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Biomedical subjects

G Curtis

Publications and source records attributed to G Curtis.

At least 19 recordsLinked to original sources

Placebo-controlled, multicenter study of sertraline treatment for obsessive-compulsive disorder.

The safety and efficacy of sertraline versus placebo were examined in a group of nondepressed outpatients with obsessive-compulsive disorder (OCD). Patients with moderate-to-severe OCD were recruited at 10 sites. After a 1-week placebo lead-in, patients were treated in a double-blind fashion for 12 weeks with sertraline or placebo. Sertraline was administered at a starting dose of 50 mg/day, with flexible titration up to 200 mg/day. The efficacy measures were the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH), and the Clinical Global Impression Scale (CGI) Severity of Illness and Improvement subscales. One hundred sixty-seven patients were randomly assigned and received at least one dose of double-blind medication: 86 received sertraline and 81 received placebo. All efficacy measures showed significantly greater improvement in the sertraline group from the end of week 8 until the end of week 12. Significantly greater improvement (p < 0.05) in the sertraline group first became apparent by the end of week 3 on the Y-BOCS and the CGI Improvement scale, and by the end of weeks 6 and 8, respectively, on the NIMH and CGI Severity scale. Sertraline was well tolerated, without serious adverse effects. In conclusion, sertraline was safe and effective in the treatment of patients with OCD.

Adult

FRAXA and FRAXE: evidence against segregation distortion and for an effect of intermediate alleles on learning disability.

There have been several claims of segregation distortion (meiotic drive) for loci associated with diseases caused by trinucleotide repeats, leading us to test for this phenomenon in a large study of the X-linked loci FRAXA and FRAXE. We found no evidence of meiotic drive in females and no convincing evidence in males, where the limitation of risk to daughters creates a testing bias for alleles of interest. Alleles for pre- and full mutation, intermediate alleles, and common alleles were analyzed separately, with the same negative results that are extended in the discussion to claims of meiotic drive for other diseases. On the other hand, an excess risk of learning difficulties was confirmed for intermediate FRAXA alleles (relative risk, 2.58 +/- .74) and suggested for intermediate FRAXE alleles. The penetrance of learning difficulty is low, the risk being estimated as .039 for FRAXA common alleles and .101 for intermediate alleles. Because of their lower gene frequency, full mutations are a less frequent cause of learning difficulty than intermediate alleles, which contribute .0020 to total prevalence and .0012 to attributable prevalence of learning difficulty.

Alleles

Recommendations for education and training of genetic nurses and counsellors in the United Kingdom.

Genetic nurses and counsellors work as part of the professional team providing clinical genetic services from regional centres in the United Kingdom. The education and training needs of genetic nurses and counsellors have not previously been formally identified. The guidelines presented have been devised to equip practitioners to fulfil their professional role as defined in a previous study, by identifying objectives, educational pathways, and means of assessment. While academic courses provide an essential framework, experiential learning in a clinical setting is also considered a vital component of the preparation for practice.

Education, Graduate

Restriction fragment length polymorphism screening of Mycobacterium tuberculosis isolates: population surveillance for targeting disease transmission in a community.

SETTING: Alabama State Tuberculosis Control Program, USA. OBJECTIVE: To combine molecular screening data with routine information to assess transmission of Mycobacterium tuberculosis and improve control efforts. DESIGN: Since January 1994, samples from tuberculosis cases statewide have been systematically analyzed by IS6110 restriction fragment length polymorphism (RFLP). All cases during 1994-1995 with a predominate RFLP pattern were evaluated and risk factors assessed. pTBN12 was used to evaluate a large cluster in the Birmingham-Jefferson County (BJC) area. RESULTS: Statewide, a common two-band pattern was found, named JH2 (99/566, 17.5%). The most important risk associated with this pattern was homelessness (odds ratio, 8.9; P < 0.001). In the BJC area, the homeless accounted for 29% (51/175) of new cases diagnosed during the study period. For the BJC homeless, there were 13 unique RFLP patterns, and JH2 was predominant (29/33, 88%) among three clusters. Secondary analysis of the homeless JH2 cluster revealed a large group that included 19 of 24 (79%) isolates analyzed. Compared with the BJC non homeless (n = 124), the homeless were younger (P < 0.001), of male gender (P < 0.001), black race (P = 0.002), and were heavy alcohol (P < 0.001) and non-injection drug (P = 0.001) users. CONCLUSIONS: By screening tuberculosis cases statewide, a common two-band RFLP pattern was identified. Its predominance is explained by an ongoing tuberculosis epidemic among Birmingham's homeless population, highlighting RFLP as a tool for population surveillance. The pattern differences observed by pTBN12 typing clearly demonstrate that the isolates might be related but are not clonal.

Adult

The role and practice of the genetic nurse: report of the AGNC Working Party.

The role of the genetic nurse has evolved historically with the emergence of clinical genetics in the field of health care. During 1994, a Practice Working Party was convened by the Genetic Nurses and Social Workers Association in response to discussion about the role of the nurse within and between regional genetics centres. The Working Party conducted a study of the current nursing practice and attitudes of nurses and clinicians to the nursing role, as a basis for future discussion and planning for educational needs. This paper describes the role of the genetic nurse within the United Kingdom and offers suggestions for assessment of competency. Strong themes emerging from respondents' comments include the need and desire for multi-professional team work, and it is apparent that most respondents felt the families' needs would best be served by a skilful combination of medical and nursing input, rather than adherence to traditional roles.

Genetic Counseling

Unusual (CGG)n expansion and recombination in a family with fragile X and DiGeorge syndrome.

In a fragile X family referred for prenatal diagnosis, the female fetus did not inherit the full fragile X mutation from her mother, but an unexpected expansion within the normal range of CGG repeats from 29 to 39 was observed in the paternal X chromosome. Also, a rare recombination between DXS548 and FRAXAC1 was recorded in the maternal meiosis. Follow up of the neonate confirmed the same DNA genotype as in the CVS, but the child died of DiGeorge syndrome after four days and was subsequently found to carry a microdeletion of chromosome 22 using probe cEO. It is suggested that in this family the deletion of chromosome 22 is likely to be a chance event but the rare recombinant and the fragile X mutation might be causally related.

Adult

Adverse effects associated with the short-term treatment of panic disorder with imipramine, alprazolam or placebo.

Side effects play a significant role in the selection of drugs to be used in panic disorder/agoraphobia whose polyphobic symptomatology often includes a suspiciousness about taking drugs and a fear of undesired side effects which may lead to the refusal of treatment. The safety, side effects and patients' acceptance of alprazolam and imipramine versus placebo were evaluated in 1168 subjects with panic disorder/agoraphobia who had been enrolled in the second phase of the Upjohn World Wide Panic Study. Side effects that worsened over baseline to a greater extent with alprazolam than with imipramine and placebo were sedation, fatigue/weakness, memory problems, ataxia and slurred speech. In the imipramine group blurred vision, tachycardia/palpitations, insomnia, sleep disturbance, excitement/nervousness, malaise, dizziness/faintness, headache, nausea/vomiting and decrease in appetite were worse than in the other groups. In the placebo group the anxious symptoms were most prominent. The highest level of compliance was shown in the alprazolam-treated group and the lowest in the placebo-treated group. Strong predictors of side effects were not observed. If a side effect profile is known, it will be easier for a clinician to choose the right drug and the appropriate management by taking into account compliance, safety and efficacy in each patient under treatment. Further information about side effects in long-term maintenance treatment would be of great clinical pertinence in ensuring safety and enhancing patients' quality of life.

Adolescent

The option to withdraw from chronic dialysis treatment.

This multidisciplinary discussion focuses on the case of a young diabetic woman who chose to stop chronic hemodialysis during a long and complicated illness. The perspective presented here include an academic lawyer's view of such medical decisions; a hospital chaplain's view of the religious framework for end-of-life situations; a clinical psychiatrist's considerations when consulted to evaluate patients in such straits; a transplant nurse's view of the opportunities for personal interaction that such clinical situations present; and a renal social worker's approach to chronic illness, advance directives, and death in the dialysis patient population. The discussion is intended to address objectively some important issues associated with death in this population, aimed at increasing our willingness to discuss these issues more openly with patients and with our colleagues.

Adult

The impact of genetic counselling on females in fragile X families.

We report a retrospective study over the period 1981-1992 of the reproductive histories of 27 women, from 21 families, who were known or possible fragile X carriers. Eighteen women had cytogenetic and DNA linkage studies to establish their carrier risk. They subsequently received definitive carrier status information following the cloning of the gene in 1991. The remaining nine women had cytogenetic and mutation studies only. For 11 of the women their carrier risk was modified over the 11 year period. The results suggest that these women at risk of having a son with fragile X have carefully considered their reproductive choices. Three of the six women who were initially sterilised have had, or are awaiting, a reversal of sterilisation following clarification of their carrier status. There were 10 pregnancies to 10 women. Seven of the pregnancies were to women at "high" (40-100%) risk of being a carrier, and in this group only one woman chose to continue the pregnancy without prenatal diagnosis. Three pregnancies were to women at "medium" or "low" (< 39%) risk of being a carrier. None of the three chose prenatal diagnosis and one affected male was born to this group.

Female

A reinvestigation of thirty three fragile(X) families using probe StB12.3.

We have reinvestigated 33 fragile X families using probe StB12.3. In 31 families the affected individual showed an insert while in 2 families no insert was detected. The insert fell into two size categories: small (less than 0.5 kb); and large (greater than 0.6 kb) accompanied by methylation of an EagI site. All individuals of either sex having a small insert were fra(X) negative and intellectually normal, while all males having a large insert were fra(X) positive and intellectually impaired. Females having a large insert were either fra(X) positive or negative and either intellectually normal or impaired. No new mutation was found. All daughters of males with a small insert had a small insert; females with a large insert produced males and females who had a large insert, while females with a small insert had offspring with either a large or a small insert. However, females with a small insert tended to fall into one of two categories: either they had only children with a small insert or only children with a large insert, there being only one exception to this rule. We found four unexpected small inserts, two in unrelated spouses and two in female carriers who proved to be compound heterozygotes, indicating that they had inherited an insert from both their parents. These observations suggest that individuals with a small insert must be not uncommon in the general population.

DNA Probes

Earliest Homo.

The origin of our own genus, Homo, has been tentatively correlated with worldwide climatic cooling documented at about 2.4 Myr (million years). It has also been conjectured that members of Homo made the first stone tools, currently dated at 2.6-2.4 Myr. But fossil specimens clearly attributable to Homo before about 1.9 Myr have been lacking. In 1967 a fossil hominoid temporal bone (KNM-BC1) from the Chemeron Formation of Kenya was described as family Hominidae gen. et sp. indet. Although a surface find, its provenance within site JM85 (BPRP site K002) was established and a stratigraphic section provided indicating the specimen's position. This evidence has been affirmed but the exact age of the fossil was never determined, and the absence of suitable comparative hominid material has precluded a more definitive taxonomic assignment. Here we present 40Ar/39Ar age determinations on material from the hominid site indicating an age of 2.4 Myr. In addition, comparative studies allow us to assign KNM-BC1 to the genus Homo, making it the earliest securely known fossil of our own genus found so far.

Animals

A family with X-linked deafness showing linkage to the proximal Xq region of the X chromosome.

Linkage analysis has been carried out in a family with severe congenital sensorineural deafness with a structural abnormality of the inner ear. Recombinations show the gene responsible for deafness in this family to lie between the loci DXS255 (Xp11.22) and DXS94 (Xq22). Close linkage was found to locus DXS159 (cpX289) in Xq12, with a LOD score of 3.155 and 0 recombination. This location is consistent with other linkage studies of X-linked deafness.

Chromosome Mapping

Inhibition of morphological transformation of C3H10T1/2CL8 mouse embryo cells by multiple carcinogen treatments.

C3H10T1/2CL8 cells treated on the first day after seeding with benzo[a]pyrene (B[a]P) and then treated again with B[a]P displayed an inhibited response of morphological transformation if the second treatment was administered from 14 days to 33 days after seeding. Under these conditions the cells exhibited up to 100% inhibition of morphological transformation, the extent of inhibition being related to the concentration of B[a]P administered in the second treatment. 3-Methylcholanthrene (3MC) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) also inhibited B[a]P-induced morphological transformation as a function of concentration when administered to cells 21 days after the initial B[a]P treatment. Delayed recovery of transformed foci was examined in cells treated with B[a]P on days 1 and 22 and scored 6-9 weeks after the first B[a]P treatment. No recovery of cell transformants was observed. Reconstruction experiments with normal and transformed C3H10T1/2CL8 cells suggested that selective cytotoxicity to incipient transformed cells could account for the inhibition by MNNG, but could not account for up to 50% of the inhibition induced by the second treatment of B[a]P or 3MC.

Animals

Viral agents in two-stage cervical carcinogenesis: an experimental study in mice.

The role of chemical and viral agents in the development of cervical cancer in mice was studied by repeated carcinogen applications, repeated intravaginal instillations of HSV type II virus, and single carcinogen application as initiating agent followed by repeated instillations of virus as promoter. In all the animals studied, repeated applications of 9,10-dimethylbenzanthracene (DMBA) induced dysplastic conditions of the cervix and vagina, mild, moderate, and severe, as well as a large number of invasive squamous cell carcinomas. DMBA alone as initiating agent did not induce tumors or marked dysplasia; when followed by repeated applications of HSV2 virus only mild dysplastic lesions occurred. Repeated applications of HSV2 alone produced inflammatory changes of the cervix and vagina. It is concluded that repeated intravaginal instillation of HSV2 virus as done in this study does not induce cervical cancer or its precursors, and in a two-stage system is only weakly a promoter of carcinogen-induced latent tumor cells.

9,10-Dimethyl-1,2-benzanthracene