Identification of accessory bile ducts at cholecystectomy

The presence of accessory channels between the liver and extrahepatic bile ducts has long been recognised by anatomists and the division of such ducts may be a cause of bile leakage following cholecystectomy. However, visualisation of accessory bile ducts at operation is difficult as they are often small and sometimes less than 1 mm in diameter. Cholangiography has been used to help in the identification of accessory ducts in 50 patients included in a prospective trial. X-rays were taken after dissection of the gall bladder from its bed and extravasation of contrast was seen on five occasions (10%) suggesting leakage from divided accessory ducts. The identification of damage to accessory bile ducts in 10% of patients suggests that this may occur more frequently than previously supposed.     

Preparation of protected peptidyl thioester intermediates for native chemical ligation by Nα‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry: considerations of side‐chain and backbone anchoring strategies,and compatible protection for N‐terminal cysteine*,†

Abstract: Native chemical ligation has proven to be a powerful method for the synthesis of small proteins and the semisynthesis of larger ones. The essential synthetic intermediates, which are C‐terminal peptide thioesters, cannot survive the repetitive piperidine deprotection steps of N^α‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry. Therefore, peptide scientists who prefer to not use N^α‐t‐butyloxycarbonyl (Boc) chemistry need to adopt more esoteric strategies and tactics in order to integrate ligation approaches with Fmoc chemistry. In the present work, side‐chain and backbone anchoring strategies have been used to prepare the required suitably (partially) protected and/or activated peptide intermediates spanning the length of bovine pancreatic trypsin inhibitor (BPTI). Three separate strategies for managing the critical N‐terminal cysteine residue have been developed: (i) incorporation of N^α‐9‐fluorenylmethoxycarbonyl‐S‐(N‐methyl‐N‐phenylcarbamoyl)sulfenylcysteine [Fmoc‐Cys(Snm)‐OH], allowing creation of an otherwise fully protected resin‐bound intermediate with N‐terminal free Cys; (ii) incorporation of N^α‐9‐fluorenylmethoxycarbonyl‐S‐triphenylmethylcysteine [Fmoc‐Cys(Trt)‐OH], generating a stable Fmoc‐Cys(H)‐peptide upon acidolytic cleavage; and (iii) incorporation of N^α‐t‐butyloxycarbonyl‐S‐fluorenylmethylcysteine [Boc‐Cys(Fm)‐OH], generating a stable H‐Cys(Fm)‐peptide upon cleavage. In separate stages of these strategies, thioesters are established at the C‐termini by selective deprotection and coupling steps carried out while peptides remain bound to the supports. Pilot native chemical ligations were pursued directly on‐resin, as well as in solution after cleavage/purification.     

Danazol administration after gonadotrophin-releasing hormone analogue reduces rebound of uterine myomas [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

We report the results of administration of danazol after suspension of gonadotrophin-releasing hormone analogue (GnRHa) therapy for uterine myomas. A total of 21 women with uterine myomas was treated with 100 mg danazol for 6 months after GnRHa therapy. Uterine volume and endocrine status were monitored monthly by ultrasound and assay of plasma gonadotrophins, oestradiol and progesterone. The results show a rebound of uterine volume about 30% less than in controls at the end of danazol therapy. Menstrual cyclicity returned after 65 +/- 3 days in 16 subjects and five patients remained amenorrhoeic. Hormone assays confirmed renewed ovarian function in the women whose menstrual periods returned. Bone mineral content was substantially reduced during GnRHa treatment but improved significantly during danazol therapy even in the women who remained amenorrhoeic. These results show the utility of danazol in prolonging the therapeutic effects of GnRHa. The mechanism by which danazol inhibits rebound of uterine volume may be due to its antiprogesterone effects on uterine myomas.      

Direct evidence that primary acquired cell-mediated immunity is less resistant than is primary thymus-dependent humoral immunity to the depressive influence of wasting protein-energy malnutrition in weanling mice.

Wasting protein-energy malnutrition (PEM) was induced in male C57BL/6J mice fed a low-protein diet ad libitum from 23 to 37 d of age. In comparison with a complete diet, the low-protein formulation reduced delayed hypersensitivity to sheep red blood cells (SRBCs) assessed on day 14 of feeding by measuring increased footpad thickness (mean +/- SD: 4 +/- 4% vs 22 +/- 8%, P less than 0.01), after immunization on day 9, and after challenge with SRBCs on day 13. By contrast, the low-protein diet did not affect the anti-SRBC hemagglutinin titer (8.3 +/- 2.2 vs 9.1 +/- 1.1, P greater than 0.30) despite profound reduction in numbers of splenic plasma cells secreting IgM-class anti-SRBCs (7.3 +/- 3.1 vs 49.9 +/- 23.8 x 10(-3), P less than 0.001), after immunization on day 9 and assessment on day 14. Thus, direct experimental evidence, previously altogether lacking, is provided in support of the concept, central to nutritional immunology, that acquired cell-mediated immunity is less resistant than is systemic humoral immunity to the depressive influence of pre-adolescent, wasting PEM.