Blood pressure tracking in urban black South African children: birth to twenty cohort.

BACKGROUND: Hypertension is an emerging public health problem in South Africa. Recent evidence from longitudinal studies has shown that hypertension in adulthood can be traced back to childhood. There is scarcity of longitudinal data on paediatric blood pressure (BP) particularly in African populations. The objective of this study is to assess the prevalence of hypertension and evaluate BP tracking between childhood and late adolescence among South African black Children. METHODS: This study utilized data from the Birth to Twenty cohort, which is comprised of children born in Soweto, Johannesburg in 1990 (N = 3273, 78.5% black). Data on BP and anthropometry were collected at six follow-up periods between ages 5 and 18 years. Blood pressure status was classified using the Fourth report on National High Blood pressure program in children and adolescents. Pearson correlation coefficients and relative risk ratios (RR) were used to describe tracking of BP between childhood and late adolescence. RESULTS: The overall point prevalence ranged from 9.2 to 16.4% for prehypertension and 8.4 to 24.4% for hypertension. Tracking coefficients ranged from 0.20 to 0.57 for SBP and 0.17- 0.51 for DBP in both sexes over the 14 years of measurement. The proportion of children who maintained an elevated BP status between childhood, adolescence and age 18 years ranged from 36.1% at age 5 years to 56.3% at age 13 years. Risk of having elevated BP at 18 years ranged from; RR: 1.60 (95 % CI: 1.29-2.00) at 5 years to RR: 2.71 (95 % CI: 2.32-3.17) at 14 years of age. CONCLUSIONS: This study reports high prevalence of elevated BP which tracks from early childhood into late adolescence. These findings emphasize the importance of early identification of children at risk of developing elevated BP and related risk factors plus timely intervention to prevent hypertension in adulthood.

Role of interleukin-1beta in a murine model of otitis media with effusion.

To clarify the role of interleukin-1beta (IL-1beta) in the pathogenesis of otitis media with effusion (OME), we developed and investigated a murine model of this disease. Specific pathogen-free male BALB/c mice received intratympanic injections of 20 microg of endotoxin derived from nontypeable Haemophilus influenzae. Three days after injection, middle ear effusions were observed through the eardrum. Similar pathological changes were observed after inoculation with 100 ng of recombinant IL-1beta. Anti-IL-1 receptor antibodies inhibited the pathological changes induced by the endotoxin. In situ hybridization showed expression of IL-1beta messenger RNA in the epithelium of the middle ear mucosa. These results suggest that IL-1beta might be associated with endotoxin-induced inflammation in the middle ear and might play an important role in the induction of otitis media with effusion.

Intranasal immunization enhances clearance of nontypeable Haemophilus influenzae and reduces stimulation of tumor necrosis factor alpha production in the murine model of otitis media.

Nontypeable Haemophilus influenzae (NTHi) is a major pathogen causing otitis media (OM). One of the outer membrane proteins of NTHi, P6, is a common antigen to all strains and is considered a candidate for mucosal vaccine. We have previously reported that intranasal immunization with P6 and cholera toxin (CT) could induce P6-specific immunoglobulin A (IgA) antibodies in the middle ear. In the present study, we assessed the effect of intranasal immunization for the protection against NTHi-induced OM. Mice were immunized intranasally with P6 and CT as an adjuvant on days 0, 7, and 14. Control mice were given phosphate-buffered saline (PBS) without antigen. One week after the final immunization, a suspension of live NTHi (10(7) CFU) was injected into the tympanic cavity to induce experimental OM. On days 3 and 7 after bacterial challenge, mice were killed and middle ear effusions (MEEs) were collected. All immunized mice showed elevated titers of P6-specific antibodies in MEEs. The rank order of specific antibody included, from highest to lowest levels, IgG, IgA, and IgM. In addition, immunized mice showed enhanced clearance of NTHi from the middle ear and the number of NTHi in MEEs of immunized mice was reduced by 97% on day 3 and by 92% on day 7 after bacterial challenge relative the number in the MEEs of control mice. The protective effect of intranasal immunization on the incidence of NTHi-induced experimental OM was evident on day 7 after challenge. By day 7, the number of MEEs in immunized mice was 64% less than that in control mice and the incidence of NTHi culture-positive MEEs in immunized mice was 56% less than that in control mice. Less stimulation of tumor necrosis factor alpha (TNF-alpha) production in the middle ear was evident on day 3 after challenge. Immunized mice showed lower concentrations of TNF-alpha in MEEs. These results indicate that intranasal immunization affords protection against experimental OM as evidenced by enhanced clearance of NTHi and less stimulation of TNF-alpha production in the middle ear. These findings suggest that a nasal vaccine might be useful for preventing OM.

Mucosal immunity of the middle ear: analysis at the single cell level.

OBJECTIVE: Studies have suggested that the middle ear is a potential site of immunological regulation and that the middle ear mucosa constitutes a part of the mucosal immune system. We clarify the characteristics of the middle ear mucosa with respect to immune potential. STUDY DESIGN: We investigated lymphocyte subsets, mRNA of cytokines, and induction of antigen-specific IgA-producing cells in the middle ear mucosa in specific pathogen-free C57BL/6 mice. RESULTS: Flow cytometric analysis showed a certain amount (10%-15%) of gammadelta T cells among CD3+ T cells. P6-specific IgA-producing cells were induced by intranasal immunization with P6 together with cholera toxin. RT-PCR assay of mucosal T cells detected mRNA of Th2 type cytokines such as IL-5 and IL-10. CONCLUSION: These findings support the fact that the middle ear is potentially an effector site of the mucosal immunity.

Increase in tonsillar germinal centre B-1 cell numbers in IgA nephropathy (IgAN) patients and reduced susceptibility to Fas-mediated apoptosis.

IgAN is a common form of primary glomerulonephritis and also a disease of tonsillar focal infection. The comprehensive mechanism underlying this disease remains to be defined. To better understand its pathogenesis, we investigated tonsillar CD5+ B cells (B-1 cells) with respect to IgA synthesis. Germinal centre (GC) B cells were isolated from the tonsils of IgAN patients and the number of B-1 cells in the GC determined by flow cytometry. GC B-1 and B-2 (CD5- B) cells were purified by cell sorter, the cells were incubated with agonist anti-CD40 MoAb and the ability for antibody production by B-1 and B-2 cells determined by ELISPOT assay. GC B-1 cells and B-2 cells were incubated with agonist anti-Fas MoAb, and apoptosis in GC B-1 cells and B-2 cells was analysed by flow cytometry. Although B-1 cells do not usually take part in the GC reaction, an increase in B-1 cell numbers was observed in the GC of tonsils from IgAN patients. These B-1 cells were likely IgA1 antibody-producing cells, since the prominent IgA subclass in IgAN is generally considered to be IgA1. Although Fas-dependent apoptosis is essential for the elimination of activated B cells, these B-1 cells showed a reduced susceptibility to Fas-mediated apoptosis. It is conceivable that activated B-1 cells may survive in the GC due to impaired apoptosis and thus produce abnormal antibodies. These findings suggest that the immune responses of B-1 cells in the tonsillar GC could thus have an impact on the pathogenesis of IgAN.

Significance of spiral ligament fibrocytes with cochlear inflammation.

It has been recently suggested that the spiral ligament fibrocytes, which interconnect with the basal cells of the stria vascularis via gap junctions, may be critical in maintaining cochlear homeostasis. In animal models of pathological conditions such as labyrinthitis and otitis media, reduced immunostaining for gap junction protein connexin 26 is observed in the spiral ligament. This suggests that disruption of the spiral ligament fibrocytes could be among the causes of cochlear dysfunction due to cochlear inflammation. Cultured spiral ligament fibrocytes have been shown to secrete chemokines and other mediators after stimulation of proinflammatory cytokine TNF-alpha or IL-1beta. Each of these mediators might induce inflammatory cell movement, which would prolong the inflammatory response. It is reasonable that such enhanced biological defense ability could be the cause of spiral ligament fibrocyte damage.

A case of giant keratoacanthoma of the auricle.

Although keratoacanthomas are not rare in the head and neck area, patients with this type of tumor rarely consult an otolaryngologists for treatment. Keratoacanthoma should be considered in the differential diagnosis of squamous cell carcinoma. This tumor grows rapidly, usually attaining a size of about 10-20 mm in approximately 6 weeks. This is followed by slow involution over a period of 2-6 months. A keratoacanthoma larger than 20-30 mm is called as 'giant keratoacanthoma' and it is scarce. We encountered a case of giant keratoacanthoma (50 mm in diameter) on the right auricle of 84-year-old Japanese woman with a 3-year history of gradual tumor growth. Several clinical and histopathological factors made the diagnosis difficult. The tumor was completely removed by surgery and diagnosed as a keratoacanthoma by histopathological examination.

Induction of specific immunoglobulin A and Th2 immune responses to P6 outer membrane protein of nontypeable Haemophilus influenzae in middle ear mucosa by intranasal immunization.

Nontypeable Haemophilus influenzae (NTHI) is a major pathogen of otitis media. One of the outer membrane proteins of NTHI, P6, is an antigen common to all strains and is considered as a candidate for mucosal vaccine. To elucidate the possibility of developing a nasal vaccine against nontypeable Haemophilus influenzae (NTHI) and to investigate mucosal immune responses in the middle ear, mice were immunized intranasally with the P6 outer membrane protein of NTHI, and P6-specific immune responses in the middle ear mucosa were examined. Mice were given with P6 and cholera toxin intranasally as an adjuvant on days 0, 7, and 14 and were killed on day 21. The P6-specific immunoglobulin A (IgA) antibody titer in ear wash was significantly elevated. Mononuclear cells were isolated from middle ear mucosa, and an increase in P6-specific IgA-producing cells was shown with an enzyme-linked immunospot assay. In addition, an increase in memory T cells in middle ear mucosa was detected with flow cytometric analysis after intranasal immunization. Moreover, in vitro stimulation with P6 resulted in proliferation of purified CD4(+) T cells from immunized mice, and these T cells expressed Th2 cytokine mRNA. These results indicate that P6-specific IgA-B-cell immune responses and selected Th2 cytokine expressing Th cells were induced in middle ear mucosa by intranasal immunization. These findings suggest that a nasal vaccine is useful for preventing otitis media with effusion.

Classification and culture of spiral ligament fibrocytes from mice.

In this study, we established an immunocytochemical strategy to classify the fibrocytes of the murine spiral ligament (SL), and SL cultures were characterized. Similar to those in other mammals, three different types of fibrocytes were identified. Type I fibrocytes, which are found lateral to the stria vascularis, showed positive immunoreactivity for caldesmon and S-100 protein and were not stained for sodium-potassium-adenosinetriphosphatase (Na-K-ATPase). Type II fibrocytes are located lateral to the spiral prominence epithelium and suprastrial region, and they were distinguishable by their positive staining for Na-K-ATPase. Type III fibrocytes, which are found adjacent to bone in the inferior region of the SL, contained caldesmon but not S-100 or Na-K-ATPase. Secondary cultures from the SL were positive for caldesmon and S-100 and negative for Na-K-ATPase, suggesting that these cells were type I fibrocytes. The present immunocytochemical approach was useful for the classification of murine fibrocyte cultures, and these cultures may benefit future immunological studies of the inner ear because mice have been well characterized immunologically.

Age-related changes in the murine cochlear lateral wall.

Cochleas from C57BL/6 mice were investigated electrophysiologically and histochemically to evaluate the pathology of presbycusis. The average auditory brainstem response thresholds from 6-week-old mice were significantly lower than those of 6-month-old mice and those of 1-year-old mice. Histologic observation revealed changes in the cochlea after age 6 months. Conventional hematoxylin and eosin (H&E) staining showed disorganization of the organ of Corti, a decrease in the number of spiral ganglion cells, and atrophy of the stria vascularis. Although H&E staining and type II collagen immunolabeling did not show obvious changes in the spiral ligament (SL), the density of connexin 26 staining was reduced in this region. Sodium-potassium-adenosinetriphosphatase immunolabeling was increased in the SL, whereas its average density was not significantly altered in the stria vascularis. These results suggest that the SL could be among the regions responsible for cochlear malfunction with aging.

Effects of influenza A virus on lectin-binding patterns in murine nasopharyngeal mucosa and on bacterial colonization.

To clarify the role of viral infection in otitis media, we intranasally inoculated mice with influenza A virus and examined histologic changes in the nasopharyngeal mucosa using a battery of lectins. Additionally, live Haemophilus influenzae or Streptococcus pneumoniae was injected into the nasopharynx after virus inoculation, and the clearance of bacteria from the nasopharynx was examined. Staining of the mucous blanket and epithelial cell surfaces in the nasopharynx with peanut agglutinin, succinyl wheat-germ agglutinin, and Bandeiraea simplicifolia agglutinin was significantly enhanced with intranasal virus inoculation when compared with that in control animals. The nasopharynx was moderately stained with Maachia amurensis agglutinin and wheat-germ agglutinin in control animals, and the staining was enhanced after virus inoculation. These findings were most remarkable 5 and 9 days after virus inoculation. The numbers of bacteria cultured from the nasopharynx were significantly increased when bacteria were injected 5 days after virus inoculation. These results suggest that an alteration in the glycoconjugate structure lining the nasopharyngeal mucosa caused by the influenza virus might be associated with the reduction in bacterial clearance.

Effect of proinflammatory cytokines on cultured spiral ligament fibrocytes.

To clarify the effect of proinflammatory cytokines on spiral ligament (SL) fibrocytes, in vitro studies were performed using secondary cell cultures. Cultures from murine SL fibrocytes were stimulated by interleukin (IL)-1beta or tumor necrosis factor (TNF)-alpha, and secretion of various mediators was measured by enzyme-linked immunosorbent assay. After stimulation with the proinflammatory cytokines, IL-6, TNF-alpha, monocyte chemoattractant protein-1, KC, macrophage inflammatory protein-2, soluble intercellular adhesion molecule-1, and vascular endothelial growth factor levels were elevated. Secretion of these chemokines and other mediators could induce inflammatory cell movement, which would prolong the inflammatory response, leading to fibrocyte damage. Given that SL fibrocytes may play a role in cochlear fluid and ion homeostasis, such fibrocyte disruption could cause cochlear malfunction.

[Clinical study of bilateral parotid tumors].

We studied retrospectively 212 patients with parotid tumors who were treated in our hospital between October 1981 and March 1998. One hundred seventy-two of the tumors were benign, and 40 of them were malignant. The tumors were bilateral in 13 patients. Since 1992, we have treated at least 1 bilateral parotid tumor patient per year, and the number of patients with bilateral parotid tumors has tended to increase. Histologically, adenolymphomas occurred in 11 patients, and there was one occurrence of pleomorphic adenoma and one occurrence of basal cell adenoma. Eighty-five percent of all bilateral parotid tumors were adenolymphomas, and the bilateral parotid tumors comprised twenty percent (11 of 53 patients) of all adenolymphomas that we encountered. Among the 13 patients with bilateral parotid tumors, 1 patient experienced them heterochronously. In 7 of the 13 patients the tumor on the opposite side was found by diagnostic imaging. One patient showed recurrence in both parotid glands 4 years after initial surgery. Comparing bilareral adenolymphomas with unilateral adenolymphomas, there was no significant difference in the age or sex of the patients. Regarding bilateral adenolymphoma, 4 patients showed a solitary tumor on either side, 4 patients showed a solitary tumor on one side and multiple tumors on the other side, and 4 patients showed multiple bilateral tumors. Regarding unilateral adenolymphoma, 38 patients showed solitary tumors and 4 patients showed multiple tumors. Bilateral adenolymphomas were more multicentric than unilateral adenolymphomas. Epstein-Barr virus-encoded RNA (EBER) was detected in 11 of the 12 bilateral adenolymphomas and in 18 of 35 patients with unilateral adenolymphoma, by in situ hybridization. EBER was detected more frequently in the multiple unilateral adenolymphomas than in the solitary unilateral adenolymphomas. Based on our experience, the bilateral parotid tumor is not rare. Care should be taken to observe the other side of the parotid gland with parotid tumors that are suspected adenolymphomas. Imaging may be helpful for the detection of bilateral tumors. A relationship may exist between Epstein-Barr virus and adenolymphoma multicentricity.

Effects of intranasal immunization on protective immunity against otitis media.

It has been reported that intranasal immunization can induce mucosal immune responses. However, the efficacy of intranasal immunization on otitis media caused by non-typeable Haemophilus influenzae (NTHi) is not yet elucidated. Mice were intranasally, orally, intratracheally or intraperitoneally immunized with outer membrane protein (OMP) isolated from NTHi, and antigen-specific immune responses were determined by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immuno-spot assay (ELISPOT). Cytokine production from splenic CD4+ T cells was examined by ELISA. Following the immunization, the clearance of NTHi from the nasal and nasopharyngeal cavity was examined. OMP-specific IgA antibody titers in nasal washes and the numbers of specific IgA-producing cells in nasal passages were significantly increased in intranasally immunized mice. Cytokine analysis showed that interferon-gamma (IFN-gamma) and interleukins IL-6 and IL-10 were predominantly produced from CD4+ T cells. The clearance of NTHi was significantly enhanced in the intranasal immunization group. Intranasal immunization is an effective vaccination regimen for the induction of OMP-specific mucosal immune responses.

[Report of two rare cases of fungal sinusitis].

Two cases of aspergillosis of the paranasal sinuses are reported. The first case was a 30-year-old man who had a 5-month history of bilateral proptosis. Physical examination revealed nasal polyps in both middle meatus. A skin test for Aspergillus was positive. Laboratory study showed levels of serum IgE and IgE specific for Aspergillus level to be elevated significantly. Computed tomography (CT) and magnetic resonance imaging (MRI) showed pansinusitis with some bone erosion. The patient underwent bilateral Caldwell-Luc procedures and external sinus surgery (frontal, ethmoid and sphenoid sinuses). Histopathological examination showed thin septate hyphae in allergic mucin. The patient is now being treated with sinus irrigation and oral administration of fluconazole and suplatast tosilate. The second case was a 78-year-old man who had a 2-month history of nasal obstruction and a 3-week history of headaches. He also had a history of diabetes mellitus. Physical examination showed swelling of the nasal septum due to abscess. CT showed an abscess in the nasal septum and opacification of the left sphenoid sinus. There was no bone destruction. The patient underwent left sphenoid sinus surgery, and histopathological examination revealed aspergillosis of the sphenoid sinus. He presented with left visual disturbance and blepharoptosis 2 months after surgery. Ocoulusion of the internal carotid artery was revealed by MR angiography and it was thought to be caused by intracranial invasion of aspergillus. Loss of consciousness and right hemiplegia ensued despite antifungal chemotherapy. The patient died about 1 year after the onset of symptoms. Case 1 was thought to involve allergic aspergillus sinusitis, and Case 2 invasive aspergillus sinusitis. We emphasize the significance of headache, diabetes mellitus and lesion in the sphenoid sinus as a sigh of intracranial aspergillus invasion, based on our experience as well as findings reported by other clinicians in the Japanese literature.

Immediate tonsillectomy for peritonsillar abscess.

OBJECTIVE: Peritonsillar abscess (PTA) is one of the most common infectious diseases of the head and neck region requiring surgical intervention to relieve symptoms such as severe throat pain, fever, dysphagia, and trismus. However, the appropriate management of PTA is still controversial. In Europe and the US, immediate tonsillectomy under general anesthesia has been accepted as the treatment for PTA. But in Japan, immediate tonsillectomy has been regarded as contraindicated for PTA because of difficulties encountered in the operation during the acute stage, as well as possible postoperative complications. METHODS: A total of 103 cases of PTA treated at our clinic during the past 16 years were reviewed; immediate tonsillectomies had been performed in 99 of them. Surgical findings, postoperative course, and bacteriological examination were surveyed. RESULTS: The results showed that immediate tonsillectomy under general anesthesia was carried out safely without complications. Dramatic relief of the symptoms was obtained within a few days following each operation. A high incidence of anaerobes was observed by bacteriological examination, suggesting that sufficient drainage is required to treat this disease. CONCLUSION: We conclude that immediate tonsillectomy should be performed for peritonsillar abscess.

Primary non-Hodgkin's lymphoma of brachial plexus.

We report the case of a 65-year-old man with non-Hodgkin's lymphoma (NHL) not only in the brachial plexus but also in the central nervous system and parotid gland. He was referred to our hospital for evaluation of a right parotid mass. He also presented with bilateral facial palsy and paralysis of the left superior limb. Computed tomography scan and magnetic resonance imaging revealed mass lesions in the right parapharyngeal space, the deep lobe of the right parotid gland. and the left brachial plexus. A gallium-67 citrate scan demonstrated abnormal uptake in the left brachial plexus. These symptoms and lesions improved during steroid therapy. However, the symptoms worsened again after steroid therapy was discontinued. We performed a right parotidectomy to confirm the diagnosis. Histopathological study revealed NHL. He was treated with combination chemotherapy, and most of the lesions and symptoms, except bilateral facial palsy, improved. Despite follow-up treatment, a brain metastasis occured, and he died 16 months after the onset of symptoms.

The influence of pneumococcal otitis media on the cochlear lateral wall.

The cochlear influence of otitis media was investigated in order to identify damaged regions causing cochlear malfunction. BALB/c mice were challenged with viable Streptococcus pneumoniae into the middle ear cavity and were killed 1 day to 1 month later for immunohistochemical analysis. Otitis media was induced in all of the animals, and some showed inflammatory cells in the cochlea. Although other changes were not obvious by hematoxylin and eosin staining, immunohistochemistry showed the presence of fibrinogen in the cochlea, mainly in the lower portion of the spiral ligament and in the spiral limbus. Immunostaining for connexin 26 was decreased in the spiral ligament, accompanied by marked fibrinogen staining. Immunostaining for sodium-potassium-adenosine triphosphatase in the stria vascularis and in the type II fibrocytes of the spiral ligament was not affected obviously. The presence of fibrinogen in the cochlea suggests disruption of the blood-labyrinth barrier caused by the middle ear inflammation. Changes in connexin 26 staining suggest the possibility that the spiral ligament could be among the regions responsible for the cochlear malfunction.

Efficacy of an antiallergic drug on otitis media with effusion in association with allergic rhinitis. An experimental study.

The effect of an antiallergic drug on the evacuation of middle ear effusion (MEE) from the tubotympanum was investigated by means of an animal model with both otitis media with effusion (OME) and allergic rhinitis. Azelastine hydrochloride (AZ), an oral antiallergic drug, was administered and the presence of MEE was investigated. Serous MEE was seen in 12 of the 13 untreated control animals on the 11th day after the experimental OME was induced, whereas MEE was detected in 9 of the 13 animals administered 1 mg/kg of AZ, but only in 4 of the 13 animals administered 2 mg/kg of AZ. In addition, the effect of AZ on MEE production was also examined in an experimental OME animal model without allergic rhinitis. Middle ear effusion was observed in all OME animals that received 2 mg/kg AZ for 5 consecutive days, before and 3 days after the experimental OME was induced. Results of the present study indicate that AZ promotes the evacuation of MEE from the tubotympanum in the OME animal model associated with nasal allergy. These data suggest that an antiallergic drug may contribute to the therapy of OME patients in association with nasal allergy indirectly, by promoting evacuation of MEE due to inhibition of type I allergic reactions in the nasopharynx.