Prevalence and short-term changes of cognitive dysfunction in young ischaemic stroke patients.

BACKGROUND AND PURPOSE: Information on the prevalence and course of post-stroke cognitive impairment in young stroke patients is limited. The aim was to assess a consecutive sample of acute young ischaemic stroke patients (18-55 years) for the presence and development of neuropsychological deficits. METHODS: Patients prospectively underwent a comprehensive clinical and cognitive assessment, examining general cognitive function, processing speed, attention, flexibility/executive function and word fluency within the first 3 weeks after hospital admission (median assessment at day 6) and at a 3 months' follow-up (FU). Cognitive dysfunction was defined in comparison to age-standardized published norms. RESULTS: At baseline (N = 114), deficits were highly prevalent in processing speed (56.0%), flexibility/executive function (49.5%), attention (46.4%) and general cognitive function (42.1%). These frequencies were comparable for those with FU assessment (N = 87). In most domains, cognitive performance improved within 3 months, except for word fluency. However, in about one-third of patients, cognitive deficits (as defined by 1.5 standard deviations below the standardized mean) were still present 3 months after stroke. At FU, 44.0% were impaired in the domain flexibility/executive function, 35.0% in processing speed and 30.0% in attention. CONCLUSIONS: The high prevalence of cognitive deficits in acute young patients with ischaemic stroke highlights the importance of early post-stroke cognitive assessment to capture a patient's dysfunction in a comprehensive manner and to offer adequate rehabilitation. The role of factors which promote neuropsychological deficits needs further exploration.

Nutritional Ketosis and photobiomodulation remediate mitochondria warding off Alzheimer's disease in a diabetic, ApoE4+ patient with mild cognitive impairment: A case report.

Alzheimer's Disease (AD) is a neurodegenerative progressive disorder for which there is currently no cure. Recent research demonstrates a robust correlation between type-2 diabetes mellitus (T2DM) and the development of MCI and AD, now referred to as type-3 diabetes. Both AD and T2DM, as metabolic pathologies, can be traced to the level of mitochondrial function. The metabolic hypothesis suggests that the cause of AD might be rooted in mitochondrial dysfunction accompanied by fuel shortage in the brain. Although glucose is known to be the deferred source of fuel for cells, ketone bodies have been observed to provide metabolically compromised brain cells with an alternative fuel source, bypassing deficiencies in GLUT transport due to increased insulin resistance. By keeping glucose and insulin levels low to allow for the production of ketones, there is evidence that mitochondrial function will be restored and cognition/memory improved. Further, visible red or near-infrared (NIR) light has been shown to heal and stimulate damaged tissue by interacting with the mitochondria to restore function. This case study evaluates the effects of a 10-week clinically prescribed ketogenic nutrition protocol combined with transcranial photobiomodulation (PBM) with a 59-year-old male, heterozygous ApoE4 carrier, with a dual diagnosis of mild AD and an 11 year history of insulin dependent type 2 diabetes (T2DM). Statistically significant results reflect an 83% reduction in HOMA-IR; 64% decrease in the triglyceride/HDL ratio; HgA1c reduction from 9.44% to 6.4%; 57% decrease in VLDL and triglycerides; and normalized cognition as measured via the MoCA (Montreal Cognitive Assessment), 26/30 post intervention.

Symptomatic stenosis of the vertebrobasilar arteries: results of extra- and intracranial stent-PTA.

BACKGROUND AND PURPOSE: About half of all transient ischaemic attacks (TIAs) or strokes in the posterior circulation are caused by the arterial stenosis. The purposes of this study were to determine the safety of stent-assisted percutaneous transluminal angioplasty (stent-PTA) and its efficacy for the prevention of recurrent stroke in patients with symptomatic artery stenosis in the extra- and intracranial posterior circulation. METHODS: Forty-six patients with a previous stroke or TIA who received balloon-mounted coronary stents for vertebral artery origin stenosis (VAOS; 29 patients) or self-expanding nitinol stents for vertebrobasilar intracranial stenosis (VBIS; 17 patients) were followed-up for a mean of 24.1 (VAOS) and 12.7 (VBIS) months. RESULTS: When all cause morbidity/mortality within 30 days from stent-PTA and stroke or death from stroke in the treated vascular territory during the first 12 months of follow-up are combined, the incidence of periprocedural complications and disease progression for the first year is 10.3% in VAOS patients and 17.6% in the VBIS group. Vessel restenosis >/=50% was found in 52.0% of VAOS and in 32.1% of VBIS patients who completed 6 months follow-up. CONCLUSIONS: We observed a higher periprocedural complication rate for patients with VBIS and a higher rate of restenosis in VAOS patients after stent-PTA for symptomatic artery stenosis.

Evaluation of a vaccine passport to improve vaccine coverage in people living with HIV.

An increased risk of vaccine-preventable infections (VPIs) is seen in people living with HIV (PLWH), and current vaccine coverage and immunity is variable. Vaccine passports have the potential to improve vaccine coverage. The objective was to assess how successful a vaccine passport was in improving vaccine coverage in PLWH. Baseline immunity to VPIs was established in PLWH attending a single HIV clinic and vaccinations required were determined based on the BHIVA Vaccination Guidelines (2015). The passport was completed and the PLWH informed about additional vaccines they should obtain from primary care. After 6-9 months the passport was reviewed including confirmation if vaccines were given. PLWH satisfaction with the system was evaluated by a survey. Seventy-three PLWH provided sufficient data for analysis. At baseline significant proportions of PLWH were not immune/unvaccinated to the main VPIs, especially human papillomavirus, pneumococcus and measles. After the passport was applied immunity improved significantly (56% overall, p < 0.01) for most VPIs; however, full coverage was not achieved. The system was popular with PLWH. The passport was successful in increasing vaccination coverage although full or near-full coverage was not achieved. A more successful service would probably be achieved by commissioning English HIV clinics to provide all vaccines.

Short communication: Association analysis of microsatellites and Mycobacterium avium subspecies paratuberculosis antibody response in German Holsteins.

Paratuberculosis in ruminants is characterized by chronic granulomatous enteritis, resulting in persistent diarrhea and progressive wasting of cattle infected with Mycobacterium avium ssp. paratuberculosis (MAP). The disease occurs worldwide with high frequency, leading to growing economic losses in beef and dairy industries. The objective of this study was to investigate associations of microsatellites (BMC9006, BB704, BB705, BB717, BB719, BMS1617, BB702, and BOBT24) located near or within candidate genes involved in response mechanisms to paratuberculosis. Pedigree information existed for 4,686 German Holstein cows that had routinely been screened for MAP status using commercially available serum antibody ELISA test. The immunoglobulin G cutoff level was used to classify all animals as positive or negative for paratuberculosis. A total of 594 (12.7%) cows tested positive for paratuberculosis. The control group comprised 585 animals testing negative for MAP. Microsatellite BMC9006 had only 3 alleles (2 of which occurred at very low frequencies in the present data set) and was therefore not informative; the remaining microsatellites showed 3 to 12 alleles. Fisher's exact and chi2 tests revealed no significant differences in microsatellite allele frequencies between the 2 groups of German Holstein cows testing positive or negative for paratuberculosis.

Neuropathological studies on cycloate-induced neuronal cell death in the rat brain.

The herbicide cycloate (carbamothioic acid, ethyl(cyclohexyl)-S-ethyl ester) given as a single oral dose to rats, caused selective neuronal cell death in two regions in the rat forebrain, the pyramidal neurons of layers II-III throughout the pyriform cortex and in granule cells of the caudal ventro-lateral dentate gyrus. Male Alderley Park rats, 6-8-week-old, were given a single oral dose of either 0 or 2000 mg/kg cycloate and killed for neuropathological investigation 1, 2, 3, 7, 14 or 28 days after dosing, using a regime of perfusion fixation with modified Karnovsky's fixative, followed by routine paraffin embedding. Seven transverse levels of brain were examined from each rat. Cycloate-induced neuronal cell death was seen in the pyriform cortex 1 day after dosing and persisted through to Day 28, the lesion was more marked in the rostral compared to the caudal region of the pyriform cortex. Neuronal cell death was also observed in the ventro-lateral caudal dentate gyrus on Days 1-14, day after dosing. In the early stages, Days 1-3 and to a lesser extent Day 7, the neuronal cell death resembled apoptosis, characterized by condensation of nuclear material, cell shrinkage and strong cytoplasmic eosinophilia. By Days 14 and 28 and to a lesser extent Day 7, the cell death resembled necrosis, i.e. karyorrhectic nuclei with pale irregular cytoplasm. Microglial accumulation was associated with the neuronal cell injury. In control brains, an occasional apoptotic body was seen in both the pyriform cortex and dentate gyrus. Our results demonstrate that cycloate is a novel neurotoxicant, which following a single large oral dose induces a cell specific and highly localized forebrain lesion. The time course data analyzed temporally, suggests that cycloate may cause an up regulation of apoptosis in selected regions of the adult brain.

Does long-term culture favor normal clonogenic cells from interferon-treated patients with chronic myelogenous leukemia?

We have tested whether peripheral blood mononuclear cells (PBMNCs) from interferon (IFN)-treated patients may lose residual BCR-ABL sequence-positive progenitor cells when long-term cultured for 35 days on allogeneic stromal cells. IFN-treated patients have low white blood cell counts and a fair number of BCR-ABL-negative colony-forming cells in the peripheral blood. Particularly, IFN responders show increased numbers of normal hematopoietic cells. We have quantitatively analyzed progenitor cells in PBMNCs of IFN-treated patients by combining the clonogenic assay in semisolid medium with interphase fluorescent in situ hybridization (FISH). Thus, the identification is possible of the BCR-ABL status of colony-forming progenitor cells. In IFN-treated patients, the number of BCR-ABL-positive CFCs is considerably decreased and BCR-ABL-negative CFCs appear in the peripheral blood. We could show that after LTC for 35 days of the same PBMNCs on irradiated allogeneic normal stromal cells residual BCR-ABL sequence-positive CFCs were still present. In some cases the relative number of BCR-ABL sequence-positive CFCs was found to be increased after LTC. A minor proportion of blood samples from IFN-treated patients did not give rise to CFCs after LTC on allogeneic stromal cells (three of 10 patients). Inter- and intraindividual variations can be found with regard to loss or gain of BCR-ABL sequence-positive colonies after LTC. We conclude that early CML progenitor cells persist in the peripheral blood of IFN-treated patients and that a certain proportion may survive long-term culture.

Electrical alternans and the onset of rate-induced pulsus alternans during acute regional ischaemia in the anaesthetised pig heart.

OBJECTIVES: Electrical alternans and mechanical alternans are both associated with cardiac ischaemia and in the case of electrical alternans there is a strong link with serious ventricular arrhythmia. We elected to investigate the relationship between electrical and mechanical alternans in control and acutely ischaemic myocardium in the intact porcine heart to determine the nature of their interaction and in particular to determine if abnormal mechanical events play a role in arhythmogenesis as has been suggested in non-ischaemic preparations. METHODS: We used rapid atrial pacing to induce regional mechanical alternans and pulsus alternans before and then at 5-min intervals after the onset of acute ischaemia induced by a 30-min ligation of a diagonal branch of the left anterior descending artery. Regional mechanical activity is measured with epicardial tripodal strain gauges and regional electrical activity is measured using suction-based monophasic action potential electrodes. To test whether alternate stretching of ischaemic segments during pulsus alternans contributed to electrical alternans we simulated pulsus alternans by clamping the proximal aorta on alternate beats. RESULTS: In control areas there was a constant discordant relationship between peak systolic pressure during alternans and action potential duration. In contrast, the ischaemic areas showed electromechanical alternans that was most frequently concordant. Clamping the proximal aorta on alternate beats produced an electrical alternans in control areas but not in the ischaemic area. CONCLUSIONS: Pulsus alternans during acute ischaemia is associated with electrical alternans that can be out of phase in control and ischaemic areas. This could increase electrical dispersion which may be pro-arrhythmic.

Sympathomimetic modulation of load-dependent changes in the action potential duration in the in situ porcine heart.

AIMS: Increased sympathetic stimulation is known to be arrhythmogenic. Likewise increased loading of the myocardium can directly generate arrhythmias. The interaction between the two on the electrophysiology of the myocardium has not been investigated before. We investigated the effect of dobutamine infusion on the shortening of the monophasic action potential duration secondary to increased loading. This was investigated during steady-state pacing and during an alteration in beat-to-beat interval in the form of a restitution curve. METHODS: Pigs were anaesthetised and their hearts exposed. Monophasic action potentials and segment lengths were recorded from the anterior surface of the left ventricle. The loading of the ventricle was increased by transiently occluding the aorta. Steady-state pacing and a restitution curve were performed. Recordings were taken before and during dobutamine infusion. RESULTS: At steady state, increased loading of the heart shortened the monophasic action potential duration by a mean (+/- s.e.m.) of 4.0 (+/- 0.5) ms (P < 0.001). During dobutamine infusion this shortening of the monophasic action potential increased. Shortening of the action potential duration increased with the dose of dobutamine up to 10 micrograms/kg/min after which a plateau was reached. By comparison to control, dobutamine depressed the electrical restitution curve at short test pulse intervals did not significantly alter the plateau. Increased loading elevated the initial section of the electrical restitution curve at short test pulse intervals and depressed the plateau in both the control recordings and those taken during dobutamine infusion. Increased loading increased the amplitude of the supernormal phase of the electrical restitution curve in control recordings and those taken during dobutamine infusion. Sympathetic stimulation by dobutamine during the steady state potentiates the effect of mechanoelectric feedback on the myocardium. The effect on the restitution curve varies with test pulse interval. At short test pulse intervals the effect of sympathetic stimulation dominates with only minor antagonistic modification by increased loading. However, at longer test pulse intervals the effect of mechanoelectric feedback is equal to that of sympathetic stimulation and is synergistic with it. CONCLUSIONS: The mechanically induced changes we describe in the normal pig heart in situ are relatively small. However, they are in the right direction to possibly contribute to arrhythmia under pathological conditions where mechanical as well as electrophysiological inhomogeneity is prominent.

Characterisation of regional myocardial dynamics during mechanical alternans in heart of anaesthetised pig.

OBJECTIVE: The aim was to investigate the behaviour of regional myocardium during mechanical alternans in a multidirectional manner. METHODS: Mechanical alternans was induced in 12 anaesthetised open chested pigs by rapid atrial pacing. In contrast to previous studies, regional mechanical activity was simultaneously assessed at up to three different sites on the left ventricle using epicardial measuring devices able to provide multidirectional information on segment motion. Pressure-length loops were plotted to assess different patterns of segmental motion. The integral of pressure and length was calculated to obtain a regional work index for each beat. RESULTS: Pressure-length loops revealed profound abnormalities in segment motion and work index during regional mechanical alternans. Myocardial segments either performed alternate amounts of positive work on each beat or alternate amounts of positive and negative work on each beat. Alternating segments contracted out of phase with each other and were occasionally stretched during systole. CONCLUSIONS: The spatio-temporal heterogeneity of regional mechanical behaviour is greatly increased during mechanical alternans.

Mechanically induced changes in action potential duration and left ventricular segment length in acute regional ischaemia in the in situ porcine heart.

OBJECTIVE: The electrophysiological events accompanying early ischaemia are important. The aim of this study was to investigate mechano-electric feedback in acute regional myocardial ischaemia in the intact heart in situ by measuring the change in action potential duration in response to increased ventricular loading imposed by transient aortic occlusion. METHODS: 11 landrace pigs were anaesthetised and their hearts exposed. A pneumatically operated blood pressure clamp was placed around the aorta. Monophasic action potentials and an index of segment motion were recorded from the epicardium in and around the ischaemic area produced by a snare placed around a coronary artery. Ventricular and systemic arterial pressures were measured. An initial aortic clamp was performed during which control recordings were taken. The coronary artery was then tied and the aorta clamped for 5-10 s every 5 min for the duration of the 30 min tie. Recordings were taken from the ischaemic area and non-ischaemic areas. RESULTS: Aortic clamp before ischaemia increased intraventricular diastolic and systolic pressure and reduced action potential duration in all the areas studied (p < 0.001). During acute regional myocardial ischaemia aortic clamping resulted in significantly more shortening of the action potential in the ischaemic area after 10 min of ischaemia than in the control area (5 ms v 10 ms, p = 0.008). Over the following 20 min the degree of shortening decreased. The greater shortening at 10 min could not be attributed to changes in the end diastolic segment length or peak ventricular pressure and could thus represent a change in the expression of mechano-electric feedback by ischaemic myocardium rather than a change in loading conditions. CONCLUSIONS: During the first 30 min following a coronary artery occlusion mechano-electric feedback in the ischaemic myocardium varies with time.

Combination of inverse electron-demand Diels-Alder reaction with highly efficient oxime ligation expands the toolbox of site-selective peptide conjugations.

A modular approach combining inverse electron-demand Diels-Alder coupling (DARinv) and oxime ligation expands the toolbox of bioorthogonal peptide chemistry. Applicability of versatile site-specific bifunctional building blocks is demonstrated by generation of defined conjugates comprising linear, cystine-bridged and multi-disulfide functional peptides as well as their conjugation with hybrid silsesquioxane nanoparticles.

Correction: Combination of inverse electron-demand Diels-Alder reaction with highly efficient oxime ligation expands the toolbox of site-selective peptide conjugations.

Correction for 'Combination of inverse electron-demand Diels-Alder reaction with highly efficient oxime ligation expands the toolbox of site-selective peptide conjugations' by S. Hörner, et al., Chem. Commun., 2015, DOI: 10.1039/c5cc03434e.

Analysis of the structure and stability of omega loop A replacements in yeast iso-1-cytochrome c.

Omega (omega)-loop A, residues 18-32 in wild-type yeast iso-1-cytochrome c, has been deleted and replaced with loop sequences from three other cytochromes c and one from esterase. Yeast expressing a partial loop deletion do not contain perceptible amounts of holoprotein as measured by low-temperature spectroscopy and cannot grow on nonfermentable media. Strains expressing loop replacement mutations accumulate holoprotein in vivo, but the protein function varies depending on the sequence and length of the replacement loop; in vivo expression levels do not correlate with their thermal denaturation temperatures. In vitro spectroscopic studies of the loop replacement proteins indicate that all fold into a native-like cytochrome c conformation, but are less stable than the wild-type protein. Decreases in thermal stability are caused by perturbation of loop C backbone in one case and a slight reorganization of the protein hydrophobic core in another case, rather than rearrangement of the loop A backbone. A single-site mutation in one of the replacement mutants designed to relieve inefficient hydrophobic core packing caused by the new loop recovers some, but not all, of the lost stability.

Magnetic resonance imaging white matter lesions and cognitive impairment in hypertensive individuals.

To search for a morphologic basis of cognitive impairment possibly associated with essential hypertension, we studied 35 otherwise asymptomatic hypertensive individuals (mean age, 38.7 years; range, 22 to 49 years) and 20 normotensive control subjects (mean age, 37.9 years; range, 26 to 49 years) using neuropsychologic tests and magnetic resonance imaging. Irrespective of drug treatment, hypertensive individuals performed significantly worse than did control subjects when assessed for verbal memory and total learning and memory capacity, while there were no differences in test results of visual memory, attention, vigilance, and reaction time. The hypertensive individuals also described themselves as less active but ranked similar on five other mood subscales. Punctate high-signal intensities of the white matter were found almost twice as often in the hypertensive group (38%) as in the control group (20%). There was no difference in test performance between hypertensive individuals with and those without white matter lesions, however. Our results confirm the presence of subtle neuropsychologic deficits and indicate a higher frequency of white matter signal abnormalities in essential hypertension, as shown on magnetic resonance imaging, but do not indicate a correlation of these findings with each other.

Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis.

We reviewed the MRIs of 49 asymptomatic volunteers (age range, 31 to 77 years) and of 50 MS patients (age range, 14 to 63) for areas of increased signal (AIS) and features discriminating MS lesions from lesions seen with normal aging. We obtained optimal specificity of MRI interpretation (100%) if we required at least two of the following three AIS features--size greater than or equal to 6 mm, abutting ventricular bodies, infratentorial location--for a positive MRI diagnosis of MS. Applying these criteria to the MRIs of elderly patients with suspected MS should significantly improve specificity (p less than 0.001) over current quantitative criteria (at least three AIS greater than or equal to 3 mm) without significantly decreasing sensitivity.

Time course of vertebral osteopenia in ovariectomized rats.

Osteopenic changes in cancellous bone tissue of the first lumbar vertebral body were characterized in ovariectomized (OVX) rats as a function of time. Female Sprague Dawley rats (240 g body weight, 90 days old) were subjected to bilateral ovariectomy or sham surgery and sacrificed at various times from 0-540 days postovariectomy. The first lumbar vertebra was processed undecalcified for quantitative bone histomorphometry. Cancellous bone volume remained relatively constant in control rats at approximately 40% throughout the duration of the study. In contrast, cancellous bone volume was moderately decreased to 30-35% in OVX rats out to 180 days postovariectomy. Vertebral osteopenia became more pronounced in OVX rats at later times as cancellous bone volume declined to approximately 20% between 180 and 270 days and remained at that osteopenic level for the duration of the study. Osteoblast and osteoclast surface were highly elevated in OVX rats at 35 days, declined gradually toward control levels out to 180 days, then increased markedly at 270 days. Mineralizing surface and bone formation rate (tissue level, total surface referent) were maximally increased in OVX rats at 35-70 days before declining toward control levels at later times. However, these parameters remained significantly increased in OVX rats relative to control rats between 270 and 540 days. Mineral apposition rate was nearly identical in control and OVX rats at all time points and declined linearly with age in both groups. Our results indicate that osteopenia and increased bone turnover occur in the lumbar vertebral bodies of OVX rats, as had been previously observed in the proximal tibial metaphyses of these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

The association between the diameter of a patent foramen ovale and the risk of embolic cerebrovascular events.

PURPOSE: We sought to determine whether the size of a patent foramen ovale affected the risk of embolic cerebrovascular events of unknown origin. PATIENTS AND METHODS: We ascertained the presence and measured the size of patent foramen ovale using multiplane transesophageal echocardiography in 121 consecutive patients younger than 60 years who had transient ischemic attacks or ischemic strokes and in 123 control subjects. None of the patients had left heart, aortic, or carotid sources of embolism, or echocardiographic signs of elevated left or right atrial pressure. We used multivariate logistic regression to determine whether the size of the patent foramen ovale was an independent risk factor for cerebrovascular events. RESULTS: The mean (+/- SD) diameter of a patent foramen ovale was significantly larger in patients (4 +/- 2 mm) than in control subjects (2 +/- 1 mm, P <0.0001). A patent foramen ovale greater than 4 mm was associated with an increased risk of transient ischemic attacks [odds ratio (OR) = 3.4; 95% confidence interval (CI), 1.0 to 11, P = 0.04], ischemic strokes (OR = 12; 95% CI, 3.3 to 44, P = 0.0001), and, especially, having evidence of two or more strokes (OR = 27; 95% CI, 4.7 to 160, P = 0.0002). CONCLUSION: The diameter of a patent foramen ovale is an independent risk factor for ischemic events, especially recurrent strokes.

CD14+ peripheral blood mononuclear cells from chronic myeloid leukemia and normal donors are inhibitory to short- and long-term cultured colony-forming cells.

Monocyte-induced cell-cytotoxicity has been implicated in the mechanism of suppression of normal haematopoietic progenitors in chronic myeloid leukemia (CML). We examined here the in vitro effect of CML-derived and normal peripheral blood (PB) monocytes on short- and long-term cultured haematopoietic progenitor cells. Short-term coculture (5 days) of CML or normal monocytes with CML or normal peripheral blood mononuclear cells (PBMNC)/CD34+ cells as targets resulted in a significant inhibition of colony-forming cell (CFC) growth. Coculture conditioned medium (CCM) from 5-days cocultures of normal or CML CD14+ monocytes with CD34+ cells were likewise inhibitory to CFC. In 5-week long-term cocultures of monocytes in direct contact with normal bone marrow (BM) progenitors, CML monocytes reduced the proportion of long-term cultured CFC (LTC-CFC) significantly to 52% of the controls, while normal monocytes had a less pronounced inhibitory effect (89% of the controls) on LTC-CFC. Reduction of LTC-CFC was great when CML monocytes and target cells were separated by a transwell membrane as compared to control cultures in the absence of CD14+ cells (53.5 vs. 9%). CCM from 5-week cocultures of normal or CML CD14+ monocytes with CD34+ progenitors from bone marrow (BM) cells were also inhibitory to CFC. No difference in cytokine levels for TNF-alpha, IFN-gamma, G-CSF, IL-10, IL-6 was detectable between CML CD14+ CCM and control CCM derived from short- and long-term cocultures. Our results suggest that CML monocytes may play a role in the inhibition of normal haematopoiesis through a yet not defined soluble factor supporting the expansion of the malignant clone in CML.

Coronary artery fistulas presenting with bacterial endocarditis.

Coronary artery fistulas are rare congenital malformations. Two cases presenting with bacterial endocarditis are described. Both were treated successfully by grafting of the coronary artery and ligation of the fistula.