Evaluation of healing by gentle touch.

OBJECTIVES: To evaluate the effectiveness and safety of healing by gentle touch in clients attending The Centre for Complementary Care (CCC) in Eskdale, Cumbria. STUDY DESIGN: An evaluation of data collected by questionnaire over 6 years. METHODS: All clients attending the CCC between 1995 and 2001 were invited to participate in this study, and data were collected from 300 subjects with a wide range of ailments who received four treatment sessions within 6 weeks. Exclusion criteria were: recent treatment at the CCC; failure to complete four treatment sessions; and age under 16 years. Outcome measures included comparison of pre- and post-treatment levels of physical (pain, disability, immobility, sleep disturbances, reliance upon medication, daily activities) and psychological (stress, panic, fear, anger, relaxation, coping, depression/anxiety) functioning; these were assessed using a questionnaire with visual analogue scales for subjective rating of symptoms and the EuroQoL (EQ-5D), a generic state-of-health measure. RESULTS: Wilcoxon signed ranks tests showed statistically significant improvements in both psychological and physical functioning, particularly in stress reduction (median stress levels fell by four points), pain relief (median pain ratings fell by two points), increased ability to cope (median improvement of three points) and increased general health ratings (median improvement of 20 points) between study entry and end of treatment (P < 0.0004 for all these symptoms). The most substantial improvements were seen in those with the most severe symptoms at study entry. No adverse effects of treatment were documented. CONCLUSIONS: This audit of treatment outcomes provides evidence consistent with the hypothesis that healing, as provided at the CCC, was associated with improved psychological and physical functioning in the majority of subjects, and is worthy of further evaluation.

Urinary hormone levels during the natural menstrual cycle: the effect of age.

A number of studies have identified hormonal changes in women during their reproductive lifespan, many focusing upon changes in women over the age of 40 years. The present study has determined the effect of increasing age on hormone levels over three decades. Daily early morning urine samples were assayed for estrone-3-glucuronide (E3 G), pregnanediol-3-glucuronide (P3 G), testosterone-17-glucuronide (T17 G), FSH and LH. An examination of the validity of using creatinine as a volume adjuster in urine samples formed an integral part of the analysis. Volunteers were healthy women who had regular (25-35 days) cycles, were not taking oral contraceptives, hormone therapies or any other medication. Three age groups were compared: 20-29 years (n=13), 30-39 years (n=9) and 40-49 years (n=13). Statistical analyses were carried out using two-way ANOVA and post hoc t-tests. Creatinine excretion, despite revealing no cycle-related variation in any age group, showed a decline with increasing age. Creatinine output was significantly lower in the 40-49 years age group in all phases of the cycle than in the 20-29 and 30-39 groups (P<0.0001). Uncorrected levels of E3 G were significantly higher in the 30-39 years group when compared with the 40-49 age group (P<0.0001). Uncorrected P3 G output was significantly higher in women aged 20-29 years than in women aged 40-49 years (P<0.001) and levels of uncorrected T17 G were higher in the 20-29 year age group when compared with the 30-39 or 40-49 years age group (P<0.0001). The present study is consistent with previous reports that have revealed a decline in creatinine clearance with increasing age, and therefore casts into some doubt the validity of using creatinine clearance as a procedure to correct for volume fluctuations in differing age groups of women. The study also demonstrates unequivocally that age-related variations in hormone levels are not restricted to women over 40 years of age. The novel finding of highly significant differences in mean levels of T17 G between the age groups is of considerable interest. It is presently unclear whether this resulted from specifically increased ovarian and/or adrenal secretion. The possible impacts of changes in testosterone levels during the female reproductive lifespan merits further study.

Understanding medicines: conceptual analysis of nurses' needs for knowledge and understanding of pharmacology (Part I).

The advent of nurse prescribing in the United Kingdom (UK), albeit from a very limited formulary at first, provides a timely prompt for careful reflection on the extents and depths of understanding of medicines required by nurses for a variety of different purposes. This paper, which is the first of a two-part work, presents a conceptual analysis of what is required for patient care and support, pro re nata (as required) administration of medicines, protocol-directed administration of medicines (dependent prescribing), independent prescribing from the current Nurse Prescribers' Formulary or independent prescribing from extended formularies or the entire British National Formulary. It includes review, with common examples, of presentational issues distinguishing between approved, generic names of medicines and trade or brand names, and some discussion of combination medicines; and of recent research that has demonstrated that patient care was improved when the bioscience knowledge of nurses increased.

Understanding medicines: extending pharmacology education for dependent and independent prescribing (Part II).

This paper relates to the extent and depth of understanding of medicines that is required for supply and administration of medicines under group protocol (dependent prescribing) (Crown 1998, 1999) for patients who are taking concurrent medications or independent prescribing from extended formularies or the entire British National Formulary. This includes a concise account of the level of understanding needed of: classifications, actions and effects (pharmacodynamics), duration of action and pharmacokinetics, interactions, and drug discovery, development and evaluation. A final section relates to aspects which students have found most challenging and provides examples of helpful explanations of concepts that have been found difficult. The limited familiarity of most nurses with chemistry is the greatest cause for anxiety, and yet it is unrealistic to argue the case for this subject as a prerequisite to a career in nursing. Instead, taking a pragmatic view of the need to meet students where they are, and making creative use of domestic analogies and images, has served to make pharmacology accessible. Examples of these aids to understanding are outlined.

Cardiovascular functioning during the menstrual cycle.

Variations in cardiovascular functioning during the 'normal' menstrual cycle have been little researched. Resting-blood pressures, resting-heart rate, rate-pressure product (RPP) and a derived index of fitness (Schneider Index) were monitored throughout natural, hormonally defined menstrual cycles. Volunteers were 26 women (20-48 years) who had regular (25-35 days) cycles. Their blood pressures and heart rate (at rest and according to Schneider's protocol) were measured at the same time daily (Monday-Friday) for 5 weeks. Daily, early morning-urine samples were assayed for sex hormones enabling accurate definition of cycle phase for each woman. Resting systolic-blood pressure was significantly higher in the ovulatory phase (P < 0.05) than in the follicular or luteal phases, but resting-diastolic pressures did not differ significantly between phases. Resting-heart rate was significantly higher in both ovulatory (P < 0.01) and luteal (P < 0.01) phases than in the menstrual and follicular phases. The Schneider Index was higher during the follicular phase than during the ovulatory (P < 0.005) or luteal (P < 0.01) phases, the RPP was higher during the ovulatory phase than during the bleeding (P < 0.05) and follicular (P < 0.005) phases. These findings provide a pattern of menstrual cycle-related variation in cardiovascular functioning that can be related to established actions of the ovarian steroids.

The effects of potassium channel blockers on progesterone-induced suppression of rat portal vein contractility.

The suppression of contractility of rat portal vein caused by progesterone appears to be due to the potassium (K+) channel opening effect of this hormone. The identity of the specific K+ channels involved has been investigated using a variety of K+ channel blockers. Incubation with 100 nM iberiotoxin antagonised the progesterone-induced inhibition of spontaneous and 20 mM K+-induced phasic activity of the portal vein such that the contractions resembled those of the non-progesterone, non-iberiotoxin control tissues treated with the corresponding solvent vehicles. Incubation with barium chloride (20 and 100 microM), 4-aminopyridine (1 mM), tetraethylammonium chloride (1 mM), glibenclamide (1 microM) or apamin (1 microM) did not, however, have the same antagonistic effect. These results suggest that progesterone's selective suppression of rat portal vein contractility is mediated by the opening of BKCa channels.

The effect of progesterone on spontaneous and agonist-evoked contractions of the rat aorta and portal vein.

The mechanisms underlying the suppression of vasocontractility caused by progesterone were investigated by studying changes in the contractile force of rat isolated aorta and portal vein, induced by altering extracellular concentrations of noradrenaline (NA) potassium ions (K+) and calcium ions (Ca2+). In the aorta, progesterone (10 microM) had a general suppressive effect on NA-, Ca2+- and K+-induced contractions. In contrast, in the portal vein a more selective suppression of contractions was observed. Both tonic and phasic components of contractions induced by cumulative addition of Ca2+ to tissues equilibrated in Ca2+-free saline were suppressed. The phasic but not tonic components of contractions induced by NA addition were suppressed. There was no significant effect on tonic contractions induced by elevated (40-120 mM) K+, but a concentration-dependent suppression of the phasic component of contractions was observed during depolarisation with smaller elevations of K+ concentrations (5-20 mM). These results suggest that on the portal vein the suppressive effect of progesterone is due to a potassium channel opening action, whilst on the aorta a different or additional mechanism of suppression exists.

Serotonin-induced contractility in human saphenous vein is inhibited by naftidrofuryl.

Vascular endothelial denudation contributes to vasospasm by causing platelet aggregation and the subsequent release of vasoconstrictors such as serotonin. It has recently been suggested that naftidrofuryl fumarate (NFT) may oppose serotonin-induced vasoconstriction. Fourteen rings of human saphenous vein from 14 patients undergoing varicose vein surgery were tested in standard organ bath experiments. Cumulative dose-response curves and maximal contraction in response to serotonin were recorded and this was repeated in the presence of NFT at 10(-6) and 10(-3) mol/l. The difference in maximal contractility between the three sets of curves was significant (P < 0.0001). Sensitivity to serotonin in each of the three curves was measured using the concentration for half-maximal response; differences were again significant (P < 0.0001). It is concluded that NFT reduces serotonin-induced contractility in a dose-dependent fashion in rings of human saphenous vein in vitro. These results suggest a possible role for NFT in reducing vasospasm and support further investigation of this drug.

Evidence that an atypical beta-adrenoceptor mediates the inhibition of spontaneous rhythmical contractions of rabbit isolated jejunum induced by ritodrine and salbutamol.

1. The nature of the adrenoceptors mediating the inhibitory action of noradrenaline, ritodrine and salbutamol on the spontaneous activity of longitudinal muscle of the rabbit jejunum in vitro was investigated by use of a range of adrenoceptor antagonists. 2. The actions of ritodrine and salbutamol were antagonized competitively by propranolol. The pA2 values of 6.4 and 6.6 respectively were smaller than those found elsewhere for beta 1- and beta 2-adrenoceptors. 3. In contrast, the responses to ritodrine and salbutamol were antagonized only by high concentrations (greater than 2.7 microM) of phentolamine and were unaffected by yohimbine (2.6 microM), mepyramine (2.5 microM) or cimetidine (4.0 microM). 4. Ritodrine which is less potent than salbutamol in tissues with typical beta 2-adrenoceptors was found to be 8 times more potent than salbutamol in the rabbit jejunum. 5. It is suggested that in the rabbit jejunum ritodrine and salbutamol may act at an atypical beta-adrenoceptor, at which propranolol is a competitive but not very potent antagonist.

New possibilities for anti-migraine drugs: prostanoid antagonists and progesterone-mimicking stabilizers of excitable cells.

Medications currently available for the prophylaxis and treatment of migraine provide only limited relief. The pathophysiology of migraine is still poorly understood but it is widely accepted that various 'triggers', including fluctuations in the concentrations of circulating ovarian steroid levels, may initiate alterations in the activity of the intracranial vasculature and its efferent and afferent innervation. Recent pharmacological studies utilizing human intracranial artery preparations have addressed two distinct therapeutic stratagems. First, aspirin-like analgesics, which inhibit prostanoid synthesis, are widely used to treat migraine headache. Recent findings suggest that the ability of mefenamic acid to antagonise certain prostanoid actions, in addition to inhibiting synthesis, enhances its effectiveness. Thus, development of selective antagonists of the intracranial vasoconstrictor and the hyperalgesic actions of prostanoids could provide effective and selective migraine remedies. Second, with regard to prophylaxis, particularly of menstrually-related migraine, drugs which mimic the vascular smooth muscle 'stabilizing' action of ovarian steroids, possibly by enhancing potassium channel activation, are likely to be effective if used at concentrations that have minimal hypotensive effects.

The effect of plasma from patients with essential hypertension on the contractility of human arteries.

The effect of plasma from patients with essential hypertension and from normotensive subjects on the contractile response to noradrenaline and potassium chloride has been investigated using human isolated arteries. After incubation with plasma from normotensive subjects, there was no change in the contractile response to either noradrenaline (-3.0 +/- 5.4%; P = NS) or potassium chloride (3.2 +/- 3.0%; P = NS). After incubation with plasma from patients with essential hypertension, the contractile response to noradrenaline was significantly increased (24.8 +/- 9.8%; P less than 0.01) whereas that to potassium chloride did not change (-0.4 +/- 3.7%; P = NS). The change in the contractile response to noradrenaline in the presence of plasma from hypertensive patients was significantly higher than that obtained in the presence of plasma from normotensive subjects (P less than 0.03) whereas that to potassium chloride was not different between groups (P = NS). These findings suggest that the increased vascular reactivity of human arteries in the presence of hypertensive plasma could be related to specific mechanisms requiring receptor-mediated activation of the vascular smooth muscle cell.

Evidence using human arterial tissue for a circulating vascular sensitizing agent in essential hypertension.

We studied the effect of plasma from 12 patients with essential hypertension and 12 normotensive subjects on the contractile response to norepinephrine in human isolated arterial spiral strips. Human mesenteric and uterine arteries were obtained during abdominal surgery; they were cut into spiral strips and set up in isolated organ baths. After the equilibration period, arterial strips were incubated for 20 min in plasma from either normotensive subjects or hypertensive patients, and the contractile responses to norepinephrine (2.96 X 10(-7) M) were recorded. Plasma from hypertensive subjects significantly increased the contractile response to norepinephrine by 25.8% (P less than 0.02). Plasma from normotensive subjects did not increase the contractile response to the pressor agent (-3.2%; P = NS). The mean change in contractile response to norepinephrine in the presence of plasma from hypertensive patients was significantly higher than that after incubation of the human arterial strips in plasma from normotensive subjects (P less than 0.02). When both groups were considered as a whole, there was a significant correlation between diastolic pressure and the change in the contractile response to norepinephrine (r = 0.52; P less than 0.01). These results suggest the existence of a circulating vascular sensitizing substance in patients with essential hypertension.

Neural and humoral factors in postoperative ileus.

Two inhibitory mechanisms in the human colon which may contribute to postoperative ileus have been studied. Dopamine, a possible peripheral neurotransmitter, inhibited isolated colonic smooth muscle strips by a direct effect in longitudinal muscle any by a nerve-mediated mechanism as circular muscle. Plasma motilin levels were suppressed pre- and per- operatively and elevation of levels postoperatively correlated with the return of normal motility and the severity of the operation.