Asthma Programme in Finland: the quality of primary care spirometry is good

AIMS: To assess the quality of primary care spirometry by visual inspection of the flow-volume expiratory curve and to study the quantity of clinical information provided on the spirometry report sheets. METHODS: Retrospective audit of 868 expiratory flow-volume curves referred to three pulmonary clinics assessed against five predefined quality criteria. Clinical information included on the spirometry report sheets was also collected. RESULTS: Quality was good in 78% of pre-bronchodilation curves and in 80% of post-bronchodilation curves. Obtaining a sharp PEF value and full vital capacity exhalation seemed to be the critical points of measurement. Inter-rater reliability of the curve assessment was mainly good. Data on where the spirometry took place, and comments on the use of respiratory medication and patient co-operation were often lacking. CONCLUSIONS: The quality of primary care spirometry was good. Adequate clinical information on the report sheets would further improve the quality of this diagnostic process.     

Dual action of adrenergic system on the regulation of thyrotrophin secretion in the male rat.

The effect of graded doses of drugs modifying adrenergic activity on basal and cold-stimulated TSH secretion was studied in male rats. alpha-methyl-p-tyrosine (aMPT) (16 h before 30 min cold-exposure), phenoxybenzamine (1 h), Ca-fusarate (1 h) and diethyldithiocarbamate (DDC) (1 and 18 h) dose-dependently depressed the cold-stimulated TSH secretion. The effect of reserpine (24 h) was not significant. Clonidine (1 h), dihydroxyphenyl-serine (DOPS) (1 h), noradrenaline (NA) (1 h), and L-Dopa (1 h) were also effective in decreasing serum TSH levels, but dopamine (DA) (ad 2 mg/kg, 1 h) had no effect. Basal TSH levels were also decreased by various doses of clonidine, DOPS and NA, given ip 1 h before sacrifice. Clonidine (1 mg/kg), NA (1 mg/kg), DA (2 mg/kg), aMPT (300 mg/kg), phenoxybenzamine (2 or 20 mg/kg), Ca-fusarate (50 mg/kg) or L-Dopa (200 mg/kg) did not modify the TRH-induced TSH response. These results cannot be explained by assuming only a stimulatory function for the adrenergic system on the secretion of TSH in the rat. The site of the possible inhibitory function of noradrenaline in the control of TSH cannot be deduced from these results, but various possibilities are discussed.     

Atrial natriuretic peptide in plasma, atria, ventricles, and hypothalamus of Long-Evans and vasopressin-deficient Brattleboro rats

To evaluate the role of vasopressin in the regulation of atrial natriuretic peptide (ANP) secretion, the plasma, atrial, ventricular, and hypothalamic levels of ANP were measured in Long-Evans (LE) and vasopressin-deficient Brattleboro (DI) rats. Total atrial immunoreactive ANP (IR-ANP) as well as right auricular IR-ANP concentration were higher in the DI than in the LE rats, whereas no significant difference was noted in left auricular IR-ANP concentration. In the left ventricle of DI rats, the IR-ANP concentration was 82% greater than that in the LE rats, while no substantial difference was found in the right ventricular IR-ANP concentration between the strains. Normal LE rats had low levels of left ventricular ANP mRNA and barely detectable ANP mRNA in the right ventricle, DI rats showed a 3-fold greater ANP mRNA concentration in the left ventricle than age-matched LE controls, and ANP mRNA levels were also increased in the left auricle of DI rats. The hypothalamic IR-ANP content, but not the concentration, was significantly increased in the DI compared to the LE rats. Despite increased cardiac IR-ANP and ANP mRNA levels, plasma IR-ANP concentrations were similar in the conscious DI rats (97 +/- 9 pg/ml; n = 13) and the LE rats (95 +/- 8 pg/ml; n = 15). Volume expansion (1.1 ml/100 g BW of 0.9% saline, iv) increased right atrial pressure and caused a significant rise in plasma IR-ANP in both strains (P less than 0.01). Elevations of plasma IR-ANP concentrations caused by volume loading were comparable in LE and DI rats in either the absence or presence of exogenous vasopressin (5 ng/kg.min, iv), which, when infused alone, did not significantly influence the plasma IR-ANP concentration. However, the relation between the change in IR-ANP concentration and the change in right atrial pressure shifted to the left, and thus, for a given increase in right atrial pressure, a greater amount of IR-ANP was released in the vasopressin-treated rats than in the control animals. These results demonstrate that although acute volume expansion does not necessarily require endogenous vasopressin for the ANP secretory response, vasopressin increased the ability of volume expansion to induce ANP release, thus modulating the direct mechanical stimulus-induced ANP secretion. The increased left ventricular levels of immunoreactive ANP and augmentation of ANP mRNA levels in Brattleboro rats despite normal left ventricular weight to body weight ratio show that increased ANP gene expression may occur in the ventricles independently of hypertrophy.     

Associations between congenital cryptorchidism in newborn boys and levels of dioxins and PCBs in placenta

In animal studies, exposure to dioxins has been associated with disrupted development of the male reproductive system, including testicular maldescent. Some polychlorinated biphenyls (PCBs) have also dioxin-like effects. In addition, one previous case-control study has reported an association between congenital cryptorchidism and colostrum PCB levels. We performed a case-control study to evaluate whether congenital cryptorchidism in boys was associated with increased levels of dioxins or PCBs in placenta reflecting foetal exposure. In addition, associations between placenta levels of these chemicals and reproductive hormone levels in boys at 3 months were studied. Placentas were collected in a Danish-Finnish joint prospective cohort study on cryptorchidism (1997-2001). The boys were examined for cryptorchidism at birth and at 3 months. Altogether, 280 placentas [112 Finnish (56 cases, 56 controls) and 168 Danish (39 cases, 129 controls)] were analysed for 17 toxic polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and 37 PCBs (including 12 dioxin-like PCBs). Infant serum samples taken at 3 months were analysed for reproductive hormones. No significant differences between cases and controls were observed in either country in dioxin WHO-TEq levels (median 9.78 vs. 8.47 pg/g fat, respectively, in Finland, and 11.75 vs. 10.88 pg/g fat in Denmark) or PCB WHO-TEq levels (median 2.12 vs. 2.15 pg/g fat in Finland, 2.34 vs. 2.10 pg/g fat in Denmark) or total-TEq levels (median 11.66 vs. 10.58 pg/g fat in Finland, 13.94 vs. 13.00 pg/g fat in Denmark). Placenta WHO-TEq levels of dioxins were not associated with infant reproductive hormone levels at 3 months. In Finland, PCB WHO-TEq levels in placenta associated positively with infant LH levels. WHO-TEq levels of dioxins and PCBs and total-TEq levels were higher in Danish than Finnish samples. In conclusion, no association between placenta levels of dioxins or PCBs and congenital cryptorchidism was found. Significant country differences in chemical levels were observed.     

Inhibition of sound-induced convulsions by metoprine in the audiogenic seizure susceptible rat

Metoprine which increases brain histamine by blocking its methylation, was recently demonstrated to inhibit electrically induced tonic convulsions in rats. Its effect was now tested on audiogenic convulsions in genetically audiogenic seizure sensitive rats. Metoprine (20 mg/kg, i.p.) reduced the severity of seizures significantly 4 and 28 h after drug administration. Also the duration of convulsions was significantly decreased. These results agree with an involvement of histaminergic neurons in convulsive phenomena perhaps as a part of an anticonvulsive inhibitory transmitter system.     

Histamine in Cerebrospinal Fluid of Children with Febrile Convulsions

Summary: Febrile convulsions (FC) are frequent acute neurologic disturbances of childhood. The cellular and neurochemical mechanisms causing FC are unclear. Among other mechanisms, the CNS histamine (HA) has been suggested to participate in seizure control and thermoregulation. We evaluated the possible role of HA in regulation of FC by measuring HA and tele-methylhis- tamine (t–MH) concentrations in the cerebrospinal fluid (CSF) of children with FC. The study group consisted of 35 children treated for acute FC in the hospital. The control groups consisted of (a) feverish children without seizures ( n =23), (b) convulsive children without fever ( n =7), and (c) children with neither fever nor convulsions ( n =21). HA was assayed by high-performance liquid chromatography (HPLC) with fluorescence detection, and t-MH was measured by gas chromatography-mass spectrometry. CSF HA concentration in the group of febrile Convulsions occur rather frequently in connection with febrile children without seizures was significantly higher (0.69 ± 0.16 pmol/ml, mean k SE) than in children with FC (0.36 ± 0.07 pmol/ml, p <0.05, analysis of variance, ANOVA). HA concentration was 0.37 ± 0.18 pmoVml in the group of nonfebrile convulsive children and 0.36 k 0.08 pmol/ml in the nonfebrile nonconvulsive group. No statistical differences in t–MH were detected between groups. The increased susceptibility to seizures during fever may be connected to the lack of increase in CSF HA in the FC group. The data support the hypothesis that the central histaminergic neuron system may be involved in inhibition of seizures associated with febrile illnesses in childhood.     

Studies on the Role of Lipid Peroxidation in the Acute Toxicity of TCDD in Rats*

Lipid peroxidation has been shown to be enhanced following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), but its role in TCDD toxicity is unclear. The present study was undertaken to further elucidate the relations between lipid peroxidation and TCDD lethality. A time course and dose-response experiment in Long-Evans (L-E; LD50 ca. 10 μg/kg) and Han/Wistar (H/W; LD50 > 3000 μg/kg) rats showed that hepatic lipid peroxidation, measured as the amount of thiobarbituric acid-reactive substances (TBA-RS), was induced by TCDD dose-dependently in L-E, but not in H/W rats. Hepatic glutathione peroxidase activity was suppressed in much the same manner in both strains. Lipid peroxidation correlated with body weight loss in L-E rats alone. When 500 μg/kg of TCDD was given to L-E rats, lipid peroxidation increased about 3-fold on Day 11 in the liver, while no change was seen in cardiac or renal TBA-RS. The pair-fed controls did not survive the 11-day test period and exhibited gastrointestinal hemorrhages. At 6 days, liver atrophy and elevated (over 2-fold) TBA-RS values were recorded in pair-fed controls but not in their TCDD-treated counterparts. TCDD decreased hepatic glutathione peroxidase activity by almost 50% at 6 days, while pair-feeding was without effect. Liver morphology was different between TCDD-treated and pair-fed rats. Moreover, the livers of TCDD-treated L-E rats contained much higher concentrations of probably peripheral fat-derived fatty acids than did the livers of pair-fed or ad libitum control rats. Restricted feeding over 6 days induced hepatic lipid peroxidation more in H/W than in L-E rats. Endotoxin increased liver TBA levels similarly in both strains having an additive effect with high doses of TCDD in H/W rats. Added as a 0.5% concentration in chow, butylated hydroxyanisole (BHA), but not ethoxyquin, tended to increase survival rate and time in L-E rats exposed to 20 μg/kg of TCDD; at 50 μg/kg the only survivor was again in the BHA group. However, neither antioxidant had any effect on initial body weight loss. It is concluded that lipid peroxidation mainly arises as a secondary phenomenon in TCDD toxicity, is not the cause of the typical histopathological liver lesion, but may contribute to lethality.     

Is histamine an anticonvulsive inhibitory transmitter?

This study was done to investigate the possible role of histaminergic systems in electroshock seizures. Brain histamine concentrations in rats were elevated by metoprine (i.p.), an inhibitor of histamine-N-methyltransferase. Animals were tested for their response to maximal electroshock (MES) at different times after the injection. Metoprine raised brain histamine concentrations and inhibited maximal hindleg extension after MES in a dose-dependent manner. Sensitivity to seizures correlated inversely with histamine concentrations. These results suggest that histaminergic neurones are involved in mechanisms which inhibit generalizations of epileptic discharges in the brain.     

Neurotransmitters in the nervous system of Macoma balthica (Bivalvia)

The distribution of histamine-, octopamine-, gamma-aminobutyric acid- (GABA) and taurine-like immunoreactivity in the bivalve mollusc Macoma balthica was studied immunocytochemically with antisera produced in rabbits. Histamine levels in the ganglia and whole animals were also measured by high-performance liquid chromatography using a postcolumn derivatization method. Immunoreactivity for these substances, except for taurine, is found in the central nervous system of this species. The most extensive neuronal system is revealed with the antiserum against histamine. All the main ganglia contain histamine-immunoreactive cell bodies, and a dense network of nerve fibers is seen in the ganglia and nerve roots. Histamine-immunoreactive nerve fibers project to the mantle edge, lips and oesophagus. The basal part of the inhalant siphon is rich in histamine-immunoreactive fibers. Unlike histamine, octopamine- and GABA-like immunoreactivities are restricted to the central nervous system. Taurine-like immunoreactivity is not found in the nervous system of this species. In the nervous system, histamine-immunoreactive cell bodies and fibers are more numerous than those that are octopamine- and GABA-immunoreactive. The distribution of these substance in the ganglia is different. GABA-immunoreactive cells are typically smaller than most of the histamine- and octopamine-immunoreactive cells. Most GABA- and octopamine-immunoreactive cells and fibers are located in the pedal ganglion. Histamine is distributed more evenly in the ganglia and nerve roots. The biochemical measurements of histamine correlate well with the immunohistochemical findings and confirm the predominant location of the amine in the nervous tissue. These results suggest that histamine is more widespread than some other putative transmitters, and support the concept that histamine may have an important role in many physiological processes in molluscs. © 1993 Wiley-Liss, Inc.