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R J Scott

Publications and source records attributed to R J Scott.

At least 91 records · Page 5Linked to original sources
PubMed1996

Oral sumatriptan in the acute treatment of migraine and migraine recurrence in general practice.

We investigated the efficacy, safety and tolerability compared with placebo of a second dose of oral sumatriptan 100 mg in 1349 general practice patients who had already treated a moderate or severe migraine headache with 100 mg sumatriptan 4 h earlier. Headache was relieved by the first sumatriptan dose in about 70% of patients, but the second dose did not produce significantly more relief than placebo, either in non-responders or in the group as a whole, nor did it reduce other symptoms (photophobia, nausea, vomiting, etc.) at 8 h, or influence the incidence of headache recurrence. The drug was well-tolerated, and a further single dose was effective in treating recurrence after initial relief. A single 100 mg dose of sumatriptan is an effective acute treatment for migraine. A second dose should be reserved for treating headache recurrence.

Acute Disease↗
PubMed1996

Correlation between the development of extracolonic manifestations in FAP patients and mutations beyond codon 1403 in the APC gene.

The APC gene was investigated in 31 unrelated polyposis coli families by SSCP analysis and the protein truncation test. Twenty-three germline mutations were identified which gave rise to a variety of different phenotypes. Some of these mutations have already been described; however we report six previously unpublished mutations. Typical disease symptoms were observed in families who harboured mutations between exon 4 (codon 169) and codon 1393 of exon 15. Mutations beyond codon 1403 were associated with more varied phenotype with respect to the development of extracolonic symptoms. In this report we provide support for the notion that there appears to be a correlation between the location of an APC mutation (beyond codon 1403) and extracolonic manifestations of familial adenomatous polyposis.

Adenomatous Polyposis Coli↗
PubMed1996

Complex genetic predisposition to cancer in an extended HNPCC family with an ancestral hMLH1 mutation.

Hereditary non-polyposis colorectal cancer (HNPCC) is characterised by a genetic predisposition to develop colorectal cancer at an early age and, to a lesser degree, cancer of the endometrium, ovaries, urinary tract, and organs of the gastrointestinal tract other than the colon. In the majority of families the disease is linked to mutations in one of the two mismatch repair genes, hMSH2 or hMLH1. We have found a novel hMLH1 nonsense mutation in a Swiss family with Lynch syndrome, which has been transmitted through at least nine generations. A different tumour spectrum of neoplasms of the skin, soft palate, breast, duodenum, and pancreas was observed in three branches of this family, where there was a virtual absence of colonic tumours. The hMLH1 mutation could not be detected in members of these branches suggesting that at least a second genetic defect predisposing to cancer is segregating in part of the kindred.

Adaptor Proteins, Signal Transducing↗
PubMed1996

BRCA1 mutations in a selected series of breast/ovarian cancer patients.

Germline mutations in the BRCA1 gene have been associated with familial breast/ ovarian cancer in large families showing high penetrance of the disease. Little is known, however, about the contribution of BRCA1 mutations to breast/ovarian cancer in small families with few affected members or in isolated early onset cases. Therefore we examined the BRCA1 gene in 63 breast/ovarian cancer patients who either came from small families with as few as one affected first degree relative, or in patients who had no family history but had developed breast cancer under 40 years of age. Using the protein truncation test, we were able to identify three unique BRCA1 germline mutations (4.8%). Two of the probands had only one affected first degree and several second degree relatives and the third had three affected first degree relatives including two sisters who, when tested, were also found to carry the mutation. There was no family history of ovarian cancer in any of the three families.

Adult↗
PubMed1995

[Tumor suppressor gen mutation in the germ line: its significance in familial and sporadic tumors].

Since the discovery of the retinoblastoma tumor suppressor gene many others have been described associated with a variety of different familial syndromes. These include the Li-Fraumeni syndrome, familial breast/ovarian cancer, multiple endocrine neoplasia (MEN1), neurofibromatosis 1 and 2, tuberous sclerosis and von Hippel-Lindau disease. Persons harboring a germ line mutation in a tumor suppressor gene are not born with disease, merely the predisposition to develop one. This is due to the fact that they have inherited only one functional copy compared to persons with no predisposition who have two copies. Germ line mutations have not to be inherited, they can result from a spontaneous mutation occurring during gametogenesis in one patient. Persons with an inherited or de-novo germ line mutation have similar risks to develop multiple cancer or to transmit the defective gene to their offspring. The genes can be analyzed by molecular genetic techniques allowing for a precise genetic diagnosis as well as reliable genetic counselling.

Eye Neoplasms↗
PubMed1995

Potter's syndrome in the second trimester--prenatal screening and pathological findings in 60 cases of oligohydramnios sequence.

Fifty-two second-trimester and eight third-trimester (> 28/40) autopsies with clinical or pathological evidence of oligohydramnios sequence ('Potter's syndrome') were reviewed. Twenty-eight cases had renal anomalies (71 per cent in terminations following prenatal ultrasound), 27 had no renal malformation (35 per cent with chorioamnionitis), and five had external assessments only. In 15 cases, the renal lesion was part of a multiple malformation syndrome. Seven cases had a lesion which either recurred in a sibling in the same family or was a recognized autosomal recessive syndrome. Three cases had an abnormal karyotype, two of which had renal anomalies. Maternal serum alpha-fetoprotein (AFP) did not discriminate between cases with renal malformations and those without. Pulmonary hypoplasia was commoner in third-trimester than in second-trimester cases. External appearance and absent umbilical artery were not reliable predictors of underlying internal anomalies. These findings reflect the shift from postnatal to prenatal diagnosis in modern practice. In this series, mainly second-trimester cases, 50 per cent of cases had no malformations, in a condition which is traditionally associated with renal disease. The high incidence of chorioamnionitis suggests that the mechanism of oligohydramnios is occult amniotic fluid leakage. Prenatal diagnosis of oligohydramnios in the second trimester is dependent on ultrasound scanning and a full post-mortem examination is necessary to identify any underlying fetal cause.

Abortion, Induced↗
PubMed1995

Novel germline APC gene mutation in a large familial adenomatous polyposis kindred displaying variable phenotypes.

The APC gene is mutated in the germline of people from families where there is a predisposition to develop polyposis coli. Many mutations have been described but the relation between their site and the phenotypic expression of the disease remains unclear. The most commonly seen mutation occurs at codon 1309. Many other mutations have been described towards the 5' end of exon 15 of the APC gene but comparatively few have been seen towards the 3' end. Recent reports have indicated the possibility of a functional boundary with respect to severity and age of onset of disease, which lies towards the 5' end of the gene. This report describes a large family whose affected members present with a very variable phenotype ranging from an early onset and severe form to a comparatively mild later onset one. The mutation that predisposes to disease in this family is at a previously undescribed site that lies towards the 3' end of exon 15 of the APC gene, which results in a stop codon. Interestingly, the stop codon is 63 codons downstream of the mutation and therefore may affect the expression of the disease. The addition of this mutation to the growing list of mutations described in the APC gene may provide some insight into the genotype/phenotype relation of the disease thus contributing to the understanding and significance of mutations at specific sites in the APC gene.

Adenomatous Polyposis Coli↗
PubMed1995

[Hereditary motor and sensory neuropathies. Clinical and molecular genetic aspects].

Hereditary motor sensory neuropathies are a heterogeneous group of inherited diseases of the peripheral nerves. In this review the clinical and genetic differences between the sub-groups of this disease will be discussed. Since the discovery of a 1.5 mb duplication on chromosome 17 p11.2-12 in most patients with a hereditary motor sensory neuropathy and a variety of different mutations on chromosomes 1 and X in other patients with a similar disease profile, Dycks' clinical classification needs to be re-evaluated. In this review Dycks' taxonomy of heridihary neuropathies will be compared to a new genetic classification and a relevant diagnostic procedure proposed when a hereditary neuropathy is suspected.

Chromosome Aberrations↗
PubMed1995

[Familial colorectal and breast carcinoma--genetic counseling and presymptomatic diagnosis].

Several types of hereditary cancer can be prevented from progressing to advanced stages by regular surveillance of the person at risk and hence by the early treatment of a developing neoplasia. Genetic counselling of such patients and their relatives is therefore an important task whose value often remains unrecognized. This is especially true for the common forms of hereditary cancer such as breast and colorectal cancer, which aggregate in up to 5% of all patients according to the rules of autosomal-dominant inheritance. Preventive measures are particularly promising in the case of familial cancer because persons at risk are motivated to seek medical help. Genetic counselling is a multifaceted process and involves more than an accurate diagnosis and risk estimate. The counseled patient expects and deserves an open and reasonable answer to his questions about the implications of his/her cancer predisposition or his family history. Accurate diagnosis of the underlying susceptibility is the cornerstone of genetic counselling because most cancers seem to have multiple causes. Different genes located on different chromosomes can independently give rise to the same malignancy. Besides heterogeneity, presymptomatic testing for inherited susceptibilities to cancer raises many issues including therapy, access, intense anxiety, and discrimination.

Adenomatous Polyposis Coli↗
PubMed1994

Intraoperative radiation (IORT) injury to sciatic nerve in a large animal model.

Peripheral nerve appears to be a dose-limiting normal tissue in the clinical application of intraoperative radiation therapy (IORT). To assess IORT injury to peripheral nerve, three groups of five beagle dogs received doses of 12, 20 or 28 Gy to the surgically exposed and isolated right sciatic nerve in the mid-femoral region using 6 MeV electrons. The left sciatic nerve of each dog served as its own control. As a surgical control five dogs received surgical exposure of the nerve only. Monthly neurologic exams, electromyogram and nerve conduction studies were performed following treatment for 12 months. After that dogs were euthanatized and histologic studies of nerves were done to define the degree of axon and myelin loss as well as presence of fibrosis and vascular lesions for different doses of IORT. Results showed that the threshold dose most likely related to expression of severe radiation damage to the nerve in this model is between 20 and 25 Gy. Radiation injury to peripheral nerve appears to be the result of direct radiation effects on Schwann cells and nerve vasculature and secondary effects resulting from damage to regional muscle and vasculature. A theoretical mechanism of radiation injury to peripheral nerve is proposed.

Animals↗
PubMed1994

Mutational analysis of the first 14 exons of the adenomatous polyposis coli (APC) gene.

In the present study, the polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) technique has been applied to the mutation analysis of the adenomatous polyposis coli (APC) gene. We examined the first 14 exons of the APC gene in 46 polyposis coli patients. Five germline mutations were observed, including a single-nucleotide substitution and small (1-4 bp) deletions leading, in 4 cases, to a stop codon. A missense mutation in exon 3 and a 1 bp deletion in exon 4 of the APC gene were observed in patients presenting with the attenuated form of FAP.

Adenomatous Polyposis Coli↗