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Biomedical subjects

D G Allen

Publications and source records attributed to D G Allen.

At least 91 records · Page 5Linked to original sources
PubMed1995

The role of intracellular acidosis in muscle fatigue.

Muscle fatigue is often accompanied by an intracellular acidosis of variable size. The variability reflects the involvement of different metabolic pathways, the presence or absence of blood flow and the effectiveness of pH-regulating pathways. Intracellular acidosis affects many aspects of muscle cell function; for instance it reduces maximal Ca(2+)-activated force and Ca2+ sensitivity, slows the maximal shortening velocity and prolongs relaxation. However, acidosis is not the only metabolic change in fatigue which causes each of the above, and there are important aspects of muscle fatigue (e.g., the failure of Ca2+ release) which do not appear to be caused by acidosis.

Acidosis↗
PubMed1995

A comparison of organochlorine removal from bleached kraft pulp and paper-mill effluents by dehalogenating Pseudomonas, Ancylobacter and Methylobacterium strains.

The relative importance of each of three dechlorinating species to overall organochlorine removal from bleached kraft-mill effluents (BKME) was assessed. Ancylobacter aquaticus A7, Pseudomonas P1, and Methylobacterium CP13, strains indigenous to a BKME treatment system, were tested for growth on chlorinated acetic acids and alcohols, and for adsorbable organic halogen (AOX) reduction in batch cultures of sterile BKME from three sources. A. aquaticus A7 exhibited the broadest substrate range, but could only affect significant AOX reduction in softwood effluents. Methylobacterium CP13 exhibited a limited substrate range, but was capable of removing significant amounts of AOX from both hardwood and softwood effluents. By contrast, Pseudomonas sp. P1 exhibited a limited substrate range and poor to negligible reductions in AOX levels from both effluent types. Mixed inocula of all three species combined and inocula of sludge from mill treatment systems removed as much AOX from softwood effluents as did pure populations of Methylobacterium CP13. When BKME was hydrolysed prior to AOX analysis, the subsequent estimates of recalcitrant, or non-hydrolysable, AOX levels were far less variable than their counterpart total AOX measures. It is suggested that this is a relevant and useful measure of AOX for biodegradation studies.

Biodegradation, Environmental↗
PubMed1995

The use of cervicography in the follow-up of cervical intraepithelial neoplasia treated by CO2 laser.

After treatment for cervical intraepithelial neoplasia (CIN) the follow-up of patients would be simplified if colposcopy could be safely omitted. A study of 50 patients was performed to determine the feasibility of such an approach. Cervical cytology, cervicography and colposcopy, with or without biopsy, was performed in each patient. From the results the following criteria for colposcopy were adopted: (a) patients thought to have CIN on cytology or cervicography, (b) inadequate cervicography picture (vagina covering cervix or poor quality photography), (c) high-risk factors present (immunosuppression, after cone biopsy, postmenopausal). In this study the number of colposcopies would have been reduced from 50 to 11 if these criteria were adopted. Cervical cytology combined with cervicography is a reasonable alternative to colposcopy and we feel this is a technique worth pursuing for the follow-up of patients treated for CIN.

Carbon Dioxide↗
PubMed1995

Invasive cervical cancer in pregnancy.

Cervical cancer is the commonest malignancy which complicates pregnancy, but the management remains controversial. We reviewed our patients in an attempt to identify the best management options which resulted in long-term survival for the mother and a live baby. The total number of pregnancies managed between January, 1981 and March, 1995 was obtained from the hospital records, and patients with invasive cervical cancer diagnosed during pregnancy or within 12 months of delivery were identified. The case records were reviewed. Between January, 1981 and March, 1995 there were 22 cases of cervical cancer diagnosed either during pregnancy or within 12 months postpartum. This gave an incidence of cervical cancer associated with pregnancy of 1 in 3,817 pregnancies or 0.26 per 1,000 pregnancies. Eleven patients had microinvasive disease. Nine were treated by cone biopsy and 2 by radical hysterectomy. Nine patients had Stage 1B and 1 had Stage 2A disease and all were treated with radical hysterectomy. One patient had Stage 3B disease and was treated with radiotherapy and chemotherapy followed by simple hysterectomy. Fourteen patients delivered vaginally. Twenty of the 22 patients were delivered of live babies which survived. The patients have been followed from 1 month to 13 years with only 1 recurrence, and all 22 remain alive. We conclude that all pregnant women should have a Pap smear performed antenatally. Cone biopsy can be safely performed in pregnancy and may be adequate treatment for microinvasive squamous cell carcinomas. Treatment, including the timing of delivery, must be individualized, with the patient playing an important decision-making role.

Adenocarcinoma↗
PubMed1995

Muscle cell function during prolonged activity: cellular mechanisms of fatigue.

Muscle performance declines during prolonged and intense activity; important components are a reduction in force production and shortening velocity and a prolongation of relaxation. In this review we consider how the changes in metabolites (particularly H+, inorganic phosphate (Pi), ATP and ADP) and changes in sarcoplasmic reticulum Ca2+ release lead to the observed changes in force, shortening velocity and relaxation. The reduced force is caused by a combination of reduced maximum force-generating capacity, reduced myofibrillar Ca2+ sensitivity and reduced Ca2+ release. The reduced maximum force and Ca2+ sensitivity are largely explained by the effects of H+ and Pi that have been observed in skinned fibres. At least three different forms of reduced Ca2+ release can be recognized but the mechanisms involved are incompletely understood. The reduced shortening velocity can be partly explained by the effects of H+ that have been observed in skinned fibres. In addition it is proposed that ADP, which depresses shortening velocity, increases during contractions to a level that is considerably higher than existing measurements suggest. Changes in Ca2+ release are probably unimportant for the reduced shortening velocity. The prolongation of relaxation can arise both from slowing of the rate of decline of myoplasmic calcium concentration and from slowing of cross-bridge detachment rates. A method of analysis which separates these components is described. The increase in H+ and the other metabolite changes during fatigue can independently affect both components. Finally we show that reduced force, shortening velocity and slowed relaxation all contribute to the decline in muscle performance during a working cycle in which the muscle first shortens actively and then is stretched passively by an antagonist muscle.

Animals↗
PubMed1995

The effects of glibenclamide on tetanic force and intracellular calcium in normal and fatigued mouse skeletal muscle.

In this study the effects of ATP-sensitive K+ channel modulators were studied in intact single fibres dissected from mouse skeletal muscle. Indo-1 was used to measure [Ca2+]i simultaneously with force during normal and fatiguing stimulation. In control fibres, opening of ATP-sensitive K+ channels with BRL 38227 produced a small reduction in tetanic force and [Ca2+]i. In contrast, glibenclamide, a selective blocker of the ATP-sensitive K+ channel, slightly increased tetanic force and [Ca2+]i in these fibres and also increased Ca2+ sensitivity. Glibenclamide produced a more marked increase in tetanic force and [Ca2+]i during the later stages of fatiguing stimulation, although this effect was observed in only 50% of fibres examined. We conclude from this study that glibenclamide produces a partial reversal of the later stages of fatigue in a subpopulation of muscle fibres. Opening of ATP-sensitive K+ channels may therefore contribute to the decline in tetanic force and [Ca2+]i characteristic of skeletal muscle fatigue.

Acidosis↗
PubMed1995

Hermeneutics: philosophical traditions and nursing practice research.

This analysis begins with the premise that nursing practice research has often ignored or suppressed the fact that nurses participate in and benefit from the same American illness care nonsystem that leaves 40 million citizens without health care. This collective denial has its historical roots in philosophic foundationalism, health care authoritarianism, and nursing's disciplinary isolation. Philosophical hermeneutics offers perspectives that emphasize the inescapability of nursing's history. This article traces some of the main themes in philosophical hermeneutics and their potential significance for nursing practice research. The relationship between hermeneutic philosophy and research methods employed in interpretive traditions (for example, grounded theory) and the role of experimental design in addressing hermeneutic questions are discussed.

Delivery of Health Care↗
PubMed1995

Effects of vincristine and prednisone on platelet numbers and function in clinically normal dogs.

Effects of a single IV administered therapeutic dose of vincristine sulfate on platelet numbers and function were evaluated in 16 clinically normal dogs over the 2 weeks after drug administration. Results were statistically compared with those of a previous control study in which the same 16 dogs were administered saline solution (IV), instead of vincristine. Of the 16 dogs, 8 were orally administered daily immunosuppressive doses of prednisone concurrently throughout the saline-control and vincristine study periods. Platelet numbers and mean platelet volume were measured, using an automated hematology analyzer. Platelet function was evaluated by turbidimetric measurement of platelet aggregation in response to collagen, platelet-activating factor, and adenosine diphosphate (ADP), and by clot retraction (diluted whole-blood method) and buccal mucosa bleeding time. Vincristine had a significant (P < 0.05) effect on circulating platelet numbers. Vincristine induced a transient mild decrease in platelet numbers, followed by a moderate increase in numbers, with peak platelet count observed 8 days after drug administration. Mean platelet volume was not significantly affected by administration of vincristine. Vincristine had no significant effects on platelet aggregation in response to collagen, low or high doses of platelet-activating factor, and a high dose of ADP. The maximal degree of platelet aggregation attained in response to a low dose of ADP was not significantly affected by prior administration of vincristine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

A meta-analysis of residual disease and survival in stage III and IV carcinoma of the ovary.

UNLABELLED: A meta-analysis of retrospective studies was performed to determine the value of cytoreductive surgery separately for Stage III and IV ovarian cancer. DESIGN: A literature search and personal communications were used to identify studies reporting patient numbers and survival data at 2 years and/or 5 years in patients with no residual, < = 2 cm and > 2 cm residual disease after surgery for Stage III and IV ovarian cancer. An odds ratio (OR) with 95% confidence intervals was performed on the data using the Cochran-Mantel-Haeszel procedure. RESULTS: The results show a survival benefit for patients with nil and < = 2 cm residual disease after surgery for both stage III and IV disease when compared to patient left with tumor masses > 2 cm. For Stage III patients the OR was 3.98 (3.31 to 4.79) at 2 years and 5.51 (4.40 to 6.90) at 5 years, indicating with 95% confidence that those with < = 2 cm residual tumor survived longer. When comparing nil and < = 2 cm residual disease survival is better for the group with nil residual with OR 3.37 (2.17 to 5.22) at 2 year and OR 4.35 (2.87 to 6.61) at 5 years. Optimal cytoreduction was also beneficial in Stage IV with OR 4.94 (2.55 to 9.57). Although it appears that maximum surgical effort is justified for stage III as well as Stage IV ovarian cancer, it must be remembered that no prospective, randomized trials have been performed. CONCLUSION: Optimal cytoreductive surgery appears to benefit the patient with ovarian cancer, but no data from prospective, randomized trials are available and tumor biology is not assessed. Very few studies report survival data based on the amount of residual disease in the separate FIGO stages. There is a need for a single, large database reporting all known variables for each patient.

Clinical Trials as Topic↗
PubMed1994

Relaxation, [Ca2+]i and [Mg2+]i during prolonged tetanic stimulation of intact, single fibres from mouse skeletal muscle.

1. In skeletal muscle there is generally a slowing of relaxation with increasing tetanus duration and it has been suggested that this is due to Ca2+ loading of parvalbumin (PA). To study this we have produced prolonged tetani in intact, single fibres from a mouse foot muscle which contain a high concentration of PA. We measured the rate of tension relaxation and also various aspects of Ca2+ handling. 2. During 'interrupted' tetani (15 repeated cycles of 100 ms with stimulation and 50 ms without) we observed a marked slowing of the relaxation both under control conditions and in acidosis (obtained by increasing the bath CO2 content). This slowing was not accompanied by any reduction of the initial rate of decline of the free myoplasmic Ca2+ concentration ([Ca2+]i), which was measured with indo-1. 3. The functioning of the sarcoplasmic reticulum (SR) pump after tetani of various durations was analysed by plotting d[Ca2+]i/dt vs. [Ca2+]i during the final slow decline of [Ca2+]i after tetani. This analysis showed that the rate of SR Ca2+ pumping after a 1 s tetanus is less than half of that after a 100 ms tetanus. 4. The amplitude of the tail of [Ca2+]i 250 ms into relaxation was measured after tetani of various durations. This amplitude increased with tetanus duration and could be fitted to the sum of one exponential and one linear function. The exponential component increased with a time constant of 0.17 s and probably reflects Ca2+ loading of PA. 5. Ca2+ binding to PA will displace Mg2+ and hence the free myoplasmic concentration of Mg2+ ([Mg2+]i) will increase. To study this we used the fluorescent Mg2+ indicator furaptra. The results showed an increase of [Mg2+]i during prolonged tetani which, after removing the Ca2+ component of the fluorescent signal, amounted to about 0.5 mM. 6. A model of Ca2+ movements and tension production in skeletal muscle was used. The model showed that the increase of the amplitude of [Ca2+]i tails after tetani of various durations can be explained by the combined effect of Ca2+ loading of PA and slowed SR Ca2+ pumping. In contrast to the experimental data, the model predicted a slight reduction of the initial rate of [Ca2+]i decline with increased tetanus duration. 7. In conclusion, we observed a marked slowing of relaxation during prolonged tetanic stimulation. Altered Ca2+ handling, including Ca2+ loading of PA, seems not to be important for this slowing. Thus, the slowing appears to be due to altered cross-bridge kinetics.

Acidosis↗
PubMed1994

The role of sarcoplasmic reticulum in relaxation of mouse muscle; effects of 2,5-di(tert-butyl)-1,4-benzohydroquinone.

1. Intracellular calcium concentration ([Ca2+]i) and force were measured from isolated single mouse skeletal muscle fibres at rest and during tetani. The actions of 2,5-di(tert-butyl)-1,4-benzohydroquinone (TBQ), an inhibitor of the sarcoplasmic reticulum (SR) Ca2+ pump, were examined at a range of concentrations (100-1000 nM). 2. TBQ increased resting [Ca2+]i, increased tetanic [Ca2+]i and slowed the rate of decline of [Ca2+]i after a tetanus. TBQ produced a small increase in tetanic force and a large slowing of the rate of relaxation after a tetanus. All these effects were reversible. 3. TBQ had no important effects on the Ca2+ sensitivity or the maximum force produced by the myofibrillar proteins. 4. Analysis of the SR Ca2+ pump function confirmed that under control conditions and at very low levels of [Ca2+]i, the relationship between [Ca2+]i and SR pump rate was a 4th power function. TBQ caused a pronounced inhibition of the pump rate and reduced the power function to < 3. 5. Muscle fibres were fatigued by repeated tetani until tetanic [Ca2+]i and force were reduced and the rate of decline of [Ca2+]i after a tetanus was slowed. Under these conditions application of TBQ caused a further slowing of the rate of decline of [Ca2+]i but still increased tetanic [Ca2+]i and force. This result suggests that slowing of the SR pump rate is not the cause of the decline in tetanic [Ca2+]i and force at the late stage of fatigue. 6. A simple model of the interactions of Ca2+, TBQ and pump proteins is described, which predicts the 4th power function of the normal pump, inhibition by TBQ, and the reduced power function in the presence of TBQ. 7. A model of Ca2+ movements and force development in muscle is described, which closely matches the experimental results under control conditions. Inhibition of the SR pump by TBQ using the model of the pump described above simulates qualitatively all the observed effects of TBQ on [Ca2+]i and force. 8. In conclusion, TBQ is a potent, specific and reversible inhibitor of the SR Ca2+ pump in intact mouse skeletal muscle. Inhibition of the pump directly affects intracellular Ca2+ handling and force production.

Animals↗
PubMed1994

The metabolic consequences of an increase in the frequency of stimulation in isolated ferret hearts.

1. The metabolic consequences of an increase in the frequency of stimulation were examined in isolated ferret hearts. Intracellular pH (pHi) and the intracellular concentrations of phosphocreatine ([PCr]i), inorganic phosphate ([Pi]i) and ATP were measured by 31P nuclear magnetic resonance (NMR) spectroscopy. 2. Increasing the stimulus rate from 0.1-0.7 to 2 Hz caused an increase in [Pi]i and a decrease recovery of both [PCr]i and [Pi]i during continued stimulation. There was no change in [ATP]i during stimulation at 2 Hz. Increasing the stimulus rate caused an intracellular acidosis of around 0.1 pH units. 3. Increasing the stimulus rate generally caused an initial increase in developed pressure, followed by a decrease over 1-2 min to a steady level slightly lower than developed pressure at the low (control) stimulus rate. The increase in stimulus rate caused a 4- to 6-fold increase in time-averaged muscle activity. 4. Both oxygen uptake and production of lactate increased on 2 Hz stimulation. Lactate production accounted for less than 5% of ATP production at low or high stimulus rates, suggesting that significant anoxia was not occurring during stimulation. The observed lactate production was, however, sufficient to explain most of the intracellular acidosis observed when the stimulus rate was raised. When glycolysis was prevented by removal of glucose and depletion of glycogen stores, 2 Hz stimulation was accompanied by an intracellular alkalosis rather than an acidosis, suggesting that lactate production by glycolysis was the cause of the intracellular acidosis. 5. Reducing the rate of glycolysis increased the size of changes in [PCr]i and [Pi]i evoked by stimulation at 2 Hz. Furthermore, there was now no partial reversal of the changes in [PCr]i and [Pi]i during 2 Hz stimulation. 6. When oxidative phosphorylation was inhibited by replacing O2 with N2, increasing the rate of stimulation from 0.1-0.7 to 1-2 Hz caused an initial increase followed by a large fall in developed pressure, which declined to a level well below that at the control stimulus rate. The increase in stimulus rate was accompanied by a large fall in [PCr]i, an increase in [Pi]i, and an intracellular acidosis of 0.1-0.3 pH units. The fall in developed pressure was consistent with the known effects of the rise in [Pi]i and the fall in pHi on the contractile apparatus.

Adenosine Triphosphate↗
PubMed1994

The distribution of intracellular calcium concentration in isolated single fibres of mouse skeletal muscle during fatiguing stimulation.

Fluorescence microscopy has been used to examine the distribution of intracellular calcium concentration ([Ca2+]i) in isolated single fibres from the mouse flexor brevis muscle during fatiguing stimulation. Under control conditions there was a virtually uniform distribution of [Ca2+]i in fura-2 loaded fibres either at rest or during short (0.35 s, 100 Hz) tetani. Fatigue produced by repeated short tetani was accompanied by an early rise, followed by a marked fall, in tetanic [Ca2+]i. Throughout the period of fatiguing stimulation the distribution of [Ca2+]i remained uniform with no detectable gradients observed. In contrast, when fatigue was produced by continuous 100 Hz stimulation, a small gradient of [Ca2+]i developed across the fibre with the [Ca2+]i in the centre of the fibre lower than that at the edge of the fibre. This gradient was apparent after 1.7 s, persisted for at least 11 s and was superimposed on a rise followed by a fall in spatially averaged [Ca2+]i. Reduction of the extracellular Na+ to 50% caused reduced force production and a reduced [Ca2+]i in the centre of the fibre. To assess the contribution of reduced response of the myofibrillar proteins to [Ca2+]i during continuous tetani, the relation between [Ca2+]i and force throughout the long tetanus was compared with that obtained in short, unfatigued tetani. These results show that in long tetani, reduced tetanic [Ca2+]i and reduced responsiveness of the myofibrillar proteins to [Ca2+]i each make important contributions to the decline of force, whereas the gradients of [Ca2+]i make only a small contribution.

Animals↗
PubMed1994

Changes in myoplasmic sodium concentration during exposure to lactate in perfused rat heart.

OBJECTIVE: The free myoplasmic sodium concentration ([Na+]i) is thought to change during acidosis and ischaemia in the mammalian heart. Although there are methods available for measuring [Na+]i in isolated cells or small preparations, none is very effective in the isolated heart, which is one of the best models for studying ischaemia. The use of a fluorescent sodium indicator, sodium binding benzofuran isophthalate (SBFI), to measure [Na+]i in the isolated, perfused rat heart is described. This method was used to estimate the activity of the Na/H exchanger under conditions resembling some aspects of ischaemia. METHODS: The acetoxymethyl ester of SBFI was loaded into the perfused rat heart via the perfusate. Fluorescence signals developed on loading and were shown to be [Na+]i sensitive. An in vivo calibration technique allowed the fluorescence signals to be converted to [Na+]i. RESULTS: The [Na+]i under control conditions was 6.4 mM. When the hearts were exposed to 20 mM lactate at the normal extracellular pH (pHo = 7.4) for 10 min, developed pressure fell abruptly and then slowly recovered [Na+]i rose slowly by 1.5 mM during lactate exposure and paralleled the recovery of pressure. Exposure to lactate at reduced extracellular pH (pHo = 6.4) produced a larger rise in [Na+]i. In the presence of the Na/H exchange inhibitor 5-(N-methyl-N-isobutyl)-amiloride exposure to lactate caused a small fall in [Na+]i at pHo 7.4 and 6.4. CONCLUSIONS: The advantages and disadvantages of SBFI as an [Na+]i indicator in the perfused heart are described. The Na/H exchanger is an important regulator of [Na+]i during lactate induced intracellular acidosis, and it remains active in the presence of a substantial extracellular acidosis. This shows that low pHo does not necessarily inhibit the Na/H exchanger. The use of SBFI to estimate [Na+]i in the perfused heart is novel and has considerable potential for studies of ischaemia and related conditions.

Amiloride↗
PubMed1994

Disposition of lupanine and 13-hydroxylupanine in man.

1. The in vivo disposition of lupanine and 13-hydroxylupanine was studied in subjects identified as poor metabolizers (PM, n = 4) and extensive metabolizers (EM, n = 7) phenotypes for cytochrome P4502D6 (CYP2D6). 2. After oral administration (40.26 mumol), the half-life (t1/2) of lupanine determined from urinary excretion rate studies in EM subjects was 6.2 +/- 0.5 h (mean +/- SEM) with 95.5 +/- 6.0% of the dose recovered unchanged within 72 h. Similarly, in PM subjects t1/2 = 6.5 +/- 0.9 h and recovery 89.9 +/- 4.5%. 3. For orally administered 13-hydroxylupanine (37.83 mumol) the t1/2 in EM subjects was 6.8 +/- 1.0 h with a recovery of 100.5 +/- 5.3%, and in PM subjects t1/2 = 5.9 +/- 1.6 h with a recovery of 102.5 +/- 4.8%. 4. The t1/2s of both lupanine and 13-hydroxylupanine respectively did not differ significantly between EM and PM phenotypes. In addition, total recovery of dose for both alkaloids was similar between phenotypes. 5. In most subjects, > 76% of lupanine and > 85% of 13-hydroxylupanine was recovered as the unchanged compound. Significant apparent partial dehydroxylation of 13-hydroxy-lupanine was observed in one EM (14% of dose) and one PM (34% of dose) subject. 6. Overall, the finding of a high urinary recovery of unchanged lupanine or 13-hydroxylupanine together with similar t1/2s for both alkaloids in EM and PM CYP2D6 phenotypes suggests that clinical toxicity is unlikely to result from the use of lupin seed in footstuffs.

Alkaloids↗