Relaxation-encoded NMR experiments for mixture analysis: REST and beer.

A new family of NMR experiments for mixture analysis (Relaxation-Encoded Selective TOCSY, REST) allows the extraction of component subspectra from mixtures. It uses isotropic mixing to label whole spin systems with the relaxation times (e.g. T1, T2) of individual spins.

Increasing the quantitative bandwidth of NMR measurements.

The frequency range of quantitative NMR is increased from tens to hundreds of kHz by a new pulse sequence, CHORUS. It uses chirp pulses to excite uniformly over very large bandwidths, yielding accurate integrals even for nuclei such as (19)F that have very wide spectra.

Measuring couplings in crowded NMR spectra: pure shift NMR with multiplet analysis.

The PSYCHE method for pure shift NMR is exploited to generate 2D J spectra with full decoupling in one dimension and multiplet structure in the other, allowing spin-spin coupling constants to be measured even in very crowded spectra. Significant improvements over existing techniques are demonstrated for the hormones estradiol and androstenedione.

"Perfecting" pure shift HSQC: full homodecoupling for accurate and precise determination of heteronuclear couplings.

Fully homodecoupled HSQC spectra can be obtained through the use of a new pulse sequence element, "perfectBIRD". By way of illustration, we show that perfectBIRD decoupling allows one-bond residual dipolar couplings (RDCs), which provide important NMR restraints for structure elucidation, to be measured with outstanding precision, even in methylene groups.

Neuroendocrine breast tumours: breast cancer or neuroendocrine cancer presenting in the breast?

Neuroendocrine tumours (NET) of the breast are rare. Diagnosis depends on close scrutiny of core- or excisional-biopsy specimens for characteristic growth patterns (papillary, nesting or mixed), which should trigger immunohistochemical staining for neuroendocrine markers (in particular chromogranin and synaptophysin). The diagnosis is confirmed if a) >50% of the tissue specimen demonstrate neuroendocrine markers and b) in-situ ductal carcinoma is identified and/or imaging modalities exclude extra-mammary sites. Our literature search including the non-English literature identified 66 articles with data on 123 cases, including our own. Oestrogen receptors are not diagnostic for NET's of the breast as they are found in tumours of non-mammary origin, too. Half of reported cases of neuroendocrine tumours have axillary lymph node involvement. Breast-conserving surgery (wide local excision ± axillary clearance) is commonly performed for suitable tumours. Chemotherapy regimens utilised are commonly either platinum- (as for small-cell cancers) or anthracycline-based (as for primary breast cancers). Best management remains unknown.

Steroid withdrawal in liver transplant recipients.

Because of troublesome side effects associated with steroid use, many transplant centers have tried to withdraw steroids from stable, solid organ transplant recipients. The objective of this study was to evaluate the ability to wean liver transplant recipients off steroids, depending on both their primary immunosuppressive regimen and their primary disease state. This was a retrospective, single-center review of steroid weaning in adult orthotopic liver transplant recipients. Based on primary immunosuppression, patients could be weaned off steroids similarly if they were taking cyclosporine or tacrolimus (53.9% vs 61.4%). When triple immunosuppressive regimens were compared with dual regimens, a difference was found in ability to wean patients off steroids (52.4% vs 74.5%, P = .001). When steroid weaning was stratified for primary immunosuppression and primary disease state, patients with autoimmune-mediated diseases (autoimmune hepatitis, sclerosing cholangitis, and primary biliary cirrhosis) were less likely to be weaned if they were receiving cyclosporine-based immunosuppressants (36.8% vs 62.2%, P = .03). In conclusion, it appears that a large number of liver transplant recipients can safely be tapered off steroids.

Noise shaping in populations of coupled model neurons.

Biological information-processing systems, such as populations of sensory and motor neurons, may use correlations between the firings of individual elements to obtain lower noise levels and a systemwide performance improvement in the dynamic range or the signal-to-noise ratio. Here, we implement such correlations in networks of coupled integrate-and-fire neurons using inhibitory coupling and demonstrate that this can improve the system dynamic range and the signal-to-noise ratio in a population rate code. The improvement can surpass that expected for simple averaging of uncorrelated elements. A theory that predicts the resulting power spectrum is developed in terms of a stochastic point-process model in which the instantaneous population firing rate is modulated by the coupling between elements.

The distribution of muscle weakness in upper motoneuron lesions affecting the lower limb.

To determine the distribution of weakness in the lower limb after upper motoneuron lesions the strength of 8 muscle groups was measured. Four groups of patients were studied: 22 control subjects, 16 patients with unilateral leg paresis, 4 patients with severe unilateral paralysis and 5 patients with paraparesis. In the testing posture (seated), patients with cerebral upper motoneuron lesions showed no selective loss of power in flexors or extensors on the contralateral side. Gravitational torques were included in the measurements. However, proximal muscles (acting at hip and knee) were significantly less severely affected than more distal muscles (acting at ankle and hallux). At any particular joint, physiological flexors and extensors were affected equally in both the hemiparetic and paraparetic subjects. As in the upper limb (Colebatch and Gandevia, 1989), the strength of muscles on the clinically unaffected side was reduced compared with control subjects, although no muscle groups were especially affected.

Deficits of thermal sensation in patients with unilateral cerebral lesions.

Using a quantitative psychophysical test, the thresholds for detection of heat and cold were determined at both wrists in 16 hemiparetic patients with unilateral cerebral lesions and 1 patient with a unilateral frontal lesion but no hemiparesis. These data were compared with normal values for the absolute thermal thresholds and the symmetry of thermal thresholds in 25 age-matched control subjects. Significant elevation of thermal thresholds was found in all patients with clinically detectable deficits of nociceptive or thermal sensations. Thresholds were also elevated in 3 of 10 hemiparetic patients with no clinical evidence of impairment of nociceptive or thermal sensations. Deficits were found in patients with superficial cortical lesions as well as in those with extensive lesions involving deep structures, including thalamus. In patients with superficial lesions, the elevation of thermal threshold was slight (less than 1 degree C) and there was often little or no sensory deficit to clinical testing. In patients with very high thermal thresholds (greater than 6 degrees C), the lesions involved deep structures and there were clinically obvious deficits of thermal and nociceptive sensations.

Stimulation of brainstem nuclei in the cat: effect on neuronal activity in the primary visual cortex of relevance to cerebral blood flow and migraine.

The electrical activity of single neurons was recorded in the primary visual cortex of anesthetized cats in order to test the hypothesis that changes in their activity might be the cause of the changes in blood flow seen after stimulation of the brainstem and in migraine. Discharge evoked by optic radiation stimulation was facilitated by conditioning stimulation (6 pulses over 24 msec) of the locus coeruleus (LC), whereas no consistent effect was exerted on resting discharge. No clear difference could be demonstrated between the effect on resting discharge of short-duration stimulation of the LC, midbrain reticular formation and dorsal raphe nucleus (DRN). Stimulation of these structures at 5/sec for 10 sec was also studied to ascertain whether long-term changes in neuronal activity could be produced, and to indicate whether changes in cerebral blood flow previously described with these parameters of stimulation were secondary to alterations in metabolic demand due to increased or decreased bulk neuronal activity. The vast majority of single neurons were unaltered by these parameters of stimulation, suggesting that cortical blood flow changes following LC and DRN stimulation are due to a direct action on the cortical microcirculation.

Massive benign thymoma presenting as ocular myasthenia.

A case of ocular myasthenia was found to be associated with a massive benign thymoma and responded to its removal. This is an exception to the generalisation that larger tumours of the thymus gland are more likely to be malignant and that thymectomy is not the treatment of choice for ocular myasthenia.

The effects of voluntary contraction on the H reflex of human limb muscles.

The effects of a voluntary contraction on the H reflexes of various muscles were quantified to determine whether the reflex responses were sufficiently reproducible to be used in diagnostic studies. During a voluntary contraction, H reflexes could be recorded reliably from tibialis anterior and abductor pollicis brevis, but accurate identification of the onset of the H wave from the on-going background EMG required duplicate averages of multiple responses. During a contraction the H reflex could be obtained at lower stimulus intensities in the forearm flexor muscles than when relaxed, and a more clear separation of the H wave from the M wave was possible. The background contraction abolished the attenuation of reflex amplitude with increasing stimulus repetition rates, such that repetition rates of up to 4 Hz could be used without significant loss of reflex amplitude. There were only small and usually insignificant differences in the latency of the H reflex or its variability when elicited with the forearm muscles relaxed and when flexor carpi radialis was contracting steadily. The reflex latencies of abductor pollicis brevis, tibialis anterior and soleus were compared with F wave latencies for these muscles. The minimal F wave latencies were shorter than the H reflex latencies for abductor pollicis brevis (mean 2.2 ms) and tibialis anterior (mean 1.0 ms) but not for soleus. Comparison of the spread of F wave latencies (F max-F min) suggests that, for soleus, F waves are recorded only from the faster conducting motor units in the pool, presumably those less readily recruited in the H reflex. It was calculated that the distribution of motor conduction velocities responsible for the F waves of abductor pollicis brevis was 8.8 m.s-1. This value underestimates the likely distribution of motor conduction velocities for the thenar muscle by as much as 50%, consistent with the view that F waves rarely occur in slowly conducting motor units, the units of lowest threshold in reflex studies. It is concluded that, for many motoneuron pools, the H reflex and the F wave appear preferentially in different motoneurons, low and high threshold, respectively, and that reflex studies can provide information not available from somatosensory evoked potentials or F wave studies.

Myokymia of the tongue in a case of brainstem tumour that simulated motor-neuron disease.

The diagnosis of a brainstem tumour, which presented as progressive bulbar palsy that resembled motor-neuron disease, was suspected because of the rare electromyographic finding of myokymia of the tongue, and was confirmed by magnetic resonance imaging.

Brain-stem facilitation of electrically evoked visual cortical response in the cat. Source, pathway and role of nicotinic receptors.

The experiments reported here show that facilitation of late components of the electrically evoked visual cortical response by electrical stimulation of the midbrain reticular formation in the cat depends on nicotinic cholinergic receptors and not on muscarinic receptors that mediate the arousal reaction. Facilitation could be elicited by stimulation of areas ranging from pons to diencephalon (maximally from the central and paralemniscal tegmental fields of the midbrain) and employed a pathway traversing the intralaminar thalamic nuclei. In contrast to the effects of this reticulocortical pathway, little facilitation was obtained from the locus ceruleus, the dorsal raphe nucleus or the medial forebrain bundle through which these two monoaminergic pathways project to the cerebral cortex.

Bulbo-cortical pathways and their possible relevance to migraine and epilepsy.

Facilitation of the visual evoked response from the reticular formation in the cat has been shown to depend on nicotinic cholinergic receptors distinct from the muscarinic cholinergic receptors responsible for the arousal reaction. An increase in the amplitude of visual evoked responses in migraineurs does not therefore imply any change in reticulocortical activity of relevance to epilepsy. Stimulation of locus ceruleus and nucleus raphe dorsalis exerted comparatively minor effects on the visual evoked response and did not alter the discharge rate of cortical neurons in the resting state. It is concluded that the changes in cerebral blood flow previously reported to result from stimulation of these monoaminergic brainstem nuclei, which resemble those observed in migraine, must be exerted directly on the cortical microcirculation and not simply follow the metabolic demand of cortical neurons. There is thus a place in the management of migraine for pharmaceutical agents acting on cerebral vessels even if the neural hypothesis for the mechanism of migraine proves to be correct.