Choice of exposure scores for categorical regression in meta-analysis: a case study of a common problem

Objective: Reporting categorical relative risk estimates for a series of exposure levels versus a common reference category is a widespread practice. In meta-analysis, categorical regression estimates a dose–response trend from such results. This method requires the assignment of a single score to each exposure category. We examined how closely meta-analytical categorical regression approximates the results of analysis based on the individual-level continuous exposure.Methods: The analysis included five studies on tea intake and outcomes related to colorectal cancer. In addition, we derived categorical mean and median values from published distributions of tea consumption in similar populations to assign scores to the categories of tea intake when possible. We examined whether these derived mean and median values well approximate the individual-level results.Results: In meta-analytical categorical regression, using the midrange scores approximated the individual-level continuous analyses reasonably well, if the value assigned to the uppermost, open-ended category was at least as high as the lower bound plus the width of the second-highest category. Categorical mean values derived from the published distributions of regular tea (in the US) and green tea (in Japan) well approximated the slope obtained from individual-level analysis.Conclusion: Publication of both the categorical and the continuous estimates of effect in primary studies, with their standard errors, can enhance the quality of meta-analysis, as well as providing intrinsically valuable information on dose–response.     

In vitro methods to study chemically-induced hepatotoxicity: a literature review

Understanding the hepatotoxicity of drugs and chemicals is essential for progress in the pharmaceutical industry, medical science and academic research. The study of hepatotoxicity in vitro is complicated by the difficulty of maintaining hepatocytes in culture due to a lack of understanding of the humoral and matrix requirements of these cells. A variety of in vitro models of the liver have been developed, such as perfused livers, liver slices and three-dimensional perfused bioreactors, but the static cell culture is the most commonly used system. In this review we present the advantages and disadvantages of each system and their roles in the study of hepatotoxicity. We will also discuss how the various culture conditions such as medium and matrix composition affect the systems. The technological advances, which started the fields of genomics, proteomics and metabonomics are playing a very important role in uncovering novel biochemical pathways and markers of toxicity. Several of these studies have focused on hepatotoxicity, particularly on the effects of acetaminophen, carbon tetrachloride and aflatoxin B1. Finally, we will discuss the new field of systems biology, which focuses on interpreting and integrating data from all of the other fields.     

Bronchodilatory effects of the aqueous extract of Gynostemma pentaphyllum and gypenosides III and VIII in anaesthetized guinea-pigs

The bronchodilatory activity of the aqueous extract of Gynostemma pentaphyllum Makino leaves was investigated in anaesthetized guinea-pigs and compared with two of its isolated gypenosides (III and VIII). The results showed that the intravenous administration of the decoction of G. pentaphyllum (2.5, 5 or 10 mg kg(-1)) decreased bronchial resistance in basal conditions and significantly (P < 0.01) reduced (68% inhibition) the bronchoconstrictor action of histamine. Furthermore, the extract antagonized (80% inhibition) the bronchoconstrictor response induced by the antigen in sensitized guinea-pigs. Gypenosides III (0.7 mg kg(-1), i.v.) and VIII (0.3 mg kg(-1), i.v.) caused a similar protective effect in both experimental models used; however, the duration and the intensity of the action was less than that of the extract containing corresponding quantities of gypenosides III and VIII. This study confirmed the validity of the traditional use of this plant in the treatment of asthma and other respiratory disorders.     

Early hypothyroidism after subtotal thyroidectomy in patients with Graves' disease--the role of the preoperative conservative treatment and hormonal status

AIM: The aim of the present study was to evaluate the role of the preoperative antithyroid drug treatment and hormonal status in the development of early postoperative hypothyroidism after subtotal thyroidectomy in patients with Graves' disease. MATERIAL AND METHODS: Eighty-five patients with Graves' disease (males : females ratio 1:5.54, age range 19 to 64, 37.52 +/- 1.09 yrs) who had previously undergone surgical treatment were enrolled in the study. All patients underwent bilateral subtotal thyroidectomy with the amount of remnant tissue of 2-3 g for each lobe (total 4-6 g). Development of early (within one year after the operation) postoperative hypothyroidism was analyzed regarding the type of the antithyroid drug, preoperative dose, duration of the preoperative medical treatment, FT3, FT4, FT3/FT4 and hTSH. RESULTS: Forty six percent of all examined patients (54.12%) were euthyroid and 39 (45.88%/)--hypothyroid. Postoperative hypothyroidism was developed by 33.33% of the patients that had received preoperatively propylthiouracil compared with 50.82% of those treated with methymazol (p > 0.05). The duration of the preoperative treatment was 38.36 +/- 3.53 months for the hypothyroid patients and 30.11 +/- 2.34 months for the euthyroid patients (p < 0.05). Postoperative hypothyroidism developed in 58.70% of the patients with preoperatively suppressed thyroid-stimulating hormone (hTSH) and in 33.33% of those with normalized values of hTSH (p < 0.05). No statistically significant between-group difference was found in the preoperative dose of antithyroid agent, mean values of free triiodothyronine (FT3), free thyroxine (FT4), FT3/FT4, thyrotropic hormone (TSH). CONCLUSIONS: Longer preoperative antithyroid drug treatment and suppression of hTSH in the preoperative period correlated with higher risk of hypothyroidism after subtotal thyroidectomy. The type and the preoperative dose of the antithyroid agent, as well as the mean values of thyroid hormones before the operation have no prognostic significance for postoperative thyroid hypofunction.     

Effect of chromium on the insulin resistance in patients with type II diabetes mellitus

INTRODUCTION: Chromium deficiency in diabetic patients is a debatable problem. The prevailing opinion suggests the presence of low serum concentrations in such patients and therefore an early, long-term addition of chromium to the standard therapy is recommended. PURPOSE: The aim of the present study was to evaluate the effect of chromium on the insulin resistance in diabetic patients with type II diabetes mellitus. MATERIAL AND METHODS: We have studied a total of 34 overweight patients with type II diabetes mellitus, who were distributed in two study sub-groups--patients with very good metabolic control and patients with bad control. For sixty days the patients of both groups received 30 microg of chromium picolinate as food additive. We measured the serum concentration of chromium (using atom-absorption methods), immune-reactive insulin and the insulin resistance index at baseline and at the end of the two-month period. RESULTS: The serum concentrations of chromium was significantly lower in diabetic patients than in the healthy individuals used as controls (2.18 +/- 0.87 nmol/l versus 4.03 +/- 0.96 nmol/l; p < 0.001). We found a significant decrease of the immune-reactive insulin and the insulin resistance index after a two-month application of chromium 30 microg daily (1 tablet of chrome picolinate). The effects of this trace element are analysed in the light of an improved first phase of secretion of insulin or facilitated post-receptor insulin sensibility as a way of potentiating the insulin action. CONCLUSION: Chromium included early in the complex therapy of diabetes is beneficial in the reduction of the degree of insulin resistance.     

Caspofungin and liposomal amphotericin B therapy of experimental murine scedosporiosis

Immunosuppressed mice were infected intravenously with conidia of Scedosporium prolificans. Treatment was begun 1 day later with liposomal amphotericin B, caspofungin, or both drugs initiated concurrently. Amphotericin B and caspofungin were each effective, but combined therapy did not appear to offer advantages over liposomal amphotericin B alone.     

Primate memory saccade amplitude after intervened motion depends on target distance

To keep a stable internal representation of the visual world as our eyes, head, and body move around, humans and monkeys must continuously adjust neural maps of visual space using extraretinal sensory or motor cues. When such movements include translation, the amount of body displacement must be weighted differently in the updating of far versus near targets. Using a memory-saccade task, we have investigated whether nonhuman primates can benefit from this geometry when passively moved sideways. We report that monkeys made appropriate memory saccades, taking into account not only the amplitude and nature (rotation vs. translation) of the movement, but also the distance of the memorized target: i.e., the amplitude of memory saccades was larger for near versus far targets. The scaling by viewing distance, however, was less than geometrically required, such that memory saccades consistently undershot near targets. Such a less-than-ideal scaling of memory saccades is reminiscent of the viewing distance-dependent properties of the vestibuloocular reflex. We propose that a similar viewing distance-dependent vestibular signal is used as an extraretinal compensation for the visuomotor consequences of the geometry of motion parallax by scaling both memory saccades and reflexive eye movements during motion through space.     

Sensory vestibular contributions to constructing internal models of self-motion

The ability to navigate in the world and execute appropriate behavioral and motor responses depends critically on our capacity to construct an accurate internal representation of our current motion and orientation in space. Vestibular sensory signals are among those that may make an essential contribution to the construction of such 'internal models'. Movement in a gravitational environment represents a situation where the construction of internal models becomes particularly important because the otolith organs, like any linear accelerometer, sense inertial and gravitational accelerations equivalently. Otolith afferents thus provide inherently ambiguous motion information, as they respond identically to translation and head reorientation relative to gravity. Resolution of this ambiguity requires the nonlinear integration of linear acceleration and angular velocity cues, as predicted by the physical equations of motion. Here, we summarize evidence that during translations and tilts from upright the firing rates of brainstem and cerebellar neurons encode a combination of dynamically processed semicircular canal and otolith signals appropriate to construct an internal model representation of the computations required for inertial motion detection.