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Biomedical subjects

A Miller

Publications and source records attributed to A Miller.

At least 415 records · Page 23Linked to original sources

Phasing the meridional diffraction pattern of type I collagen using isomorphous derivatives.

The meridional X-ray diffraction pattern of wet rat tail tendon contains information about the one-dimensional structure, or axial projection of electron density distribution of the type I collagen fibril. Using synchrotron radiation we have determined the intensities of the first 50 meridional X-ray diffraction reflections. The approach of isomorphous addition with reagents, selected using criteria of chemical reactivity, which label at fewer sites than the stains used in previous studies was applied to phase these 50 reflections to produce a one-dimensional electron density distribution map of a single D-repeat of the collagen fibril. This method is not model-dependent and thus constitutes the first unambiguous determination of the meridional phases of type I collagen.

Animals↗

Routine intraoperative angioscopy in lower extremity revascularization.

The inability to see through blood remains the main obstacle to the widespread and routine use of angioscopy. Local irrigation with a balanced salt solution is presently the most widely used method to clear the blood. By applying basic principles of irrigation and using a unique, dedicated, irrigation pump, we found that routine angioscopy during lower extremity revascularization that yields consistent high-quality studies is feasible, clinically useful, and safe. Between May 1, 1987, and July 31, 1988, 136 intraoperative angioscopies were performed during 112 peripheral bypass procedures, 15 thrombectomies, 2 embolectomies, and 7 miscellaneous revascularization procedures. Mean total irrigation fluid used in the peripheral bypasses was 398 mL (range, 0 to 1400 mL). Good visual quality was obtained in more than 80% of angioscopies and the failure rate was only 1.8%. On the basis of the findings in 71 of the 136 angioscopies, 78 clinical or surgical decisions were made. No complications were directly attributable to the insertion of the angioscope or use of the pump.

Angiography↗

Further studies on the use of serum gastrin levels in assessing the significance of low serum B12 levels.

The reported incidence of low serum vitamin B12 levels in patients ranges from 4% to 8%. In only a small percentage can this be ascribed to readily diagnosed pernicious anemia, malabsorption syndrome, or to gastrointestinal surgery. This leaves a number of patients in whom the meaning of the low serum B12 is not immediately apparent. In 71 patients with intact gastrointestinal tracts, hematological indices did not adequately separate patients with decreased absorption of unbound B12 from those with normal absorption. A low absorption of B12, either unbound or food-bound, was found, however, when the level of serum gastrin was elevated. In contrast, a normal absorption of unbound B12 was likely (95% of 44 patients) when the serum gastrin was normal.

Absorption↗

Intraoperative angioscopy: principles of irrigation and description of a new dedicated irrigation pump.

The value of intraoperative angioscopy in the detection and immediate correction of technical errors and deficiencies during vascular surgery has been previously documented. The inability to see through blood remains the most significant limitation to the general application of angioscopy. Local irrigation with a balanced salt solution is the most commonly used method to clear the blood from a restricted field in a particular vessel. We have developed a new catheter irrigation pump system (maximum flow rate 340 ml/min) to establish and maintain visibility of the field during intraoperative angioscopy. Furthermore, we have demonstrated the safety of irrigating with high volume flows in the peripheral arteries and defined the basic principles of irrigation for angioscopy. The prototype pump tested in this study provides a wide range of flow rates and permits precise measurements of the fluid delivered. The instrument's display and its control with a single foot pedal makes its use relatively simple, obviating the need for additional support personnel while increasing the efficacy and safety of the angioscopic examination and increasing the number of situations where angioscopy may be very useful.

Animals↗

Primary response to lysozyme (HEL) and HEL-LPS in neonatal A/J mice: presence of characteristic adult pattern of regulatory idiotype and fine specificity restriction.

The adult primary murine plaque-forming cell (PFC) response to hen egg-white lysozyme (HEL) is characterized by a predominant idiotype (IdXE) (congruent to 50% of population) and a predominant specificity (congruent to 50% of population) for a determinant dependent on the 3 amino-terminal residues of HEL (TIP-dependent PFC). IdXE and TIP specificity, however, are not congruent: approximately 1/3 of each population do not overlap (1). To determine whether these characteristics result from a prolonged selection process during development, we compared the neonatal A/J response profile to HEL-CFA with the adult A/J response and found that the adult pattern was present for mice immunized as early as 5 days of age. At 5 days, A/J splenic PFC were 80% TIP dependent, 71% IdXE positive compared to the adult levels of 56% (+/- 14) TIP dependent, 43% (+/- 19) IdXE positive. To attempt to address the B cells directly and avoid the need for antigen-specific T-dependent processes, we studied the PFC response to HEL-LPS conjugates in adult and 12-day-old A/J mice. At the earliest age studied (12 days), the indirect splenic PFC had similar idiotypy and specificity as the adult, and the response was similar to that induced by HEL-CFA. Although the absolute IgM PFC level was equal in adult and neonate, only 11% of the adult PFC response was IgM while a large proportion of the 12-day-old HEL-LPS response was IgM. This IgM PFC response was also characterized by the same idiotypy and specificity as the IgG PFC response. These results suggest that the characteristic adult mosaic of specificity and idiotypy in the anti-HEL response may exist prior to antigenic stimulation since it occurs as early as 5 days after immunization and in the IgM PFC responses. Although IdXE predominance may merely reflect the germ line repertoire, T cells may also be involved in an idiotype-based selection, the mechanism of which has not been determined.

Age Factors↗

Cimetidine as an immunomodulator in the treatment of herpes zoster.

As there is evidence of a possible immunoregulatory role for H2-histamine receptor antagonists, we carried out a prospective randomized trial to evaluate the in vivo and in vitro effect of cimetidine, an H2-blocker, in the treatment of herpes zoster infection. Cimetidine treatment shortened the median interval until the first decrease in pain, the median interval until the complete resolution of pain and promoted faster complete healing of skin lesions than symptomatic treatment. The immunological trends observed in vitro support an important role for histamine in the induction of immunosuppression, as measured by the response to the mitogen phytohemagglutinin. This effect of histamine was antagonized by cimetidine.

Adjuvants, Immunologic↗

Quaternary salts of 2-[(hydroxyimino)methyl]imidazole. 2. Preparation and in vitro and in vivo evaluation of 1-(alkoxymethyl)-2-[(hydroxyimino)methyl]-3-methylimida zolium halides for reactivation of organophosphorus-inhibited acetylcholinesterases.

A series of structurally related mono- and bis-1,3-disubstituted 2-[(hydroxyimino)methyl]imidazolium halides were evaluated in vitro for their ability to reactivate electric eel, bovine, and human erythrocyte (RBC) acetylcholinesterases (AChE) inhibited by ethyl p-nitrophenyl methylphosphonate (EPMP) and 3,3-dimethyl-2-butyl methyl-phosphonofluoridate (soman, GD). All new compounds were characterized for (hydroxyimino)methyl acid dissociation constant, nucleophilicity, octanol-buffer partition coefficient, reversible AChE inhibition, and kinetics of reactivation of EPMP-inhibited AChEs. For GD-inhibited AChEs, maximal reactivation was used to compare compounds since rapid phosphonyl enzyme dealkylation "aging" complicated interpretation of kinetic constants. For comparison, we also evaluated three known pyridinium therapeutics, 2-PAM, HI-6, and toxogonin. In vivo evaluation in mice revealed that when selected imidazolium compounds were coadministered with atropine sulfate, they were effective in providing lifesaving protection against both GD and EPMP challenges. This was a major accomplishment in the search for effective anticholinesterase therapeutics--the synthesis and preliminary evaluation of the first new monoquaternary soman antidotes with potencies superior to 2-PAM. Significantly, there was an apparent inverse relationship between in vitro and in vivo results; the most potent in vivo compounds proved to be the poorest in vitro reactivators. These results suggested that an alternative and possibly novel antidotal mechanism of protective action may be applicable for the imidazolium aldoximes. Selected compounds were also evaluated for their inhibition of AChE phosphorylation by GD and antimuscarinic and antinicotinic receptor blocking effects.

Animals↗

Invasive carcinomas of the urinary bladder. Evaluation of tunica muscularis mucosae involvement.

Awareness of the existence of a tunica muscularis mucosae in the urinary bladder complicates the assessment of muscle invasive carcinomas on bladder biopsy. Sixty cystectomy specimens and select bladder biopsies were reviewed to analyze this problem. The patterns of development of the tunica muscularis mucosae were categorized as continuous, interrupted, scattered, or absent. Most bladders demonstrated several patterns of development rather than a uniform appearance. The most frequently observed pattern was that of scattered smooth muscle fibers seen in 33 of 40 (82.5%) cases. The rarity of carcinomatous invasion limited to the tunica muscularis mucosae is emphasized. The authors conclude that the potential for overstaging bladder carcinomas because of misinterpretation of this structure is small.

Biopsy↗

Internal connectivity is pervasive among primary and secondary anti-hen egg white lysozyme (HEL) IgG monoclonal antibodies.

Twenty-one primary and 18 secondary monoclonal antibodies (mAb) with specificity for hen egg white lysozyme (HEL) were tested in pair-wise combinations for connectivity, that is, reactivity with each other in the absence of HEL, by an ELISA assay. All mAb reacted with at least one other, and a large proportion of the mAb, 7 of 16 primary and 11 of 18 secondary mAb, were reactive with 5 or more of the other mAb. Moreover, each gave a unique pattern of reactivity. Reactivity between mAb derived from primary and secondary hybridomas was also extensive. Some 'highly connective' mAb reacted with almost every other mAb tested. Two 'mini-networks' in the primary and secondary mAb, respectively, were identified through an ELISA binding assay and an inhibition study. Within these mini-networks (nets), members that bear IdC1 do not react with each other but bind to other members bearing IdC2. This type of interaction, as well as that between different nets defines a complicated network. No obvious correlation with fine specificity, presence of IdXE (a regulatory idiotype in the primary anti-HEL response), nor variable gene coding was apparent. Exact repeats of sequence were found for two pairs of mAb from independently selected hybridomas, i.e. in each case a primary and secondary hybridoma, indicating that high connectivity is associated with strong selection during B cell maturation following antigen stimulation.

Animals↗

Measuring physical activity in midlife women.

Women's risks for osteoporosis and cardiovascular disease are increasing. Although it is known that these risks decline with physical activity, it is difficult to associate specific risk levels with specific activity levels. Measuring activity levels is complex and problematic, especially in women. The present study explored the validity of a particular measure, the retrospective survey questionnaire, used with a female population to gauge physical activity, both occupational and leisure. To measure construct validity, four retrospective measures were administered to a sample of 43 middle-aged women representing three occupational groups (teachers, clerical workers, nurses) known to differ in activity levels. In addition, measurement approaches were triangulated by including a prospective measure, a beeper-cued record kept by subjects. A significant difference was noted among the groups on retrospective and prospective occupational activity measures, with clerical workers having the lowest levels of energy expenditure. The retrospective occupational measure correlated positively and significantly with the beeper-cued record kept during work; however, no correlation was found between the retrospective leisure measure and the beeper-cued record. These data suggest that the retrospective measure is appropriate for measuring the occupational dimension of physical activity. Additional study is required to identify women's leisure pursuits and the dimension of their household activities.

Adult↗

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Delivery of Health Care↗

Repair of a false aneurysm of the aortic arch.

A 66-year-old man having previously undergone repair of aneurysms of the ascending, transverse and infrarenal aorta, presented with a large false aneurysm of the aortic arch. Successful repair of the aneurysm was achieved under a state of profound hypothermia and circulatory arrest. The patient remains well and free from aortic aneurysmal disease two years after surgery.

Aged↗

Surgical staging of carcinoma of the ovaries.

One hundred and eighty-seven patients with stages I, II and III optimal (metastatic lesions of less than 3 centimeters) epithelial carcinoma of the ovaries were evaluated preoperatively and had standardized exploration and biopsy. The protocol called for examination and biopsy of the peritoneum, diaphragm, omentum, pelvic and para-aortic lymph nodes and aspiration of ascites or peritoneal washings for cytologic examination. Of those patients with metastases to the omentum, the clinical impression did not correlate with pathologic findings in 45 per cent. The findings were similar for diaphragmatic lymph nodes (50 per cent), pelvic lymph nodes (71 per cent) and para-aortic lymph nodes (96 per cent). Nine of 97 patients clinically thought to have stage I disease had the stage elevated to II and III based on pathologic findings. Similarly, 15 patients thought to have stage II were found to have stage III based on histopathologic findings. There were 74 complications in 54 patients, with 29 having at least one complication. Surgical exploration for early stage carcinoma of the ovary should include biopsy of the retroperitoneal pelvic and para-aortic lymph nodes, excision of the infracolic omentum, biopsies of pelvic and abdominal peritoneum, including the right diaphragm, and peritoneal cytologic studies.

Adenocarcinoma↗