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Biomedical subjects

D M Carter

Publications and source records attributed to D M Carter.

At least 19 recordsLinked to original sources

Interactions between canine plasminogen and 8-anilino-1-naphthalene sulfonate: structural insights from a fluorescent probe.

Canine plasminogen (DPgn) binds the fluorescent molecule, 8-anilino-1-naphthalene sulfonate (ANS). Binding is favored by low pH as shown by steady-state fluorescence, native PAGE and isothermal titration calorimetry. Binding occurs at multiple sites. A strong site binds ANS with a Ka of 3.3 x 10(4) M(-1). Two weaker sites were observed with association constants of 6.2 x 10(3) M(-1) and 360 M(-1), respectively. ANS binds equally well to both the closed and opened conformations of DPgn at pH 3.0. At low pH there are changes in protein tertiary structure as monitored by sedimentation velocity analysis and circular dichroism. Binding sites for ANS were located in the proteolytic domain as well as the kringle domains. However, it is unlikely that binding occurs within the lysine binding sites of each respective kringle. Taken together, the data suggest that ANS may be binding to a pH induced molten globule state of DPgn.

Amino Acid Sequence↗

Enzymatic methylation of arsenic compounds. VII. Monomethylarsonous acid (MMAIII) is the substrate for MMA methyltransferase of rabbit liver and human hepatocytes.

Inorganic arsenite is methylated by some, but not all, animal species to dimethylarsinic acid (DMA). The monomethyl compound containing arsenic in an oxidation state of +3 has been proposed as an intermediate. Using highly purified arsenic methyltransferase from rabbit liver and the partially purified enzyme from Chang human liver hepatocytes, the activity of methylarsonic acid (MMAV) and methylarsonous acid (MMAIII) as a substrate has been characterized by Michaelis-Menten kinetics. The rabbit liver enzyme has a greater affinity for MMAIII (Km = 0.92 x 10(-5) M) than MMAV (Km = 7.0 x 10(-5) M) since the smaller the Km the greater the affinity. In addition, a dithiol, reduced lipoic acid or dithiothreitol, appears to be more active than GSH in satisfying the thiol requirement of the enzyme. Although investigators have been unable to detect the arsenic methyltransferase in surgically removed human liver, its presence in Chang human hepatocytes now has been established. The Km for MMAIII, 3.04 x 10(-6), using MMAIII methyltransferase from Chang human hepatocytes was not greatly different from that of the rabbit liver enzyme.

Animals↗

Undetectable serum prostate-specific antigen associated with metastatic prostate cancer: a case report and review of the literature.

A 63-year-old man, who had undergone prostatectomy for prostate cancer that was positive for prostate-specific antigen (PSA) was examined and found to have metastatic disease, proven radiologically and pathologically, but with an undetectable PSA and highly elevated prostatic acid phosphatase (PAP). Prostatic acid phosphatase levels fell in response to chemotherapy but his clinical status continued to deteriorate. A review of the literature is presented and several possible explanations for PSA remaining undetectable in these situations are discussed. The authors conclude that although PSA can be used to monitor the majority of patients postprostatectomy, physicians may still need to rely on clinical suspicion, serum PAP, and bone scan for the detection of recurrent disease.

Acid Phosphatase↗

Patients' strategies for coping with auditory hallucinations.

Many patients with psychotic disorders experience persistent auditory hallucinations despite rigorous pharmacological treatment. The experience of auditory hallucinations can heighten anxiety and depression. The high risk of suicide among patients experiencing auditory hallucinations is well recognized. Research in this area has been restricted to small samples or has collected information only on the use of such strategies without investigating their efficacy. The Mental Health Research Institute Unusual Perceptions Schedule incorporates a module focusing on coping strategies. This schedule was administered to 100 subjects, with the aim of investigating the relationship between strategy use and effectiveness, as well as the characteristics of subjects and their disorders. Eighty-one percent of the subjects were worried or upset by their hallucinations. The majority (66%) of the subjects reported they had ways of managing the voices, and 69% of them described at least some success using one or more strategies. There was a striking lack of correspondence between the number of subjects using a method and its related efficacy. No relationship was found between length of illness and number of strategies used. Multidimensional scaling of use and efficacy data revealed three groups of strategies. These groups do not correspond to previous classifications made on the basis of features of the strategies themselves. The pattern of results also suggests that training methods might be used to increase the options for patients troubled by auditory hallucinations.

Adaptation, Psychological↗

The development and reliability of the Mental Health Research Institute Unusual Perceptions Schedule (MUPS): an instrument to record auditory hallucinatory experience.

The Mental Health Research Institute Unusual Perceptions Schedule (MUPS) is a comprehensive instrument developed to record subjects' experiences of auditory hallucinations as completely as possible. The Schedule comprises a semi-structured interview and documents the physical characteristics of auditory hallucinations such as their onset and course, number, volume, tone, location, as well as other phenomena associated with them such as delusions. In addition, other aspects of hallucinations, such as coping strategies, contributing factors and subjects' personal views and reactions are also explored. In a sample of 100 subjects drawn primarily from the in-patient wards at Royal Park Hospital the MUPS was found to be an acceptable instrument to subjects in the field. Interrater reliability assessed in a subsample of 30 subjects was found to be high at the level of the individual items. Whether used in whole or part, the MUPS provides a reliable and acceptable method of assessing patients' experience of auditory hallucinations.

Adaptation, Psychological↗

Homicide and other injuries as causes of maternal death in New York City, 1987 through 1991.

OBJECTIVES: We attempted to document the role of homicide and other injuries as causes of maternal death and to compare the risk of fatal injury among pregnant women with that in the general population. STUDY DESIGN: We reviewed New York City medical examiner records of 2331 women aged 15 to 44 years who died of injury in 1987 through 1991. Pregnancies were identified from autopsy information. RESULTS: A total of 115 (39%) of 293 deaths in currently or recently pregnant women were attributable to injury. These 115 deaths included homicide (63%), suicide (13%), motor vehicle crashes (12%), and drug overdoses (7%). Minority women were overrepresented among the injury deaths (black 53%, Hispanic 24%, white 19%). Recent substance use was documented in 48% of the injury deaths. Pregnancy was documented on only 35% of the 115 death certificates. The risk of fatal injury is similar for currently pregnant women and for women in the general population, except for an increased risk of homicide among pregnant black women. CONCLUSIONS: Homicide and other injuries are major contributors to maternal mortality and should be (but rarely are) included routinely in maternal mortality surveillance systems. Prenatal and postpartum clinic visits represent an ideal time to implement interventions to prevent injuries among pregnant women.

Accidents, Traffic↗

Plastic and reconstructive surgery in epidermolysis bullosa: clinical experience with 110 procedures in 25 patients.

We present clinical experience with 110 reconstructive procedures in 25 patients with epidermolysis bullosa, a group of rare heritable disorders characterized by marked fragility of the skin and mucosa. We discuss management of hand and foot deformities unique to epidermolysis bullosa patients, excision of squamous cell carcinoma, and reconstruction of oral, nasal, and ocular tissues. All patients underwent these procedures without major surgical or anesthetic complications. We analyze surgical outcome and formulate guidelines to avoid damaging the skin and mucosa.

Adolescent↗

Anesthetic management in epidermolysis bullosa: review of 129 anesthetic episodes in 32 patients.

BACKGROUND: Anesthetic and monitoring instrumentations such as endotracheal intubation may cause skin and mucosal damage with potentially serious consequences in patients with epidermolysis bullosa (EB). OBJECTIVE: This study defines the risks of skin and mucosal damage from anesthetic and monitoring techniques in patients with EB and formulates management guidelines. METHODS: We retrospectively analyzed the outcome of 129 anesthetic episodes in 32 patients with various types of EB. RESULTS: Serious complications did not occur in any patient with EB from the use of endotracheal intubation, face mask, nerve blocks, local anesthetics, and intravenous or intramuscular anesthetic agents. CONCLUSION: With appropriate precautions, patients with EB can undergo standard anesthetic techniques with only minor and infrequent complications.

Adolescent↗

Atypical melanocytic lesions in epidermolysis bullosa.

We report a 6-year-old female with recessive dystrophic epidermolysis bullosa (RDEB) who presented with a very large acquired melanocytic lesion. The lesion demonstrated many features both clinically and histologically that made the distinction from malignant melanoma difficult. The pathogenesis of this lesion and other unusual melanocytic lesions seen in the setting of acute and chronic blistering disorders seems related to repeated episodes of disruption of the dermal-epidermal junction.

Child↗

Home nutrition survey in the UK: the patient's perspective.

A detailed survey questionnaire compiled by the executive committee of Patients on Intravenous and Nasogastric Nutrition Therapy (PINNT) was circulated in November 1991 to the postal addresses of all full (patient) members of PINNT in the UK. The objective of the survey was to identify current practices and problems of home nutrition support as seen from the patients perspective. 128 questionnaires were distributed. 87 (68%) analysable questionnaires were completed and returned. 77 were for parenteral nutrition (HPN) patients and 10 for patients on enteral nutrition (HEN). Areas of concern for patients include the practicalities of administration of lipid and additives, and problems associated with the appearance of air in infusion bags. Although most patients appeared happy with the home nutrition support services 18% commented on particular negative aspects. This survey highlights such areas which may not be identified during routine patient/clinician contact.

Journal Article↗

Epidermolysis bullosa.

Epidermolysis bullosa is a group of genetically determined diseases characterized by abnormal fragility of the skin and mucosa. In this chapter, we review current thinking about classification, pathogenesis, and molecular genetics, and we discuss management guidelines.

Epidermolysis Bullosa↗

Lack of efficacy of phenytoin in recessive dystrophic epidermolysis bullosa. Epidermolysis Bullosa Study Group.

BACKGROUND: Recessive dystrophic epidermolysis bullosa is an uncommon, severely disabling, heritable disorder characterized by abnormal fragility of the skin. Open trials have suggested that phenytoin is an effective treatment, and this therapy is now widely used. METHODS: To determine the efficacy of phenytoin in the treatment of recessive dystrophic epidermolysis bullosa, we performed a randomized, double-blind, placebo-controlled, crossover trial in 36 patients. Each treatment was given for five to seven months, separated by a two-month period. We measured the total number of blisters and erosions on the entire body, the size of three plaques containing blisters and erosions, and the number of blisters and erosions in the three plaques at the beginning and end of each treatment period in each patient. RESULTS: Twenty-two patients completed both courses of therapy, seven patients completed one course, and seven patients withdrew before completing a single course. There was no significant difference in disease activity between phenytoin treatment and placebo treatment, as measured by changes in the number of blisters and erosions on the entire body (7 percent decrease vs. 6 percent increase), in the area of three designated plaques (0.4 percent decrease vs. 0.2 percent increase), or in the number of blisters and erosions in the designated plaques (12 percent decrease vs. 31 percent increase). CONCLUSIONS: Phenytoin is not an effective treatment for patients with recessive dystrophic epidermolysis bullosa.

Adolescent↗

The insulin-like growth factor I receptor is overexpressed in psoriatic epidermis, but is differentially regulated from the epidermal growth factor receptor.

Insulin-like growth factor I (IGF-I)/somatomedin C is an important mediator of keratinocyte growth in vitro, and the expression of IGF-I receptors in the basal layer of normal epidermis suggests that this growth pathway may function in the regulation of keratinocyte growth in vivo as well. The pattern of IGF-I receptor expression in normal skin is distinct from that of the epidermal growth factor (EGF) receptor, suggesting that these receptors might be differentially regulated. The purpose of this study was to obtain a better understanding of IGF-I receptor function in the skin by examining IGF-I receptor expression in psoriatic epidermis and in cultured human keratinocytes. Our findings indicate that IGF-I receptor expression is increased in psoriasis as measured by protein tyrosine kinase assays of biopsy extracts and by immunohistochemical staining with an IGF-I receptor-specific monoclonal antibody. Unlike EGF receptor expression, which is also increased in psoriatic epidermis, the pattern of IGF-I receptor expression corresponds closely with the increased size of the keratinocyte proliferative compartment in psoriasis. Biochemical agents that diminish EGF receptor ligand binding (phorbol ester or calcium ionophore treatment) produce opposite effects on the IGF-I receptor. These results suggest that cellular expression and differential regulation of both growth factor receptor systems may control critical aspects of epidermal proliferation or function.

Antibodies, Monoclonal↗

Gastrointestinal manifestations of epidermolysis bullosa. A study of 101 patients.

One hundred one patients with EB were evaluated by a combination of prospective and retrospective review, and analyzed regarding the nature, incidence, and prevalence of their gastrointestinal (GI) manifestations. Involvement of the GI tract is a well-known extracutaneous manifestation of dystrophic EB, but it also occurred in more than one-half and one-third, respectively, of those with junctional and simplex EB. Most of the serious consequences, such as esophageal strictures and microstomia, occurred in recessive dystrophic EB but were also seen, although infrequently, in the junctional and simplex forms. The majority of patients with dysphagia had an esophageal stricture, and the cervical esophagus was the most common location. The onset of dysphagia generally occurred in the first decade of life, in patients much younger than previously recognized. Diagnostic endoscopy did not reveal lesions which could not have been detected radiographically. Lower GI complaints were common, especially constipation and perianal blistering, and affected all types of EB. These complaints contributed substantially to management problems but they did not correlate with colonic pathology and appeared to reflect anal or perianal disease.

Adolescent↗

Studies of the effect of cyclosporine in psoriasis in vivo: combined effects on activated T lymphocytes and epidermal regenerative maturation.

Cyclosporine (CSA) decreases lymphokine synthesis and keratinocyte proliferation in vitro, but its in vivo mechanism of action in treating recalcitrant psoriasis is incompletely understood. Ten psoriasis patients were treated with CSA (2-7.5 mg/kg/d) with clinical improvement in nine of 10 patients. Skin biopsies before and after 1-3 months of CSA treatment were studied for evidence of immune and keratinocyte activation using immunoperoxidase and Northern blotting analysis. The number of activated, IL-2 receptor+ T cells in plaques after CSA treatment was reduced in all patients by a mean of 60%. Seven of 10 patients showed a decrease in keratinocyte HLA-DR expression; five of seven showed a decrease in gamma-IP-10 immunoreactivity, suggesting a decline in gamma interferon levels in plaques after CSA therapy. We studied the effect of CSA treatment in vivo on TGF-alpha, IL-6, and keratin K16 expression, three markers of keratinocyte growth activation. Expression of keratinocyte TGF-alpha and IL-6, which are elevated in active psoriatic epidermis, did not change in these patients after CSA treatment. The majority of patients (five of eight) continued to express the hyperproliferative keratin K16 after CSA treatment. Our results suggest that the predominant direct mechanism of action of Cyclosporine in vivo is a diminution of T-cell activation in plaques, with attendant decreased lymphokine production.

Cyclosporine↗

Junctional epidermolysis bullosa of the larynx. Report of a case and literature review.

Epidermolysis bullosa (EB) is a group of rare inherited disorders in which minor trauma causes blister formation in the skin and mucosa, including the esophagus. Morbidity varies with the type of disease and ranges from occasional trivial skin blisters to death in infancy. Laryngeal involvement presenting as hoarseness and respiratory distress has been reported in nine patients, five of whom had junctional EB. We present the sixth case of junctional EB with laryngeal involvement, and offer guidelines for otolaryngologists and anesthesiologists caring for these fragile patients.

Child, Preschool↗