Viral and rickettsial etiology of an outbreak of acute respiratory tract infection

An outbreak of 111 cases of acute respiratory tract infection was recorded in a community of the town "T" in April-May 1984. The clinical picture was severer than usual; 28% of the cases had to be hospitalized, average absenteeism being as high as 26 days per case. Serological investigations demonstrated the previous circulation of influenza virus B/Singapore/222/79 and the simultaneous circulation during the outbreak of influenza virus A/England/333/80 (H1N1) and of Rickettsia burneti (as also ascertained by isolation in the chick embryo of the former and by visualization by immunofluorescence in exfoliated cells of the latter pathogen). The association of the two etiological agents appears to account for the severe and protracted course of the disease.     

The HTR1B 861G>C receptor polymorphism among patients suffering from alcoholism, major depression, anxiety disorders and narcolepsy

The HTR1B receptor gene has been linked to antisocial alcoholism in a Finnish population and an American Indian tribe [Lappalainen et al. , Arch. Gen. Psychiatry, 55 (1998) 989]. Using a candidate gene approach, we genotyped 209 patients with alcoholism, 108 patients with major depression, 32 patients with panic disorder, 50 patients with generalized anxiety disorder, 58 patients with narcolepsy and 74 healthy volunteers for the HTR1B 861G>C polymorphism. There was a higher frequency of the HTR1B 861G alleles among the alcohol-dependent patients as compared to the control subjects (chi(2)=4.02, d.f.=2, P=0.04). However, the association resulted from higher frequencies of the opposite alleles (HTR1B 861G), as originally reported by Lappalainen et al. (1998). Although the association in our study might be due to a type I error, the higher degree of HTR1B allele sharing within both populations could also argue for another alcoholism-relevant gene within the proximity of the HTR1B gene on human chromosome 6.     

No Association Between the Dopamine D2 Receptor Taq I A1 Allele and Earlier Age of Onset of Alcohol Dependence According to Different Specified Criteria

BACKGROUND: The presence of the A1 allele of the dopamine D2 receptor TaqI restriction fragment length polymorphism has been reported to be associated with an earlier age of onset of alcohol dependence as a marker for severity. METHODS: We tested this hypothesis with special regard to the definition of the age of onset of alcoholism in 243 patients with alcohol dependence, according to DSM-IV criteria assessed by the standardized interview Münchner Composite International Diagnostic Interview (M-CIDI), consecutively admitted for detoxification. Additionally, the Addiction Severity Index (ASI) was performed. The TaqIA polymorphism was amplified by polymerase chain reaction (PCR), and the PCR product was digested by the restriction enzyme TaqI. Patients were subsequently divided into an A1 (presence of at least one A1 allele, n = 88) and an A2 group (absence of an A1 allele, n = 155). The following criteria for different definitions of age of onset were used: (1) age of onset of the first occurring symptom necessary for the diagnosis of alcohol dependence according to M-CIDI; (2) age of onset of the last symptom of alcohol dependence according to M-CIDI; (3) age of onset of more than 3 drinking days per week on a regular basis according to ASI; (4) age of onset of more than 3 drinking days-of more than five drinks per drinking day-or at least one binge drinking episode per week on a regular basis according to ASI. RESULTS: The frequency of the A1 allele in our patient sample was 0.208. No statistically significant association between the A1 allele and the age of onset of alcoholism was found. The mean age of onset according to criterion 1 was 30.4 +/- 10.8 years for the A1 group and 30.2 +/- 10.2 years for the A2 group (p = 0.89); for criterion 2, it was 33.3 +/- 10.0 years for the A1 group and 33.9 +/- 10.2 years for the A2 group (p = 0.77); for criterion 3, it was 18.0 +/- 7.5 years for the A1 group and 18.1 +/- 6.1 years for the A2 group (p = 0.92); and for criterion 4, it was 22.3 +/- 9.7 years for the A1 group and 21.8 +/- 8.5 years for the A2 group (p = 0.76). CONCLUSIONS: No association was found between the A1 polymorphism and age at onset of alcohol dependence according to different specified criteria.     

Add-on combination and maintenance treatment: case series of five obese patients with different eating behavior

Obesity is a general medical condition associated with an increase in morbidity and mortality. Although it would be desirable to use efficacious prevention programs, the success rates reported to date have been rather disappointing. In this observational study, a new drug treatment regimen was evaluated in five obese patients with a mean age of 39.6 +/- 4.2 years and an initial body mass index between 34.5 and 38.3 kg/m for a period of 96 weeks. The patients showed restrained and unrestrained eating patterns according to a German version of the Three-Factor Eating Questionnaire and were treated in an add-on regimen with the combination of three drugs with different anorectic properties that were consecutively introduced in an interval of 16 weeks. First, orlistat (120 mg three times a day) was given as a monotherapy. Sibutramine (15 mg in the morning) and then topiramate (in a dose dependent on appetite suppression and side effects) were added for a total duration of 48 weeks. A 48-week maintenance and relapse prevention treatment period with topiramate monotherapy followed the discontinuation of orlistat and sibutramine. This outpatient treatment procedure was tolerated well, although side effects occurred in all patients depending on the phase of the treatment regimen. After 96 weeks, the mean body mass index was 25.7 +/- 1.2 kg/m. Moreover, a normalization of eating patterns according to the Three-Factor Eating Questionnaire could be noticed. Factor 3, hunger, was significantly reduced. This treatment plan may be highly effective and safe in a subpopulation of obese patients.     

Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression

OBJECTIVE: Current clinical knowledge holds that antidepressants have a delayed onset of efficacy. However, the delayed onset hypothesis has been questioned recently by survival analytical approaches. We aimed to test whether early improvement under antidepressant treatment is a clinically useful predictor of later stable response and remission. METHOD: We analyzed data from a randomized double-blind controlled trial with mirtazapine and paroxetine in patients with major depression (DSM-IV). Improvement was defined as a 17-item Hamilton Rating Scale for Depression (HAM-D-17) score reduction of > or = 20%. Stable response was defined as > or = 50% HAM-D-17 score reduction at week 4 and week 6, and stable remission as a HAM-D-17 score of < or = 7 at week 4 and week 6. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Improvement occurred in a majority of the analyzed patients within 2 weeks (mirtazapine: 72.7% of 109 patients; paroxetine: 64.9% of 103 patients). Early improvement was a highly sensitive predictor of later stable response or stable remission for both drugs. NPV approached maximum values as early as week 2 for mirtazapine and week 3 for paroxetine. After 2 weeks of treatment with mirtazapine and 3 weeks with paroxetine, almost none of the patients who had not yet improved became a stable responder or stable remitter in the later course. CONCLUSION: Our results strongly suggest that early improvement predicts later stable response with high sensitivity. These empirically derived data question the delayed onset hypothesis for both antidepressants tested and provide important clinical clues for an individually tailored antidepressant treatment.     

Changes in plasma low-density lipoprotein (LDL)- and high-density lipoprotein cholesterol in hypo- and hyperthyroid patients are related to changes in free thyroxine, not to polymorphisms in LDL receptor or cholesterol ester transfer protein genes

Thyroid function disorders lead to changes in lipoprotein metabolism. Both plasma low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) increase in hypothyroidism and decrease in hyperthyroidism. Changes in LDL-C relate to altered clearance of LDL particles caused by changes in expression of LDL receptors on liver cell surfaces. Changes in cholesterol ester transfer activity partly explain changes in HDL-C. It has been suggested that the magnitude of these changes is related to polymorphisms of involved genes. The aim of the present study is to investigate whether the polymorphic AvaII restriction site in exon 13 of the LDL receptor gene and the polymorphic TaqIB site in intron 1 of the cholesterol ester transfer protein are associated with the magnitude of the changes in plasma LDL-C and HDL-C, respectively, in the transition from the hypo- or hyperthyroid to the euthyroid state. From a consecutive group of 66 untreated hypothyroid and 60 hyperthyroid patients, 47 Caucasians in each group were analyzed. Fasting LDL-C and HDL-C were measured at baseline and 3 months after restoration of the euthyroid state. Genotype was determined by means of PCR techniques. The homozygous presence of a restriction site was designated as +/+, heterozygous as +/-, and absence as -/-. Trend analysis was done with ANOVA. Among hypo- or hyperthyroid patients, subgroups with different genotypes did not differ in thyroid function pre- or post treatment. The mean decrease in LDL-C (mmol/L +/- SD) in hypothyroid patients with different AvaII genotypes did not differ: - 1.07 +/- 1.44 (-/-, N = 15), -1.25 +/- 1.53 (+/-, N = 19), and -1.18 +/- 1.01 (+/+, N = 13) mmol/L [not significant (NS)]; neither did the mean increase in hyperthyroid patients: 1.07 +/- 0.90 (-/-, N = 18), 0.92 +/- 1.00 (+/-, N = 21), and 1.20 +/- 0.45 (+/+, N = 6) (NS). The mean decrease in HDL-C (mmol/L +/- SD) in hypothyroid patients with different TaqIB genotypes did not differ: -0.22 +/- 0.26 (-/-, N = 13), -0.15 +/- 0.23 (+/-, N = 21), and -0.12 +/- 0.22 (+/+, N = 9) (NS); neither did the mean increase in hyperthyroid patients: 0.29 +/- 0.39 (-/-, N = 7), 0.26 +/- 0.23 (+/-, N = 22), and 0.19 +/- 0.31 (+/+, N = 18) (NS). Changes in LDL-C and HDL-C correlated with the logarithm of the change in free T4 (fT4), expressed as the fT4 posttreatment/fT4 pretreatment ratio (r = -0.81, P < 0.001; and r = -0.62, P < 0.001, respectively). In conclusion, in the transition from hypo- or hyperthyroidism to euthyroidism, no association is found between AvaII genotype and changes in plasma LDL-C nor between TaqIB genotype and changes in HDL-C. Changes in LDL-C and HDL-C correlate with changes in fT4.     

Adenylyl cyclase activity is increased in younger, but decreased in older, alcoholic patients after detoxification

Acute and chronic administration of ethanol leads to alterations of the adenylyl cyclase (AC) signal transduction pathway. This study examined whether the formation of cAMP by AC in lymphocytes correlates with age in alcoholic patients and in healthy controls. Blood was drawn for preparation of lymphocyte membranes and for determination of basal, GTPgammaS-stimulated, and forskolin-stimulated AC activity from 68 actively drinking alcoholic patients (age, mean +/- SD: 45 +/- 10; range: 26-69 years) after ethanol detoxification. The patients' AC activity correlated negatively with age. In contrast, no effect of age was observed in the healthy controls (age, mean +/- SD: 42 +/- 11; range: 24-65 years). The age-related decrease in AC activity of alcoholic patients could not be attributed to the duration of regular alcohol intake. It was partly due to the large variance of AC activity in younger and middle-aged alcoholics.     

Rapid detection by immunofluorescence of multiple viral infections in patients with keratitis

The presence of 12 viral (herpes 1 and 2, influenza A(H1N1), A(H3N2) and B, parainfluenza 1, 2, 3, adenovirus 5) and inframicrobial (Chlamydia, mycoplasma, Rickettsia burneti) antigens was investigated by direct or indirect immunofluorescence (IF) reactions in exfoliated conjunctival cells from 110 patients with nonbacterial keratitis and keratoconjunctivitis. A rapid etiological diagnosis could be obtained in 101 (92%) of the cases, parainfluenza and herpes antigens being the most frequently detected. In most of the cases the simultaneous presence of several antigens was made evident. Encouraging results were obtained by the application of a specific treatment based on the diagnosis provided by the IF reaction.