Renal growth after neonatal urinary tract infection

This study presents the result of 12–21 years' follow-up in a group of children with neonatal urinary tract infection (onset within 1 month after birth) in whom early renal growth retardation was noted without concomitant classical renal scarring. In all cases the neonatal infection was diagnosed and treated within a few days of onset and the patients were closely supervised thereafter. Renal length, parenchymal thickness and area were measured at urography. At first follow-up (22 children, mean age 4.1 years) a significant reduction of renal parenchymal thickness was noted. Long-term follow-up (18 patients, mean age 17 years) demonstrated a normalization of renal size in the entire group, although less complete in the subgroup with reflux. There were two major findings in the present study. Firstly, renal growth retardation was seen after neonatal infection, both with and without reflux. Secondly, normalization of renal size in previously small kidneys was demonstrated, suggesting that growth retardation can be a reversible phenomenon. The tendency for such normalization was slightly more marked in children without reflux. Reduction of parenchymal thickness without calyceal deformity, therefore, does not necessarily mean irreversible damage, and differentiation between permanent scarring and temporary growth retardation can thus only be made at later follow-up, possibly not until after puberty. The demonstration of renal growth retardation in spite of early diagnosis and treatment emphasizes the great vulnerability of the kidney in the newborn.     

Natural killer cell activity and CSF monoamine metabolites in suicide attempters

The aim of this study was to investigate markers of serotonin and immune function in suicidal patients. Cytotoxic activity of natural killer cells (NK) and CD16 lymphocytes were studied in 28 suicide attempters and 26 healthy controls, and related in patients to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF). Patients with CSF 5-HIAA below the median had significantly lower NK cell activity than other patients. CD16 cell frequency was significantly lower in patients than in controls, and patients also tended to have lower NK cell cytotoxicity than healthy controls. There were no statistically significant correlations between 4-hydroxy-3methoxyphenyl glycol (HMPG), homovanillic acid (HVA), CSF cortisol and NK cell activity. The results support the hypothesis of compromised immune function in suicidal patients with evidence of disordered serotonin function.     

Intrascrotal adenomatoid tumors

Adenomatoid tumors are regarded as uncommon neoplasms of the paratesticular tissues, probably of mesothelial origin. The majority of cases reported have involved the epididymis. We report our experience with 8 cases of testicular tumors and 11 of epididymal adenomatoid tumors during a 13-year period, and review the relevant literature. The incidence of adenomatoid tumors relative to all tumors in the testis was 6.9% (8 of 116), exceeding that of Leydig cell tumors, which were previously believed to be the most common benign testicular neoplasms. The adenomatoid tumors included 38% epididymal tumors (11 of 29). The clinical course of the tumors was benign, without recurrences. Local excision is regarded as the treatment of choice for epididymal and testicular adenomatoid tumors.     

Ethanolamine oleate sclerotherapy for hydroceles and spermatoceles: a survey of 158 patients with ultrasound followup.

Sclerotherapy with 5% ethanolamine oleate was used to treat 102 hydroceles in 100 patients and 63 spermatoceles in 58 patients. Scrotal ultrasound examination was performed before the sclerotherapy and at each followup visit. Of the hydroceles 98% were cured completely and 68% were cured after only 1 sclerosant instillation, while 60% of the spermatoceles resolved completely and 33% partially, with 7% failures. No hydroceles recurred during an average followup of 43 months, whereas spermatocele recurred in 4 patients more than 1 year after successful treatment, with a mean followup of 46 months. Approximately half of the patients experienced pain after treatment, 3 had infection and 2 had hematoma. No changes in the structure or size of the testicles were found by ultrasound during followup. Ethanolamine oleate sclerotherapy is a safe, effective and economical form of outpatient therapy that can be recommended as primary treatment for hydroceles in adults and as an alternative to surgery for spermatoceles with 1 to 3 cysts in elderly men in whom fertility is not important.     

The use of oral sedatives in dental care

Oral administration of tranquillizing and anxiety-suppressing drugs has long been the commonest method of achieving light sedation. The benzodiazepines are the drugs of first choice. Benzodiazepines given orally may be indicated to avoid 'treatment stress', alleviate mild anxiety before dental treatment, and facilitate sleep on the night before the treatment. Furthermore, they could be used for the dental treatment of medically poor risk patients, particularly those with cardiovascular disease. The drug can be given either in a fractionated dose or a single dose. The recommended doses for diazepam vary from 0.1–0.8 mg/kg body weight, depending on age, with higher doses in children and lower doses in elderly patients. Few side effects are reported.     

The program for phenotyping of genetically modified animals at AstraZeneca

Genetically modified mice offer a wide range of possibilities in preclinical drug discovery, e.g. for use in target identification, target validation and disease model generation. However, genomic modification and alteration in gene expression may cause unpredicted phenotypic alterations in the organism other than the intended ones. The aim of this study was to determine the importance of establishing the phenotype of transgenic and knockout mice models for use in pharmaceutical research.

A total number of 51 mouse models (transgenic and knockout) produced at AstraZeneca during a 4 year period were subjected to a thorough phenotyping package covering clinical as well as morphological aspects. Phenotype abnormalities were recorded in 36 (70.6%) of the mouse models. The majority of findings were considered to be minor in magnitude. Histopathological changes related to the genotype of the animals were observed in 33% of the mouse models, underlining the importance of pathology in the phenotyping program.     

Mechanisms of otitis media development. Involvement of neurogenic inflammation

The mucosal lining of the middle ear cavity, in particular that of the tympanic membrane and its pars flaccida, exhibits a number of sensory nerves containing the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP). The mucosa is not only rich in nerves and blood vessels but also contains numerous mast cells. It is possible that interactions between histamine-containing mast cells and SP-containing and CGRP-containing nerves--neurogenic inflammation--is one of the mechanisms involved in vessel permeability changes in otitis media with effusion.     

The Stockholm breast cancer screening trial — 5-year results and stage at discovery

In screening programmes it is important to assess a preliminary effectiveness of the screening method as soon as possible in order to forecast survival figures. In March 1981 a controlled single-view mammographic screening trial for breast cancer was started in the south of Stockholm. The population invited for screening mammography consisted of 40,000 women aged 40–64 years, and 20,000 women served as a well-defined control group. The main aim of the trial was to determine whether repeated mammographic screening could reduce the mortality in the study population (SP) compared to the control population (CP).The cumulative number of advanced mammary carcinomas in the screening and the control populations from the first five years of screening have shown a tendency towards more favourable stages in the screened population aged 40–64 years. A breakdown by age suggests an effect in age group 50–59 years, but not yet in age groups 40–49 and 60–64 years.When comparing the rates of stage II+ cancer, an increased number is found in the study group. As the total rate of breast cancer is higher in SP than in CP, there ought to be a concealed group of stage II+ cancers in the CP which makes the comparison biased. A new approach has been designed, where an estimation of the hidden number of stage II+ cancers in CP is added to the clinically detected cases, and in this respect a comparison has shown a decrease in the cumulative number of advanced cancers in the SP in relation to the CP (p<0.05). According to this it could be important to add the estimated number of undetected, hidden cases in the control group in order to utilize the difference in detection rate in the screening- and control group respectively.     

Neutralization assay using a modified vaccinia virus Ankara vector expressing the green fluorescent protein is a high-throughput method to monitor the humoral immune response against vaccinia virus

Vaccination against smallpox is again considered in order to face a possible bioterrorist threat, but the nature and the level of the immune response needed to protect a person from smallpox after vaccination are not totally understood. Therefore, simple, rapid, and accurate assays to evaluate the immune response to vaccinia virus need to be developed. Neutralization assays are usually considered good predictors of vaccine efficacy and more informative with regard to protection than binding assays. Currently, the presence of neutralizing antibodies to vaccinia virus is measured using a plaque reduction neutralization test, but this method is time-consuming and labor-intensive and has a subjective readout. Here, we describe an innovative neutralization assay based on a modified vaccinia virus Ankara (MVA) vector expressing the green fluorescent protein (MVA-gfp). This MVA-gfp neutralization assay is rapid and sensitive and has a high-throughput potential. Thus, it is suitable to monitor the immune response and eventually the efficacy of a large campaign of vaccination against smallpox and to study the vector-specific immune response in clinical trials that use genetically engineered vaccinia viruses. Most importantly, application of the highly attenuated MVA eliminates the safety concern in using the replication-competent vaccinia virus in the standard clinical laboratory.