Mechanism of persistent infection associated with peritoneal implants.

The ability of rabbits to clear an intraperitoneal injection of Pseudomonas aeruginosa in the presence or absence of a surgically implanted peritoneal device was investigated. Sham-operated rabbits without an implant eliminated a P. aeruginosa challenge of 5 x 10(6) cfu/ml; lavage fluid and peritoneal tissues became culture-negative within 96 h. However, peritonitis developed in rabbits that were given the same number of bacteria in the presence of an implant; high bacterial counts were recovered from the lavage fluid and the device itself. Scanning and transmission electronmicroscopy revealed bacterial biofilms on the surface of the device. Insertion of pre-colonised devices demonstrated a rapid multiplication of sessile organisms within the resulting bacterial biofilm. Counts reached a plateau of about 1 x 10(7) cfu/cm2 of Silastic by day 16 and fluctuated around this level until the end of the study. Pre-immunisation with formalin-killed whole cells of P. aeruginosa did not reduce this bacterial growth despite high levels of specific IgG. The results confirm the failure of peritoneal defences to clear an infection in the presence of an implant following either challenge with planktonic bacteria or insertion of a pre-colonised device, and demonstrate the rapid development of bacterial biofilms on the surface of the implant which appear to protect the bacteria from host defences, even when primed by pre-immunisation.     

Protein engineering and the study of structure--function relationships in receptors

Protein engineering is a powerful tool for studying relationships between receptor structure and function--providing that it is used and interpreted appropriately. Site-directed mutagenesis, deletion mutagenesis and construction of chimaeric proteins have all been used to characterize receptors. In this review, Walter Ward, David Timms and Alan Fersht describe the application of protein engineering, illustrating important concepts with experimental data. They explain that detailed study of function requires careful dissection of mechanistic steps. Care must also be taken when selecting replacement residues; mutation should not cause delocalized structural reorganization or else the true significance of functional change will remain unclear.     

Zinc deficiency and hyperprolactinaemia are not reversible causes of sexual dysfunction in uraemia

We selected a group of male dialysis patients complaining of sexual dysfunction in whom penile vascular insufficiency and drug-induced impotence had been excluded. Monitoring of nocturnal penile tumescence was used to confirm organic disturbance. Patients with normal serum prolactin concentrations (n = 18) had significantly lower serum zinc values than normal controls (P less than 0.001) and were entered in a 6-month double-blind study comparing oral zinc acetate with placebo. Patients with elevated prolactin concentrations (n = 8) were entered in a 3-month double-blind crossover study comparing oral pergolide mesylate with placebo. In the zinc study, serum zinc concentrations increased (P less than 0.05) in the zinc-treated but not the placebo-treated group. One of nine patients receiving zinc reported improved sexual function, as did two of nine patients receiving placebo. There were no significant changes in sperm counts, nocturnal penile tumescence, testosterone, sex hormone binding globulin or gonadotrophin concentrations in either treatment group. In the pergolide study, serum prolactin values decreased (P less than 0.01) in the pergolide but not in the placebo treatment period. One patient reported improved sexual function during the pergolide treatment period and two during the placebo period. There were no significant changes in sperm counts, nocturnal penile tumescence, testosterone, sex hormone binding globulin or gonadotrophin concentrations after pergolide. These studies show no benefit of zinc or pergolide compared with placebo in the treatment of uraemic impotence.     

Atlantoaxial instability in Down's syndrome: clinical and radiological screening

One hundred and thirty children with Down's syndrome were screened for the presence of atlantoaxial instability, using both clinical examination and radiographs of the cervical spine taken in flexion and hyperextension views. Seven children were found to have radiological evidence of atlantoaxial instability, with an atlanto-dens interval greater than 5.0 mm in one or all positions. Although a full clinical history was obtained from the attending parent and each child underwent a complete neurological examination, there were no factors detected which differentiated between those with radiological evidence of atlantoaxial instability and those with a normal atlantodens distance. It is recommended that children with Down's syndrome be screened twice, at the ages of 5-10 years and at 15 years.     

Carrier diagnosis of Duchenne muscular dystrophy using restriction fragment length polymorphisms

Molecular probes that are tightly linked to and flank the Duchenne muscular dystrophy (DMD) locus, have been used to characterize DMD mutations and diagnose female carriers. Deletions within the Xp21 region were identified for 8 of 71 families studied. Using both DNA and CK studies, accurate (96 to 98%) carrier or noncarrier diagnoses were made for 51 of 75 females at risk in 24 families with a single affected male. DNA studies resulted in an alteration of predicted risk in 40% of the cases. Recombinant diagnostic methods are useful for carrier detection in families with one or more affected males.     

Cytosolic aldehyde dehydrogenase (ALDH1) variants found in alcohol flushers

Although mitochondrial aldehyde dehydrogenase (ALDH2) has been thought to play a major role in acetaldehyde detoxification, and the high incidence of 'alcohol flushing' among Orientals is attributed to the inherited deficiency of ALDH2, the role of cytosolic aldehyde dehydrogenase (ALDH1) cannot be ignored. On the premise that alcohol flushing in Caucasians could be related to ALDH1 abnormalities, we examined the enzyme properties and electrophoretic mobilities of ALDH1 partially purified from red blood cells of nine unrelated alcohol flushers. One exhibited very low activity (10–20% of control level), and another exhibited moderately low activity (60%) and altered kinetic properties. The electrophoretic mobilities of these two samples were also distinguishable from the control samples. Immunological quantitation indicated that the amounts of ALDH1 protein in these two samples were not reduced in parallel with their enzyme deficiency. In the first case, the two characteristics, i.e. very low enzyme activity and alcohol flushing, were inherited by her daughter.     

Repetitive endoscopic sinus surgery failure: a role for radical surgery?

OBJECTIVES: Endoscopic sinus surgery (ESS) is considered to be the golden standard for surgery in patients with chronic rhinosinusitis and nasal polyposis. However, there is still a small group of patients unresponsive despite repetitive surgery. Radical surgery aimed at reduction of the inflammatory burden and optimization of drainage of the sinuses has been suggested as a last resort for these patients. STUDY DESIGN: A prospective, questionnaire-based study was conducted in a group of 23 patients who underwent Denker's procedure for refractory chronic rhinosinusitis. Symptoms were evaluated before Denker's procedure and 12 months and 2 years after surgery. RESULTS: Patients reported improvement of feelings of congestion in 74%, rhinorrhea in 70%, and nasal obstruction in 60% of the cases. The following postoperative improvements were statistically significant: rhinorrhea (P = 0.001), feelings of congestion (P = 0.02), and nasal obstruction (P = 0.03). Reduced olfactory perception and asthma did not improve. CONCLUSION: Radical surgery may be a viable treatment option in case of recurrent ESS failure. EBM rating: C-4.     

Concurrent oral and genital infection with HPV DNA types 6 and 11 in a heterosexual male

Objective Detection of HPV DNA in oral and genital lesions of a heterosexual male. 4 months after oral and vaginal intercourse with a woman with vulvar warts. Passible modes of acquisition of oral HPV infection in the male sexual partner are discussed. Setting Genitourinary Medicine clinic. Methods Polymerase chain reaction amplification of genomic DNA from oral and genital lesions. HPV DNA typing by dot blot hybridization. Results HPV DNA types 6 and 11 were identified in a polypoid tongue lesion and in a penile wart from the male sexual partner. Conclusions The acquisition of oral HPV infection in the male sexual partner may have resulted from genital-oral HPV transfer, either by direct contact with vulvar warts or by digital self-inoculation.