No regression of renal AL amyloid in monoclonal gammopathy after successful autologous blood stem cell transplantation and significant clinical improvement.

BACKGROUND: High-dose chemotherapy followed by autologous blood stem cell transplantation induces remission of plasma cell dyscrasia in patients with AL amyloidosis. The impact of this treatment on the glomerular amyloid mass is still unknown. METHODS: In the present study, the quantity of the renal amyloid mass before and more than 3 years after high-dose melphalan treatment and autologous blood stem cell transplantation was assessed in two patients. At the time of the second renal biopsy, both patients were in complete remission without detectable serum and urinary monoclonal IgA-lambda and a normal percentage of plasma cells in the bone marrow. RESULTS: In both patients with biopsy-proven AL amyloidosis, urinary protein excretion decreased from 7 g/24 h to <2 g/24 h more than 3 years after autologous blood stem cell transplantation. In contrast, glomerular amyloid deposits persisted, as shown in the second biopsy. CONCLUSION: Despite complete remission of the plasma cell dyscrasia and improvement of glomerular permeability, the amount of glomerular amyloid mass did not regress.     

Intraocular pressure and aqueous humor flow during a euglycemic-hyperinsulinemic clamp in patients with type 1 diabetes and microvascular complications

Background  

Microvascular complications, including retinopathy and nephropathy are seen with type 1 diabetes. It is unknown whether functional changes in aqueous humor flow or intraocular pressure (IOP) develop in parallel with these complications. This study was designed to test the hypothesis that clinical markers of microvascular complications coexist with the alteration in aqueous humor flow and IOP.     

Logistic multiple regression analysis of factors predicting recurrence of hyperthyroidism after medical treatment of toxic diffuse goitre.

In order to determine which factors predict the outcome of short term antithyroid drug treatment we studied 42 patients with diffuse goitre in whom 43 instances of thyrotoxicosis were treated. Treatment duration ranged from 24 to 61 wk (median 30 wk). All patients received high-dose carbimazole and thyroid hormone substitution. Patients in remission were followed for 39 to 134 wk (median 73 wk). The relapse rate at 1 yr and at 2 yr after cessation of antithyroid drug treatment was 51%. Of the parameters studied presence or absence of eye signs and initial serum levels of thyroxine, triiodothyronine and immunoglobulin-G in the relapse group and in the remission group showed significant differences in univariate analysis. No significant differences were found for age, sex, family history of thyroid disease, thyroid gland volume or TSH-receptor stimulating autoantibodies. Linear discriminant analysis shows that of the four remaining factors thyroxine is not important in separating both groups. Cox analysis yields only initial serum triiodothyronine and eye signs as significant prognostic factors. With these two factors 18 out of 23 predictions of remission and 16 out of 18 predictions of relapse in the 41 patients with known initial serum triiodothyronine concentrations are correct. Such predictions can be used in the choice of therapy, short-term medical treatment for patients with a low risk and long-term medical treatment or, at the appropriate time, a destructive form of therapy for patients with a high risk of relapse.     

Cardiac function predicts mortality following thoracoabdominal and descending thoracic aortic aneurysm repair.

OBJECTIVE: Previous studies have identified age, renal failure and aneurysm extent as predictors of mortality following thoracoabdominal and descending thoracic aortic aneurysm (TAA) repair. We studied the impact of coronary artery disease (CAD) and cardiac function on 30-day mortality following TAA repair. METHODS: Between February 1991 and May 2001, we performed 854 TAA repairs. Two hundred ninety-one patients (34%) had a history of coronary artery disease. One hundred forty-one/291 (49%) had undergone coronary artery bypass surgery (CAB) prior to TAA repair. We conducted multivariable analyses of known risk factors along with the left ventricular ejection fraction (EF) and prior CAB to determine the adjusted effect of CAD on outcome. RESULTS: Mortality in patients with CAD was 54/291 (18%) compared to 75/563 (13%) without CAD (P<0.05). In patients who had prior CAB, mortality was 31/141 (22%) compared to 98/713 (14%) patients without prior CAB, (P<0.02). In multivariable analysis, the effects of CAD and CAB on mortality were eliminated by consideration of a low EF (defined as less than 50%). CONCLUSION: Impaired left ventricular function appears to be the strongest cardiac predictor of mortality for TAA repair, independent of the presence of coronary artery disease or coronary artery bypass revascularization.     

Spontaneous ovarian hyperstimulation mimicking an ovarian tumour

Ovarian hyperstimulation syndrome in a spontaneous singletonpregnancy is exceedingly rare. We report a case of ovarian hyperstimulationpresenting as bilateral ovarian masses in association with spontaneouspregnancy, occurring in a woman with disturbed liver function.A possible mechanism is discussed.     

Histopathologic and dietary prognostic factors for canine mammary carcinoma

Summary Histologic and dietary prognostic factors for survival following naturally occurring breast cancer were studied for 145 pet dogs. Information was collected from the dog's owner and veterinarian regarding medical and reproductive history, nutritional status, treatment, tumor recurrence, and length of survival. The usual intake of all dog and table foods consumed 1 year prior to diagnosis was obtained using a validated quantitative food frequency questionnaire. A histologic malignancy score was derived based on 7 histopathologic criteria. The mean age of the dogs was 10.4 ± 2.5 years; 37% had been ovariohysterectomized prior to diagnosis. Product-limit estimates of survival indicated that 6 factors, namely body conformation 1 year prior to diagnosis (p = 0.03), histologic tumor type (p = 0.004), histologic malignancy score (p = 0.02), histologic invasion (p = 0.002), tumor recurrence (p<0.0001), and completeness of surgery (p = 0.01) were of prognostic significance. In addition, when dogs were characterized by the percent of total calories they derived from fat and protein, the median survival time for dogs in the low fat group (<39%) with protein >27%, 23–27%, and <23% was 3 years, 1.2 years, and 6 months, respectively (p = 0.008). For dogs in the high fat group (39%), there was no difference in survival for the different intake levels of dietary protein (p = 0.84). When these data were fitted to a proportional hazards model, recurrence, histologic score, tumor type, percent of calories derived from protein, fat group, and a protein-fat group interaction term were statistically significant. Predicted 1 year survival for dogs on a low fat diet with 15%, 25%, and 35% of total calories derived from protein was 17%, 69%, and 93%, respectively.     

Presence and measurement oftele-methylhistamine in mast cells

The histamine metabolitetele-methylhistamine (t-MH) was identified and measured in crude and purified peritoneal mast cells (MCs). Peritoneal dialysates, peritoneal cells, and purified MCs all containedt-MH in concentrations representing about 0.2% of the corresponding histamine (HA) levels.T-MH levels in crude cells represented about 70% of the total dialysate levels, indicating the presence of extracellular as well as intracellulart-MH.T-MH levels per MC in purified fractions were similar to those of crude fractions, indicating a MC origin for the intracellulart-MH. Histamine methyltransferase activity was not detected in crude or purified MC fractions, and incubations with the monoamine oxidase inhibitor pargyline failed to increase the content or release oft-MH in either fraction, suggesting a very slow or non-existent histamine methylation in MCs. Compound 48/80 produced a temperature-dependent release of HA andt-MH in crude and purified preparations, and Triton X-100 also released both amines. In all cases, the degree of release of both amines was correlated, consistent with a granular origin fort-MH in MCs. The low concentrations oft-MH in MCs do not necessarily indicate a role for MCs in HA metabolism, but suggest thatt-MH may be a valuable marker for non-MC HA.     

No evidence for involvement of the calpain-10 gene 'high-risk' haplotype combination for non-insulin-dependent diabetes mellitus in early onset obesity

In light of evidence of linkage of obesity to chromosome 2q31-q37, we hypothesized that the calpain-10 gene 'high-risk' haplotype combination for non-insulin-dependent diabetes mellitus (NIDDM) is involved in early onset obesity. We screened the NIDDM 'high-risk'-haplotype combination formed by the alleles 112 and 121 of the polymorphisms UCSNP-43, -19, and -63 in 166 families consisting of an extremely obese child or adolescent (mean BMI percentile: 99.3+/-1.38), one or more obese sibs (mean BMI percentile: 97.42+/-2.88), and both of their parents. Genotyping for three calpain-10 gene polymorphisms was performed by polymerase chain reaction (PCR) with (a) length polymorphism detection (UCSNP-19) or (b) allele-specific PCR (UCSNP-43 and -63). To allow for correct haplotype assignment all individuals were additionally genotyped for two microsatellite markers (D2S125 and D2S2338). We followed a hierarchical test procedure. As the first step, model-free linkage analysis was performed using maximum likelihood binomial statistics. The second stage consisted of a one-sided asymptotic pedigree disequilibrium test for the UCSNP-43 and on an exploratory level for the other SNP-markers and all haplotypes formed by the three SNPs. The final stage investigated the reported haplotype combination. We failed to detect an initial linkage of obesity to this region (LOD score <0.4). All subsequent exploratory analyses were negative. Our analysis of the relationship between the NIDDM 'high-risk' haplotype combination and extreme early onset obesity revealed no evidence for linkage and association.