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Biomedical subjects

J R Clarke

Publications and source records attributed to J R Clarke.

At least 91 records · Page 5Linked to original sources

Detection of treponemal DNA in the CSF of patients with syphilis and HIV infection using the polymerase chain reaction.

The polymerase chain reaction (PCR) was used to detect Treponema pallidum DNA in the cerebrospinal fluid (CSF) of patients with and without syphilis. The CSF from 10 of 19 patients with positive serological tests for syphilis who were being investigated for late syphilis were treponemal DNA-positive. In contrast, the CSF from only one of 30 patients with no known history of syphilis was DNA-positive. CSF from 28 HIV-positive patients was also tested. Fourteen of these patients had central nervous system (CNS) disease and seven were DNA-positive, whereas none of the 14 without CNS disease were DNA-positive. Five of the seven DNA-positive patients had a history of syphilis. Such a history in an HIV-positive patient who had CNS disease was predictive of finding treponemal DNA in the CSF. The PCR had a sensitivity of 47% and a specificity of 93% for detecting a known history of syphilis and is a potentially useful tool in treponemal diagnosis.

Acquired Immunodeficiency Syndrome↗

Avoidance of used endometrial sites by blastocysts of the bank vole, Clethrionomys glareolus.

In bank voles blastocysts arising from mating immediately after parturition do not implant in used zones of the preceding pregnancy but in the regions between them. However, if mating is postponed until 12 or more days after parturition blastocysts do implant in used zones of the previous pregnancy. Implantations also occur at zones used two pregnancies previously. It seems likely that the absence of implantations at recently used zones of the uterus is determined by the uterus rather than blastocysts.

Animals↗

Contamination of endoscopes used in AIDS patients.

Contamination of twenty endoscopes used in patients with AIDS was assessed. The suction-biopsy, air, and water channels and the insertion tube were sampled after use, after washing in detergent, and after disinfection for 2 min in 2% alkaline glutaraldehyde. The polymerase chain reaction with Southern blotting, cell cultures, and antigen immunoassay were used to detect human immunodeficiency virus (HIV). Samples were also examined for cytomegalovirus, adenoviruses, enteroviruses, herpes simplex virus, myxoviruses, hepatitis B surface antigen, fungi, and bacteria. Seven of twenty unwashed endoscopes were contaminated by HIV. Commensal bacteria were found in all endoscopes, Candida albicans in six, Staphylococcus aureus in five, and Pseudomonas aeruginosa in five. Washing alone removed all detectable organisms from 66 of 68 contaminated sites; Neisseria spp were recovered from two air channels after washing but not after disinfection. Washing achieved a mean reduction of 4.93 (95% confidence interval 3.69-6.17) colony forming units per ml.

Acquired Immunodeficiency Syndrome↗

Appendicitis. The computer as a diagnostic tool.

At present there is no definitive test for appendicitis and no clear set of signs and symptoms, so that diagnosis is uncertain and probabilistic. A computer model for analyzing clinical data can improve physician accuracy in diagnosing appendicitis by assessing the outcome probabilities associated with the treatment options. Should a definitive test become available, the computer model will aid clinicians in determining when to test. Once our proposed model has been validated, it will not only improve physician decision-making, but also provide quality assurance feedback, generate reports for documentation, and compile a data base of many cases for study and reference.

Appendicitis↗

The type-specific epitopes of the Epstein-Barr virus nuclear antigen 2 are near the carboxy terminus of the protein.

The Epstein-Barr virus nuclear antigen 2 (EBNA 2) shows serotype variation and two serologically distinct groups of viruses have been identified. These correspond to the two hybridization groups of viruses (A and B) that are distinguished by a highly substituted nucleic acid sequence in the middle of the open reading frame of the EBNA 2 gene. An epitope survey of the EBNA 2-coding region was carried out using a new prokaryotic expression vector tailored to express DNA fragments from the M13 sequencing libraries of the B95-8 (type A) and Jijoye (type B) prototype virus strains. Short overlapping stretches of EBNA 2 sequence were expressed as fusion proteins and used in Western blotting with human sera that contained serotype-specific antibodies. The type A-specific epitope was located between residues 378 and 435 of the B95-8 EBNA 2 polypeptide and the type B-specific epitope mapped between residues 390 and 454, at the carboxy terminus of the Jijoye polypeptide chain. All of the type-specific anti-EBNA 2 sera tested reacted with fusion proteins containing one or other of these epitopes. Despite the direct correlation between the hybridization and serological phenotypes, the type-specific epitopes appear to lie in the relatively conserved carboxy-terminal region of EBNA 2. There was no indication that the residues of the non-homologous region contributed to the formation of antibody-combining sites.

Amino Acid Sequence↗

Ovarian interstitial tissue of the wood mouse, Apodemus sylvaticus.

The ovary of the wood mouse contains an unusually large amount of interstitial tissue which appears to develop from undifferentiated cells of the ovarian stroma and also by transformation of theca or granulosa cells of atretic follicles. The cells are characterized by the presence of smooth endoplasmic reticulum, rounded mitochondria with tubular cristae, and abundant, large (1.5 micron diameter) lipid droplets containing cholesterol and its esters. 3 beta-Hydroxysteroid dehydrogenase activity occurs in the interstitial cells. Their ultrastructural characteristics suggest that the cells are not very active, but their abundance and the considerable amount of steroid hormone precursor they contain may compensate for low secretory activity and they may be an important and (from a developmental viewpoint) early source of steroid hormone.

3-Hydroxysteroid Dehydrogenases↗

Artificial intelligence: a computerized decision aid for trauma.

A computerized decision support system has been developed to advise ATLS-trained surgeons on the initial definitive management of patients with penetrating injuries of the abdomen immediately following resuscitation and stabilization. The program was developed as an "expert system," using the techniques of artificial intelligence. It is able to suggest: the need for further examination; additional tests; diagnoses; and treatments. In this study, the advice offered by the expert system was compared to that of physicians-in-training. Five actual patient care situations were presented to the system and to 13 medical students and surgical residents: four MS-III, three PGY-I, three PGY-III, and three PGY-V. The suggestions of each of the 13 trainees, the advice of the expert system, and the actual management were blinded. Five surgeons versed in trauma and otherwise not involved in the project judged whether each of the 15 purported management plans was acceptable and ranked them in order of preference. Only the actual care and the advice from the system were judged acceptable for all five problems. The rankings of the expert system were better than those of any individual trainee. The differences were statistically significant for two of the three chief residents, five of nine residents overall, and all four students. This preliminary validation of a prototype expert system is encouraging for the prospect of a computerized decision support system that can help surgeons make initial definitive management plans for patients with major trauma.

Abdominal Injuries↗

Treatment of senile entropion with botulinum toxin.

Botulinum toxin was used to treat senile entropion in 12 patients by injection into the preseptal orbicularis muscle of the lower lids. It produced relief of symptoms in 10 patients but this was transient, lasting for an average of 14.8 weeks before orbicularis function returned. The technique is simple and easy to perform, and may be useful in selected patients, but surgery offers a more permanent result.

Acetylcholine↗

Tracheal pressure and impedance as determinants of gas exchange during high frequency ventilation.

This work explores the use of catheter pressure transducers to measure time averaged, mean squared pressure (MSP) in the trachea of anesthetized animals during high frequency ventilation using a prototype Emerson oscillator with a 25 ml stroke volume at 15 and 34 Hz. Tidal volume and MSP were varied by shunting a portion of the ventilator output for the study of the effect of driving pressure on ventilation. A given level of ventilation was accomplished at a lower driving pressure at the lower frequency. Both ventilation as assessed by a modified nitrogen washout procedure and gas exchange were related to MSP and oscillatory frequency by the substitution of MSP/Z2 for alveolar ventilation in the equations of Jaeger et al. (1984). The technique and equations describing it were validated by the prediction of impedance changes resulting from shifts in oscillatory frequency. The calculated impedances matched experimentally measured values found in dogs by other investigators. Catheter pressure transducers are thus shown to be a useful tool for quantifying high frequency ventilation when coupled with a knowledge of respiratory impedance. The technique offers advantages over existing techniques, the most notable being ease of use due to the catheters' exceptional frequency response.

Animals↗

Synthesis of cytomegalovirus DNA is an antiviral target late in virus growth.

The mechanism of action of 9-(1,3-dihydroxypropoxymethyl)guanine (DHPG) and phosphonoformic acid (PFA) but not 5-fluorouridinedeoxyribose (FUdR), provides selective action against cytomegalovirus (CMV)-coded events and this was used to demonstrate that the synthesis of viral DNA was continuous during the extended phase of virus growth. The synthesis de novo of viral DNA was measured by restriction enzyme analysis after exposure to [32P]orthophosphate and its interruption by DHPG or PFA resulted in a cessation in the extrusion of infective virus from treated cells. The rate of decline in infectivity appeared to correspond to the failure of cells to maintain the synthesis of late proteins once DNA synthesis was blocked. Thus, regulation of late protein synthesis appeared to be linked to synthesis de novo of viral DNA even at late stages in CMV growth. The synthesis of the polyamines spermidine and spermine, considered obligatory for CMV growth, was unaffected by early or late inhibition of viral DNA and this showed that some virus-induced events were unaffected by the restriction on virus growth by DHPG. This provided evidence that polyamine biosynthesis was a target independent of viral DNA synthesis per se, which may be important in future considerations of combined drug therapies.

Acyclovir↗

Comparison of the gonadal response of wild and laboratory field voles (Microtus agrestis) to different photoperiods.

Weanling male and female field voles from laboratory stock and from the F1 generation of wild-caught animals were placed in a long (16L:8D) or short (6L:18D) photoperiod for 28 or 56 days. Both types of field vole showed the well-established effect of photoperiod upon sexual maturation, with animals in the long photoperiod having larger and more active gonads than animals in the short photoperiod. After 28 and 56 days laboratory stock females were more mature, sexually, and had a higher growth rate than did Wild F1 females. There was no difference between the two types of males at 28 days, but by 56 days laboratory stock males were more sexually mature and had a higher growth rate than did Wild F1 males. These differences between the two types occurred in the long and short photoperiods. There was no interaction between photoperiod and type of vole. The use of laboratory stock animals in experiments could lead to an incorrect assessment of the effect of photoperiod in the control of seasonal breeding in wild populations.

Animals↗

Hormonal requirements and the influence of age on the decidual cell reaction in the bank vole (Clethrionomys glareolus).

Laboratory bred bank voles of different age and reproductive status were bilaterally ovariectomized, treated with exogenous oestrogen or progesterone or both, and given an artificial decidual stimulus (crushing with artery forceps). An hormonal regimen of oestrogen (100 ng) followed by progesterone (1 mg) and small amounts of oestrogen (10 ng) was necessary for maximal development of the decidual cell reaction (DCR). A DCR did not develop if the animals were treated with only oestrogen or progesterone. Middle-aged virgin females 5-7 months old had larger responses than did young virgin females 2-3 months old, and parous females, 15-19 months old and having had at least 10 litters, had a response similar to that of virgin females of about the same age. The size of the DCR in old parous females was inversely related to the time elapsing since the last litter. It is concluded that in its hormonal requirements for a successful DCR the bank vole is similar to the mouse. The results also suggest that the increase in fertility of bank voles up to the age of about 100 days may in part be explained by increased response of the endometrium to blastocysts. The reduction in size of the DCR in old animals is a consequence of ageing rather than of repeated pregnancies.

Aging↗

Effect of nutrition, temperature and photoperiod on the rate of sexual maturation of the field vole (Microtus agrestis).

Weanling male and female field voles were placed in long or short photoperiods, kept at 18 degrees C or 4 degrees C, and fed (ad libitum) diets containing 24%, 16%, 8% and 4% protein, for 6 weeks. Animals in the long photoperiod were more sexually mature than were animals in the short photoperiod. Temperatures had no effect on females, but did affect males: those kept at 4 degrees C had heavier testes and wider seminiferous tubules than those kept at 18 degrees C. There was little difference between the animals on 24%, 16% and 8% protein diets. Animals on 4% protein diets had retarded growth rates and were significantly less sexually mature than those on the other 3 diets, males having smaller testes and seminal vesicles and narrower seminiferous tubules and females having smaller ovaries and uteri.

Animal Nutritional Physiological Phenomena↗

Is there gender bias in the evaluation of surgical residents?

Although it might be assumed that the performance of surgical residents is assessed by faculty without regard to gender, no study to date has been undertaken to evaluate this. for 19 years, the Department of Surgery in our institution has had female faculty members to evaluate residents and, with the exception of 1969, female residents to be evaluated. All residents are evaluated by supervisory faculty after each clinical rotation. The same evaluation process has been used throughout this time, assessing residents on a five-point scale (1 = best) in each of six attributes: ethics, judgment, technical skills, knowledge, interpersonal skills, and work habits. The faculty evaluations of general surgery residents from academic years 1967 to 1985 were reviewed. A total of 2356 evaluations of 144 residents (22% female) by 69 faculty members (22% female) was available. For valid comparison, a subset of 702 evaluations was selected. Included were only those evaluations in which residents at the same level of training during the same academic year were evaluated by the same faculty members and in which both the resident and faculty groups had both male and female members. The average scores for male and female residents were nearly identical as determined by male and female faculty members, and no differences were statistically significant. In our program, with more than 20% women residents and faculty members over a 19-year period, no bias related to gender was demonstrated.

Clinical Competence↗

Prognostic factors in upper G.I. bleeding.

This presentation draws upon the experience of the O.M.G.E. Multi-national Upper G.I. Bleeding Survey, using data collected during 1980-1982 by 185 clinicians from 44 centres in 21 countries to discuss two questions. First, can prognostic factors be identified in patients presenting to hospital with upper G.I. bleeding, and if so what are they? Second, is it possible - by combining the two technologies of endoscopy and computers - to provide an individual patient with a short-term prognostic prediction sufficiently accurate to affect patient management. Amongst 4,010 patients, a number of clinical factors were found to affect short-term prognosis. These included patient age, previous history of heart or liver disease, confusion and dehydration on admission, jaundice, and ascites. Identification of the bleeding source via endoscopy was shown to aid short-term prognosis - especially in the period of the 2nd to 10th days post-admission. Use of computer analysis enabled "high risk" patients to be defined (of whom 63.8% suffered further bleeding and 30.0% died), and also a comparable "low risk" group (of whom only 4% suffered further bleeding and none died). Finally, "time-dependence" studies have been used to identify a group of patients who (by the 2nd day post-admission) have a residual risk of further bleeding sufficiently low (well under 1%) to suggest that considerable resources can be saved by the judicious use of endoscopy and computer science.

Age Factors↗

Gonadal development and gonadotrophin secretion in the male vole (Microtus agrestis) after an abrupt change in photoperiod.

Male voles were reared from birth to age 28 days in 6L:18D. Pairs of animals showing similar sexual development were assigned at random to 16L:8D or 6L:18D. Treatments continued for a further 56 days. Increase in the activity of the hypothalamo-hypophysial system occurred within 4 days of exposure to 16L:8D, as shown by significant elevation of plasma LH and FSH. Pituitary LH did not increase until Day 7, and pituitary FSH did not increase until Day 21. After exposure to 16L:8D for 4 days, pituitary FSH was lower than in corresponding animals in 6L:18D. These discrepancies between pituitary and plasma values of gonadotrophins indicate that increase in hormone release occurs before synthesis is fully stimulated. Enhanced output of testicular hormones probably began between Day 7 and Day 14, as indicated by an increase in seminal vesicle weight, yet plasma and pituitary concentrations of LH and FSH remained elevated. This suggests that long photoperiods may cause direct stimulation of the hypothalamo-hypophysial system which increasing values of testicular hormones are initially unable to inhibit. The response of this system in voles to an abrupt change from a non-stimulating to a stimulating photoperiod has a time course resembling that for the Soay ram but appreciably slower than for the Japanese quail.

Animals↗

Effect of male presence and of photoperiod on the sexual maturation of the field vole (Microtus agrestis).

The effect of mature males on the sexual development of young female and male field voles, reared in either long (stimulating) or short (inhibiting) photoperiods, was examined. Females reared in the presence of a mature male had a more advanced state of sexual maturation (as indicated by uterine weight) than did females reared in isolation from males, in long and short photoperiods (P less than 0.01). No interaction between photoperiod and male presence was found. Augmented uterine growth occurred not only when young females were separated from mature males by a wire mesh or solid metal screen but also when they were merely exposed to bedding previously used by mature males. Castrated males had no effect on the sexual development of females. The effect of mature males on the sexual development of young males was less clear, although there was some indication that the presence of adult males inhibited their sexual development in long and short photoperiods. For males and females, growth rate was stimulated by long photoperiod, but no effect of male presence on growth rate was found.

Animals↗