The pharmacology of dichloroacetate

Dichloroacetate (DCA) exerts multiple effects on pathways of intermediary metabolism. It stimulates peripheral glucose utilization and inhibits gluconeogeneis, thereby reducing hyperglycemia in animals and humans with diabetes mellitus. It inhibits lipogenesis and cholesterolgenesis, thereby decreasing circulating lipid and lipoprotein levels in short-term studies in patients with acquired or hereditary disorders of lipoprotein metabolism. By stimulating the activity of pyruvate dehydrogenase, DCA facilitates oxidation of lactate and decreases morbidity in acquired and congenital forms of lactic acidosis. The drug improves cardiac output and left ventricular mechanical efficiency under conditions of myocardial ischemia or failure, probably by facilitating myocardial metabolism of carbohydrate and lactate as opposed to fat. DCA may also enhance regional lactate removal and restoration of brain function in experimental states of cerebral ischemia. DCA appears to inhibit its own metabolism, which may influence the duration of its pharmacologic actions and lead to toxicity. DCA can cause a reversible peripheral neuropathy that may be related to thiamine deficiency and may be ameliorated or prevented with thiamine supplementation. Other toxic effects of DCA may be species-specific and reflect marked interspecies variation in pharmacokinetics. Despite its potential toxicity and limited clinical experience, DCA and its derivatives may prove to be useful in probing regulatory aspects of intermediary metabolism and in the acute or chronic treatment of several metabolic disorders.     

A central mechanism of acute baroreflex resetting in the conscious dog

The role of the central nervous system in the mechanism(s) involved in acute carotid baroreflex resetting was studied in six conscious, chronically instrumented, aortic-denervated dogs. Dogs were prepared for reversible vascular isolation of the carotid sinuses. Acute baroreflex resetting was induced by holding the left carotid sinus pressure (LCcsp) at a given value for 20 minutes using a pulsatile pressure control system while at the same time keeping the right carotid sinus pressure (RCSP) at a subthreshold level (approximately 40 mm Hg). At the end of the 20 minutes, the LCcsp) was reduced to approximately 20 mm Hg, and a baroreflex (RCSP-mean arterial pressure [MAP]) curve was generated on the right carotid sinus using static-step increases in carotid sinus pressure. At the control LCcsp of 100 mm Hg, the RCSP-MAP baroreflex had a threshold pressure (Pth) of 86.6 +/- 3.1 mm Hg and a set point pressure (Psp) of 104.7 +/- 2.5 mm Hg. Increasing LCcsp) to 140 mm Hg for 20 minutes caused these parameters for the right carotid baroreflex to increase. Pth and Psp increased by 18.4 +/- 4.0 and 14.2 +/- 3.0 mm Hg, respectively (p less than 0.05). The baroreflex curve, therefore, was shifted upward and to the right. Decreasing LCcsp to 60 mm Hg caused Pth and Psp to decrease by 24.7 +/- 5.0 and 18.1 +/- 2 mm Hg, respectively (p less than 0.05). The baroreflex curve was therefore shift downward and to the left. The percent of resetting of Pth and Psp was 46 +/- 9% and 36 +/- 8%, respectively, when LCcsp was 140 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Subacute cutaneous lupus erythematosus during PUVA therapy for psoriasis: case report and review of the literature

Lesions typical of subacute cutaneous lupus erythematosus developed in an elderly woman after 6 months of PUVA (8-methoxypsoralen and longwave ultraviolet light) therapy for psoriasis. Pancytopenia, antibodies to double-stranded DNA, and hypocomplementemia developed concurrently with the appearance of the cutaneous lesions. With discontinuation of photochemotherapy, the cutaneous lesions disappeared and the pancytopenia improved.     

C4 concentrations and C4 deficiency alleles in systemic lupus erythematosus.

In a study of 66 patients with systemic lupus erythematosus (SLE) and 80 controls it was found that the presence of two deficiency (null) alleles of C4 had a significant effect on mean C4 concentrations in serum. In six controls who each had two C4 null alleles the mean C4 concentration in serum was 56% lower than in 43 controls without C4 null alleles; the nadir of the C4 concentration in four patients with SLE with two null alleles was also lower by a mean of 55% than in 32 patients who did not have null alleles. Reduced production of C4 allotypes in subjects with two null alleles may be an important determinant of total C4 concentration in patients with SLE. For optimal interpretation of C4 concentrations in SLE, C4 allotyping appears to be indicated, particularly to identify patients who have two null alleles of C4.     

Research in physical medicine and rehabilitation. V. Data entry and early exploratory data analysis

The process of data entry and initial analysis to locate data errors is described. Basic terms are defined and a simple method of entering data by using word processing software is illustrated. Data checking is done by using visual check of the raw data. Statistical programs are then used to locate possible data errors by finding data points (outliers) that are very different from the average. Special graphic output of statistical programs, scatterplots and box and whisker plots can be used to further locate questionable data. Examples of data entry forms and annotated step by step data cleaning with the use of inexpensive programs for personal computers are presented.     

A patient with right and left atrial membranes: the role of transesophageal echocardiography and magnetic resonance imaging in diagnosis

A patient who had right and left atrial membranes was examined. The diagnosis and the hemodynamic significance of both membranes were detailed by transesophageal echocardiography and were confirmed by magnetic resonance imaging. Transesophageal imaging was found to be superior to routine echocardiography in visualization of these atrial structures.