Differential diagnostic considerations in microcephalic dwarfism

PURPOSE: While the rare Seckel-Syndrome is defined by clear criteria, clinical and radiologic findings for microcephalic osteodysplastic primordial dwarfism (MOPD) make an exact diagnosis and classification difficult. By comparing our patients to previously described cases of MOPD we evaluate the hypothesis that this disorder has a greater heterogeneity than has been believed up until now. Furthermore the differential diagnosis of the MOPD-complex is discussed. RESULTS: Two cases that show typical growth retardation, microcephalus and facial anomalies as well as osteodysplastic deformities including hip dysplasia are presented. The parents of both children are consanguineous and of Arabic race. In one of the children growth hormone levels were noticeably decreased. In discrepancy to the Seckel-syndrome both children showed no signs of mental retardation, therefore the classification into the heterogeneous group of microcephalic osteodysplastic primordial dwarfism (MOPD) is the most likely diagnosis. CONCLUSION: It is suggested that microcephalic osteodysplastic primordial dwarfism (MOPD) has a greater clinical and radiological expression than has been assumed up until now. Whether our results are merely a variant or suggest a new subtype of the MOPD can only be resolved by further cases. The exact pathogenesis of the disease currently remains unknown but the most probable cause is an autosomal recessive inheritance.     

Positive influence of the Delta32CCR5 allele on response to highly active antiretroviral therapy (HAART) in HIV-1 infected patients

The heterozygous 32 base pair deletion of the chemokine receptor 5 (Delta32CCR5) has been associated with a more benign course of HIV-1-infection. To study the influence of Delta32CCR5 on the response to antiviral therapy we analyzed the presence of Delta32CCR5 by PCR in PBMC from 107 randomly selected HIV-1-infected patients treated with HAART for at least three months. 24 of 107 patients were heterozygous for Delta32CCR5 (22.4%). Before initiation of HAART Delta32CCR5 heterozygous patients (d/w) did not differ from homozygous CCR5 wild-type patients (w/w) regarding viral load and CD4 counts. After a median treatment time on HAART of 17.5 months (d/w, range 6-31 months, p = n.s.) or 19 months (w/w, range 3-33 months) all 24 patients (100%) with the Delta32CCR5 mutation, but only 58/83 patients (69.9%) with wild-type CCR5 showed a suppression of HIV-1-viremia below 500 copies/ml (p = 0.0020). Furthermore, 20/24 (83.3%) of the Delta32CCR5 heterozygous patients achieved CD4 counts above 200/microliter, but only 57/83 (68.7%) of the patients homozygous for CCR5 wild-type (p = 0.011). Our data indicate that the presence of heterozygous Delta32CCR5 is associated with a better response to HAART suggesting that therapeutic strategies targeting CCR5 could be of value for a sustained suppression of HIV-1 by HAART.     

Economic evaluation of pertussis prevention by whole-cell and acellular vaccine in Germany

Acellular pertussis vaccines are less reactogenic than whole cell pertussis vaccines, but they are also more expensive. Based on simulation models, we compared the costs and effects of three alternative pertussis vaccination strategies in German children to ”no prevention”: (1) vaccination with whole-cell vaccine at 45% coverage (vaccine efficacy 90%), (2) vaccination with acellular vaccine at 45% coverage (vaccine efficacy 85%), and (3) vaccination with acellular vaccine at 90% coverage. In the two low coverage scenarios expected annual savings in direct medical costs through prevention of disease were larger for whole-cell than for acellular vaccination (252 vs 216 million DM, respectively). Direct costs for treating the more important adverse events induced by whole-cell vaccination (16.9 million DM annually) did not outweigh the higher direct costs of pertussis infections not prevented with the acellular vaccine and the higher price of the acellular vaccine. However, vaccination with acellular pertussis vaccine rapidly becomes as cost saving as vaccination with whole-cell vaccine as soon as vaccination coverage can be raised from 45% to 52.5% with acellular vaccine. Acellular vaccination is also the superior alternative when considering indirect cost savings resulting from reduction in work-loss due to adverse events. Conclusion In our simulations, the most cost-effective pertussis prevention strategy was the use of an effective whole-cell vaccine with a high coverage rate. Introduction of the more expensive acellular pertussis vaccines becomes cost saving if at least a 7.5% increase in coverage is achieved. If also non-medical indirect costs to parents resulting from vaccine associated side-effects are accounted for, acellular vaccines may be more cost-effective also in countries with already high whole-cell vaccine coverage. Received: 22 April 1997 / Accepted in revised form: 21 November 1997     

Immunogenicity and reactogenicity of a Haemophilus influenzae type b tetanus conjugate vaccine when administered separately or mixed with concomitant diphtheria-tetanus-toxoid and acellular pertussis vaccine for primary and for booster immunizations

With an increasing number of new vaccines available for routine childhood immunization, combination vaccines are needed in order to maintain or achieve a high compliance with recommended immunization programmes. In a prospective, randomized, comparative, multi-centre study, 822 healthy infants were enrolled to receive three doses of either a candidate or a commercially available Haemophilus influenzae type b (Hib) vaccine concomitantly with diphtheria-, tetanus- acellular pertussis (DTaP) vaccine. Study subjects were randomly allocated to one of the following groups: (1) separate, or (2) mixed injection of DTaP and candidate Hib vaccine, or (3) separate injection of DTaP and commercial Hib vaccine. One year later the first 189 study subjects received either separate or mixed injections of the same Hib and DTaP vaccines as booster doses. Evaluation of reactogenicity was based on diary cards completed by parents. Immunogenicity was documented by measuring IgG antibody concentrations in serum samples taken before and 4 weeks after primary and booster vaccination. No serious adverse events occurred and most local and systemic reactions were mild to moderate. Booster doses were more reactogenic than primary doses with all groups. Antibody concentrations against pertussis antigens were similar to those seen with DTaP alone. All but one subject had protective antibody concentrations against diphtheria and tetanus. Primary immune response to the Hib vaccine was significantly lower in the group receiving the mixed Hib-DTaP vaccine, however, ≥95% of vaccinees had anti-Hib antibody concentrations ≥0.15 μg/ml and there was a marked booster response (>100-fold) in all groups. Conclusions Mixing DTaP and Hib vaccines for primary immunization caused a decrease in anti-Hib antibody response, although after primary immunization as after booster doses, all subjects showed antibody concentrations considered to be protective for invasive Hib disease. Mixing of the vaccines did not result in increased reactogenicity. Received: 13 June 1997 / Accepted in revised form: 4 September 1997     

Factors associated with tobacco sales to minors: lessons learned from the FDA compliance checks

CONTEXT: Tobacco products continue to be widely accessible to minors. Between 1997 and 1999, the US Food and Drug Administration (FDA) conducted more than 150,000 tobacco sales age-restriction compliance checks. Data obtained from these checks provide important guidance for curbing illegal sales. OBJECTIVE: To determine which elements of the compliance checks were most highly associated with illegal sales and thereby inform best practices for conducting efficient compliance check programs. DESIGN AND SETTING: Cross-sectional analysis of FDA compliance checks in 110,062 unique establishments in 36 US states and the District of Columbia. MAIN OUTCOME MEASURE: Illegal sales of tobacco to minors at compliance checks; association of illegal sales with variables such as age and sex of the minor. RESULTS: The rate of illegal sales for all first compliance checks in unique stores was 26.6%. Clerk failure to request proof of age was strongly associated with illegal sales (uncorrected sales rate, 10.5% compared with 89.5% sales when proof was not requested; multivariate-adjusted odds ratio [OR], 0.03; 95% confidence interval [CI], 0.03-0.04). Other factors associated with increased illegal sales were employment of older minors to make the purchase attempt (adjusted ORs for 16- and 17-year-old minors compared with 15-year-olds were 1.52 [95% CI, 1.46-1.63] and 2.43 [95% CI, 2.31-2. 59], respectively), attempt to purchase smokeless tobacco (adjusted OR, 2.16 [95% CI, 1.90-2.45] vs cigarette purchase attempts), and performing checks at or after 5 PM (adjusted OR, 1.28 [95% CI, 1. 21-1.35] vs before 5 PM). Female sex of clerk and minor, Saturday checks, type of store (convenience store selling gas, gas station, drugstore, supermarket and general merchandise), and rural store locations also were associated with increased illegal sales. CONCLUSIONS: This analysis found that a request for age verification strongly predicted compliance with the law. The results suggest several ways in which the process of compliance checks might be optimized. JAMA. 2000;284:729-734     

Biological factors of post-traumatic stress: neuroendocrine aspects

The core symptoms of post-traumatic stress disorder (PTSD) include persistent reexperiencing of the traumatic event, avoidance of stimuli associated with the trauma, and autonomic hyperarousal. Many neurotransmitter systems and neurobiologic mechanisms may account for these primary symptoms of PTSD. Severe psychological trauma results in the parallel activation of these systems, producing an array of adaptive behavioral and physiologic responses necessary for survival. The pathophysiology of PTSD may involve dysfunction of several brain structures, particularly the amygdala, locus coeruleus, and hippocampus, as well as noradrenergic system and hypothalamic-pituitary-adrenal (HPA) axis. The neuroendocrinology of PTSD, and specifically hypothalamic-pituitary-adrenal axis alterations, are ways of examining biologic heterogeneity following trauma and its possible clinical implications. The decreased levels of cortisol, the increased responsiveness of glucocorticoid receptors, the increased sensitivity of the HPA negative feedback inhibition and its progressive sensitization are the neuroendocrine alterations specifically associated with the development of PTSD.     

Besonderheiten der Pharmakotherapie bei Frauen im Alter

Elderly women have a higher risk of adverse drug reactions due to altered pharmacokinetics, pharmacodynamics, the increased prevalence of chronic diseases and multiple medication. The physician cannot rely on external evidence, as clinical studies rarely focus on drug safety and efficacy in the elderly. Additionally, no registries on drug therapy exist for this vulnerable age group. Therefore, careful consideration should be given to the indications for drug use, and the knowledge of prescribed and non-prescribed existing therapies. The disease, its therapy and vigilance for adverse drug reactions and potential drug interactions should be carefully discussed with the patient. An exact knowledge of differences in geriatric drug therapy is critical for the treatment of elderly women.