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Biomedical subjects

G Horne

Publications and source records attributed to G Horne.

At least 19 recordsLinked to original sources
PubMed2006

Medical optimisation can reduce morbidity and mortality associated with elective aortic aneurysm repair.

OBJECTIVES: Patients with aortic aneurysms have significant comorbidities which influence outcome. Our practice includes comprehensive assessment to identify comorbidities, allowing subsequent medical optimisation prior to aneurysm repair. The aim of this study was to assess this process and to identify any factors predictive of outcome. DESIGN: Prospective observational study. MATERIALS: Medical case notes of 200 patients referred with aortic pathology. METHODS: Data analysed included preoperative, perioperative and postoperative factors. Multiple logistic regression analysis was performed to identify predictors of outcome. RESULTS: Following assessment 17 patients (8.5%) were found to be unfit for intervention and 165 patients (82.5%) proceeded to aneurysm repair. In this group assessment uncovered previously undiagnosed cardiac, respiratory and renal comorbidity in 19%, 57% and 29% of patients respectively. Multiple logistic regression analysis indicated that optimisation by a renal physician reduced post-operative renal impairment (OR 0.12, 95% CI 0.03-0.45, P=0.002) while optimisation by a cardiologist reduced respiratory complications (OR 0.7, 95% CI 0.05-0.99, P=0.049). An abnormal echocardiogram was associated with pneumonia (OR 6.9, 95% CI 1.6-29, P=0.01) and death (OR 7.9, 95% CI 1.15-54, P=0.036). CONCLUSION: Pre-operative assessment identifies previously undiagnosed comorbidity in a significant proportion of patients. Subsequent medical optimisation may reduce post-operative morbidity and mortality.

Aged↗
PubMed2006

Multimodal immunosuppressant therapy in steroid-refractory common variable immunodeficiency sprue: a case report complicating cytomegalovirus infection.

Immunodeficient patients can develop malabsorption, mimicking celiac disease clinically and histologically. Such individuals may also occasionally require immunosuppressive therapy for autoimmune disorders. We have identified a patient with common variable immunodeficiency (CVID)-associated sprue complicated by duodenal cytomegalovirus (CMV) infection following corticosteroid and ancillary immunomodulatory therapy. Ganciclovir and a modification of the immunosuppressant regimen improved both clinical symptoms and villous atrophy. To our knowledge, this is original documentation of duodenal CMV infection secondary to immunomodulatory therapy for steroid-refractory CVID-sprue.

Adrenal Cortex Hormones↗
PubMed2004

Live birth with sperm cryopreserved for 21 years prior to cancer treatment: case report.

Advances in cancer treatment have led to significant improvements in the likelihood of reaching remission and long-term survival for men. Chemo- and radiotherapy-induced infertility are significant treatment side effects. Cryopreservation before the start of treatment enables sperm to be stored, thereby preserving the man's potential fertility. Here, we describe the successful use (with ICSI) of sperm cryopreserved prior to cancer treatment, for a total of 21 years. We believe this to be the longest period of sperm cryopreservation, resulting in a live birth, so far reported in the literature.

Adolescent↗
PubMed2002

Semen cryopreservation, utilisation and reproductive outcome in men treated for Hodgkin's disease.

Between 1978 and 1990, 122 men underwent semen analysis before starting sterilising chemotherapy for Hodgkin's disease. Eighty-one (66%) had semen quality within the normal range, 25 were oligospermic (<20 x 10(6) sperm per ml) and five were azoospermic (no sperm in the ejaculate). Semen from 115 men was cryopreserved and after a median follow-up time of 10.1 years, 33 men have utilised stored semen (actuarial rate 27%) and nine partners have become pregnant resulting in 11 live births and one termination for foetal malformation. Actuarial 10 year rates of destruction of semen before death or utilisation and death before utilisation are 19% and 13% respectively. This retrospective cohort study demonstrates that approximately one-quarter of men utilising cryopreserved semen after treatment for Hodgkin's disease obtain a live birth. The high non-utilisation rate is intriguing and warrants further investigation.

Antineoplastic Agents↗
PubMed2001

Total synthesis of nucleobase-modified adenophostin A mimics.

The adenophostins exhibit approximately 10-100 times higher receptor binding and Ca2+ mobilising potencies in comparison with the natural second messenger D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. Despite many synthetic attempts to determine the minimal structural requirement for this unusual behaviour of the adenophostins, few related simplified analogues displaying higher activity than that of Ins(1,4,5)P3 have been reported. However, biological evaluation of such analogues has revealed that one of the key factors for the enhanced biological activity is the adenine moiety. To further understand the effect that the adenine base has upon the activity of the adenophostins, congeners in which this functionality is replaced by uracil, benzimidazole, 2-methoxynaphthalene, 4-methylanisole and 4-methylnaphthalene using the common intermediate 1,2-di-O-acetyl-5-O-benzyl-3-O-(3,4-di-O-acetyl-2,6-di-O-benzyl-alpha-D-glucopyranosyl)-ribofuranose have been synthesised using a base replacement strategy. The synthesis of the uracil and benzimidazole analogues was achieved using the Vorbrüggen condensation procedure. The 1'-C-glycosidic analogues were prepared using Friedel-Crafts type C-aryl glycosidation reactions. Phosphate groups were introduced using the phosphoramidite method with subsequent removal of all-benzyl protecting groups by catalytic hydrogenation or catalytic hydrogen transfer. Apart from one analogue with an alpha-glycosidic linkage all compounds were more potent than Ins(1,4,5)P3 and most tended more towards adenophostin in activity. These analogues will be valuable tools to unravel the role that the adenine moiety plays in the potent activity of the adenophostins and demonstrate that this strategy is effective at producing highly potent ligands.

Adenosine↗
PubMed2001

Hip fracture incidence in New Zealand, revisited.

AIM: Earlier predictions of the incidence of hip fractures in the older adult population suggested that by 2011 the rate would rise to epidemic proportions. The purpose of this study was to compare the number hip fractures occuring in New Zealand from 1988 to 1999 with the hip fracture rate predicted in 1990 by Rockwood, Horne and Cryer. METHODS: Data on the number of patients admitted to New Zealand hospitals with a diagnosis of fractured neck of femur were obtained, and compared with weighted regression and baseline predictions of Rockwood et al. RESULTS: The numbers of hip fractures for females, from 1988 to 1993, were similar to the number predicted, yet have been significantly lower than stated predictions since 1995. For males, hip fracture numbers since 1995 were less than the weighted regressions predicted (NS). CONCLUSIONS: Numbers of hip fractures since 1995 have been fewer than predicted. Possible reasons for maintaining the rates of hospitalisation due to fractured neck of femur at pre-1995 levels, are discussed.

Accidental Falls↗
PubMed2001

Synthesis of the enantiomers of 6-deoxy-myo-inositol 1,3,4,5-tetrakisphosphate, structural analogues of myo-inositol 1,3,4,5-tetrakisphosphate.

D-myo-Inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] is produced rapidly from the established second messenger D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P4] in stimulated cells. Despite extensive investigations, in particular concerning its potential role in mediating cellular Ca2+ influx, no exact cellular function has been described for this inositol phosphate; however, binding sites have been identified in a number of tissues and it has been shown to act synergistically with Ins(1,4,5)P3. To assist in the elucidation of the mechanism of action and structural requirements within the Ins(1,3,4,5)P4 moiety that are necessary for recognition and activation of the receptor, structural analogues of this tetrakisphosphate are required. Routes for the synthesis of racemic 6-deoxy-myo-inositol 1,3,4,5-tetrakisphosphate [6-deoxy-DL-Ins(1,3,4,5)P4] and the chiral antipodes D- and L-6-deoxy-myo-inositol 1,3,4,5-tetrakisphosphate are described here. The racemic tetrakisphosphate was synthesised from DL-1,2-O-isopropylidene-myo-inositol in eight steps. Deoxygenation at C-6 was achieved following the Barton-McCombie procedure. Both chiral tetrakisphosphates were synthesised through resolution of racemic cis-diol 6-deoxy-1,4,5-tri-O-p-methoxybenzyl-myo-inositol with the chiral auxiliary (S)-(+)-O-acetylmandelic acid. Absolute configuration was confirmed by synthesis of the known D-6-deoxy-myo-inositol. Both D-6-deoxy-Ins(1,3,4,5)P4 and its enantiomer will be useful tools to unravel the enigmatic role of Ins(1,3,4,5)P4 in the polyphosphoinositide pathway of signal transduction.

Animals↗
PubMed2001

Achieving pregnancy against the odds: successful implantation of frozen-thawed embryos generated by ICSI using spermatozoa banked prior to chemo/radiotherapy for Hodgkin's disease and acute leukaemia.

Two cases are reported of successful pregnancies following long-term semen banking prior to chemotherapy and radiotherapy for malignancy. With the first case, the patient banked semen at the age of 20 years prior to chemotherapy for Hodgkin's disease; 11 years later the thawed semen was used for IVF with intracytoplasmic sperm injection (ICSI), resulting in twins being born following the transfer of frozen-thawed embryos. In the second case, the patient banked semen at the age of 17 years prior to chemotherapy and radiotherapy for acute myeloid leukaemia; 8 years later it was used for ICSI, resulting in triplets being born following the transfer of frozen-thawed embryos. These cases support long-term semen banking for men whose future fertility may be compromised by suppression of spermatogenesis secondary to administration of chemo/radiotherapy treatment. The advent of successful ICSI combined with embryo cryopreservation has increased the chance of thawed cryopreserved semen achieving fertilization. Banking of a single ejaculate prior to commencement of chemotherapy/radiotherapy treatment may preserve potential fertility without compromising the oncology treatment.

Adolescent↗
PubMed2001

Structural determinants of adenophostin A activity at inositol trisphosphate receptors.

Adenophostin A is the most potent known agonist of inositol 1,4,5-trisphosphate (InsP(3)) receptors. Ca(2+) release from permeabilized hepatocytes was 9.9 +/- 1.6-fold more sensitive to adenophostin A (EC(50), 14.7 +/- 2.4 nM) than to InsP(3) (145 +/- 10 nM), consistent with the greater affinity of adenophostin A for hepatic InsP(3) receptors (K(d) = 0.48 +/- 0.06 and 3.09 +/- 0.33 nM, respectively). Here, we systematically modify the structures of the glucose, ribose, and adenine moieties of adenophostin A and use Ca(2+) release and binding assays to define their contributions to high-affinity binding. Progressive trimming of the adenine of adenophostin A reduced potency, but it fell below that of InsP(3) only after complete removal of the adenine. Even after substantial modifications of the adenine (to uracil or even unrelated aromatic rings, retaining the beta-orientation), the analogs were more potent than InsP(3). The only analog with an alpha-ribosyl linkage had massively decreased potency. The 2'-phosphate on the ribose ring of adenophostin A was essential and optimally active when present on a five-membered ring in a position stereochemically equivalent to its location in adenophostin A. Xylo-adenophostin, where xylose replaces the glucose ring of adenophostin A, was only slightly less potent than adenophostin A, whereas manno-adenophostin (mannose replacing glucose) had similar potency to InsP(3). These results are consistent with the relatively minor role of the 3-hydroxyl of InsP(3) (the equivalent is absent from xylo-adenophostin) and greater role of the equatorial 6-hydroxyl (the equivalent is axial in manno-adenophostin). This is the first comprehensive analysis of all the key structural elements of adenophostin A, and it provides a working model for the design of related high-affinity ligands of InsP(3) receptors.

Adenosine↗
PubMed2000

Use of in-vitro fertilisation embryos cryopreserved for 5 years or more.

Human embryos cryopreserved after in-vitro fertilisation can be stored initially for 5 years, and the storage period may be extended to a maximum of 10 years. Of 1344 embryos cryopreserved between 1988 and 1994 at two centres in Manchester, 67% (904 embryos) have had to be destroyed at the end of the first 5-year interval, even if the couples involved remain childless.

Cryopreservation↗
PubMed2000

Control of an outbreak of respiratory syncytial virus infection in immunocompromised adults.

Respiratory syncytial virus (RSV) is increasingly recognized as an important pathogen in immunocompromised adults, particularly those receiving bone marrow transplants, and, given the ease with which it spreads, represents a significant nosocomial problem. We describe an outbreak of RSV infection involving eight patients on a haematology/oncology ward which was controlled by early screening of patients and staff. Positive patients were cohort nursed on a separate ward and basic infection control measures including use of gowns and gloves were enforced. Children under age 12 were denied ward access. All patients with lower respiratory tract infection, and bone marrow transplant recipients with upper respiratory symptoms, were treated with nebulized ribavirin. There were no deaths. We conclude that awareness of the risk of RSV infection in immunocompromised patients coupled with rapid diagnosis and treatment, screening of symptomatic patients and staff, cohort nursing of cases and basic infection control procedures can prevent spread of RSV infection and reduce morbidity.

Adult↗
PubMed1999

Surgical repair for recurrent anterior instability of the shoulder.

BACKGROUND: The outcome of surgical repair for recurrent anterior instability of the shoulder at the Wellington Hospital was reviewed. METHODS: A retrospective review was undertaken of patients undergoing surgical repair for recurrent anterior instability of the shoulder at Wellington Hospital between October 1989 and November 1996. Patients were asked to complete two shoulder-specific questionnaires, and the range of motion, stability, and strength was evaluated clinically. RESULTS: A total of 37 patients (38 shoulders) who had recurrent anterior dislocation of the shoulder that was unresponsive to a physician-directed rehabilitation programme were managed with open surgical repair. Procedures included the Putti-Platt, Bristow, Magnuson-Stack, Botychev, and Bankart repairs. The mean age at the time of surgery was 24 years and the male-to-female ratio was 11.3:1. Surgery was performed on the dominant side in 63.2% of shoulders. The postoperative redislocation rate was 39.4% at an average of 4.6 years follow-up. Three patients have since required revision of their surgical repair and one patient is awaiting revision. A total of 63.2% of patients were unable to return to their previous level of sports. Differences existed between the motion in the surgically treated shoulder when compared with the contralateral side. Patients reported the most functional difficulty in throwing, working overhead, pulling, and working at shoulder level. CONCLUSIONS: The results of the present study indicate a high redislocation rate, and highlight the challenges in restoring a stable, mobile, functional shoulder.

Activities of Daily Living↗
PubMed1998

A 3 year retrospective review of intrauterine insemination, using cryopreserved donor spermatozoa and cycle monitoring by urinary or serum luteinizing hormone measurements.

Insemination with donor spermatozoa is an integral part of infertility treatment. For the last 3 years in our unit, intrauterine insemination with donor spermatozoa (IUID) has been used in preference to vaginal insemination. In this retrospective study, patients were offered an initial course of five single intrauterine inseminations with cryopreserved donor spermatozoa and treatment was then reviewed. A total of 389 patients received 1465 inseminations. In all, 1119 cycles were monitored using luteinizing hormone serum analyses and 346 cycles using the urine home test kits. The clinical pregnancy rate per insemination for the cycles monitored by the serum assay was 18.0% (202/1119) compared with the urine cycles (13.7%, 46/346) (P <05). The pregnancy loss rate was not significantly different (14.4%, 29/202 and 21.7%, 10/46) (serum and urine cycles respectively). The viable clinical pregnancy rate was significantly higher (P <03) for the serum cycles than for the cycles using the urinary monitoring (15.5%, 173/1119 and 10.4%, 36/346 respectively). The cycles monitored by serum assay had a significantly higher cumulative viable clinical pregnancy rate (P <0001) of 70.2% after nine inseminations compared with the urine monitored cycles of 54.8%. The majority of patients opted for the serum cycles, with a minority self-selecting the urine cycles mainly for travelling convenience. The explanation for the significant differences between the viable clinical pregnancy rates per insemination and the cumulative viable clinical pregnancy rates may be due to the sensitivity of the urine home test kit or the patients' interpretation of the result.

Cryopreservation↗
PubMed1997

A prospective evaluation of cryopreservation strategies in a two-embryo transfer programme.

A total of 364 consecutive patients requesting in-vitro fertilization (IVF) treatment were divided randomly into two groups. In the first group, two embryos in the original IVF cycle were allowed to divide prior to transfer, with any remaining embryos being cryopreserved at the pronucleate (PN) stage. In the second group, all the embryos were allowed to divide to the early cleavage (EC) stage, and the best two replaced; any suitable remaining embryos were frozen at the 2- to 4-cell stage. A total of 134 cycles (36.8%) fulfilled the study criteria for a fresh embryo replacement and supernumerary embryos cryopreserved. In the PN group, 72 out of 182 (39.6%) patients had a fresh embryo replacement accompanied by embryo cryopreservation, which was not significantly different from the EC group (62/182; 34.1%). The livebirth rate per fresh embryo transfer in the EC group (17/62; 27.4%) was significantly higher than that for the PN group (8/72; 11.1%; P < 0.05). Embryo survival following thawing was similar for the PN (96/129; 74.4%) and EC (79/102; 77.4%) stages. Although not significant, the livebirth rate following the transfer of thawed embryos was higher in the PN group (11/44; 25.0%) than in the EC group (4/38; 10.5%). Following one fresh and two freeze-thaw embryo replacements, the observed cumulative viable pregnancy rates were comparable for patients in both the PN (40.2%) and EC (41.1%) groups.

Adult↗
PubMed1996

Forearm and wrist fractures in mountain bike riders.

AIMS: To identify the different types of fractures of the forearm caused by mountain bike accidents, and to assess the physical and social consequences of these injuries. METHODS: All the forearm fractures recorded in the Wellington Hospital fracture logs between July 1992 and July 1994 were reviewed in December 1994. Mountain bike accidents were identified in 37 patients. 11 patients could not be contacted and one patient declined participation, leaving 25 patients who participated in the study. Those who took part each completed a questionnaire and were examined. The radiographs of each patient were also reviewed. RESULTS: Nine of the fractures occurred in the proximal third of the forearm and 16 occurred in the distal third. The most common fracture was that of the radial head (9). When functionally assessed 15 patients were graded excellent, 5 satisfactory, 4 unsatisfactory, and 1 patient was graded as poor. The average time off work was 28 days, with no change of occupation being necessitated in any of the patients. Eight patients had to make changes to their recreational activities. CONCLUSIONS: The results of the study suggest that mountain bike accidents can result in significant injury. With adequate medical attention it appears that the majority of cases recover well, and experience only minimal discomfort without significant long term physical and social consequences.

Adolescent↗