Search PubMed⌕ Search

Biomedical subjects

C M Lawrence

Publications and source records attributed to C M Lawrence.

At least 37 records · Page 2Linked to original sources

Treatment options for giant congenital naevi.

Giant congenital naevi (GCN) are disfiguring, potentially malignant pigmented naevi present at birth. The naevus cells in GCN are found throughout the dermis and sometimes penetrate the subcutaneous septa. It is claimed that superficial, more heavily pigmented and biologically different naevus cells reside in the upper dermis. Partial removal of these superficial naevus cells by dermabrasion, laser therapy, curettage or shave excision is less traumatic than excision surgery and produces an acceptable cosmetic result. However, none of these techniques or excision of GCN to superficial fat completely removes the risk of malignant transformation.

Humans↗

Anastomotic infections in lung transplant recipients.

OBJECTIVES: Anastomotic infections are an uncommon but potentially devastating complication after lung transplantation. The incidence, microbiology, predisposing factors, and clinical outcomes of anastomotic infections have not been well described. METHODS: We performed a retrospective chart review of the first 283 lung or heart-lung transplant recipients performed at Duke University Medical Center and identified all cases of anastomotic infection. RESULTS: Fifteen patients (5.3%) developed anastomotic infections. Aspergillus caused infection in six patients, Candida in eight patients and Staphylococcus aureus in one patient. Bilateral or right lung transplantation and the use of induction immunosuppression with monoclonoal or polyclonal antibodies are associated with a higher incidence of anastomotic infections. All patients with fungal anastomotic infections were treated with a combination of systemic and inhaled antifungal agents. All patients had improvement of their anastomotic sites after treatment and no patients developed anastomotic dehiscence. CONCLUSIONS: Anastomotic infection is an infrequent complication after lung transplantation, and is caused predominately by fungal pathogens. In contrast to previous reports, anastomotic dehiscence did not occur in any patient in our series. Treatment with the combination of inhaled and systemic antimicrobial agents may have favorably affected clinical outcomes.

Adult↗

Crystal structure of the ectodomain of human transferrin receptor.

The transferrin receptor (TfR) undergoes multiple rounds of clathrin-mediated endocytosis and reemergence at the cell surface, importing iron-loaded transferrin (Tf) and recycling apotransferrin after discharge of iron in the endosome. The crystal structure of the dimeric ectodomain of the human TfR, determined here to 3.2 angstroms resolution, reveals a three-domain subunit. One domain closely resembles carboxy- and aminopeptidases, and features of membrane glutamate carboxypeptidase can be deduced from the TfR structure. A model is proposed for Tf binding to the receptor.

Amino Acid Sequence↗

The long-term results of cartilage removal alone for the treatment of chondrodermatitis nodularis.

Cartilage excision alone has been demonstrated to be an effective technique in the treatment of chondrodermatitis nodularis (CDN), and in the short term is associated with an 80% cure rate. The objective of this study was to demonstrate that long-term disease control could be achieved using this surgical technique. Set in three hospital dermatology departments, 94 patients with CDN affecting the helix and antihelix were contacted by postal questionnaire at least 6 months after surgery. Replies were received from 77; 11 patients had died and six could not be traced. The main outcome measure was the identification of those patients in remission and those with disease recurrence. Sixty-two helix lesions were followed up for a mean of 52 months (range 8-99). There was recurrence in 10 patients (all men; 16%). Twenty antihelix lesions were followed up for a mean of 55 months (range 8-93). There was recurrence in five patients (all women; 25%). In conclusion, this study confirms that only cartilage needs to be excised for the long-term effective treatment of CDN. The only relevant aetiological factor identified was that all except one patient slept on the same side as the CDN. We believe that pressure on the ear during sleep causes CDN. This is most evident on the most protuberant part of the ear.

Adult↗

Mohs' micrographic surgery for basal cell carcinoma.

Mohs' surgery for basal cell carcinoma (BCC) is widely recommended by dermatologists as first line surgical therapy for recurrent or ill-defined skin tumours. The technique assumes that BCC spread by contiguous growth and that all tumour cells have to be removed. Advocates claim that Mohs' surgery provides a better chance of cure, and because less uninvolved tissue is excised the smaller defect can be readily closed resulting in a superior cosmetic result. This review examines the evidence for these claims.

Basal Cell Carcinoma↗

Rabbit antithymocyte globulin decreases acute rejection after lung transplantation: results of a randomized, prospective study.

STUDY OBJECTIVES: The efficacy of antithymocyte induction therapy in lung transplantation is controversial, and its use varies from center to center. We hypothesized that rabbit antithymocyte globulin (RATG) induction therapy would decrease acute rejection after lung transplantation, and we designed a single-center, randomized, prospective study to test this hypothesis. DESIGN: A total of 44 single or bilateral adult lung transplant recipients were randomly assigned to receive either RATG induction therapy (dosage, 1.5 mg/kg/d for 3 days) at the time of transplantation, along with conventional immunosuppression (cyclosporine, azathioprine, and prednisone), or conventional immunosuppression alone with no induction therapy. RESULTS: Although a similar number of biopsies were performed in each group, the number of patients experiencing biopsy-proven grade II or greater acute rejection was significantly reduced in the group receiving RATG induction therapy (23% incidence), as compared to the patients treated with conventional immunosuppression alone (55% incidence; p = 0.03). In addition, there was a nonsignificant reduction in the incidence of bronchiolitis obliterans syndrome at the conclusion of the study in patients who received RATG induction (20%), as compared to patients in the control group (38%). The incidence of posttransplant infections and malignancies were similar between the two groups. CONCLUSION: Induction therapy with RATG significantly reduces the incidence of acute allograft rejection after lung transplantation.

Acute Disease↗

A simplified protocol of steroid injection for psoriatic nail dystrophy.

Subjects seeking therapy for psoriatic nail dystrophy were recruited from routine clinics and involved digits were scored between 0 and 3 for severity of each of five features: subungual hyperkeratosis, pitting, onycholysis, ridging and thickening. These features were re-scored 2 months after injection of triamcinolone acetonide (0.4 mL, 10 mg/mL) into the nail bed and matrix following ring block, and then at 3-monthly intervals. A second injection was offered at 2 months if warranted by poor response. Forty-six digits were injected in 19 subjects (12 women, 7 men, mean age 48 years) receiving a mean of 1.2 doses. Follow-up ranged from 3 to 17 months (mean 9.4). Results are given for responses sustained up until the last follow-up. Onycholysis was present in 36 digits (78%) and improved in 18 (50%) of these. Pitting was present in 20 (43%), improving in nine (45%) and remaining unchanged in 11 (55%). Subungual hyperkeratosis was present in 16 (35%) and always improved after injection. Ridging was also present in 16 (35%) and improved in all but one instance. Thickening was present in 12 cases (26%), improving in 10 (83%) and remaining unchanged in the rest. Although onycholysis and pitting are the most common elements of psoriatic dystrophy we show that they are the least responsive to steroid injected in this fashion. However, subungual hyperkeratosis, ridging and thickening respond well, with benefit sustained for at least 9 months. When these are the dominant features of a nail dystrophy, treatment according to the protocol in this study appears justified.

Adult↗

Mohs' surgery of periocular basal cell carcinoma using formalin-fixed sections and delayed closure.

Mohs' surgery of periocular basal cell carcinoma (BCC) ensures a high cure rate with maximal preservation of normal tissue. The formalin-fixed paraffin-embedded tissue technique allows Mohs' surgery to be performed using routine pathology facilities and permits the efficient use of operating room personnel and theatre time. The inevitable delay between excision and closure may potentially result in a poor functional and cosmetic outcome, particularly around the eye. We prospectively studied all patients with periocular BCC treated with this technique at our unit between 1985 and 1996. One hundred and twenty-three periocular BCCs in 120 patients were treated. Microscopic clearance was achieved in all cases. Closure was performed on average 5 days after the initial excisional stage. Closing procedures included direct closure, flaps and grafts. Significant complications affecting outcome were noted in only two patients. Eighty-eight per cent of patients assessed had a functional and cosmetic result regarded as excellent, good or adequate. Mohs' surgery of periocular BCC using formalin-fixed paraffin-embedded tissue and delayed closure results in a satisfactory functional and cosmetic outcome and offers a viable alternative to the frozen section fresh tissue technique.

Adult↗

Acute infiltration by non-Hodgkin's B-cell lymphoma of lesions of disseminated herpes zoster.

A man with a 15-year history of non-Hodgkin's lymphoma presented with disseminated herpes zoster which initially responded to aciclovir. This was shortly followed by an acute exacerbation in the sites previously affected which was apparently resistant to antiviral therapy. Biopsy revealed a dense monomorphic lymphocytic infiltrate below active herpes zoster which had the same morphology and immunoreactivity as the underlying lymphoma. His clinical condition resolved with further chemotherapy for his lymphoma and continued treatment with aciclovir.

Herpes Zoster↗

Candidal anastomotic infection in lung transplant recipients: successful treatment with a combination of systemic and inhaled antifungal agents.

Anastomotic infection is an uncommon but potentially life-threatening complication after lung transplantation. We recently encountered three lung transplant recipients with invasive candidal anastomotic infection. Two patients were admitted with dyspnea and fever, and one asymptomatic infection was detected on surveillance bronchoscopy. All three patients were treated similarly with a combination of intravenous amphotericin B, inhaled amphotericin B, and oral fluconazole. The combination of systemic and inhaled antifungal agents successfully treated all three cases of anastomotic infection.

Administration, Inhalation↗

X-ray crystal structure of HLA-DR4 (DRA*0101, DRB1*0401) complexed with a peptide from human collagen II.

Genetic predisposition to rheumatoid arthritis (RA) is linked to the MHC class II allele HLA-DR4. The charge of the amino acid at DRbeta71 in the peptide-binding site appears to be critical in discriminating DR molecules linked to increased disease susceptibility. We have determined the 2.5 A x-ray structure of the DR4 molecule with the strongest linkage to RA (DRB1*0401) complexed with a human collagen II peptide. Details of a predicted salt bridge between lysine DRbeta71 and aspartic acid at the P4 peptide position suggest how it may participate in both antigen binding and TCR activation. A model is proposed for the DR4 recognition of collagen II (261-273), an antigen immunodominant in human-transgenic mouse models of RA.

Alleles↗

Structural determinants of nucleotide coenzyme specificity in the distinctive dinucleotide binding fold of HMG-CoA reductase from Pseudomonas mevalonii.

The 102-residue small domain of the 428-residue NAD(H)-dependent HMG-CoA reductase of Pseudomonas mevalonii (EC 1.1.1.88) binds NAD(H) at a distinctive, non-Rossmann dinucleotide binding fold. The three-dimensional structure reveals that Asp146 lies close to the 2'-OH of NAD-. To investigate the role of this residue in determination of coenzyme specificity, Asp146 was mutated to Ala, Gly, Ser, and Asn. The mutant enzymes were analyzed for their ability to catalyze the oxidative acylation of mevalonate to HMG-CoA using either the natural coenzyme NAD+ or the alternate coenzyme NADP+. Mutation of Asp146 to Ala or Gly increased the specificity for NADP+, expressed as the ratio of kcat/K(m) for NADP+ to kcat/K(m) for NAD+, 1200-fold (enzyme D146G) and 6700-fold (enzyme D146A). Mutation of Asp146 was accompanied by 565-fold (D146G) and 330-fold (D146A) increases in kcat/K(m) for NADP+ and 2-fold (D146G) and 20-fold (D146A) decreases in kcat/K(m) for NAD+. To further improve NADP+ specificity, Gln147, Leu148, Leu149, or Thr192 of enzyme D146G or D146A was replaced by lysine or arginine, which could stabilize the 2'-phosphate of NADP+. Enzymes D146G/T192K, D146G/T192R, D146G/L148K, D146A/L148K, and D146A/L148R exhibited 3200-, 4500-, 56000-, 72000-, and 83000-fold increases in the specificity for NADP+ relative to the wild-type enzyme.

Amino Acid Sequence↗

Micrographic surgery for subungual squamous cell carcinoma.

Eight patients were treated for subungual squamous cell carcinoma (4 female, 4 male; mean age 61 years). History of disease ranged from 9 months to 14 years (mean 4.7 years). Outpatient surgery under local anaesthetic was performed using Mohs micrographic surgery and formalin-fixed histological specimens. Tumour clearance was achieved after 2-6 procedures (median 3) over a mean period of 6.9 days. In all cases the wounds were allowed to heal by secondary intention and the distal phalanx was preserved. During a mean follow-up period of 3.1 years (range 0.5-6), no recurrence was seen and involved digits remained functional. Mohs micrographic surgery can provide a valuable alternative to amputation for subungual squamous cell carcinoma.

Aged↗

Diagnostic yield of bronchoscopies after isolated lung transplantation.

Lung transplantation has become an acceptable therapeutic option for end-stage pulmonary diseases. The most common causes of long-term mortality after transplantation are infections and obliterative bronchiolitis (OB). While acute rejection has been shown to be associated with an increased risk of development of OB, cytomegalovirus (CMV) pneumonitis is more controversial as a risk factor for OB. Surveillance bronchoscopies are therefore advocated as a method of detecting silent episodes of CMV pneumonitis or acute rejection. We performed 226 bronchoscopies in 43 lung transplant recipients over 34 months. One hundred fifty-seven of the 226 bronchoscopies were performed according to a surveillance protocol. Acute rejection was diagnosed if lung histologic study revealed grade 2 to 4 rejection or if prompt reversal of clinical deterioration occurred after initiation of pulse steroid therapy. CMV pneumonitis was diagnosed when transbronchial biopsy histologic specimens revealed evidence of CMV inclusion bodies, or when CMV was recovered on BAL fluid in the presence of allograft deterioration. The proportion of patients who were free from any episode of acute rejection or CMV pneumonitis after transplantation was determined by Kaplan-Meier analysis. Twenty-one percent of our transplant recipients were free from acute rejection or CMV pneumonitis after a mean follow-up of 13 months. All patients who had acute rejection or CMV pneumonitis had the initial episode in the first 4 months after transplantation. Patients free of acute rejection or CMV pneumonitis 4 months after transplantation continued to be event free for the duration of follow-up. Our data suggest that surveillance bronchoscopy can be aborted in patients who are free from acute rejection or CMV pneumonitis by 4 months after transplantation. The role of surveillance bronchoscopy in decreasing the incidence of OB or improving survival can be determined only by future randomized prospective trials.

Acute Disease↗

Nail surgery: an assessment of indications and outcome.

To examine the merits of nail surgery, we studied the surgical investigation, treatment and the outcome of 78 consecutive patients with nail pathology in the context of their complaint. A diagnosis was reached in 74/78 patients. Thirty-six out of seventy-eight (46%) of patients had tumours, 17/78 (22%) had a dermatosis, 21/78 (27%) had infection or trauma and 4/78 (5%) remained undiagnosed. The presenting complaint was treated with substantial or complete resolution in 66/78 (87%) patients. Ninety-seven per cent (35/36) of those with tumours were cured, including all 5/36 with malignant and dysplastic tumours. Post-operative splitting of the nail was seen in only one patient due to secondary infection of a longitudinal nail unit biopsy. Information from this study demonstrates the diagnostic and therapeutic value of nail surgery within dermatology.

Adolescent↗