Systemic amyloidosis from A (AA) to T (ATTR): a review.

Systemic amyloidosis is a rare protein misfolding and deposition disorder leading to progressive organ failure. There are over 15 types of systemic amyloidosis, each caused by a different precursor protein which promotes amyloid formation and tissue deposition. Amyloidosis can be acquired or hereditary and can affect various organs, including the heart, kidneys, liver, nerves, gastrointestinal tract, lungs, muscles, skin and soft tissues. Symptoms are usually insidious and nonspecific resulting in diagnostic delay. The field of amyloidosis has seen significant improvements over the past decade in diagnostic accuracy, prognosis prediction and management. The advent of mass spectrometry-based shotgun proteomics has revolutionized amyloid typing and has led to the discovery of new amyloid types. Accurate typing of the precursor protein is of paramount importance as the type dictates a specific management approach. In this article, we review each type of systemic amyloidosis to provide the practitioner with practical tools to improve diagnosis and management of these rare disorders.

Antibacterial prophylaxis with ciprofloxacin for patients with multiple myeloma and lymphoma undergoing autologous haematopoietic cell transplantation: a quasi-experimental single-centre before-after study.

OBJECTIVES: We aimed to study whether ciprofloxacin prophylaxis reduces infectious complications in patients undergoing autologous haematopoietic cell transplantation (AHCT). METHODS: This is a quasi-experimental, retrospective, before-after study. We compared the incidence of bacterial-related complications among 356 patients with multiple myeloma (MM) (n = 202) and lymphoma (n = 154) who underwent AHCT with (n = 177) or without (n = 179) ciprofloxacin prophylaxis between 03/2007 and 10/2012 and between 10/2012 and 07/2016, respectively, at a single centre. RESULTS: Febrile neutropaenia, bacteraemia, and pneumonia were significantly more common among patients who underwent AHCT during the second study period and did not receive antibacterial prophylaxis compared with patients who underwent AHCT during the first study period and received antibacterial prophylaxis (89.9% (161/179) vs. 83.1% (147/177), difference 6.9%, 95% CI 0-14.1%, P = 0.002; 15.1% (27/179) vs. 4.5% (8/177), difference 10.6%, 95% CI 4.4-16.9%, p < 0.0001; 12.3% (22/179) vs. 6.2% (11/177), difference 6.1%, 95% CI 0-12.3%, p = 0.04, respectively). The number-needed-to-treat to prevent one episode of bacteraemia, pneumonia, and febrile neutropaenia was 8.6, 8.5, and 13.7, respectively. Patients with ciprofloxacin prophylaxis had higher rates of ciprofloxacin-resistant bacteraemia (62.5% (5/8) vs. 18.5% (5/27), difference 44%, 95% CI 7-70%, p = 0.01). In multivariate analysis, ciprofloxacin prophylaxis significantly decreased the odds of bacteraemia (OR 0.19, 95% CI 0.07-0.52; p < 0.0001) and pneumonia (OR 0.37, 95% CI 0.16-0.85, p = 0.02). CONCLUSION: According to our single-centre experience, patients with MM and lymphoma undergoing AHCT may benefit from antibacterial prophylaxis with ciprofloxacin.

Predicting midsagittal pharynx shape from tongue position during vowel production.

The shape of the pharynx has a large effect on the acoustics of vowels, but direct measurement of this part of the vocal tract is difficult. The present study examines the efficacy of inferring midsagittal pharynx shape from the position of the tongue, which is much more amenable to measurement. Midsagittal magnetic resonance (MR) images were obtained for multiple repetitions of 11 static English vowels spoken by two subjects (one male and one female). From these, midsagittal widths were measured at approximately 3-mm intervals along the entire vocal tract. A regression analysis was then used to assess whether the pharyngeal widths could be predicted from the locations and width measurements for four positions on the tongue, namely, those likely to be the locations of a receiver coil for an electromagnetometer system. Predictability was quite high throughout the vocal tract (multiple r> 0.9), except for the extreme ends (i.e., larynx and lips) and small decreases for the male subject in the uvula region. The residuals from this analysis showed that the accuracy of predictions was generally quite high, with 89.2% of errors being less than 2 mm. The extremes of the vocal tract, where the resolution of the MRI was poorer, accounted for much of the error. For languages like English, which do not use advanced tongue root (ATR) distinctively, the midsagittal pharynx shape of static vowels can be predicted with high accuracy.

Correlational cuing as a function of target complexity and target-flanker similarity.

It is generally assumed that the correlational cuing effect (CE) between targets and correlated flankers is due to learning association between the flankers and their correlated responses. The present study challenges this view. Experiment 1 shows that the CE for targets composed of color is eliminated as soon as the correlation is removed. Experiment 2 shows that the CE during training is not due to association of the flankers with responses. Experiment 3 shows that at least some of the CE during training with the correlation is due to repetition priming of the display. Experiment 4 replicates the results of Experiment 1 for orientation targets. In Experiments 5-7, more typical tasks with letter targets are examined, and it is demonstrated that preexperimental similarity between targets and correlated flankers is crucial. The CE for correlated but dissimilar target-flanker pairs, similar to that for color and orientation targets, is confined to on-line processes that occur during training. The CE is transferred, however, for correlated and similar target-flanker pairs. We propose that, at least for the simple stimulus to response mapping used in our study, the CE is not due to learning at all. Instead it is due to (1) on-line processes, such as repetition priming, that occur during training with the correlation and (2) a regular flanker effect (see, e.g., B. A. Eriksen & C. W. Eriksen, 1974) that occurs for similar target-flanker pairs.

Intra- and cross-dimensional visual search for single-feature targets.

Cross-dimensional visual search for single-feature targets that differed from the distractors along two dimensions (color and orientation) was compared with intradimensional search for targets that differed from the distractors along a single dimension (either orientation or color). The design of the first three experiments differed from those of previous studies in that participants were required to respond differently to each of the targets. Experiments 1-3 were similar except that in Experiment 1, the distractors were homogeneous; in Experiment 2, two types of distractors were used in equal proportions; and in Experiment 3, two types of distractors were used but one of the distractors was a singleton. The findings, contrary to those of previous studies, revealed that cross-dimensional search is at least as efficient and for some targets even more efficient than intradimensional search. These results suggest that the details of stimulus-to-response mapping are essential in comparing intra- and cross-dimensional tasks. Experiment 4 used a priming design and did not support an explanation based on grouping processes. We outline an explanation for all the findings based on a recent cross-dimensional response selection model by Cohen and Shoup (1997).

Structural properties of six tibial fixation methods for anterior cruciate ligament soft tissue grafts.

This study compared the stiffness (K), yield load (YL), and slippage (SL) of six tibial fixation methods. These properties were determined from load-to-failure and cyclic tests of double-looped tendon grafts fixed to both animal and young human tissue. Tandem washers (K = 259 N/mm, YL = 1159 N, SL = 0.5 mm) and the Washerloc (K = 248 N/mm, YL = 905 N, SL = 2.0 mm) were the two best fixations. At 500 N of load, which is the estimated daily tension of an anterior cruciate ligament graft during intensive rehabilitation, slippage was significantly greater in either of the other two methods for sutures tied to a post (4.9 mm), double staples (3.3 mm), and a 20-mm spiked metal washer (3.5 mm). Interference screw fixation performed well in animal tissue (YL = 776 N), but was significantly worse in young human tissue (YL = 350 N), with 57% of the fixations failing before 500 N of load. Animal tissue should not be used to estimate the performance of interference screw fixation in human tissue. Because 57% of the interference screw fixations using human tissue failed at loads below 500 N, their ability to provide adequate fixation during intensive rehabilitation should be questioned. However, both the Washerloc and tandem washers and screws provide fixation structural properties in young human tibia that should be appropriate for intensive rehabilitation.

Demographic aspects of Paget's disease of bone in the Negev of southern Israel.

In a mainly retrospective but partly prospective survey of the period 1968-1993 in southern Israel, 61 cases of Paget's disease of bone were identified. Fifty six percent were of non-Afro-Asian origin and 44% originated from Afro-Asia, which is approximately the inverse of the ratio in the local general population. The largest single groups from non-Afro-Asia and Afro-Asia originated, from Romania and Tunisia, respectively, and Australia and Argentina were also disproportionately prominent as countries of origin. Israel itself was the origin of few patients. All the patients were Jews except for one Bedouin Arab, which is far different from the distribution of Bedouins and Jews in both the surveyed area and the hospital population. The differences between these groups numerically and against the background local population may well have been statistically significant had the circumstances enabled greater randomness in the collection of the data analyzed. It is surmised that in southern Israel the prevalence of Paget's disease of bone is about 1%, similar to that in southern Europe.

Prostanoids in renal failure induced by converting enzyme inhibition in sodium-depleted rats.

Clearances of inulin (CIn) and p-aminohippurate (CPAH) were measured in four groups of rats before and after intravenous administration of acetylsalicylic acid (ASA): 1) controls, on normal Na intake, 2) captopril-treated (30 mg.kg-1.day-1) on normal Na intake, 3) Na depleted, and 4) Na depleted, captopril-treated. In Na-depleted animals, CIn and CPAH were similar to controls but decreased significantly with ASA. In Na-depleted, captopril-treated rats, CPAH was slightly decreased, but CIn was significantly reduced (P less than 0.01). Both were not affected by ASA. Urine output was unchanged and the kidneys appeared normal on histological examination. The production of prostaglandins E2 (PGE2), F2 alpha (PGF2 alpha), and thromboxane B2 (TxB2) was measured in isolated glomeruli, cortical tubule suspensions, and medullary and papillary slices. Captopril increased PGE2 production by glomeruli and PGF2 alpha and TxB2 synthesis in papillary slices. Na depletion selectively enhanced the production of PGE2 by glomeruli and papillae. In contrast, the synthesis of prostanoids was significantly decreased in captopril-treated, Na-depleted rats. These findings suggest that in this model, functional nonoliguric renal failure may be related to abnormalities of prostanoid synthesis.

Total parathyroidectomy with autotransplantation in haemodialysed patients with secondary hyperparathyroidism--should it be abandoned?

The development of secondary hyperparathyroidism is almost universal in patients with end-stage renal disease. Medical management frequently fails and in such circumstances parathyroidectomy becomes a necessity. Total parathyroidectomy with autotransplantation of parathyroid tissue into the patient's forearm has been advocated as the surgical procedure of choice. In a previous publication we reported our experience with this technique in six haemodialysed patients. We now extend our follow-up to 19 patients over an observation period ranging from 6 to 66 months. Five of these patients required graft removal because of recurrent secondary hyperparathyroidism. Despite total graft removal, two patients had clinical and laboratory evidence of persistent hyperparathyroidism. Histology of the removed graft tissue demonstrated severe hyperplasia as well as invasion of adjacent muscle, adipose tissue, and vascular channels by parathyroid cells. This raises the possibility of local and distant metastatic spread of parathyroid tissue resulting in hyperparathyroidism. We suggest that parathyroid autotransplantation is potentially hazardous and should in fact be abandoned.

High incidence of hypertension in older patients after unilateral nephrectomy. A retrospective study.

Twenty-six normotensive patients, who underwent unilateral nephrectomy for nontumoral urological diseases, were reevaluated. The mean postoperative follow-up period was 13.8 +/- 0.7 years. Eleven patients developed hypertension, and 15 patients remained normotensive. The former were 47.1 +/- 3.3 years old, and the latter 36.5 +/- 2.9 years old at the time of nephrectomy (P less than 0.02). The mean preoperative systolic blood pressure was higher in the group of 11 hypertensive patients (126.7 +/- 2.4 mm Hg) than in the 15 normotensive patients (118.2 +/- 2.9 mm Hg), P less than 0.04. Preoperative diastolic blood pressure was similar in the two groups (77.8 +/- 1.5 vs. 75 +/- 2 mm Hg). Preoperative and follow-up serum creatinine levels were similar in both groups. Mean creatinine clearance (Ccr) at the time of follow-up was not significantly different in the hypertensive patients compared with the normotensive patients. One patient developed proteinuria and chronic renal failure (Ccr of 31 ml/min). Two other patients with normal Ccr had a daily protein excretion of 840 and 2,000 mg/24 h, respectively. The incidence of hypertension, after nephrectomy, of 75% in patients greater than 55 years old seems to be significantly higher than the 30% reported in an aged-matched normal Israeli population. This did not apply to the patients less than 55 years old. In most of the cases, long-term follow-up did not reveal significant uninephrectomy induced changes in renal function.

Effect of vasoactive agents on prostanoid synthesis in isolated rat glomeruli.

We studied the influence of vasoactive substances (angiotensin II, epinephrine, norepinephrine and acetylcholine) on the synthesis of prostanoids in isolated rat glomeruli. A significant increase of prostaglandin E2, and of thromboxane B2, but not of prostaglandin F2 alpha synthesis was observed after the administration of angiotensin II at physiological doses. Neither catecholamines nor acetylcholine influenced prostaglandin synthesis. The stimulation of vasoactive prostaglandins by angiotensin II, may modify the hemodynamic status of the glomerulus.

Successful parathyroid gland autotransplantation after total parathyroidectomy in dialysis patients.

Secondary hyperparathyroidism is one of the major complications encountered in patients on maintenance dialysis. Medical management is frequently unsuccessful, and there is often a need to perform a parathyroidectomy. Recurrent clinical secondary hyperparathyroidism may occur as a sequela of subtotal parathyroidectomy and necessitate a reexploration of the neck. Total parathyroidectomy followed by autotransplantation of parathyroid tissue into the patient's forearm bypasses the need for a second operation, and it provides a simple ambulatory procedure, under local anesthesia, for the removal of hyperplastic parathyroid tissue. The results in six patients indicate that this new procedure should be considered the treatment of choice for this condition.