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Depression is the most common psychiatric condition found in older people. It is associated with increased mortality and adversely affects quality of life. Although the majority of depressive episodes are seen and treated in primary care, studies suggest in primary care there is under-detection and inadequate management of depression in older people. In line with national policy in the UK this paper argues that training needs to be multidisciplinary and multiagency, and meet the requirements of local needs. It outlines a course that meets the expectation that specialist mental health workers such as mental health nurses should provide training and advice for those providing care and treatment in primary care. The paper reports upon the design and evaluation of a pilot multidisciplinary training course for health professionals and voluntary sector workers in the detection and management of depression in the older person. The course consisted of three 1-day workshops and four consecutive courses were offered, with a total of 40 health professionals and voluntary sector workers completing the training. The training was evaluated using a questionnaire examining knowledge and confidence and by a scenario using an older person whom was potentially depressed. Results found a significant difference between pre- and post-test for knowledge of depression in the older person and confidence in both detecting and managing depression. Results of the scenario revealed that there was a significant change from pre- to post-test training in the type of questions participants would ask the older person to detect and assess depression. There was also a significant increase in the ability to identify types of interventions and local services available, which would help an older person with depression. The implications, limitations and future directions for research are discussed.

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A major problem with experiments involving the correction of cystic fibrosis by gene transfer has been reliably detecting the transgenic message and distinguishing this from an endogenous message and from vector DNA. We have exploited the SV40 small T antigen intron present in an expression vector containing the CFTR cDNA (pCFAS) using a primer directed to the spliced sequence to allow specific and precise detection of the transgeneic message.

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OBJECTIVE: To determine the prevalence of the most common cystic fibrosis mutations in pregnancies complicated by fetal echogenic bowel by using DNA testing. METHODS: Forty-five pregnancies with fetal echogenic bowel were studied prospectively for cystic fibrosis mutations. Using polymerase chain reaction, DNA from fetal amniocytes (n = 21), fetal blood (n = 5), or parental blood (n = 19) was amplified and tested for delta F508, G551D, G542X, and 621 + 1G-->T cystic fibrosis mutations, which account for about 85% of the mutations in the British population. In selected cases, further mutations were tested according to the parental ethnic background. RESULTS: Only one of the 26 fetuses screened was heterozygous for cystic fibrosis mutations. Among 38 parental samples screened from the remaining 19 pregnancies, cystic fibrosis mutations were detected in two cases, only one of the parents being a carrier in each case. The prevalence of cystic fibrosis carrier status in fetal and parental samples (1:26 and 1:19, respectively) is within the expected prevalence in the British population (1:25). No fetuses were affected by cystic fibrosis in this series, but five were found to have growth restriction, two trisomy 21, two congenital infection, and two bowel obstruction. CONCLUSION: Our results suggest that ultrasonographic detection of fetal echogenic bowel is not associated with an increased prevalence of cystic fibrosis mutations in pregnancies at low risk for this disease.

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Phase one clinical trials for gene therapy of cystic fibrosis are in progress using either liposomes or adenoviral vectors for CFTR gene transfer to epithelial cells in the airways. In addition to electrophysiological measurements, expression of vector CFTR is usually assessed by RT-PCR. We have developed a CFTR-expression vector, pCFAS, that simplifies the distinction of transgene-derived CFTR mRNA from endogenous mRNA. Two point mutations were introduced into CFTR cDNA which eliminated a SphI restriction site and created a new, unique AgeI restriction site. Neither mutation altered the predicted amino acid sequence of the protein. Restriction digestion of RT-PCR products from cells transfected with pCFAS allowed the differentiation of transgene and endogenous CFTR transcripts. To verify function of the mutated CFTR, the plasmid was transferred into freshly obtained nasal epithelial cells from CF patients ex vivo using cationic liposomes. Fluorescence microscopy using the halide-sensitive fluorophore SPQ demonstrated restoration of cAMP-mediated Cl- secretion. This plasmid will be useful for CFTR gene transfer studies in vitro and in vivo.

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We have assessed the effect of screening for cystic fibrosis (CF) carrier status on anxiety levels, attitudes, knowledge and actions of participants in a pilot programme conducted through primary health care services. Over 3000 individuals were screened and 100 carriers with no previous family history were identified. Varying degrees of anxiety were found to be associated initially with a positive result, but most of this was allayed by genetic counselling, and we find no adverse long-term psychological consequences in carriers. Most discussed carrier status with their partner (89%), parents, other relatives and also with friends; 87% of partners to whom testing was suggested have been screened. Those testing positive indicated that knowledge of carrier status would be considered in future reproductive decisions, and after 6 months carriers retained a reasonable level of knowledge about CF and its inheritance. Carriers and non-carriers uniformly approve of screening and are glad to have been tested. Knowledge of CF in the sample of non-carriers has also increased after testing, suggesting screening may improve understanding of CF among the entire target population. Fears of possible social costs of screening may be ill-founded.

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OBJECTIVE: To evaluate the uptake of cystic fibrosis carrier testing offered through primary health care services. DESIGN: Carrier testing for cystic fibrosis was offered to patients of reproductive age through primary health care services. SETTING: Three general practice surgeries and four family planning clinics in South West Hertfordshire District Health Authority. SUBJECTS: Over 1000 patients aged 16-44 attending two general practices and four family planning clinics and a stratified random sample of patients aged 16-44 from one general practice's age-sex register. RESULTS: When screening was offered opportunistically the uptake was 66% in general practice and 87% in family planning clinics. Ten per cent of those offered a screening appointment by letter took up the invitation. Of the screened population, 76% had previously heard of cystic fibrosis, 35% realised it is inherited, and 18% realised that carriers need not have any family history. If they found themselves in an "at risk" partnership 39% would consider not having children and 26% would consider terminating an affected pregnancy, but in each case most people were unsure how they would react. CONCLUSIONS: Most people offered a cystic fibrosis test opportunistically wish to be tested, and the responses of those tested indicate that knowledge of carrier state would be considered in future reproductive decisions.

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Data are presented for delta F508 screening and KM19/XV2c haplotype analysis of 195 cystic fibrosis (CF) chromosomes from the British Caucasian population. We report the frequency of delta F508 in this group to be 80% and find pronounced disequilibrium between the deletion and the KM 2, XV 1 haplotype. Haplotype analysis of 71 normal chromosomes is also presented. We report one individual who had meconium ileus and who does not have the delta F508 mutation on either chromosome.

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Human primary thyroid follicular epithelial cells were transfected with a plasmid containing an origin-defective SV40 genome (SVori-) to produce several immortal cell lines. Two of the 10 cell lines analysed expressed specific features of thyroid epithelial function (iodide-trapping and thyroglobulin production). These two lines were characterised in detail and found to be growth factor-independent, capable of anchorage-independent growth at low frequency but non-tumorigenic in nude mice. These differentiated, These differentiated, partially transformed cell lines were shown to be suitable for gene transfer at high frequency using simple coprecipitation techniques.

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Using polymerase chain reaction amplification and oligonucleotide probing, the activation of ras oncogenes in 24 benign and 20 malignant human thyroid neoplasms was examined. The frequency of ras oncogene activation was similar at all stages of tumorigenesis in this system, being found in 33% of adenomas overall (50% of microfollicular tumours), 53% of differentiated follicular carcinomas and 60% of undifferentiated carcinomas. This supports the contention that mutation of these oncogenes occurs at an early step in tumorigenesis. The predominant amino acid substitution in the differentiated tumours was glutamine to arginine at position 61 of Ha-ras or N-ras, but this mutation was not found in any of the undifferentiated tumours. It was noted that while transition mutations predominated in differentiated tumours (both benign and malignant), transversions were more common in the undifferentiated tumours.

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Activated ras oncogenes have been detected in a number of rodent tumour model systems (Balmain et al., 1986; Barbacid 1987), in which chemical carcinogens have been the most widely used inducing agents. We have investigated the involvement of activated oncogenes in a single well-characterised tumour model, rat thyroid neoplasia, produced not only by chemical carcinogen (nitrosomethylurea, NMU) and by ionizing radiation but also by elevated trophic stimulation alone. We have indentified a striking specificity in patterns of ras oncogene activation, with exclusively Ha-ras activated in 87% of NMU-induced tumours and exclusively Ki-ras activated in 60% of radiation-induced tumours.

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Human thyroid epithelial (follicular) cells give rise to two malignant tumors--"follicular" carcinomas, which metastasize almost exclusively via the bloodstream, and "papillary" carcinomas, which metastasize predominantly via lymphatics (Williams, E. D. In: W. Duncan (ed.), Recent Results in Cancer Research: Thyroid Cancer, pp. 47-55. Berlin: Springer-Verlag, 1980). We have investigated whether this contrast in biological behavior might be associated with different patterns of oncogene activation. DNA transfection analysis of five follicular and ten papillary cancers indeed showed a statistically significant difference in the pattern of genes responsible, activated ras oncogenes being found in 80% of follicular tumors but only 20% of papillary tumors. In addition, in follicular cancers we have found activation of all three ras oncogenes (H-ras, K-ras, and N-ras), the first time that this has been demonstrated in a primary human tumor type (as opposed to cell lines). We suggest therefore that ras activation may be an important determinant of metastatic capability in these epithelial cancers.

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One hundred seventy-eight men and women with acute gonorrhea were treated by intramuscular administration of cefuroxime. Use of 1 g of cefuroxime plus 1 g of probenecid gave a cure rate of 95.5%, which compared well with that of a standard treatment of 5 x 10(6) units of intramuscularly administered benzyl penicillin plus 1 g of probenecid. The latter gave a cure rate of 97.2% in a concurrent series of 178 patients. A subsequent comparison of 163 patients who received 750 mg of cefuroxime plus 1 g of probenecid with 145 patients who received 1.5 g of cefuroxime alone showed cure rates of 95.1% and 97.2%, respectively. Only two cases of possible hypersensitivity to cefuroxime were found. It is concluded that cefuroxime is a valuable drug for single-session treatment of acute gonorrhea in both men and women.

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Some intrauterine devices are of low radiographic density and require careful technique for their demonstration. The main indications for radiology are to exclude deformity, which reduces the loop's efficiency, perforation of the uterus, or expulsion of the loop.

PIP: The radiographic identification of various IUDs is discussed. Radiography may be requested to verify that such devices as the Lippes loop of Saf-T-Coil have assumed their original shape after insertion, to exlude uterine perforation, and to diagnose expulsion of an IUD. The radiographic properties of various IUDs are reviewed.

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