Gabapentin in bipolar disorder.
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Retinoic acid (RA) and its parent compound, retinol (ROH, vitamin A), have been recognized as important immunopotentiating agents. Previous studies from our laboratory have demonstrated that RA can augment formalin-treated Staphylococcus aureus (SAC)-stimulated immunoglobulin (Ig) synthesis of cord blood mononuclear cells (CBMC). To determine the mechanism(s) by which RA modulates Ig synthesis, we studied the effects of RA on B cells and cytokine production. The addition of RA (10(-5) to 10(-10) M) to Epstein-Barr virus (EBV)-transformed B-cell clones derived from either adult or cord blood B cells augmented Ig secretion twofold. In contrast, cell proliferation was inhibited as measured by 3H-thymidine incorporation. We evaluated two cytokines known to be constitutively produced by EBV cell lines, IL-1 and IL-6. While RA had no effect on IL-1 production, IL-6 synthesis was greatly enhanced (20- to 45-fold), which was also reflected by an increase in steady-state mRNA levels for IL-6 but not TNF-alpha or TGF-beta on Northern blot analysis. Polyclonal rabbit anti-IL-6 antibodies were used to block the augmenting effects of RA on Ig synthesis of adenoidal B cells. RA-induced augmentation in IgG and IgA synthesis was blocked 58 and 29%, respectively, by anti-IL-6 antibodies. These studies suggest that the enhancing effects of RA on Ig synthesis are mediated, at least in part, by the autocrine or paracrine effects of IL-6 on B-cell differentiation.
Treatment of nasal septal deformity in childhood has received growing acceptance in recent years. Traditionally, concern about the role of the septum in the overall growth of the midface has led otolaryngologists to take a very cautious approach to correction of septal deformities in children. However, a great deal of evidence now suggests that severe traumatic septal deviation can and should be corrected early in childhood to prevent future nasal and systemic complications. Closed manipulation of the septum in the first 1-2 days of an infant's life has been performed by many otolaryngologists with good results. The use of this technique, however, is usually limited to those subluxations of anterior cartilage which are diagnosed immediately or very shortly after birth. We present a case of severe traumatic nasal deformity presenting with obstructive asleep and awake apnea and cyanosis at the age of 8 days. The child underwent limited septoplasty using endoscopic techniques at age 14 days with resolution of both the apneic and cyanotic episodes immediately post-operatively. This unusual presentation and the literature surrounding infant nasal/septal surgery are discussed.
Congenital stridor is a common problem that has many very different etiologies. A complete history and physical examination will allow the astute clinician to direct the laboratory evaluation efficiently. Establishing a relationship with a specialist will be useful for consultation when considering a referral in questionable situa.
The cellular immune responses to nontypable Haemophilus influenzae in adenoids were determined in children by measuring lymphocyte blast transformation and antibody secretion in response to the P6 outer membrane protein. In the lymphocyte transformation assay, stimulation index of adenoid lymphocytes stimulated by P6 in otitis children (2.34 +/- 0.25) was significantly lower than that in non-otitis children (3.91 +/- 0.64, p <0.05). The number of IgM as well as IgA secreting cells after 8 days' culture with P6 were significantly smaller in otitis children (IgM: 7,534 +/- 2,843/10(6) lymphocyte; IgA: 1,573 +/- 620/10(6) lymphocyte) than those in non-otitis children (IgM: 12,994 +/- 2,533, p <0.05; IgA: 2,828 +/- 528, p <0.05). These data suggest that P6 protein is a target for the cellular immune response of the adenoid, and failure of adenoid lymphocytes to recognize it as a specific immunogen may be one of the causes of recurrent otitis media.
Tonsillectomy and adenoidectomy (T&A) is a common surgical procedure for which many different surgical techniques have been described. However, detailed information is lacking regarding complications or recovery rates for any particular procedure. A newly described technique for T&A, microbipolar dissection (MBPD) is being compared with cold knife dissection with suction cautery of bleeding vessels (CKC) in a prospective study of 200 children aged 2-16 years. Patients are randomly assigned and stratified by age-group into one of two treatment arms. Intraoperative and post-operative measures of T&A effectiveness relative to complications and patient recovery rate are being studied. The preliminary data presented here focus on the reliability of the measures and potential clinical relevance of the findings in 129 of these children, with anticipated confirmation of these tentative results after completion of the larger cohort. Thus far it appears that post-operative bleeding rates are significantly reduced, recovery rate is improved, and return to normal activities are all better in the MBPD patients. Although these data reflect small numbers of children and must be interpreted with caution, it appears that MBPD T&A holds great promise in reducing the morbidity associated with the CKC technique of T&A.
Lymphoid dendritic cells play an essential role in antigen presentation in primary immune responses and are believed to be important in normal healthy responses of the mucosal immune system. The microanatomical distribution of HLA-DR-positive/S100 antigen-positive dendritic cells was analyzed in 10 normal palatine tonsils. Tonsil biopsies were obtained from 8 normal children undergoing otolaryngological surgery for reasons completely unrelated to tonsil disease. Two samples of normal adult tonsil were also obtained. Standard immunohistochemical methods, with antigen retrieval, were used to detect cell surface markers in formalin-fixed and/or frozen tissue specimens. The clinical identification of these tonsils as normal was confirmed by their microscopic appearance. HLA-DR antigen expression was restricted to lymphocytes, macrophages and dendritic cells; all normal epithelia were negative. S100-positive dendritic cells were readily detected in surface and crypt epithelium and were rare in submucosal sites or follicles. T cells were observed as frequently as dendritic cells in epithelial sites. Dendritic cell density was highest in extrafollicular T cell areas, where CD4-positive lymphocytes were especially abundant. A significant correlation was observed between the total number of different bacterial species isolated from individual normal tonsils and the frequency of dendritic cells in both the crypt epithelium and extrafollicular T cell areas. The number of dendritic cells at the tonsil surface was not similarly related to the bacterial flora.
Thirty-one children, 2.6-12.2 years (mean = 7.9 +/- 5.0) were divided into four clinical categories: normal controls (n = 7), recurrent tonsillitis (n = 8), idiopathic tonsillar hyperplasia (n = 9) and recurrent tonsillitis with hyperplasia (n = 7). Immunohistopathologic studies were performed to determine the presence and location of HLA-DR, S-100 positive antigen presenting dendritic cells (DCs) in six microanatomic compartments: surface and crypt epithelium and submucosae, extrafollicular areas and lymphoid follicles. The results were analyzed in the context of the clinical history, bacteriology, and routine histopathology. The distribution of DCs was altered significantly with disease fewer numbers of DCs were found in the surface epithelium and greater numbers in the crypts and extrafollicular areas, than in normals, p <0.01. The surface : crypt ratio of DCs was 1:1 for normal tonsils, but dropped to 1:3 in disease. Chronic cryptitis was more common in disease and correlated strongly to the presence of beta-lactamase producing microorganisms (R = 1.0). An increased total bacterial concentration was correlated with increased numbers of DCs in the surface epithelium (R = 0.5, p <0.009). In summary, the microanatomical distribution of DCs within the tonsil is significantly altered in disease. These alterations appear to be influenced by potentially pathogenic bacteria more often found in the crypts of abnormal tonsils.
Craniofacial dysostosis (Crouzon syndrome) is a syndrome characterized by premature closing of calvarial and cranial base sutures as well as those of the orbit and maxillary complex. Orofacial manifestations of this disease include maxillary hypoplasia, external nasal deformity, and prognathism. Airway distress is a well described feature of this syndrome, and both upper and lower airway obstruction may be present in the Crouzon syndrome. Obstructions in the upper airway have been reported secondary to septal deviation, midnasal and choanal abnormalities, and nasopharyngeal narrowing. This study presents a child with the Crouzon syndrome who required tracheotomy during the first 2 years of life for airway obstruction caused in the newborn period (first 6 months) by midnasal stenosis and laser (6 months to 2 years) compounded by soft palate obstruction at the level of the oro/hypopharynx. A review of the English language literature revealed one similar patient presentation but no comprehensive review of this subject. Previously reported airway anomalies are reviewed and airway management is discussed in patients with Crouzon syndrome.
As home care tracheotomy has become a viable option for children with long-term canulation, medical personnel are challenged to provide as safe an environment as possible out of the hospital for these children. The tools used in the training of the families and other caregivers have received little attention in the literature. This study describes the development of a home-care tracheotomy manual for parents. The use of appropriate content presented in an organized, informative and pleasing fashion at the appropriate reading level is stressed. The evaluation of the manual by parents with children who have a child with a tracheotomy is also described.
The effect of post-operative diet selection on the recovery rate of 100 children ages 3-17 years undergoing tonsillectomy and adenoidectomy (T & A) was studied. In the first 12 h after T & A children were allowed either a 'restricted' diet of only soft foods and liquids or a 'non-restricted' diet of foods preselected and usually eaten by the child. Parental evaluation of the child's general well being, pain level and nausea were evaluated. The number of episodes of emesis, doses of acetominophen and the list of foods and drinks consumed were also recorded. No significant differences in any aspect of recovery were noted between groups. However, a trend towards decreased nausea and parental perception of a more successful general recovery was noted at 12 h in the 'non-restricted' group. Children in the 'non-restricted' group were able to eat foods more often associated with their regular diet. No child from either group experienced any immediate or delayed complications. Implications for children and their families undergoing T & A are discussed.
Tonsillar tissue lymphocyte (TTL) function as measured by immunoglobulin production was assessed in vitro in 60 tonsils, 51 diseased and 9 normal controls. The diseased specimens were from children (aged 3 to 10 years) clinically classified as having recurrent tonsillitis (RT), idiopathic tonsillar hyperplasia (ITH), or recurrent tonsillitis with hyperplasia (RT/H). TTLs were challenged with intact, heat-inactivated bacteria found in the core of diseased tonsils--Streptococcus pyogenes (SP) and Haemophilus influenzae type B (HIB) as well as the dominant bacterium (DB) grown from that particular tonsillar core. The phytomitogen, leukoagglutinin (LA), was used as a nonspecific activator. Qualitative immunoglobulin production was assessed for the immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) classes. Immunoglobulin-specific production was quantified at the basal level, and at 2, 4, and 6 days following stimulation. Stimulation with HIB produced the greatest amount of IgG and IgM in TTLs from control tonsils. The DB was a relatively weak stimulator of normal (control) TTLs, yet produced relatively brisk IgG responses in the RT and ITH categories. It did, however, yield only marginal IgM secretion in these groups. IgA was consistently produced after stimulation in diseased TTLs, yet was not elicited from normal TTLs. The aforementioned findings suggest a differential qualitative and quantitative immunoglobulin response for healthy, recurrently infected, and hyperplastic tonsils. Lymphocyte hypofunction along with structural changes associated with hyperplasia may be central to the etiology of chronic tonsillar disease. The tonsillar immunologic response in disease and health is discussed.
The risk of hemorrhage after tonsillectomy and adenoidectomy (T + A) was studied in 1061 children. Twenty-seven (2.5%) had at least one abnormality on a preoperative coagulation profile consisting of a prothrombin time (PT), partial thromboplastin time (PTT), bleeding time (BT) and platelet count (PC). Of these 27 who had an initially abnormal test (PTT or bleeding times only), 8 had diagnosed coagulopathies by hematology evaluation (Group A), and 17 had repeat tests which returned to normal (Group B). Two borderline tests (PTT) were not repeated (Group C). Sixty-four patients (6.0%) bled after T + A. Six of these (9.3%) had an initially abnormal coagulation profile--one in Group A (12.5%), four in Group B (23.5%) and 1 in Group C (50%). This is in contrast to the bleed rate of 5.7% for the 1034 children with normal coagulation profiles. Although it is not surprising that 6 (22.2%) children with an initially abnormal coagulation profile bled, of note is that 4 of them had an initially abnormal coagulation profile which upon repeat testing returned to normal. However, none of these four bleeders required active intervention for control. Coagulopathies were newly diagnosed in 7 (0.57% of total group; 25.9% of 27 with abnormal laboratory values). One additional child had a known intrinsic platelet dysfunction prior to surgery. Only one child was newly identified by a positive family history for abnormal bleeding. These results suggest that new hematologic disorders were diagnosed infrequently. An initially abnormal coagulation profile may identify those more likely to bleed after surgery (22.6% vs. 5.5%). A coagulation profile which includes a PTT and BT may be a valuable screening tool for children undergoing T + A.
Needle aspiration for the treatment of peritonsillar abscess was assessed in 43 consecutive children aged 7 to 18 years (mean age, 13.9 +/- 2.5 years) during the 3-year period from 1988 through 1991. A positive aspirate was obtained in 31 (76%) of the 41 patients who cooperated for needle aspiration; a mean of 2.9 +/- 1.9 mL of pus was withdrawn. Of the 31 children with a positive aspirate, in 27 (87%) the abscess resolved, two (6%) required a second aspiration for resolution, and two (6%) underwent immediate tonsillectomy for persistent abscess. Of the 10 children (24%) with negative aspirations, in six (60%) the abscess resolved with antibiotic treatment alone, three (30%) underwent immediate (quinsy) tonsillectomy, and in one (10%) the abscess spontaneously drained. No bleeding, airway obstruction, or anesthetic complications occurred. Needle aspiration of peritonsillar abscess in children, with tonsillectomy reserved for nonresponders, appears to be an efficacious and safe method of treatment.
Adenoid physiology as reflected in the qualitative and quantitative bacteriology and immune cell distribution was correlated with clinical presentation in 69 children (16 to 130 months of age) undergoing adenoidectomy for obstructive adenoid hyperplasia (n = 38) or chronic adenoid infection (n = 31) and in 16 adenoid core biopsy specimens from 16 nondiseased controls. In the control adenoids, few potentially pathogenic bacteria were found as the dominant bacteria in the adenoid core (25%), and significantly greater concentrations of nonpathogens (commensals) were isolated (P < .01). Potential pathogens as the dominant bacteria were found twice as often in obstructive adenoid hyperplasia (62%) and in chronic adenoid infection (55%) (P < .05). Haemophilus influenzae was most common in the diseased adenoids, 53% in obstructive adenoid hyperplasia and 48% in chronic adenoid infection, compared with only 19% in the controls (P < .05). No significant differences in lymphocyte density, B and T cells, as well as T-helper subsets, were found between clinical classifications. However, T-suppressor cells, monocytes-macrophages, and natural killer cells were significantly increased in chronic adenoid infection only (P < .05). The findings in this study support roles for both alterations in bacterial homeostasis and an altered immune profile in the etiology of chronic adenoid disease in children.
The effect of postoperative diet and activity instructions on the recovery rate after tonsillectomy and adenoidectomy (T & A) was assessed in 92 children ages 3 to 14 years. Two types of postoperative instruction were randomly assigned: 'Restricted', which advised limited, stay at home activities and a soft food liquid diet for 7-10 days, and 'nonrestricted', which advised return to activity and diet as tolerated by the child. Parental evaluation of the levels of pain, activity, and diet using an equal intervals scale was obtained. The number of doses of pain medication, the types of food eaten and postoperative complications were also recorded. No significant differences were found between the two groups in pain level, activity tolerance, return to normal diet, and numbers of doses of pain medication at day 3 and day 7 after surgery. More 'junk' food and spicy foods were eaten in the 'nonrestricted' group. Postoperative hemorrhage requiring intervention occurred in one child in each group. Implications for the children and their families undergoing T & A are discussed with attention to a review of the literature.
A prospective, randomized, double-blind study to determine the postoperative efficacy of steroids in tonsillectomy was performed in 49 children. A single dose of intravenous dexamethasone or placebo was administered after each child was anesthetized. Postoperatively each child was examined for objective signs of trismus (measured by interincisor distance), temperature elevation, and weight loss, as well as for subjective signs of mouth odor, oral intake, pain, level of activity, and analgesic usage. There were no statistical differences noted in any of the variables compared in the two groups and the complication rates were also similar.
Tonsillar tissue lymphocyte (TTL) function as measured by lymphocyte proliferation was assessed in vitro in 38 tonsils--30 diseased and 8 normal controls. TTLs from diseased and control tonsils were challenged with intact, heat-inactivated bacteria which may be found in the core of diseased tonsils; these bacteria were Streptococcus pyogenes and Hemophilus influenzae type B (HIB), as well as the dominant bacterium (DB) grown from that particular tonsillar core. The phytomitogen leukoagglutinin (LA) was used as a nonspecific activator. Lymphocyte proliferation was quantified and reported using a stimulation index (SI) which was based upon viable cell counts at 2, 4, and 6 days following inoculation. Overall, the greatest degree of lymphocyte proliferation in diseased TTLs (SI = .91) was produced by HIB. However, both SP and HIB produced more lymphocyte proliferation in the nondiseased TTLs than in the diseased TTLs (P < .01). H influenzae (non-B) and group A beta-hemolytic streptococci were the pathogens most frequently cultured as the dominant bacteria from the core of diseased tonsils; Streptococcus viridans was most frequently cultured in nondiseased tonsils. The DB caused greater TTL proliferation in diseased (SI = .89) versus control (SI = .63) TTLs (P < .001). These findings suggest a differential proliferative response in vitro for diseased and nondiseased TTLs in response to specific bacteria. The role of possibly pathogenic bacteria and commensals, as well as the implications for clinical disease, are discussed.