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Biomedical subjects

M Jackson

Publications and source records attributed to M Jackson.

At least 19 recordsLinked to original sources

Conformation of magainin-2 and related peptides in aqueous solution and membrane environments probed by Fourier transform infrared spectroscopy.

The conformational properties of the magainin family of antimicrobial peptides in aqueous solution and in model membranes have been probed by Fourier transform infrared spectroscopy. The magainins were found to be structureless in aqueous solution at neutral pD, confirming other studies by Raman and circular dichroism spectroscopy. Increasing the pD to 10 induced the formation of predominantly alpha-helical secondary structures, with some beta-sheet. In the presence of negatively charged liposomes (dimyristoylphosphatidylglycerol), the peptides folded into alpha-helical secondary structures with some beta-sheet structure evident. On the other hand, in the presence of zwitterionic phospholipids (dimyristoylphosphatidylcholine), the spectra were identical to those in aqueous solution. For some magainins, the interaction with charged liposomes was modulated by the presence of cholesterol; cholesterol was found to promote the formation of beta-sheet structures, as evidenced by the appearance of amide I bands at 1614 and 1637 cm-1. Differences in structure were observed between the amidated and nonamidated forms of some peptides. From the data, a mechanism of antimicrobial action of the magainin family of peptides is proposed.

Amino Acid Sequence

Current imaging of childhood urinary infections: prospective survey.

OBJECTIVES: To assess whether ultrasonography alone is adequate for routine screening of childhood urinary infection, whether clinical features determine the need for further investigations, and which investigations are most appropriate. DESIGN: Prospective survey of children with proved urinary infection and a preinvestigation record of clinical features. Ultrasonography and intravenous urography were routine, with choice of further studies determined by ultrasonographic findings. SETTING: A children's hospital and two district general hospitals in Mersey region. MAIN OUTCOME MEASURES: Sensitivity and specificity of ultrasonography both generally and in relation to clinical features. Accuracy of intravenous urography compared with radioisotope examinations. RESULTS: Specificity of ultrasonography was good (99% (95% confidence interval 96% to 100%)) but sensitivity modest (43% (32% to 55%)), principally with respect to detecting vesicoureteric reflux and renal scarring. Among older children (aged 2-10 years) with positive ultrasound results and fever or vomiting the sensitivity in detecting reflux (with and without renal scarring) was 78% (62% to 89%) and the specificity 69% (60% to 78%); in detecting renal scarring (with and without reflux) the sensitivity was 100% (80% to 100%) and specificity 65% (56% to 74%). Renal scarring and obstructive uropathies were better assessed by radioisotope examinations than by intravenous urography. CONCLUSIONS: Ultrasonography alone is inadequate for routine screening of childhood urinary infection. Though further investigations remain advisable in infants, in older children they can be restricted to a minority who have positive ultrasound examinations or have had fever or vomiting. Radioisotope examinations largely eliminate the need for intravenous urography.

Child

Halogenated alcohols as solvents for proteins: FTIR spectroscopic studies.

Fourier transform infrared (FTIR) spectroscopy has been applied to investigate the secondary structure of proteins and polypeptides in halogenated alcohols. Each alcohol studied was able, as a pure liquid, to induce conversion of the beta-sheet protein concanavalin A into a predominantly alpha-helical configuration. In 2H2O/alcohol mixtures, helicogenisis was also apparent, decreasing in the order dichloroethanol greater than bromoethanol greater than trifluoroethanol greater than chloroethanol greater than fluoroethanol. At concentrations below those found to be helicogenic, disruption of the protein secondary structure by the alcohols resulted in pronounced aggregation. At concentrations insufficient to cause noticeable disruptions of the secondary structure at room temperature, the thermal stability of the protein was greatly reduced. We suggest the helicogenic effect exhibited by halogenated alcohols to be related to a combination of a relatively low dielectric constant and a high dipole moment, the latter causing disruption of the internal hydrogen bond networks and the former causing refolding to a helical configuration. The results presented here highlight the risk of using halogenated alcohols, both as solvents for proteins and as a test of the intrinsic capacity of proteins and peptides to adopt helical secondary structures.

Alcohols

Serum electrolytes and capillary blood gases in the management of hypertrophic pyloric stenosis.

The purpose of this study was to assess whether the concentration of serum chloride and other variables, namely serum sodium, potassium and bicarbonate, can be used to predict metabolic acid-base status in infants with hypertrophic pyloric stenosis (HPS) and to assess whether such a prediction is influenced by the state of hydration. One hundred and sixty-three infants with HPS who had at least one set of serum electrolyte and capillary blood gas estimations performed after admission were studied retrospectively. A further 25 infants who had their electrolyte and blood gases measured after at least 12 h of rehydration and correction of the serum sodium and chloride abnormalities were studied prospectively. Stepwise multiple regression analysis, using standard bicarbonate as the dependent variable, revealed serum chloride concentration to be the most powerful independent predictor of standard bicarbonate level (r = -0.69, P less than 0.0001). Other variables did not improve the correlation significantly. In the retrospective study of untreated patients, the calculation of a 90 per cent prediction interval for the model indicated that if the serum chloride level is less than 96 mmol/l, one could be 95 per cent confident (one tail) that the patient was alkalaemic. To be 95 per cent confident that the patient was not alkalaemic, the serum chloride level would have to be greater than 121 mmol/l. The prospective study found that following rehydration a serum chloride level greater than or equal to 106 mmol/l more accurately predicted absence of alkalaemia. We conclude that predictability of acid-base status from measurement of serum chloride depends on the state of hydration of the patient.

Acid-Base Imbalance

Inspiratory work imposed by continuous positive airway pressure (CPAP) machines: the effect of CPAP level and endotracheal tube size.

Inspiratory work imposed by Continuous Positive Airway Pressure (CPAP) machines has been a matter of concern. The imposed inspiratory work of CPAP machine circuits (Wcir) and the effect of the total breathing apparatus with endotracheal tube (ETT) and connector included in the circuit (Wapp), were measured in three continuous flow (CF) and various configurations of three demand flow (DF) CPAP machines. The performance was assessed at 0, 5, 10 and 15 cmH2O CPAP using a Michigan Instruments Test Lung Model 1600, internal compliance set at 50 ml/cmH2O, driven at square wave inspiratory flows (VI) of 20, 40 and 60 l/min at a tidal volume of 500 ml. Work, expressed in mJ/l, was calculated from the area of pressure-volume loops. Inspiratory work, Wcir and Wapp, was dependent upon the particular CPAP machine, VI and ETT size, but not upon CPAP level, being maximum at VI 601/min and with ETT 7.0 mm i.d. Work values (Wcir) varied from 50 to 325 mJ/l with both CF and DF machines and up to 1100 mJ/l with ETT and connector (Wapp). No consistent advantage of CF over DF machines was demonstrated. There was little advantage of high gas flows (greater than 5 l/min) in various DF circuits. Within an individual machine maximum negative pressures generated during inspiration correlated with both Wcir and Wapp.

Equipment Design

Isolated sternal fracture: a benign injury?

Since seat belt legislation was introduced in this country in 1983, we have seen an increasing number of patients admitted to our unit for observation following seat belt related sternal fractures. In order to determine the value of routine admission of patients with isolated sternal fracture we have reviewed a series of 104 consecutive patients admitted between February 1983 and February 1990 with this injury. Of these, 90 were sustained in road accidents, 79 of which were as a consequence of seat belt use. The average age of these patients was 54.5 years (range 11-85 years) with an average duration of hospital stay of 2.9 nights. No serious complications were observed. These findings suggest that there may be no need to admit these patients solely for observation if their initial clinical condition is satisfactory and there are no abnormalities identified by an anteroposterior chest radiograph and electrocardiography.

Accidents, Traffic

Borna disease virus-specific antigens. II. The soluble antigen is a protein complex.

Borna disease virus-specific soluble antigen from persistently infected rat brains was purified to homogeneity using preparative sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The soluble antigen is a complex of three proteins with apparent molecular weights of 35 kDa, 38 kDa and 24 kDa. The 35/38 kDa antigen double band was separated into its two components. The 24 kDa protein has no common epitopes with the 35/38 kDa protein.

Animals

Optical disguising of orbital deformity with prism and cylinder lenses.

This paper describes the way in which prism and cylinder lenses may be used to disguise orbital dystopia when the affected eye is blind. The lenses used can correct the height of the eye, the opening of the eyelids or the rotation or slant of the eye. Four cases are presented to illustrated this technique, which may be used either instead of, or as an adjunct to orbital surgery. An investigation of these effects is described using a mannikin head fitted with an optician's trial frame, with measuring by the reflex metrograph. This revealed that an inferiorly displaced eye may be elevated by 4 to 5 mm, that the vertical eyelid opening may be widened (or narrowed) by just under 20% and that an adverse slant of the eye may be rotated in either direction by about 4 degrees.

Adolescent

Radiation-sensitive irs mutants rejoin DNA double-strand breaks with efficiency similar to that of parental V79 cells but show altered response to radiation-induced G2 delay.

Induction and repair of DNA double-strand breaks (dsb) was investigated in plateau phase Chinese hamster V79 cells and three radiosensitive mutant cell lines derived from them, irs-1, irs-2 and irs-3, using a pulsed-field gel electrophoresis assay, Asymmetric Field Inversion Gel Electrophoresis (AFIGE). There was no difference in the induction of DNA dsb per Gy and dalton between the radiosensitive mutant cells and wild-type V79 cells despite the wide differences in their radiosensitivity. Also, repair of DNA dsb proceeded in all cell lines with similar kinetics. In contrast to these observations at the DNA level, irradiation of exponentially growing cells showed a prolonged delay in G2 for irs-2 cells and a shortened delay in G2 for irs-1 cells, as compared to wild-type V79 cells. These results confirm previous observations suggesting that a deficiency in the rejoining of DNA dsb is unlikely to be the cause of the increased radiosensitivity of irs cells, and implicate alterations in postirradiation cell cycle progression as a possible cause for this phenomenon, although the mechanism is not known.

Animals

The pulmonary autograft--a permanent aortic valve.

Between 1969 and 1991, 339 patients had an aortic valve replacement with their own living pulmonary valve at the National Heart Hospital, Guy's Hospital and the Harley Street Clinic, London. The longest follow-up is 24 years and cumulative follow-up is 3774 patient-years. No form of anticoagulation was used and there were no emboli. There were 25 hospital deaths (7.4%) but only 1 death since 1976. Late deaths occurred in 38 patients mainly from technical mal-insertion. Bacterial endocarditis occurred in 11 patients. Thirty-eight patients were re-operated upon and account for 15 of the late deaths. Freedom from re-operation was 85% and the actuarial patient survival was 80% at 20 years. There has been no evidence of primary tissue degeneration and explanted valves showed normal cusp cellularity. Accumulating evidence suggests that the cusps not only survive permanently but can grow with the patient making the operation ideal for children.

Adolescent

Level of DNA double-strand break rejoining in Chinese hamster xrs-5 cells is dose-dependent: implications for the mechanism of radiosensitivity.

Rejoining of DNA double-strand breaks (dsb) was measured in a dsb repair-deficient mutant of CHO cells, xrs-5, after exposure to various doses of X-rays in the range between 15 and 50 Gy. For the experiments plateau-phase cultures were employed and dsb assayed by a pulsed field gel electrophoresis assay, the asymmetric field inversion gel electrophoresis (AFIGE). The half-times of dsb rejoining were larger in xrs-5 than in parental CHO cells and increased in both cell lines with increasing dose of radiation. The fraction of dsb remaining unrejoined after 240 min incubation at 37 degrees C was also higher in xrs-5 than in CHO cells, but decreased with decreasing dose of radiation. Although a decrease in the fraction of unrepaired dsb with decreasing dose has also been reported for repair-proficient cell lines, the extent of the phenomenon and its dependence on dose are entirely different in xrs-5 cells. We propose that this decrease in the fraction of unrejoined dsb with decreasing dose of radiation derives from the genetic alterations underlying the increased sensitivity to radiation of xrs-5 cells, and should be considered whenever results at the DNA level are correlated to results at the cell level. It is likely that similar responses will also be observed in other radiation-sensitive mutant cell lines deficient in dsb repair. There was no difference in the induction of dsb per Gy and dalton, as measured with AFIGE, between CHO and xrs-5 cells tested either in the exponential or in the plateau phase of growth.

Animals

Triple therapy for advanced squamous cell cancer of the head and neck.

This study presents the results of treatment for Stage III and IV squamous cell carcinoma of the head and neck at the Princess Alexandra Hospital and Queensland Radium Institute, Brisbane. Patients were treated using a programme of sequential chemotherapy, surgery and radiotherapy. Between 1980 and 1988, 116 patients commenced the programme and 85 completed the treatment as planned. The Price-Hill regimen of chemotherapy was used until 1986 after which time it was replaced by cisplatin/5-fluorouracil (5FU). Two courses were usually given achieving an overall response rate of 36% (12% complete response). Cisplatin/5FU produced an overall response rate of 56% compared with 24% for the Price-Hill regimen. Radical surgical resections were performed using a free flap reconstruction in the majority of patients. Radiotherapy fields usually covered the primary site and both cervical lymph node areas to a dose of 50-60 Gy in 5-6 weeks. The lengthy treatment was generally well tolerated although there were two chemotherapy and two perioperative deaths. The overall actuarial survival for the 85 patients completing the triple therapy was 60%. These patients were analysed in more detail for possible prognostic factors.

Antineoplastic Combined Chemotherapy Protocols

Psychodynamics and psychotherapy on an acute psychiatric ward. The story of an experimental unit.

The treatment of severely disturbed patients is strengthened in an important way by listening closely to them and by attempting to understand their experience in the depth that is made possible by the use of psychoanalytic concepts. It follows that the practice of clinical psychiatry in the UK would be greatly improved by the introduction of a psychoanalytic and psychotherapeutic perspective into the acute ward. This paper reviews the work done on a ward at the Maudsley Hospital in which this approach was the practice.

Acute Disease

Clinical experience and physiologic results with an implantable intratracheal oxygen catheter.

Ten patients with chronic lung disease received an implanted ITOC. Seven patients continue to use their catheters after a mean period of 14.75 months. Four catheters were removed, 2 at 1 month, 1 after 10 months and 1 after 13 months. One patient requested a second catheter. Three patients experienced mucus plug formation; this was transient in two patients, but led to removal of the catheter in the third. To determine the degree of oxygen-saving afforded by the ITOC, SaO2 was measured at rest and during exercise for eight of the ten subjects using a double-blind technique. The calculated oxygen savings were around 40 percent both at rest and during exercise. The ITOCs were well received by the majority of our patients and were shown to produce a useful saving of oxygen which is of benefit to patients using portable systems and those who require high oxygen flow rates.

Adult

Tirandalydigin, a novel tetramic acid of the tirandamycin-streptolydigin type. I. Taxonomy of the producing organism, fermentation and biological activity.

Tirandalydigin is a new tetramic acid antibiotic which was discovered in a screen designed to find compounds with activity against pathogenic anaerobic bacteria. It was named tirandalydigin because it possesses structural features that are common to both tirandamycin and streptolydigin. The producing culture, strain AB 1006A-9, is a Streptomyces and was compared to the streptomycetes that synthesize tirandamycin and streptolydigin. It is closely related to the former culture and was named Streptomyces tirandis subsp. umidus. Tirandalydigin has MICs in the range of 0.5 to 32 micrograms/ml against many pathogenic anaerobes, streptococci, enterococci and legionellae.

Aminoglycosides

Inter-machine variability in the stability of continuous positive airway pressure.

Two studies were performed to investigate the differences in pressure stability performance of the continuous positive airway pressure (CPAP) machines used by our patients. The variations of mask pressures during each respiratory cycle were measured during overnight studies of two groups of patients with obstructive sleep apnoea, who were using either a Sleep-Easy III CPAP machine or a Si-Plan CPAP unit. The patients were well-matched for age, weight and neck circumference. The group using the Si-Plan unit had more constant mask pressures and were using lower CPAP pressures (mean 10.6 cmH2O) than those using the Sleep-Easy III machine (mean 13.8 cmH2O) (p less than 0.02). The pressure stability performance of five CPAP machines used by our patients was also compared using standardized simulated patient breaths produced by a negative pressure cuirass pump. There were large differences between the machines in ability to maintain a constant pressure. Using a tidal volume of 0.5 l and peak flow rates of between 20-40 l.min-1 the pressure variation ranged from 0-67% of the minimum inspiratory pressure. The maintenance of a constant pressure during inspiration and expiration lowers the mean pressure required to eliminate obstructive sleep apnoeas and reduces the likelihood of pressure related side-effects.

Adult