherapy, Adjuvant , Cohort Studies , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Middle Aged , Neoadjuvant Therapy , Ovarian Neoplasms/surgery , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Progression-Free Survival , Prospective Studies , Retrospective Studies , Young Adult
3.
Genes Immun ; 11(8): 609-21, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20861866

ABSTRACT

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the developed world. We conducted a genome-wide association study in a series of families enriched for AMD and completed a meta-analysis of this new data with results from reanalysis of an existing study of a late-stage case-control cohort. We tested the top findings for replication in 1896 cases and 1866 controls and identified two novel genetic protective factors for AMD. In addition to the complement factor H (CFH) (P=2.3 × 10⁻64) and age-related maculopathy susceptibility 2 (ARMS2) (P=1.2 × 10⁻6°) loci, we observed a protective effect at rs429608, an intronic SNP in SKIV2L (P=5.3 × 10⁻¹5), a gene near the complement component 2 (C2)/complement factor B (BF) locus, that indicates the protective effect may be mediated by variants other than the C2/BF variants previously studied. Haplotype analysis at this locus identified three protective haplotypes defined by the rs429608 protective allele. We also identified a new potentially protective effect at rs2679798 in MYRIP (P=2.9 × 10⁻4), a gene involved in retinal pigment epithelium melanosome trafficking. Interestingly, MYRIP was initially identified in the family-based scan and was confirmed in the case-control set. From these efforts, we report the identification of two novel protective factors for AMD and confirm the previously known associations at CFH, ARMS2 and C3.


Subject(s)
Complement Factor H/genetics , DNA Helicases/genetics , Macular Degeneration/genetics , Proteins/genetics , Vesicular Transport Proteins/genetics , Adult , Aged , Aged, 80 and over , Alleles , Genome-Wide Association Study , Genotype , Humans , Middle Aged , Polymorphism, Single Nucleotide
4.
J Psychopharmacol ; 24(10): 1439-45, 2010 Oct.
Article in English | MEDLINE | ID: mdl-19351803

ABSTRACT

This article presents a systematic, retrospective case-note survey of a specialist obsessive-compulsive disorder (OCD) outpatient service. We explore the frequency of 'high-dose' selective serotonin reuptake inhibitor (SSRI) prescribing and describe clinical outcomes in a naturalistic clinical setting. Patients receiving high doses were compared with 'control' cases at the following three time-points: referral, initiation of high-dose SSRI and last clinical assessment.Twenty-six (13.5%) out of 192 patients received high-dose treatment for 3-364 weeks (mean 81.5 weeks; SD = ±95.1). At referral, high-dose patients were significantly more likely than controls to be male, and to have received Cognitive Behavioural Therapy (CBT), although illness severity and complexity did not differ. At initiation of dose escalation, however, high-dose patients were significantly more symptomatic than controls (Yale-Brown Obsessive Compulsive Scale score [Y-BOCS 25.4 vs. 17.7]). At the last assessment, patients on high-dose treatment showed significant within-group improvements (Y-BOCS 25.35 vs. 20.95), although endpoint scores for the high-dose group remained significantly higher than control patients treated for a matched period (Y-BOCS 21.0 vs. 15.5), suggesting enduring treatment-resistance. Frequency of adverse effects did not significantly differ between the two groups. Our results suggest that high-dose SSRI was associated with clinical improvement and well-tolerated in a particularly refractory OCD sample.


Subject(s)
Obsessive-Compulsive Disorder/drug therapy , Selective Serotonin Reuptake Inhibitors/administration & dosage , Selective Serotonin Reuptake Inhibitors/therapeutic use , Adult , Cognitive Behavioral Therapy/statistics & numerical data , Diagnostic and Statistical Manual of Mental Disorders , Drug Monitoring , Female , Humans , Male , Medical Records , Middle Aged , Obsessive-Compulsive Disorder/therapy , Outpatient Clinics, Hospital/statistics & numerical data , Practice Patterns, Physicians' , Retrospective Studies , Selective Serotonin Reuptake Inhibitors/adverse effects , Severity of Illness Index , Sex Characteristics , Treatment Outcome , Young Adult
5.
J Psychopharmacol ; 23(1): 6-13, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18515449

ABSTRACT

The association between schizophrenia and obsessive-compulsive disorder (OCD) is complex. This study systematically examined a UK cohort of clozapine-treated individuals with schizophrenia/schizoaffective disorder. Fourteen of 59 cases (24%) scored positively on item H of the Mini-International Neuropsychiatric Interview (MINI) for OCD. The mean Yale- Brown Obsessive-Compulsive Scale (Y-BOCS) score in MINI-positive cases was 17.6 (SD+/-6.3). Sixty-four percent scored 16 or more on the Y-BOCS, representing clinically meaningful illness severity. Seven (50%) patients with OCD had previously received the diagnosis by their treating clinicians and were already receiving with selective serotonin re-uptake inhibitors (SSRIs) treatment. OCD cases scored significantly worse than their non-OCD counterparts on the Abnormal Involuntary Movement Scale (P=0.01) and the Simpson Angus Scale (SAS; P=0.01). There was also a non-significant trend toward higher ratings for OCD cases on the Clinical Global Impression-Schizophrenia scale (P=0.06). Comparing the OCD cases taking SSRI (n=7) with those not on SSRI (n=7), significant differences emerged on the SAS (P=0.03). Our results suggest that OCD is common among patients receiving clozapine for schizophrenic disorders and that the comorbidity is associated with greater motoric impairment. The role of medication in this condition remains unclear.


Subject(s)
Antipsychotic Agents/adverse effects , Clozapine/adverse effects , Obsessive-Compulsive Disorder/drug therapy , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Adult , Cohort Studies , Cross-Sectional Studies , Diazepam/therapeutic use , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Muscarinic Antagonists/therapeutic use , Obsessive-Compulsive Disorder/diagnosis , Psychotic Disorders/complications , Psychotic Disorders/diagnosis , Psychotic Disorders/epidemiology , Schizophrenia/complications , Schizophrenia/diagnosis , Schizophrenia/epidemiology , Selective Serotonin Reuptake Inhibitors/therapeutic use , Severity of Illness Index , United Kingdom/epidemiology
6.
Genes Immun ; 9(3): 231-9, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18340363

ABSTRACT

Complement factor H (CFH) is a key regulator of the alternative pathway of complement and its mutations have been associated with membranoproliferative glomerulonephritis type II, atypical hemolytic uremic syndrome and age-related macular degeneration (AMD), suggesting that alternative pathway dysregulation is a common pathogenetic feature of these ocular and renal conditions. In this study we tested the hypothesis that common CFH variants have a global role in renal function in the Australian population-based Blue Mountains Eye Study (BMES). We replicated the association of I62V with estimated glomerular filtration rate (GFR; P=0.017) and creatinine clearance (CRCL; P=0.015). The minor allele of I62V (G) was deleterious: adding one copy of the G allele decreased GFR/CRCL by approximately 0.98 ml min(-1) per 1.73 m(2) (95% confidence interval (CI): 0.97, 0.99). We also replicated the association of Y402H with AMD and provided an unbiased estimate of population attributable risk (PAR). The minor allele of Y402H (C) was deleterious: the odds ratio estimate of CC genotype compared to TT was 1.87 (95% CI: 1.44, 2.45). The PAR of the C allele was estimated as 0.22 (95% CI: 0.15, 0.28). In summary, in the BMES population we confirmed the association between I62V and renal function, as measured by the estimated GFR, plus the association of Y402H with both early- and late-stage AMD.


Subject(s)
Complement Pathway, Alternative/genetics , Genetics, Population , Kidney/pathology , Macular Degeneration/epidemiology , Macular Degeneration/genetics , Phenotype , Complement Factor H/genetics , Gene Frequency , Humans , Mutation, Missense/genetics , New South Wales/epidemiology , Odds Ratio
8.
Teratog Carcinog Mutagen ; Suppl 1: 225-33, 2003.
Article in English | MEDLINE | ID: mdl-12616613

ABSTRACT

The year 2001 witnessed the sequencing of 90% of the euchromatic region in the human genome but the ultimate goal to delineate the positions of all genes is yet to be achieved. Fluorescence In Situ Hybridization (FISH) is one of the methods for localizing genes on chromosomes. In the present study, diagnostic utility of single-, dual-, and multicolor FISH was evaluated for prenatal diagnosis, cancer genetics, and screening of various congenital anomalies (sex chromosomal and autosomal). Centromeric probes for chromosomes X and Y were used for screening minor aneuploid cell lines (XXY, XO, and XXX) in the cases of primary amenorrhea and suspected Klinefelter syndrome. The cases with ambiguous genitalia were analyzed using a probe specific for the sex-determining region (SRY). Suspected cases of Down syndrome were subjected to FISH using probe specific for chromosome 21. FISH was also used to study gene alterations in retinoblastoma and myeloid leukemias. Prenatal diagnosis was done to screen for aneuploidies of chromosomes 13, 18, 21, X, and Y using FISH on uncultured cells from amniotic fluid and chorionic villi sampling. The screening for common aneuploidies was extended to abortuses from spontaneous abortions. Using FISH, low-level mosaicism could be identified in some cases of primary amenorrhea and suspected Klinefelter syndrome. Submicroscopic gene rearrangements could be detected using FISH in cases of ambiguous genitalia and cancers. Further interphase FISH could provide results within 24 hours. To conclude, FISH adds to the diagnostic utility of routine cytogenetics and its use on interphase nuclei overcomes the difficulty of conventional cytogenetics, thereby reducing the time between sampling and diagnosis to 24 hr.


Subject(s)
Cytodiagnosis/methods , Cytogenetics/methods , Antineoplastic Agents/therapeutic use , Bone Marrow Transplantation , Cell Line , Chromosome Painting , Female , Genetic Testing , Humans , In Situ Hybridization, Fluorescence , Infant, Newborn , Interferon-alpha/therapeutic use , Leukemia, Myeloid/diagnosis , Leukemia, Myeloid/drug therapy , Leukemia, Myeloid/genetics , Leukemia, Myeloid/therapy , Male , Neonatal Screening , Pregnancy , Pregnancy Complications/diagnosis , Prenatal Diagnosis , Prognosis , Sex Chromosome Disorders/diagnosis , Sex Chromosome Disorders/genetics
9.
J Affect Disord ; 72(2): 177-84, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12200208

ABSTRACT

BACKGROUND: Remission from major depression may be conceptualised in terms of a cut-off score on an appropriate rating scale. Candidate values proposed hitherto have not been directly validated. METHOD: The relationship between The Clinical Global Impression Scale for Severity (CGI-S) and the Montgomery-Asberg Depression Rating Scale (MADRS) was explored in 684 major depressed patients (1114 observations). The value on the MADRS which had greatest concordance with remission, as defined by the CGI-S, was computed using two models. Concordance between clinician and patient judgements of global illness were also compared. RESULTS AND CONCLUSION: The two models yielded optimal definitions of remission of <9 and <10 on the MADRS. Either value offers a workable operationalisation of remission and there is little to choose between them. CLINICAL RELEVANCE: The data confirm that MADRS <10 should provide the clinician with a valid, and reasonably objectifiable, target for remission


Subject(s)
Depressive Disorder, Major/diagnosis , Surveys and Questionnaires , Adult , Aged , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Remission, Spontaneous , Reproducibility of Results , Severity of Illness Index
10.
J Affect Disord ; 71(1-3): 181-7, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12167514

ABSTRACT

BACKGROUND: This paper describes the relationship between entry criteria and eligible population for inclusion in Major Depression (MD) clinical trials. Inclusion criteria for a MD study typically require patients to pass a threshold score on a depression rating scale, most commonly the HAM-D or MADRS. A Score To Enter (STE) of > or = 17 on the HAM-D 17-item scale is a typical value, although higher values (i.e. > or = 22 or even > or = 25 points) are often used. It is commonly supposed that patients with higher baseline scores form a more sensitive sample for discriminating active drug from placebo. METHOD: We present data from a sample of depressed hospital outpatients and describe their general characteristics. We then introduce a model, based upon this sample, which predicts the impact of STE on eligible trial population. RESULTS AND CONCLUSION: A small increase in STE has a marked effect on eligible population: an increase in HAM-D (17 item) STE from 17 to 21 and 25 reduces the eligible population by 42 and 76%, respectively. These predictions are reasonably robust when our model is validated with known clinical trial data. CLINICAL RELEVANCE: Our findings have major implications for planning and managing Major Depression trials as higher STEs substantially restrict the proportion of patient eligible for study.


Subject(s)
Clinical Trials as Topic , Depressive Disorder/psychology , Depressive Disorder/therapy , Eligibility Determination , Sample Size , Adolescent , Adult , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Research Design , Severity of Illness Index
11.
Int J Psychiatry Clin Pract ; 6(2): 73-81, 2002.
Article in English | MEDLINE | ID: mdl-24931932

ABSTRACT

INTRODUCTION: This paper describes a pilot study of reliability in the risk assessment of people with mental health problems. Specifically, we explore the evidence for professional and gender bias in ratings, in addition to the general level of agreement between raters. METHOD: Six professional groups (psychiatrists, junior psychiatric doctors, nurses, community psychiatric nurses, social workers and occupational therapists) participated in the study and rated 159 patients on a nine-item scale which assessed different components of risk. RESULTS: Contrary to some earlier work, we found no clear evidence that any one group consistently rated more extremely than any other group. Women were more cautious than men in their ratings, and this concurs with previous studies. Finally, a reliability study of randomly selected pairs of raters showed only moderate levels of agreement and, in some instances, the levels of disagreement were high enough to warrant concern. CONCLUSION: These findings are discussed in the context of current risk assessment practice and the problems associated with investigating reliability in naturalistic settings and designing appropriate rating tools for risk. (Int J Psych Clin Pract 2002; 6: 73-81).

12.
Hum Mol Genet ; 10(22): 2501-8, 2001 Oct 15.
Article in English | MEDLINE | ID: mdl-11709537

ABSTRACT

Non-syndromic low frequency sensorineural hearing loss (LFSNHL) affecting only 2000 Hz and below is an unusual type of hearing loss that worsens over time without progressing to profound deafness. This type of LFSNHL may be associated with mild tinnitus but is not associated with vertigo. We have previously reported two families with autosomal dominant LFSNHL linked to adjacent but non-overlapping loci on 4p16, DFNA6 and DFNA14. However, further study revealed that an individual with LFSNHL in the DFNA6 family who had a recombination event that excluded the DFNA14 candidate region was actually a phenocopy, and consequently, DFNA6 and DFNA14 are allelic. LFSNHL appears to be genetically nearly homogeneous, as only one LFSNHL family is known to map to a different chromosome (DFNA1). The DFNA6/14 critical region includes WFS1, the gene responsible for Wolfram syndrome, an autosomal recessive disorder characterized by diabetes mellitus and optic atrophy, and often, deafness. Herein we report five different heterozygous missense mutations (T699M, A716T, V779M, L829P, G831D) in the WFS1 gene found in six LFSNHL families. Mutations in WFS1 were identified in all LFSNHL families tested, with A716T arising independently in two families. None of the mutations was found in at least 220 control chromosomes with the exception of V779M, which was identified in 1/336 controls. This frequency is consistent with the prevalence of heterozygous carriers for Wolfram syndrome estimated at 0.3-1%. An increased risk of sensorineural hearing loss has been reported in such carriers. Therefore, we conclude that mutations in WFS1 are a common cause of LFSNHL.


Subject(s)
Hearing Loss, Sensorineural/genetics , Membrane Proteins/genetics , Alleles , Auditory Threshold , Base Sequence , Chromosomes, Human, Pair 4/genetics , DNA/chemistry , DNA/genetics , DNA Mutational Analysis , Family Health , Female , Gene Frequency , Haplotypes , Hearing Loss, Sensorineural/pathology , Humans , Male , Microsatellite Repeats , Mutation , Mutation, Missense , Pedigree , Polymorphism, Single Nucleotide , Polymorphism, Single-Stranded Conformational
13.
Int Clin Psychopharmacol ; 15(4): 197-206, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10954059

ABSTRACT

Several case reports have engendered concern about the safety of coadministering lithium and selective serotonin reuptake inhibitor (SSRI) antidepressants and there are theoretical reasons to suppose that lithium and serotonergic antidepressants may be associated with dangerous interactions. Systematic reports regarding combination therapy with lithium and SSRI antidepressants were assimilated for the purpose of this review. Although there are many publications, few are directly informative as to safety and tolerability. A total of 503 patients are considered in systematic reports and, among these, no serious or life-threatening adverse events can be identified. Such data as there are demonstrate little potential for toxic interactions between lithium and SSRIs, although new, non-serious, adverse events do frequently arise. The evidence for the efficacy of addition of lithium to SSRIs in treatment refractory depression is only provisional.


Subject(s)
Antimanic Agents/administration & dosage , Bipolar Disorder/drug therapy , Depressive Disorder, Major/drug therapy , Lithium Carbonate/administration & dosage , Selective Serotonin Reuptake Inhibitors/administration & dosage , Antimanic Agents/adverse effects , Bipolar Disorder/diagnosis , Bipolar Disorder/psychology , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/psychology , Drug Therapy, Combination , Humans , Lithium Carbonate/adverse effects , Selective Serotonin Reuptake Inhibitors/adverse effects , Treatment Outcome
14.
Ophthalmic Epidemiol ; 7(4): 285-91, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11262675

ABSTRACT

There is a consistent correlation between sporadic hereditary retinoblastoma and parental age. It has been proven beyond doubt that the birth rank is correlated with parental age. In the present study, a test for the effect of birth rank was performed in order to assess the risk of developing retinoblastoma with increased parental age. The study of the effect of birth rank showed a significant association between sporadic retinoblastoma (bilateral and unilateral) and late para, indicating that fresh germline mutations must have taken place in some of the sporadic cases. An investigation of the effect of birth rank on familial cases, obtained from published papers and our own series, showed that familial retinoblastoma is significantly associated with early para, suggesting early parental age. Further analysis of the mean paternal and maternal ages of sporadic cases (bilateral and unilateral) showed that the mean paternal age of sporadic bilateral (sporadic hereditary) cases was higher than that of sporadic unilateral cases (p<0.05). No such correlation was seen with mean maternal age. Thus, the present study shows that a high paternal age may be associated with sporadic bilateral (sporadic hereditary) retinoblastoma.


Subject(s)
Maternal Age , Paternal Age , Retinal Neoplasms/epidemiology , Retinoblastoma/epidemiology , Adult , Age Factors , Female , Genetic Predisposition to Disease , Humans , Incidence , India/epidemiology , Infant, Newborn , Male , Middle Aged , Retinal Neoplasms/congenital , Retinal Neoplasms/genetics , Retinoblastoma/congenital , Retinoblastoma/genetics , Risk Factors
15.
J Environ Pathol Toxicol Oncol ; 18(4): 339-47, 1999.
Article in English | MEDLINE | ID: mdl-15281247

ABSTRACT

In a prospective study of 50 patients with retinoblastoma, a 10-year-old girl with unilateral (right eye) retinoblastoma was found to have 45,X karyotype. Because there is increasing evidence of nongonadal neoplasia occurring in patients with Turner syndrome in addition to the gonadal tumor from dysgenetic gonads, we reviewed the occurrence of nongonadal neoplasia in Turner syndrome cases. Of all the nongonadal neoplasia, neurogenic tumors show a preponderence among children and young adults with Turner syndrome. To the best of our knowledge, this is the first reported case of Turner syndrome with retinoblastoma. The available literature strongly suggests that patients with Turner syndrome may be at risk of developing neurogenic tumors. Further studies are necessary to identify the role of some X-linked genes that escape X-inactivation in tumorigenesis in patients with Turner syndrome.


Subject(s)
Chromosomes, Human, X , Genetic Diseases, X-Linked , Retinal Neoplasms/complications , Retinoblastoma/complications , Turner Syndrome/complications , Child , Female , Humans , Male , Retinal Neoplasms/genetics , Retinal Neoplasms/pathology , Retinoblastoma/genetics , Retinoblastoma/pathology , Turner Syndrome/genetics , Turner Syndrome/pathology
16.
J Affect Disord ; 47(1-3): 87-96, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9476748

ABSTRACT

BACKGROUND: Much attention is being given to developing clinical practice guidelines for management of mental health disorders. The aim of this study was to field test a prototype protocol for the pharmacologic treatment of Major Depression. METHOD: The protocol consisted of four, six week, treatment phases with critical choices in therapy defined by scores on the MADRS (Montgomery Asberg Depression Rating Scale). Observational data as collected on the behaviour of the protocol in terms of relevance, acceptability, ease of use and effectiveness. RESULTS: Effectiveness of the protocol was good for those patients who were retained within it, with three quarters of them attaining remission. However more than half of all patients dropped out-non attendance and adverse events being the most common reasons for this. CONCLUSION: The protocol for the treatment of Major Depression appeared relevant, easy to use and potentially effective. LIMITATION: Problems with non-adherence by both doctors and patients posed major challenges to the protocol's design. Such difficulties demonstrate the need to field test any proposed design as preconceptions about a protocol's performance may be misplaced. CLINICAL RELEVANCE: The protocol tested represents progress towards the goal of developing optimal strategies for the use of pharmacotherapeutic agents in the treatment of depression.


Subject(s)
Depressive Disorder/drug therapy , Lithium/therapeutic use , Lofepramine/therapeutic use , Paroxetine/therapeutic use , Adolescent , Adult , Aged , Clinical Protocols , Depressive Disorder/diagnosis , Depressive Disorder/psychology , Female , Humans , Male , Middle Aged , Patient Compliance , Patient Dropouts , Psychiatric Status Rating Scales , Research Design/standards , Treatment Outcome
17.
Int J Psychiatry Clin Pract ; 2(4): 251-4, 1998.
Article in English | MEDLINE | ID: mdl-24927087

ABSTRACT

Fourteen patients with major depression, resistant to previous pharmacotherapies, were treated by the addition of lithium (target range 0.6-0.8 mmol/l) to nefazodone (≥400 mg/day) and were prospectively monitored for 6 weeks to assess safety and tolerability. There were 42 emergent adverse events-most commonly headache, nausea, gastro-intestinal disturbances, tremor, polyuria/polydipsia, dry mouth and tiredness. Information on ten additional patients receiving combined treatment with lithium and nefazodone was collected by retrospective chart review, and it was found that similar adverse events (tremor, dry mouth and tiredness) had occurred in these patients. We conclude that when lithium is added to nefazodone, new adverse events do occur, but that the treatment is safe and tolerable.

18.
Br J Gen Pract ; 47(417): 233-4, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9196968

ABSTRACT

About 1% of patients in general practice take antidepressants for long periods. Many receive repeat prescriptions, without review. It might be assumed that these patients are well and are on adequate maintenance treatment. Our findings refute this assumption; of 78 patients on long-term repeats, only a third were in remission and a fifth had Beck Depression Inventory scores suggesting persisting syndromal major depression. Subtherapeutic dosing of classic tricyclics was the norm rather than the exception. Patients on long term antidepressant treatment need regular review and adequate treatment to ensure remission is maintained.


Subject(s)
Antidepressive Agents/administration & dosage , Depressive Disorder/drug therapy , Adult , Aged , Aged, 80 and over , Antidepressive Agents, Tricyclic/administration & dosage , Family Practice , Female , Humans , Long-Term Care , Male , Middle Aged , Personality Inventory , Selective Serotonin Reuptake Inhibitors/administration & dosage , Treatment Outcome
19.
J Laryngol Otol ; 111(2): 109-12, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9102432

ABSTRACT

Otosclerosis is an early-middle adult life genetic disease affecting bone remodelling in the ear. Current knowledge of otosclerosis as an inherited disease dates to the mid-19th century, and we report here an attempt to understand the genetics of otosclerosis and detect its heterogeneity. The analysis was conducted on 151 otosclerotic families. The results of our study indicate that while heredity plays an important role in the manifestation of the disease a substantial portion of otosclerotic cases could arise due to non-genetic causes.


Subject(s)
Otosclerosis/genetics , Adolescent , Adult , Age of Onset , Aged , Female , Genes, Dominant , Heterozygote , Humans , India , Male , Middle Aged , Otosclerosis/etiology
20.
Acta Genet Med Gemellol (Roma) ; 46(4): 193-8, 1997.
Article in English | MEDLINE | ID: mdl-9862007

ABSTRACT

The polymorphisms of constitutive heterochromatin regions, present on chromosomes 1, 9, 16 and Y, are inherited in a Mendelian fashion. The C-band heteromorphism has been reported to be associated with various types of cancer. Heterochromatin is considered to play a role in protecting genome against the mutagens. Changes in the quantity and proportion of the different types of satellite DNA might increase the genetic susceptibility in people with heterochromatic variations, which in turn cause chromosome instability and predispose the individual to cancer. We report a case of bilateral retinoblastoma with complete absence of pericentromeric heterochromatin on one of the chromosomes number 9. A similar deficiency of pericentromeric heterochromatin on chromosome number 9 and 16 has been reported in a phenotypically normal individual and a Down syndrome case, respectively. This deficiency was found to be inherited from the father in all the three cases. Complete absence of pericentromeric heterochromatin of chromosome 9 is not being reported in association with cancer syndromes. Further studies are necessary to understand the role of this factor in normals and in those with cancer susceptibility, specially with retinoblastoma and the paternal origin of this deficiency.


Subject(s)
Chromosome Deletion , Heterochromatin/genetics , Retinoblastoma/genetics , Chromosomes, Human, Pair 9 , Humans , Infant , Karyotyping , Male , Radiography , Retinoblastoma/diagnostic imaging , Retinoblastoma/physiopathology
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