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Biomedical subjects

S E Jones

Publications and source records attributed to S E Jones.

At least 19 recordsLinked to original sources

Analysis of differentially expressed genes in retinitis pigmentosa retinas. Altered expression of clusterin mRNA.

The molecular and cellular processes underlying photoreceptor degeneration in retinitis pigmentosa (RP) are unknown. We have investigated gene expression in diseased retinas using differential hybridization screening of a retinal cDNA library with probes derived from normal and RP retinal RNA. Most differential clones detected corresponded to transcripts absent from the dystrophic state, including e.g. opsin. However, one clone was noticeably increased in RP in comparison with the control: partial sequencing showed it encoded clusterin. Increased expression of clusterin has been identified in several cases of tissues undergoing apoptosis (programmed cell death), and our finding suggests that the degenerative changes in advanced RP may represent another example of apoptosis, possibly with common causative mechanisms.

Adult

A phase II study of piritrexim in patients with advanced squamous head and neck cancer.

Piritrexim (PTX) is a newly developed lipid-soluble folate antagonist that crosses the cell membrane by a simple, rapid, carrier-independent diffusion process. A Phase II study was conducted to evaluate the activity of PTX in 34 patients with previously chemotherapy-naive squamous cell cancer of the head and neck area (SCCHN). Among them, 30 patients had received previous radiation therapy and/or surgery. Of 33 patients who could be examined, 3 had a complete response (CR), 6 had a partial response (PR), 11 had no change, and 13 had disease progression. The overall response rate (CR + PR) was 27% (9 of 33; 95% confidence interval, 13% to 46%). The response duration ranged from 36 to 360 + days (median, 162) and was similar to the best studies reported with methotrexate. The three most severe side effects (Grades 3 and 4 by World Health Organization criteria) were leukopenia, thrombocytopenia, and mucositis. These occurred in 41%, 26%, and 15% of the 34 patients, respectively. This study established PTX as an agent with some activity in SCCHN. The use of PTX in combination chemotherapeutic regimens needs to be explored.

Adult

Using decision analysis to calculate the optimum treatment for microinvasive cervical cancer.

Decision theory was used to calculate the optimum treatment of microscopic squamous cervical cancer using probabilities obtained from an exhaustive literature review and a range of plausible value estimates. This showed that if there is no vascular involvement, survival is maximised by conservative treatment if tumour invasion is less than 3 mm while treatment by radical surgery results in maximal survival rates if the tumour invasion is over 3 mm. Radical surgery also maximises survival for smaller lesions where lymph channel involvement is present, especially if a surgical mortality at the lower end of the reported range is assumed. Refinement of our analysis to include an assessment of patient values showed that these conclusions are still valid regardless of the patient's relative preference for death from surgery or death from cancer. However, the wish to preserve fertility sharply reduces the overall net benefit of surgery. Conservative treatment becomes the preferred option for all microinvasive lesions even for patients who are prepared to trade-off a small (e.g. 2%) risk of death in order to retain their fertility.

Adult

Day-case surgery.

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Ambulatory Surgical Procedures

Developmental profile of a fetuin-like glycoprotein in neocortex, cerebrospinal fluid and plasma of post-natal tammar wallaby (Macropus eugenii).

A fetuin-like glycoprotein (FLG) has been shown to be present in early cortical plate cells in the developing brain of the tammar wallaby (Macropus eugenii). The developmental sequence of the occurrence of glycoprotein-positive fibres and cells in the dorsolateral telencephalic wall from newborn to day 40 is described. The level of FLG in CSF (cerebrospinal fluid) and plasma of the tammar wallaby has also been measured during pouch life. The presence of FLG in early postnatal fibre systems and in some cells in the primordial plexiform layer, as well as in early cortical plate cells of the tammar is similar to that of fetuin in fetal brain in sheep, pig and cow, and alpha 2HS glycoprotein in human fetal brain. The sequence of appearance of FLG-positive cells during neocortical development in the tammar is strikingly similar to that of a transient population of early cortical plate cells previously described in fetal cat and sheep cortex. During postnatal development, levels of FLG in tammar plasma and CSF follow a pattern different from that of other species. The developmental expression of all three related glycoproteins in their respective species is discussed.

Animals

A method for measuring nasal and lung uptake of inhaled vapor.

This paper describes apparatus and methods for measuring uptake of inhaled vapors in the nose and lungs of dogs. The system allows sampling of air from the trachea at specific times during inspiration and expiration without surgical manipulation of the animal, thus allowing repeated studies in the same animal. During exposure, the dogs are anesthetized and cyclic respiratory patterns are maintained by means of an external respirator. A pneumotachograph installed in the exposure line is connected to a respiratory monitoring system that both monitors the dog's respiratory pattern and triggers sampling at specific times in the respiratory cycle. Air sampling, both at the nose and within the trachea, can be done during the entire breathing cycle or during specific portions of it. Vapors are sampled at a point just external to the dog's nose and from within the trachea through a modified endotracheal tube. To develop and demonstrate the system, three beagle dogs were exposed to 2,4-dimethylpentane and 1.3-dioxolane at nominal vapor concentrations of 500 ppm; vapor sampling was triggered for the entire inspiratory and expiratory portions of the breathing cycle during 10-min exposures. After correcting data to account for vapor that desorbed from the nasal passages during exhalation (after initially being absorbed in the nose during inhalation), net nasal uptake of 2,4-dimethylpentane was 28.3%; net nasal uptake of 1,3-dioxolane was 66.6%. Lung uptake was 14.0% for 2,4-dimethylpentane and 2.1% for 1,3-dioxolane. The system was developed for use with dogs, but it can be adapted for use with any animal species that can be intubated with endotracheal vapor sampling tubes.

Absorption

Needles on wheels.

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Catheterization, Peripheral

Papaveretum infusions in infants under 6 months of age.

The effectiveness of a continuous low dose papaveretum infusion for the relief of postoperative pain was assessed in 29 infants aged 1-6 months nursed on the infant surgical ward following major abdominal surgery. Trained nursing staff were able to adjust the dosage within prescribed guidelines and satisfactory analgesia was obtained with a regimen which delivered up to 0.0375 mg/kg/hour, approximately half the dose recommended in children older than 12 months. There was one case of clinically significant respiratory depression.

Female

Cerebral blood flow in the anaesthetized immature sheep fetus and the response to hypercapnia.

Regional cerebral blood flow (CBF) has been measured in eight anaesthetized, exteriorized, fetal sheep between 58 and 62 days gestation; four were controls, four were hypercapnic (PaCO2 = 78 +/- 5 mmHg, mean +/- S.E.M.). Blood flow values were calculated from quantitative autoradiography following the infusion of [14C]iodoantipyrine into a cannulated fetal placental vein, for the cerebellum, medulla, and five layers of the developing neocortex: cortical plate (CP), subplate zone (SP), intermediate zone (IZ), subventricular zone (SV), and the ventricular zone (VZ). The highest control CBF rates were recorded in the cortical plate (49.3 +/- 7.4 ml min-1 (100 g)-1, mean +/- S.E.M., posterior cortex) and in the ventricular zone (40.5 +/- 4.8, posterior cortex), which at this stage of development are the regions of greatest cell density. The lowest CBF rates were recorded in the subplate zone (23.8 +/- 6.8, anterior cortex) and in the intermediate zone (23.4 +/- 7.6, anterior cortex), which are the regions of lowest cell density. Experimentally induced hypercapnia increased CBF in all brain regions and enhanced the regional pattern of flow. The results provide evidence that CBF in the immature fetal sheep brain (at 58-62 days gestation) is heterogeneous under both control and hypercapnic conditions (especially in the neocortex). Blood vessels of the fetal sheep brain at this early stage of development are clearly responsive to CO2.

Animals

Phase II study of mitoxantrone, leucovorin, and infusional fluorouracil for treatment of metastatic breast cancer.

A new combination of mitoxantrone, folinic acid (leucovorin), and infusional fluorouracil (5-FU) was administered to 57 previously treated patients with metastatic breast cancer to evaluate the response rate, response duration, and toxicity of this regimen. Fifty-three patients who received 313 courses of therapy were assessable for response and toxicity. Median age was 48 years (range, 33 to 80 years), and the patients had received an average of 1.5 chemotherapy regimens before this study. Of 53 assessable patients, 24 (45%, or 42% of all entered patients) experienced partial responses (PRs) with a median duration of 6 months (range, 2 to 13 months). Nine (69%) of 13 assessable patients without prior doxorubicin treatment responded, compared with 15 (38%) of 40 with prior doxorubicin (P less than .05). Toxicity was generally mild with dose reductions necessitated more often by mucositis and/or diarrhea than by myelosuppression. One patient with prior high-dose doxorubicin treatment developed congestive heart failure. The combination of mitoxantrone, leucovorin, and infusional 5-FU is an active and well-tolerated regimen for metastatic breast cancer and deserves further evaluation in patients without prior doxorubicin therapy.

Adult

General practitioner obstetrics in Bradford.

The standard of obstetrics care by general practitioners in Bradford was assessed by reviewing the case records of all women who in 1988 were booked for delivery under their general practitioner but subsequently required transfer to consultant care. A total of 5885 women were delivered in Bradford during 1988. Of 1289 booked under their general practitioner, 637 required transfer to consultant care. In 259 cases transfer occurred during labour; only 37 of these women were visited by their general practitioner. Many of the problems that precipitated transfer were predictable and some were considered preventable: 263 of the women transferred were considered unsuitable for booking by general practitioners. The perinatal mortality among women booked under their general practitioner was 10.1/1000 and the stillbirth rate 7.8/1000. These figures are high and suggest a need for tighter controls over the qualifications and experience of doctors participating in a fully integrated system of obstetric care.

Consultants