Auditing and improving notification and chemoprophylaxis in bacterial meningitis.

STUDY OBJECTIVE--The aim was to audit, against agreed standards, the control of bacterial meningitis, in particular completeness of notification and appropriateness of distribution of chemoprophylaxis to contacts; and to implement appropriate changes and monitor their impact. DESIGN--The first phase involved determination, for the years 1983 and 1984, of completeness of notification by comparison with a comprehensive case register. Information about chemoprophylaxis was obtained from case notes, questionnaires to general practitioners and other records. The second phase involved introducing a programme of clinician education in the hospital with the poorest observed notification performance and re-examining performance during 1988. Districtwide education regarding chemoprophylaxis was undertaken and the situation re-examined in 1988. SETTING--The study took place in Mid Glamorgan Health Authority (population 536,000), with four acute hospitals. POPULATION--Consisted of all the residents of Mid Glamorgan Health Authority. MAIN RESULTS--During the first phase of the audit only 28 out of 79 cases of bacterial meningitis were notified (35%). Performance in one hospital was significantly worse than in the other three. Chemoprophylaxis was distributed to 20 out of 26 (77%) cases of meningococcal meningitis but inappropriate drugs were used in four cases and prophylaxis was distributed more widely than is recommended in 10 cases. In the phase 2 re-examination, a significant improvement in notification was observed in the hospital where special measures were taken, with no change in a "control" hospital. Chemoprophylaxis improved throughout the District, although rifampicin continued to be distributed too widely. CONCLUSIONS--As a result of this audit, measurable improvements in both infectious disease notification and chemoprophylaxis practice were obtained by the education of clinicians. The study provides a good example of a completed audit cycle in public health medicine.     

The comparative roles of dopaminergic and serotonergic mechanisms in mediating quipazine induced locomotor activity

Summary Quipazine maleate (50–100g) injected bilaterally into the nucleus accumbens septi (NAS) of unpretreated rats produced a marked dose-dependent rise in locomotor activity (LA) that was nearly devoid of the stereotypies seen after the systemic or intrastriatal administration of this piperazine derivative. Injection of a low dose of the dopamine blocking agent haloperidol resulted in a marked antagonism of the LA elicited by quipazine (50g) in the NAS; but methysergide, a central serotonin antagonist, was without effect. These results indicate that quipazine induced LA is mediated, at least partially, by DA receptors situated in the NAS, and that serotonin receptors do not play a significant role in this behavior.     

Verbal fluency and executive dysfunction in amyotrophic lateral sclerosis (ALS)

Neuropsychological investigations of amyotrophic lateral sclerosis (ALS) patients have revealed variable results on specific tests, despite a similar overall cognitive profile of predominantly executive dysfunction with some evidence of memory impairment. The most striking and consistent deficit is found using tests of verbal fluency. The current investigation explored why verbal fluency is particularly sensitive to the impairment in ALS, by investigating some of the underlying cognitive processes: (i) intrinsic response generation; (ii) phonological loop functions; and (iii) simple word retrieval. Twenty-two ALS patients and 25 healthy controls were investigated. The battery included: (i) written and spoken letter-based fluency, category fluency, design fluency; (ii) the Phonological Similarities effect and Word Length Effect; and (iii) computerised sentence completion and confrontational naming. The tests were designed to control for motor speed and to accommodate for the range of disabilities that are present in ALS patients. Significant impairments were found on some tests of intrinsic response generation, namely the Written Verbal Fluency Test, Category Fluency Test (generation of animal names) and Design Fluency Test. Phonological loop functions appeared to be intact with evidence of both the Phonological Similarities and Word Length Effects, but the ALS patients displayed significantly reduced working memory capacity. No deficits were found on tests of simple word retrieval. The findings indicate that verbal fluency impairments in ALS patients result from a higher order dysfunction, implicating deficits in the supervisory attentional system or central executive component of working memory, and are not caused or exaggerated by an impairment in phonological loop functions or in primary linguistic abilities. The study also demonstrates the importance of controlling for differences in motor speed, which may have served to exaggerate the presence of cognitive deficits in ALS patients reported by some other studies.     

Shaking infant trauma induced by misuse of a baby chair.

A 2 month old infant presented with bilateral subdural haemorrhages and bilateral subhyaloid haemorrhage. The parent admitted to forceful bouncing of the child in a baby rocker. Experiments showed that violent rocking in the chair could produce extreme alternating acceleration/deceleration forces in excess of those induced by shaking alone. Such handling could not be interpreted as accidental mismanagement and the abusive nature of the process was graphically shown in video recordings of the experiment. Prosecution resulted in a conviction for cruelty, and a suspended sentence.     

II. Vinzenz Czerny (1842–1915): Grand Seigneur of Oncologic Surgery—Life, Influence, and Work of the Second Congress President of the ISS/SIC

Vinzenz Czerny, chairman and professor of surgery in Freiburg im Breisgau and in Heidelberg, Germany, is the typical example of a prominent surgeon with an elegant technique, who was also a keen observer and scientist at the turn of the nineteenth into the early twentieth century. Starting his career in Vienna, Austria, he can be looked upon as the most important disciple of Theodor Billroth. Whereas Billroth may be regarded as the father of modern gastrointestinal surgery, Czerny can be considered the father of modern surgery for intestinal malignancies and multimodal treatment. The early history of visceral cancer therapy is linked with his career. He became a surgeon of the highest rank, with great clinical skill, rare judgment, and vision who contributed essentially to the development of modern surgery. From his early education he maintained a lifelong affection for the natural sciences and was an excellent physiologist and pathologist. During his professional life he successfully built up a well deserved reputation for general and cancer surgery and for the introduction of radio- and chemotherapy into the treatment of tumors. Czerny founded and chaired the first experimental Institute for Cancer Research in Germany. Two years later, in 1908, he presided at the 2nd Congress of the International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC) in Brussels, a congress that was almost entirely devoted to the etiology of visceral cancer and the progress and achievements of its treatment. Czerny left a clear legacy of opinion and methods on which the modern era of surgical cancer treatment is based.     

Prognostic impact of ANX7-GTPase in metastatic and HER2-negative breast cancer patients.

PURPOSE: ANX7-GTPase located on chromosome 10q21 is significantly altered and associated with hormone-refractory metastatic prostate cancers. Therefore, we investigated whether levels of ANX7 correlate with breast cancer progression and survival EXPERIMENTAL DESIGN: A diagnostic tumor tissue microarray containing 525 human breast tissue specimens at different stages of the disease was assayed for ANX7 using immunocytochemical methods with ANX7 monoclonal antibody. A separate prognostic tumor tissue microarray containing 553 human breast tissue specimens annotated with clinicopathological parameters was assayed for ANX7, HER2, estrogen receptor, progesterone receptor, and p53 protein. RESULTS: We report here for the first time that the expression of ANX7-GTPase is significantly enhanced and associated with the presence of metastatic disease (P < 0.0001) in the 525 human breast tissue specimens analyzed. Furthermore, using a separate 553 case retrospective prognostic tumor tissue microarray, we found that increased ANX7 expression is also significantly associated with poor overall patient survival (P < 0.014). This is particularly true when restricted to patients in whom the BRE clinical grade is 2 (P < 0.001) or for whom there is a lack of HER2 expression (P < 0.002). Finally, Cox regression analysis shows that as the expression of ANX7 rises, the probability of survival decreases by more than 10-fold for those patients with HER2-negative tumors. These latter patients represented 66% of the population affected with breast cancer in this study. CONCLUSIONS: High levels of ANX7 in tumor correlate strongly with poor survival of HER2-negative patients and the most aggressive forms of breast cancer. This is the first study to demonstrate that ANX7 antibody has the potential for development into an in vivo diagnostic and therapeutic tool. This simple and reliable immunohistochemical assay may therefore become an important biomarker for metastatic breast cancer diagnosis and management of HER2-negative breast tumor patients.     

Human autologous tumor-specific T-cell responses induced by liposomal delivery of a lymphoma antigen.

PURPOSE: The idiotype (Id) of the immunoglobulin on a given B-cell malignancy is a clonal marker that can serve as a tumor-specific antigen. We developed a novel vaccine formulation by incorporating Id protein with liposomal lymphokine that was more potent than a prototype, carrier-conjugated Id protein vaccine in preclinical studies. In the present study, we evaluated the safety and immunogenicity of this vaccine in follicular lymphoma patients. EXPERIMENTAL DESIGN: Ten patients with advanced-stage follicular lymphoma were treated with five doses of this second generation vaccine after chemotherapy-induced clinical remission. All patients were evaluated for cellular and humoral immune responses. RESULTS: Autologous tumor and Id-specific type I cytokine responses were induced by vaccination in 10 and 9 patients, respectively. Antitumor immune responses were mediated by both CD4+ and CD8+ T cells, were human lymphocyte antigen class I and II associated, and persisted 18 months beyond the completion of vaccination. Specific anti-Id antibody responses were detected in four patients. After a median follow-up of 50 months, 6 of the 10 patients remain in continuous first complete remission. CONCLUSIONS: This first clinical report of a liposomal cancer vaccine demonstrates that liposomal delivery is safe, induces sustained tumor-specific CD4+ and CD8+ T-cell responses in lymphoma patients, and may serve as a model for vaccine development against other human cancers and infectious pathogens.     

胰腺癌与饮食、幽门螺旋菌和宿主的炎性细胞素遗传多态性

Pancreaticcancerisanot -infrequentcauseofcancerdeath ,rankingbelowonlylung ,prostateorbreast,andcolorectalcancerinmanycountries .Germlinemutationsandchronic pancreatitishavebeenimplicatedinasmallfractionofcases .Cigarettesmokingistheoneestablishedriskfactorforthisdis ease,howeveritsunderlyingmechanismofactionisuncertain .Wehaveproposedintheetiologythesyn ergisticinvolvementofdietaryorotherN -ni trosamineorN -nitrosamideexposures,andofcon ditionsofchronicexcessgastricorduodenalacidity .Chronic…     

Involvement of deprivation and environmental lead in neural tube defects: a matched case-control study

OBJECTIVE: To analyse the prevalence of neural tube defects in small geographical areas and seek to explain any spatial variations with reference to environmental lead and deprivation. SETTING: The Fylde of Lancashire in the north west of England. DESIGN: Cases were ascertained as part of a prospective survey of major congenital malformations in babies born in the Fylde to residents there between 1957 and 1981. A matched case-control analysis used infants with cardiovascular system, alimentary tract, and urinary system malformations as controls. Conditional logistic regression was used to assess the effects of more than 10 micrograms/l lead in drinking water and the Townsend deprivation score. RESULTS: The prevalence of neural tube defects in 1957-73 was higher in Blackpool, Fleetwood, and North Fylde, whereas the three control groups showed no significant spatial variation. In 1957-81 mothers living in electoral wards with either a higher proportion of houses with more than 10 micrograms/l lead in the water or a higher deprivation score had a greater risk of having a baby with a neural tube defect. For spina bifida and cranium bifidum alone, this was also true. For anencephaly, deprivation was less important although the effect of lead was still seen. In some neural tube defects, lead may act independently of other possible factors associated with deprivation. It seemed unlikely that lead levels changed significantly during the survey. The percentage of houses with 10 micrograms/l or more of lead in the water in 1984-5 was similar to that found in Great Britain 10 years previously. CONCLUSION: There is evidence to suggest that lead is one cause of neural tube defects, especially anencephaly. This could link the known preventive actions of hard water and folic acid. Calcium is a toxicological antagonist of lead. One cause of a deficiency of folic acid is impaired absorption secondary to zinc deficiency, which may be produced or exacerbated by lead.