Phase Variation Mediates Reductions in Expression of Surface Proteins during Persistent Meningococcal Carriage

Asymptomatic and persistent colonization of the upper respiratory tract by Neisseria meningitidis occurs despite elicitation of adaptive immune responses against surface antigens. A putative mechanism for facilitating host persistence of this bacterial commensal and pathogen is alterations in expression of surface antigens by simple sequence repeat (SSR)-mediated phase variation. We investigated how often phase variation occurs during persistent carriage by analyzing the SSRs of eight loci in multiple isolates from 21 carriers representative of 1 to 6 months carriage. Alterations in repeat number were detected by a GeneScan analysis and occurred at 0.06 mutations/gene/month of carriage. The expression states were determined by Western blotting and two genes, fetA and nadA, exhibited trends toward low expression states. A critical finding from our unique examination of combinatorial expression states, “phasotypes,” was for significant reductions in expression of multiple phase-variable surface proteins during persistent carriage of some strains. The immune responses in these carriers were examined by measuring variant-specific PorA IgG antibodies, capsular group Y IgG antibodies and serum bactericidal activity in concomitant serum samples. Persistent carriage was associated with high levels of specific IgG antibodies and serum bactericidal activity while recent strain acquisition correlated with a significant induction of antibodies. We conclude that phase-variable genes are driven into lower expression states during long-term persistent meningococcal carriage, in part due to continuous exposure to antibody-mediated selection, suggesting localized hypermutation has evolved to facilitate host persistence.     

Parturition lines in modern human wisdom tooth roots: do they exist,can they be characterized and are they useful for retrospective determination of age at first reproduction and/or inter-birth intervals?

Background: Parturition lines have been described in the teeth of a number of animals, including primates, but never in modern humans. These accentuated lines in dentine are comprised of characteristic dark and light component zones.

Aim: The aim of this study was to review the physiology underlying these lines and to ask if parturition lines exist in the third molar tooth roots of mothers known to have had one or more children during their teenage years.

Methods: Brief retrospective oral medical obstetric histories were taken from four mothers and compared with histological estimates for the timing of accentuated markings visible in longitudinal ground sections of their wisdom teeth.

Results: Evidence of accentuated markings in M3 root dentine matched the age of the mother at the time their first child was born reasonably well. However, the dates calculated for inter-birth intervals did not match well.

Conclusions: Parturition lines corresponding to childbirth during the teenage years can exist in human M3 roots, but may not always do so. Without a written medical history it would not be possible to say with confidence that an accentuated line in M3 root dentine was caused by stress, illness or was a parturition line.     

Complications of varicella in healthy children in Izmir, Turkey

BACKGROUND: The purpose of the paper was to evaluate the indications of hospital admissions and complications of varicella infection in immunologically healthy children. METHODS: Between 1997 and 2001, patient records of children hospitalized due to varicella infection were reviewed. Incidence and clinical spectrum of complications and their distribution related to age and seasonal variations were analyzed. RESULTS: A total of 178 immunocompetent children were hospitalized for varicella complications during the study period. This resulted in a crude incidence of 6.3/100 000 population at risk. All hospital admissions were due to accompanying complications. The majority of complications occurred in preschool-age children with a median age of 3 years. No gender predominance was found. The most frequent complications were infectious complications, which were observed in 79 children (44%). Superinfections of the skin were present in 24 patients. Pneumonia was observed in 59 children: 49 had bacterial, 10 had viral pneumonia. Pyogenic arthritis was seen in two children and one had concomitant osteomyelitis. Group A beta-hemolytic streptococci were recovered from two patients with invasive bacterial infections. A total of 68 (38%) neurologic complications were observed. Cerebellar ataxia was present in 24, encephalitis was present in 17. Infectious complications occurred more frequently in younger children (median age: 2 years), whereas neurologic complications occurred at an older age (median age: 6 years). Hematologic complications were seen in nine children. There was a seasonal distribution of complications with a peak in January. CONCLUSION: Complications of varicella requiring hospitalization in immunocompetent children are more frequent than previously thought.     

Intestinal obstruction due to rectal endometriosis

We report a case of a premenopausal woman with severe constipation causing intermittent obstruction. Colonoscopy revealed a tight rectal stricture; however, mucosal biopsies were normal. Exploratory surgery revealed an intense fibrotic reaction involving the rectum and uterus, necessitating a simultaneous low anterior resection and hysterectomy. Pathology established a diagnosis of endometriosis. Preoperative diagnosis of rectal endometriosis can be difficult to establish. Endometrial deposits do not invade the mucosa; therefore, colonoscopy with biopsies are frequently non-diagnostic. Surgery may be the only definitive way to obtain a certain diagnosis. In cases involving rectal strictures of unknown etiology in premenopausal women, rectal endometriosis must be included in the differential diagnosis.     

Induction chemotherapy with cisplatin and 5-fluorouracil followed by chemoradiotherapy or radiotherapy alone in the treatment of locoregionally advanced resectable cancers of the larynx and hypopharynx: results of single-center study of 45 patients

BACKGROUND: Induction chemotherapy with cisplatin and fluorouracil and radiotherapy is an effective alternative to surgery in patients with carcinoma of the larynx and hypopharynx who are treated for organ preservation. METHODS: We designed a protocol to evaluate the possibility of organ preservation in patients with advanced, resectable carcinoma of the larynx and hypopharynx. Forty-five eligible patients who were followed up between April 1999 and May 2001 were enrolled. Initially, these patients were treated with two cycles of induction chemotherapy consisting of cisplatin, 20 mg/m2/day on days 1 to 5, and 5-fluorouracil, 600 mg/m2/day by continuous infusion on days 1 to 5. Patients who had a complete response to chemotherapy were treated with definitive radiotherapy; patients who had a partial response to chemotherapy were treated with chemoradiotherapy. Cisplatin, 35 mg/m2/week, was introduced throughout the duration of radiotherapy. Patients who had no response or progressive disease underwent surgery with postoperative radiotherapy. Patients with N2 or N3 positive lymph nodes underwent neck dissection after the treatment. RESULTS: The mean age was 56.6 years (range, 34-75 years). The overall response rate to induction chemotherapy was 71.1%, with a 17.8% complete response rate and 53.3% partial response rate. With a median follow-up of 13.7 months, 23 (51.1%) of all patients and 63.3% of surviving patients have had a preservation of the larynx or hypopharynx and remain disease free. The most common toxicities were nausea and vomiting and mucositis. CONCLUSION: Organ preservation, with multimodality treatment, may be achievable in some of the patients with resectable, advanced larynx or hypopharynx cancers without apparent compromise of survival.     

Association of fallopian tube cancer and polymyositis. Apropos of 1 case

A 51-year-old woman consulted for pelvic pain, metrorrhagia and leukorrhea. Physical examination revealed a renitent and mobile mass in the pelvis. A right lateral uterine mass with hydroxalpinx was found at ultrasonography. Pathology examination of the right annexectomy specimen provided the definitive diagnosis: fallopian tube cancer with polymyositis. No residual tumor was found at total hysterectomy with total bilateral annexectomy. The patient was lost to follow-up for three years without complementary treatment then consulted later for functional disability of the upper then lower limbs with myalgia, swallowing disorders and left supraclavian node enlargement resulting from pelvic relapse of the right fallopian tube adenocarcinoma and left supraclavian metastasis with paraneoplastic polymositis. The patient was given 6 courses of chemotherapy with radiotherapy (45 Gy) centered on the left clavian region. The patient exhibited a spectacular response, and remains in complete remission 50 months after diagnosis. The association of a fallopian tube tumor with polymyositis is exceptional, requiring rapid anticancer treatment effective against the cancer and the paraneoplastic polymyositis.