Rapid antibody response after vaccination with a virosomal hepatitis a vaccine.

BACKGROUND: This study was designed to assess the early antibody kinetics after a priming dose, and the extent of the antibody increase after a booster dose of an inactivated virosomal hepatitis A virus (HAV) vaccine (Epaxal). PATIENTS AND METHODS: This was an open, uncontrolled study in 30 healthy subjects. The vaccine was injected intramuscularly on day 1 and month 12. Serum antibody titers were measured by ELISA on day 1 (pre dose) and at various time points thereafter until month 12 (pre-booster dose). After the booster dose, antibody titers were measured at various intervals until month 24. Neutralizing antibody titers were measured in 12 subjects a number of times during the 1st month by an antibody neutralization assay. Titers > or = 10 mIU/ml were considered seroprotective. RESULTS: ELISA antibody titers showed a rapid increase post vaccination. By day 15, 96% of subjects were seroprotected, which increased to 100% by day 22 (n = 27 evaluable subjects, aged 18-43 years; 13 male, 14 female). All subjects achieved seroprotective HAV-neutralizing antibody titers by day 11 (n = 12). The booster vaccination at month 12 resulted in a strong response in all subjects, with a sustained anti-HAV antibody titer (1,155 mIU/ml) at month 24. Both the priming and booster doses were well tolerated. CONCLUSION: Primary vaccination with this virosomal HAV vaccine is well tolerated and induces a rapid HAV-neutralizing antibody response resulting in seroprotection in all subjects within 10 days. In addition, the booster vaccination results in prolonged seroprotective antibody levels.

Association of dopaminergic and serotonergic genes with tardive dyskinesia in patients with chronic schizophrenia.

Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic drugs that are dopamine D2 receptor blockers. Serotonin receptor antagonism has been proposed as a common mechanism contributing to the low extrapyramidal side effect profile of atypical antipsychotic drugs. We evaluated candidate dopamine and serotonin genes for association with drug-induced TD. We examined three polymorphisms in the dopamine D2 receptor gene (DRD2), two sites in the 3' region of the dopamine transporter (DAT) gene, two sites in the promoter and coding region of the dopamine D4 (DRD4) receptor gene, as well as polymorphic sites in the serotonin 6 receptor gene, the serotonin transporter gene and the tryptophan hydroxylase gene, for association with TD susceptibility. Schizophrenic patients with (n=59) and without TD (n=63), matched for antipsychotic drug exposure and other relevant variables, were studied. No significant associations were found. Within the limitations imposed by the size of the clinical sample, these findings suggest that the above polymorphic loci do not contribute significantly to risk for TD. Further examination of loci that yielded positive results at a trend level and investigation of other candidate genetic loci coding for antipsychotic drug targets is warranted.

Association between the serotonin 2A receptor gene and tardive dyskinesia in chronic schizophrenia.

Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic drugs that are dopamine D2 receptor blockers.(1) Serotonin receptor antagonism has been proposed as a common mechanism contributing to the low extrapyramidal effects profile of atypical antipsychotic drugs.(2) We examined the association of three polymorphisms in the 5-HT2A receptor gene (HTR2A) with TD susceptibility--T102C(3) and his452tyr(4) in the coding region and A-1438G(5) in the promoter--in matched schizophrenia patients with (n = 59, SCZ-TD-Y) and without TD (n = 62, SCZ-TD-N) and normal control subjects (n = 96). The T102C and the A-1438G polymorphisms are in complete linkage disequilibrium but not his452tyr. There was a significant excess of 102C and -1438G alleles (62.7%) in the SCZ-TD-Y patients compared to SCZ-TD-N patients (41.1%) and controls (45.9%; chi(2) = 12.8, df = 2, P = 0.002; SCZ-TD-Y vs SCZ-TD-N, chi(2) = 11.4, df = 1, P = 0.0008, OR 2.41, 95% CI 1.43-3.99) and of 102CC and -1438GG genotypes (SCZ-TD-Y 42.4%, SCZ-TD-N, 16.1%, controls 20.8%, chi(2) = 13.3, df = 4, P = 0.01). The 102CC and the -1438GG genotypes were associated with significantly higher AIMS trunk dyskinesia scores (F = 3.9; df = 2, 116; P = 0.02) and more incapacitation (F = 5.0; df = 2, 115; P = 0.006). The his452tyr polymorphism showed no association with TD. These findings suggest that the 5-HT2A receptor gene is significantly associated with susceptibility to TD in patients with chronic schizophrenia. Previously reported association of the T102C and A-1438G polymorphisms with schizophrenia(6) may reflect association of a sub-group of patients with a susceptibility to abnormal involuntary movements related to antipsychotic drug exposure.

Dose-dependent olanzapine-associated leukopenia: three case reports.

Leukopenia and agranulocytosis are well reported and dangerous haematological side-effects associated with the use of typical and atypical antipsychotics. These potentially life-threatening phenomena have led to treatment discontinuation and the consequent reemergence of psychiatric symptoms. We report three cases of patients who developed leukopenia during olanzapine treatment. In each case, the leukopenia was dose-dependent. Reduction in the dose of olanzapine was followed by normalization of the white blood count which allowed continuation of the medication. These cases suggest the possibility that, in some patients, leukopenia or agranulocytosis during olanzapine treatment might be dose-related. Thus, olanzapine dose reduction may permit treatment continuation where this is clinically indicated. In our cases, haematological side-effects were satisfactorily controlled by dose reduction without allowing the reemergence of psychiatric symptoms. This clinical management may offer an alternative to treatment suspension. A careful monitoring of the white blood count is obviously recommended. Olanzapine may be considered a potential and safer treatment for a this specific group of patients.

Intermittent, luteal phase nefazodone treatment of premenstrual dysphoric disorder.

Three outpatients who fulfilled full DSM-IV diagnostic criteria for premenstrual dysphoric disorder (PDD) were successfully treated with intermittent (luteal phase) nefazodone. They received the medication at low doses of up to 100 mg/day (50 mg b.i.d.), for 2 weeks through the luteal phase of the menstrual cycle only. All the patients reported a marked symptomatic improvement, including full remission of their emotional symptoms, and two achieved in addition full remission of their somatic symptoms. Side-effects reported during the treatment were mild. The use of luteal phase nefazodone seems to be a promising treatment strategy for the management of PDD. It offers advantages over daily dosing throughout the menstrual cycle, such as reduced incidence and severity of side-effects, and avoids the stigma that may accompany the continuous use of psychopharmacological treatment, with the advantage that compliance may be improved.

LSD-induced hallucinogen persisting perception disorder treatment with clonidine: an open pilot study.

A pilot open study was conducted in order to evaluate the efficacy of clonidine in the treatment of LSD-induced hallucinogen persisting perception disorder (HPPD). Eight patients fulfilled entrance criteria. All complained of HPPD for at least 3 months and were drug free at least 3 months. They received fixed low doses of clonidine, 0.025 mg, three times a day for 2 months. They were evaluated by the Clinical Global Impression Scale (CGI) and a self-report scale on the severity of symptoms (graded 0-5). Patients scored an average of 5.25 (SD = 0.46) on the CGI and 4 on the self-report scale at baseline, indicating marked psychopathology. One patient dropped out at week 3 and a second patient dropped out at week 5. Of the six patients remaining at the end of 2 months, the average CGI score was 2.5 (SD = 0.55) and the self-report scale score was 2, indicating mild symptomatology. LSD-related flashbacks associated with excessive sympathetic nervous activity may be alleviated with clonidine in some patients.

Plasma proteins modified by tyrosine nitration in acute respiratory distress syndrome.

The present study identifies proteins modified by nitration in the plasma of patients with ongoing acute respiratory distress syndrome (ARDS). The proteins modified by nitration in ARDS were revealed by microsequencing and specific antibody detection to be ceruloplasmin, transferrin, alpha(1)-protease inhibitor, alpha(1)-antichymotrypsin, and beta-chain fibrinogen. Exposure to nitrating agents did not deter the chymotrypsin-inhibiting activity of alpha(1)-antichymotrypsin. However, the ferroxidase activity of ceruloplasmin and the elastase-inhibiting activity of alpha(1)-protease inhibitor were reduced to 50.3 +/- 1.6 and 60.3 +/- 5.3% of control after exposure to the nitrating agent. In contrast, the rate of interaction of fibrinogen with thrombin was increased to 193.4 +/- 8.5% of the control value after exposure of fibrinogen to nitration. Ferroxidase activity of ceruloplasmin and elastase-inhibiting activity of the alpha(1)-protease inhibitor in the ARDS patients were significantly reduced (by 81 and 44%, respectively), whereas alpha(1)-antichymotrypsin activity was not significantly altered. Posttranslational modifications of plasma proteins mediated by nitrating agents may offer a biochemical explanation for the reported diminished ferroxidase activity, elevated levels of elastase, and fibrin deposits detected in patients with ongoing ARDS.

Association between the serotonin 2C receptor gene and tardive dyskinesia in chronic schizophrenia: additive contribution of 5-HT2Cser and DRD3gly alleles to susceptibility.

RATIONALE: Tardive dyskinesia (TD) is a longterm adverse effect of dopamine receptor blockers. The dopamine D3 receptor gene (DRD3) ser9gly polymorphism has been previously associated with susceptibility to TD. Serotonin receptor antagonism has been proposed as a common mechanism contributing to the low extra-pyramidal effects profile of atypical antipsychotic drugs. OBJECTIVES: To examine the association of a functional polymorphism in the 5-HT2C receptor gene (HT2CR) with TD and the joint contribution of HT2CR and DRD3 to susceptibility. METHODS: Case control association analysis of allele and genotype frequencies among schizophrenia patients with (n=55) and without TD (n=60), matched for antipsychotic drug exposure and other relevant variables, and normal control subjects (n=97). Parametric analyses of the contribution of 5-HT2Cser and DRD3gly alleles to dyskinesia scores. RESULTS: We found a significant excess of 5-HT2Cser alleles in schizophrenia patients with TD (27.2%) compared to patients without TD (14.6%) and normal controls (14.2%; chi2=6.4, df 2, P=0.03) which was due to the female patients (chi2=8.6, df 2, P=0.01). Among the female TD patients there was an excess of cys-ser and ser-ser genotypes (chi2= 11.9, df 4, P=0.02). Analysis of covariance (ANCOVA), controlling for age at first antipsychotic treatment, revealed a significant effect of 5-HT2C genotype on orofacial dyskinesia (OFD) scores (F=3.47, df 2, P=.03). In a stepwise multiple regression analysis, 5-HT2C and DRD3 genotype (5-HT2Cser and DRD3gly allele carriage) respectively contributed 4.2% and 4.7% to the variance in OFD scores. CONCLUSIONS: These findings support a small but significant contribution of the HT2CR and DRD3 to susceptibility to TD, which is additive in nature.

A rare short allele of the serotonin transporter promoter region (5-HTTLPR) found in an aggressive schizophrenic patient of Jewish Libyan origin.

The serotonin transporter gene (SLC6A4), which plays a key role in the serotonergic pathway in the brain, is a candidate for mediating genetic susceptibility to various psychiatric disorders. There are two predominant alleles in the polymorphic promotor region [5-HT transporter gene-linked polymorphic region (5-HTTLPR)] of this gene: a long and a short allele with 16 and 14 repeat units, respectively. The short allele has lower activity and is associated with several psychiatric disorders and personality traits. We identified and sequenced a novel allele with 13 repeat units, 23 base pairs shorter than the common short allele. This unique allele was detected in a schizophrenic patient of Jewish Libyan origin. The patient exhibited extreme aggressive behavior and committed suicide after several attempts. The novel short allele was not detected in 172 healthy control subjects and 361 patients with various mental disorders. The presence of a very short unique allele in a severely aggressive schizophrenic patient may reflect a specific effect on the particular phenotype, although it is unlikely that this allele has a major contribution to susceptibility to schizophrenia. The role of the allele in serotonin transport and possible association with disease phenotype should be further investigated.

Genotypic association between the dopamine D3 receptor and tardive dyskinesia in chronic schizophrenia.

Dopamine receptor antagonism is a common mechanism underlying the therapeutic efficacy of all classical antipsychotic drugs. It is also thought to underlie the propensity of these agents to induce the movement disorder, tardive dyskinesia (TD), in one fifth of chronically exposed schizophrenia patients. We examined the polymorphic serine to glycine substitution in the first exon of the gene encoding the dopamine D3 receptor (DRD3) inn 53 schizophrenia patients with TD, 63 matched patients with similar antipsychotic exposure but no TD and 117 normal controls. There was a difference in allele frequency that was of borderline significance (P = 0.055), due to an excess of the DRD3gly allele (allele 2) in the schizophrenia patients with TD. The difference in genotype distribution among the groups was highly significant (chi2 = 19.1, d.f. 4, P = 0.0008) due to an excess of the DRD3ser-gly genotype in the schizophrenia patients with TD. The difference between the schizophrenia patients with TD and the controls was highly significant (chi2 = 19.0, d.f. 2, P = 0.00007), even after correction for multiple testing, as was the difference between the combined group of schizophrenia patients and the controls (chi2 = 12.2, d.f. 2, P = 0.002). Comparing the schizophrenia patients with and without TD, genotypes containing the gly allele (DRD3ser-gly and DRD3gly-gly genotypes combined) were significantly associated with dyskinesia (OR = 2.62, 95% CI 1.18-5.59, P = 0.02). DRD3 genotype and age at first antipsychotic treatment contributed significantly to total score on the Abnormal Involuntary Movements Scale (AIMS). The contribution of DRD3 to the variance in AIMS total was 5.2% and the total proportion of the variance accounted for by these two variables together was 11.9%. These results support and extend the report by Steen et al (1997) of an association between DRD3 and TD in schizophrenia patients.

Prevalence of Bartonella henselae and Bartonella clarridgeiae in an urban Indonesian cat population.

We studied evidence of Bartonella henselae and Bartonella clarridgeiae infection in 54 cats living in Jakarta, Indonesia. By using an indirect immunofluorescence assay, we found immunoglobulin G antibody to B. henselae in 40 of 74 cats (54%). The blood of 14 feral cats was cultured on rabbit blood agar plates for 28 days. Bartonella-like colonies were identified as B. henselae or B. clarridgeiae by using restriction fragment length polymorphism analysis and direct sequencing of the PCR amplicons. Of the cats sampled in the study, 6 of 14 (43%; all feral) were culture positive for B. henselae; 3 of 14 (21%; 2 feral and 1 pet) culture positive for B. clarridgeiae. This is the first report that documents B. henselae and B. clarridgeiae infections in Indonesian cats.

Olanzapine treatment in patients with typical and atypical neuroleptic-associated agranulocytosis.

Two cases are reported of patients who developed agranulocytosis after treatment with typical and atypical antipsychotics. The patients were successfully treated with olanzapine. We suggest the consideration of olanzapine as a safer treatment in patients who require immediate continuation of antipsychotic medication and have a prior history of classic and atypical neuroleptic-induced agranulocytosis.

Safety and characterization of the immune response engendered by two combined measles, mumps and rubella vaccines.

We performed a randomized trial to compare the safety and immunogenicity of two combined measles, mumps and rubella vaccines in healthy children 14-24 months of age. Triviraten Berna Vaccine (Swiss Serum and Vaccine Institute), contains the Edmonston Zagreb 19 strain of measles virus, the Rubini mumps virus strain and the Wistar RA 27/3 rubella strain while MMR-Vax (Merck, Sharp & Dohme, West Point, PA) contains the Enders attenuated Edmonston measles strain, the Jeryl Lynn mumps strain and the Wistar RA 27/3 rubella strain. Immunization with Triviraten Berna was associated with a significantly lower incidence of swelling and redness at the injection site in addition to a reduced rate of fever compared with MMR-Vax. Seroconversion rates for the measles and rubella vaccine components were comparable in all tests used. However, seroconversion for the mumps vaccine component was test-dependent. Using an ELISA, the seroconversion rate following immunization with MMR-Vax was significantly (P < 0.01) higher than for Triviraten Berna. In contrast, nearly identical rates were obtained using an indirect immunofluorescence test. Both vaccines were equally effective at engendering antibodies capable of neutralizing wild type mumps virus. Geometric mean ELISA antibody titers against measles and mumps virus were higher following immunization with MMR-Vax while that for rubella was higher after immunization with Triviraten Berna. A small number (N = 13) of adolescents immunized either with MMR-Vax or Triviraten Berna were reimmunized with Triviraten Berna and various humoral and cellular response parameters to the measles and mumps vaccine components analyzed. While few subjects mounted a humoral antibody response to measles, most likely due to elevated baseline titers, there was a marked lymphoproliferative response. Anti-mumps virus ELISA antibody titers were higher both at baseline and after reimmunization in subjects who received MMR-Vax for primary immunization. However, there was no difference in either neutralizing titer or proliferative response in subjects primed with MMR-Vax or Triviraten Berna either before or after reimmunization.

Immunogenicity of trivalent subunit versus virosome-formulated influenza vaccines in geriatric patients.

The safety and immunogenicity of a commercial trivalent subunit influenza vaccine and an experimental virosome-formulated influenza vaccine were evaluated among geriatric patients in a double-blind, randomized manner. The virosome vaccine was produced by incorporating hemagglutinin (HA) into the membrane of liposomes composed of phosphatidylcholine. Both vaccines elicited a significant (P < 0.01) rise in the geometric mean anti-HA antibody titer to all three vaccine components 1 month after immunization. However, significantly (P < 0.005) more subjects vaccinated with the virosome preparation mounted a more than fourfold rise to the A/Singapore and A/Beijing strains compared with those who received subunit vaccine. The percentage of patients who attained protective levels (anti-HA titer > or = 40) of anti-A/Beijing antibody was also significantly (P < 0.005) higher in the virosome group. Subjects who possessed non-protective baseline antibody levels to the A/Singapore and A/Beijing strains were more likely (P < 0.005-0.030) to achieve protective levels after immunization with the virosome vaccine than with the subunit vaccine. Of particular clinical significance was the fact that 68.4% of subjects immunized with the virosome vaccine attained protective levels of antibody to all three vaccine components versus 38% for the subunit vaccine (P = 0.010).

Immunogenicity and protectivity of a new liposomal hepatitis A vaccine.

In this study we investigated a new liposomal hepatitis A vaccine (Epaxal) developed by the Swiss Serum and Vaccine Institute clinically and immunologically using a one dose priming schedule and a booster injection after 1 year. This vaccine contains formalin inactivated hepatitis A virus particles attached to phospholipid vesicles together with influenza virus haemagglutinin. Two doses of the vaccine were administered at months 0 and 12 in 117 volunteers. Blood samples were drawn at days-7, 14 and 28 and after 6, 12 and 13 months, local and systemic reactions were monitored by means of questionnaires. Immunogenicity was evaluated as usual by the determination of anti-HAV from the collected sera using the ELISA technique. In order to evaluate the protective efficacy of the vaccine induced antibodies a sample of 25 sera mainly from vaccinees showing low ELISA titres was additionally analysed by means of a virus NT. The vaccine was excellently tolerable and highly immunogenic. Seroconversion evaluated by ELISA was 97 and 99%, respectively, 14 and 28 days after the first dose and 100% after the second dose. NT titres were well correlated with ELISA titres and showed similar seroconversion rates even in the early phase of immunization. The results of this study show that with two doses of the liposomal hepatitis A vaccine administered at months 0 and 12 early protection within 14 days and long lasting immunity can be achieved.

Mutations in purine nucleoside phosphorylase deficiency.

Purine nucleoside phosphorylase deficiency is an inherited disease of purine metabolism characterized clinically as combined immunodeficiency. The molecular defects have been published for 4 different alleles in 3 patients. We report four new mutations including two amino acid substitutions, A174P and G190V, a single codon deletion, delta I129, and a point mutation in intron 3 which leads to aberrant splicing and creation of a premature stop codon in exon 4 (286-18G-->A). Of the previously reported mutations, E89K was found in one additional patient, and R234P was found in 3 unrelated patients, making R234P the most common mutation reported to date in this disease.

Pulsed alexandrite laser technology for noninvasive hair removal.

OBJECTIVE: Determination of the efficacy of pulsed Alexandrite Laser technology for rapid noninvasive hair removal. SUMMARY BACKGROUND DATA: Although previous studies have already shown that Ruby lasers are capable of noninvasive hair removal, a technology for the substantial increase of treatment speed is of great interest. METHODS: We have used a 2 msec free running pulsed Alexandrite (lambda = 755 nm) laser operated at a repetition rate of up to 5 pps at energy fluences of 25-40 J/cm2 to treat a wide range of body sites on 126 patients in conjunction with a fiber delivery system and a transparent target ruler. A transparent gel was used as epidermal heat sink. The study lasted 15 months. Pretreatment as well as follow-up hair count per cm2 was performed to determine the level of success. Treatments were repeated when 1-2 mm growth was observed. RESULTS: The average hair count before the second treatment was found to be close to 65% of the pretreatment count. The average hair count 3 months after the last treatment, was found to be lower than 12%. The interval between treatments ranged from 4 weeks to 3 1/2 months. CONCLUSIONS: The 2 msec pulsed Alexandrite laser technology is effective for the removal of unwanted hairs, ranging from fair to dark, except when hairs are absent in the shaft depending on the stage of their growth cycle. This results in the necessity of a few treatments or touchups. Adverse effects are minimal and transient.

Single-dose intramuscular ketorolac versus diclofenac for pain management in renal colic.

A double-blind controlled study was designed to compare the effective- ness of a single intramuscular dose of 60 mg ketorolac with that of 75 mg diclofenac in the treatment of renal colic and to monitor side effects. Fifty-seven patients completed the study, 27 in the ketorolac group and 30 in the diclofenac group. Effectiveness of treatment was monitored by pain relief reported on a 4-point verbal scale at different time points. At 60 minutes 77.8% and 86.6% (P = 0.4) of patients, and at 120 minutes 81.5% and 96.6% (P = .1 5) of patients, reported significant pain relief following ketorolac and diclofenac doses, respectively. Both groups had an equal 92% significant pain relief at discharge from the emergency department. Both drugs were well tolerated by the patients. Ketorolac therefore, seems as effective as diclofenac in the treatment of renal colic.