Cephalometric templates based on the Bolton standards

An accurate, simple, rapid method of cephalometric profile analysis is proposed. Templates, derived photographically from the 9-year through 18-year male-female Bolton standard tracings, are used to define the optimal locations for any selected hard or soft tissue dentofacial landmarks. Discrepancies between the ideal and actual positions of each landmark are immediately apparent and graphically reveal existing deformities. No tracing or measurements are required, as the analysis is performed directly on the patient's cephalogram. The construction of the templates and their application to clinical cases are described.     

Nasal glomangioma

Glomus tumours have been reported in various sites viz. skin, subcutaneous tissue, muscle and viscera. The involvement of nasal mucosa by this lesion is extremely rare. A rare case of Glomangioma involving nasal mucosa in a 19 year old male presenting as nasal obstruction and painless bleeding is described and the pertinent literature is reviewed.     

Modification of estrone at the 6, 16, and 17 positions: novel potent inhibitors of 17beta-hydroxysteroid dehydrogenase type 1

The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) catalyze the interconversion between the oxidized and reduced forms of androgens and estrogens at the 17 position. The 17beta-HSD type 1 enzyme (17beta-HSD1) catalyzes the reduction of estrone to estradiol and is expressed in malignant breast cells. Inhibitors of this enzyme thus have potential as treatments for hormone dependent breast cancer. Here we report the syntheses and biological evaluation of novel inhibitors based on the estrone or estradiol template. These have been investigated by modification at the 6, 16 or 17 positions or combinations of these in order to gain information about structure-activity relationships by probing different areas in the enzyme active site. Activity data have been incorporated into a QSAR with predictive power, and the X-ray crystal structures of compounds 15 and 16c have been determined. Compound 15 has an IC50 of 320 nM for 17beta-HSD1 and is selective for 17beta-HSD1 over 17beta-HSD2. Three libraries of amides are also reported that led to the identification of inhibitors 19e and 20a, which have IC50 values of 510 and 380 nM respectively, and 20 h which, having an IC50 value of 37 nM, is the most potent inhibitor of 17beta-HSD1 reported to date. These amides are also selective for 17beta-HSD1 over 17beta-HSD2.     

Influence of aggregation on immunogenicity of recombinant human Factor VIII in hemophilia A mice

Recombinant human factor VIII (rFVIII), a multidomain glycoprotein is used in replacement therapy for treatment of hemophilia A. Unfortunately, 15%-30% of the treated patients develop inhibitory antibodies. The pathogenesis of antibody development is not completely understood. The presence of aggregated protein in formulations is generally believed to enhance the immune response. rFVIII has a tendency to aggregate but the effect of such aggregation on the immunogenicity of rFVIII is not known. We have, therefore, characterized aggregated rFVIII produced by thermal stress and evaluated its effect on the immunogenicity of rFVIII in hemophilia A mice. Aggregated rFVIII alone and mixtures of rFVIII with aggregated rFVIII were less immunogenic than native rFVIII. In vitro Th-cell proliferation studies and cytokine analyses conducted on splenocytes obtained from immunized animals suggest that aggregated rFVIII behaves as a unique antigen compared to native monomeric rFVIII. The antigenic properties of the aggregated and native rFVIII were compared using ELISAs (epitope availability) and cathepsin-B (an antigen processing enzyme) digestion. The data suggest significant differences in the antigenic properties of rFVIII and aggregated rFVIII. Overall it appears that aggregated rFVIII does not enhance the immunogenicity (inhibitor development) of rFVIII in hemophilia A mice but rather acts as a distinct antigen.     

Electrolyte disturbances in acute diarrhoea

Summary A clinical and biochemical study of 100 cases of acute diarrhoea in infancy was done. 75 cases each showed low serum values of sodium and potassium, and chloride was low in 59% and bicarbonate in 66%. Blood urea was raised in 53 cases. From the Department of Pediatrics. Guntur Medical College, Guntur, A.P.     

Exemestane in metastatic breast cancer: effective therapy after third-generation non-steroidal aromatase inhibitor failure

Exemestane is a potent steroidal aromatase inhibitor (AI) with activity in post-menopausal women with metastatic breast cancer, with a reported clinical benefit (CB) rate of 24.3% after prior AI therapy. Data on 114 patients (112 female, 2 male) were obtained retrospectively at two cancer centres. Sixty-five percent of patients were confirmed as oestrogen receptor (ER) positive. All patients had received prior third-generation AI therapy. Responses were seen in 5% and the overall CB rate (CR+PR+SD24 weeks) was 46%. Median PFS and OS were 18 and 61 weeks, respectively. In patients with visceral disease, the CBR was 33%. Patients with known ER-positive disease had a CBR of 47%, and a median TTP of 19 weeks. No benefit was seen in patients with known ER-negative disease. Survival was better in those with CB (median survival not reached in those with CB, 28 weeks in those without CB P<0.0001). Efficacy persisted in those patients who had received 3 prior lines of hormonal therapy, including adjuvant treatment. These data confirm exemestane to be an effective therapy after third-generation non-steroidal AI in post-menopausal ER-positive metastatic breast cancer, including visceral disease.     

Death following external carotid artery embolization for a functioning glomus jugulare chemodectoma. Case report.

A 24-year-old man with left sixth through twelfth cranial nerve palsies and severe, fluctuating, systemic arterial hypertension was found to have a large, vascular, catecholamine-forming glomus jugulare chemodectoma. After his electrolyte imbalance was corrected, left external carotid embolization (using Gelfoam) was carried out. The systemic blood pressure stabilized at around 160/100 mm Hg over the next 12 hours. Ten hours later the hitherto conscious patient developed acute arterial hypotension, lapsed into coma, and died. Autopsy showed tumor infarction, swelling, cerebellar tonsillar herniation, and medullary compression. An unusual complication of glomus tumor embolization is highlighted. The roles of preliminary decompressive surgery and urgent resuscitation by vasopressors are discussed.