The tarsal pillar technique for narrowing and maintenance of the interpalpebral fissure.

We describe a tarsorrhaphy technique whereby an ipsilateral upper-eyelid tarsal pillar is sutured to a corresponding lower-eyelid recipient site. This technique allows maintenance of a narrowed interpalpebral fissure indefinitely, yet is easy to reverse without incurring lid-margin damage. Additionally, the procedure can be adjusted postoperatively to either narrow or widen the initial surgical result. We report our combined surgical experience in 35 consecutive procedures using this technique to treat eyes with exposure-related keratopathy of varied etiology, including facial nerve palsies, combined facial nerve palsy and trigeminal neuropathy with an anesthetic cornea, Graves' disease, congenital craniofacial anomalies, and severe keratitis sicca syndrome. The procedure was successful in improving exposure keratopathy symptoms in all 35 cases. Complications, reflecting the authors' learning curve with this new procedure, included intermarginal pyogenic granulomas, stretching of the tarsal pillar, minor lower-eyelid-margin eversion, and tarsal pillar dehiscence.     

Adenomyosis:common and uncommon manifestations on sonography and magnetic resonance imaging.

OBJECTIVE: The purpose of this presentation is to show the imaging findings of the common and uncommon variants of adenomyosis as seen on sonography and magnetic resonance imaging (MRI). METHODS: A 3-year database search was performed to identify women who had pelvic sonography and pelvic MRI within a 6-month interval. Images of these cases were retrospectively reviewed. RESULTS: Eighty women were identified. Adenomyosis was diagnosed on MRI, which was used as the reference standard, in 45 of these women. The correct diagnosis was made on sonography in 73% of the cases. CONCLUSIONS: Awareness of the spectrum of imaging features of adenomyosis is important to use sonography effectively for diagnosing this entity and to help avoid misdiagnosis.     

Blepharochalasis.

Blepharochalasis is an uncommon disorder distinguished by recurrent episodes of eyelid oedema in young patients. A hypertrophic form, manifested as fat herniation, and an atrophic form, manifested as fat atrophy, have been described. Ptosis with excellent levator function, laxity of the lateral canthal structures with rounding of the lateral canthal angle, nasal fat pad atrophy, and redundant eyelid skin develop after many episodes of eyelid swelling. Fine wrinkling, atrophy, and telangiectasias characterise the excess eyelid skin. We describe four cases of this syndrome in which external levator aponeurosis tuck, blepharoplasty, lateral canthoplasty, and dermis fat grafts were used to correct atrophic blepharochalasis after the syndrome had run its course.     

Normal or early development of puberty despite gonadal damage in children treated for acute lymphoblastic leukemia

To determine the timing of pubertal development and the frequency of gonadal dysfunction in children who survive acute lymphoblastic leukemia, we assessed pubertal status and the plasma levels of sex steroids, gonadotropin, and inhibin in 45 children (20 girls and 25 boys) who had received combination chemotherapy along with 24 Gy of irradiation to the cranium (modified LSA2L2 protocol). We also reexamined testicular biopsy specimens, obtained at the time of the cessation of chemotherapy, for the presence of germ cells. Germ-cell damage, indicated by marked elevations in the plasma level of follicle-stimulating hormone (P less than 0.001 for the comparison with normal children), was evident in both sexes and was confirmed in the boys by the absence of germ cells in the testicular biopsy specimens and by the small size of the testes for pubic-hair stage. Only 44 percent of the pubertal girls had measurable plasma inhibin levels, as compared with more than 93 percent of normal pubertal girls. Although plasma sex-steroid levels were normal, the secretion of luteinizing hormone in response to stimulation with gonadotropin-releasing hormone was elevated in the pubertal children (P less than 0.01 for the comparison with normal controls)--a finding that suggests compensation for decreased gonadal function. Despite clear evidence of gonadal damage, girls had early menarche at a mean age (+/- SD) of 11.95 +/- 0.91 years, as compared with the Australian standard of 12.98 +/- 1.11 years (P less than 0.01). Thus, in girls, puberty was early despite primary gonadal damage. Thirteen of 23 boys reached puberty at a mean age of 12.36 +/- 0.73 years. We conclude that treatment for acute lymphoblastic leukemia may lead to primary gonadal damage in both sexes, regardless of the age at treatment, but that the secondary characteristics of puberty develop at a normal age or, in girls, relatively early.     

SHIP represses mast cell activation and reveals that IgE alone triggers signaling pathways which enhance normal mast cell survival

The hemopoietic specific, Src homology 2-containing inositol 5' phosphatase (SHIP) hydrolyzes the phosphatidylinositol (PI)-3-kinase generated second messenger, PI-3,4,5-trisphosphate (PIP(3)), to PI-3,4-bisphosphate (PI-3,4-P(2)) in normal bone marrow derived mast cells (BMMCs). As a consequence, SHIP negatively regulates IgE+antigen (Ag)-induced degranulation as well as leukotriene and inflammatory cytokine production. Interestingly, in the absence of SHIP, BMMCs degranulate extensively with IgE alone, i.e. without Ag, suggesting that IgE alone is capable of stimulating signaling in normal BMMCs and that SHIP prevents this signaling from progressing to degranulation. To test this, we compared signaling events triggered by monomeric IgE versus IgE+Ag in normal BMMCs and found that multiple pathways are triggered by monomeric IgE alone and, while they are in general weaker than those stimulated by IgE+Ag, they are more prolonged. Moreover, while SHIP prevents this IgE-induced signalling from progressing to degranulation or leukotriene production it allows sufficient production of autocrine acting cytokines, in part by activation of NFkappaB, to enhance BMMC survival. Interestingly, the activation of NFkappaB and the level of cytokines produced are far higher with IgE than with IgE+Ag. Moreover, IgE alone maintains Bcl-X(L) levels and enhances the adhesion of BMMCs to fibronectin and this likely enhances their survival still further.     

Differential association of phosphatases with hematopoietic co-receptors bearing immunoreceptor tyrosine-based inhibition motifs

A novel family of inhibitory co-receptors has been recently defined according to the presence in their intracytoplasmic domain of immunoreceptor tyrosine-based inhibition motifs (ITIM). In particular, this family includes a low-affinity receptor for IgG, FcγRIIB, which is widely expressed on hematopoietic cells, as well as killer cell inhibitory receptors (KIR) for major histocompatibility complex (MHC) class I proteins, expressed on both T and natural killer (NK) lymphocytes. FcγRIIB and KIR inhibitory function depends upon the tyrosine phosphorylation of their respective ITIM. Phosphorylated FcγRIIB and KIR ITIM bind the tandem SH2 tyrosine phosphatases, SHP-1 and SHP-2. Recently, FcγRIIB has been shown to associate with a polyphosphate inositol 5-phosphatase, SHIP, which appears to be involved in its inhibitory function. Using cell lysate adsorption to phosphorylated ITIM peptides and surface plasmon resonance, we demonstrate here that, in contrast to FcγRIIB, KIR (CD158b: p58.2) do not bind to SHIP, and only recruit SHP-1 and SHP-2. In addition, we show that point mutation of the amino acid residue in position tyrosine-2 of FcγRIIB and KIR ITIM abolihes their binding to SHP-1 and SHP-2, but leaves intact the association of SHIP with FcγRIIB ITIM. These data contribute to the structural definition of ITIM and document a differential recruitment of phosphatases by distinct ITIM. These findings also reveal that diverse strategies of inhibition are used by distinct members of the ITIM-bearing co-receptor family.     

Infectious influenza A and B virus variants with long carboxyl terminal deletions in the NS1 polypeptides

An influenza A virus, A/turkey/Oregon/71, was shown by protein gel analysis to code for an NS1 protein approximately half the size of those of other influenza A viruses. Sequence analysis of the NS gene of this virus revealed a 10 nucleotide deletion resulting in an NS1 protein of only 124 amino acids. This truncated NS1 polypeptide retained its karyophilic pattern as detected by indirect immunofluorescence analysis of virus infected cells. Also, A/turkey/Oregon/71 virus grew to high titer in embryonated chicken eggs comparable to other influenza A viruses. We also identified a laboratory variant of an influenza B virus, clone 201, which codes for a truncated NS1 protein. Sequence analysis revealed a 13 nucleotide deletion resulting in a shortened NS1 protein of only 127 amino acids as compared to other influenza B virus NS1 proteins possessing a length of 281 amino acids. Again as shown for the NS1 proteins of other influenza B viruses the NS1 polypeptide of B virus clone 201 was found to localize in the nucleus of infected cells. It appears that large deletions in the carboxyl terminus of the NS1 proteins of influenza A and B viruses can be tolerated without affecting the functional integrity of the NS1 polypeptide.     

Evaluation of a protocol for the non-operative management of perforated peptic ulcer

BACKGROUND: The non-operative management of perforated peptic ulcer has previously been shown to be both safe and effective although it remains controversial. A protocol for non-operative management was set up in this hospital in 1989. Adherence to the guidelines in the protocol has been audited over a 6-year period with a review of outcome. METHODS: The case-notes of patients with a diagnosis of perforated peptic ulcer were reviewed. Twelve guidelines from the protocol were selected for evaluation of compliance to the protocol. RESULTS: Forty-nine patients underwent non-operative treatment initially. Eight patients failed to respond and underwent operation. Complications included abscess formation (seven patients), renal failure (one), gastric ileus (one), chest infection (two), and cardiac failure and stroke (one). Four deaths occurred in this group. Adherence to certain protocol guidelines was poor, notably those concerning prevention of thromboembolism, use of antibiotics, use of contrast examination to confirm the diagnosis and referral for follow-up endoscopy. Two gastric cancers were detected on subsequent endoscopy. CONCLUSION: This experience demonstrates that non-operative treatment can be used successfully in a general hospital. Adherence to protocol guidelines was found to be variable and the protocol has therefore been simplified. This study highlights the need for an accurate diagnosis and the importance of follow-up endoscopy.