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Biomedical subjects

D Ralph

Publications and source records attributed to D Ralph.

At least 19 recordsLinked to original sources
PubMed2002

Semen production in adolescent cancer patients.

BACKGROUND: The influence of an accompanying person (parent, guardian or nurse) on the ability of an adolescent (post-pubescent, <20 years of age) to produce a semen sample for cryopreservation, is undetermined, as is the potential for use of urine samples to retrieve sperm in those adolescents that are unable to produce a semen sample. METHODS: The records from 1991-2000 inclusive were reviewed to derive those adolescent patients who were unable to produce semen for cryopreservation prior to undergoing treatment for a malignant condition. RESULTS: During the study period 238 adolescents attended our unit of whom 205 (86.1%) banked semen ('producers'). The remaining 33 adolescents (13.9%) were initially unable to produce a sample ('non-producers'), four of these provided a urine specimen for analysis (12.1%) and of these one had sufficient sperm for cryopreservation. Of the 'accompanied' patients 29.7% (19/64) were non-producers while in the 'unaccompanied' patients only 8.0% (14/174) were non-producers (chi(2) = 16.58, P < 0.001). The relative risk (RR) of not producing a semen sample for the accompanied group of patients was greater than that for the unaccompanied group (RR = 3.689, 95% confidence interval: 2.0-6.9). One patient returning alone successfully provided a semen sample for storage. CONCLUSION: Units should consider the effect of the presence of an accompanying person when an adolescent is unable to produce a semen sample and should consider requesting urine to retrieve sperm.

Adolescent↗
PubMed2002

Semen quality and cryopreservation in adolescent cancer patients.

BACKGROUND: Adult cancer patients are routinely offered pre-treatment sperm cryopreservation. However, only recently has the welfare of adolescent cancer sufferers gained momentum, including their infertility, and unsurprisingly relatively little is known about their semen quality and feasibility of cryopreservation. METHODS AND RESULTS: A total of 238 adolescent cancer patients referred to our centre between 1991 and 2000, from post-pubertal age up to 19 years 11.9 months, were included. Their semen was processed after appropriate counselling. Semen cryopreservation was possible in 205 of the initial 238 patients referred (86.1%). The pathology of the cancer cases included Hodgkin's lymphoma, non-Hodgkin's lymphoma, osteosarcoma, Ewing's sarcoma, acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), testicular, leukaemia, and others. The mean sperm counts were broadly uniform across the disease and age groups, except for the AML group. There was no cancer group analysed in which sperm could not be stored. Semen volume was broadly uniform across the disease groups, except the ALL and Ewing's sarcoma groups, which showed relatively lower and higher mean semen volumes respectively. Older adolescent patients appeared to have a higher mean semen volume. CONCLUSIONS: Semen cryopreservation was possible in most adolescent cancer cases regardless of age or diagnosis. In all cases the quality of the semen was potentially useful for assisted conception procedures. An offer to freeze sperm in all patients aged >12 years should be made. Adequate support and counselling of both the boys and their parents is essential.

Adolescent↗
PubMed2002

Oxygen free radicals and the penis.

Penile erection is dependent upon vascular smooth muscle relaxation in erectile tissue and penile arteries, the principal mediator of relaxation being nitric oxide (NO). Evidence from basic scientific studies indicates that oxidative stress mediated through the superoxide radical (superoxide) and other reactive oxygen species (ROS) may be central to impaired cavernosal function in erectile dysfunction (ED). Increased inactivation of NO by superoxide results in impaired penile NO transmission and smooth muscle relaxation. Furthermore, propagation of endothelial dysfunction by ROS may result in chronic impairment of penile vascular function, a process analogous to early atherogenesis. Indeed, ED and atherosclerosis are closely linked through shared risk factors. Given our current understanding of ED pathophysiology, antioxidants may be of benefit in both the short- and long-term. Evidence supporting the paradigm of antioxidant therapy for the prevention or treatment of ED is presented herein.

Animals↗
PubMed2001

Penile resurfacing for extensive genital warts.

Complete surgical excision followed by reconstruction, of diseased penile skin may result in sexual dysfunction due to tethering of the underlying Buck's fascia by the graft. We describe penile resurfacing for extensive condyloma accuminata, a novel technique that circumvents this complication without compromising clearance of this particular lesion.

Aged↗
PubMed2001

Gaining consent to freeze spermatozoa from adolescents with cancer: legal, ethical and practical aspects.

Sperm banking for early adolescent cancer patients requires delicate, sensitive handling and, in the UK, consideration is required of statutory elements. No information at present exists about how adolescents with cancer are normally treated or counselled for sperm banking. Here we highlight the type of issues in relation to fertility preservation faced by clinicians and those faced by adolescents at a sperm storage laboratory. We explore the very real difficulties of bringing together these medical fields of assisted reproduction, oncology and the various pieces of legislation and focus specifically on gaining consent. Attention is paid to counselling and communication to help the patient reach an effective and informed decision to store spermatozoa. The role of parents in contributing towards communication and support, together with the legal constraints in decision making, is acknowledged. How absolute and fully 'informed' consent should be will always remain a contentious issue amongst the various specialists and disciplines. In relation to sperm storage, as a minimum the patients should understand the process that they are undertaking so that it is undertaken freely and without pressure. The practical approach to gaining consent that we are using seems a logical and practical method to help early adolescent patients to store spermatozoa.

Adolescent↗
PubMed2000

Testicular tissue cryopreservation in boys. Ethical and legal issues: case report.

Sperm preservation prior to chemotherapy and radiotherapy is common practice in adult males. Spermatozoa are usually retrieved from an ejaculated sample although there are occasions when testicular tissue is used as the source. These techniques of sperm preservation present minimal ethical objections as the patients give their informed consent. Sperm preservation in children presents practical and ethical dilemmas in that the children cannot always give their informed consent, there are no regulatory guidelines and there is no guarantee that spermatogenesis is occurring. With the rapid advances in reproductive technology and the possible future use of immature germ cells by in-vitro maturation or transplantation, the demand for immature testicular tissue preservation is likely to increase. More information for the parents and oncologists with regard to this subject is needed to allow informed decisions to be made on behalf of the children. These issues are discussed using two cases of children having testicular tissue preservation.

Adolescent↗
PubMed1999

Cleavage of double-stranded copy RNA by RNase 1 and RNase T1 provides a robust means to detect p53 gene mutations in clinical specimens.

Detecting somatic mutations in patient specimens is challenging because of the wide variation in quality and quantity of genomic DNA in clinically derived material. In cancer specimens, the challenge of detecting mutations is usually compounded by the presence of large numbers of nonmutated normal cells that dampen the relative signal that can be obtained from employing any mutation detection strategy. In the case of somatic mutations in the gene encoding the tumor suppressor, p53, a clinically useful mutation detection assay must be able to detect a wide variety of types of mutations scattered over five coding exons and their flanking intron sequences. This study examined the ability of a mutation detection strategy, termed NIRCA, to identify single-base mutations in the clinically relevant domain of the p53 gene. This strategy relies on RNase digestion-mediated cleavage of double-stranded copy RNA transcribed in vitro from polymerase chain reaction (PCR)-amplified genomic templates to detect mismatched base pairs resulting from hybridization of complimenting mutant and wild-type copy RNA strands. This assay system was found to robustly detect all twelve possible mismatches and the plus one and minus one frame shifts. Furthermore, the assay could detect mutations in clinical specimens when the mutant alleles composed as few as 4% of the total population of alleles isolated in bulk specimen genomic DNA. This mutation detection strategy worked efficiently in bladder, breast, colon and lung tumors as well as sediments from bladder cytology specimens.

Humans↗
PubMed1999

Interleukin-8 serum levels in patients with benign prostatic hyperplasia and prostate cancer.

OBJECTIVES: Using arbitrarily primed polymerase chain reaction (AP-PCR) ribonucleic acid (RNA) fingerprinting, we discovered a messenger RNA (mRNA) that encoded the cytokine interleukin-8 (IL-8) that was up-regulated in the peripheral blood leukocytes (PBLs) of patients with metastatic prostate cancer (CaP) compared with similar cells from healthy individuals. We compared the total prostate-specific antigen (PSA) levels, the free/total (f/t) PSA ratios, and the immunoreactive IL-8 serum concentrations in patients with either biopsy-confirmed benign prostatic hyperplasia (BPH) or CaP. METHODS: The sera from 35 apparently healthy normal volunteers and 146 patients with biopsy-confirmed BPH and CaP obtained from two academic centers were retrospectively examined to determine the serum levels of IL-8, total PSA (tPSA), and the f/t PSA ratio. Logistic regression and trend analysis statistical methods were used to assess the results. RESULTS: Normals (n = 35), BPH patients (n = 53), patients with clinical Stages A to C CaP (n = 81), and patients with metastatic CaP (n = 1 2) had mean levels of IL-8 of 6.8, 6.5, 15.6, and 27.8 pg/mL, respectively. The IL-8 serum concentrations correlated with increasing CaP stage and also differentiated BPH from clinical Stages A, B, C, or D CaP better than tPSA and performed similarly to the f/t PSA ratio. The combination of the IL-8 levels and f/t PSA ratios using multivariate logistic regression analysis distinguished BPH from Stages A, B, C, or D CaP or only Stages A and B with a receiver operating characteristic area under the curve of 89.8% and 87.5%, respectively (P <0.0001). CONCLUSIONS: The IL-8 serum concentration in our clinically well-defined patient sample was independent of the f/t PSA ratio as a predictor of CaP. When test samples are controlled for extraneous clinical origin of inflammation or infection, the combination of the IL-8 and f/t PSA assay results may offer an improved approach for distinguishing BPH from CaP.

Adult↗
PubMed1999

Prosthesis implantation after radial free flap phalloplasty in patients with bladder exstrophy.

METHODS: Inflatable penile prosthesis were implanted into sensate radial free-flap phalloplasties in two adult patients with bladder exstrophy. RESULTS: Neither patient reported loss of sensation, and both were able to inflate the prosthesis and engage in sexual intercourse three months later. CONCLUSION: The construction of a functional neophallus is well described however has not previously been reported in exstrophy patients who are suited to this procedure due to the presence of crura, and the absence of a neourethra. Scarring from previous reconstructive procedures however may make implantation difficult, and long-term follow up is required to evaluate this procedure in patients with bladder exstrophy.

Adult↗
PubMed1999

Quantitative sensory and autonomic testing in male diabetic patients with erectile dysfunction.

OBJECTIVE: To correlate abnormalities of nerve fibres in the lower limbs with erectile dysfunction in male diabetic patients, using a range of quantitative sensory and autonomic function tests. PATIENTS AND METHODS: The study included 68 male diabetic patients with symptomatic erectile dysfunction and 11 matched diabetics without erectile dysfunction; none had clinical evidence of peripheral vascular disease or psychological disorder. Patients were evaluated with a symptom questionnaire based on the Michigan Neuropathy Screening Instrument questionnaire and examined clinically. Sural and peroneal nerve-conduction studies, and quantitative sensory and autonomic tests (vibration, thermal, light-touch thresholds, sensory and autonomic cutaneous axon-reflexes) were used to detect nerve abnormalities in the lower limbs, which were correlated with erectile dysfunction. RESULTS: Symptoms of neuropathy were more common in the group with male erectile dysfunction (MED), but statistically significant only for neuropathic pain (53% MED, 18% nonMED, P<0.05, chi-square test) and gastroparesis (44% MED, 0% nonMED, P<0.05). Tests of unmyelinated afferents (warming perception and capsaicin-induced sensory axon-reflex vasodilatation) were most often abnormal, sometimes with no other abnormalities on tests or neurological examination. However, abnormality of warm perception was not significantly different between groups (81% MED, 70% nonMED), suggesting that it is a poorer discriminant than abnormal sensory axon-reflex vasodilatation (89% MED, 22% nonMED, P<0.001). The only other significant test difference was decreased sural nerve action potential (70% MED, 22% non-MED, P<0.01). CONCLUSIONS: There appeared to be preferential involvement of unmyelinated sensory fibres that mediate axon-reflex vasodilatation in the limbs of diabetic patients with erectile dysfunction. This test appears to be a helpful indicator of neurological involvement in erectile dysfunction, and may be used to monitor the effect of new treatments.

Adult↗
PubMed1999

Gonadal tissue cryopreservation in boys with paediatric cancers.

In considering gonadal tissue cryopreservation in children about to undergo chemotherapy or radiotherapy for cancer, numerous issues need to be confronted. This relates firstly to a dearth of information available on the subject of children's gonads coupled to ill-defined fertility preservation procedures, technologies and perhaps less well-publicized regulatory, ethical and legal controls. There may be benefits in considering gonadal tissue preservation for children prior to chemotherapy or radiotherapy, in the hope that future technologies can utilize their immature gametes. Whether or not freezing of gonadal tissue is encouraged prior to cancer therapy, there is a growing demand from parents and clinicians for more information to be made available. This paper reviews our current knowledge of children's gonads in terms of physiology and of fertility experience gained after childhood cancer treatment. It further examines the various issues and concerns regarding children's gonadal tissue storage, its potential use, the present law and the demands and pressures under which clinicians find themselves with patients and parents. This information is important for both the counselling process and decision-making when presented with potential fertility issues in paediatric oncology patients.

Child↗
PubMed1995

16S rRNA gene sequence of Neorickettsia helminthoeca and its phylogenetic alignment with members of the genus Ehrlichia.

Neorickettsia helminthoeca (tribe Ehrlichieae, family Rickettsiaceae) is the agent of salmon poisoning disease, which affects members of the family Canidae. This bacterium is unusual in that it is the only known obligately intracellular bacterium that is transmitted via a helminth vector. The nucleotide sequence of the N. helminthoeca 16S rRNA gene was determined and compared with the sequences of intracellular bacteria belonging to the alpha subgroup of the Proteobacteria. The N. helminthoeca sequence was most similar to the sequences of two Ehrlichia species, Ehrlichia risticii and Ehrlichia sennetsu (levels of sequence similarity, > 95%). All other members of the tribe Ehrlichieae, including members of the other Ehrlichia species, and the related species Cowdria ruminantium and Anaplasma marginale, were only distantly related phylogenetically (levels of sequence similarity, 84 to 86%). Our results corroborate the results of previous ultrastructural and Western blot (immunoblot) comparisons of N. helminthoeca with other ehrlichial species. The genus Ehrlichia is phylogenetically incoherent and can be separated into three identifiable clusters of species. Each cluster is closely associated with a species classified in another non-Ehrlichia bacterial genus. The close relationships among N. helminthoeca, E. risticii, and E. sennetsu and the striking differences between these organisms and other members of the tribe Ehrlichieae suggest that in the future, these organisms should be treated as members of a new bacterial genus separate from the genus Ehrlichia.

Animals↗