Endoscopic reconstruction of traumatic membranous urethral transection

Newer endoscopic techniques derived from percutaneous renal manipulations are well suited for endoscopic reconstruction of traumatic short total membranous urethral transections. Four men and 1 child underwent successful endoscopic membranous urethral reconstruction. All 4 men are voiding with good flow and normal control more than 1 year after any endoscopic manipulation.     

The Ethics of Caring for Conjoined Twins The Lakeberg Twins

In June 1993, conjoined twins Amy and Angela Lakeberg became the focus of national attention. They shared a complex six-chambered heart and one liver; only one could survive separation surgery, and even her chances were slim. The medical challenge was great and the ethical challenges were even greater.     

Stimulated pressure response of the ileocolonic junctional zone and its use as a continence mechanism in a canine model

Summary Mechanisms for maintaining passive continence in the efferent limb of urinary diversions include compression of tissue, peristalsis, equilibration of pressure and use of valves. Motor activity and pressure in the ileum, ileocecal valve (ICV) and the colon were evaluated in dogs. Spontaneous activity and pressure were compared with stimulated pressure response and activity. Stimulation was performed at the pelvic nerve and the small nerves in the mesenterium, as well as direct neurostimulation of the bowel. Resting pressure at the ICV was 12.7±0.4 cmH₂O rising to 26.4±2.2 cmH₂O during spontaneous depolarization. Stimulation of the pelvic nerve resulted in increased colonic motor activity with unchanged pressure. Electric stimulation of small mesenterical nerves to the ICV increased pressure in the ICV to 35.0±4.1 cmH₂O, while direct myoelectric stimulation of the ICV zone increased the intraluminal pressure to 75.0±3.2 cmH₂O. Termination of the electric stimulation was followed by a slow decrease of pressure to the resting level a period of 30–45 s. Maintaining continence at the ICV with long-term constant or intermittent stimulation seems feasible.     

Chloroplast and mitochondrial DNA are paternally inherited in Sequoia sempervirens D. Don Endl

Restriction fragment length polymorphisms in controlled crosses were used to infer the mode of inheritance of chloroplast DNA and mitochondrial DNA in coast redwood (Sequoia sempervirens D. Don Endl.). Chloroplast DNA was paternally inherited, as is true for all other conifers studied thus far. Surprisingly, a restriction fragment length polymorphism detected by a mitochondrial probe was paternally inherited as well. This polymorphism could not be detected in hybridizations with chloroplast probes covering the entire chloroplast genome, thus providing evidence that the mitochondrial probe had not hybridized to chloroplast DNA on the blot. We conclude that mitochondrial DNA is paternally inherited in coast redwood. To our knowledge, paternal inheritance of mitochondrial DNA in sexual crosses of a multicellular eukaryotic organism has not been previously reported.     

Ultrastructure of another spiral organism associated with human gastritis

Summary Campylobacter pylori may not be the only organism that causes active chronic gastritis in man. We report two cases of gastric infection with a spiral organism distinct fromC. pylori. The first patient is a 36-year-old female who presented with epigastric pain and abdominal colic present since childhood and who had 14 cats. Endoscopy was normal. The second patient kept two dogs. Histology of gastric mucosal biopsy specimens in both patients revealed active chronic gastritis, most severe in body mucosa. Giemsa stain revealed bacteria with four to eight spirals, 0.5 m in diameter and 3–7 m in length. The organisms had multiple sheathed flagella at the pole and smooth cell walls without axial filaments. The organisms resembled the gastric spirillum that has been seen in cats, dogs, and nonhuman primates. After antibacterial therapy with bismuth subsalicylate, amoxicillin, and metronidazole, the organisms disappeared in both patients and the gastritis healed.UnlikeC. pylori, this new spirillum prefers to colonize gastric mucosa containing parietal cells. Whereas this type of organism is a common commensal in other mammals, it appears to be associated with and a possible cause of gastritis in humans.     

Temporal Variation of the Merozoite Surface Protein-2 Gene of Plasmodium falciparum

Extensive polymorphism of key parasite antigens is likely to hamper the effectiveness of subunit vaccines against Plasmodium falciparum infection. However, little is known about the extent of the antigenic repertoire of naturally circulating strains in different areas where malaria is endemic. To address this question, we conducted a study in which blood samples were collected from parasitemic individuals living within a small hamlet in Western Irian Jaya and subjected to PCR amplification using primers that would allow amplification of the gene encoding merozoite surface protein-2 (MSP2). We determined the nucleotide sequence of the amplified product and compared the deduced amino acid sequences to sequences obtained from samples collected in the same hamlet 29 months previously. MSP2 genes belonging to both major allelic families were observed at both time points. In the case of the FC27 MSP2 family, we observed that the majority of individuals were infected by parasites expressing the same form of MSP2. Infections with parasites expressing 3D7 MSP2 family alleles were more heterogeneous. No MSP2 alleles observed at the earlier time point were detectable at the later time point, either for the population as a whole or for individuals who were assayed at both time points. We examined a subset of the infected patients by using blood samples taken between the two major surveys. In no patients could we detect reinfection by a parasite expressing a previously encountered form of MSP2. Our results are consistent with the possibility that infection induces a form of strain-specific immune response against the MSP2 antigen that biases against reinfection by parasites bearing identical forms of MSP2.The development of a host-protective immune response against Plasmodium falciparum takes several years and many episodes of infection, at least for children living in areas where malaria is endemic. One of the reasons for this is believed to be the large number of distinct parasite strains circulating within an area of endemicity and the assumption that exposure must occur to a sufficiently large sample of these before lasting immunity is induced. However, the detailed epidemiology of endemic malaria infection remains poorly understood at the molecular level, and there is surprisingly little nucleotide sequence data to support the concept of a large repertoire of antigenically distinct strains.There are at least six antigenically diverse proteins of the asexual stage that are known to be the target of potentially protective host responses. The definition of antigenically distinct strains involves identification of the allelic form expressed at all antigenically diverse loci—the extended antigenic haplotype. The loci would include merozoite surface protein-1 to -3 (3), apical membrane antigen-1 (17), S-antigen (6), and P. falciparum erythrocyte membrane protein-1 (PfEMP-1) (5). Such a complete molecular definition of infecting parasites is a highly ambitious task, particularly in the case of blood samples collected from patients harboring mixed infections. Accordingly, most studies focus on one or other of the antigenically diverse antigens. We have elected to study merozoite surface protein-2 (MSP2) (27), a 45- to 50-kDa glycoprotein anchored in the merozoite surface by a glycosylphosphatidylinositol anchor. This surface protein is a promising candidate for inclusion in a malaria subunit vaccine, as both in vitro and in vivo studies have demonstrated the ability of immune responses to MSP2 to inhibit parasite multiplication (23, 25). However, the efficacy of any subunit vaccine containing a single form of MSP2 may be limited by the presence of antigenically distinct parasite strains within an area of endemicity. We will adopt the recently proposed convention for parasite genes and gene products of denoting the gene sequence as MSP2 and the protein as MSP2.Sequence polymorphism has been described for MSP2 genes of both laboratory-maintained isolates (29) and field isolates (14, 16, 19, 30). Comparison of MSP2 gene sequences from these isolates reveals highly conserved 5′ and 3′ sequences that flank a central variable region. This central region is composed of repeats flanked by nonrepetitive sequences. The nonrepetitive sequences are one or other of two distinct forms that define two allelic families, FC27 and IC-1/3D7 (29). The central repeats are more variable and define the individual alleles of MSP2. There is a correlation between the general form of the central repeat sequence and the allelic family. For example, FC27 family members have variants of a central 96-bp pair sequence that may be present in one to four copies followed by a 21-bp partial repeat and a variably represented 36-bp sequence that may be present in one to five copies. In contrast, alleles belonging to the 3D7 family show a central repeat region made up of variable numbers of 12- to 24-bp repeats separated by repeating 6-bp sequences.Field studies aimed at defining the antigenic diversity of MSP2 have approached the problem by determining MSP2 gene structure by various forms of PCR. The rationale for this is that P. falciparum is haploid and MSP2 has been shown to be present in all laboratory and field isolates examined (8–10, 15). Most studies examining the distribution and frequency of different allelic forms of MSP2 have enumerated the presence of the allelic families (11, 12, 14). Whereas a skewed distribution of predominantly 3D7 family alleles exists among laboratory-adapted strains, in the field a more even distribution of FC27 and 3D7 alleles occurs. Often FC27 family alleles are more prevalent than 3D7 alleles, and novel FC27 and 3D7 family alleles have been found in field malaria strains (14, 16). Some field studies examining recurrent MSP2 infections have been performed, but these have classified MSP2 alleles on the basis of family and length of the central repeat region (7, 11, 14). This makes it difficult to form conclusions about the repertoire of repeat sequences in the circulating pool of parasites and to infer the possible action of immune responses to MSP2 repeats. We were interested to examine the sequences of MSP2 alleles circulating in an area of endemicity over time and to determine the persistence of various MSP2 alleles within a localized area. This study describes MSP2 genotypes from malaria-infected inhabitants of the Oksibil region of Irian Jaya and allows comparison of the variation in MSP2 sequences seen over a 2.5-year period within the region as a whole and in particular individuals.     

Progression of self-reported symptoms in laboratory animal allergy

BACKGROUND: Laboratory animal allergy is a common illness among workers exposed to laboratory animals and can progress to symptoms of asthma. OBJECTIVES: This study evaluates the continuum of disease from allergy symptoms to asthma symptoms in a dynamic cohort of workers exposed to animals in a pharmaceutical company. METHODS: Data arose from annual questionnaires administered to workers in a surveillance program established to monitor exposure to animals and the development of allergy. The life-table method was used to compare asthma-free survival between workers with and without symptoms of allergy. A Cox proportional hazards model was used to examine the effects of covariates on the development of asthma. RESULTS: A total of 603 workers contributed 2527.4 person-years to the study over the 12.3-year period. The probabilities of experiencing asthma symptoms by the 11th year of follow-up were 0.367 for workers with allergy symptoms and 0.052 for those without allergy symptoms. The hazard ratio for asthma symptoms when comparing workers with and without allergy symptoms was 7.39 (95% CI, 3.29-16.60) after adjustment for sex and family history of allergy. Female subjects developed asthma at a rate 3.4 times that of male subjects. CONCLUSIONS: This study supports the hypothesis that laboratory animal allergy symptoms are a major risk factor for the development of asthma. It also suggests a heightened risk of asthma for women who work with laboratory animals, a finding that has not been previously reported.     

P67L: a cystic fibrosis allele with mild effects found at high frequency in the Scottish population.

Only three mutant cystic fibrosis (CF) alleles have to date been established as conferring a dominant mild effect on affected subjects who are compound heterozygotes. We now add a fourth, P67L, which occurs on about 1.4% of Scottish CF chromosomes. Among 13 patients (12 unrelated) with this allele, the average age at diagnosis was 22.5 +/- 11.3 years. None of the cases had consistently raised sweat chloride concentrations, the average value being 57 +/- 9 mmol/l; 77% of the patients were pancreatic sufficient. When compared to three other established mild CF alleles, R117H, A455E, and 3849 + 10kb C-T, a compound heterozygote for P67L has minimal disease and clinical suspicions are unlikely to be confirmed other than by DNA typing.