A complicated simple fall--an atypical case of serogroup Y meningococcal pneumonia with secondary septicaemia and literature review.

An elderly lady was admitted for pain management and rehabilitation following a fall. During her stay she developed a new heart murmur and sepsis. Subacute bacterial endocarditits was excluded, empirical ciprofloxacin was initiated and later converted to aztreonam with gentamicin for clinical deterioration. Subsequent investigations revealed meningococcal Y septicaemia secondary to pneumonia, with a possible oropharynx focus. Upon discharge she had returned to baseline state. The case reflects an unusual and increasing cause of pneumonia. A steady increase of infective serogroup Y isolates over the past 12-years in England, with tendency towards elderly makes it a significant differential among the general medical population. This trend corresponds with the US, but is yet unknown whether to be a periodic cycle or true change in dominance and, or, virulence among serogroups. If the latter were true, it would support the inclusion of serogroups beyond menigitides C in the vaccination program.

The role of continuous subcutaneous insulin infusion therapy in patients with diabetic gastroparesis.

AIMS/OBJECTIVE: To describe the effectiveness of continuous subcutaneous insulin infusion (CSII) in patients with symptomatic diabetic gastroparesis and unstable glycaemic control. METHODS: Data from 26 patients with symptomatic diabetic gastroparesis and unstable glycaemic control using multiple-dose insulin (MDI) regimens, and subsequently managed with CSII, were analysed. RESULTS: Following initiation of CSII, the median length of inpatient bed days associated with hospital admissions related to gastroparesis and glycaemic instability was reduced from 8.5 (range 0-144) days patient( -1) year( -1) prior to CSII to 0 (range 0-15) days patient( -1) year( -1). The median HbA(1c) reduction with CSII was 1.8% (22 mmol/mol; p < 0.05). The median capillary blood glucose (CBG) with CSII was significantly lower than with MDI: 7.7 mmol/l (range 3.8-15.4 mmol/l) vs 9.8 mmol/l (range 2.3-27 mmol/l), respectively, p < 0.001. Glycaemic variability with CSII was significantly reduced compared with MDI: CBG CV 0.37 vs CV 0.53, respectively, p < 0.001. CONCLUSIONS/INTERPRETATION: CSII therapy in patients with diabetic gastroparesis results in significant improvement in glycaemic control and reductions in glycaemic variability and number of hospital inpatient bed days.

Protein conformational stability in the hydrofluoroalkane propellants tetrafluoroethane and heptafluoropropane analysed by Fourier transform Raman spectroscopy.

Due to the inherent structural instability of proteins, development of chlorofluorocarbon (CFC) free metered dose inhalers (MDIs) containing these biomolecules is beset with numerous challenges. In assessing the conformation of proteins in any medium, both secondary and tertiary structures need to be elucidated. This study uses Fourier transform (FT-) Raman spectroscopy to probe protein conformational stability in hydrofluoroalkane (HFA) propellants. Assignments of molecular modes for lysozyme as a solid and in aqueous solution, and for the first time, HFAs tetrafluoroethane (HFA 134a) and heptafluoropropane (HFA 227) are given. The Raman spectra provided molecular structural information on the peptide backbone, disulfide bonds and C-C stretching vibrations of hen egg lysozyme, enabling the secondary conformation of protein in HFA propellants to be determined; structural integrity of this robust model protein was maintained in both propellants. These results demonstrate that FT-Raman may be a useful tool for the optimisation of protein MDI formulations.

Solution and adsorption behaviour of lecithin surfactants in CFC suspensions: a light scattering study in aerosol propellants.

The behaviour of the lecithin Epikuron 200 was studied in solution in a chlorofluorocarbon (CFC) aerosol propellant (P113) using light scattering to determine the micellar structure as a function of temperature. At room temperature Epikuron 200 formed micelles with a radius of approximately 25 nm. The radius increased with decreasing temperature until a phase boundary was reached at 15-16 degrees C, below which the micellar radius increased rapidly to 150-250 nm. This was accompanied by a large increase in the viscosity and turbidity of the solution. We consider that this behaviour is due to the formation of large wormlike micelles similar to those reported for lecithin in cyclohexane. The adsorption of Epikuron 200 on salbutamol sulphate was measured over this temperature range. The adsorbed amount of Epikuron 200 increased with decreasing temperature, and the hemimicelle concentration decreased rapidly at a temperature corresponding to the threshold for the formation of wormlike micelles. It is likely that these structures do form in CFC-MDI systems (particularly during cold-fill formulation), and that the structure of the adsorbed surfactant layer changes at low temperature. This may have implications for the formulation of stable aerosol suspensions.

Measurement of markers of osteoclast and osteoblast activity in patients with acute and chronic diabetic Charcot neuroarthropathy.

Excess osteoclast activity is believed to be responsible for the early bone changes associated with Charcot neuroarthropathy in diabetes mellitus. Markers of osteoclast and osteoblast activity were measured in four groups of patients: 16 with an acute Charcot foot, 16 with a chronic Charcot foot, 10 diabetic controls, and 10 non-diabetic controls. Serum carboxyterminal telopeptide of type 1 collagen (1CTP), a marker of osteoclastic bone resorption, was significantly raised in the dorsal venous arch of the acute Charcot foot, 6.1 +/- 1.5 microg l(-1) (mean +/- SD) compared with the chronic Charcot foot 4.1 +/- 1.4, diabetic controls 3.3 +/- 1.4, and non-diabetic controls 2.8 +/- 1.4, p < 0.0001. This local increase in 1CTP was also reflected systemically in a study subgroup of 6 patients with acute Charcot neuroarthropathy, in whom peripheral antecubital vein 1CTP was 9.2 +/- 2.6 compared with 9.0 +/- 3.1 in the foot. In 6 chronic Charcot neuroarthropathy patients, foot (3.8 +/- 1.3) and systemic (4.0 +/- 1.5) 1CTP values were similar. Serum procollagen carboxyterminal propeptide (P1CP), an indicator of osteoblastic bone formation, was not significantly different between the feet of patients with acute Charcot neuroarthropathy 112 +/- 1.5 microg l(-1), patients with chronic Charcot neuroarthropathy 109 +/- 1.5 microg l(-1), diabetic controls 93.5 +/- 2.3 microg l(-1), and non-diabetic controls 90.1 +/- 1.5 microg l(-1). These results suggest that the acute Charcot foot demonstrates excess osteoclastic activity without concomitant increase in osteoblastic function. This may be important in its pathogenesis.

Screening for diabetic retinopathy in primary care: retinal photography alone can be used efficiently and effectively to exclude those with sight threatening lesions.

BACKGROUND: Good screening performance of retinal photography and ophthalmoscopy together in screening for diabetic retinopathy in primary care have been reported. This study reanalysed the data to evaluate the screening performance of photography alone. METHODS: One thousand and ten patients screened by fundal photography and ophthalmoscopy were studied retrospectively. Fundal photographs were quality graded with poor quality pictures being excluded from the analysis. Each patient was reviewed initially by both retinal photographs and ophthalmoscopy by an ophthalmologist, the "gold standard". Six months later the fundal photographs were reviewed and reported in a blinded manner by the ophthalmologist. RESULTS: Two thousand and fourteen photographs were obtained, of which 162 (8%) had to be excluded because of poor quality. On review of the remaining 1852 photographs in isolation, of 77 cases of severe retinopathy as determined by the "gold standard", 67 had severe changes on photography--detection rate 87%. Of the 1775 cases without sight threatening retinopathy only five were judged to have sight threatening changes on photography--false positive rate 0.3%. Considering sight threatening and background retinopathy together, the detection rate was 69% (257 of 375) and the false positive rate 1.6% (23 of 1477). CONCLUSION: Good quality fundal photographs alone seem specific enough to screen for sight threatening diabetic retinopathy, but will underdetect background retinopathy.

Characterization of surfactant effect on aggregates in model aerosol propellent suspensions.

A novel technique of rheometry combined with image analysis to study model aerosol suspensions used in inhalation technology has been used. The role of surfactants in the stability and aggregation of such suspensions was also investigated. Addition of increasing concentrations of sorbitan monooleate (Span 80) to suspensions of micronized polar solids in model CFC suspensions caused marked changes in aggregate morphology and suspension stability. The aggregate behaviour was characterized in a modified constant stress rheometer by use of image analysis techniques, allowing the measurement of particle size, elongation and fractal dimension as a function of shear stress. This method was used to study the effect of Span 80 on suspensions of lactose and salbutamol sulphate in P113. Lactose suspensions showed a gradual reduction in aggregate size, and more spherical structure, with increasing surfactant concentration. Salbutamol sulphate suspensions displayed a more prominent transition from an aggregated state to a weakly aggregated state at 0.02% w/w surfactant. Both suspensions were disaggregated by shear, the resulting fractal properties of the aggregates in shear demonstrating the increased particle mobility caused by the surfactant.

The effect of surfactant and solid phase concentration on drug aggregates in model aerosol propellent suspensions.

The effect of increasing solid phase concentration on the morphology and flocculation rate of model aerosol suspensions has been investigated. Suspensions of micronized salbutamol sulphate and lactose in trichlorotrifluoroethane (P113) were studied under conditions of increasing shear stress. By use of image analysis techniques, measurement of aggregate size, fractal dimension and rate of aggregation was performed. The effect of the surfactant sorbitan monooleate on morphology and flocculation rate was also studied. Increased solid phase concentration caused an increase in the rate of aggregation and average aggregate size at a given value of shear stress. Surfactant addition retarded the aggregation rate, and caused a shift from a diffusion-limited cluster aggregation to a reaction-limited cluster aggregation mechanism. The aggregate profiles showed a corresponding change from rugged and crenellated without surfactant, to increasingly smooth and Euclidian with increasing surfactant concentration. The morphological changes were characterized by a decrease in the average boundary fractal dimension which also correlated well with the corresponding reduction in aggregation rate.

The splanchnic circulation and postural hypotension in diabetic autonomic neuropathy.

Postural hypotension results from sympathetic failure to cause superior peripheral vasoconstriction. The importance of the splanchnic circulation was studied by measuring mesenteric artery blood flow with duplex Doppler scanning. Nine normal and 9 Type 1 diabetic controls were compared to 8 Type 1 patients with autonomic neuropathy whose pressure fell 40-113 mmHg (range) on tilting. Measurements were made supine and after vertical tilt, fasting without insulin and after a 550 kcal meal. Superior mesenteric artery diameter decreased on tilting in normal controls but not in diabetic control or neuropathy groups (supine vs tilted: controls. 6.3 +/- 0.9 to 5 +/- 0.9 mm, p = 0.004, diabetic controls: 6.0 +/- 0.6 to 6.0 +/- 1.0 mm, and neuropathy group: 6.4 +/- 0.9 to 5.6 +/- 0.9 mm), but proportional blood flow changes were similar in all subjects (controls: 407 +/- 154 to 255 +/- 67 ml min-1 (-31%, p = 0.03), diabetic controls: 379 +/- 140 to 306 +/- 149 ml min-1 (-8%, p = 0.28), neuropathy group: 639 +/- 371 to 435 +/- 142 ml min-1 (-23%, p = 0.10). Postprandially supine superior mesenteric artery flow increased in all subjects but this did not affect the degree of systolic blood pressure drop on tilting (fasting vs postprandial blood flow: controls: 407 +/- 154 to 775 +/- 400 ml min-1 (p = 0.04), diabetic controls: 379 +/- 140 to 691 +/- 262 ml min-1 (p = 0.01), neuropathy group: 639 +/- 371 to 943 +/- 468 ml min-1 (p < 0.06)). The similarity of superior mesenteric artery responses to tilting in the three groups, and the lack of exacerbation of postural hypotension in the presence of postprandial hyperaemia indicates that control of splanchnic blood flow is less important in the aetiology of diabetic autonomic postural hypotension than previously thought.

Postural hypotension in diabetic autonomic neuropathy: a review.

Postural hypotension is uncommon in diabetes but can occur secondary to autonomic neuropathy. Symptoms are rare and include dizziness, weakness, blurred vision, tiredness, and loss of consciousness. The pathophysiology of postural hypotension is not clear, but changes in intravascular volume, heart rate, cardiac output, and splanchnic vascular resistance are similar in patients and controls. The main factors producing hypotension are a blunted catecholamine response to standing, and failure of lower limb vascular resistance to increase adequately. Treatment for symptomatic postural hypotension includes avoidance of dehydration, adequate salt intake, and fludrocortisone. Other treatments are reviewed but are less helpful. Patients with postural hypotension have intermittent symptoms over the years but rarely become severely disabled. They have a poorer prognosis than patients with symptomatic autonomic neuropathy without postural hypotension.

Lower limb venous pressure in diabetic neuropathy.

OBJECTIVE: Distended turgid veins have been noted in the feet of patients with diabetic neuropathy. This study assessed the supine venous pressure and its correlation with diabetic neuropathy and arteriovenous (AV) shunting in the feet of type I and type II diabetic subjects. RESEARCH DESIGN AND METHODS: Seventeen patients with chronic Charcot joints, 11 patients with a history of neuropathic foot ulceration, 14 diabetic control subjects, and 11 normal control subjects were studied. Neuropathy was assessed by vibration and thermal thresholds and standard cardiovascular autonomic neuropathy tests. Supine venous pressure was measured by insertion of a 21-gauge needle connected to a strain gauge manometer into the veins on the dorsum of the foot. Venous PO2 was used as a measure of AV shunting. RESULTS: Venous pressure was raised in the group with chronic Charcot joints (18.9 +/- 4.2 mmHg, P < 0.001 vs. the diabetic control group [11.3 +/- 2.6 mmHg]), the normal control group (12.3 +/- 2.3 mmHg, mean +/- SD), and the diabetic group with a history of neuropathic foot ulceration (16.0 +/- 3.7 mmHg, P = 0.008 vs. diabetic control subjects and P = 0.04 vs. normal control subjects), with a maximum of 28 mmHg. Venous pressure was correlated with heart rate variation to deep breathing, r = -0.61 (P = 0.001), vibration threshold, r = 0.56 (P = 0.001), Valsalva ratio, r = -0.64 (P -= 0.001), warm threshold, r = 0.69 (P = 0.001), and venous PO2, r = 0.43 (P = 0.02). There was no correlation with skin temperature, duration of diabetes, age, HbA1c, random blood glucose, ankle/brachial Doppler index, height, or serum creatinine. CONCLUSIONS: Venous pressure is much higher in the neuropathic diabetic limb and is correlated with the severity of neuropathy and with AV shunting.

Rheology of model aerosol suspensions.

The rheological properties of model aerosol suspensions at phase fractions of less than 5% w/v (phase ratio of 0.05) were investigated. The rheological profiles of lactose in chloroform, lactose in trichlorofluoromethane (Propellent 11, P11), and salbutamol sulphate in P11 have been investigated in the presence and absence of lecithin, a phospholipid surface-active agent. The relative viscosities of these disperse systems correlated with the increasing disperse phase fractions and the addition of surfactant was found to reduce these viscosities to a relative viscosity of approximately 1.0. The results suggest that the relative viscosity is a useful indicator of flocculation in these systems, and may be valuable in formulation development.