Efficacy of a two-component acellular pertussis vaccine in infants

OBJECTIVE: This case-control study investigated the protective efficacy against pertussis of three doses of a two-component acellular pertussis vaccine (manufactured by Biken in Japan) combined with diphtheria and tetanus toxoids (manufactured by Connaught Laboratories in the US) in infants. METHODS: A case-control study was performed in 63 pediatric practices in Germany. Prospective recruitment of 16,780 infants ages 6 to 17 weeks took place between February, 1993, and July, 1994. According to parental choice infants received either Biken acellular pertussis vaccine combined with diphtheria and tetanus toxoids (DTacP) (74.6%) at approximately 2, 4 and 6 months of age, or a licensed German diphtheria-tetanus toxoids-whole cell pertussis vaccine (10.9%), diphtheria-tetanus toxoids vaccine (12.5%) or no vaccine (2.0%). Prospective surveillance of pertussis cases between February, 1993, and May, 1995, was accomplished by culturing all infants < or =2 years of age presenting with cough > or = 7 days. A pertussis case was defined as any cough of 21 days or longer plus a positive Bordetella pertussis culture or household contact exposure. RESULTS: We identified 241 pertussis cases prospectively by 11,017 B. pertussis cultures and 949 controls matched for age were selected from the same pediatric practices. Medical history and demographic and vaccine status data were collected from each case and for four controls. Data were analyzed through conditional logistic regression taking into account individual matching and adjusting for potential confounding variables. DTacP combined with diphtheria and tetanus toxoids vaccine was 82% protective (95% confidence interval, 68 to 90), diphtheria-tetanus toxoids-whole cell pertussis vaccine was 96% protective (95% confidence interval, 78 to 99). Protection against typical B. pertussis infection characterized by paroxysmal cough lasting > or =21 days was 96% (95% confidence interval, 87 to 99) for DTacP and was 97% (95% confidence interval, 79 to 100) for diphtheria-tetanus toxoids-whole cell pertussis vaccine. Adjustment for potentially confounding variables did not change the results significantly. CONCLUSIONS: Three doses of the two-component acellular pertussis vaccine protected infants against pertussis disease during the period before the recommended booster vaccination. For typical pertussis disease as defined by the WHO efficacy was high and similar to that of a licensed German diphtheria-tetanus toxoids-whole cell pertussis vaccine.     

Economic evaluation of hysteroscopic endometrial ablation versus vaginal hysterectomy for menorrhagia

PURPOSE: To assess the efficacy and safety of percutaneous catheter drainage combined with alcohol sclerosis in the treatment of postoperative lymphoceles. PATIENTS AND METHODS: Thirteen patients with 14 postoperative symptomatic lymphoceles were treated. Drainage catheters were inserted under ultrasound (n = 13) or computed tomographic (n = 1) guidance. Lymphocele sclerosis was performed by instilling 10-100 mL of absolute alcohol into the lymphocele cavity and aspirating the alcohol after 30 minutes. Sclerosis sessions were carried out one to three times per day, usually three times per week. Catheter sinograms were obtained and prophylactic antibiotics administered. Imaging was repeated if symptoms or signs of recurrence developed. RESULTS: Successful drainage and sclerosis were achieved in all 13 patients. One patient with a recurrence was successfully treated with repeated drainage and alcohol ablation. No adverse effects of alcohol instillation were seen. The mean duration of catheterization was 36 days (range, 17-65 days; median, 30 days). CONCLUSION: Percutaneous drainage combined with alcohol ablation is a safe and effective treatment of postoperative lymphoceles.     

Immune recognition of viral antigens

The response exhibited by the immune system to viral and other foreign antigens consists of antibody-mediated and T cell-mediated immunity. Structural and molecular biological studies have shown that the antibody response is tailored to provide exquisite specificity by generating binding pockets that are complementary in shape as well as in charge to the antigen. On the other hand, the cellular response uses T-cell receptors (TCRs) and the major histocompatibility complex (MHC) antigens. Structural information on the TCRs is not yet available, but the crystal structures of several MHC class I molecules have shown how one MHC molecule can bind many different peptide sequences that share only the common anchor residue positions that determine allele specificity. MHC class I interactions with the peptide backbone at the N and C termini explain the high specificity of the binding groove for peptide ligands and suggest a universal mode of recognition for peptides to MHC class I molecules. Peptide-MHC class II interactions are less well understood, although recent structural work has shown important differences in the binding clefts of MHC class I and II that lead to longer peptides being bound to class II molecules. Detailed analysis at the molecular level has indicated that conformational changes in both antibodies and MHC molecules occur upon antigen binding.(ABSTRACT TRUNCATED AT 250 WORDS)     

What difference a decade makes? [management issues]

This paper discusses the results of a survey conducted by a team of researchers from Ashridge Business School that aimed to determine how managers and management practices have changed over the last 10 years. The survey considered a range of issues related to three broad themes, namely, organizational challenges, individual challenges, and the challenges of learning and development. The survey found that for the vast majority of managers in all industry sectors, the pressures of running an organization that is profitable, growing and competitive have not gone away. However, evidence suggests that these issues are perhaps slightly less dominant on the management agenda than in 1994. The survey concluded that there is a good deal that organizations might do to create a better working environment.     

Two structural adaptations for regulating transmitter release at lobster neuromuscular synapses

The distal accessory flexor muscle (DAFM) in the lobster (Homarus americanus) walking leg consists of 5 muscle fiber bundles. All five bundles, one proximal, one distal, and 3 medial, are innervated by one excitatory and one inhibitory motor neuron. Both neurons release more transmitter on the distal bundle than on the proximal bundle. The aim of our studies was to investigate the structural basis of this differentiation. Thin sections cut at 50 microns intervals showed a similar number of excitatory synapses on the two bundles. Freeze-fracture views of excitatory synapses showed that synapse size, active zone number per synapse, and intramembrane particle density in the postsynaptic membrane are similar proximally and distally. Active zones at synapses on the distal bundle are larger and contain about 50% more large intramembrane particles, which are thought to include the voltage-gated Ca2+ channels that couple the action potential to transmitter release, than their counterparts on the most proximal bundle. This difference in channel number appears to produce a disproportionate increase in the probability of transmitter release sufficient to account for most of the proximal-distal disparity in the amplitude of the excitatory postsynaptic potential. In contrast, staining the inhibitor for antibodies to the inhibitory neurotransmitter, GABA, showed that it forms more varicosities on the distal bundle than on the proximal bundle. Because most of the synapses are located in the varicosities, differences in synapse number likely regulate the proximal-distal disparity in the amount of inhibitory transmitter released. Therefore, the regional differentiation in the amount of transmitter released in the DAFM appears to be based on two distinct mechanisms. In the inhibitor, transmitter release appears to be regulated differentially by differences in synapse number. In the excitor, transmitter release appears to be regulated differentially from a similar number of synapses by differences in active zone structure.     

Mode of vascularization of control and basic fibroblast growth factor-stimulated prefabricated skin flaps

This study, using 62 rabbits, examines the rate and pattern of vascular outgrowth from a subcutaneously implanted vascular pedicle, how the newly formed vessels connect to preexisting skin vessels, and whether local application of basic fibroblast growth factor can accelerate the angiogenic process. When the femoral artery and vein of rabbits are implanted beneath the skin, angiogenesis from both the pedicle and small blood vessels within the adjacent skin begins within 3 days. Perfusion with India ink reveals connections between the pedicle and dermal vessels as early as 5 days after implantation of the pedicle. Provided the pedicle does not thrombose, skin flaps based on it may survive completely when elevated as early as 2 weeks after implantation. Flap survival depends on the development of a small number of vascular connections between vessels arising from the pedicle and preexisting dermal vessels. If elevation is delayed until 4 weeks after implantation a flap may survive even if its pedicle has thrombosed. Prolonged release of basic fibroblast growth factor adjacent to the pedicle significantly increases the survival of flaps elevated 1 week after implantation but does not alter the survival of flaps elevated at 2 and 4 weeks.     

Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of mutations found in hereditary nonpolyposis colorectal cancer

Mutations in the human mismatch repair protein hMSH2 have been found to cosegregate with hereditary nonpolyposis colorectal cancer (HNPCC). Previous biochemical and physical studies have shown that hMSH2 forms specific mispair binding complexes with hMSH3 and hMSH6. We have further characterized these protein interactions by mapping the contact regions within the hMSH2-hMSH3 and the hMSH2-hMSH6 heterodimers. We demonstrate that there are at least two distinct interaction regions of hMSH2 with hMSH3 and hMSH2 with hMSH6. Interestingly, the interaction regions of hMSH2 with either hMSH3 or hMSH6 are identical and there is a coordinated linear orientation of these regions. We examined several missense alterations of hMSH2 found in HNPCC kindreds that are contained within the consensus interaction regions. None of these missense mutations displayed a defect in protein-protein interaction. These data support the notion that these HNPCC-associated mutations may affect some other function of the heterodimeric complexes than simply the static interaction of hMSH2 with hMSH3 or hMSH2 with hMSH6.