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Biomedical subjects

J M Simpson

Publications and source records attributed to J M Simpson.

At least 73 records · Page 4Linked to original sources

Testing the gonadal regression-cytoprotection hypothesis.

Germinal damage is an almost universal accompaniment of cancer treatment as the result of bystander damage to the testis from cytotoxic drugs and/or irradiation. Cancer treatment for the most common cancers of the reproductive age group in men has improved such that most are now treated with curative intent, and many others are treated with likelihood of prolonged survival, so that the preservation of fertility is an important component of posttreatment quality of life. This has led to the consideration of developing adjuvant treatments that may reduce the gonadal toxicity of cancer therapy. One dominant hypothesis has been based on the supposition that the immature testis was resistant to cytotoxin damage. Hence, if hormonal treatment were able to cause spermatogenic regression to an immature state via an effective withdrawal of gonadotrophin secretion, the testis might be maintained temporarily in a protected state during cytotoxin exposure. However, clinical studies have been disappointing but have also been unable to test the hypothesis definitively thus far, due to the inability to completely suppress gonadotrophin secretion. Similarly, experimental models have also given conflicting results and, at best, a modest cytoprotection. To definitively test this hypothesis experimentally, we used the fact that the functionally hpg mouse has complete gonadotrophin deficiency but can undergo the induction of full spermatogenesis by testosterone. Thus, if complete gonadotrophin deficiency were an advantage during cytotoxin exposure, then the hpg mouse should exhibit some degree of germinal protection against cytotoxin-induced damage. We therefore administered three different cytotoxins (200 mg/kg procarbazine, 9 mg/kg doxorubicin, 8 Gy of X irradiation) to produce a range of severity in testicular damage and mechanism of action to either phenotypically normal or hpg mice. Testis weight and homogenization-resistant spermatid numbers were measured to evaluate the potential protective effects on spermatogenesis. Although the three cytotoxins produced a range of severity of spermatogenic damage, there was no evidence of cytoprotection in the hpg mice that were completely gonadotrophin deficient at the time of treatment. These findings cast doubt on the validity of the hypothesis that spermatogenic regression via gonadotrophin withdrawal can protect the mouse testis against cytotoxin-mediated spermatogenic damage.

Animals↗

Who comes to a workplace health risk assessment?

Workplace health promotion initiatives have proliferated, but there are difficulties in recruiting employees of lower socioeconomic status and at higher risk of disease. A survey of health behaviors and attitudes was administered in 20 worksites and the opportunity to attend a health risk assessment promoted. Those more likely to attend were women, those of higher occupational prestige, and those from a non-English-speaking background. After adjustment for these variables, the only health behavior associated with attendance was smoking status. Perceived risk of lung cancer was significant, even after adjustment for smoking status. Stage of readiness to change health behaviors was associated with attendance, with those in the preparation stage being more likely to attend than those in the precontemplation stage. However, this association was statistically significant only for fruit and vegetable consumption. There was no relation between attendance and support for health promotion, perceived general health, or other perceived risk of disease. These findings suggest that additional risk communication strategies and environmental support are required to involve those with less prestigious occupations.

Journal Article↗

Delirium in hospital: does it increase length of stay?

OBJECTIVE: To determine the effect of delirium, as a comorbid diagnosis in hospitalised patients, on patient length of stay (LOS). METHOD: Prospective study comparing LOS of delirious patients with controls matched by age, gender, principal diagnosis and date of admission. Medical and surgical inpatients of Westmead Hospital with delirium were identified from a Consultation Liaison (CL) psychiatry database and were matched with controls from the hospital medical records. RESULTS: Delirious patient LOS was found to be significantly longer (2.2-fold; 95% confidence interval 1.5-3.3) than matched controls. CONCLUSIONS: Delirium, as a comorbid diagnosis in general hospital patients, is associated with an increased use of resources. Its early diagnosis may limit this and morbidity.

Adolescent↗

Fetal tachycardias: management and outcome of 127 consecutive cases.

OBJECTIVE: To review the management and outcome of fetal tachycardia, and to determine the problems encountered with various treatment protocols. STUDY DESIGN: Retrospective analysis. SUBJECTS: 127 consecutive fetuses with a tachycardia presenting between 1980 and 1996 to a single tertiary centre for fetal cardiology. The median gestational age at presentation was 32 weeks (range 18 to 42). RESULTS: 105 fetuses had a supraventricular tachycardia and 22 had atrial flutter. Overall, 52 fetuses were hydropic and 75 non-hydropic. Prenatal control of the tachycardia was achieved in 83% of treated non-hydropic fetuses compared with 66% of the treated hydropic fetuses. Digoxin monotherapy converted most (62%) of the treated non-hydropic fetuses, and 96% survived through the neonatal period. First line drug treatment for hydropic fetuses was more diverse, including digoxin (n = 5), digoxin plus verapamil (n = 14), and flecainide (n = 27). The response rates to these drugs were 20%, 57%, and 59%, respectively, confirming that digoxin monotherapy is a poor choice for the hydropic fetus. Response to flecainide was faster than to the other drugs. Direct fetal treatment was used in four fetuses, of whom two survived. Overall, 73% (n = 38) of the hydropic fetuses survived. Postnatally, 4% of the non-hydropic group had ECG evidence of pre-excitation, compared with 16% of the hydropic group; 57% of non-hydropic fetuses were treated with long term anti-arrhythmics compared with 79% of hydropic fetuses. CONCLUSIONS: Non-hydropic fetuses with tachycardias have a very good prognosis with transplacental treatment. Most arrhythmias associated with fetal hydrops can be controlled with transplacental treatment, but the mortality in this group is 27%. At present, there is no ideal treatment protocol for these fetuses and a large prospective multicentre trial is required to optimise treatment of both hydropic and non-hydropic fetuses.

Adenosine↗

Pap smears in general practice: a secondary analysis of the Australian Morbidity and Treatment Survey 1990 to 1991.

We investigated the characteristics of Australian general practice that predict performance of Pap smears by secondary analysis of the Australian Morbidity and Treatment Survey 1990 to 1991. Chi-squared analysis identified potential associations between Pap smear rate and patient, doctor and practice variables. Significant associations were examined using logistic regression and generalised estimating equations. Participants were 495 general practitioners who collected information on 113,468 doctor-patient encounters, of which 43,211 encounters involved females aged 18 to 70 years. Pap smear encounter (2449) were identified and classified as patient-requested (62 per cent), diagnostic (5 per cent) or opportunistic (33 per cent). The large difference in the unadjusted Pap smear rates per 100 female encounters for female general practitioners (11.7) and male general practitioners (4.2) required separate analysis by sex of the general practitioner. For male general practitioners, a Pap smear was less likely: as patient age increased; for new patients; for general practitioners with less general practice experience; for general practitioners with no postgraduate qualifications; with metropolitan practice location; and if the practice had more than 25 per cent of patients with English as a second language. For female general practitioners, a Pap smear was less likely: for older known patients; as the age of the general practitioners increased; and for management of fewer problems per 100 encounters. A Pap smear was less likely to be opportunistic: as patient age increased; for general practitioners who were Australian graduates; and for general practitioners with no postgraduate qualifications. Consideration of patient, doctor, and general practice characteristics may facilitate the design of interventions to improve cervical cancer screening.

Adolescent↗

Progression and regression of low-grade epithelial abnormalities of the cervix.

The records of 738 women with low-grade cervical epithelial abnormalities were examined for changes in degree of cervical disease and lesion size, as well as sociodemographic and behavioural factors which influence the development of invasive cancer of the cervix. Survival analysis was used to determine the predictors and rates of progression and regression. The results suggest that about 80% of the low-grade epithelial abnormalities of the cervix will not progress within 2 years. The only predictors of progression were a biopsy diagnosis of CIN 1 and the size of the lesion. Predictors of regression were older age, older age at first intercourse, greater parity, fewer sexual partners, and absence of a past history of genital herpes. Although progression rates of low-grade abnormalities of the cervix were very low, CIN 1 lesions were 2.4 times (95% CI: 1.6 to 3.7) more likely to progress than lower-grade lesions and large lesions (> 1/2 ectocervix) were 2.0 times (95% CI: 1.2 to 3.3) more likely to progress than small ones (< 1/4 ectocervix).

Adolescent↗

Natural history and outcome of aortic stenosis diagnosed prenatally.

OBJECTIVE: To document the growth of the left heart structures and outcome of fetuses with aortic stenosis. DESIGN: Retrospective echocardiographic and clinical study. SETTING: Tertiary centre for fetal cardiology. PATIENTS: 27 consecutive fetuses with aortic stenosis. MAIN OUTCOME MEASURES: Survival of affected fetuses. Measurement of left ventricular end diastolic volume (LVEDV), aortic root diameter, and ejection fraction. RESULTS: Before 25 weeks' gestation, the LVEDV was normal or increased in all cases. In six of eight fetuses studied sequentially, the LVEDV fell across normal centiles. Initial ejection fraction was reduced in 23 fetuses (88%). Before 28 weeks' gestation, the aortic root was normal in all but one case, but after 29 weeks, 11 of 13 fetuses had values below the 50th centile. In two fetuses prenatal aortic valvoplasty was attempted, 10 babies had postnatal interventions, and there were six survivors. Biventricular repair was attempted in eight cases, of whom five survived. A first stage Norwood operation was performed in three babies, of whom one survived. The four fetuses with the highest aortic root z scores had successful biventricular repair. The two fetuses with initially normal ejection fractions survived. Successful biventricular repair was achieved even where the LVEDV was below the 5th centile. CONCLUSIONS: In aortic stenosis diagnosed prenatally, failure of growth of the left ventricle and aortic root often occurs. The outcome of affected fetuses is better than previously reported. Prenatal echocardiography may assist selection of suitable candidates for biventricular versus Norwood repair.

Aortic Valve↗

Prenatal diagnosis of 22q11 deletions: a series of five cases with congenital heart defects.

We report a series of five patients with congenital heart defects in whom a prenatal diagnosis of 22q11 deletion has been made. The accurate cardiac and cytogenetic diagnoses were made between 20 and 23 weeks' gestation in all cases and the cardiac findings were all confirmed postnatally. The cardiac abnormalities included tetralogy of Fallot with absent pulmonary valve, pulmonary atresia with VSD, common arterial trunk, and left atrial isomerism with double outlet right ventricle. The problems of genetic counselling in these cases are discussed. A recommendation is made to test all fetuses with conotruncal heart abnormalities detected prenatally for a 22q11 deletion, whereas guidelines for other congenital heart disease types are less clear.

Chromosome Deletion↗

Australasian perfusion incident survey.

An anonymous postal survey about perfusion accidents, incidents and safety procedures was conducted retrospectively in all identifiable cardiac surgery units in Australia and New Zealand over an 18-month period from January 1994 to July 1995. Responses were received from 69% of all eligible perfusionists representing 39 to 42 operating units. The most frequent incidents reported were heater/cooler failure (43% of respondents), urgent return to bypass following circuit disposal (38%), air embolus in a circuit not reaching the patient (24%), accidental cannula displacement (28%), protamine-induced circuit clotting postbypass (20%), hospital power failure (31%) and oxygenator membrane leaks (24%). There were 11 serious injuries and 10 deaths reported, giving an overall rate of serious injury or death of one in 1300 cases. However, the perfusion-related injury rate was lower, at one injury or death per 2500 perfusions. The use of safety equipment was widespread with low-level alarms in use by all respondents, bubble detectors by 74%, arterial line filters by 82% and written or computerized checklists by 80%. While the rate of injury was lower than that reported in surveys done elsewhere, the rate of reporting of incidents was greater and this may reflect a changing attitude of perfusionists to accountability in the delivery of their services. The data suggest that the level of safety in perfusion in Australasia is high but that improved incident reporting may help to further improve practices.

Australia↗

Composite cardiovascular risk outcomes of a work-site intervention trial.

OBJECTIVES: Two composite outcome measures were used to assess the efficacy of work-site risk factor interventions: the Framingham multiple logistic function and a standardized composite equation that was an unweighted combination of risk factors. METHODS: Twenty-eight work sites in Sydney, Australia, were randomly assigned to health risk assessment, risk factor education, behavioral counseling, or behavioral counseling plus incentives. RESULTS: Over 12 months, scores on the multiple logistic function increased for the behavioral counseling plus incentives condition relative to the other conditions. Standardized scores decreased for behavioral counseling relative to the incentive condition and the average of all other conditions. CONCLUSIONS: Behavioral counseling produces larger changes in the life-style behaviors contributing to coronary heart disease risk than other commonly used interventions.

Cardiovascular Diseases↗

Cervical disk disease and the keyhole foraminotomy: proven efficacy at extended long-term follow up.

Eighty-four consecutive patients with posterolateral cervical disk herniation treated by keyhole foraminotomy between 1980 and 1987 were reviewed. Radicular pain was the most common presenting complaint. Weakness was present in 59 patients. Sixty patients were available for long-term follow up, averaging 6.1 years. Fifty-six patients' results were graded as excellent. Three patients had good results and one fair result was noted. There were no poor results. Preoperative pain symptoms were relieved in all patients. There were no significant complications. The posterolateral keyhole foraminotomy is an efficient means of decompressing lateral soft disk herniations, without the risk of an anterior approach or iliac crest bone harvest. Careful patient selection and use of an operative microscope are essential in obtaining consistent, excellent results.

Adult↗

Effect of high glucose on permeability of retinal capillary endothelium in vitro.

PURPOSE: To study the effect of high glucose on the permeability of bovine retinal capillary endothelial cell (BRCEC) monolayers. METHODS: The paracellular permeability of second-passage BRCEC cultured on millipore filters in two chamber transwell inserts was assayed by measuring the peak trans-monolayer electrical resistance and percent equilibration of 14C-inulin 48 hours after it had been added to the luminal chamber. RESULTS: High glucose increased the paracellular permeability of BRCEC monolayers independently of its hypertonic action (5 mM glucose: 154.2 +/- 21.2 and 19.5 +/- 2.4; 30 mM glucose: 134.2 +/- 5.1 [P = 0.01] and 23.5 +/- 2.1 [P = 0.01]; 5 mM glucose + 25 mM mannitol: 168.7 +/- 13.7 ohm.cm2 [P = 0.04] and 19.3% +/- 1.2% 48-hour equilibration of inulin [P = 0.008]). In a separate series of experiments, the authors were unable to show that either aminoguanidine or ponalrestat prevented the effect of high glucose on permeability (30 mM glucose 95.1 +/- 16.7 and 45.4 +/- 5.6; 5 mM glucose: 122.9 +/- 14.2 [P = 0.02] and 36.6 +/- 5.6 [P = 0.001]; 30 mM glucose + aminoguanidine 87.9 +/- 17.5 [P = 0.04] and 75.3 +/- 14.9 [P = 0.6]; 30 mM glucose + ponalrestat 79.9 +/- 12.7 ohm.cm2 [P = 0.1] and 48.2 +/- 2.5% 48-hour equilibration of inulin [P = 0.15]). Ponalrestat did not abrogate the effect of high glucose despite its ability to reduce a high glucose-induced increase in BRCEC intracellular sorbitol levels. CONCLUSIONS: The data are consistent with a role for increased paracellular permeability in breakdown of the blood-retinal barrier in diabetic retinopathy, which appears to be independent of both nonenzymatic glycosylation and the polyol pathway.

Animals↗

Incidence of congenital heart defects in fetuses of diabetic mothers: a retrospective study of 326 cases.

The aim of this study was to quantify the risk of congenital heart disease in diabetic mothers referred for fetal echocardiography. Of 326 diabetic pregnancies seen over a 5-year period, ten (3.1%) resulted in a fetus with congenital heart disease. Nine (90%) of the ten cardiac lesions were identified prenatally, but one fetus had a ventricular septal defect that was overlooked antenatally. Postnatal follow-up was obtained in 312 cases (95.7%). Prenatal echocardiographic examinations were performed at 18-38 weeks of gestation (median 25 weeks) and the median gestational age at diagnosis of congenital heart disease was 22 weeks (range 19-30 weeks). Following the detection of a severe cardiac anomaly, the pregnancy was terminated in three cases. Of the seven continuing pregnancies, two resulted in spontaneous intrauterine death and two babies died within the first 6 months of life. The three survivors are clinically well, but one has required postnatal catheter intervention. Our results confirm that diabetic women are at increased risk of having a baby with congenital heart disease and detailed fetal echocardiography should therefore be offered to all diabetic women during pregnancy.

Adult↗

The significance of echogenic foci in the fetal heart: a prospective study of 228 cases.

The purpose of this study was to determine the pathological significance of echogenic foci in the heart of fetuses with no other sonographic abnormalities and in the absence of other risk factors for chromosomal abnormality. A total of 228 fetuses were identified with single or multiple echogenic foci. This represents 6.9% of the total number of fetuses scanned. The most frequent finding was a single echogenic focus in the left ventricle (n = 136; 60%) but multiple foci were observed in 33%. An echogenic focus in the right ventricle occurred in 16 cases (7%). Karyotypic abnormalities were diagnosed postnatally in two fetuses. One of these fetuses, with an echogenic focus in each ventricle, had trisomy 21, and the other, with two echogenic foci in the left ventricle, had an unbalanced translocation. The vast majority of fetuses which had echogenic foci were normal, but there was a risk of karyotypic abnormality of 1%.

Adult↗

Predicting nonattendance for colposcopy clinic follow-up after referral for an abnormal Pap smear.

This is retrospective cohort study of women who were recommended for further assessment or treatment after their first visit to a gynaecologist for an abnormal Pap smear. The sample included women who first attended a private outpatient colposcopy service in Canberra between 1 January 1989 and 30 April 1990. Only women who had never previously seen a gynaecologist for an abnormal Pap smear were included in the sample. The nonattendance rate was 2.2 women per 100 women-months (n = 493). Cox proportional hazards modelling was used to examine the relationships between sociodemographic and clinic variables and nonattendance. After adjusting for age and the degree of abnormality on presenting smear, women without private health insurance and women who had had treatment were less likely to continue attending. The current focus on identifying barriers to screening services needs to be broadened to consider attendance at all points along the screening pathway.

Adult↗

Indications for laser surgery in the treatment of degenerative disk disease of the lumbar spine.

Percutaneous laser diskectomy has recently been promoted as a viable alternative in treatment of the symptomatic lumbar disk herniation. Careful scrutiny of the literature, including the natural history of low back disorders and results of various surgical techniques in controlled studies, makes it clear that percutaneous laser diskectomy adds little to our surgical armamentarium. As surgeons, we should be encouraged to make treatment decisions in the best interests of our patients, based on unbiased, prospective scientific studies.

Humans↗

Comparison between allograft plus demineralized bone matrix versus autograft in anterior cervical fusion. A prospective multicenter study.

STUDY DESIGN: This study analyzed the fusion results of an allograft-demineralized bone matrix composite versus autograft in a prospective series of patients undergoing surgery for cervical disc disease. OBJECTIVES: To determine the fusion rates of allograft-demineralized bone matrix composite in anterior cervical fusion as compared with the gold standard autograft. SUMMARY OF BACKGROUND DATA: For the anterior cervical fusion, the use of freeze-dried allograft is well documented in the literature, citing its effectiveness and inferior fusion rates. The use of demineralized bone matrix in conjunction with freeze-dried allograft in anterior cervical fusion has not been reported. METHODS: This study was done in a prospective fashion in two medical centers. One group received autograft from the anterior iliac crest, whereas others received freeze-dried allograft augmented with demineralized bone matrix (Grafton, Osteotech, Inc., Shrewsbury, New Jersey). For the autograft group, the standard Smith-Robinson grafting technique was used. For the allograft composite group, demineralized bone matrix was pasted onto the freeze-dried allograft and into the disc space before graft insertion. The autograft group consisted of 38 patients with age ranging 26-71 years (mean, 46.1 years) and follow-up periods of 12-33 months (mean, 18.4 months). There were 19 one-level, 17 two-level, and two three-level fusions. Similarly, the allograft group consisted of 39 patients with age ranging 28-80 years (mean, 48.0 years) with follow-up period of 12-31 months (mean, 17.5 months). There were 19 one-level, 16 two-level, and four three-level fusions. Clinical and radiographic follow-up evaluations were completed at 3-month intervals. Radiographs taken 12 months after surgery were analyzed blindly. RESULTS: Pseudarthrosis developed in 46.2% of patients (33.3% of levels) in the allograft-demineralized bone matrix group compared with 26.3% (22% of levels) in the autograft group (P = 0.11 for patients, P = 0.23 for levels). For patients undergoing two-level fusions, 37.5% of allograft-demineralized bone matrix failed compared with 23.5% of autografts. For single-level fusions, 47.4% of allograft patients developed a pseudarthrosis compared with 26.3% in the autograft group. Graft collapse of > or = 3 mm was noted in 11% of the autograft group versus 19% in the allograft-demineralized bone matrix group (P = 0.32). Graft collapse of > or = 2 mm occurred in 24.4% of autograft patients compared with 39.7% of the allograft-demineralized bone matrix group (P = 0.09). Smokers had an increased rate of pseudarthrosis (47.1%) compared with nonsmokers (27.9%, P = 0.13). CONCLUSIONS: The study revealed that the allograft-demineralized bone matrix construct gives a higher rate of graft collapse and pseudarthrosis when compared with autograft in a prospective series, although the differences were not statistically significant. The pseudarthrosis rate in the series may be high because of the large percentage of smokers and radiographic evaluation techniques. For the purpose of solid radiographic fusion, the use of autograft is recommended in anterior cervical surgery until other acceptable osteoinductive materials are developed.

Adult↗