Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A long-term study of 17 patients with paroxysmal nocturnal hemoglobinuria revealed an unexpectedly high incidence of functional and anatomic renal abormalities. All patients demonstrated varying degrees of hematuria and proteinuria distinct from hemoglobinuria. All patients also had granular casts in multiple urinalyses. Evaluation of renal function revealed hyposthenuria, abnormal tubular function and declining creatinine clearance. Radiologically, one or more of these demonstrated enlarged kidneys, renal cortical infarcts and thinning, papillary necrosis, acute renal atrophy, retroperitoneal hematoma and ureteral infarction, which were confirmed by autopsy studies. Hypertension developed in 7 patients. Urinary tract infection was uncommon and no patient had a clinical history compatible with chronic or acute pyelonephritis. Contrary to usual opinion our compatible clearly showed evidence of frequent and widespread renal pathology in paroxysmal nocturnal hemoglobinuria most likely due to repeated microvascular thromboses similar to the venous trombosis involving other organs in this disorder. Since most of these patients present initially to urologists knowledge of this entity is mandatory.
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PMID:Urologic manifestations of paroxysmal nocturnal hemoglobinuria. 114 29

Renal biopsy specimens of 29 Japanese non-insulin dependent diabetes mellitus (NIDDM) patients were examined by quantitative electron microscopic morphometry. In NIDDM the relative increase of percent total mesangium and mesangial capillary surface density (S/Vb) and the relative decrease of peripheral capillary surface density (S/Va) were compared with disease controls. However, mesangial-GBM-epithelial surface density (S/Vc) was not different between both groups. These results suggest that the increased mesangial matrix expands directly towards the capillary lumen as well as along the inner surface of GBM, and narrows the capillary lumen and filtration surface. The duration of diabetes mellitus (DM) did not correlate with all morphological parameters. The mesangial expansion correlated with urinary protein excretion and decreased creatinine clearance (CCr). GBM thickening correlated with proteinuria, but not with CCr. The degree of these morphological changes could be the indicators of hypertension of NIDDM patients. Areas of thin GBM were occasionally noticed in glomeruli which revealed thick GBM extensively, although the mechanism of GBM thinning is not known at the present time.
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PMID:An electron microscopic study of glomeruli in Japanese patients with non-insulin dependent diabetes mellitus. 151 97

In a fetal ovine model the renal effects of different anatomic levels of fetal urinary obstruction were studied. Parameters of prenatal renal growth and differentiation were characterized and correlated with the patterns of renal response to in utero obstruction. Complete ureteral or urethral obstruction was produced in the sheep fetus at 55 to 60 days of gestation. Animals were delivered and sacrificed at near term (140 days), and the kidneys were removed and prepared for analysis. Parameters examined included weight, histology, glomerular number and total surface area, as well as urinary sodium, creatinine, osmolarity and N-acetyl glucosaminidase. Three patterns of response were identified, producing hydronephrotic, cystic or dysgenetic kidneys. Hydronephrotic kidneys were usually the result of bladder outlet obstruction or ureteral obstruction with spontaneous urinary decompression. These kidneys were large (20.7 gm. versus normal 10.8 gm., p less than 0.0001), with thinning of cortical parenchyma that was structurally intact. Glomerular number and surface area were normal. Cystic kidneys were large (14.2 gm., p less than 0.05) with grossly visible cysts and an effaced medulla. Cortical structure was distorted by cysts but basic elements were intact. Glomerular number and surface area were not reduced. Dysgenetic kidneys were small (3.9 gm., p less than 0.0001) with markedly abnormal cortical structure and little recognizable medulla. Histological elements similar to fetal structures were present, including cuboidal/columnar tubular epithelium and peritubular mesenchymal collars. Glomerular number and surface area were significantly less than normal (p less than 0.001). The kidneys contralateral to unilaterally obstructed kidneys were significantly larger than normal (16.2 gm., p less than 0.0001), with normal histology, glomerular number and surface area, indicating in utero contralateral renal hypertrophy. Urinary sodium was variably affected in the hydronephrotic kidneys and was identical to plasma in the dysgenetic kidneys. These results indicate the technical feasibility of in utero models of urinary obstruction. Renal growth and patterns of differentiation were markedly affected by in utero obstruction. They should be a major focus in the investigation of congenital obstructive uropathy, since normal processes of renal growth and differentiation form the basis for postnatal function.
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PMID:The response of the fetal kidney to obstruction. 164 May 11

Spontaneous fractures were reported to be rare (less than 1%) in 1664 hospital admissions for hip fracture in the 1950s in Sweden. We report 11 fluoride-treated postmenopausal patients who developed spontaneous fractures of the femoral necks, all subcapital initially. In 7 patients who continued treatment there were later femoral neck or shaft fractures; in 6, these were bilateral (one followed a fall). In all there were 19 spontaneous fractures: 5 were asymptomatic, including 2 with deformity; 12 fractures required surgery. Five were incomplete (stress) fractures. All were treated with supplementary calcium 1 g daily; 10 had vitamin D supplementation. In all patients where the timing was known, the initial and subsequent fractures were preceded by, or associated with increased bone turnover as measured by plasma alkaline phosphatase (pAlP) (i.e., they were all "good responders"). Two had pretreatment hip fractures following falls. We compared these 11 (Group 1) and another identically treated group of 14 patients (Group 2), without spontaneous femoral fractures and not different in mean age, pretreatment vertebral fractures, years since menopause, fluoride dosage, and plasma creatinine. Group 1 had a lower (p less than 0.05) index of cortical bone in the femoral neck, as assessed by the ratio "calcar width/femoral neck minimum width." The 6 biopsied fluorotic patients from Group 1 had a higher (p less than 0.05) bone fluoride content than the 4 biopsied fluorotic patients from Group 2. Furthermore, histological cortical features of thinning, increased porosity, and advanced tunneling resorption characterized Group 1 posttreatment biopsies. There were no significant differences in peak pAlP responses in the two groups. Mild asymptomatic vitamin D excess may have been a contributing factor in three Group 1 patients. Two further treatment groups have been studied more recently by forearm single-photon absorptiometry (SPA) at two sites; a cyclic NaF group (Group 3) and a calcium +/- vitamin D group (Group 4). Neither showed significant changes in forearm cortical bone density on treatment for 2 and 1.5 years, respectively, but Group 3 showed a significant increase in density at an ultradistal (60% trabecular) site. The pAlP response in Group 3 was significantly less than in Group 1. Spontaneous femoral neck or shaft fractures did not occur in either Groups 3 or 4. Therefore, we recommend: (1) Avoidance of sodium fluoride (NaF) treatment if pretreatment femoral fracture or thin femoral neck cortices exist.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Spontaneous hip fractures in fluoride-treated patients: potential causative factors. 233 31

Chronic, rapid ventricular pacing produces congestive heart failure in the dog. Using echocardiography, the features of developing heart failure were analysed and the capacity of this model for recovery was assessed once pacing had been discontinued. Fifteen dogs were studied; nine were paced at 250 beats/min (bpm) to severe heart failure (5.0 +/- 1.8 weeks) and six served as sham controls. In the paced animals at severe heart failure, two-dimensional echocardiography demonstrated a significant increase in diastolic cross-sectional cardiac area (from 11 +/- 3 to 16 +/- 2 cm2, p less than 0.05), associated with a marked fall n area ejection fraction (54 +/- 8 to 21 +/- 8%, p less than 0.05), and significant left ventricular wall thinning (from 6.0 +/- 0.7 to 4.7 +/- 0.9 mm, p less than 0.05). In addition, significant increases in heart rate (77 +/- 7 to 126 +/- 13 bpm, sinus rhythm; p less than 0.05), respiratory rate (41 +/- 13 to 80 +/- 20 cycles/min, p less than 0.05), and body weight (21 +/- 1 to 24 +/- 3 kg, p less than 0.05) were noted. Serum sodium fell (146 +/- 3 to 140 +/- 8 mmol/L, p less than 0.05), while blood urea nitrogen (6 +/- 2 to 10 +/- 2 mmol/L, p less than 0.05) and creatinine (86 +/- 12 to 101 +/- 15 mmol/d, p less than 0.05) increased. Recovery was characterized by rapid improvement such that all measured parameters normalized by 1 week, except for cross-sectional cardiac area which remained dilated up to 4 weeks (14 +/- 3 cm2, p less than 0.05 versus control).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recovery from heart failure: structural and functional analysis in a canine model. 322 85

To determine whether bone loss in patients with chronic cholestatic liver disease is the consequence of a high or low bone turnover state, 30 female patients with biopsy-proven primary biliary cirrhosis underwent iliac crest biopsy following double tetracycline labeling. The mean trabecular bone volume was decreased as a result of trabecular plate thinning in both the premenopausal (p less than 0.02) and postmenopausal (p less than 0.05) patients, compared to age- and sex-matched controls. Indications that osteoblastic function was impaired included a significantly lower mean wall thickness (p less than 0.01) and mean osteoid seam width (p less than 0.05), and this in association with a decreased mineral appositional rate and prolonged mineralization lag time was suggestive of a defect in matrix synthesis. Further evidence of impaired osteoblastic activity was the significantly lower bone formation rate at both tissue (p less than 0.001) and basic multicellular unit levels (p less than 0.05) in the postmenopausal patients. Total resorption surfaces and fasting urinary calcium/creatinine ratios were significantly increased (p less than 0.005 and 0.05, respectively) in the premenopausal patients and mean interstitial bone thickness reduced in both pre- and postmenopausal patients, suggesting that increased resorption may also contribute to bone loss in primary biliary cirrhosis.
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PMID:Low bone turnover state in primary biliary cirrhosis. 380 93

Long-term study of 21 PNH patients revealed an unexpectedly high incidence of functional and anatomic renal abnormalities. Most patients demonstrated varying degrees of hematuria and proteinuria distinct from hemoglobinuria. Evaluation of renal function revealed hyposthenuria, abnormal tubular function, and declining creatinine clearance. Radiologically these patients had enlarged kidneys, cortical infarcts, cortical thinning, and papillary necrosis which were confirmed by autopsy studies. Hypertension developed in eight patients. Urinary tract infection was uncommon. The renal findings bear striking similarity to those of sickle cell anemia. Contrary to the usual opinion, out studies clearly showed evidence of widespread renal pathology in PNH most likely due to repeated microvascular thrombosis similar to the venous thrombosis involving other organs in this disorder.
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PMID:The kidneys in paroxysmal nocturnal hemoglobinuria. 744 17

The proband was a 14-year-old girl with hematuria and proteinuria. Many members of her maternal pedigree had hematuria and proteinuria. Her mother, younger brother (age 12 years) and younger sister (age 9 years) had microscopic hematuria and proteinuria with normal renal function. Her mother had nephrotic syndrome during pregnancy and a renal biopsy was performed. Light microscopic findings of the renal biopsy specimen revealed mild mesangial proliferation and irregularity of glomerular basement membrane. The pedigree showed no chronic renal failure and no deafness. The proband had experienced microscopic hematuria and occasionally macroscopic hematuria since 3 years of age. Proteinuria increased steadily and at the age of 14 years, she had nephrotic syndrome and renal dysfunction (creatinine clearance of 57.9 ml/min/1.48 m2). Renal biopsy was performed and light microscopic findings showed segmental mesangial cell proliferation and numerous interstitial foam cells without significant findings by immunofluorescent study. Electron microscopic examination showed splitting into many layers and thinning of the glomerular basement membrane. She had no complaint of hearing. However, audiological studies detected bilateral low-tone (from 125 Hz to 1000 Hz) sensorineural hearing difficulty, ranging from 30 to 40 dB. High scores on the short increment sensitivity index (SISI) test suggested inner ear hearing difficulty. Audiogram of her brother revealed also low-tone sensorineural hearing loss. Hereditary nephritis with the characteristic lesion of the glomerular basement membrane and sensorineural hearing difficulty has been known as Alport syndrome. Alport syndrome associated with familial low-tone hearing difficulty has not been reported previously.
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PMID:Hereditary nephritis associated with low-tone sensorineural hearing difficulty: a case report. 869 14

Controlled clinical trials in renal transplantation have demonstrated that mycophenolate mofetil is well tolerated and has lower renal transplant rejection rates than azathioprine regimens. This study reports on the clinical experiences at two institutions with mycophenolate mofetil (MMF) for severe lupus nephritis. Twelve patients with relapsing or resistant nephritis previously treated with cyclophosphamide therapy and one patient who refused cyclophosphamide as initial therapy for diffuse proliferative nephritis but accepted MMF were included. During combined MMF/prednisone therapy, serum creatinine values remained normal or declined from elevated values: mean change in serum creatinine was -0.26+/-0.46 microM/L, P = 0.039. Proteinuria significantly decreased: mean change in urine protein-to-creatinine ratios was -2.53+/-3.76, P = 0.039. Decreased serum complement component C3 and elevated anti-double-stranded DNA antibody levels at baseline improved in some, but not all, patients. The mean initial dose of MMF was 0.92 g/d (range, 0.5 to 2 g/d). The mean duration of therapy was 12.9 mo (range, 3 to 24 mo). Adverse events included herpes simplex stomatitis associated with severe leukopenia (n = 1), asymptomatic leukopenia (n = 2), nausea/ diarrhea (n = 2), thinning of scalp hair (n = 1), pancreatitis (n = 1), and pneumonia without leukopenia (n = 1). Recurrence of the pancreatitis led to discontinuation of MMF in this patient; all other adverse events resolved with dose reduction. It is concluded that MMF is well tolerated and has possible efficacy in controlling major renal manifestations of systemic lupus erythematosus. Controlled clinical trials are needed to define the role of MMF in the management of lupus nephritis.
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PMID:Mycophenolate mofetil therapy in lupus nephritis: clinical observations. 1020 68

Thin basement membrane disease (TBMD) is a condition originally defined as diffuse thinning of the glomerular basement membrane (GBM) associated with hematuria in all patients. Although proteinuria has been described in up to 60% of patients with TBMD, it is almost always mild, with a 24-hour excretion mostly of less than 500 mg. We describe eight patients (four men and four women between 32 and 66 years of age) with TBMD who presented with heavy proteinuria or nephrotic syndrome. Among the seven cases with family history, hematuria was noted in five. All patients had a long history of microscopic hematuria, with episodic gross hematuria in two. Renal biopsies showed diffuse thinning of the GBM in each patient (mean between 185.3 x 29.8 nm and 232.6 x 34.5 nm versus control between 325 x 35 nm and 350 x 15 nm). Three cases showed thinning of GBM only (group I); the remaining five cases showed thinning of GBM associated with focal segmental glomerulosclerosis. All three patients of group I presented with nephrotic syndrome and normal renal function. Treatment with steroids resulted in remission of nephrotic syndrome in two, whereas nephrotic syndrome persisted in the untreated patient. Among the five patients in group II, nephrotic syndrome and normal renal function at presentation were noted in two, whereas the other three had heavy proteinuria (2.2, 2. 5, and 2.6 g/d, respectively) associated with mildly decreased renal function (serum creatinine 1.8, 1.3, and 1.5 mg/dL, respectively). At last follow-up, although the renal function was stable in all five, only the three who received steroid treatment had remission or marked improvement of proteinuria. Hematuria, however, persisted in all eight patients of both groups. Whether specific gene mutations are translated into structural changes responsible for both excessive GBM thinning and increased transcapillary permeability remains to be elucidated. Alternatively, the heavy proteinuria/nephrotic syndrome may not be related to TBMD, but rather is the manifestation of associated glomerular diseases. Follow-up, including a response to steroids, supports the latter hypothesis.
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PMID:Thin basement membrane disease with heavy proteinuria or nephrotic syndrome at presentation. 1073 8


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