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Biomedical subjects

S A Holmes

Publications and source records attributed to S A Holmes.

At least 19 recordsLinked to original sources

Management of colovesical fistulae associated with pelvic malignancy.

Thirteen patients with malignant colovesical fistulae are presented. The underlying pathology was cancer of the colon (seven cases), bladder (four cases) and cervix (two cases). The series demonstrates that wide surgical excision may be needed to achieve tumour clearance and that this may necessitate pelvic exenteration. Three patients who underwent inadequate tumour excision developed recurrence in the bladder, two with a fatal outcome. Wide excision of the bladder may be performed without urinary diversion by subtotal cystectomy and a reconstructive procedure. Substitution cystoplasty was performed on two patients at the time of tumour excision. Urinary tract involvement by such tumours is often extensive and optimal results may be achieved with a multidisciplinary approach.

Aged

Eosinophilic prostatitis and prostatic specific antigen.

Eosinophilic prostatitis is a rare form of abacterial prostatitis with uncertain aetiology. Its clinical presentation, like other types of abacterial prostatitis, commonly mimics carcinoma of the prostate. Transrectal ultrasound may be helpful in the diagnosis of prostatitis but histological confirmation is necessary. Prostatic specific antigen has been widely used in the diagnosis and follow-up of patients with prostatic carcinoma. High levels of this antigen (greater than 30 micrograms/l) have been claimed to be highly specific for prostate cancer, although lesser elevations may also occur in patients with large benign prostate glands and in bacterial prostatitis. We report 3 patients with histologically proven eosinophilic prostatitis and high levels of prostatic specific antigen. This diagnosis may closely mimic carcinoma of the prostate and must be excluded by histological examination of biopsy material before treatment for presumed prostate carcinoma is initiated.

Antigens, Neoplasm

Cystectomy and substitution enterocystoplasty: alternative primary treatment for T2/3 bladder cancer.

The optimal treatment for invasive bladder cancer remains controversial. Although external beam radiotherapy is able to eradicate the disease in a number of patients, the difficulty is selecting those who will respond. Those who do develop a local recurrence will require a salvage cystectomy combined with urinary diversion. The results of performing cystectomy and bladder reconstruction as a primary procedure are presented and the concept of combining this with chemotherapy as an alternative strategy for the management of bladder cancer is discussed.

Adenocarcinoma

Encrustation of intraprostatic stents--a comparative study.

Metallic stents have been used in the management of prostatic disease in patients unfit for surgery. A variety of stents have become available but the optimum design and metal of construction has not yet been defined. This study examined one of the potential complications of stent insertion by demonstrating that they are susceptible to encrustation. Using an in vitro model it compares the ability of the different materials used in their construction to resist this encrustation. Titanium appears less able to resist deposition than the other metals examined. The long-term complication of encrustation may inhibit the use of some of these stents.

Calcium Phosphates

Potential use of tissue adhesive in urinary tract surgery.

The search for a tissue adhesive which obviates the need for suture materials in the apposition of wound edges is not new. The early adhesive products lacked the required safety and efficacy. Experimental use of a new fibrin adhesive has shown that it may have potential use where inflammatory reaction to the suture material is undesirable or water-tight sealing of the anastomosis is required.

Animals

The development of synthetic polymers that resist encrustation on exposure to urine.

The consequences of long-term exposure of synthetic materials to urine have prevented the development of alloplastic replacement of diseased or damaged parts of the urinary tract. Similarly, urethral and ureteric catheters require regular replacement if the complications of encrustation and blockage are to be avoided. The mechanism of encrustation is not understood completely and thus it is unclear why certain materials appear better able to resist encrustation. This study has involved the development of a new encrustation model to provide a reproducible and quantitative assessment of the susceptibility of polymers to encrustation. This model will allow beneficial characteristics of co-polymer design to be recognised, with the aim of finding new materials that are tolerant of exposure to urine. Results of co-polymers examined show that the incorporation of fluorine-containing components confers significant resistance to the formation of encrustation. It is suggested that the physico-chemical properties of polymer surfaces may be important determinants of resistance to encrustation.

Calcium

Finasteride in the treatment of benign prostatic hyperplasia. A urodynamic evaluation.

A group of 69 men with bladder outflow obstruction due to benign prostatic hyperplasia (BPH) were treated in a double-blind, placebo-controlled study with finasteride (Proscar, MK-906), a 5-alpha reductase inhibitor, 5 mg or 10 mg/day or placebo for 3 months; subsequently, 20 patients received finasteride 5 mg/day for a further 9 months in an open extension study. In treated patients dihydrotestosterone declined by over 60%, remaining unchanged with placebo. Symptom scores fell significantly in all 3 groups. Mean maximum flow rates fell slightly in placebo-treated patients but improved by 1.5 ml/s in the 10 mg group and by 3.3 ml/s in the 5 mg group. After 1 year's treatment, the reduction in symptom score and increase in flow rate were well maintained; the mean prostate volume was reduced by 14% and prostatic specific antigen declined by 28%. It was concluded that finasteride shows some efficacy in the treatment of BPH, with minimal toxicity, but 12 months of therapy or longer may be necessary to achieve maximal effect.

Aged

Surgical reinforcement of gender identity in adolescent intersex patients.

The presentation of phenotypic gender ambiguity at the time of adolescence is uncommon. Surgical reinforcement of gender, or reassignment is often complex and multistage. We present 2 cases of children who developed secondary sexual characteristics contrary to their chromosome status who, because of their late presentation, required significant surgical intervention to reinforce the gender assigned to them. We review some of the surgical techniques involved.

Adolescent

Diagnosis and management of renal angioma.

Five patients with symptomatic renal angiomata are described. All presented with heavy haematuria and unilateral ureteric obstruction without evidence of a mass distorting the renal architecture. Renal angiomata are most easily diagnosed by selective renal angiography. They may be treated by intraarterial embolization, avoiding the need for major ablative surgery.

Adult

Organization and nucleotide sequence of the human KIT (mast/stem cell growth factor receptor) proto-oncogene.

We have cloned and sequenced the human KIT proto-oncogene, which contains 21 exons and spans more than 34 kb of DNA on chromosome segment 4q12. We also establish physical linkage between the KIT gene and the related PDGFRA gene. The organization of the KIT gene is virtually identical to that of the homologous FMS gene, located on chromosome 5. Together, these data suggest that the KIT and PDGFRA genes on chromosome 4 and the FMS and PDGFRB genes on chromosome 5 arose by duplication of a common ancestral gene, followed by duplication of a chromosome.

Amino Acid Sequence

Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism.

Piebaldism is an autosomal dominant disorder of melanocyte development and is characterized by congenital white patches of skin and hair from which melanocytes are completely absent. A similar disorder of the mouse, "dominant white spotting" (W), results from mutations of the c-kit proto-oncogene, which encodes the cellular tyrosine kinase receptor for the mast/stem cell growth factor. We have identified c-kit gene mutations in three patients with piebaldism. A missense substitution (Phe----Leu) at codon 584, within the tyrosine kinase domain, is associated with a severe piebald phenotype, whereas two different frameshifts, within codons 561 and 642, are both associated with a variable and relatively mild piebald phenotype. This is consistent with a possible "dominant negative" effect of missense c-kit polypeptides on the function of the dimeric receptor.

Amino Acid Sequence

Mutations of the KIT (mast/stem cell growth factor receptor) proto-oncogene account for a continuous range of phenotypes in human piebaldism.

Piebaldism is a rare autosomal dominant disorder of pigmentation, characterized by congenital patches of white skin and hair from which melanocytes are absent. We have previously shown that piebaldism can result from missense and frameshift mutations of the KIT proto-oncogene, which encodes the cellular receptor tyrosine kinase for the mast/stem cell growth factor. Here, we report two novel KIT mutations associated with human piebaldism. A proximal frameshift is associated with a mild piebald phenotype, and a splice-junction mutation is associated with a highly variable piebald phenotype. We discuss the apparent relationship between the predicted impact of specific KIT mutations on total KIT-dependent signal transduction and the severity of the resultant piebald phenotypes.

Amino Acid Sequence