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Biomedical subjects

T Todd

Publications and source records attributed to T Todd.

At least 19 recordsLinked to original sources

Severe factor X deficiency due to a homozygous mutation (Cys364Arg) that disrupts a disulphide bond in the catalytic domain.

Severe factor X deficiency (<0.01 IU mL(-1)) is a rare disorder producing a major bleeding tendency including umbilical cord, joint and intracranial haemorrhage. We present the first case of a child homozygous for a g.1177T > C missense alteration, predicted to disrupt the catalytic domain, and resulting in severe FX deficiency. The child suffered intracranial haemorrhage and now receives regular prophylaxis with a prothrombin complex concentrate. Our experience and a review of the literature suggest that optimal frequency of dosing is likely to be two or three times weekly and that the risk of thrombosis is very small.

Adolescent↗

Induction chemotherapy with mitomycin, vindesine, and cisplatin for stage III unresectable non-small-cell lung cancer: results of the Toronto Phase II Trial.

PURPOSE: The 5-year survival rates with surgical resection for preoperatively identified stage IIIA N2 non-small-cell lung cancer (NSCLC) are less than 10%. A pilot study of mitomycin, vindesine, and cisplatin (MVP) induction chemotherapy was undertaken in an attempt to improve the curative potential of surgery in this group of patients. PATIENTS AND METHODS: Thirty-nine patients with mediastinoscopy stage IIIA N2 NSCLC received two cycles of MVP. Responding patients underwent thoracotomy for resection and two further courses of MVP. RESULTS: The overall response rate was 64% (25 of 39) with three complete and 22 partial responses. Twenty-two patients were resected, which included a radical mediastinal node dissection. Eighteen resections were complete and four were incomplete. Pathologically, three patients (7.7%) had no tumor remaining. Toxicity included two postoperative deaths secondary to a bronchopleural (BP) fistula, mitomycin pulmonary toxicity in two patients, and septic deaths in four patients. Twenty-eight patients have died; 20 have recurrent or progressive disease. Eight of the 18 patients completely resected have recurred, with a median time to recurrence of 20.6 months. Sites of recurrence include two locoregional, five distant (two in brain), and one in both. Median survival of all 39 patients is 18.6 months, with a 3-year survival of 26%. The median survival for those patients completely resected was 29.7 months with a 3-year survival of 40%. CONCLUSIONS: We conclude (1) that MVP is an effective but toxic chemotherapeutic regimen for limited NSCLC; (2) the median survival seems to be prolonged; and (3) the role of induction chemotherapy followed by surgery in stage IIIA N2 NSCLC requires a phase III randomized trial to compare it with other treatment modalities.

Adult↗

What makes Susie cry? A symptom-context study of family therapy.

The aim of this investigation was to examine the context of recurrent crying episodes during family therapy sessions. We tested the relative contribution of social versus individual intrapsychic variables within a 10-session, videotaped, structural family therapy. Segments of therapy before crying episodes when compared with control (non-crying) segments were found to have higher levels of the following variables: involvement with others in the room, rejection, and concern about supplies. Two family variables were also higher before crying episodes: family discussion about patient, and patient receives hostility. A stepwise discriminant function analysis using these variables indicated that family discussion about the patient was most important in signaling onset of crying. The results are discussed in terms of individual and family theories of symptom formation as illuminated through this case study.

Adolescent↗

Psychopathology among cocaine abusers entering treatment.

A number of different indicators of psychopathology were assessed in this study of 76 cocaine and crack abusers who entered outpatient treatment in New York City between June and December 1987. The majority (75%) had used cocaine for 4 years or more, and the majority (62%) spent over one thousand dollars a month on cocaine in the 6 months before entry into treatment. Forty-seven percent of the sample were found to be clinically depressed. Phobic disorders were the only other axis I diagnoses found in addition to depression, and all persons who were found to have phobic disorders also were diagnosed as having some form of depressive disorder. The four most common axis II diagnoses were antisocial personality (21%), passive-aggressive (21%), borderline (18%) and self-defeating (18%). Subjects were classified as falling into one of the following three categories of a newly developed "psychopathology classification": a) no diagnosed psychopathology except substance abuse or dependency; b) one or more axis II diagnoses, but no axis I diagnoses except for substance abuse or dependency; c) at least one axis I diagnosis in addition to drug disorders whether or not accompanied by an axis II diagnosis. Mean scores on subscales and total score on the SCL-90, as well as total score on the Beck Depression Inventory, were ordered by category of the classification scheme, with those having no diagnosed psychopathology except substance abuse having the lowest score and persons in the third category having the highest score.(ABSTRACT TRUNCATED AT 250 WORDS)

Cocaine↗

Equilibrium analysis of binding of Candida albicans to human buccal epithelial cells.

The effect of growth temperature on the binding of Candida albicans to human buccal epithelial cells (BECs) was examined using an equilibrium of binding analysis. Candida albicans was cultured in M9 medium either for 12 h at 25 degrees C or for 9 h at 25 degrees C and then shifted to 37 degrees C for 3 h. The temperature shift did not result in germ tube formation; however, the adherence of C. albicans to BECs was altered. Shifting temperature increased the yeast's ability to bind to BECs. A Langmuir adsorption isotherm was used to calculate the maximum number of available binding sites (N) and the apparent association constants of binding (Ka) for all resolvable adhesin-receptor interactions. Three classes of adhesin-receptor interactions were resolved when the yeast was cultured at 25 degrees C and included a low copy number site (N = 3.0 cfu/BEC; Ka = 2.11 X 10(-6) mL/cfu), a medium copy number site (N = 23.6 cfu/BEC, Ka = 8.21 X 10(-7) mL/cfu), and a high copy number site (N = 91.7 cfu/BEC, Ka = 3.35 X 10(-8) mL/cfu). Two classes of adhesin-receptor interactions were resolved when the incubation temperature was shifted to 37 degrees C: a low copy number site (N = 4.5 cfu/BEC, Ka = 3.98 X 10(-6) mL/cfu) and a high copy number site (N = 150.5 cfu/BEC, Ka = 8.47 X 10(-8) mL/cfu). Augmented C. albicans adherence to BECs due to the elevated growth temperatures appears to result from a temperature-regulated alteration in the C. albicans adhesin that recognizes a high copy number receptor site with relatively low affinity.

Bacterial Adhesion↗

Characterization of the Pseudomonas aeruginosa pilus adhesin: confirmation that the pilin structural protein subunit contains a human epithelial cell-binding domain.

Previous studies have suggested that the Pseudomonas aeruginosa PAK pilus adhesin moiety resides in an epithelial cell-binding domain located in the C-terminal region of the PAK pilin structural protein. Synthetic peptides Ac17red (a synthetic peptide with a sequence identical to that of PAK pilin residues 128 to 144, with the Cys-129 and Cys-142 residues being in the reduced state) and Ac17ox (a synthetic peptide with a sequence identical to that of PAK pilin residues 128 to 144, with a formed disulfide bridge between the amino acid residues Cys-129 and Cys-142), which should contain the epithelial cell-binding domain, were synthesized. Ac17red and Ac17ox both bound to buccal epithelial cells (BECs) and to ciliated tracheal epithelial cells (TECs). Ac17ox had a Km of 6.40 microM for binding to BECs, while Ac17red had a Km of 9.87 microM. Ac17red bound to the same receptor sites that purified pili did and competitively inhibited the binding of purified PAK pili to BECs. BEC glycoproteins with molecular masses of 82, 55 to 51, and 40 kilodaltons immobilized on nitrocellulose exhibited periodate-sensitive receptor activity for Ac17red; similar activity has been found for PAK pili. Ac17red, Ac17ox, and PAK pili bound to the cilia and luminal portions of the cytoplasmic membrane of human TECs, the same regions to which P. aeruginosa whole cells bind. PAK pilin has an epithelial cell-binding domain that resides in the C-terminal region of the protein.

Bacterial Adhesion↗

Role of pili in adhesion of Pseudomonas aeruginosa to human respiratory epithelial cells.

The ability of pili from Pseudomonas aeruginosa K (PAK) to act as an adhesin to human respiratory epithelial cells was examined using an in vitro adhesion assay. Equilibrium analysis of PAK binding to human buccal epithelial cells (BECs) and tracheal epithelial cells (TECs) by means of a Langmuir adsorption isotherm revealed that the maximum numbers of binding sites per epithelial cell (N) were 255 for BECs and 236 for TECs, with apparent association constants (Ka) of 2.8 x 10(-9) and 5.8 x 10(-9) ml/CFU, respectively. Trypsinization of the BECs before the binding assay increased N to 605 and decreased the Ka to 1.7 x 10(-9) ml/CFU. Addition of homologous pili to the binding assay with BECs or TECs or the addition of anti-pilus Fab fragments inhibited PAK adherence. Binding of purified pili to BECs was shown to reach saturation. Purified pili and PAK competed for the same receptor on the BEC surface. Further, by using peptide fragments of PAK pilin (derived from the native pili or produced synthetically) in the binding assay for PAK to BECs, we have presumptively identified the pilus binding domain in the C-terminal region of the pilin and shown that the C-terminal disulfide bridge is important in maintaining the functionality of the binding domain.

Bacterial Adhesion↗

Characterization of the binding of Pseudomonas aeruginosa alginate to human epithelial cells.

The alginate produced by Pseudomonas aeruginosa has been reported to play a role in the adhesion of this bacterium to epithelial cell surfaces, although some controversy concerning this role exists. To clarify this controversy, we investigated the ability of alginate to bind to human buccal epithelial cells (BECs) and human tracheal epithelial cells (TECs). Alginate from P. aeruginosa 492c bound to both BECs and TECs. Alginate from strain 492c was found to be multivalent and thus capable of agglutinating both BECs and TECs. The multivalency of alginate complicated the determination of the number of alginate-specific receptors on the BEC and the apparent association constant (Ka). By using the analysis of Hogg and Winzor (Biochim. Biophys. Acta 843:159-163, 1985), an average valency of 2.6 BEC binding domains per alginate molecule was determined, and the maximum binding capacity per BEC was calculated to be 5.8 X 10(-4) micrograms, with a Ka of 4.1 X 10(-2) ml/micrograms. The binding of alginate to immobilized BECs (where only 50% of the BEC surface is exposed) yielded values of 2.52 X 10(-4) micrograms of alginate per BEC for the maximum binding capacity per BEC and a Ka of 3.30 X 10(-2) ml/micrograms. The alginate-specific site on the BEC surface was trypsin sensitive. Alginate from P. aeruginosa 492a did not bind to BECs, differing substantially from that of strain 492c. The data presented here demonstrate that alginate purified from some strains of P. aeruginosa may bind to TECs and BECs in a defined, specific manner, whereas alginate from other strains does not, reflecting structural diversity in P. aeruginosa alginates.

Adhesins, Bacterial↗

Adherence of Pseudomonas aeruginosa to cilia of human tracheal epithelial cells.

Pseudomonas aeruginosa was found to adhere selectively to cilia of human ciliated tracheal epithelial cells (TECs). P. aeruginosa bound in equal numbers to TECs of smokers and nonsmokers, with the mean adhesion index for binding of P. aeruginosa 492c to TECs of healthy individuals (+/- standard deviation) being 6.83 +/- 6.00 bacteria per TEC.

Adult↗

Pharyngeal reconstruction: current controversies.

Total pharyngeal reconstruction following ablative surgery has made significant advances over the past 10 years with the development of new techniques and the refinement of older methods. The reconstructive methods utilized by the authors in 26 cases over the past three years are presented. The methods employed were classified into three groups. Group A (N = 3) were reconstructed using myocutaneous flaps, Group B (N = 17) were repaired by primary gastric transposition, and Group C (N = 6) were handled using a free vascularized jejunal graft. Twenty-two of the patients received preoperative irradiation. The selection of appropriate procedure and technique, and the complications and limitations of each method are discussed.

Female↗

Cardiac tamponade as a complication of thin-needle aspiration lung biopsy.

Thin-needle aspiration lung biopsy has become an important diagnostic technique in chest disease. Complications, other than pneumothorax, are infrequent. We report a case of acute cardiac tamponade complicating biopsy of a lesion near the mediastinum. Caution should be exercised in selecting patients for, and in performing biopsies in, or close to the mediastinum.

Adult↗

Predicting the outcome of psychotherapy. findings of the Penn Psychotherapy Project.

Our study of predictability of outcomes of psychotherapy used predictions of two kinds: (1) direct predictions by patients, therapists, and clinical observers; and (2) predictive measures derived from the same sources. Seventy-three nonpsychotic patients were treated in psychoanalytically oriented psychotherapy (mean, 44 sessions). Two thirds of the therapists were residents in psychiatry; one third were more experienced. The two main composite outcome measures, measured at termination, were Raw Gain (residualized) and Rated Benefits, which intercorrelated at .76. Most patients improved and showed a considerable range of benefits. The clinical observers' direct predictions of Rated Benefits were highest (.27, P less than 905). The success of the predictive measures were generally insignificant, and the best of them were in the .2 to .3 range meaning that only 5% to 10% of the outcome variance was predicted. The Prognostic Index Interview variables did the best (eg, emotional freedom composite, .30; a crossvalidation for 30 patients was .39 (P less than .05). Neither the therapist measures nor the early psychotherapy session measures predicted significantly. Reanalysis of the similar Chicago Counseling Center study, in our terms, showed a similar low level of prediction success, eg, adequacy of functioning, marital status match, and length of treatment predicted significantly in both studies.

Adolescent↗