Orthostatic challenge reveals impaired vascular resistance control,but normal venous pooling and capillary filtration in familial dysautonomia

Patients with familial dysautonomia (FD) frequently have profound orthostatic hypotension without compensatory tachycardia. Although the aetiology is presumed to be sympathetic impairment, peripheral vascular responses to orthostasis have not been assessed. The aim of this study was to evaluate the control of vascular responses to postural stress in FD patients. Measurements of heart rate, blood pressure, cardiac stroke volume and cardiac output (CO), by impedance cardiography, and calf-volume changes, by impedance plethysmography, were taken from nine FD patients and 11 control subjects while supine and during head-up tilt. During leg lowering, we also assessed the venoarteriolar reflex by measuring skin red-cell flux. Head-up tilting for 10 min induced sustained decreases in mean arterial pressure in the FD patients, but not in the controls. Total peripheral resistance (TPR, i.e. mean arterial pressure/CO) increased significantly in the controls (39.8+/-6.8%), but not in the FD patients. Calf-volume changes during tilting, when normalized for the initial calf volume, did not differ significantly between the patients (4.62+/-1.99 ml.100 ml(-1)) and the controls (3.18+/-0.74 ml.100 ml(-1)). The vasoconstrictor response to limb lowering was present in the patients (47.7+/-9.0% decrease in skin red-cell flux), but was impaired as compared with the controls (80.7+/-3.4%) ( P <0.05). The impaired vasoconstriction during limb lowering and absent increase of TPR during tilting confirm that orthostatic hypotension in FD is due primarily to a lack of sympathetically mediated vasoconstriction without evidence of abnormally large shifts in blood volume towards the legs during orthostasis. This may be due, in part, to a preserved myogenic response to increased vascular pressure in the dependent vascular beds.     

The incidence of positive margins with breast conserving therapy following mammotome biopsy for microcalcification

BACKGROUND AND OBJECTIVES: The ability to achieve clean margins with breast conserving therapy varies greatly even when the diagnosis of carcinoma is known beforehand. Although several reports reveal that the incidence of positive margins decreases after stereotaxic core biopsy of nonpalpable lesions and fine-needle aspiration biopsy of palpable lesions, the data on the results following mammotome biopsy (mmbx) is scanty. METHODS: Two hundred and ninety-eight biopsy specimens for mammographically indeterminate microcalcification from 1/97 through 3/30/98 were reviewed. Biopsies were performed using the biopsys method utilizing an 11-gauge multidirectional, vacuum-directed device. RESULTS: Ten percent (n = 31) of the mammotome biopsies were atypical and 9% (n = 27) were malignant. These 58 cases (19%) were recommended for surgical excision. The incidence of positive margins in this subset was determined. Of patients who underwent lumpectomy as their initial surgical procedure 69% had negative surgical margins. Seventy-seven percent of patients with carcinoma diagnosed by mammotome biopsy had definitive initial surgery with a single surgical procedure. CONCLUSIONS: Mmbx facilitates fewer surgical procedures to achieve negative margins, and thus provides a better cosmetic result.     

Bladder outlet obstruction versus impaired detrusor contractility: the role of outflow

The uroflow curves of 45 men with either bladder outlet obstruction or impaired detrusor contractility were retrospectively reviewed. The definitive diagnoses were attained by clinical and video-urodynamic studies with simultaneous detrusor pressure and uroflow measurements. Eight parameters were analyzed to determine if uroflow can differentiate obstruction from impaired contractility. There were no differences between the 2 groups in any of the parameters. This finding suggests that uroflowmetry as a single examination cannot distinguish between bladder outlet obstruction and impaired detrusor contractility.     

Evaluation of autonomic dysfunction in familial dysautonomia by power spectral analysis

We examined the nature and extent of the autonomic control defect in patients with autonomic dysfunction using power spectral analysis of heart rate fluctuations. Heart rate variability and respiratory patterns were monitored and discrete blood pressure measurements were made during supine and standing positions in 10 ambulatory patients with familial dysautonomia and in controls. Postural hypotension without compensatory tachycardia was confirmed in the patients upon standing. The balance between sympathetic and parasympathetic activity was compared in both positions by quantifying the power of the low (0.04-0.095 Hz) and high (respiratory) frequency fluctuations in instantaneous heart rate. After changing from supine to standing position there was a small decrease in the low frequency power of heart rate fluctuations in the patients as opposed to a significant increase in controls. The mean power of fluctuations occurring at high frequency decreased only slightly in the patients compared to a marked decrease in the controls. We conclude that the fall in blood pressure, lack of appropriate heart rate modulation, and failure to increase low frequency heart rate power which occurred in the patients upon standing, are all due to lack of increased sympathetic output under the influence of gravity. The failure to decrease power in the respiratory frequency peak in the patients, suggests an abnormal retention of parasympathetic activity. This may be explained by parasympathetic compensation for the substantial sympathetic loss, or by a lack of appropriate inhibition of parasympathetic tone from baroreceptors or supraspinal structures.     

Measurement of effective renal plasma flow: a comparison of methods

We have compared two in vitro methods and three variations of kidney background (BG) subtraction within a gamma camera method (41 examinations, 31 patients) for determination of effective renal plasma flow (ERPF) using 131I orthoiodohippurate (OIH). Method I: plasma samples at 20 and 45 min after OIH injection, ERPF = dose X slope/intercept; Method II: 45-min plasma sample, ERPF = -51.1 + 8.21x + 0.019x2, x = dose/45-min plasma activity/I. Individual kidney and total ERPF were determined from gamma camera (GC) methods using renal uptake 1-2 min after injection. All methods were compared against Method I (previously validated against paraaminohippurate (PAH) clearances). Method II, which requires one blood sample is more accurate than GC methods. GC methods are insensitive to operator variability in placement of renal and BG regions of interest. They may be useful to follow changes in relative or total ERPF, but accurate depth correction of renal data is suggested. In vitro, blood sample-based methods are more accurate.     

Interaction of neuropeptides and biogenic amines on cyclic adenosine monophosphate accumulation in hypothalamic nuclei

Neuropeptides and biogenic amines known to be present in neurons or afferent terminals in the paraventricular nucleus (PVH), supraoptic nucleus (SON) and/or lateral hypothalamus (LH) were added to small areas of these structures obtained by micropuncture and cyclic adenosine monophosphate (cAMP) levels were measured. cAMP accumulation occurred in PVH, SON and LH in response to neuropeptides of the secretin family, such as vasoactive intestinal peptide (VIP) and in response to catecholamines. Bradykinin, alpha-melanocyte-stimulating (alpha-MSH), luteinizing hormone-releasing hormone (LH-RH), oxytocin and carbamylcholine stimulated cAMP accumulation selectively in one or two of the above structures. Glucagon, cholecystokinin (CCK), somatostatin (SRIF), corticotropin-releasing factor (CRF), thyrotropin-releasing hormone (TRH), adrenocorticotropin (ACTH), melanocyte-stimulating hormone (MSH), methionine enkephalin (Met-Enk), beta-endorphin, neurotensin, bombesin and angiotensin II did not effect cAMP levels while leucine enkephalin (Leu-Enk), arginine vasopressin and gamma-aminobutyric acid (GABA) elicited regionally selective decreases in basal levels of cAMP. When interactions between some of these compounds were measured, VIP and norepinephrine exerted a more than additive effect on cAMP elevation in the PVH, while the effect on cAMP of the SON and LH was additive.     

COLD PRESSOR TEST DEMONSTRATES RESIDUAL SYMPATHETIC CARDIOVASCULAR ACTIVATION IN FAMILIAL DYSAUTONOMIA

Objectives: Patients with polyneuropathy and antibodies to myelin-associated glycoprotein (MAG) and sulphated glucuronyl paragloboside (SGPG) differ from chronic inflammatory demyelinating polyneuropathy (CIDP) because of a slower, progressive course, symmetrical and predominantly sensory involvement of legs, predominantly distal slowing of motor conductions, and poorer response to therapy. We studied whether a wide set of electrophysiologic parameters may differentiate these two neuropathies. Methods: We reviewed the electrophysiological studies of 10 patients with anti-MAG/SGPG antibodies and 22 with CIDP examining: (1) motor conduction velocity and distal compound muscle action potential amplitude; (2) conduction block (CB) and temporal dispersion; (3) distal motor latency and terminal latency index (TLI); (4) F wave and proximal conduction time; and (5) sensory conduction and occurrence of abnormal median with normal sural sensory potential. Results: Anti-MAG/SGPG neuropathies showed: (1) more severe involvement of peroneal nerves; (2) more frequent disproportionate distal slowing of motor conductions (TLI less than or equal to 0.25) and absent sural potential; and (3) no CB. However 3/22 CIDP patients also had at least two nerves with TLI 0.25 and no CB. Conclusions: Electrophysiologic findings suggest in anti-MAG/SGPG neuropathy a length-dependent process with a likely centripetal evolution. A disproportionate slowing of conduction in distal segments of motor nerves suggests the diagnosis of anti-MAG/SGPG neuropathy, although it is not pathognomonic.