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Biomedical subjects

J Harper

Publications and source records attributed to J Harper.

At least 91 records · Page 5Linked to original sources
PubMed1994

Implants of polymer-encapsulated human NGF-secreting cells in the nonhuman primate: rescue and sprouting of degenerating cholinergic basal forebrain neurons.

Baby hamster kidney (BHK) cells were genetically modified to secrete high levels of human nerve growth factor (BHK-hNGF). Following polymer encapsulation, these cells were implanted into the lateral ventricle of four cynomolgus monkeys immediately following a unilateral transection/aspiration of the fornix. Three control monkeys received identical implants, with the exception that the BHK cells were not genetically modified to secrete hNGF and thus differed only by the hNGF construct. One monkey received a fornix transection only. All monkeys displayed complete transections of the fornix as revealed by a comprehensive loss of acetylcholinesterase-containing fibers within the hippocampus ipsilateral to the lesion. Control monkeys that were either unimplanted or received BHK-control (non-NGF secreting) cell implants did not differ from each other and displayed extensive losses of choline acetyltransferase and p75 NGF receptor (NGFr)-immunoreactive neurons within the medial septum (MS; 53 and 54%, respectively) and vertical limb of the diagonal band (VLDB; 21 and 30%, respectively) ipsilateral to the lesion. In contrast, monkeys receiving implants of BHK-hNGF cells exhibited a only a modest loss of cholinergic neurons within the septum (19 and 20%, respectively) and VLDB (7%). Furthermore, only implants of hNGF-secreting cells induced a dense sprouting of cholinergic fibers within the septum, which ramified against the ependymal lining of the ventricle adjacent to the transplant site. Examination of the capsules retreived from monkeys just prior to their death revealed an abundance of cells that produced detectable levels of hNGF in a sufficient concentration to differentiate PC12A cells in culture. These findings support the use of polymer-encapsulated cell therapy as a potential treatment for neurodegenerative diseases such as Alzheimer disease where basal forebrain degeneration is a consistent pathological feature. Moreover, this encapsulated xenogeneic system may provide therapeutically effective levels of a number of neurotrophic factors, alone or in combination, to select populations of neurons within the central nervous system.

Acetylcholine↗
PubMed1994

Percutaneous fluoroscopic gastrostomy. A safe option?

OBJECTIVE: To assess the safety of percutaneous fluoroscopic gastrostomy (PFG) tube insertion for enteral nutrition. DESIGN AND SETTING: The records of 70 consecutive patients who had a PFG procedure at a tertiary referral hospital (Princess Alexandra Hospital) were analysed retrospectively. MAIN OUTCOME MEASURE: Incidence of morbidity and mortality from PFG. RESULTS: Sixty-nine of 70 procedures were successfully performed. There were two deaths secondary to aspiration pneumonia and a morbidity rate of 13%. These figures are comparable with results from other series. CONCLUSION: PFG is a safe, effective procedure for enteral nutrition.

Adolescent↗
PubMed1994

The effects of finasteride (Proscar) on hair growth, hair cycle stage, and serum testosterone and dihydrotestosterone in adult male and female stumptail macaques (Macaca arctoides).

Finasteride, a 5 alpha-reductase inhibitor, was administered orally (1 mg/kg.day) for 6 months to six male and five female stumptail macaques. Vehicle was given to five male and five female animals over the same period of time. Hair weights in a defined 1-in.2 area of frontal scalp were measured periodically every 1-2 months, and serum was collected for measurement of testosterone and dihydrotestosterone. In addition, scalp biopsies were taken before and 6 months after treatment to evaluate the micromorphometry of hair follicles. Results showed that both male and female serum dihydrotestosterone levels were significantly reduced (60-70%) by finasteride treatment. Both males and females showed statistically significant increases in mean hair weight over the treatment period compared to controls (P = 0.034). In addition, there was a statistically significant increase in mean follicle length (measured histologically in scalp biopsies) compared to baseline in the finasteride-treated animals (P = 0.028). These data show that an inhibition of 5 alpha-reductase in the stumptail macaque can reverse the balding seen with age in both the male and female animals.

Animals↗
PubMed1993

Transfer of embryos into the uterus: how much do technical factors affect pregnancy rates?

OBJECTIVE: Our objective was to identify the effect on outcome of (a) ultrasound-assisted embryo transfer, (b) the use of different embryo transfer catheters, and (c) the length of time the patients remain in the supine position after embryo transfer. SETTING: The setting was a private fertility center. SUBJECTS: This was a prospective study of 178 in vitro fertilization and embryo transfers (IVF-ET) and 63 frozen embryo replacements (FER). RESULTS: The pregnancy rate was 28.7% following IVF-ET and 31.8% for FER. Ultrasound-assisted transfer did not affect the outcome (29 vs 30.3%). There was no difference in the performance of the Wallace and Frydman catheters with regard to outcome (30.3 vs 30.7%). Although there was an increase in pregnancy rate as the time interval in the supine position after ET increased, this needs a larger study. CONCLUSION: The parameter studies did not affect the outcome of IVF/ET or FER. Some factors encouraged us to recommend ultrasound-assisted transfer in some cases, and the use of a Frydman catheter for transfer and to encourage the supine position after transfer for longer periods.

Abdomen↗
PubMed1993

HPV DNA and the risk of squamous intraepithelial lesions of the uterine cervix in young women.

A population-based case-control study of college students was undertaken to estimate the effect of a positive clinical test for human papillomavirus (HPV) DNA (the Virapap test) on the rate of squamous intraepithelial lesions (SIL) of the uterine cervix. When age, multiple lifetime sexual partners, and oral contraceptive use were controlled by logistic regression, the adjusted odds ratio (OR) for a positive Virapap test was 7.3 (3.3, 17) for a cytologic diagnosis of SILs and 3.4 (1.4, 8.5) for a cytologic diagnosis of squamous intraepithelial lesions of undetermined significance (equivocal atypia). When case status was defined as patients whose Pap smears were confirmed histologically as high-grade SIL, the adjusted OR was 10.3 (3.3, 32), reflecting the high proportion of individuals with SILs who were harboring high-grade squamous intraepithelial lesions. These results confirm the many previous findings of a strong association between HPV DNA, and demonstrate that strength of the association persists when important confounding variables are controlled. This suggests a causal role for HPV in cervical neogenesis. Believing that HPV infection is a major causal agent for cervical cancer precursors suggests that in this time of rapidly increasing HPV prevalence, especially among young persons, the incidence of cervical neoplasia will rise. This underscores the importance of increasing the availability, usage, and perhaps the frequency of Pap smear screening.

Adolescent↗
PubMed1993

Detection of aneuploidy and chromosomal mosaicism in human embryos during preimplantation sex determination by fluorescent in situ hybridisation, (FISH).

Five couples at risk of producing offspring with X-linked recessive disease underwent in vitro fertilisation with a view to preimplantation determination of embryo sex and selective transfer of females. On day three postinsemination, one or two blastomeres were removed by embryo biopsy, and used for dual fluorescent in situ hybridisation with X and Y chromosome-specific DNA probes. In two cases, two female embryos were transferred and one pregnancy, (sex confirmed), is ongoing at 19 weeks. All eight embryos from one couple were of such poor quality that diagnosis was possible in one only. In the remaining two cases no embryos were transferred due to the detection of an abnormal number of X chromosome signals. Investigation of the biopsied embryos that were not transferred revealed evidence of mitotic non-disjunction in one and of complete X monosomy in a second. A surviving fetus with this latter constitution would have developed Turner syndrome and would also have been at high risk of X-linked disease. The use of fluorescent in situ hybridisation rather than the polymerase chain reaction allowed the detection of abnormal copy numbers of X chromosomes thus preventing the transfer of potentially abnormal zygotes.

Adult↗
PubMed1993

Collagen characterization in volume-overload- and pressure-overload-induced cardiac hypertrophy in minipigs.

Previous studies in several different species have shown reduced extractability of collagens in some types of cardiac hypertrophy (volume overload) but not others (pressure overload). The objective of the present study was to examine collagen proteins from the same species (minipigs) with both pressure-overload- and volume-overload-induced cardiac hypertrophy. Hypertrophy was induced by two methods: thoracic banding of the aorta to create pressure overload and arteriovenous shunt to cause volume overload in a porcine model. Collagen types I, III, IV, and V were isolated by pepsin digestion from normal and hypertrophied pig left ventricle tissues. Types I and III collagens from normal and hypertrophied samples, when separated from types IV and V, were digested with cyanogen bromide (CB), and the peptides were examined. Collagen concentration was increased in myocardium removed from hearts subjected to volume overload and unchanged in hearts subjected to pressure overload. The extractability of total collagen was unaffected in pressure-overloaded left ventricles but lower in samples from volume-overloaded hearts. CB digestion cleaved all of the types I and III collagens into similar smaller CB peptides with the exception of a 100-kDa peptide that was observed in both control and hypertrophied hearts. This peptide corresponds to one of the high-molecular-weight peptides found in canine heart tissue. The mature collagen cross-link hydroxylysylpyridinoline (HP) was identified in normal and hypertrophied types I and III collagen from porcine sources. Pressure-overload- and volume-overload-induced cardiac hypertrophy in the pig produced different alterations in the extracellular matrix.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1992

The influence of ovarian response on gamete intra-Fallopian transfer outcome in older women.

Fecundity declines with increasing age in women. The pregnancy rate is lower in in-vitro fertilization/embryo transfer (IVF/ET) in women aged greater than or equal to 40 years. We analysed 349 consecutive gamete intra-Fallopian transfer (GIFT) cycles in women aged greater than or equal to 40 years to identify factors which affected the outcome. A maximum of four oocytes were transferred in GIFT as recommended by the Interim Licensing Authority; 61 women (17.5%) had a positive serum beta-human chorionic gonadotrophin, 35 (10%) had a miscarriage and 26 (7.5%) delivered live infants. The pregnancy rate was lower than with younger women while the conception loss was higher. Pregnancy and delivery rates increased as the number of oocytes retrieved increased but declined again if greater than 10 oocytes were retrieved. If 1-3 oocytes were retrieved, the pregnancy rate was 9.7% and the delivery rate was 3.9%; if 4-10 oocytes were retrieved, the pregnancy rate was 22.1% and the delivery rate was 10.1%, and when greater than 10 oocytes were retrieved, the rates were 17.6 and 5.9% respectively. The highest pregnancy rate was when four oocytes were transformed in GIFT (22.4%) and the delivery rate was 10.0%. An adequate response to long down-regulation with gonadotrophin-releasing hormone agonist was also a factor associated with high delivery rates (13.5%). We conclude that the delivery rate after GIFT in women aged greater than or equal to 40 years is low, but there is a subgroup who have an acceptable delivery rate because of a good ovarian response. In this group, pituitary down-regulation improves the outcome of treatment.

Adult↗
PubMed1992

Inhibitors of collagenase in ligaments and tendons of rabbits immobilized for 4 weeks.

Our laboratories have previously measured the capacity for collagenase production by normal and immobilized rabbit periarticular connective tissues (PCT), i.e., anterior cruciate ligaments (ACL), medial collateral ligament (MCL) and patellar tendon (PT). Rabbit limbs were immobilized for 4 weeks and then the tissues were cultured for 4 days. Collagenase and inhibitor (TIMP) were measured in the medium. Collagenase activity was significantly decreased in the medium from all experimental tissues, relative to the levels in contralateral control tissues. On the other hand there was no significant change in inhibitor levels in the three experimental tissues. These results support the idea that collagenase is decreased due to decreased enzyme expression and not to increased inhibitor production.

Animals↗
PubMed1991

Cancer and health screening in Canterbury general practices.

The general practitioners in the Canterbury Area Health Board area were surveyed for their screening policies for cancer and medical conditions. Responses were obtained from 210 (79%), 55% of whom had age/sex registers. Ninety-seven percent provided cervical smears, usually at 1-2 year intervals; 62% offered a female smear taker. Smears were initiated opportunistically by 76%, by age/sex register (47%) or on request by 27%. Breast cancer was screened by 69% using mammography and by 59% using breast physical examination; 73% taught breast self examination. Mammography was recommended every two years for women aged 50-64 years by 45% of responders, and annually to women aged 40-50 years by 19%. Mammography was initiated opportunistically by 88%, on request by 70% and using an age/sex register by 21%. Melanoma was screened by 66%, colorectal cancers in those at high risk by 42%. Testicular self examination was promoted by 43%. Ninety-one percent screened for hypertension, and 51% for hyperlipidaemia, 54% for diabetes mellitus in people without risk factors. Smoking (97%) and alcohol intake (82%) were usually inquired for, and safe sex practices by 59%. Established screening modalities were recommended by most practitioners, but the frequency exceeded current guidelines in many cases; opportunistic screening predominated.

Family Practice↗
PubMed1991

Congenital malignant melanoma of the eye.

Twenty-three cases of congenital malignant melanoma have previously been reported. Here the authors report the first case of a congenital malignant melanoma arising in the eye. A newborn girl had a large pigmented ocular tumor, hepatomegaly, and multiple pigmented skin and choroidal lesions. The histopathologic diagnosis was of a malignant melanoma with hepatic metastases. The skin and choroidal lesions were considered to be congenital melanocytic nevi. The most plausible pathogenetic link between these two conditions was that the malignancy had arisen as a second-hit mutation within a choroidal congenital melanocytic nevus. Despite widespread metastases the baby, treated by surgery and chemotherapy, survives in good health, aged 2 years, 10 months.

Eye Neoplasms↗
PubMed1991

The reproductive outcome following a superhigh response to stimulation in gamete intrafallopian transfer program.

A retrospective analysis was carried out to assess the outcome of gamete intrafallopian transfer (GIFT) in cycles when more than 10 oocytes were retrieved (superhigh responders) from October 1987 through June 1989. There were 276 (13%) cycles with more than 10 oocytes retrieved among all GIFT cycles initiated during the period. Clomiphene citrate and gonadotropin were employed for ovarian stimulation in 105 (38%) cycles, and gonadotropin releasing hormone agonist in the remaining 171 (62%) cycles, employing either the flare (104 cycles) or the pituitary down-regulation (67 cycles) protocol. A maximum number of four oocytes was transferred per GIFT (3.5 +/- 0.4). The mean number of oocytes retrieved was 14.7 +/- 4.4 (range, 11 to 35). A significantly younger age group (less than 30 years) of patients was noticed in the study (31.9), and fewer women aged 40 and over (6.2%), compared to the general population of our patients. The pregnancy rate was 33.3% (n = 92) per cycle, with a delivery rate of 23.6% (n = 64) per cycle; the pregnancy loss rate was 30.8%. The reproductive outcome was lower in women aged 40 and over (pregnancy rate was 23.5%, but delivery rate was only 5.8% per cycle). The delivery rate was lower in the clomiphene citrate- and gonadotropin-stimulated cycles (51.7% per pregnancy) in relation to gonadotropin-releasing analogue and gonadotropin cycles (76.6% per pregnancy) and significantly so compared with the pituitary down-regulation protocol (83.3% per pregnancy). We conclude that a superhigh response develops more in younger women, and in such circumstances, the use of pituitary down-regulation with gonadotropin-releasing hormone will improve the reproductive outcome.

Adult↗
PubMed1991

Children's play: the differential effects of intrafamilial physical and sexual abuse.

This study investigated the play of sexually abused, physically abused, physically and sexually abused, and nonabused children between the ages of 3.5 years and 10 years. Using a modified form of the Lowenfeld World Technique, we observed each child in four individual sessions in which the child was asked to create a world picture in the sandtray. Their worlds were drawn up, photographed, and analyzed according to three differing criteria. The results indicated both structural and thematic differences across the four groups. The controls made representational and phantasy worlds whose themes were domestic and phantasy wish fulfillment. The sexually abused children's worlds were representational and mixed, and themes focused on sexuality and the need for protection and nurturance. The physically abused created representational and phantasy worlds in which were displayed considerable aggression and disorganization; and their themes were concerned with conflict, chaos, and phantasy wish fulfillment. The physically and sexually abused were the most diverse; and although their worlds were representational and phantasy ones displaying considerable aggression, thematic content was conflictual in a quarter of cases but also ranged over all categories except domestic.

Child↗
PubMed1991

Pregnancy following gamete intra-fallopian transfer (GIFT) with cryopreserved semen from infertile men following therapy to lymphomas or testicular tumour: report of three cases.

Cryopreserved spermatozoa from men having treatment for lymphoma or testicular tumour have been reported to function sub-optimally. We report on three successful pregnancies following gamete intra-Fallopian transfer (GIFT) using such cryopreserved sperm samples. In one case, ovum donation was required since the woman had premature ovarian failure.

Adult↗