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Biomedical subjects

C M Ward

Publications and source records attributed to C M Ward.

At least 19 recordsLinked to original sources

Identification of aspartic acid 514 through glutamic acid 542 as a glycoprotein Ib-IX complex receptor recognition sequence in von Willebrand factor. Mechanism of modulation of von Willebrand factor by ristocetin and botrocetin.

As the first step in hemostasis, the binding of von Willebrand factor (vWF) to the platelet membrane glycoprotein (GP) Ib-IX complex is essential for platelet adhesion at high-shear blood flow. This interaction in vivo requires the prior binding of vWF to the subendothelial matrix, a process which exposes a normally cryptic binding site on vWF for the GP Ib-IX complex. This process can be mimicked in vitro by modulators such as ristocetin or the snake venom protein botrocetin or by desialation of vWF. We have previously localized the GP Ib binding site on vWF to a monomeric dispase fragment which extends from Leu-480/Val-481 to Gly-718 in the primary sequence of mature vWF [Andrews, R. K., Gorman, J. J., Booth, W. J., Corino, G. L., Castaldi, P. A., & Berndt, M. C. (1989) Biochemistry 28, 8326-8336]. This fragment also contains a distinct binding site for botrocetin. Analysis of synthetic peptides corresponding to hydrophilic stretches of sequence within this fragment indicated that the sequence Asp-514-Glu-542 represents a major adhesive sequence involved in receptor recognition. This peptide inhibited both the ristocetin- and botrocetin-mediated binding of vWF to either platelets or purified GP Ib-IX complex (IC50 approximately 50-200 microM) as well as the asialo-vWF- and bovine vWF-dependent agglutination of platelets. Both the N- and C-terminal halves of the peptide were inhibitory but less so than the intact peptide. This peptide also inhibited botrocetin binding to vWF, suggesting that botrocetin modulates vWF-GP Ib interaction by binding in close proximity to the vWF adhesion sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

New grafts for old? A review of alternatives to autologous skin.

Immediate resurfacing of skin defects is a challenging prospect, especially in patients with extensive full-thickness burns. Currently, split-thickness autografts offer the best form of wound coverage, but limited donor sites and their associated morbidity have prompted the search for alternatives. The application of allogeneic skin is restricted by availability and the risk of transmission of infection, whilst synthetic skin substitutes are simply expensive dressings. The problems of limited expansion may be overcome by culturing keratinocytes in vitro. Unlike autologous cells, allogeneic keratinocytes are available immediately, although they survive for less than a week when applied to full-thickness skin defects. Moreover, the absence of a dermal component in these grafts predisposes to instability and contracture. A cross-linked collagen and glycosaminoglycan dermal substitute, covered with thin split-skin grafts or cultured autologous keratinocytes, shows promise in burns patients. An alternative is a collagen matrix populated by allogeneic fibroblasts and overlaid with cultured autologous or allogeneic keratinocytes. The clinical application of cultured grafts remains imperfect but offers the prospect of immediate coverage and massive expansion.

Culture Techniques

Hypoglycaemia in insulin dependent diabetic patients attending an outpatients' clinic.

One hundred and fifty-eight patients with insulin dependent diabetes mellitus attending two Auckland outpatient clinics answered a questionnaire about hypoglycaemia. Almost all (98%) had experienced hypoglycaemic episodes and for 30% these were a major problem. Seventy-seven percent reported nocturnal hypoglycaemia, 39% of whom required external assistance during episodes. Forty-three percent had experienced coma, or convulsions during hypoglycaemia and a small group, 7%, had recurrent severe episodes. Twenty percent carried no diabetic identification and 13% did not routinely carry a glucose supply. Only 38% of patients kept glucagon at home. Forty percent of patients driving vehicles had experienced hypoglycaemia while driving and 13% reported traffic accidents attributed to hypoglycaemia. Hypoglycaemia is a major problem for many patients taking insulin. Improved education, wider availability of glucagon and more liberal glycaemic control of patients with problematic hypoglycaemia may be advisable.

Adolescent

Surgery of 346 patients with unoperated cleft lip and palate in Sri Lanka.

By means of a surgical expedition involving an independently financed team of surgeons, anesthetists and nurses, 410 operations were performed on 346 patients in the course of 52 operating days. This paper describes the preoperative, operative, and postoperative scenarios and how clinical practice was tailored to adapt to a new environment without compromising standards. The differences between operating on the lip and palate in the adult compared to younger children are highlighted. The clinical research implications are more evident from other papers on this topic published in this journal, but the enlightenment of working and teaching in a third world country cannot be underestimated.

Adolescent

Surgery of cleft lip and palate in Sri Lanka.

By means of a surgical expedition involving an independently financed team of surgeons, anaesthesists and nurses, 410 operations were performed on 346 patients in the course of 52 operating days. This paper simply outlines the preoperative, operative, and postoperative scenarios and how clinical practise was tailored to adapt to a new environment without compromising standards.

Adolescent

Surgical treatment of grade III gynaecomastia.

Gross enlargement of the male breast with skin redundancy and ptosis cannot be effectively managed by subcutaneous mastectomy alone. A technique is described in which the excess breast tissue and skin are excised along a design which allows the nipple-areolar complex, mounted on a vertical deepithelialised pedicle, to lie in a natural position. A horizontal scar is an unavoidable exchange for this particular operation.

Gynecomastia

Sri Lankan cleft lip and palate project: a preliminary report.

By means of a surgical expedition involving an independently financed team of surgeons, anaesthetists, nurses, orthodontists and speech therapists, 195 patients in Sri Lanka with cleft lip and palate were treated over a period of 4 weeks while over 300 patients were examined in detail to assess faciomaxillary growth, components of speech and the psychosocial impact of the untreated deformity in childhood and adult life. Lip surgery proved to be simple and safe but in certain older patients palatal closure was complicated by wide palatal shelf displacement, mucosal fibrosis and heavy bleeding. This is a preliminary report and much data has yet to be analysed but there is little doubt that impaired facial growth following palatal repair is predominantly an iatrogenic deformity.

Adolescent

An abnormality of nail growth associated with median nerve damage.

It has been recognised for a long time that damage to the median or ulnar nerves is usually followed by slowing of growth of the fingernails. In the past, this has always been ascribed to immobilization of the appropriate digits, rather than to a neurotrophic factor. No other nail changes appear to have been described in association with nerve damage. We present two patients with marked nail changes following median nerve injury, in which immobilization does not appear to be responsible.

Adolescent

The uses of external nipple-areola prostheses following reconstruction of a breast mound after mastectomy.

Following reconstruction of the breast after mastectomy it is common practice to allow a "settling" period before grafting the nipple-areola complex. A selection of external nipple-areola prostheses are described which can be used until surgical reconstruction can be carried out and which are helpful in determining the correct position of the nipple-areola grafts. It has been found that some patients actually prefer to use the prostheses permanently for dress purposes rather than undergo an additional operation.

Breast

Rhinophyma.

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Aged

An analysis, from photographs, of the results of four approaches to elongating the columella after repair of bilateral cleft lip.

A system for subjective and objective clinical analysis of the lower third of the nose before and after lengthening the columella was devised, and used the study of photographs of 77 patients who had had lengthening done by one of 4 approaches. It was found that each method was equally effective in lengthening the columella and in restoring a normal relationship between the structures in the tip of triangle (the basal view of the nose). However, there were certain peculiar advantages and disadvantages of each surgical technique, and these are discussed.

Adolescent