Visceral Pathology Research Articles

Fixed Drug Eruption: Primary Site Involvement on Maximal Points of Head’s Zones

The principles behind the primary localization of lesions in fixed drug eruption are still unknown. Studies investigating the predilection areas indicated drug-related, trauma-related or inflammation-related specific site involvement in fixed drug eruption. This study presents new findings of primary site involvement on the maximal points of Head's zones. In the 3 cases reported here, fixed drug eruption lesions were located at specific sites; the so-called maximal points of Head's zones, which are known to be the most active dermatomal areas of an underlying visceral pathology. An underlying internal disturbance was found in all 3 patients, corresponding to the organ-related maximal point of Head's zones in each case. In conclusion, the primary location of the fixed drug eruption lesions on the maximal points of the Head's zones according to the well-known neurophysiological map is an important observation in studying the predilection areas.

Diagnosis and Management of Enteric Disease and Abdominal Catastrophe in Peritoneal Dialysis Patients With Peritonitis

Peritoneal dialysis (PD)-associated peritonitis rates have decreased significantly in recent years, especially Staphylococcus epidermidis and Staphylococcus aureus infections. Rates of gram-negative, polymicrobial, and fungal peritonitis have remained steady. The reported mortality of gram-negative and polymicrobial peritonitis varies widely (4%-50%). Most likely, the reason for this variability is that prognosis depends on the underlying etiology more than the specific microorganisms isolated. Gram-negative, polymicrobial, and fungal infection have variable association with documented visceral disease, and the highest mortality occurs in reports with the highest prevalence of intra-abdominal pathology. The odds ratio of death in PD patients with documented abdominal catastrophe and peritonitis is reported to be 20:1 compared with all other causes. Further reductions in PD-associated peritonitis mortality are likely to depend on earlier diagnosis and better management of intra-abdominal pathology. Presentation with hypotension, sepsis, lactic acidosis, and/or elevation of peritoneal fluid amylase should raise immediate concern for "surgical" peritonitis. Suspicion for visceral disease should also be high in patients with gram-negative, polymicrobial, and fungal infection or those who fail to improve rapidly as judged by clinical signs and symptoms, cell counts, and repeat cultures. Nonlocalizing physical examination and negative or nonspecific results of abdominal computed tomography do not rule out serious intra-abdominal disease. Immediate initiation of broad antibiotic coverage including for anaerobic infection is indicated when bowel pathology is suspected. Urgent surgical consultation, with active discussion and participation by the nephrologist, is advisable when visceral pathology is suspected and the patient is unstable or fails to improve rapidly.

417. Combination Brain and Systemic Injections of AAV Results in Whole Body Therapy and Extension of Lifespan in the Niemann-Pick Mouse

The majority of lysosomal storage diseases contain both CNS and visceral pathology. Many experimental designs use either intracranial injection of viral vectors to treat the neurodegenerative phenotype of the disease, or systemic delivery to treat the viscera. In this study, we tested whether a combination of brain and systemic injections of adeno-associated virus (AAV) vectors could increase lifespan, provide whole body reversal of pathology, and improve motor and cognitive function in the acid sphingomyelinase knock out (ASMKO) mouse model of Niemann-Pick disease. ASMKO mice at 4 weeks of age were injected systemically with AAV8- hASM, and subsequently, the same animals were injected into the brain with AAV2-hASM. All the mice treated by combination injections survived to 54 weeks of age. This was a significant improvement over untreated ASMKO mice, animals that had been treated by systemic injection only or by brain injection only, which had median life spans of 34 weeks, 45 weeks, and 43 weeks, respectively. Thus the brain alone injections did not protect animals from dying. Animals treated by the combination therapy also displayed normal weight gain, and significant functional recovery on the rotarod (motor task) and the Barnes maze (cognitive task) throughout the time course of the study. These data support the contention that combination therapy can improve the quality of life before and within the time frame of extended survival.

TRAUMATIC ISOLATED PERICARDIO-DIAPHRAGMATIC RUPTURE

Pericardio–diaphragmatic rupture is an uncommon problem that poses a diagnostic challenge to surgeons. This article reports an unusual case of traumatic pericardio-diaphragmatic rupture in a 36-year-old male who has no additional intraabdominal visceral injury or thoracic pathology. There was a 7 cm lateral tear on the left dome of the diaphragm and a 2 cm medial tear, also involving pericardio-diaphragmatic junction, with the heart uninjured. The partially herniated stomach was easily pulled out from the thorax cavity through the diaphragmatic rupture. The rupture was reparied by interrupted non-absorbable sutures. The patient had no complaints on his follow up.

Osteopenia prevalence in ankylosing spondylitis and its correction with alphacalcidol

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

Gaucher disease type 1: Revised recommendations on evaluations and monitoring for adult patients

For patients with type 1 Gaucher disease, challenges to patient care posed by clinical heterogeneity, variable progression rates, and potential permanent disability that can result from untreated or suboptimally treated hematologic, skeletal, and visceral organ involvement dictate a need for comprehensive, serial monitoring. An updated consensus on minimum recommendations for effective monitoring of all adult patients with type 1 Gaucher disease has been developed by the International Collaborative Gaucher Group (ICGG) Registry coordinators. These recommendations provide a schedule for comprehensive and reproducible evaluation and monitoring of all clinically relevant aspects of this disease. The initial assessment should include confirmation of deficiency of beta-glucocerebrosidase, genotyping, and a complete family medical history. Other assessments to be performed initially and at regular intervals include a complete physical examination, patient-reported quality of life using the SF-36 survey, and assessment of hematologic (hemoglobin and platelet count), visceral, and skeletal involvement, and biomarkers. Specific radiologic imaging techniques are recommended for evaluating visceral and skeletal pathology. All patients should undergo comprehensive regular assessment, the frequency of which depends on treatment status and whether therapeutic goals have been achieved. Additionally, reassessment should be performed whenever enzyme therapy dose is altered, or in case of significant clinical complication.

Brain transplantation of genetically modified bone marrow stromal cells corrects CNS pathology and cognitive function in MPS VII mice.

Current therapies for lysosomal storage diseases (LSDs), enzyme replacement therapy and bone marrow transplantation are effective for visceral organ pathology of LSD, but their effectiveness for brain involvement in LSDs is still a subject of controversy. As an alternative approach, we transplanted genetically modified bone marrow stromal (BMS) cells to lateral ventricle of newborn mucopolysaccharidosis VII (MPS VII) mice. MPS VII is one of LSDs and caused by deficiency of beta-glucuronidase (GUSB), resulting in accumulation of glycosaminoglycans (GAGs) in brain. At 2 weeks after transplantation, the GUSB enzyme-positive cells were identified in olfactory bulb, striatum and cerebral cortex, and the enzymatic activities in various brain areas increased. The GAGs contents in brain were reduced to near normal level at 4 weeks after transplantation. Although GUSB activity declined to homozygous level after 8 weeks, the reduction of GAGs persisted for 16 weeks. Microscopic examination indicated that the lysosomal distention was not found in treated animal brain. Cognitive function in MPS VII animals as evaluated by Morris Water Maze test in treated mice showed a marked improvement over nontreated animals. Brain transplantation of genetically modified BMS cells appears to be a promising approach to treat diffuse CNS involvement of LSDs.

Different genetic control of cutaneous and visceral disease after Leishmania major infection in mice.

The mouse strains BALB/cHeA (BALB/c) and STS/A (STS) are susceptible and resistant to Leishmania major-induced disease, respectively. We analyzed this difference using recombinant congenic (RC) BALB/c-c-STS/Dem (CcS/Dem) strains that carry different random subsets of 12.5% genes of the strain STS in a BALB/c background. Previously, testing the resistant strain CcS-5, we found five novel Lmr (Leishmania major response) loci, each associated with a different combination of pathological and immunological reactions. Here we analyze the response of RC strain CcS-16, which is even more susceptible to L. major than BALB/c. In the (CcS-16 x BALB/c)F(2) hybrids we mapped three novel loci that influence cutaneous or visceral pathology. Lmr14 (chromosome 2) controls splenomegaly and hepatomegaly. On the other hand Lmr15 (chromosome 11) determines hepatomegaly only, and Lmr13 (chromosome 18) determines skin lesions only. These data confirm the complex control of L. major-induced pathology, where cutaneous and visceral pathology are controlled by different combinations of genes. It indicates organ-specific control of antiparasite responses. The definition of genes controlling these responses will permit a better understanding of pathways and genetic diversity underlying the different disease phenotypes.

Plasmid-based gene transfer ameliorates visceral storage in a mouse model of Sandhoff disease.

Sandhoff disease is a severe neurodegenerative disorder with visceral involvement caused by mutations in the HEXB gene coding for the beta subunit of the lysosomal hexosaminidases A and B. HEXB mutations result in the accumulation of undegraded substrates such as GM2 and GA2 in lysosomes. We evaluated the efficacy of cationic liposome-mediated plasmid gene therapy using the Sandhoff disease mouse, an animal model of a human lysosomal storage disease. The mice received a single intravenous injection of two plasmids, encoding the human alpha and beta subunits of hexosaminidase cDNAs. As a result, 10-35% of normal levels of hexosaminidase expression, theoretically therapeutic levels, were achieved in most visceral organs, but not in the brain, 3 days after injection with decreased levels by day 7. Histochemical staining confirmed widespread enzyme activity in visceral organs. Both GA2 and GM2 were reduced by almost 10% and 50%, respectively, on day 3, and by 60% and 70% on day 7 compared with untreated age-matched Sandhoff disease mice. Consistent with the biochemical results, a reduction in GM2 was observed in liver cells histologically as well. These initial findings support further development of the plasmid gene therapy against lysosomal diseases with visceral pathology.

Endogenous kynurenines as targets for drug discovery and development.

The kynurenine pathway is the main pathway for tryptophan metabolism. It generates compounds that can modulate activity at glutamate receptors and possibly nicotinic receptors, in addition to some as-yet-unidentified sites. The pathway is in a unique position to regulate other aspects of the metabolism of tryptophan to neuroactive compounds, and also seems to be a key factor in the communication between the nervous and immune systems. It also has potentially important roles in the regulation of cell proliferation and tissue function in the periphery. As a result, the pathway presents a multitude of potential sites for drug discovery in neuroscience, oncology and visceral pathology.

Bone Marrow Stem Cell Gene Therapy of Arylsulfatase A-Deficient Mice, Using an Arylsulfatase A Mutant That Is Hypersecreted from Retrovirally Transduced Donor-Type Cells

Arylsulfatase A (ASA)-deficient mice represent an animal model for the fatal lysosomal storage disease metachromatic leukodystrophy, which is characterized by widespread intralysosomal deposition of sulfatide. Bone marrow stem cell gene therapy in mice, using a retroviral vector mediating expression of wild-type human ASA, has the potential to ameliorate the visceral pathology, but improves the prevailing brain disease and neurologic symptoms only marginally. One factor that influences the efficacy of bone marrow transplantation therapy in lysosomal storage diseases is the secretion level of the therapeutic enzyme from donor-type cells. Here we test the potential of a hypersecreted glycosylation variant of ASA. Although this mutant lacks mannose 6-phosphate residues it is taken up by cells by a mannose 6-phosphate receptor-independent pathway and causes partial metabolic correction of ASA-deficient mouse cells. Retrovirally mediated transfer of the mutant cDNA into ASA-deficient mice results in the sustained expression of the transgene. Serum levels argue for an increased secretion of the glycosylation mutant also in vivo. Tissue levels were reduced to 2% in liver and up to 40% in kidney compared with animals treated with the wild-type enzyme, indicating reduced endocytosis. Thus, the limited uptake of the variant enzyme outweighs the putative advantageous effect of improved supply. Although the mutant enzyme is able to correct the metabolic defect partially, histological examinations did not reveal any reduction of sulfatide storage in treated animals. Surprisingly, analysis of neurologic symptoms indicated a significant improvement of the gait pattern.

A mutation in the ovine cathepsin D gene causes a congenital lysosomal storage disease with profound neurodegeneration.

The neuronal ceroid lipofuscinoses (NCLs) constitute a group of neurodegenerative storage diseases characterized by progressive psychomotor retardation, blindness and premature death. Pathologically, there is accumulation of autofluorescent material in lysosome-derived organelles in a variety of cell types, but neurons in the central nervous system appear to be selectively affected and undergo progressive death. In this report we show that a novel form of NCL, congenital ovine NCL, is caused by a deficiency in the lysosomal aspartyl proteinase cathepsin D. A single nucleotide mutation in the cathepsin D gene results in conversion of an active site aspartate to asparagine, leading to production of an enzymatically inactive but stable protein. This results in severe cerebrocortical atrophy and early death, providing strong evidence for an important role of cathepsin D in neuronal development and/or homeostasis.

Peripheral neuropathies causing chronic pelvic pain

Chronic pelvic pain is usually assumed to be visceral in origin by both patients and physicians. Because of the phenomenon of viscerosomatic convergence, it may be impossible to distinguish the origin without a meticulous history, physical examination, and nerve blocks. Error in diagnosis and treatment may lead to unhelpful surgery and poor results. Peripheral somatic neuropathies often mimic internal organ pathology. Similarly, visceral pathology can produce changes in peripheral somatic nerves that must also be addressed if maximum pain relief is to be attained. Awareness of peripheral neuropathies will favor more effective treatment for these patients.

Alleviation of neuronal ganglioside storage does not improve the clinical course of the Niemann-Pick C disease mouse

Niemann-Pick disease Type C (NP-C) is a progressive neurodegenerative disorder caused by mutations in the NPC1 gene and characterized by intracellular accumulation of cholesterol and sphingo-lipids. The major neuronal storage material in NP-C consists of gangliosides and other glycolipids, raising the possibility that the accumulation of these lipids may participate in the neurodegenerative process. To determine if ganglioside accumulation is a crucial factor in neuropathogenesis, we bred NP-C model mice with mice carrying a targeted mutation in GalNAcT, the gene encoding the beta-1-4GalNAc transferase responsible for the synthesis of GM2 and complex gangliosides. Unlike the NP-C model mice, these double mutant mice did not exhibit central nervous system (CNS) accumulation of gangliosides GM2 or of glycolipids GA1 and GA2. Histological analysis revealed that the characteristic neuronal storage pathology of NP-C disease was substantially reduced in the double mutant mice. By contrast, visceral pathology was similar in the NP-C and double mutant mice. Most notably, the clinical phenotype of the double mutant mice, in the absence of CNS ganglioside accumulation and associated neuronal pathology, did not improve. The results demonstrate that complex ganglioside storage, while responsible for much of the neuronal pathology, does not significantly influence the clinical phenotype of the NP-C model.

Facilitating survival and recovery by removing autogenic pathology from the clinical picture

For the most part, the clinical picture is the expression of autogenic pathology and, unless the anatomical insult represents a major structural compromise, it contributes little to the clinical picture. Autogenic pathology created by the processing of peripheral neurological impulses altered by the presence of anatomical insults is created independently of the gravity of the anatomical insults. Even in the presence of a survivable insult, autogenic pathology is often fatal. Each successful resuscitation effort identifies a patient with a survivable insult who almost died before autogenic pathology was removed by cerebral anoxia, and/or electric shock. Similar patients who suffer terminal brain damage cannot be identified. Cardinal receptors furnish the embryo with its first neural contact with its environment. On completion of embryological migration, they occupy a position in the skin overlying the root of their spinal nerve. Cardinal receptors are functionally segmented to the specific distribution of their spinal nerve and use the stable neurological impulses from the skin to furnish the cadence by which peripheral impulses are processed and valued. Selected cardinal receptors may be specifically stimulated by saline infiltration that produces intradermal blebs in the skin overlying their spinal nerve's root. An augmented burst of infiltration pain immediately followed by symptomatic relief identifies monitoring cardinal receptors. The identification of monitoring receptors confirms the presence of pathology found within the specific distribution of their spinal nerve. Peripheral impulses processed within the cadence of highly stimulated cardinal receptors are assigned an insignificant value. Assigning an insignificant value to peripheral impulses altered by the presence of an anatomical insult removes autogenic pathology from the clinical picture. The immediate onset of profound symptomatic relief heralds the removal of autogenic pathology. Visceral pathology is monitored by bilateral pairs of cardinal receptors so it produces discomfort perceived without specific location information. Therefore, the specific visceral distribution has been discounted and is virtually unknown. However, when visceral pathology is correlated with bilateral pairs of monitoring cardinal receptors there are no patient variations.

Adenovirus-mediated gene transfer and expression of human beta-glucuronidase gene in the liver, spleen, and central nervous system in mucopolysaccharidosis type VII mice.

Mucopolysaccharidosis type VII (Sly syndrome) is a lysosomal storage disease caused by inherited deficiency of the lysosomal enzyme beta-glucuronidase. A murine model of this disorder has been well characterized and used to study a number of forms of experimental therapies, including gene therapy. We produced recombinant adenovirus that expresses human beta-glucuronidase and administered this recombinant adenovirus to beta-glucuronidase-deficient mice intravenously. The beta-glucuronidase activities in liver and spleen were elevated to 40% and 20%, respectively, of the heterozygote enzymatic level at day 16. Expression persisted for at least 35 days. Pathological abnormalities of these tissues were also improved, and the elevated levels of urinary glycosaminoglycans were reduced in treated mice. However, the beta-glucuronidase activity in kidney and brain was not significantly increased. After administration of the recombinant adenovirus directly into the lateral ventricles of mutant mice, the beta-glucuronidase activity in crude brain homogenates increased to 30% of heterozygote activity. Histochemical demonstration of beta-glucuronidase activity in brain revealed that the enzymatic activity was mainly in ependymal cells and choroid. However, in some regions, the adenovirus-mediated gene expression was also evident in brain parenchyma associated with vessels and in the meninges. These results suggest that adenovirus-mediated gene delivery might improve the central nervous system pathology of mucopolysaccharidosis in addition to correcting visceral pathology.

Obtaining automated diagnostic information and pain relief

The silent confluent flow of a conglomerate of sensory related signals is automatically delegated to the total specific distribution of a single spinal nerve. This silent confluent flow may be accessed, evaluated, and modified by using intradermal saline infiltration to stimulate the sensory receptors located in the skin overlying its nerve root. An unmistakable augmented burst of infiltration pain immediately followed by profound long lasting pain relief identifies a spinal nerve monitoring peripheral pathology. The identification of a monitoring spinal nerve tentatively confirms the presence of pathology confined to the specific peripheral distribution of that specific spinal nerve. The practically unknown visceral distribution proves to be specific and visceral pathology echoes through its collated spinal nerve without patent variation. Practically cost free and without side effects or contraindications dermatomal infiltration opens a whole new chapter in the field of diagnosis as it may be used to determine the presence of pathology, to locate that pathology to the specific distribution of a specific spinal nerve or nerves, and to produce unequalled pain relief.

Neuropathie abdominale à expression motrice d'origine diabétique. À propos d'un cas

Authors report a case of diabetic truncal neuropathy presenting as a painful abdominal swelling. This entity, which frequently is probably under estimated, may mimic abdominal visceral pathology and patients may be subjected unnecessary to extensive diagnosis procedures.

Celiac territory ischemic syndrome in visceral artery occlusion

Abdominal angina that is characterized by postprandial pain, and often associated with weight loss, is a well-recognized symptom complex of mesenteric artery insufficiency (mesenteric territory symptoms). In the past 5 years, we have observed six patients with atypical symptoms who had mesenteric artery occlusion combined with stenosis or occlusion of the celiac artery. Atypical symptoms included severe nausea and vomiting at the sight or smell of food, anorexia, weight loss, and right upper quadrant or epigastric discomfort (celiac territory symptoms). An extensive work-up to rule out gastric, pancreatic, biliary, or colonic pathology was undertaken in these patients. The findings included gallbladder dysfunction, diffuse micro-ulceration of gastric mucosa, and colonic mucosal ulceration. The diagnosis of visceral artery occlusion was initially missed in all six patients. Four patients had cholecystectomy. Visceral angiography confirmed occlusion of the celiac, superior, and inferior mesenteric arteries. Five patients had dramatic resolution of symptoms after restoration of visceral circulation. One patient who developed intestinal infarction before revascularization died. Symptoms suggesting upper abdominal visceral pathology may be a manifestation of celiac artery stenosis/occlusion coexisting with mesenteric artery occlusive disease. Visceral angiography should be part of the work-up in these patients for early diagnosis and prompt management.

Ruling Out Danger.

In brief Thoracic pain can stem from a variety of causes, some serious, some less so. In active patients, the source is usually musculoskeletal, originating from the spine, ribs, sternum, or anterior shoulder, but cardiac and other visceral pathology must be ruled out. A systematic approach to obtaining a detailed description of the patient's pain and making an exact anatomic diagnosis can help the clinician institute the most effective treatment.