The effect of pioglitazone and extended-release niacin on HDL-cholesterol in diabetes patients in a real-world setting.

OBJECTIVE: This retrospective study was designed to assess the effects of the combination of pioglitazone and extended-release niacin on the lipid panel, particularly HDL-cholesterol, when used in patients with type 2 diabetes in an endocrinology specialty practice. METHODS: The electronic medical records of 434 adult patients with type 2 diabetes receiving extended-release niacin and pioglitazone were screened for review. Patients with type 2 diabetes and hyperlipidemia were included for review if they received the combination of pioglitazone at doses ≥ 15 mg/day and extended-release niacin (Niaspan) at doses ≥ 1000 mg/day for ≥6 months. Statistical analysis used paired t-tests with p < 0.05 as statistically significant. Both ANOVA and the Tukey-Kramer test for multiple comparisons (α = 0.05) were also used. RESULTS: A total of 47 patients, 83% were men with average age of 58, met all eligibility criteria for the study. Compared with baseline, a statistically significant increase in HDL-C (+ 25.13%, p < 0.0001) was observed at the conclusion of combination therapy. The HDL-C levels progressively increased with duration of combination treatment, and were not correlated with concomitant statin use. Significant decreases in total cholesterol and triglycerides were detected, and HbA1c decreased 0.84% during combination therapy for all therapies combined. CONCLUSION: The combination of pioglitazone and extended-release niacin in patients with type 2 diabetes and hyperlipidemia, used in commonly prescribed doses for at least 6 months, resulted in statistically significant improvements in HDL-C, total cholesterol, and triglycerides, and did not result in deteriorations in glycemic control.

Fate of the mate: the influence of delayed graft function in renal transplantation on the mate recipient.

Delayed graft function (DGF) in a deceased-donor renal recipient is associated with allograft dysfunction 1-year posttransplant. There is limited research about the influence to allograft function on the mate of a DGF recipient over time. Using a retrospective cohort design, we studied 55 recipients from a single center. The primary outcome was the change in glomerular filtration rate (GFR) 1-year posttransplant. The secondary outcome was the GFR at baseline. We found that mates to DGF recipients had a mean change in GFR 1-year posttransplant of -11.2 mL/min, while the control group had a mean change of -0.4 mL/min. The difference in the primary outcome was significant (p = 0.025) in a multivariate analysis, adjusting for cold ischemic time, panel reactive antibody level, allograft loss, human leukocyte antibody (HLA)-B mismatches and HLA-DR mismatches. No significant difference between groups was found in baseline GFR. In conclusion, mates to DGF recipients had a significantly larger decline in allograft function 1-year posttransplant compared to controls with similar renal function at baseline. We believe strategies that may preserve allograft function in these'at-risk'recipients should be developed and tested.

Genetic and pharmacologic evidence that Rac1 GTPase is involved in regulation of platelet secretion and aggregation.

BACKGROUND: Rac1 GTPase, a member of the Ras-related Rho GTPase family, is the major Rac isoform present in platelets and has been shown to be involved in cell actin cytoskeleton reorganization and adhesion. Agonists that induce platelet secretion and aggregation also activate Rac1 GTPase, raising the possibility that Rac1 GTPase may be involved in regulation of platelet function. OBJECTIVES: To rigorously define the role of Rac1 in platelet regulation. METHODS: We have used a dual approach of gene targeting in mice and pharmacologic inhibition of Rac1 by NSC23766, a rationally designed specific small molecule inhibitor, to study the role of Rac1 in platelet function. RESULTS: Platelets from mice as well as human platelets treated with NSC23766 exhibited a significant decrease in: (i) active Rac1 species and phosphorylation of the Rac effector, p21-activated kinase; (ii) expression of P-selectin and secretion of adenosine triphosphate induced by thrombin or U46619; and (iii) aggregation induced by adenosine 5'-diphosphate, collagen, thrombin and U46619, a stable analog of thromboxane A(2). NSC23766 did not alter the cAMP or cGMP levels in platelets. Consistent with the requirement of Rac1 for normal platelet function, the bleeding times in Rac1(-/-) mice or mice given NSC23766 were significantly prolonged. CONCLUSIONS: Our data show that deficiency or inhibition of Rac1 GTPase blocks platelet secretion. The inhibition of secretion, at least in part, is responsible for diminished platelet aggregation and prolonged bleeding times observed in Rac1 knockout or Rac1 inhibitor-treated mice.

Ahaustral colonic segment following trauma: a possible sign of seromuscular tear.

Although traumatic seromuscular tears of the colon are often managed conservatively, it is pertinent to detect the tear since it poses a risk for acute or delayed perforation. Unfortunately, clinical findings are inadequate for detecting and monitoring this lesion. Therefore, this complication has not been recognized prior to laporatomy. We have noted that an ahaustral colonic segment following trauma may be a potential marker for seromuscular tear.

Ureteropelvic junction obstruction associated with extrarenal pelvis: A potential cause of cystic abdominal mass anterior to a normal-appearing kidney in the newborn.

An extrarenal pelvis is associated with the absence of central sinus echoes on sonography. However, central sinus echoes are normally inapparent in some newborns. Furthermore, true absence of a central sinus may cause calices to simulate normal renal pyramids so that the kidney appears normal in a fetus or newborn. This case illustrates the potential for an obstructed extrarenal pelvis in a fetus or newborn to distend so that it is mistaken on sonography for a cystic anterior abdominal mass unrelated to the kidney. However, the absence of central sinus echoes should suggest the diagnosis of an obstructed extrarenal pelvis if the adjacent cystic abdominal mass is positioned to obstruct an intrarenal pelvis.

Ossifying renal cell carcinoma.

In older children, ossifying renal cell carcinoma is a potential explanation for a network of well-organized, curvilinear high-attenuation areas in a renal mass. Since ossification of renal cell carcinoma is a favorable tumor marker that implies a less extensive resection, it is important to anticipate this tumor before surgical resection is undertaken.

Phosphorus deficiency in Lupinus albus. Altered lateral root development and enhanced expression of phosphoenolpyruvate carboxylase.

The development of clustered tertiary lateral roots (proteoid roots) and the expression of phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31) in roots were studied in white lupin (Lupinus albus L.) grown with either 1 mM P (+P-treated) or without P (-P-treated). The +P-treated plants initiated fewer clustered tertiary meristems and the emergence of these meristems was delayed compared with - P-treated plants. Proteoid root zones could be identified 9 d after emergence in both P treatments. Amounts of PEPC mRNA, PEPC specific activity, and enzyme protein were greater in proteoid roots than in normal roots beginning at 10, 12, and 14 d after emergence, respectively. The increases in PEPC mRNA, PEPC enzyme, and PEPC specific activity suggest that this enzyme is in part under transcriptional regulation. Recovery of organic acids from root exudates coincided with the increases in PEPC specific activity. The -P-treated plants exuded 40-, 20-, and 5-fold more citrate, malate, and succinate, respectively, than did +P-treated plants. Data presented support the hypothesis that white lupin has concerted regulation of proteoid root development, transcriptional regulation of PEPC, and biosynthesis of organic acids for exudation in response to P deficiency.

Root Carbon Dioxide Fixation by Phosphorus-Deficient Lupinus albus (Contribution to Organic Acid Exudation by Proteoid Roots).

When white lupin (Lupinus albus L.) is subjected to P deficiency lateral root development is altered and densely clustered, tertiary lateral roots (proteoid roots) are initiated. These proteoid roots exude large amounts of citrate, which increases P solubilization. In the current study plants were grown with either 1 mM P (+P-treated) or without P (-P-treated). Shoots or roots of intact plants from both P treatments were labeled independently with 14CO2 to compare the relative contribution of C fixed in each with the C exuded from roots as citrate and other organic acids. About 25-fold more acid-stable 14C, primarily in citrate and malate, was recovered in exudates from the roots of -P-treated plants compared with +P-treated plants. The rate of in vivo C fixation in roots was about 4-fold higher in -P-treated plants than in +P-treated plants. Evidence from labeling intact shoots or roots indicates that synthesis of citrate exuded by -P-treated roots is directly related to nonphotosynthetic C fixation in roots. C fixed in roots of -P-treated plants contributed about 25 and 34% of the C exuded as citrate and malate, respectively. Nonphotosynthetic C fixation in white lupin roots is an integral component in the exudation of large amounts of citrate and malate, thus increasing the P available to the plant.

Multipolypoid intussusceptum: a distinctive appearance of ileoileocolic intussusception at the ileocecal valve.

Objective. To determine whether ileoileocolic intussusception can be diagnosed by a distinctive appearance during pneumatic reduction. Materials and methods. We reviewed the clinical, pathologic, and imaging findings of 11 patients with ileoileocolic intussusceptions seen in our hospital between January 1989 and July 1994. The patients ranged in age from 4 months to 4 years and 2 months. We specifically evaluated the appearance of these intussusceptions on air enemas performed in nine of these patients. Another 22 air enemas of all patients with surgically proven ileocolic intussusception seen during the same time period were also reviewed for comparison. Results. In seven of the nine patients with ileoileocolic intussusception who had air enemas, the intussusceptum clearly had two or more separate polypoid components once it was reduced to the cecum. This distinctive appearance was not seen until the intussusceptum was tethered at the ileocecal valve. The intussusceptum was also reduced to the cecum in 19 patients from the control group with ileocolic intussusception. In contrast to the ileoileocolic intussusceptums, these intussusceptums were either smoothly marginated (16 patients) or slightly lobular (three patients). Conclusion. In most patients with ileoileocolic intussusception, the intussusceptum has two or more polypoid components at the level of the ileocecal valve which are easily distinguished from the smoothly marginated or slightly lobular intussusceptum seen with ileocolic intussusception.

Induction of gastroduodenal prolapse by antral heterotopic pancreas.

Ectopic pancreas is the most common congenital anomaly in the gastric antrum. In some patients, there is a distinct tendency for this lesion to produce intermittent crampy abdominal pain by provoking gastroduodenal prolapse. This condition should be considered after a more distal prolapse from intussusception is excluded. An upper gastrointestinal series performed during an episode of symptoms may be diagnostic of this entity.

Unilateral abdominal wall hypoplasia: radiographic findings in two infant girls.

Prune belly syndrome (PBS) is defined as an association of abdominal wall deficiency, genitourinary anomalies, and, in males, cryptorchism. Although PBS is more common in males, females can also have the condition. In both sexes, expression of the disease is often incomplete and prognosis depends upon the specific abnormalities present. PBS in girls or incomplete expression of PBS is called pseudoprune belly syndrome (PPBS). We recently evaluated two baby girls with PPBS. Both girls had unilateral abdominal wall hypoplasia associated with cardiac, genitourinary, gastrointestinal, pulmonary, and musculoskeletal involvement that ranged from normal to severe. One of the patients also demonstrated congenital cytomegalovirus (CMV) infection and focal jejunal hypoganglionosis. Since CMV has been associated with both aganglionosis and PBS, it is possible that CMV induced both conditions in this patient.

Phosphorus Stress-Induced Proteoid Roots Show Altered Metabolism in Lupinus albus.

Proteoid roots develop in Lupinus albus L. in response to nutrient stress, especially P. Proteoid roots excrete citrate and thus increase the availability of P, Fe, and Mn in the rhizosphere. In an effort to understand citrate synthesis and organic acid metabolism in proteoid roots of lupin, we have evaluated in vitro enzyme activities of citrate synthase (CS), malate dehydrogenase (MDH), and phosphoenolpyruvate carboxylase (PEPC) in proteoid and normal roots of plants grown with or without P. Organic acid concentrations, respiration rates, and dark 14CO2-labeling patterns were also determined. The in vitro specific activities of CS, MDH, and PEPC and in vivo dark 14CO2 fixation were higher in proteoid roots compared to normal roots, particularly under P stress. Western blot analysis showed that PEPC enzyme protein was more highly expressed in -P proteoid roots compared to other tissues. The majority of the fixed 14C was found in organic acids, predominantly malate and citrate. A larger fraction of citrate was labeled in P- stressed proteoid roots compared to other root tissue. Respiration rates of proteoid roots were 31% less than those of normal roots. The data provide evidence for increased synthesis of citrate in proteoid roots compared to normal roots, particularly under P stress. A portion of the carbon for citrate synthesis is derived from nonautotrophic CO2 fixation via PEPC in proteoid roots.

A device for urologic post-surgical monitoring.

This article reports on the preliminary development of an instrument that is intended to monitor catheterized, post-TURP patients specifically to assist care-providers in the reduction of clot retention. The primary objective of the instrument is to detect conditions that indicate an alarm condition for which the probability of clot retention is considered to be high. In response to an alarm, intervention by means of increased irrigation flow rate or other action is expected. The density of outflow consisting of the mixture of irrigation fluid, urine, and blood from the prostate, is monitored optically. Multiple transducer sites along the catheter improve the monitoring by minimizing the effects of bubbles and particulates in the stream. Development of algorithms for processing the data have concentrated on the use of fuzzy logic in keeping with the linguistic descriptors used by medical experts. This allows the formulation of decision rules that mimic the knowledge base and syntax used by care providers who judge the conditions of the outflow and make decisions about the patient's condition and the optimum flow rate for irrigation fluid. A laboratory prototype has been completed and tested in vitro; a second-generation prototype has been designed in preparation for a clinical study.

Plain film identification of inverted Meckel diverticulum.

Inversion is a potentially serious complication of Meckel diverticulum. Since inversion provokes gangrene and small bowel obstruction, diagnosis by enteroclysis or imaging studies can conflict with the need for timely surgical intervention. We have noted that plain films may predict this lesion when a solitary mottled polypoid lesion occupies the ileum at the site of a small bowel obstruction.

Modeling imager deterministic and statistical modulation transfer functions.

A unified two-step approach for evaluation of deterministic and statistical modulation transfer functions (MTF's) is applied to a time-delay-and-integration charge-coupled imager. The deterministic MTF's include the well-known spatial and temporal aperture MTF's, as well as the charge-coupled imager interpixel and intrapixel synchronism MTF's, which are derived here. These latter MTF's originate from nonsynchronous motion (velocity mismatch) between the image on the focal plane and the charge packets. The statistical evaluation results in phase and jitter MTF's.

Distention of the posterior urethra: association with nonneurogenic neurogenic bladder (Hinman syndrome).

In nonneurogenic neurogenic bladder (NNNB), or Hinman syndrome, a functional bladder outlet obstruction is produced by voluntary contraction of the external sphincter during voiding. To determine whether any radiographic findings are diagnostic of this condition, the authors reviewed the genitourinary images of six boys in whom NNNB was diagnosed in the past 5 years. In contrast to true neurogenic bladder, findings of elongated, trabeculated, high-volume bladders with substantial postvoid residuals, obstructive uropathy, and vesicoureteral reflux were not associated with clinical, radiographic, or urodynamic evidence of an underlying neurologic abnormality. Furthermore, four boys had distention of the posterior urethra that the authors believe is suggestive of this condition. In these patients, the posterior urethra appeared entirely normal during early voiding, but distended after contraction of the external sphincter as voiding progressed. This posterior urethral distention may worsen the symptoms of enuresis, but may also reduce or retard the damage to the proximal urinary tract.