A review of the pharmacological and clinical profile of mirtazapine

The novel antidepressant mirtazapine has a dual mode of action. It is a noradrenergic and specific serotonergic antidepressant (NaSSA) that acts by antagonizing the adrenergic alpha2-autoreceptors and alpha2-heteroreceptors as well as by blocking 5-HT2 and 5-HT3 receptors. It enhances, therefore, the release of norepinephrine and 5-HT1A-mediated serotonergic transmission. This dual mode of action may conceivably be responsible for mirtazapine's rapid onset of action. Mirtazapine is extensively metabolized in the liver. The cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4 are mainly responsible for its metabolism. Using once daily dosing, steady-state concentrations are reached after 4 days in adults and 6 days in the elderly. In vitro studies suggest that mirtazapine is unlikely to cause clinically significant drug-drug interactions. Dry mouth, sedation, and increases in appetite and body weight are the most common adverse effects. In contrast to selective serotonin reuptake inhibitors (SSRIs), mirtazapine has no sexual side effects. The antidepressant efficacy of mirtazapine was established in several placebo-controlled trials. In major depression, its efficacy is comparable to that of amitriptyline, clomipramine, doxepin, fluoxetine, paroxetine, citalopram, or venlafaxine. Mirtazapine also appears to be useful in patients suffering from depression comorbid with anxiety symptoms and sleep disturbance. It seems to be safe and effective during long-term use.     

Transfer factor and cellular immune response in urinary tract infections in children.

Cellular immune responses in vivo and in vitro were studied in 20 children with chronic or relapsing urinary tract infections. Skin tests revealed decreased immune responses to PPD in cases with chronic or recurrent pyelonephritis and to OM, in these cases and in cases of lower urinary tract infections. Blast transformation responses to PPD, OM and PHA were at least as high as in controls. Administration of chromatographically purified fraction from human leucocyte transfer factor resulted in a positive skin reaction with antigen concentration, which before TF administration had caused a negative reaction. The results suggest that the action of the transfer factor component used in this study is based on an immunologically nonspecific stimulation of the cellular immune response.     

Predictive value of clinical and radiological findings in inflicted traumatic brain injury

Aims: The aim of this study is to evaluate the value of early radiological investigations in predicting the long‐term neurodevelopmental outcome of infants with inflicted traumatic brain injury (ITBI). Methods: Clinical and radiological investigations of 24 infants with ITBI were performed during the acute phase of injury (1–3 days), and during the early (4 days up to 3 months) and late (>9 months) postinjury phases. The clinical outcome in survivors (n = 22) was based on the Rankin Disability Scale and the Glasgow Outcome Score. Results: Five out of 24 infants (21%) had a poor neurodevelopmental outcome (death and severe disability), 17 infants (71%) had different developmental problems and 2 infants were normal at the mean age of 62 (54–70) (95% CI) months. A low initial Glasgow Coma Scale score of 8 or below [p < 0.05, OR 13.0 (1.3–133.3)], the development of brain oedema [p < 0.005, OR 13.0 (1.6–773)], focal changes in the basal ganglia during the acute phase [p < 0.01, OR 45 (2.1–937.3)], the development of new intracerebral focal changes early postinjury [p < 0.05, OR 24.1(1.0–559.1)], a decrease in white matter [p < 0.01, OR 33 (1.37–793.4)] and the development of severe atrophy before 3 months postinjury [p < 0.05, OR 24 (11.0–559.1)] were significantly correlated with a poor neurodevelopmental outcome. Conclusions: Early clinical and radiological findings in ITBI are of prognostic value for neurodevelopmental outcome.     

Predisposing and provoking factors in childhood headache

Objective.–To study the differences in predisposing and provoking factors between childhood migraine and nonmigrainous headache.
Background.–Information on the predisposing and provoking factors of headache could help to find ways to prevent it. Differences in predisposing and provoking factors between migraine and nonmigrainous headache are largely unknown.
Methods.–An unselected, population-based, prospective, follow-up study on the occurrence of headache in schoolchildren was carried out in 1290 children aged from 8 to 9 years. The children who had reported headache during the 6 months prior to the study ( n = 725) were sent a more detailed questionnaire about factors that might give rise to headache. Six hundred twenty-two (86%) children returned questionnaires that were completed to an acceptable degree.
Results.–The occurrence of familial paroxysmal headache and unhappiness in the family independently predicted the occurrence of migraine in children, but this was not the case for nonmigrainous headache.
Conclusions.–In particular, the family occurrence of paroxysmal headache increases the risk of migraine in a child. The risk is still greater if their living conditions are experienced as unsatisfactory by the family.     

Colorectal cancer screening in Finland: details of the national screening programme implemented in Autumn 2004

Colorectal cancer mortality can be reduced by repeated faecal occult blood (FOB) testing followed by colonoscopy for test positives. The object of this report is to describe how to launch a new screening programme in such a way that its effectiveness can be reliably evaluated. The programme is based on gradual expansion over time with individual-level randomization into screening or control arms among a target population aged 60-69 years in Finland. The target population will be sampled from the population register for invitees and controls by municipality and by birth cohort. The non-invited controls will gradually be screened only after the six-year implementation period. After 10 years, the programme covers the entire target population. The effects of screening will be evaluated, comparing the incidence of and mortality from colorectal cancer in those invited to screening with controls. The primary screening test is a biannual guaiac-based FOB test with three test cards for consecutive samples. In September-December 2004, around 5000 test-kits were sent to 22 piloting municipalities. In 2005, the programme expands both among municipalities and the target population, resulting in nearly 20,000 individual requests. The implementation of colorectal cancer screening in Finland in this way meets the criteria for a randomized controlled trial and the requirements for a public health programme. It allows unbiased research data to be collected while introducing the programme and may set an example for the introduction of all national screening programmes.     

Sustained activation of p38 mitogen-activated protein kinase contributes to the vascular response to injury

The vascular response to mechanical injury involves inflammatory and fibroproliferative processes that result in the formation of neointima and vascular remodeling. The complex cellular interactions initiated by vascular injury are coordinated and modulated by the elaboration of cytokines and growth factors. The production and transduction of many of these mediators require phosphorylation of p38 mitogen-activated protein kinase (MAPK). In the present investigation, we examined the pattern and localization of p38 MAPK activation following balloon vascular injury. The effects of long-term and selective inhibition of p38 MAPK with SB 239063 (trans-1-(4-hydroxycyclohexyl)-4-(4-fluorophenyl)-5-[2-methoxy)pyrimidin-4-yl]imidazole) were also investigated in a model of vascular injury. Western blotting and immunohistochemical staining demonstrated that phospho-p38 MAPK was increased following balloon injury of the rabbit iliofemoral artery. The p38 MAPK activation was noted as early as 15 min after balloon injury and remained elevated for at least 28 days. Phospho-p38 MAPK immunoreactivity (IR) was localized primarily in regions of dedifferentiated, smooth muscle alpha-actin-positive cells in all lamina of the vessel wall. Phospho-p38 MAPK IR was not correlated with the localization of macrophage or proliferating cells (proliferating cell nuclear antigen; PCNA +). Long-term treatment (4 weeks) with SB 239063 (50 mg/kg/day, p.o.) reduced the vascular response to injury in the hypercholesterolemic rabbit. SB 239063 had no effect on platelet-derived growth factor (PDGF)-stimulated migration or proliferation of rabbit vascular smooth muscle cells (VSMCs) in culture. However, SB 239063 produced a concentration-dependent inhibition of transforming growth factor (TGF)-beta-stimulated fibronectin production in VSMCs. In conclusion, sustained activation of p38 MAPK plays an important role in the vascular response to injury and inhibition of p38 MAPK may represent a novel therapeutic approach to limit this response.     

Tension-type headache in children and adolescents

Although tension-type headache is at least as prevalent as migraine in children and adolescents, in contrast to migraine, childhood tension-type headache has received limited research attention. Follow-up studies have shown that migraine may reverse in tension-type headache and vice versa. In addition, children with frequent episodic tension-type headache may be at increased risk of chronic tension-type headache. It is very important to recognize these children and to intervene. Further studies are needed to clarify the pathophysiology of pediatric tension-type headache.     

Antibiotic concentrations in liquor compared to the minimal inhibitory concentrations of isolates in paediatric bacterial meningitis. The Finnish Study Group

The susceptibilities of 171 bacteria which caused meningitis in 200 children were tested for their susceptibility as minimal inhibitory concentrations (MICs) for the antibiotics used in therapy. These antibiotics were chloramphenicol, ampicillin, cefotaxime and ceftriaxone. The MICs were compared to the minimal concentrations of the drugs seen in the cerebrospinal fluid (CSF) samples. The minimal bacteriostatic capacity (lowest concentration in CSF/MIC) of both cephalosporins was superior to that of chloramphenicol and ampicillin. The correlation of the finding with the speed of liquor sterilization in the treatment groups is discussed.