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Biomedical subjects

J Monaghan

Publications and source records attributed to J Monaghan.

At least 19 recordsLinked to original sources
PubMed2005

Improving patient and carer communication, multidisciplinary team working and goal-setting in stroke rehabilitation.

OBJECTIVE: To determine the extent to which three forms of multidisciplinary team (MDT) care in stroke rehabilitation meet the standards set by the United Kingdom National Service Framework (NSF). DESIGN: Consecutive assessment of the three forms of care was completed. SUBJECTS: The study included three groups of 25 stroke inpatients on the stroke rehabilitation ward. INTERVENTION: (1) A standard weekly MDT meeting using a standard form for documentation; (2) a standard MDT meeting using a newly devised form; and (3) a novel MDT ward round using the new form, and attended by doctors. RESULTS: MDT ward rounds result in significantly better consideration of patients' needs (median 7 per patient compared with 0 and 5 in phases one and two), enhanced SMART (specific, measurable, achievable, realistic and time framed) goal-setting (median 3 per patient compared to 1 in phases one and two); greater patient involvement (12 patients compared to 0 and 4 in phases one and two); and improved team working (measured using the team climate inventory) than do MDT meetings. CONCLUSIONS: In the present study, standard weekly MDT meetings did not meet the standards set for MDT care by the NSF. The use of a MDT ward round allows these standards to be achieved.

Aged↗
PubMed2004

The role of human papillomavirus type 16 and the fragile histidine triad gene in the outcome of cervical neoplastic lesions.

The presence of high-risk human papillomavirus, loss of heterozygosity on chromosome 3p and fragile histidine triad gene expression were assessed as potential markers of cancer and CIN progression in 83 cervical cancers and 74 cervical intraepithelial neoplasia grade 1 lesions. Human papillomavirus type 16 was an indicator of vascular involvement in cancers. Loss of heterozygosity, especially in the fragile histidine triad gene intron 5, was an indicator of high-grade tumours, greater tumour depth and lymph node involvement. Abnormal fragile histidine triad gene expression was more frequent in cervical intraepithelial neoplasia grade 1 lesions with increased risk of disease progression.

Acid Anhydride Hydrolases↗
PubMed2001

Huntington disease phenocopy is a familial prion disease.

Huntington disease (HD) is a common autosomal dominant neurodegenerative disease with early adult-onset motor abnormalities and dementia. Many studies of HD show that huntingtin (CAG)n repeat-expansion length is a sensitive and specific marker for HD. However, there are a significant number of examples of HD in the absence of a huntingtin (CAG)n expansion, suggesting that mutations in other genes can provoke HD-like disorders. The identification of genes responsible for these "phenocopies" may greatly improve the reliability of genetic screens for HD and may provide further insight into neurodegenerative disease. We have examined an HD phenocopy pedigree with linkage to chromosome 20p12 for mutations in the prion protein (PrP) gene (PRNP). This reveals that affected individuals are heterozygous for a 192-nucleotide (nt) insertion within the PrP coding region, which encodes an expanded PrP with eight extra octapeptide repeats. This reveals that this HD phenocopy is, in fact, a familial prion disease and that PrP repeat-expansion mutations can provoke an HD "genocopy." PrP repeat expansions are well characterized and provoke early-onset, slowly progressive atypical prion diseases with an autosomal dominant pattern of inheritance and a remarkable range of clinical features, many of which overlap with those of HD. This observation raises the possibility that an unknown number of HD phenocopies are, in fact, familial prion diseases and argues that clinicians should consider screening for PrP mutations in individuals with HD-like diseases in which the characteristic HD (CAG)n repeat expansions are absent.

Amino Acid Sequence↗
PubMed2001

Does long-term follow-up have a role for node negative squamous carcinoma of the vulva? The Gateshead experience.

A retrospective review was performed of 138 cases of squamous vulval cancer referred to Gateshead between 1986 and 1997, with a median follow-up of 48 months. Eighteen recurrences were detected, 11 within one year of surgery. All nine patients with groin/distant recurrence (including 4 presenting initially with local recurrence only) died of vulval cancer. Vulval pain, bleeding or other symptoms heralded all recurrences. Routine review was ineffective in detecting recurrence. Eight cases were detected by general practitioners, three by specialists, and one was self-diagnosed. Six of these had had clinical review less than two months previously. Follow-up does not appear to offer early detection or survival advantages. Patient education, with symptom-triggered rapid clinic access, may be more effective. Prospective research is indicated to assess both the effectiveness and psychological implications of routine follow-up and alternative strategies.

Adult↗
PubMed2000

Association between high-risk HPV types, HLA DRB1* and DQB1* alleles and cervical cancer in British women.

Cervical scrapes from 116 British women referred with cervical cancer were tested for the presence of high oncogenic risk human papillomavirus (HPV) genotypes (HPV(hr)). Ninety-four per cent of the scrapes had one or more of these virus types and 66% were HPV16-positive. HPV18 was more frequent in adenocarcinoma. No evidence was found for an increased cancer risk associated with the HPV16 E6 350G variant. The HLA DRB1* and DQB1* alleles in these women and in 155 women with normal cytology and negative for HPV(hr) DNA were compared. DQB1*0301 alone (2P = 0.02) and in combination with DRB1*0401 (2P = 0.02) was found to be associated with cervical cancer. This was more marked in cancers positive for HPV types other than HPV16. In contrast, DRB1*1501 alone and in combination with DQB1*0602 was not significantly elevated in cancers overall, but did show some excess in HPV16-positive cancers (2P = 0.05), associated with HPV16-positive cervical cancers. Taking all cancers together, a marginally significant protective effect was found for DQB1*0501 (2P = 0.03) but no protective effect could be seen for DRB1*1301.

Adenocarcinoma↗
PubMed1998

Safety, pharmacokinetics, and antiretroviral activity of the potent, specific human immunodeficiency virus protease inhibitor nelfinavir: results of a phase I/II trial and extended follow-up in patients infected with human immunodeficiency virus.

The safety, antiretroviral activity, and pharmacokinetic profile of nelfinavir, a potent and specific inhibitor of human immunodeficiency virus (HIV) protease, were assessed in a small open-label phase I/II dose-ranging study in protease inhibitor-naive HIV-positive men. A total of 22 patients with baseline plasma HIV RNA > or = 20,000 copies/mL and CD4+ counts between 200 and 500 cells/mm3 were enrolled in the study. Of the 22 patients, 20 were evaluated for activity; 10 patients assigned to 771 mg/day base equivalent (300 mg three times daily) and 10 patients assigned to 1,026 mg/day base equivalent (600 mg twice daily) given monotherapy. A capsule formulation of nelfinavir was used. The initial study period was 28 days; patients showing a virologic response of 1 log10 reduction were eligible for enrollment in an extension phase and addition of nucleoside analogues. A maximally tolerated dose of nelfinavir was not established. A dose-response relationship was observed for four (40%) patients in the 771-mg group and six (60%) patients in the 1,026-mg group experiencing a reduction from baseline in plasma HIV RNA of at lest 1 log during the 28-day study. Of these patients, five sustained the reduction in plasma HIV RNA beyond day 28 (2 patients receiving 771 mg/day and 3 patients receiving 1,026 mg/day). Median increases from baseline in CD4+ counts at day 28 were 216 cell/mm3 and 86 cell/mm3 in the 771-mg and 1,026-mg groups, respectively. After oral administration, median nelfinavir plasma concentrations on day 28 reached a maximum at 1 hour (2,966 ng/mL) in the 771-mg group and at 3 hours (3,157 ng/mL) in the 1,026-mg group. Data for 22 patients were included in the safety analysis; 12 patients (55%) reported at least one grade 2 or worse (moderate, severe, or very severe) adverse event. The most common grade 2 or worse adverse event was diarrhea, reported by two patients (20%) receiving 771 mg/day and seven patients (70%) receiving 1,026 mg/day; followed by nausea, flatulence, asthenia, and headache (each reported in 1 patient [10%] in the 771-mg group) and dizziness (reported in 1 patient [10%] receiving 1,026 mg/day). In the small subgroup (n = 6) who continued taking nelfinavir for longer periods (between 8 and 15 months), virologic responses were sustained in the majority of patients with good tolerability. Nelfinavir is an active HIV-protease inhibitor with favorable pharmacokinetics, good tolerability, and sustained antiviral effects. Results of this early phase I/II dose-ranging study provided data for the safety and antiretroviral activity of nelfinavir and led to the selection of higher doses for phase II/III trials to further optimize virologic and immunologic responses.

Adolescent↗
PubMed1998

An examination of the renal transplant evaluation process focusing on cost and the reasons for patient exclusion.

A medical evaluation of prospective renal transplant recipients is performed to identify conditions that may exclude patients from transplantation because of unacceptable risks. Protocols for evaluating potential transplant candidates are available, but there is little information about reasons for excluding patients from transplantation. To assess the effectiveness and cost of our renal transplant-recipient evaluation process, we retrospectively reviewed patients excluded from renal transplantation between January 1993 and December 1995 to categorize the reasons for exclusion. We also examined the costs of the evaluation. The study group included all adults referred for kidney-only transplantation during the study period who were excluded from transplantation (n=125). Demographics of the 160 patients with end-stage renal disease (ESRD) who underwent renal transplantation during the study period were also examined. Compared with the patients who underwent transplantation, the excluded patients were older (48+/-14 v 43+/-12 years; P=0.006) and more likely to be women (66 of 125 patients; 53% v 57 of 160 patients; 36%; P=0.005) and diabetic (59 of 125 patients; 47% v 30 of 160 patients; 19%; P=0.005). The most common reason for excluding patients was medical contraindication (46%), followed by patient declined (25%), obesity (10%, defined as a body mass index [BMI] > or = 35), patient death (6%), and insurance/financial (5%). The medical reasons for exclusion were heart disease (38%), noncompliance (28%), miscellaneous (22%), and cancer (12%). Tests performed after the initial evaluation included cardiac testing (stress thallium or echocardiography and coronary angiography) in 50 patients, Doppler studies of the lower extremities in 28 patients, and hepatitis C polymerase chain reaction (PCR) or recombinant immunoblot assay (RIBA) assays in 8 patients. The cost of standard pretransplantation blood work for selected tests (ABO blood group typing, HLA, hepatitis B and C, and cytomegalovirus) was $709. Deferring such routine pretransplantation blood work until after the patient education session and history and physical examinations by nephrology and surgery in the 31 patients (25%) who declined transplantation at the initial visit would have resulted in considerable savings. Our evaluation process now includes prereferral information on a prospective recipient's medical problems, height and weight, and basic screening laboratory tests. This protocol has resulted in a more efficient and cost-effective evaluation process. Further examination of the cost-effectiveness of the transplant evaluation process is warranted.

Adult↗
PubMed1998

Lectins in the vulva. I. Normal vulvar epithelium and epithelium adjacent to vulvar intraepithelial neoplasia and squamous cell carcinoma.

Lectins were used to investigate the cell surface oligosaccharide expression in normal vulvar epithelium from premenopausal and postmenopausal volunteer women. In addition, histologically normal epithelium adjacent to high-grade vulvar intraepithelial neoplasia (VIN III) and adjacent to vulvar tumors was examined with lectins for evidence of a possible "field change" surrounding these vulvar lesions. Seventeen vulvar biopsies were obtained prospectively from volunteer women, and 20 and 40 cases, respectively, of VIN III and vulvar squamous cell carcinoma were randomly chosen from pathology archives. Thirteen of the 20 VIN cases and all 40 vulvar carcinomas contained at least 2 cm of histologically normal-appearing epithelium adjacent to the vulvar lesion suitable for analysis. No alterations to lectin binding in normal vulvar epithelium with respect to patient age, menopausal status, phase of menstrual cycle, estrogen therapy, or history of cervical intraepithelial neoplasia were shown. ABO blood group antigen status affected epithelial binding for lectins HPA and UEAI (p < 0.005 and p < 0.001, respectively). In addition, lectins SNA, MPA, and LCA identified markers of cellular differentiation and maturation. T-antigen expression (as shown by the lectin PNA) was almost universally present in histologically normal epithelium adjacent to VIN and vulvar tumors, contrasting with the lack of PNA binding in normal vulvar epithelium from volunteer women (p < 0.001 and p < 0.001), a finding suggestive of a local "field change" surrounding preinvasive and invasive vulvar lesions.

ABO Blood-Group System↗
PubMed1998

Lectins in the vulva. II. Vulvar intraepithelial neoplasia and squamous cell carcinoma.

This study used lectins as histologic probes to determine the cell surface oligosaccharide expression in different grades and types of vulvar intraepithelial neoplasia (VIN). Lectin binding patterns in metastasizing and non-metastasizing squamous cell carcinomas (SCCs) of the vulva were also compared to correlate lectin binding patterns with metastatic potential and other clinical/tumor characteristics. Twenty cases each of VIN epithelium, metastasizing SCC, and non-metastasizing vulvar carcinoma were randomly chosen from the pathology archives. Sixteen lectins were used to probe individual terminal oligosaccharide residues in formalin-fixed, paraffin-embedded tissue specimens from these cases through an indirect immunohistochemical technique. There were no differences in lectin binding patterns between the different histologic subtypes of VIN. In addition, there were no consistent differences between metastasizing and non-metastasizing primary tumors and no major differences in staining patterns between nodal metastases and the corresponding primary tumors. Furthermore, there was no identifiable correlation between lectin binding patterns and subsequent survival or local or regional recurrence; however, lectin staining of invasive tumor cells did appear to be related to local invasiveness. In addition, positive PNA binding was found to be a constant finding in each of the VIN and invasive SCC cases, confirming that the T-antigen becomes unmasked during the process of vulvar carcinogenesis. However, poorly-differentiated areas consistently showed absent lectin binding, suggesting loss of specific glycosyl transferase activities. In addition, the blood group "A" antigen appears to be lost during the process of tumorgenesis, although the blood group "O" antigen appears to be preserved.

Carcinoma in Situ↗
PubMed1997

Cytokine-mediated nitric oxide release--a common cytotoxic pathway in host-versus-graft and graft-versus-host reactions?

Serial cytokine and nitrate (as a measure of nitric oxide production) levels were assayed in nine consecutive patients undergoing allogeneic haemopoietic stem cell transplants. They were compared to those in 13 patients undergoing autologous transplants (transplant controls), 15 neutropenic patients with infective complications (patient controls) and 27 blood donors (normal controls). Peak nitrate, interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) levels were significantly higher in four allogeneic transplant patients with major non-infective complications compared to those without such complications, and control groups. Cytokine and nitrate levels peaked during conditioning therapy in the patients with veno-occlusive disease (one patient) and fulminant cholestatic liver failure (one patient), indicating that tissue damage may have been initiated during chemoradiotherapy in these patients, whereas peak levels occurred 2-3 days before graft rejection (one patient) and severe graft-versus-host disease (one patient), indicating a role for cytokine-induced nitric oxide release in the pathophysiology of these immune-mediated complications. Based on the data presented, it can be tentatively postulated that nitric oxide is a common proximate regulator of the immune response in host-versus-graft and graft-versus-host reactions.

Adolescent↗
PubMed1997

Fertility measures in women after extracorporeal shockwave lithotripsy of distal ureteral stones.

Long-term effects of extracorporeal shockwave lithotripsy (SWL) on female fertility remain a concern. Thirty-nine women of childbearing age who were treated for distal ureteral stones were surveyed. The mean age of these women was 33 years, and the average stone size was 6.9 mm. The mean calculated radiation exposure to the ovaries and the uterus was 7.53 and 10.9 mSv, respectively. Ten women (26%) attempted to become pregnant. No fertility problems were noted in these women, and 11 healthy babies were delivered. These preliminary findings provide further information regarding the safety of SWL in the treatment of distal ureteral stones in women of reproductive age.

Adolescent↗
PubMed1993

Recurrent squamous cell carcinoma of the vulva: a study of 73 cases.

In a study of 73 patients, diagnosed with recurrent squamous cell carcinoma of the vulva between 1975 and 1990, the effect of clinical variables on the outcome was evaluated. The overall 5-year survival rate was 35.2%. Of the 73 patients, 33 (45.2%) originally had Stage I or II disease and 40 (54.8%) Stage III or IVA; 49 (67.1%) recurred less than 2 years and 24 (32.9%) more than 2 years after initial surgery; and 39 (53.4%) recurred on the vulva only, while 34 (46.6%) recurred beyond the vulva. Of 59 patients who had groin lymph node dissection at initial surgery, 26 (44%) had negative and 33 (56%) had positive nodes. By means of univariate analyses, a significant worsening in outcome was demonstrated with advancing original stage of disease (P < 0.001), positivity of groin lymph nodes (P < 0.01), shortening of recurrence-free interval (P < 0.001), and extension of recurrence beyond the vulva (P < 0.001). In a multivariate analysis (Cox proportional hazards model) recurrence site was the strongest and the only significant predictor of survival. The death risk showed a 3.7-fold increase (95% confidence intervals: 1.6 to 8.7, P = 0.002) for recurrence beyond the vulva over recurrence on the vulva only. For patients who recurred in the vulva only, wide radical local excision provided acceptable survival results, while for all other patients, regardless of type of treatment, the outcome was poor.

Adult↗
PubMed1993

Role of extracorporeal shock-wave lithotripsy in treatment of urolithiasis in patients with medullary sponge kidney.

In an effort to identify the role of extracorporeal shock-wave lithotripsy (ESWL) in the treatment of patients with medullary sponge kidney, a retrospective review of our experience with the Dornier HM-3 lithotriptor is presented. From 1986-1991 17 patients with medullary sponge kidney ranging in age from twenty-eight to fifty-eight years received 31 treatments to a total of 24 renal units. Follow-up ranged from four to fifty-six months with an average follow-up of twenty-five months. ESWL appears to have a role in the treatment of symptomatic urolithiasis in patients with medullary sponge kidney. There may also be some benefit in treating parenchymal calcifications. No significant side effects from the treatment were noted.

Adult↗
PubMed1990

Phase II studies of ifosfamide alone and in combination in cancer of the cervix.

A series of phase II studies using ifosfamide (IFX) as a single agent and in combination with cisplatin and bleomycin (BIP) in advanced and recurrent cervical cancer have been coordinated at the West Midlands CRC Clinical Trials Unit (Birmingham, UK). The aims of these studies were to identify single agents and combination regimens that may be of value for palliation and have potential for use as neoadjuvant and adjuvant therapy at the time of primary treatment. A total of 79 patients with disease non-amenable to radical local therapy were treated with single-agent IFX or the BIP combination. In 30 patients treated with single-agent IFX, 10 objective responses (30%) were seen, with 1 complete response. In 49 patients treated with BIP, 34 objective responses (69%) were seen, with 10 complete responses (20%). Toxicity included alopecia, nausea and vomiting, myelosuppression, infection, reduction in renal function and disturbance of consciousness. These data indicate that IFX is highly active in cervix cancer and, in combination with bleomycin and cisplatin, can be used for effective palliation and cytoreduction in greater than 70% of patients. IFX-containing regimens have potential for use as neoadjuvant and adjuvant therapy in patients at high risk of recurrence with conventional treatment. These hypotheses are currently being tested in prospective randomised trials.

Adult↗
PubMed1990

The potential for adjuvant therapy in early-stage cervical cancer.

Adjuvant therapy may potentially improve prognosis in women with early-stage cervical cancer who are at high risk of relapse after primary therapy. Patients with lymph node involvement at surgery are at high risk of recurrence and may benefit from adjuvant therapy, but many patients are treated with radical radiotherapy. At present there is no method of accurately identifying patients at high risk of recurrence in the latter group. A retrospective analysis of 141 surgically managed cases with stage I/II a cervical cancer is presented. The study aims were to characterize patients at high risk of relapse, identify independent prognostic variables predicting for relapse and, using these variables, develop a model, that would accurately predict high-risk patients. Univariate analysis identified depth of invasion, substage, lymph node involvement, lymphatic and blood vessel invasion and tumour differentiation as significant prognostic variables. After stratification for depth of invasion, which did not conform to the proportional hazards assumption implicit in the Cox model, Cox regression analysis showed substage, lymphatic and vascular invasion and histological tumour type to be independent prognostic variables. Using these variables, classification models were constructed that would be applicable to patients treated with either surgery or radiotherapy. Applying the models to 110 cases with greater than 18 months follow-up, 11/18 (61%) and 11/19 cases (58%) predicted as being at high risk of relapse have developed recurrence. Highly active chemotherapy is now available for this disease. We have demonstrated that combined bleomycin, ifosfamide and cisplatin (BIP) is one of the most active regimens in this disease. BIP produces cytoreduction in around 70% of patients with recurrent and primary advanced disease. Responses are achieved rapidly and acute radiotherapy toxicity is not enhanced by giving chemotherapy prior to radical local radiotherapy. A multicentre, prospective randomized trial testing the role of BIP as adjuvant therapy in patients with positive nodes at radical hysterectomy is now in progress. A complementary study testing the role of adjuvant chemotherapy in high-risk patients treated with radical radiotherapy is in preparation.

Adenocarcinoma↗