Heart rate variability: response following a single bout of interval training.

We investigated the effect of exercise on heart rate variability by analysing the heart rate power spectrum prior to, and 1 and 72 h following, an interval training session. Subjects initially performed a graded test to exhaustion to determine maximal oxygen uptake (VO(2) max) and the running speed at which VO(2) max was first attained (vVO(2) max). The training session was completed on a separate day and comprised six 800 m runs at 1 km x h (-1) below vVO(2) max. Prior to the training session (pre), 1 h following the training session (+ 1h), and 72 h following the training session (+ 72 h), subjects sat quietly in the laboratory for 20 min whilst breathing frequency was maintained at 12 breath x min (-1). Cardiac cycle R-R interval data were collected over the final 5 min of each 20 min period and analysed by means of autoregressive power spectral analysis to determine the high frequency (HF) and low frequency (LF) components of heart rate variability. Heart rate was higher, and the standard deviation of the R-R intervals was lower, at + 1 h than for pre or + 72 h (p < 0.05). The HF and the LF components of heart rate variability were also lower (p < 0.05) for + 1 h than for pre or + 72 h when the data were expressed in ms(2). However, no changes in the LF:HF ratio were observed, and the changes in the HF and LF components disappeared when the data were expressed as a fraction of the total power. Whilst these findings illustrate the importance of controlling the timing of exercise prior to the determination of heart rate variability, the time course of the post-exercise heart rate variability response remains to be quantified.

Non-albicans Candida spp. causing fungaemia: pathogenicity and antifungal resistance.

Non-albicans Candida (NAC) species cause 35-65% of all candidaemias in the general patient population. They occur more frequently in cancer patients, mainly in those with haematological malignancies and bone marrow transplant (BMT) recipients (40-70%), but are less common among intensive care unit (ITU) and surgical patients (35-55%), children (1-35%) or HIV-positive patients (0-33%). The proportion of NAC species among Candida species is increasing: over the two decades to 1990, NAC represented 10-40% of all candidaemias. In contrast, in 1991-1998, they represented 35-65% of all candidaemias. The most common NAC species are C. parapsilosis (20-40% of all Candida species), C. tropicalis (10-30%), C. krusei (10-35%) and C. glabrata (5-40%). Although these four are the most common, at least two other species are emerging: C. lusitaniae causing 2-8% of infections, and C. guilliermondii causing 1-5%. Other NAC species, such as C. rugosa, C. kefyr, C. stellatoidea, C. norvegensis and C. famata are rare, accounting for less than 1% of fungaemias in man. In terms of virulence and pathogenicity, some NAC species appear to be of lower virulence in animal models, yet behave with equal or greater virulence in man, when comparison is made with C. albicans. Mortality due to NAC species is similar to C. albicans, ranging from 15% to 35%. However, there are differences in both overall and attributable mortality among species: the lowest mortality is associated with C. parapsilosis, the highest with C. tropicalis and C. glabrata (40-70%). Other NAC species including C. krusei are associated with similar overall mortality to C. albicans (20-40%). Mortality in NAC species appears to be highest in ITU and surgical patients, and somewhat lower in cancer patients, children and HIV-positive patients. There is no difference between overall and attributable mortality, with the exception of C. glabrata which tends to infect immunocompromised individuals. While the crude mortality is low, attributable mortality (fungaemia-associated mortality) is higher than with C. albicans. There are several specific risk factors for particular NAC species: C. parapsilosis is related to foreign body insertion, neonates and hyperalimentation; C. krusei to azole prophylaxis and along with C. tropicalis to neutropenia and BMT; C. glabrata to azole prophylaxis, surgery and urinary or vascular catheters; C. lusitaniae and C. guilliermondii to previous polyene (amphotericin B or nystatin) use; and C. rugosa to burns. Antifungal susceptibility varies significantly in contrast to C. albicans: some NAC species are inherently or secondarily resistant to fluconazole; for example, 75% of C. krusei isolates, 35% of C. glabrata, 10-25% of C. tropicalis and C. lusitaniae. Amphotericin B resistance is also seen in a small proportion: 5-20% of C. lusitaniae and C. rugosa, 10-15% of C. krusei and 5-10% of C. guilliermondii. Other NAC species are akin to C. albicans-susceptible to both azoles and polyenes (C. parapsilosis, the majority of C. guilliermondii strains and C. tropicalis). Therefore, 'species directed' therapy should be administered for fungaemia according to the species identified-amphotericin B for C. krusei and C. glabrata, fluconazole for other species, including polyene-resistant or tolerant Candida species (C. lusitaniae, C. guilliermondii). In vitro susceptibility testing should be performed for most species of NAC in addition to removal of any foreign body to optimize management.

Invasive disease due to extended spectrum beta-lactamase-producing Klebsiella pneumoniae in a neonatal unit: the possible role of cockroaches.

We recently experienced an outbreak of nosocomial disease due to extended spectrum beta-lactamase-producing Klebsiella pneumoniae in a neonatal unit infested with cockroaches. Organisms isolated from cockroaches were indistinguishable by pulsed-field gel electrophoresis from those colonizing infants or causing clinical disease using. Cockroach elimination together with standard infection-control measures resulted in control of the outbreak. We suggest cockroaches are possible vectors of pathogenic bacteria in the hospital environment.

Early investigation and initiation of therapy for invasive pulmonary aspergillosis in leukaemic and bone marrow transplant patients.

Invasive fungal infections are an increasingly common problem in cancer patients and in other vulnerable groups. Invasive pulmonary aspergillosis (IPA) in the neutropenic host presents particular challenges in terms of diagnosis and therapy. Against the background of a recognized problem of invasive aspergillosis in haematology/oncology patients treated at the Christie Hospital, we undertook a prospective study in patients at risk for IPA. The aim of the study was to improve outcome by using the linked strategies of first, early diagnosis, and secondly, early aggressive therapy with a lipid-associated formulation of amphotericin B, amphotericin B colloidal dispersion ('Amphocil'). Early investigation comprised the use of high-resolution computerized tomography scanning of the thorax and fibreoptic bronchoscopy to obtain bronchoalveolar lavage specimens, processed using conventional detection and culture methods. Using this approach, the incidence of proven or probable IPA in patients with acute leukaemia was 9%. Prompt initiation of amphotericin B colloidal dispersion therapy led to a successful outcome in 11 of 13 patients, compared with a mortality of 100% in historical controls.

PCR-ELISA for the early diagnosis of invasive pulmonary aspergillus infection in neutropenic patients.

AIM: To evaluate a newly developed aspergillus mitochondrial gene PCR-ELISA assay for the early diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients. METHODS: The aspergillus mitochondrial gene was chosen for the amplification target for use with a solution hybridisation assay with colorimetric end stage detection in microtitre plate format (PCR-ELISA). The study group comprised neutropenic patients undergoing febrile episodes not responding to standard antibacterial antibiotics. Patients underwent computed tomography and bronchoscopy. Bronchoalveolar lavage (BAL) fluids were examined by culture and PCR. RESULTS: The aspergillus mitochondrial gene PCR-ELISA was both sensitive (100%) and specific (100%) for IPA in neutropenic patients. All 12 patients with definite or probable IPA had PCR positive BAL fluids. None of the patients with undiagnosed or confirmed infections of other aetiologies were mitochondrial PCR positive. Speciation based upon amplicon size difference was possible. CONCLUSIONS: Aspergillus mitochondrial DNA PCR-ELISA on BAL fluid is useful in the early diagnosis of IPA in neutropenic patients alone or, potentially, as an indication for thoracic computed tomography.

Evaluation of routine surveillance urine cultures in rehabilitation ward admissions: a prospective study.

OBJECTIVE: To assess the value of routine surveillance urine cultures and the prevalence of bacteriuria in the younger disabled patient subgroup admitted to the younger disabled unit (YDU). Most of these patients do require some form of assisted urinary drainage. DESIGN: A prospective study of 50 consecutive patients admitted to the YDU for short-term rehabilitation were screened by obtaining relevant clinical details and urine specimens at weekly intervals. INTERVENTIONS: Relevant clinical details were retrieved from case notes and minimum of two urine specimens were collected for culture from each patient. MAIN OUTCOME MEASURES: Presence of positive urine culture, sensitivity and clinical symptoms were recorded. RESULTS: Out of 50 patients studied, 27 were on some form of urinary drainage. Urine culture and sensitivity results were positive in 35 patients. Cultures were predominantly mixed growth or coliform organisms. CONCLUSIONS: Majority of patients were admitted with asymptomatic bacteriuria. There was no evidence to suggest that these short-term rehabilitation patients acquired nosocomial uropathogens and routine surveillance urine cultures were not particularly useful in this setting.

Fatal Candida tropicalis fungaemia in a leukaemic patient receiving fluconazole prophylaxis.

A 50-year-old man with newly diagnosed acute myeloid leukaemia developed breakthrough candidaemia while receiving fluconazole as antifungal prophylaxis during remission-inducing chemotherapy. Candida tropicalis was isolated; the strain was resistant to fluconazole on in vitro sensitivity testing, a phenomenon which has not been previously reported in this setting.

A silicon micromachined device for use in blood cell deformability studies.

An application of silicon micromachining to the analysis of blood cell rheology is described. The system, based upon a micromachined flow cell, provides a specific measurement of each cell in a statistically significant population in terms of both flow velocity profile and an index of cell volume while the cells flow through an array of microchannels. The rationale, design, and fabrication of the silicon micromachined flow cell is discussed. Interrelated considerations determining the design of the associated fluidic, mechanical, imaging, and real-time image analysis subsystems are examined. Sample data comparing normal and iron deficiency anaemic blood are presented to illustrate the potential of this technique.

Glycosylated plasma protein measurement by a semi-automated method.

A semi-automated method for determination of glycosylation of plasma proteins using the thiobarbituric acid method is described. Plasma samples (100 microL) and a plasma pool used as a secondary standard were incubated in 0.3 M oxalic acid at 100 degrees C for exactly 2 h. The hydroxymethyl furfural released and the total protein were measured concurrently on a Technicon AAII Autoanalyzer. Addition of 10 or 20 mmol glucose to plasma samples caused a minimal increase in the measured glycosylated protein. Within-batch and between-batch coefficients of variation were 3.1% and 4.9% respectively. The mean glycosylated protein levels for 52 normals and 48 maturity-onset diabetics were (+/- 1SD) 0.96 +/- 0.13 and 1.75 +/- 0.32 nmol HMF/mg protein/2 h incubation.

Severe retinopathy and mild carbohydrate intolerance: possible role of insulin deficiency and elevated circulating growth hormone.

8 patients with severe progressive diabetic retinopathy despite continued mild carbohydrate intolerance on diet therapy alone were studied; each patient had presented initially with visual deterioration and none had experienced hyperglycaemic symptoms. By comparison with 8 carefully matched diet-treated diabetics without retinopathy, the retinopathy patients had increased circulating growth hormone levels and relative insulin deficiency. Several other factors of possible importance in the aetiology of microangiopathy, including circulating intermediary metabolites, platelet aggregation, blood viscosity, and lipids were similar in the two groups. It is possible that hypoinsulinaemia together with growth hormone excess may contribute to the development of eye disease in these patients with otherwise mild diabetes.

Loss of diabetic control and increased protein glycosylation following minor intercurrent infections.

To investigate the effect of intercurrent infections, 30 insulin-dependent diabetics and 12 normal subjects were followed prospectively during one winter, with short-term periods of control being assessed by the degree of glycosylation of plasma proteins. Eight diabetics and 7 normal subjects developed an intercurrent infection. During stable control, the diabetics had a mean +/- 1 S.D. glycosylation of 0.90 +/- 0.06 nmol HMF/mg protein/2 hour incubation, compared with the normal subjects of 0.63 +/- 0.04 nmol HMF/mg protein/2 hour. Following infection, there was no increase in glycosylated plasma protein in the normal subjects, but the diabetics increased at 3 and 6 days to 1.07 +/- 0.17 and 1.12 +/- 0.17 nmol HMF/mg protein/2 hour respectively (p less than 0.05 and p less than 0.01). This was similar to levels (1.09 +/- 0.20 nmol HMF/mg protein/2 hour) found in 12 diabetic subjects admitted to hospital because of marked loss of control with ketonuria. The marked protein glycosylation effect of temporary loss of glucose control following 'minor' intercurrent infections suggests that more attention should be paid to diabetic control during brief illnesses.

Abnormal endothelial release of fibrinolytic activity and fibronectin in diabetic microangiopathy.

Endothelial cell function in Type 1 (insulin-dependent) diabetic patients, both with and without retinopathy, was assessed by measuring the plasma fibrinolytic activity and fibronectin after 10 min venous stasis induced by a sphygmomanometer cuff. After venous stasis, diabetic subjects with proliferative retinopathy had fibrinolytic responses (median 0.13 increasing to 0.26 U/ml) in the low normal range, which were significantly less (p less than 0.005) than control subjects (0.17-0.68 U/ml) and diabetic patients with minimal retinopathy (0.16-0.68 U/ml; p less than 0.01). Plasma fibronectin levels were similar in the different groups, but after venous stasis, rose significantly in the diabetic patients, both in those with proliferative retinopathy (mean 317-399 micrograms/ml; p less than 0.002) and without retinopathy (312-371 micrograms/ml; p less than 0.05) but not in normal subjects (304-333 micrograms/ml). These changes in fibrinolytic activity and fibronectin were independent of blood glucose, glycosylated haemoglobin, or indices of sensory or autonomic nerve function. These disturbances of endothelial function, together with known abnormalities of haemostatic variables and microvascular reflexes, might convert a usually temporary obstruction of capillary blood flow into a pathological capillary closure, and might contribute to the inexorable progression of advanced diabetic microangiopathy in spite of good diabetic control.

Effect of a long-acting octapeptide analogue of somatostatin on growth hormone and pancreatic and gastrointestinal hormones in man.

1. The biochemical specificity and duration of action of a single 5 mg subcutaneous dose of des-AA1,2,4,5,12,13-D-Trp8-somatostatin were evaluated in eight patients with symptomatic pancreatic endocrine tumours. 2. There was a reduction by more than 50% for at least 10 h in plasma concentrations of growth hormone, glucagon, gastrin and motilin and for 4--5 h in plasma insulin, pancreatic polypeptide, gastric inhibitory polypeptide and enteroglucagon. 3. This study shows that this octapeptide analogue of somatostatin, like somatostatin itself, lacks specificity in the hormones it suppresses. However, its prolonged duration of action against several hormones when given subcutaneously suggests that it may be of therapeutic use in a number of disease states where excessive plasma concentrations of one or more of these hormones occur.