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Biomedical subjects

C Schultz

Publications and source records attributed to C Schultz.

At least 37 records · Page 2Linked to original sources
PubMed1994

Current radiosurgery practice: results of an ASTRO survey. Task Force on Stereotactic Radiosurgery, American Society for Therapeutic Radiology and Oncology.

PURPOSE: Although there is increasing interest in radiosurgery, little quantitative data regarding current patterns of radiosurgery practice are available. We developed a radiosurgery questionnaire to obtain information on radiosurgery practice. METHODS AND MATERIALS: We distributed the questionnaire to the entire membership of the American Society of Therapeutic Radiology and Oncology in early 1993. Responses were obtained from 74 facilities that practice radiosurgery, corresponding to over 6000 treatments carried out since 1983 by 135 radiation oncologists and 130 physicists. RESULTS: Most respondents were found to work within a multidisciplinary team, consisting of the following specialists (average hours devoted per patient on day of treatment in parentheses): radiation oncologist (3.8), neurosurgeon (3.2), physicist (6.1), radiologist (0.7), nurse (2.7), other (3.0). On average, neurosurgeons and nurses who perform Gamma Knife radiosurgery devote significantly more time-per-patient on the day of treatment than their peers who perform linac radiosurgery. On average, less experienced radiation oncologists and physicists (< or = 24 months experience, or < or = 50 patients treated) devote significantly more time-per-patient on the day of treatment than their more experienced peers. Although there are many more linac radiosurgery facilities than Gamma Knife facilities, on average the number of patients treated per month per facility is significantly larger at the latter. On average, follow-up responsibilities are nearly equally shared by radiation oncologists and neurosurgeons, except at Gamma Knife facilities, where neurosurgeons assume a larger percentage of follow-up responsibility. The percentages of patients treated at linac facilities for metastases or primary CNS malignancy are larger than the corresponding percentages at Gamma Knife facilities; the opposite is true for arteriovenous malformation, acoustic neuroma, and meningioma. CONCLUSION: Current radiosurgery practice usually involves a team approach, with participation of specialists from radiation oncology, neurosurgery, physics, radiology, and nursing. The average number of M.D. and Ph.D. hours required per treatment on the day of radiosurgery is high.

Canada↗
PubMed1994

Respiratory manifestations of rigid spine syndrome.

Thoracic abnormalities and respiratory muscle function were investigated in nine patients with rigid spine syndrome. A severe restrictive chest wall defect and limited mobility of the spine associated with clinically significant respiratory muscle weakness were present in all patients. Respiratory muscle strength and endurance were less than 60% of control values. Slight to moderate scoliosis was present in five patients and absent in four. Scoliosis appeared to have only a minor additional effect on respiratory muscle function. Six patients were emaciated, and one patient was underweight, but no relationship was seen between body mass index and respiratory muscle strength. Respiratory muscle function was more impaired in patients with hypoventilation than in normocapnic patients. Respiratory muscle involvement appears to be a significant feature of rigid spine syndrome, terminating in hypercapnic ventilatory failure in some patients.

Adolescent↗
PubMed1994

[Cysts of second branchial cleft: review of 32 operated cases].

The aim of this work was to analyze retrospectively the clinical features of 32 patients aged 23.9 years (21 female) with the histological diagnosis of second branchial cleft cyst. In 28 patients, the cyst was localized below the mandibular angle. The presenting symptom was a cervical tumor in 30 patients and pain in eight. Fourteen aspiration punctures was performed obtaining 8 purulent and 6 straw colored aspirates. The preoperative diagnosis was correctly made in only 19 patients; the principal confounding diagnosis was tuberculous adenitis. All patients were operated performing a complete cystectomy in 30 and partial cystectomy in two. Three patients had a surgical wound infection and the cysts recurred 5 months and 4 years after operation in the two patients subjected to partial cystectomy. The histological study revealed squamous epithelial with underlying lymphoid tissue. It is concluded that aspiration puncture is useful for the correct diagnosis and that the cyst must be completely eradicated to avoid recurrences.

Adolescent↗
PubMed1994

Membrane-permeant derivatives of cyclic AMP optimized for high potency, prolonged activity, or rapid reversibility.

A novel membrane-permeant derivative of cAMP, cAMP acetoxymethyl ester (cAMP/AM), was synthesized via silylated intermediates. Its ability to induce Cl- secretion by T84 cells, a human colon cancer cell line, was compared with that of two other membrane-permeant cAMP derivatives that were recently introduced, N6,O2'-dibutyryl-cAMP acetoxymethyl ester (bt2cAMP/AM) and Sp-5,6-dichlorobenzimidazole-1-beta-D-ribofuranoside 3',5'-cyclic phosphorothioate (Sp-5,6-DCl-cBIMPS). All of these compounds are powerful activators of Cl- secretion when applied extracellularly, with EC50 values of 60 microM, 0.7 microM, and 3 microM, respectively. However, cAMP/AM was expected to be readily degraded inside cells, in contrast to the cyclophosphodiesterase-resistant Sp-5,6-DCI-cBIMPS or the only slowly metabolizable N6-butyryl-cAMP derived from bt2cAMP/AM. Reversibility of cAMP/AM action was demonstrated by wash-out experiments; Cl- secretion induced by high doses of cAMP/AM (100 microM) could be quickly abolished by rinsing of the cells, whereas similar experiments with bt2cAMP/AM and Sp-5,6-DCI-cBIMPS showed much slower decreases. Even more sensitive to residual cAMP derivatives was the synergistic effect of carbachol, which was applied after the incubation with membrane-permeant derivatives and their subsequent wash-out. Although doses of cAMP derivatives that barely activated Cl- secretion were readily capable of inducing a synergistic response with carbachol, cells incubated with high doses of cAMP/AM (100 microM) and subsequently washed showed only a nonsynergistic carbachol response, in contrast to cells incubated with bt2cAMP/AM or Sp-5,6-DCI-cBIMPS. We therefore characterize cAMP/AM as a membrane-permeant derivative of cAMP that is easily metabolizable inside cells and hence is most useful for applications where a transient intracellular cAMP signal is desired. In contrast, completely nonmetabolizable Sp-5,6-DCI-cBIMPS seems to be more useful in longer incubations that require steady levels of cAMP-dependent protein kinase activation. bt2cAMP/AM combines the advantages of intracellular trapping by ester hydrolysis and reduced cyclophosphodiesterase sensitivity of its active intracellular product, which probably lead to its particularly high potency.

Cell Membrane↗
PubMed1993

Secondary structure and temperature-induced unfolding and refolding of ribonuclease T1 in aqueous solution. A Fourier transform infrared spectroscopic study.

The secondary structure of ribonuclease T1 (RNase T1) in aqueous solution and its temperature-induced structural changes have been investigated by Fourier-transform infrared (FT-IR) spectroscopy. 13 to 14% alpha-helix and 32 to 33% beta-sheet were estimated from the resolution-enhanced FT-IR spectra, in agreement with the crystal structure which indicates 16% alpha-helix and 35% beta-sheet. Specific IR-marker bands are assigned to the different beta-sheet structures, to the slightly bent alpha-helix, and to beta-turn and irregular conformations present in RNase T1. The temperature dependence of the infrared spectra shows that the thermal unfolding and refolding of RNase T1 is fully reversible. This permitted the detailed analysis of structural changes that occur as a function of temperature by evaluating quantitatively the various secondary structure-related amide I band components and some amino acid side-chain vibrations as specific monitors. The secondary structure of RNase T1 is essentially retained in the temperature range between 20 and 50 degrees C. Significant perturbation of protein structure is initiated between 50 and 55 degrees C within regions of beta-sheet structures while the alpha-helix remains virtually intact up to 55 degrees C suggesting a "premelting" of RNase T1. Between 55 and 60 degrees C, a highly co-operative unfolding process is indicated by the simultaneous breakdown of all secondary structure components and by distinct changes of some specific side-chain vibrations. An analysis of the amide I band contour of RNase T1 at 70 degrees C proves that the unfolded state is predominantly, but not completely, irregular or "random coil". Residual, turn-like structures persisting even in the unfolded state are suggested by minor, turn related band components in the amide I region. From IR-spectra collected along a linear temperature gradient, intensity/temperature and frequency/temperature profiles were constructed using some peptide backbone and amino acid side-chain marker bands as local, structure-sensitive monitors. From these profiles individual transition temperatures tm and transition enthalpies delta H (van't Hoff) were calculated. The tm and delta H values revealed a small but distinct hysteresis between repetitive cycles of unfolding and refolding of the protein, suggesting slow refolding kinetics of RNase T1. Furthermore, the various infrared "marker bands" indicate a slightly different response towards temperature increase/decrease for different regions of the protein. The data demonstrate that infrared spectroscopy permits both the detailed analysis of structural changes occurring in a protein as a function of temperature and the determination of thermodynamic parameters characterizing its folded/unfolded state transition.

Amides↗
PubMed1993

Secondary structure and temperature behavior of the acetylcholine receptor by Fourier transform infrared spectroscopy.

Fourier transform infrared spectroscopy (FT-IR) was used to test the secondary structure of purified acetylcholine receptor membranes from Torpedo californica. The secondary structure was estimated using the spectral features observed in the structure sensitive region of amide I and amide I' (between 1600 and 1700 cm-1), taking advantage of Fourier self-deconvolution and second-derivative techniques along with least-squares band fitting procedures. At least six different amide I' band components could be resolved in D2O and were tentatively assigned to beta-structures (1680 and 1636 cm-1), alpha-helices (1657 cm-1), aperiodic structures and/or distorted helices (1646-1648 cm-1), and turns (1690 and 1668 cm-1), respectively. The beta-band around 1637 cm-1, in particular, turned out to be complex since it reproducibly exhibited weak features near 1630 and 1627 cm-1, thereby suggesting the presence of different chain interacting beta-structures. The band near 1657 cm-1 was assigned to alpha-helices which transverse the membrane bilayers, while 1646-1648-cm-1 component was tentatively attributed to aperiodic structures and alpha-helices localized within the "globular head" of the receptor protein protruding from the membrane surface into the surrounding water. Least-squares band fitting procedures were applied in order to estimate relative amounts of secondary structures. The results suggest 36-43%, 32-33%, 14-24%, and 18-19% for beta-, alpha-helical, turn, and "rest" structures, respectively. Additionally, the temperature- and time-dependent variations of the secondary structure was tested by evaluating the changes of amide I and amide II band components of receptor membranes dispersed in H2O and D2O.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Acetoxymethyl esters of phosphates, enhancement of the permeability and potency of cAMP.

Acetoxymethyl esters of alkyl or aryl phosphates can be prepared by reacting their trialkylammonium or silver salts with acetoxymethyl bromide. Because acetoxymethyl esters are rapidly cleaved intracellularly, they facilitate the delivery of organophosphates into the cytoplasm without puncturing or disruption of the plasma membrane. In addition, acylation of free hydroxyls, for example with butyryl groups, is useful both for synthetic convenience and increased hydrophobicity of the permeant derivatives. The highly polar intracellular messengers cAMP and cGMP were thus converted into uncharged membrane-permeant derivatives. Extracellularly applied N6,2'-O-dibutyryl cAMP acetoxymethyl ester (Bt2cAMP/AM) is shown to simulate intracellular cAMP in three model systems, namely dissociation of cAMP-dependent protein kinase in fibroblasts, activation of Cl- secretion of monolayers of the human colon epithelial cell line T84, and dispersion of pigment granules in angel fish melanophores. Bt2cAMP/AM is effective at concentrations two or three orders of magnitude less than those required for commonly used membrane-permeant cAMP derivatives such as Bt2cAMP, 8-Br-cAMP, and 8-pCPT-cAMP lacking the acetoxymethyl ester. This methodology should be of general utility for the intracellular delivery of phosphate-containing second messengers.

Animals↗
PubMed1992

Academic emergency medicine: a national profile with and without emergency medicine residency programs.

STUDY OBJECTIVE: Formal data are lacking regarding emergency departments in academic medical centers, particularly those without an emergency medicine residency program. The Education Committee of the Society for Academic Emergency Medicine conducted a survey to define a national profile of academic emergency medicine. DESIGN: Prospective survey with telephone follow-up. SETTING: Academic medical centers. PARTICIPANTS: One hundred twenty-three academic medical centers as defined by the Association of American Medical Colleges. RESULTS: Results were obtained from 94 (78%) institutions: 27 (29%) had an emergency medicine residency program and 67 (71%) had no emergency medicine residency program. Significant differences were found between those with and without emergency medicine residency programs regarding 24-hour attending coverage (96% versus 73%), mean weekly clinical faculty hours (26 versus 33), the number of emergency medicine board-certified faculty, faculty recruitment difficulties (25% versus 75%), and the presence of a curriculum for housestaff (96% versus 38%). No significant differences were noted regarding the presence of a curriculum for medical students (78% versus 64%). Of the 67 institutions with no emergency medicine residency programs, 42% were actively planning a program, and 42% would consider future development of a program. CONCLUSION: This article provides the first comprehensive profile of emergency medicine in the Association of American Medical Colleges academic medical centers. Programs with emergency medicine residency programs provided more 24-hour attending coverage, had more emergency medicine board-certified faculty, and reported less difficulty recruiting additional faculty than institutions with no emergency medicine residency program. Both need to expand their undergraduate educational activities. Many institutions with no emergency medicine residency program are attempting to develop emergency medicine residency programs.

Academic Medical Centers↗
PubMed1992

[Histologic reactions of the bone-implant zone and cortical bone area after long-term hip replacement].

29 femora with cemented hip endoprostheses and 17 age related controls were analyzed regarding different histological criteria. All specimens were processed to undecalcified ultra thin grindings and in addition a few to surface stained block-grindings. The reactions at the bone implant interface in cases without loosening of the implant are: accumulation of macrophages and multinucleated giant cells, fibrous tissue membranes with a mean thickness of 103 microns and mineralization defects near the cement. The mean rate of direct bone/bone-cement contact is 2.7% of the whole cement surface. The phenomenons at the interface were explained as being the result of micromovement and resulting from wear and tear. The cortical bone demonstrates a remarkable loss of bone (up to 60% after 12 years) following an increase of osteoclastic resorption with no change of osteoblast activity. The localization of the bone loss indicates a relation to the new load situation after implantation.

Aged↗
PubMed1991

In vivo study of the state of order of the membranes of gram-negative bacteria by Fourier-transform infrared spectroscopy (FT-IR).

Temperature-induced order/disorder transition profiles were obtained from the membranes of intact Gram-negative bacterial cells by FT-IR analysis of the frequency shifts of the acyl chain methylene symmetric stretching band as a monitor. Cells grown at different temperatures yielded distinct transition profiles. At the individual growth temperatures, however, the nearly alike frequency values indicated a very similar 'state of order' of the bacterial membranes. The FT-IR data were complemented by GC analysis of whole cell fatty acid composition. The FT-IR data obtained in vivo gave direct evidence of the adaptation of the 'state of order' and 'fluidity' of bacterial membranes to varying growth temperatures.

Cell Membrane↗
PubMed1990

cis,cis-cyclohexane 1,3,5-triol polyphosphates release calcium from Neurospora crassa via an unspecific Ins 1,4,5-P3 receptor.

We investigated the effects of new inositol 1,4,5-trisphosphate analogues on the release of Ca2+ from isolated vacuoles of Neurospora crassa. Tri-O-butyryl-inositol 1,4,5-trisphosphate and a set of cis,cis-cyclohexane 1,3,5-triol bis-(CHT-P2) and trisphosphates (CHT-P3) gave an increase in free Ca2+ as measured directly with fura-2, a Ca2(+)-chelator. However, inositol 1,4-bisphosphate, 6-O-palmitoyl-inositol 4,5-bisphosphate and trans-cyclohexane 1,2-diol bisphosphate (trans CHD-P2) did not induce Ca2(+)-release. These results suggest that the 1,5-bisphosphate position in inositol 1,4,5-trisphosphate (Ins 1,4,5-P3) is the only essential arrangement for receptor binding to vacuoles of Neurospora crassa. The structures of these analogues are discussed on the basis of a general concept for the design of new Ins 1,4,5-P3 analogues.

Benzofurans↗
PubMed1990

Patterns and extent of isotype-specificity in the murine H chain switch DNA rearrangement.

We have analyzed the configuration of the H chain locus of 41 hybridomas by Southern blot analysis. Each H chain switch region was determined to be germ line, rearranged, or deleted. Including 13 previously analyzed hybridomas, 60% of those with rearrangements on both alleles showed a correlation of the two alleles, i.e., both the expressed and the nonexpressed alleles have rearranged to the same H chain constant region gene segment. When the two H chain alleles did not rearrange to the same gene, they often rearranged to neighboring H chain genes. These results support a role for isotype-specific factors in H chain switch recombination. The action of these isotype-specific factors may be propagated to some extent along the chromosome, which would lead to rearrangements to neighboring genes.

Alleles↗
PubMed1990

Chloroquine poisoning in a child.

Chloroquine poisoning in children, although infrequent, is extremely dangerous because of the narrow margin between therapeutic and toxic doses. Children clinically present with apnea, seizures, and cardiac arrhythmias. We present the case of a 12-month-old infant, the second-youngest patient reported in the US literature to die from chloroquine poisoning. A serum level of 4.4 mg/L (13.64 mumol/L) was obtained after the infant ingested only one tablet (300 mg). This establishes a new minimal lethal dose/blood level for children. Although some pediatric and adult pharmacokinetic and clinical similarities exist, the outcome is different. Pediatric mortality is 80%, whereas adult mortality is only 10%. Pediatric ingestion cases are primarily unintentional, and most adult cases are suicide attempts. Current treatment in adults includes a protocol of diazepam and epinephrine. Further studies involving children and these medications and other modalities are needed to improve survival.

Apnea↗
PubMed1990

Synthetic and computer-assisted analyses of the pharmacophore for the benzodiazepine receptor inverse agonist site.

The structural requirements for ligand binding to the benzodiazepine receptor (BzR) inverse agonist site were probed through the synthesis and in vitro evaluation of 3-substituted beta-carbolines 6, 7, 11, 12, gamma-carboline 13, and diindoles 18-21, 23-25, 27, 28, and 34. On the basis of the apparent binding affinities of these and other analogues, a hydrogen bond acceptor site (A2) on the receptor is proposed to interact with the N(9) hydrogen atom of the beta-carbolines or the N(7) hydrogen nuclei of the diindoles. Likewise, a proposed hydrogen bond donating site (H1) interacts with the N(2) nitrogen atom of the beta-carbolines or the N(5) nitrogen atom of the diindoles. It appears that interaction with both sites is a prerequisite for high affinity since analogues which have either one or both of these positions blocked exhibit substantial reduction in affinity. Moreover, H1 appears to be capable of engaging in a three-centered hydrogen bond with appropriately functionalized ligands, which explains the increase in potency observed in the following series of 3-substituted beta-carbolines: the n-butyl (12, IC50 = 245 nM), n-propoxy (9, IC50 = 11 nM), and propyl ketone (11, IC50 = 2.8 nM) congeners. In addition to H1 and A2, there appears to be a relatively narrow hydrophobic pocket in the binding cleft that can accommodate substituents at the 3-position of the beta-carbolines which have chain lengths less than or equal to C5. There is a 1 order of magnitude decrease in affinity between n-propoxy analogue 9 (IC50 = 11 nM, chain length = 4) and n-butoxy derivative 7 (IC50 = 98 nM, chain length = 5). Furthermore, alpha- and gamma-branching [e.g. ethoxycarbonyl (2), IC50 = 5 nM and tert-butoxycarbonyl (31) IC50 = 10 nM] but not beta- and delta-branching [e.g. isopropoxy (6), IC50 = 500 nM and (neopentyloxy) carbonyl (48), IC50 = 750 nM] at position 3 are tolerated. Occupation of this hydrophobic pocket is clearly important for high affinity as evidenced by the relatively low affinity of 30, a beta-carboline which possesses a hydrogen atom at the 3-position. This same hydrophobic pocket is partially filled by the D and E rings of the diindoles, which accounts for the high affinity of several members of this series. An excluded volume analysis using selected 3-substituted beta-carbolines and ring-E substituted pyridodiindoles is consistent with the presence of this hydrophobic pocket (see Figure 1).(ABSTRACT TRUNCATED AT 400 WORDS)

Binding Sites↗