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Biomedical subjects

B Powell

Publications and source records attributed to B Powell.

At least 19 recordsLinked to original sources

Hair follicle differentiation: expression, structure and evolutionary conservation of the hair type II keratin intermediate filament gene family.

During hair follicle development several cell streams are programmed to differentiate from the cell population of the follicle bulb. In the hair cells, a number of keratin gene families are transcriptionally activated. We describe the characterization of the type II keratin intermediate filament (IF) gene family which is expressed early in follicle differentiation. In sheep wool, four type II IF proteins are expressed. One gene has been completely sequenced and the expression of three of the genes examined in detail. The sequenced gene encodes a 55 x 10(3) Mr protein of the type II keratin IF protein family, designated KII-9 in the new nomenclature we have adopted and described in the Introduction. The gene has a similar exon/intron structure to the epidermal type II keratin IF genes. In situ hybridization experiments show that the genes are expressed in the hair cortical cells but not in the cells of the outer root sheath, inner root sheath or medulla. During hair keratinocyte differentiation the type II IF genes are sequentially activated and coexpressed in the same cells. Expression is first detected in cells in the middle of the follicle bulb located near the dermal papilla and, subsequently, two of the genes are transcriptionally activated in the differentiating keratinocytes as they migrate upwards, in the upper part of the bulb. A fourth type II IF gene is activated later. The genes with the same expression pattern are also closely related in sequence and a number of conserved elements are present in the promoters of those genes, including a novel element which is also found in the promoter of a coexpressed type I IF gene and three other hair keratin genes.

Amino Acid Sequence

Performance characteristics of contemporary hemodialysis and venovenous hemofiltration in acute renal failure.

UNLABELLED: Modality choice in the treatment of acute renal failure (ARF) should be based on the match between individual patient needs and the characteristics of available therapies. Considerations include access, risk of bleeding, hemodynamic instability, and ability to remove excess volume. We prospectively studied 547 consecutive treatments for ARF in 110 patients to determine the performance features of modalities based on single-vessel venous access: hemodialysis (HD) and venovenous hemofiltration (VVH). All treatments were performed in an 18-month period at a single center. Patients' ages ranged from 16 to 84 years; 26 were trauma cases; 69 patients expired during their hospitalization. Mean number of treatments per patient was 4.97. Mean treatment duration was 197 min. Heparin was used unless active bleeding was present or felt to be a high risk; mean dose required was 2628 units. Pressor therapy was in progress prior to initiation of 260 (48%) of treatments. RESULTS: pretreatment and posttreatment mean systolic and diastolic BP were unchanged for the group. Forty-three (7.9%) treatments were terminated prematurely; of these only 27 (4.9%) were due to hypotension. No patient developed clinically apparent bleeding during any treatment. Contemporary equipment and techniques allow for provision of high-quality intermittent therapy for ARF, with excellent hemodynamic stability. Shorter, single-vein access treatments are advantageous for severely ill or injured patients who often undergo invasive monitoring and multiple studies or procedures.

Acute Kidney Injury

Perceptual dysfunction in hemiplegia and automobile driving.

Sixteen post-stroke, hemiplegic patients, who requested that they be allowed to return to driving, were extensively evaluated by a physiatrist, psychologist, occupational therapist, and driver training specialist. After they completed a driver training program, the patients were divided into three groups based on their driving program success and follow-ups. Significant differences in the psychological test results were found between Group I (those who drove without any difficulty) and Groups II and III (those who drove limited distance or who failed driver training). Results suggest that patients with significant cognitive and perceptual problems who take training and limit their driving can be safe drivers when they return to driving.

Accidents, Traffic

Enhanced anti-tumour activity of carmustine (BCNU) with tumour necrosis factor in vitro and in vivo.

The effects on experimental melanoma of a combination of recombinant human tumour necrosis factor alpha (rhTNF alpha) and carmustine (BCNU) were studied in vitro and in vivo. In vitro, BCNU alone was cytotoxic to murine B16 melanoma cells, and at all concentrations of BCNU this toxicity was increased by the addition of TNF. In vivo, BCNU and TNF, when given separately, caused tumour growth delay of B16 melanoma and of human melanoma xenografts in immune-deprived mice. The combination of TNF at low dose 2.5 x 10(5) U kg-1 = 122 ng kg-1) with BCNU (35 mg kg-1) resulted in significant growth delay (compared with either drug alone) in B16 melanoma (P = 0.005). There was no significant increase in toxicity as assessed by weight loss and peripheral blood counts. Experiments with human melanoma xenografts yielded similar results (P = 0.001) but only at higher doses of TNF (1 x 10(6) U kg-1 = 489 ng kg-1). The enhancement of BCNU cytotoxicity by TNF may be important if it can be translated into patients with melanoma. A randomised study is now underway to investigate the clinical potential of this observation.

Animals

VirA, a coregulator of Ti-specified virulence genes, is phosphorylated in vitro.

High-level expression of a chimeric virA gene was obtained by replacing the first 524 codons of virA with the first half of trpE. The encoded fusion protein was isolated and found to exhibit autokinase activity. Therefore, a kinase domain is in the C-terminal portion of VirA, and protein phosphorylation may be an important feature of VirA function.

Bacterial Proteins

The timing of amputation for lower limb trauma.

We reviewed 35 patients who had an amputation following the failure of treatment for severe lower limb trauma. Seven of the amputations were for ischaemia, within one month of injury; 13 were between one month and one year for infection complicating loss of wound cover in un-united fractures; and 15 were later than one year after injury, mainly for infected non-union. The latter group of patients had had an average of 12 operations and 50 months of treatment, including eight months in hospital. We used a new limb injury score based on damage to the individual tissue elements; this indicated that, even in the absence of neurovascular injury, the presence of severe damage to skin, bone and muscle, with wound contamination, particularly in the lower tibia, had a poor prognosis. We therefore recommend, to avoid multiple operations, with prolonged hospitalisation and suffering, that these patients should have early independent review by orthopaedic and plastic surgeons with the aim of establishing an accurate prognosis for the salvage of a useful limb.

Adolescent

Iatrogenic lithotripsy failure: penetration of shock waves through tape.

Foam tape used to protect epidural catheters during immersion in a Dornier HM3 lithotriptor was identified retrospectively as the cause of poor stone fragmentation. Studies of shock wave penetration through various protective type materials indicate that a particular water repellant tape is least likely to impair shock wave penetration.

Adhesives

Tissue expanders in surgery.

The technique of tissue expansion using inflatable expanders has gained widespread attention in the surgical literature. We give two examples of its use and emphasise possible complications which may arise. The search for methods to close complex wounds, often associated with radiation-damaged tissue or exposed bone, has resulted in a progression from random skin flaps to axial pattern flaps with a longer length to breadth ratio guaranteed by anatomically constant vessels. Musculocutaneous, fasciocutaneous and free flaps have been described over the body surface allowing complex reconstruction at local and distant sites. The use of expansion is of particular value in allowing local tissue to fill defects with minimal functional and aesthetic disturbance. In the face and scalp, in particular, tissue expansion appears to be a promising method of at least partially removing disfiguring lesions and is useful in reconstruction following traumatic loss. The concept of tissue expansion in medicine is not new. During pregnancy the abdominal skin becomes gradually stretched over the expanding uterus. Large skin excisions can be carried out in abdominoplasty following weight loss. Skin and mucosa can be seen to expand rapidly over benign enlarging neoplasms. The serial excision of large naevi has been practised for many years by plastic surgeons. Skin grafts placed over fasciotomy wounds to obtain tension-free closure can be subsequently excised in stages to obtain a minimally stretched linear scar.

Adult

Synergy between high-dose cytarabine and asparaginase in the treatment of adults with refractory and relapsed acute myelogenous leukemia--a Cancer and Leukemia Group B Study.

One hundred ninety-five adult patients with refractory or first relapse acute myelogenous leukemia (AML) were randomly assigned to receive high-dose cytarabine (HiDAC), 3 g/m2 as a three-hour intravenous (IV) infusion every 12 hours for four doses, followed by 6,000 IU/m2 asparaginase (ASNase) administered at hour 42, or HiDAC without ASNase. Treatment was repeated on day 8. The median patient age was 52 years. There was an overall superior complete remission (CR) rate for HiDAC/ASNase (40%) v HiDAC (24%), P = .02. Subset analysis according to prior response and age showed the following CR rates: 54% from HiDAC/ASNase treatment of refractory AML in patients less than 60 years, and 31% in patients greater than 60 years; CR from HiDAC in the same refractory groups were 18% (less than 60) and 0% (greater than 60); 37% from HiDAC/ASNase treatment of relapsed AML in patients less than 60 years, and 43% in patients greater than 60 years; CRs from HiDAC in the same relapsed groups were 33% (less than 60) and 21% (greater than 60). Toxicity in the two treatment arms was comparable and consisted primarily of leukopenia, thrombocytopenia, mild hepatic dysfunction, diarrhea, conjunctivitis and serositis, and hyperglycemia. There was only one case of transient cerebellar toxicity and no cutaneous toxicity. Median time to full hematologic recovery was 5 weeks. There was an overall survival benefit for patients treated with HiDAC/ASNase (19.6 weeks) compared with HiDAC (15.9 weeks), P = .046, primarily attributable to effects in refractory patients. Median time to failure for refractory patients who achieved CR was 38.5 weeks with HiDAC/ASNase, and 13.3 weeks for those treated with HiDAC. For relapsed patients in CR from HiDAC/ASNase the median time to failure was 17.7 weeks and 18.3 weeks for HiDAC. The overall 42% CR rate from HiDAC/ASNase v 12% from HiDAC in patients with refractory AML indicates that HiDAC/ASNase is not cross-resistant with standard-dose cytarabine (SDAC) and anthracyclines. We conclude that HiDAC/ASNase has substantial activity in poor-prognosis AML and that this combination warrants further trials in earlier stage disease.

Antineoplastic Combined Chemotherapy Protocols

Prospective use of saliva lithium determinations to monitor lithium therapy.

A mathematical equation (y = 2.27x -0.45) relating saliva (y) to plasma (x) lithium concentrations was previously determined by one of the authors. A prospective study is reported here in which the correlation coefficient between the predicted and the observed plasma concentrations in a new group of 25 patients was r = 0.89 (p less than 0.001). The study demonstrates that saliva lithium determinations can be safely used to monitor lithium therapy.

Bipolar Disorder

The use of extracted teeth to evaluate clinical measurements of periodontal disease.

Clinical indicators of periodontal disease, Gingivitis Index, Gingival crevicular fluid and pocket depth measurements were obtained from the gingiva surfaces of 30 teeth. The gingival margins were marked on the surfaces of the teeth prior to extraction. The extracted teeth were stained with hematoxylin and air dried, and the distances from the groove to the base of the calculus, plaque, and connective tissue attachment were obtained. The plaque-free zone was also measured. Comparisons were made between clinical and tooth surface measurements. A high correlation was found between clinical pocket depth measurements and tooth surface parameters. The correlations between all tooth surface parameters and GCF were statistically significant. The G.I. was significantly correlated only with the penetration of calculus into the pocket. The clinical pocket depth was statistically the same as the distance from the gingival groove to the coronal connective tissue attachment. The plaque-free zone appeared to represent the junctional epithelium.

Dental Calculus