Diana Wood

Reliability of drop size from multi-dose eye drop bottles : Is it cause for concern?

Purpose Responses to topically applied ocular drugs vary between patients. The volume of drug instilled is of particular importance as one of many sources of response variation, but the reliability of drop volume from eye drop bottles is unknown. Hence, the repeatability of drop volume and factors affecting this for a variety of drug manufacturers were considered in this study.Methods Nineteen bottles, one from each primary manufacturer in the UK, were examined. The mass of all drops expelled from each bottle was measured with respect to the bottle type, handling angle, drop number, drug and concentration. The accuracy (repeatability and trueness) of drops from each bottle was also evaluated.Results Drop volume varied significantly between drug manufacturers, ranging from 33.8 µl to 63.4 µl. The handling angle of the bottle also influenced drop volume, with angles less than 60° giving smaller drops. Drop number exhibited no significant effect upon drop volume. However, the drug type and its concentration did significantly affect the volume of the drop expelled from the bottle, with higher concentrations giving rise to larger drops. Repeatability coefficients across the range of bottles varied between ± 2.24 µl and ± 10.76 µl (mean ± 5.07 µl).Conclusions It is well reported that drug volume instilled has a significant effect on the degree of response. However, there are currently no official regulations concerning eye drop volume in either the UK or the USA. Since drop volume has been shown to vary significantly depending upon a variety of factors, it may be appropriate that the regulatory bodies consider the consequences of variable drop size.

A simple method to investigate the inhibitory effects of drugs on gastric emptying in the mouse in vivo

INTRODUCTION The aim was to develop a simple method to study modification of gastric motility in the mouse in vivo. METHODS Mice were fed a hydrated diet in which the fluid content of standard laboratory chow was increased by adding water. Gastric emptying was assessed at specified times following a 1-h treatment period with orally administered pharmacological agents. RESULTS We demonstrated consistent and progressive gastric emptying over a 4-h period, stomach content being decreased from 7.52+/-0.90 at time zero to 2.80+/-0.25 mg/g body weight after 4 h. Results demonstrated typical effects of inhibitory agents (atropine and morphine) and showed inhibitory effects of three potassium channel opening agents, pinacidil, cromakalim, and SDZ PCO400: the residue remaining in the stomach was increased by 3.66+/-0.84, 6.56+/-1.35, and 5.68+/-1.33 mg/g body weight respectively 1 h after treatment with 10 mg/kg of these agents, compared to vehicle controls. DISCUSSION The inhibitory activity observed correlated well with previous studies on the effects of potassium channel opening agents on mouse gastrointestinal motility in vivo and in vitro. The present model may thus be of value in the pharmacological investigation of gastrointestinal motility owing to cost and convenience advantages, together with the possibility of its application to studies using transgenic animals.

Comparative effects of K+ channel modulating agents on contractions of rat intestinal smooth muscle.

The effects of six K+ channel openers were investigated on contractions of the rat ileum longitudinal muscle-myenteric plexus preparation elicited by electrical field stimulation and by K+. Levcromakalim, pinacidil, RP 49356 (N-methyl-2-(3 pyridyl)-tetrahydrothiopyran-2-carbothioamide-1-oxide) and SDZ PCO 400 ((3S,4R)-3, 4-dihydro-3-hydroxy-2, 2-dimethyl-4-[(3-oxo-1-cyclopenten-1-yl)oxy]-2H-1-benzopyran-6-car bonitrile) completely abolished contractions elicited by electrical stimulation and caused complete relaxation of contractions elicited by K+ with comparable IC50 values. Minoxidil sulphate was much less potent and diazoxide was without effect in either protocol. The relaxant effects of these agents were antagonized by glibenclamide, tetraethylammonium and yohimbine in a manner which was not surmountable. The present study indicates that the relaxant effect of these compounds in intestinal smooth muscle is mediated through glibenclamide-sensitive ATP-dependent K+ channels. These compounds did not preferentially inhibit either direct smooth muscle- or nerve-mediated responses. The present data may point to differences in the channels or their regulatory sites, in intestinal, compared with vascular, smooth muscle.

A novel system for the objective classification of iris colour and its correlation with response to 1% tropicamide

Iris colour can provide an enormous amount of information about an individual. In addition to changes with pathological conditions, the colour of the iris can be a particularly useful indicator of how well a person will respond to a topically applied ocular drug. Until recently, classification of iris colour has been subjective, ranging from a basic description (‘light’ and ‘dark’) to more detailed grading systems, such as a comparison with preset photographic standards. However, variability within observers and differences in the interpretation between observers can influence the results. Objective techniques, in this respect, possess several advantages. They are able to detect differences in colour that subjective techniques are incapable of and they provide continuous data rather than discrete categories, thus improving the accuracy of drug response predictions. This study assessed iris colour by objective means. Slit‐lamp photographs of various coloured irides were taken under standardised conditions. The slides were then scanned into a computer and the colour analysed using a calibrated software package. To establish the optimum colour parameter to be used for predictions of drug response, several parameters were calculated and compared with the subject response to 1% tropicamide (maximum change in pupil size, time to maximum change and total duration of effect). Many parameters had strong correlations with drug response, but the parameters ‘z’, ‘b’ (the proportion of blue in the image) and ‘y’ (the proportion of yellow in the image) were found to exhibit the highest correlations. They also showed better correlations with drug response than did a current iris colour grading system.

Eye drop container delivery: a source of response variation?

Variations in response to topically applied ocular drugs (e.g. mydriatics and cycloplegics) and their possible aetiology have been studied previously. It appears that individual patient differences, external influencing factors and the characteristics of the particular drug may all govern the response. One factor worthy of note in this regard is the possibility of variation in the drug volume instilled. Single-use eye drop containers known as Minims are commonly used during ophthalmic diagnostic procedures. However, in this study the drop volume was shown to vary considerably, depending upon the angle at which the Minims container was held, the particular drug and the number of drops previously expelled from the unit.

Elemental Diets in the Repair of Small Intestinal Damage

We have investigated the possible benefits of elemental diets, especially a diet supplemented with L-glutamine, on maintenance of intestinal absorptive function in rat small intestine damaged by 5-fluorouracil. Although a standard rat diet sustained better body growth in control rats, each of the elemental diets and the diet containing intact casein in place of hydrolyzed casein was beneficial in promoting less body weight loss during the 3 d after 5-fluorouracil injection. The same significant benefit was seen in absorptive activity measured in small intestine in vitro 3 d after the cytotoxic injury. Glutamine supplementation, however, did not confer any significant advantages, although it did cause significant elevation of muscle glutamine pools. This elevation was substantially less than the corresponding increase in muscle glycine content after dietary supplementation with glycine.

Patients’ experiences with home parenteral nutrition: a literature review

Aim The aim of this review is to summarise the literature relating to patients’ experiences with home parenteral nutrition (HPN). Method This literature review is based on searches of CINAHL, PubMed, Web of Knowledge and Web of Science for articles published between 1970 and 2013. Additional studies were included from Department of Health publications, NICE clinical guidance, UK patient support group with interests in HPN or intestinal failure (IF). Results Patients with severe IF have been successfully treated with HPN since the 1970s. Early published studies evaluated clinical outcomes such as catheter-related infections, metabolic complications, thrombosis of the catheterised vein and liver impairment. Since the 1980s questionnaire studies were used to evaluate the quality of life (QoL) of patients treated with HPN. These early studies used QoL assessment tools which were not validated for patients treated with HPN. Internationally, there were published qualitative research studies which explored the experiences of patients treated with HPN. Conclusions The long-term outcome of patients treated with HPN continues to attract research interest. The review of the literature did not identify any published qualitative studies on the experiences of patients treated with HPN in the UK, suggesting a gap in the research. The UK National Health Service advocates a patient-centred approach for service design and delivery in primary and secondary care. This literature review has highlighted opportunities for qualitative research into the experiences of patients living with HPN to achieve better understanding and awareness of the rehabilitation of these patients.

Characterisation of the effects of potassium channel modulating agents on mouse intestinal smooth muscle

The actions of agents which modulate ATP‐sensitive potassium (KATP) channels in excitable cells were investigated in an in‐vitro preparation of mouse ileum from which the mucosa was removed. A range of potassium channel openers of diverse structure, cromakalim (0.1–100 μM), pinacidil (0.1–200 μM) and its analogue P1060 (0.1–200 μM), SDZ PCO400 ((‐)‐(3S,4R)‐3,4‐dihydro‐3‐hydroxy‐2,2‐dimethyl‐4‐(3‐oxo‐cyclopent‐1‐enyloxy)‐2H‐1‐benzopyran‐6‐carbonitrile) (0.3–60 μM), caused concentration‐related reduction in twitch height of electrical field stimulated ileum. P1060 and SDZ PCO400 were the most potent agents; diazoxide (0.1–100 μM) was without effect. The order of inhibitory potency, based on EC50 values (concentration of a relaxant producing 50% of the maximum inhibition of twitch) was: P1060 = SDZ PCO400 > cromakalim > pinacidil. The relaxant effect of the potassium channel openers was antagonised by the sulfonylureas glibenclamide (0.1‐1.0 μM) and glipizide (3–30 μM) but the nature of the antagonism differed. Antagonism of P1060 and SDZ PCO400 by glibenclamide appeared to be competitive whereas the antagonism of relaxation induced by cromakalim and pinacidil was apparently not competitive. Both phentolamine (1–10 μM) and tolbutamide (100–300 μM) showed competitive antagonism of the actions of pinacidil while yohimbine (1–20 μM) did not antagonise relaxation and appeared to have actions at sites other than the KATP channel in this preparation. The relative effectiveness of the antagonists on pinacidil‐induced relaxation was found to be: glibenclamide >phentolamine >tolbutamide >yohimbine, which is in agreement with studies in other tissues. The results show that many structurally diverse potassium channel openers are potent relaxants of mouse ileum. These observations are consistent with the existence of ATP‐dependent K+ channels in murine intestinal muscle which, however, differ somewhat in properties from those reported for vascular muscle and pancreatic β‐cells.

Evaluation of the pinhole pupillometer

Evaluation of pupil diameter is used in many clinical and research fields to aid diagnosis of neurological disorders and to monitor pharmacological effects upon the eye. Methods used to determine pupillary diameter have evolved from simple scale measurements to much more complex systems, supposedly improving accuracy and repeatability. However, many techniques are restricted to the consulting room or research laboratory due to the size of the equipment, its cost, or the expertise required.

Patients' experiences with home parenteral nutrition: A grounded theory study

BACKGROUND & AIMS Parenteral nutrition (PN) provides nourishment and hydration as an intravenous infusion to patients with intestinal failure (IF). The aim of the study is to generate theory that explains the experiences of adult patients living with home parenteral nutrition (HPN) and complex medication regimens. METHODS A grounded theory methodology was used to explore the experiences of twelve patients receiving HPN. A semi-structured interview was conducted and recorded in each participants home setting. Each interview was transcribed verbatim. The simultaneous process of data collection and analysis was followed reflecting the principles of the constant comparative approach. RESULTS A total of 15 patients gave written consent, with 12 of them agreeing to be interviewed. All the participants had previously undergone surgery as a result of chronic ill health or sudden illness. Analysis revealed two core categories: stoma and HPN, and these were supported by the subcategories: maintaining stoma output, access to toilets, managing dietary changes, maintaining the HPN infusion routine, access to technical help to set up an HPN infusion, mobility with HPN equipment and general health changes. The strategy of living with loss was demonstrated by all the participants, and this was supported by the action strategies of maintaining daily activities and social interactions. CONCLUSIONS This study generates new understanding and insight into the views and experiences of patients receiving HPN in the UK. The findings from these participants have been shown to resonate with the Kubler-Ross Model [1] of the five stages of grief. The theory of living with loss was generated by the use of a grounded theory methodology. This small scale exploratory study reveals opportunities for improvements in practice to be considered by the nutrition support team (NST) and other healthcare professionals involved in the patients hospital stay prior to discharge on HPN.