Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
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Mitochondrial disorder is a relatively rare disease during childhood. Previous studies concluded that renal complications in this disease most often occur in patients with mitochondrial encephalomyopathies. We describe a boy with mitochondrial disease who presented with proteinuria while lacking neuromyopathy. Proteinuria was detected at the age of 6 years, including large amounts of low-molecular-weight proteins such as beta(2)- and alpha1-microglobulin. Renal functions were normal. Proximal tubular dysfunction and other renal manifestations were absent. Episodic neurologic problems such as migraine and nervous system diseases including epilepsy, depression, schizophrenia and amytrophic lateral sclerosis (ALS) were found in the boy's family members. Renal tubular basement membrane atrophy and interstitial fibrosis with mononuclear cell infiltration were observed. Ultrastructural examination showed mitochondria, mainly in the proximal tubules, which varied in size and had disoriented cristae. Mutation analysis using mitochondrial DNA (mtDNA) extracted from renal tissues demonstrated a A-->G point mutation at nucleotide position 3243 in the tRNA(Leu(UUR)) gene, while there was no mutation found in mtDNA extracted from peripheral leukocytes. Awareness among pediatricians of mitochondrial disorders, detection of low-molecular-weight proteinuria, renal ultrastructural examination and mutation analysis of mtDNA obtained from renal tissues could be important for early diagnosis of this disease.
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PMID:A boy with mitochondrial disease: asymptomatic proteinuria without neuromyopathy. 1464 37

In 2002, a 38-year-old woman was referred to the department of dermatological sciences for the evaluation of erythematous-infiltrated lesions with prominent purpuric and erosive components distributed on her face, upper chest, and extensor surfaces of the limbs, which developed over a 3-month period. In 1997 the patient suffered from polyarthralgia (proximal interphalangeal,knee, wrist, and metacarpophalangeal joints) associated with morning stiffness. In 1999 she was admitted to a psychiatric unit for depression with episodes of lipothymia. In the same year, since she developed diffuse and persistent urticarial manifestations with angioedema and livedo reticularis of the limbs in association with anticardiolipin antibodies, vasculitis was proposed. Upon examination, erythematous-infiltrated and erosive lesions in association with serohemorrhagic crusts were present on the face,neck, chest, upper trunk, and extensor surfaces of the upper limbs and thighs (Figures 1-3). Telangiectasias were especially evident on the cheeks, where prominent edema conferred her face a moon-like appearance (Figure 1). Laboratory investigations disclosed microcytic anemia, elevated erythrocyte sedimentation rate, proteinuria (30 mg/dL), positive antinuclear antibodies (1:80) with diffuse fluorescence pattern, lowered complement levels (C3: 31 mg/dL, C4: 3 mg/dL), circulating immunocomplexes binding Clq, and high titers of anti-TSH receptor antibodies. Indirect immunofluorescence was negative for the detection of anti-basement membrane zone antibodies. Histological examination of the lesional skin of the shoulder documented epidermal atrophy, marked vacuolar degeneration of the basal cell layer, colloid bodies, and a perivascular lymphohistiocytic infiltration of the upper and deep dermis (Figure 4). Direct immunofluorescence performed on affected skin showed junctional granular deposition of IgG, C3,and Clq in association with perivascular C3 and Clq deposits in the upper dermis; direct immunofluorescence on sun-protected,non-lesional skin showed similar immunological deposition both at the basement membrane zone and in the perivascular dermis.Based upon the clinical, histologic, and immunopathologic findings, we proposed the diagnosis of systemic lupus erythematosus with maculopapular and erosive skin lesions. The patient was treated with methylprednisolone IV (pulse therapy, 250 mg) tapered over 10 days and later continued p.o. After a few weeks, significant improvement of cutaneous manifestations was noted.
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PMID:Systemic lupus erythematosus with unusual maculopapular and erosive cutaneous lesions. 1536 71

This study was conducted with 3 objectives in mind: first, to identify the toxic fraction (aqueous or organic) in leaves and flowers; second, to identify diagnostic marker(s) of toxicosis in cats; and, third, to evaluate the morphologic effects of intoxication. The study was conducted in 2 phases. Phase 1 was to identify which extract, organic or aqueous, was nephrotoxic and also to determine the appropriate dose for use in the phase 2 studies. Results indicated that only the aqueous extracts of leaves and flowers were nephrotoxic and pancreotoxic. To identify the proximate toxic compound, cats in the phase 2 study were orally exposed to subfractions of the aqueous flower extract, 1 subfraction per cat. Results confirmed vomiting, depression, polyuria, polydipsia, azotemia, glucosuria, proteinuria, and isosthenuria as toxic effects of the Easter lily plant. Another significant finding in serum was elevated creatinine kinase. Significant histologic kidney changes included acute necrosis of proximal convoluted tubules and degeneration of pancreatic acinar cells. Renal ultrastructural changes included swollen mitochondria, megamitochondria, edema, and lipidosis. Subfraction IIa3 of the aqueous floral extract contained most of the toxic compound(s). These studies reproduced the clinical disease, identified the most toxic fraction of the Easter lily, and helped characterize the clinical pathology, histopathology, and ultrastructural pathology associated with the disease.
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PMID:A comprehensive study of Easter lily poisoning in cats. 1558 68

The diversity of clinical presentations of lupus nephritis parallel the diversity of pathologic lesions seen in the kidneys of patients with SLE. Renal manifestations range from asymptomatic hematuria or proteinuria to overt nephritic and nephrotic syndromes, rapidly progressive glomerulonephritis, and chronic renal failure. Subclinical nephropathy both during presentation and during monitoring of disease activity is frequently missed because of the notorious unreliability of routine screening urinalyses performed in high-throughput clinical pathology laboratories. Requisitions for urine microscopy should be flagged for special attention in patients at risk for lupus nephritis. Depression of classic complement pathway components and high titers of anti-DNA, anti-nucleosome, or anti-Clq antibodies identify patients are increased risk of renal involvement or flares of nephritis. Several disease activity and damage indexes are available, but they are mostly used in clinical research setting and none has achieved wide use for standard clinical practice.
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PMID:Clinical presentation and monitoring of lupus nephritis. 1573 84

The (NZBxNZW) F(1) mouse develops a spontaneous autoimmune disease process with striking similarities to human systemic lupus erythematosus (SLE). In female (NZBxNZW) F(1) mice, the production of IgG antinuclear antibodies, including antibodies to double-stranded DNA (dsDNA), is associated with the development of a severe immune complex-mediated glomerulonephritis that results in death from renal failure in virtually all animals by 12 months of age. Since B-1 and marginal zone (MZ) cells represent a potential source of pathogenic antibodies and because B cell superantigens have been demonstrated to reduce B-1 and MZ cells in vivo, we tested the effect of repeated injections of the superantigen protein A (SpA) from S. aureus on the disease of this lupus model. We found that weekly intraperitoneal injections of SpA delay the progression of serum anti-DNA IgG and reduce proteinuria early in young female (NZBxNZW) F(1) mice. This superantigen also induced a specific depression in the numbers of peritoneal B-1 cells, as compared to mice treated with a control protein. These results support the role of B-1 cells in the development of the autoimmune disease in this mouse model and suggest that B cell superantigens may be useful in the management of autoimmune conditions.
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PMID:Effect of the B cell superantigen protein A from S. aureus on the early lupus disease of (NZBxNZW) F1 mice. 1582 73

In an attempt to survey the attitude of the heads of some distinguished transplant programs in the Middle East countries towards the follow-up and complications that may ensue in the live renal allograft donors, we sent a questionnaire to 29 active renal transplant centers in the Kingdom of Saud Arabia (KSA) and some other Middle East countries, which together perform about 1500 living renal transplantations annually. The study was performed during November-December, 2005. Th questionnaire was intended to evaluate the presence of a protocol that guides the physicians in their selection, work-up and follow-up of the live renal allograft donors, the presence of regular time schedule for follow-up of the donors during the first year and thereafter, and the tests performed during these clinic visits, the physicians' perception towards the life-long health insurance of the live donors as well as the physicians' estimates of the major complications that may occur in the live donors such a hypertension, proteinuria, chronic renal failure, early surgical complications and depression. There were 20 responses (69%) from transplant centers that together perform about 1200 (80%) living rena transplantations annually. There were 18 (90%) respondents who had a protocol to guide the selection o the live renal allograft donors, 10 (52.6%) had a written policy for post-donation follow-up of live renal allograft donors, 15 (83.3%) would see the donors for the first time within three months post-discharge, 10 (66.7%) would see the donors every three months thereafter during the first year and 11 (68.8%) would see them once a year after the first year. There was a consensus among the respondents to monitor the renal function tests that include plasma urea creatinine and urinalysis. The post donation incidence of hypertension, proteinuria, chronic renal failure, early surgical complications and psychological problems such as depression was estimated by more than 80% of the respondents as 1-5%. We conclud that the current practices concerning the follow-up of renal allograft live donors by the dialysis centers i the Middle East seem promising. However, this being a questionnaire survey, results may not be totall accurate. Prospective studies are required to ensure that protocols for follow-up are abided by.
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PMID:Attitude of transplant centers in the Middle East towards the follow-up of renal allograft live donors. 1690 32

This report described an interim analysis of a investigator-driven multicenter trial in renal transplant recipients: the Prospective Quality of life Renal Transplantation Switch Study; Tacrolimus-based immunosuppression ("PQRST study"). Patients included in the trial initially treated with cyclosporine-based immunosuppression after renal transplantation who experienced side effects, such as hypertension, hyperlipidemia, hypertrichosis, or other adverse reactions, were converted to a tacrolimus-based immunosuppressive regimen (n = 31). Steroids were subsequently discontinued between 3 and 6 months after the conversion. As of today 19/31 (50%) patients have been successfully weaned off steroids with the remaining patients in this process. In this interim analysis, with a follow-up ranging from 1 to 18 months both patient and graft survivals were 100%. No patient experienced an acute rejection episode; none of the grafts were lost. Blood pressure decreased in 22/31 (71%) of the patients. No patient developed de novo diabetes or other serious side effect related to the conversion. Three patients were withdrawn from the trial because of side effects: bleeding, depression, and proteinuria. However, none of these adverse events were felt to be directly related to the change of the immunosuppressive regimen to tacrolimus monotherapy. In conclusion, conversion from cyclosporine to tacrolimus-based therapy was safe and well tolerated; it may improve the cardiovascular risk profile after kidney transplantation.
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PMID:Steroid-free immunosuppression in kidney transplant recipients and prograf monotherapy: an interim analysis of a prospective multicenter trial. 1709 29

Fatal cytauxzoonosis is described in a captive reared lioness (Panthera leo) and its 6-month-old cub. Clinical signs in the lioness included loss of weight, depression, anaemia, loss of hair, dark discolored urine, tachypnoea, nystagmus, deaphness and staggering gait. The cub died after a short period of depression. In the lioness, laboratory examination revealed normochromic normocytic anaemia, neutrophilia, lymphopenia, monocytosis, eosinopenia, thrombocytopenia, proteinuria, pyuria, haematuria and increased. At necropsy the lioness showed marked pulmonary edema and slight gelatinous translucent edema in the mediastinum, petechiae and echymosis disseminated in the serosae, and the intestinal content was red and semiliquid. The cub presented hemothorax, endocardial and pulmonary edema, petechiae in the cardiac serosae, hepatic and splenic congestion and segments of the small intestine with blood stained fluid contents and reddish mesenteric lymph nodes. Histopathological examination of liver, spleen, heart, lungs, intestines, pancreas, mesenteric lymph nodes, kidneys, skeletal muscle, brain and skin revealed large number of intravascular macrophages with their cytoplasm filled with various schizogonic stages of a Theileriidae. Electron microscopy confirmed the presence of schizonts in endothelial-associated macrophages. The diagnosis was established by the finding of the pathognomonic schizonts in macrophages within blood vessels in several organs and tissues from both lions. This is the first report of feline cytauxzoonosis in P. leo and of a confirmed infection by Cytauxzoon felis in felidae in South America.
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PMID:Fatal cytauxzoonosis in captive-reared lions in Brazil. 1730 59

An Asian multiparous woman weighing 47 kg, who suffered from a rare myopathy, congenital fibre type disproportion, was given morphine 10 mg intramuscularly for labour analgesia. After delivery, she had diastolic hypertension and proteinuria and was prescribed magnesium sulphate. Some hours later she became unresponsive with little respiratory effort. Blood gas analysis revealed a respiratory acidosis. Naloxone administration reversed the symptoms. Further doses were required as the respiratory depression recurred. Opioid-related narcosis is the most likely diagnosis in this case. Other possible differential diagnoses were magnesium overdose or a post-ictal state. The presence of a myopathy could render this patient susceptible to the respiratory effects of opioids. Other explanations for an exaggerated and delayed response to opioids include co-administration of other respiratory depressant drugs such as magnesium sulphate, co-morbidity such as renal impairment and genetic variability in the metabolism of morphine. Robust guidelines and highlighting patients with risk factors are required to prevent this complication from recurring.
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PMID:Opioid-related narcosis in a woman with myopathy receiving magnesium. 1764 82

Case history The two obese mandrills (Mandrillus sphinx) showed clinical signs of depression, anorexia, hyperglycemia, hypertriglyceridemia, glucosuria, proteinuria and ketonuria. Septic bed sore wounds were noted on both fore and hind limbs. Results Histopathological study revealed severe islet amyloidosis in both mandrills. Immunohistochemical study using polyclonal anti-cat amylin antibody confirmed derivation of the islet amyloid from islet amyloid polypeptide (IAPP). Cardiomyopathy and myocardial fibrosis were also evident. Conclusions The present study documents diabetes mellitus in two obese mandrills. Diabetes in these animals had features very similar type 2 diabetes mellitus of humans, including the development of severe, IAPP-derived islet amyloidosis. The mandrill may, therefore, serve as an animal model of human type 2 diabetes mellitus.
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PMID:Spontaneous diabetes mellitus in captive Mandrillus sphinx monkeys: a case report. 1819 24


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