Bioabsorbable miniplating versus metallic fixation for metacarpal fractures

Bioabsorbable implants offer an attractive alternative to metallic implants to stabilize small bone fractures in the hand. Self-reinforced bioabsorbable miniplating for metacarpal fractures was studied in bones from cadavers and compared with standard metallic fixation methods. One hundred twelve fresh-frozen metacarpals from humans had three-point bending and torsional loading after transverse osteotomy followed by fixation using seven methods: (1) dorsal and (2) dorsolateral 2-mm self-reinforced polylactide-polyglycolide 80/20 plating, (3) dorsal and (4) dorsolateral 2-mm self-reinforced poly-L/DL-lactide 70/30 plating, (5) dorsal 1.7-mm titanium plating, (6) dorsal 2.3-mm titanium plating, and (7) crossed 1.25-mm Kirschner wires. In apex dorsal and palmar bending, dorsal self-reinforced polylactide-polyglycolide and poly-L/DL-lactide plates provided stability comparable with dorsal titanium 1.7-mm plating. When the bioabsorbable plates were applied dorsolaterally, apex palmar rigidity was increased and apex dorsal rigidity was decreased. Bioabsorbable platings resulted in higher torsional rigidity than 1.7-mm titanium plating and in failure torque comparable with 2.3-mm titanium plating. Low-profile selfreinforced polylactide-polyglycolide and poly-L/DL-lactide miniplates provide satisfactory biomechanical stability for metacarpal fixation. These findings suggest that bioabsorbable miniplating can be used safely in the clinical stabilization of metacarpal and phalangeal fractures.     

Effect of ciprofloxacin on the pharmacokinetics of ropivacaine

OBJECTIVE: To assess the effect of ciprofloxacin on the pharmacokinetics of ropivacaine. METHODS. In a double-blind, randomised, cross-over study, nine healthy volunteers were treated for 2.5 days with 500 mg oral ciprofloxacin or placebo twice daily. On day 3, they received a single dose of 0.6 mg/kg ropivacaine intravenously over 30 min. Ropivacaine, 3-hydroxyropivacaine (3-OH-ropivacaine), and (S)-2',6'-pipecoloxylidide (PPX) in venous plasma and urine were measured for up to 12 h and 24 h, respectively. RESULTS: Ciprofloxacin decreased the mean clearance (CL) of ropivacaine by 31% (P<0.05), with a considerable inter-individual variation (range from -52% to +39%). It also decreased the area under the plasma concentration-time curve (AUC) of 3-OH-ropivacaine by 38% (P<0.05) and urinary excretion of 3-OH-ropivacaine by 27% (P<0.05). Ciprofloxacin increased the AUC of PPX by 71% (P<0.01) and urinary excretion of PPX by 97% (P<0.01). CONCLUSION: Ciprofloxacin modestly decreased the mean ropivacaine CL by inhibiting the CYP1A2-mediated formation of 3-OH-ropivacaine. At the same time, the CYP3A4-mediated formation of PPX was increased. There was a marked inter-individual variation in the extent of the interaction, and, for some individuals, the concomitant use of ciprofloxacin with ropivacaine might produce toxic symptoms.     

Changes in hippocampal histamine receptors across the hibernation cycle in ground squirrels

Hibernation is a physiological state characterized by a dramatic reduction in various functions, such as body temperature, heart rate, and metabolism. The hippocampus is thought to be important for regulation of the hibernation bout because it remains electrophysiologically active throughout this extremely depressed state. The question arises as to what neuronal influences act within the hippocampus during hibernation to sustain its activity. We hypothesized that histaminergic input might be an important contributor. Brain histamine is involved in functions relevant to hibernation, such as the regulation of diurnal rhythms, body temperature, and energy metabolism. Furthermore, we have previously shown that the histaminergic system appears to be activated during the hibernating state. In this study, we used receptor binding autoradiography, in situ hybridization, and GTP-gamma-S binding autoradiography to study changes in histamine receptors across the hibernation bout. We were able to demonstrate an increase in histamine H1 and H2 receptors in the hippocampus during hibernation, whereas the mRNA expression and receptor density of the inhibitory H3 receptor decreased. Histamine H3 receptors were shown to exhibit both histamine-activated and constitutive GTP-gamma-S-binding activity in the ground squirrel hippocampus, both of which decreased during hibernation, indicating a decrease in H3 receptor G-protein activation. Taken together, our results indicate that histamine may be involved in maintaining hibernation by sustaining hippocampal activity, possibly through H1 and H2 receptor activity and decreased inhibition by H3 receptors. The involvement of brain histamine, which is generally thought of as an arousal molecule, in maintaining a depressed state of the brain suggests a more general role for the amine in controlling arousal state.     

Identification of rat H3 receptor isoforms with different brain expression and signaling properties

We identified the cDNAs of three functional rat H3 receptor isoforms (H3A, H3B, and H3C) and one nonfunctional truncated H3 receptor (H3T). The H3A, H3B, and H3C receptor isoforms vary in the length of their third intracellular loop; the H3B and H3C receptor lack 32 and 48 amino acids, respectively. Transient expression of the H3A, H3B, and H3C receptors in COS-7 cells results in high affinity binding for the H3 antagonist [125I]iodophenpropit, which is displaced by selective H3 agonists and antagonists. The three isoforms differentially couple to the Gi protein-dependent inhibition of adenylate cyclase or stimulation of p44/p42 mitogen activated protein kinase (MAPK), a new signaling pathway for the H3 receptor. Whereas the H3A receptor was less effective in inhibiting forskolin-induced cAMP production compared with the H3B or H3C receptor, this isoform was more effective in the stimulation of p44/p42 MAPK. The H3 receptor isoforms also displayed differential CNS expression in key areas involved in regulation of sensory, endocrine, and cognitive functions. A differential H3 receptor isoform expression was seen in, for example, hippocampus, where a characteristic dorsoventral distribution was revealed. Differential H3 receptor expression was also characteristic for the cerebellum, indicating possible histaminergic regulation of motor functions. The identification of these new H3 receptor isoforms and their specific signaling properties adds a new level of complexity to our understanding of the role of histamine, and the H3 receptor in brain function. The heterogeneous distribution of the isoforms suggests that H3 receptor isoform-specific regulation is important in several brain functions.     

Incremental cost‐effectiveness of double‐reading mammograms

Background. Double reading is a widely used criterion standard in breast cancer screening despite a lack of evidence of the costeffectiveness of the second reading. This study evaluates the incremental costeffectiveness of such a strategy.Design. Costeffectiveness analysis: Nationwide populationbased semiannual screening program for women aged 50–59 in Finland. Participation rate was 91%. All mammograms (95,423) performed during 1990–1995 in three screening centers of the Finnish Cancer Society were read by two radiologists with gradings recorded. The effectiveness of the double reading was the difference in cancers detected in the double compared to that of the single reading. Incremental costs of the double reading for the health care and nonhealth care and the time costs were estimated. The main outcome measure was the incremental cost per additional cancer found as a result of the doublereading strategy.Results. The total number of cancers detected with the double and single reading were 290 and 261, respectively. A significantly higher ratio of carcinoma in situ was the causative pathology in cancers detected only by the second reader. The cost per cancer detected with a single reading was US$ 18,340. The incremental cost of any additional cancer found was US$ 25,523, that is, a 39% higher cost per additional cancer found by double reading.Conclusions. The additional cost per cancer detected by double reading is not drastically higher than with single reading. However, the additional cost per life year saved may be much higher.     

Effect of rifampicin on the pharmacokinetics and pharmacodynamics of nateglinide in healthy subjects

AIMS: Our aim was to investigate the effects of rifampicin on the pharmacokinetics and pharmacodynamics of nateglinide, a novel short-acting antidiabetic drug. METHODS: In a randomized crossover study with two phases, 10 healthy volunteers took 600 mg rifampicin or placebo orally once daily for 5 days. On day 6 of both phases, they ingested a single 60 mg dose of nateglinide. Plasma nateglinide and blood glucose concentrations were measured for up to 7 h postdose. RESULTS: Rifampicin decreased the mean AUC(0,7 h) of nateglinide by 24% (range 5-53%; P = 0.0009) and shortened its half-life (t(1/2)) from 1.6 to 1.3 h (P = 0.001). However, the peak plasma nateglinide concentration (Cmax) remained unchanged. The AUC(0,7 h) of the M7 metabolite of nateglinide was decreased by 19% (P = 0.002) and its t(1/2) was shortened from 2.1 to 1.6 h by rifampicin (P = 0.008). Rifampicin had no significant effect on the blood glucose-lowering effect of nateglinide. CONCLUSIONS: Rifampicin modestly decreased the plasma concentrations of nateglinide probably by inducing its oxidative biotransformation. In some patients, rifampicin may reduce the blood glucose-lowering effect of nateglinide.     

Distribution of histamine in the developing peripheral nervous system

The presence and ontogenetic distribution of histamine was studied in the developing peripheral nervous system of the rat by using an indirect immunofluorescence technique and a specific rabbit anti-histamine antiserum. Histamine immunoreactivity (IR) first appeared in peripheral nerves on embryonic day 14. The number and intensity of histamine-immunoreactive nerves was highest on embryonic days 16–18. During development starting from embryonic day 14, motoneurones in ventral horns of the spinal cord at cervical, thoracic and lumbar levels contained histamine IR. A subpopulation of sensory neurones in dorsal root ganglia exhibited histamine IR. Histamine IR was also present in nerve fibres of ventral and dorsal roots of spinal cord, as well as in spinal nerves. Population of neurones and nerve fibres in sympathetic and pelvic ganglia as well as in myenteric ganglia of the intestine were also labelled with the histamine antiserum. In peripheral target organs, histamine IR was observed in nerve fibres around bronchi of the lungs, in the atria of the heart, in the adrenal gland, in the intestinal wall, in muscular tissues and in subepithelial tissue of the skin.The results of this study indicate that histamine is widely distributed in different types of neurones and nerve fibres of the developing peripheral nervous system.     

Three levels of dietary calcium-effects on blood pressure and electrolyte balance in spontaneously hypertensive rats

Summary The effects of three levels of calcium intake on blood pressure (BP) and electrolyte balance were studied for 12 weeks in spontaneously hypertensive rats (SHR): the chow of the SHR-1 group contained 1.1% calcium, and that of the supplemented groups 2.1% (SHR-2) and 3.1% (SHR-3) calcium. Wistar-Kyoto rats on a 1.1% calcium diet (WKY-1) served as normotensive controls. After 10 and 12 weeks BP was significantly lower in both calcium-supplemented groups than in the SHR-1 group, the SHR-2 and SHR-3 groups not deviating from each other. Platelets and lymphocytes were used as experimental cell models to study the effects of the calcium diets on intracellular free calcium ([Ca²⁺]_i) level, which was measured by the fluorescent indicator quin-2. At the end of the study [Ca²⁺]_i was lower in both cell types in SHR-2 and SHR-3 than in SHR-1, the supplemented groups being comparable to each other. In platelets [Ca²⁺]_i still remained higher in the calcium-treated than the WKY-1 group, while in lymphocytes the levels were similar between SHR-2, SHR-3 and WKY-1. Plasma sodium, calcium and magnesium levels did not differ in the SHR groups, but plasma potassium was higher in both supplemented groups than in SHR-1. Plasma renin activity was comparable in SHR-1, SHR-2 and WKY-1, but was suppressed in the SHR-3 group. Creatinine clearance in the SHR-3 group was higher than in SHR-1 and SHR-2, but still remained lower than in WKY 1. High calcium intake was associated with a dose-dependent increase in urinary magnesium excretion, while the excretions of sodium and potassium were proportional to the intakes. The tissue Na⁺ :K⁺ ratio in abdominal aorta and tail artery was reduced in SHR-2,.but only a nonsignificant tendency was observed in SHR-3 when compared with the SHR-1 group.In summary, high calcium intake reduces [Ca²⁺]_i in both platelets and lymphocytes in SHR, suggesting that alterations in cellular calcium regulation may explain the BP-lowering effect of calcium supplementation. Elevation of dietary calcium level from 1.1% to 2.1% is associated with a lowering of the Na⁺ :K⁺ ratio in the arterial wall. A further increase in calcium content from 2.1% to 3.1% appears to have a favourable effect on renal function in SHR, but also aggravates magnesium loss into the urine. During the higher supplemented calcium intake, suppression of the renin-angiotensin system seems to be involved in the lowering of BP. Correspondence to H. Wuorela at the above address     

Assessment of cardiovascular risk in primary health care

Objective

This study aimed at investigating whether cardiovascular risk factors and their impact on total risk estimation differ between men and women.

Design

Cross-sectional cohort study.

Subjects

Finnish cardiovascular risk subjects (n = 904) without established cardiovascular disease, renal disease, or known diabetes.

Main outcome measures

Ankle-brachial index (ABI), estimated glomerular filtration rate (eGFR), oral glucose tolerance test, and total cardiovascular risk using SCORE risk charts.

Results

According to the SCORE risk charts, 27.0% (95% CI 23.1–31.2) of the women and 63.1% (95% CI 58.3–67.7) of the men (p < 0.001) were classified as high-risk subjects. Of the women classified as low-risk subjects according to SCORE, 25% had either subclinical peripheral arterial disease or renal insufficiency.

Conclusions

The SCORE system does not take into account cardiovascular risk factors typical in women, and thus underestimates their total cardiovascular risk. Measurement of ABI and eGFR in primary care might improve cardiovascular risk assessment. especially in women.Key Words: Ankle-brachial index, cardiovascular risk estimation, gender difference, glucose disorders, renal functionMore women than men die from cardiovascular disease in Europe, but the non-conventional risk factors in women may remain undiagnosed or ignored.

• In a cohort of middle-aged cardiovascular risk subjects in primary care, 27% of the women and 63% of the men (p < 0.001) were classified as high-risk subjects according to the SCORE risk charts.
• Of the women classified as low-risk subjects according to SCORE, 25% had either subclinical peripheral arterial disease or renal insufficiency.
• Measurement of ABI and eGFR in primary care might improve cardiovascular risk assessment, especially in women.