160 research outputs found
The Acute Porphyric Attack: A Difficult Diagnosis for a Potential Lethal Event in Emergency Medicine
The porphyrias are a heterogeneous group of metabolic
disorders due to an inherited (but in some forms the disturbance may
also be acquired) enzymatic deficiency in the metabolic pathway
of heme biosynthesis. The variable degree of block in the heme
biosynthetic pathway due to the enzyme deficiency results in
accumulation of different metabolic intermediates, whose toxicity is
responsible for the peculiar (cutaneous and/or neurovisceral) clinical
pictures observed in each of these diseases. According to the clinical
features, the porphyrias are classified as \u201cacute\u201d (or neuropsychic)
[characterized by acute neurovisceral crises (the acute porphyric
attack) involving the autonomic and/or central nervous system, but
also the liver and the kidney] and \u201con acute\u201d (or dermatological)
(mostly presenting with cutaneous lesions, due to photosensitivity).
The acute porphyrias are often misdiagnosed diseases: the acute
porphyric attack may in fact mimic many other more common medical
and neuropsychiatric conditions; its delayed diagnosis and treatment
(or its inappropriate treatment) may result in a fatal outcome. For
these reasons, many different specialists, such as surgeons,
psychiatrists, gastroenterologists, neurologists, emergency
physicians and dermatologists may be variably involved in the
diagnostic process, especially in those cases presenting with
acute and life-threatening clinical features. An early and definitive
diagnosis is mandatory to improve outcomes and to assure that
potentially harmful drugs are avoided. To date, the availability of an
adequate treatment has significantly improved the outcome of the
acute porphyric attacks, so the knowledge about the management of
these events may be relevant for the physicians working in internal
and emergency medicine units
Mechanisms of Neuronal Damage in Acute Hepatic Porphyrias
Porphyrias are a group of congenital and acquired diseases caused by an enzymatic
impairment in the biosynthesis of heme. Depending on the specific enzyme involved, different types
of porphyrias (i.e., chronic vs. acute, cutaneous vs. neurovisceral, hepatic vs. erythropoietic) are
described, with different clinical presentations. Acute hepatic porphyrias (AHPs) are characterized
by life-threatening acute neuro-visceral crises (acute porphyric attacks, APAs), featuring a wide
range of neuropathic (central, peripheral, autonomic) manifestations. APAs are usually unleashed by
external “porphyrinogenic” triggers, which are thought to cause an increased metabolic demand for
heme. During APAs, the heme precursors -aminolevulinic acid (ALA) and porphobilinogen (PBG)
accumulate in the bloodstream and urine. Even though several hypotheses have been developed to
explain the protean clinical picture of APAs, the exact mechanism of neuronal damage in AHPs is
still a matter of debate. In recent decades, a role has been proposed for oxidative damage caused by
ALA, mitochondrial and synaptic ALA toxicity, dysfunction induced by relative heme deficiency on
cytochromes and other hemeproteins (i.e., nitric oxide synthases), pyridoxal phosphate functional
deficiency, derangements in the metabolic pathways of tryptophan, and other factors. Since the
pathway leading to the biosynthesis of heme is inscribed into a complex network of interactions,
which also includes some fundamental processes of basal metabolism, a disruption in any of the steps
of this pathway is likely to have multiple pathogenic effects. Here, we aim to provide a comprehensive
review of the current evidence regarding the mechanisms of neuronal damage in AHPs
Challenges in diagnosis and management of acute hepatic porphyrias: from an uncommon pediatric onset to innovative treatments and perspectives
Acute hepatic porphyrias (AHPs) are a family of four rare genetic diseases resulting from a deficiency in one of the
enzymes involved in heme biosynthesis. AHP patients can experience potentially life-threatening acute attacks,
characterized by severe abdominal pain, along with other signs and symptoms including nausea, mental confusion,
hyponatraemia, hypertension, tachycardia and muscle weakness. Some patients also experience chronic manifestations
and long-term complications, such as chronic pain syndrome, neuropathy and porphyria-associated kidney
disease. Most symptomatic patients have only a few attacks in their lifetime; nevertheless, some experience frequent
attacks that result in ongoing symptoms and a significant negative impact on their quality of life (QoL). Initial diagnosis
of AHP can be made with a test for urinary porphobilinogen, -aminolaevulinic acid and porphyrins using a
single random (spot) sample. However, diagnosis is frequently missed or delayed, often for years, because the clinical
symptoms of AHP are non-specific and mimic other more common disorders. Delayed diagnosis is of concern as
some commonly used medications can trigger or exacerbate acute attacks, and untreated attacks can become severe,
potentially leading to permanent neurological damage or fatality. Other attack triggers include hormonal fluctuations
in women, stress, alcohol and low-calorie diets, which should be avoided in patients where possible. For the management
of attacks, intravenous hemin is approved, whereas new therapeutic approaches are currently being investigated
as a baseline therapy for prevention of attacks and improvement of QoL. Among these, a novel siRNA-based
agent, givosiran, has shown very promising results in a recently concluded Phase III trial and has been approved for
the management of AHPs. Here, we propose a challenging case study-with a very unusual pediatric onset of variegate
porphyria-as a starting point to summarize the main clinical aspects (namely, clinical manifestations, diagnostic challenges,
and therapeutic management) of AHPs, with a focus on the latest therapeutic innovations
MARKERS OF ENDOTHELIAL DYSFUNCTION AS PREDICTORS OF ASCITIC DECOMPENSATION IN PATIENTS WITH LIVER CIRRHOSIS.
A computer simulation protocol to assess the accuracy of a Radio Stereometric Analysis (RSA) image processor according to the ISO-5725
Radio-Stereometric-Analysis and x-ray fluoroscopy are radiological techniques
that require dedicated software to process data. The accurate calibration of
these software is therefore critical. The aim of this work is to produce a
protocol for evaluating the softwares' accuracy according to the ISO-5725. A
series of computer simulations of the radiological setup and images were
employed. The noise level of the images was also changed to evaluate the
accuracy with different image qualities. The protocol was tested on a custom
software developed by the authors. Radiological scene reconstruction accuracy
was of (0.092 +- 0.14) mm for tube position, and (0.38 +- 0.31) mm / (2.09 +-
1.39) deg for detectors oriented in a direction other than the source-detector
direction. In the source-detector direction the accuracy was of (2.68 +- 3.08)
mm for tube position, and of (0.16 +- 0.27) mm / (0.075 +- 1.16) deg for the
detectors. These disparate results are widely discussed in the literature.
Model positioning and orientation was also highly accurate: (0.22 +- 0.46) mm /
(0.26 +- 0.22) deg. Accuracy was not affected by the noise level. The protocol
was able to assess the accuracy of the RSA system. It was also useful to detect
and fix hidden bugs. It was also useful to detect and resolve hidden bugs in
the software, and in optimizing the algorithms
In Vivo Model of Osteoarthritis to Compare Allogenic Amniotic Epithelial Stem Cells and Autologous Adipose Derived Cells
SIMPLE SUMMARY: An early resolution of osteoarthritis (OA), through minimally invasive orthobiological solutions, would be important to enable a return to daily and sport activities, and delay prosthesis solutions. No study has yet evaluated amniotic epithelial stem cells (AECs) in OA. They could be considered a valid alternative to adipose derived cells, expanded or concentrated, because they differentiate into three lineages and express mesenchymal and embryonic markers, without a tumorigenic phenotype. The innovative aspects of this study are the comparison of three injective orthobiological treatments, the in vivo use of AECs in OA, and the evaluation of structural and inflammatory fronts of OA for up to six months. ABSTRACT: The challenge of osteoarthritis (OA) is to find a minimally invasive orthobiological therapy to contrast OA progression, on inflammatory and structural fronts. The aim of the present study is to compare the effects of an intra-articular injection of three orthobiological treatments, autologous culture expanded adipose-derived mesenchymal stromal cells (ADSCs), autologous stromal vascular fraction (SVF) and allogenic culture expanded amniotic epithelial stem cells (AECs), in an animal model of OA. OA was induced in 24 sheep by bilateral lateral meniscectomy and, at 3 and 6 months post-treatment, the results were analyzed with macroscopy, histology, histomorphometry, and biochemistry. All the three treatments showed better results than control (injection of NaCl), but SVF and AECs showed superiority over ADSCs, because they induced higher cartilage regeneration and lower inflammation. SVF showed better results than AECs at 3 and 6 months. To conclude, SVF seems to be more favorable than the other biological options, because it is easily obtained and rapidly used after harvesting, with good healing potential. AECs cause no discomfort and could be also considered for the treatment of OA joints
Endothelial Dysfunction in Acute Hepatic Porphyrias
Background Acute hepatic porphyrias (AHPs) are a group of rare diseases caused by
dysfunctions in the pathway of heme biosynthesis. Although acute neurovisceral attacks are the
most dramatic manifestations, patients are at risk of developing long-term complications, several of
which are of a vascular nature. The accumulation of non-porphyrin heme precursors is deemed to
cause most clinical symptoms. AimWe measured the serum levels of endothelin-1 (ET-1) and nitric
oxide (NO) to assess the presence of endothelial dysfunction (ED) in patients with AHPs. Forty-six
patients were classified, according to their clinical phenotype, as symptomatic (AP-SP), asymptomatic
with biochemical alterations (AP-BA), and asymptomatic without biochemical alterations (AP-AC).
Results Even excluding those under hemin treatment, AP-SP patients had the lowest NO and highest
ET-1 levels, whereas no significant differences were found between AP-BA and AP-AC patients.
AP-SP patients had significantly more often abnormal levels of ED markers. Patients with the highest
heme precursor urinary levels had the greatest alterations in ED markers, although no significant
correlation was detected. Conclusions ED is more closely related to the clinical phenotype of AHPs
than to their classical biochemical alterations. Some still undefined disease modifiers may possibly
determine the clinical picture of AHPs through an effect on endothelial functions
PRP Augmentation for ACL Reconstruction
Current research is investigating new methods to enhance tissue healing to speed up recovery time and decrease the risk of failure in Anterior Cruciate Ligament (ACL) reconstructive surgery. Biological augmentation is one of the most exploited strategies, in particular the application of Platelet Rich Plasma (PRP). Aim of the present paper is to systematically review all the preclinical and clinical papers dealing with the application of PRP as a biological enhancer during ACL reconstructive surgery. Thirty-two studies were included in the present review. The analysis of the preclinical evidence revealed that PRP was able to improve the healing potential of the tendinous graft both in terms of histological and biomechanical performance. Looking at the available clinical evidence, results were not univocal. PRP administration proved to be a safe procedure and there were some evidences that it could favor the donor site healing in case of ACL reconstruction with patellar tendon graft and positively contribute to graft maturation over time, whereas the majority of the papers did not show beneficial effects in terms of bony tunnels/graft area integration. Furthermore, PRP augmentation did not provide superior functional results at short term evaluation
Recognized and Emerging Features of Erythropoietic and X-Linked Protoporphyria
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inherited
disorders resulting from defects in two different enzymes of the heme biosynthetic pathway, i.e.,
ferrochelatase (FECH) and delta-aminolevulinic acid synthase-2 (ALAS2), respectively. The
ubiquitous FECH catalyzes the insertion of iron into the protoporphyrin ring to generate the final
product, heme. After hemoglobinization, FECH can utilize other metals like zinc to bind the
remainder of the protoporphyrin molecules, leading to the formation of zinc protoporphyrin.
Therefore, FECH deficiency in EPP limits the formation of both heme and zinc protoporphyrin
molecules. The erythroid-specific ALAS2 catalyses the synthesis of delta-aminolevulinic acid
(ALA), from the union of glycine and succinyl-coenzyme A, in the first step of the pathway in the
erythron. In XLP, ALAS2 activity increases, resulting in the amplified formation of ALA, and iron
becomes the rate-limiting factor for heme synthesis in the erythroid tissue. Both EPP and XLP lead
to the systemic accumulation of protoporphyrin IX (PPIX) in blood, erythrocytes, and tissues
causing the major symptom of cutaneous photosensitivity and several other less recognized signs
that need to be considered. Although significant advances have been made in our understanding of
EPP and XLP in recent years, a complete understanding of the factors governing the variability in
clinical expression and the severity (progression) of the disease remains elusive. The present review
provides an overview of both well-established facts and the latest findings regarding these rare
diseases
17)脊椎々間板手術症例の検討 : とくに椎間板障害例における手術適応について(第399回千葉医学会整形外科例会,第8回千葉整形外科災害外科臨床懇談会,千葉県労災指定医集談会)
<p>Data are expressed as medians and interquartile ranges; comparisons among time points, as determined by Friedman-ANOVA test, and between L-PRP and HA treatments, as determined by the Mann-Whitney U test, are not significant. w = week, m = month</p
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