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Biomedical subjects

P Kuhn

Publications and source records attributed to P Kuhn.

At least 37 records · Page 2Linked to original sources
PubMed2000

A scandal in Salzburg or Freud's surreptitious role in the 1908 Abraham-Jung dispute.

The author argues that it was Freud's ambition to discover the 'caput Nili' in neuropsychology and that his discourse of anxiety informed his early dialogues with the Zurich School at the Burghölzli as he tried to persuade Bleuler and Jung, experts in dementia praecox (paranoia), to replace their toxic theory with his psychosexual theory. Although Karl Abraham adopted the libido theory, Freud's campaign to persuade Jung backfired on the eve of the First International Psychoanalytical Congress in Salzburg in 1908. Freud denied Jung's theoretical apostasy by reconfiguring an Abraham-Jung plagiarism dispute into a priority dispute and then insisted that both men collude with his narration. It is argued that Freud's narrative tyranny, his 'cover-story', recycled by Jones, occludes the significance of Salzburg from the psychoanalytic discourse.

Austria↗
PubMed2000

Major factors influencing breastfeeding rates: Mother's perception of father's attitude and milk supply.

OBJECTIVE: To determine factors influencing feeding decisions, breastfeeding and/or bottle initiation rates, as well as breastfeeding duration. SETTING: A family medicine practice of a 530-bed community-based hospital in northwestern Pennsylvania. PARTICIPANTS: All mothers whose infants received well-child care from birth to 1 year of age. OUTCOME MEASURE: A survey of 28 simple questions was developed and mailed to 245 mothers. The survey assessed: 1) demographics, 2) prenatal and postnatal care, 3) sources of breastfeeding information, 4) timing of decision, 5) preference, 6) type of feeding selected, 7) duration of breastfeeding, 8) factors influencing decisions to breastfeed and/or to bottle-feed, and 9) factors that would have encouraged bottle-feeding mothers to breastfeed. RESULTS: The breastfeeding initiation rate was 44.3%. By the time the infant was 6 months old, only 13% of these were still breastfeeding. The decision to breastfeed or to bottle-feed was most often made before pregnancy or during the first trimester. The most common reasons mothers chose breastfeeding included: 1) benefits the infant's health, 2) naturalness, and 3) emotional bonding with the infant. The most common reasons bottle-feeding was chosen included: 1) mother's perception of father's attitude, 2) uncertainty regarding the quantity of breast milk, and 3) return to work. By self-report, factors that would have encouraged bottle-feeding mothers to breastfeed included: 1) more information in prenatal class; 2) more information from TV, magazines, and books; and 3) family support. CONCLUSIONS: To overcome obstacles, issues surrounding perceived barriers, such as father's attitude, quantity of milk, and time constraints, need to be discussed with each parent. To achieve the goal of 75% of breastfeeding mothers, extensive education regarding the benefits must be provided for both parents and optimally the grandmother by physicians, nurses, and the media before pregnancy or within the first trimester.

Adult↗
PubMed1999

Crystallization and preliminary crystallographic study of stonustoxin, a protein lethal factor isolated from the stonefish (Synanceja horrida) venom.

Crystals of stonustoxin have been obtained and diffract to 3.4 A resolution. Stonustoxin is a protein lethal factor isolated from the venom of the stonefish, Synanceja horrida. The crystals belong to the tetragonal space group P422, with unit cell constants a = b = 109.0 A, c = 245.7 A. A native stonustoxin molecule has two subunits, designated alpha and beta, respectively, and there is one stonustoxin molecule per asymmetric unit.

Animals↗
PubMed1999

[Antiallergy drugs and respiratory diseases in children].

Second generation antihistamines (anti H1) are effective for seasonal and perennial rhinoconjunctivitis curative or preventive treatment in children. They are better tolerated than first generation drugs. They probably do not act specifically against asthma itself, but are nevertheless useful for relief of nasal obstruction, which is an asthmogenic factor frequently linked with bronchial asthma. The therapeutic relevance of oral ketotifen and inhaled chromones (sodium cromoglycate, nedocromil sodium) is unequally considered among pediatricians. However, their efficacy has been clearly demonstrated as a ground treatment in mild-to-moderate asthmatic children. Chromones are also useful in preventing exercise-induced asthma. Because of their low cost and the lack of potential side effects, and according to the guidelines established in 1997 by the National Heart, Lung and Blood Institute, they should be prescribed at first sight in these indications.

Adolescent↗
PubMed1999

A professor through the looking-glass. Contending narratives of Freud's relationships with the sisters Bernays.

In 1982 Peter Swales claimed that Minna Bernays, Freud's sister-in-law, aborted Freud's child in Merano in September 1900. Letters published subsequently reveal flaws in Swales's hypothesis. Drawing on current literary theories the author recontextualises the 'aliquis slip' within a new narrative of the Freuds' 1900 summer holiday, revealing not an abortion crisis but Freud's momentary fear that his wife Martha was again pregnant. A chronological reconstruction of the production the 'aliquis slip' and Freud's financial error offers new ways of reading Freud's subsequently composed texts. A precision dating of the 'table d'hôte dream' allows it to be set within its syntagmatic chain, thereby suggesting Freud's marital crisis and bitterness at his failed professorial application. It is a cocaine anniversary dream dredging up a sixteen-year grudge against Martha and the recently elevated Professor Königstein, both of whom Freud still held responsible for his failure to best Koller in discovering the anaesthetic properties of cocaine in eye surgery.

Correspondence as Topic↗
PubMed1999

Treatment outcomes for female octogenarians with breast cancer.

Scant information is available comparing the treatment outcomes of minor surgery (lumpectomy) versus extensive treatment (radical and simple mastectomy or lumpectomy and radiation) in octogenarians with breast cancer. Medical records of women (ages 80-89) who received treatment for breast cancer from 1984 through 1994 were reviewed. All patients were stage T1 or T2, and none had palpable lymph nodes. The recurrence rate, disease-free interval, and death rate for both groups were compared. Of the 41 patients representing 43 minor surgeries, 12 per cent (5 of 41) of patients developed recurrence, all of which were related to the primary breast tumor. The mean disease-free interval was 28.6 +/- 24.7 months (range, 6-65). Forty-six per cent (18 of 39) of patients died, 10 per cent (4 of 39) from recurrence and metastatic disease from breast cancer and 36 per cent (14 of 39) from other causes. Of those who underwent extensive treatment, 14.6 per cent (7 of 48) of patients experienced recurrence, all related to the primary breast tumor. The mean disease-free interval was 24.0 +/- 21.9 months (range, 2-71). Forty-eight per cent (23 of 48) of patients died, 10 per cent (5 of 48) from recurrence and metastatic disease from breast cancer and 37 per cent (18 of 48) from other causes. None of the differences between the minor surgery versus extensive treatment groups were statistically significant. The recurrence rate, disease-free interval, and death rate from recurrent disease are similar for patients undergoing minor surgery compared with those undergoing extensive treatment.

Aged↗
PubMed1998

The 1.25 A resolution refinement of the cholera toxin B-pentamer: evidence of peptide backbone strain at the receptor-binding site.

Crystals of the 61 kDa complex of the cholera toxin B-pentamer with the ganglioside GM1 receptor pentasaccharide diffract to near-atomic resolution. We have refined the crystallographic model for this complex using anisotropic displacement parameters for all atoms to a conventional crystallographic residual R=0.129 for all observed Bragg reflections in the resolution range 22 A to 1.25 A. Remarkably few residues show evidence of discrete conformational disorder. A notable exception is a minority conformation found for the Cys9 side-chain, which implies that the Cys9-Cys86 disulfide linkage is incompletely formed. In all five crystallographically independent instances, the peptide backbone in the region of the receptor-binding site shows evidence of strain, including unusual bond lengths and angles, and a highly non-planar (omega=153.7(7) degrees) peptide group between residues Gln49 and Val50. The location of well-ordered water molecules at the protein surface is notable reproduced among the five crystallographically independent copies of the peptide chain, both at the receptor-binding site and elsewhere. The 5-fold non-crystallographic symmetry of this complex allows an evaluation of the accuracy, reproducibility, and derived error estimates from refinement of large structures at near-atomic resolution. We find that blocked-matrix treatment of parameter covariance underestimates the uncertainty of atomic positions in the final model by approximately 10% relative to estimates based either on full-matrix inversion or on the 5-fold non-crystallographic symmetry.

Binding Sites↗
PubMed1998

The 0.78 A structure of a serine protease: Bacillus lentus subtilisin.

Ultrahigh-resolution X-ray diffraction data from cryo-cooled, B. lentus subtilisin crystals has been collected to a resolution of 0.78 A. The refined model coordinates have a rms deviation of 0.22 A relative to the same structure determined at room temperature and 2.0 A resolution. Several regions of main-chain and side-chain disorder have been identified for 21 out of 269 residues in one polypeptide chain. Hydrogen atoms appear as significant peaks in the Fo - Fc difference electron density map, and carbon, nitrogen, and oxygen atoms can be differentiated. The estimated standard deviation (ESD) for all main-chain non-hydrogen bond lengths is 0.009 A and 0.5 degrees for bond angles based on an unrestrained full-matrix least-squares refinement. Hydrogen bonds are resolved in the serine protease catalytic triad (Ser-His-Asp). Electron density is observed for an unusual, short hydrogen bond between aspartic acid and histidine in the catalytic triad. The hydrogen atom, identified by NMR in numerous serine proteases, appears to be shared by the heteroatoms in the bond. This represents the first reported correlation between detailed chemical features identified by NMR and those in a cryo-cooled crystallographic structure determination at ultrahigh resolution. The short hydrogen bond, designated "catalytic hydrogen bond", occurs as part of an elaborate hydrogen bond network, involving Asp of the catalytic triad. While unusual, these features appear to have conserved analogues in other serine protease families although specific details differ from family to family.

Aspartic Acid↗
PubMed1998

A bisubstrate analog induces unexpected conformational changes in phosphoglycerate kinase from Trypanosoma brucei.

The glycolytic enzyme phosphoglycerate kinase (PGK) catalyzes phosphoryl transfer between 1,3-bis-phosphoglycerate and ADP to form 3-phosphoglycerate and ATP. During catalysis, a major hinge bending motion occurs which brings the N and C-terminal enzyme domains and their bound substrates together and in-line for phosphoryl transfer. We have crystallized Trypanosoma brucei PGK in the presence of the bisubstrate analog, adenylyl 1,1,5,5-tetrafluoropentane-1, 5-bisphosphonate, and solved the structure of this complex in two different crystal forms at 1.6 and 2.0 A resolution, obtained from PEG 8000 and ammonium phosphate solutions, respectively. These high resolution structures of PGK:inhibitor complexes are of particular interest for drug design since Trypanosoma brucei, the causative agent of African sleeping sickness, relies on glycolysis as its sole energy source. In both structures, the inhibitor is bound in a fully extended conformation with its adenosine moiety assuming exactly the same position as in ADP:PGK complexes and with its 5' phosphonate group occupying part of the 1,3-bis-phosphoglycerate binding site. The bisubstrate analog forces PGK to assume a novel, "inhibited" conformation, intermediate in hinge angle between the native structures of open and closed form PGK. These structures of enzyme-inhibitor complexes demonstrate that PGK has two distinct hinge points that can each be independently activated. In the "PEG" structure, the C-terminal hinge is partially activated while the N-terminal hinge point remains in an open state. In the "phosphate" structure, closure of the N-terminal hinge point is also evident. Finally and most unexpectedly, both complex structures also contain a 3 A shift of a helix that lies outside the flexible hinge region. We propose that a transient shift of this helix is a required element of PGK hinge closure during catalysis.

Animals↗
PubMed1998

Prospective comparison of flecainide versus sotalol for immediate cardioversion of atrial fibrillation.

This study sought to compare the efficacy and safety of intravenous flecainide and sotalol for immediate cardioversion of atrial fibrillation. We performed a prospective, randomized, single-blind, multicenter trial, including 106 hemodynamically stable patients with atrial fibrillation, stratified according to duration of the arrhythmia. Exclusion criteria included severely reduced left ventricular systolic function, recent antiarrhythmic therapy, and hypokalemia. Patients were randomly assigned to receive either intravenous flecainide or intravenous sotalol. Trial medication was given at a dose of 1.5 mg/kg body weight (maximum 150 mg). Overall, 28 of 54 patients (52%) given flecainide and 12 of 52 patients (23%) given sotalol converted to sinus rhythm during the first 2 hours after start of the infusion (p = 0.003). Multivariate analysis confirmed that treatment allocation to flecainide, an arrhythmia duration of < or = 24 hours, higher plasma magnesium level at baseline, higher age for men, and lower age for women independently increases the probability of conversion. The frequency of adverse effects was not significantly different in the 2 treatment groups.

Age Factors↗
PubMed1998

Structure at 0.85 A resolution of an early protein photocycle intermediate.

Protein photosensors from all kingdoms of life use bound organic molecules, known as chromophores, to detect light. A specific double bond within each chromophore is isomerized by light, triggering slower changes in the protein as a whole. The initial movements of the chromophore, which can occur in femtoseconds, are tightly constrained by the surrounding protein, making it difficult to see how isomerization can occur, be recognized, and be appropriately converted into a protein-wide structural change and biological signal. Here we report how this dilemma is resolved in the photoactive yellow protein (PYP). We trapped a key early intermediate in the light cycle of PYP at temperatures below -100 degrees C, and determined its structure at better than 1 A resolution. The 4-hydroxycinnamoyl chromophore isomerizes by flipping its thioester linkage with the protein, thus avoiding collisions resulting from large-scale movement of its aromatic ring during the initial light reaction. A protein-to-chromophore hydrogen bond that is present in both the preceding dark state and the subsequent signalling state of the photosensor breaks, forcing one of the hydrogen-bonding partners into a hydrophobic pocket. The isomerized bond is distorted into a conformation resembling that in the transition state. The resultant stored energy is used to drive the PYP light cycle. These results suggest a model for phototransduction, with implications for bacteriorhodopsin, photoactive proteins, PAS domains, and signalling proteins.

Bacteria↗
PubMed1998

Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA.

Topoisomerases I promote the relaxation of DNA superhelical tension by introducing a transient single-stranded break in duplex DNA and are vital for the processes of replication, transcription, and recombination. The crystal structures at 2.1 and 2.5 angstrom resolution of reconstituted human topoisomerase I comprising the core and carboxyl-terminal domains in covalent and noncovalent complexes with 22-base pair DNA duplexes reveal an enzyme that "clamps" around essentially B-form DNA. The core domain and the first eight residues of the carboxyl-terminal domain of the enzyme, including the active-site nucleophile tyrosine-723, share significant structural similarity with the bacteriophage family of DNA integrases. A binding mode for the anticancer drug camptothecin is proposed on the basis of chemical and biochemical information combined with these three-dimensional structures of topoisomerase I-DNA complexes.

Antineoplastic Agents, Phytogenic↗
PubMed1998

'A pretty piece of treachery': the strange case of Dr Stekel and Sigmund Freud.

Freud claimed he broke with Stekel not because of 'scientific differences' but because of 'exclusively ... personal qualities'. The author offers an alternative version of this significant fragment of psychoanalytic history by suggesting that Freud acted out of revenge for the humiliation that he believed Stekel and Adler inflicted upon him at the 1910 Nuremberg Congress. He suggests that casting the story of the break between Stekel and Freud in the narrative shadow of Robert Louis Stevenson's novella 'Jekyll and Hyde' highlights the extent to which Freud involved himself in the murkier aspects of the politics of the International Psychoanalytical Association and the Vienna Psychoanalytic Society. Ultimately, however, he argues, Freud was cynically prepared to use and then callously sacrifice Stekel, one of his oldest and most loyal followers, in his increasingly bitter struggles against Adler and Jung. He also touches upon the role of the 'Secret Committee' in the 'Stekel Affair' and the wider ramifications of Jung's unexpected return from America at the height of the 'Freud resignation crisis'. He further suggests that Jung's subsequent meeting with Bergmann may have been a significant factor in precipitating Jung's decision to break his personal relationship with Freud.

Austria↗
PubMed1997

Crystal structure of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenase and the enzyme-product complex.

Inosine-5'-monophosphate dehydrogenase (IMPDH) is an attractive drug target for the control of parasitic infections. The enzyme catalyzes the oxidation of inosine monophosphate (IMP) to xanthosine monophosphate (XMP), the committed step in de novo guanosine monophosphate (GMP) biosynthesis. We have determined the crystal structures of IMPDH from the protozoan parasite Tritrichomonas foetus in the apo form at 2.3 A resolution and the enzyme-XMP complex at 2.6 A resolution. Each monomer of this tetrameric enzyme is comprised of two domains, the largest of which includes an eight-stranded parallel beta/alpha-barrel that contains the enzyme active site at the C termini of the barrel beta-strands. A second domain, comprised of residues 102-220, is disordered in the crystal. IMPDH is expected to be active as a tetramer, since the active site cavity is formed by strands from adjacent subunits. An intrasubunit disulfide bond, seen in the crystal structure, may stabilize the protein in a less active form, as high concentrations of reducing agent have been shown to increase enzyme activity. Disorder at the active site suggests that a high degree of flexibility may be inherent in the catalytic function of IMPDH. Unlike IMPDH from other species, the T. foetus enzyme has a single arginine that is largely responsible for coordinating the substrate phosphate in the active site. This structural uniqueness may facilitate structure-based identification and design of compounds that specifically inhibit the parasite enzyme.

Amino Acid Sequence↗
PubMed1997

Perinatal ultrasonography and magnetic resonance imaging findings in congenital hydrocephalus associated with fetal intraventricular hemorrhage.

OBJECTIVE: We present the case histories of three premature infants with congenital posthemorrhagic hydrocephalus. STUDY DESIGN: The timing of the lesion was monitored in utero in two of the three cases. Magnetic resonance imaging studies (prenatal in one case, within 24 hours of birth in all three cases) established the duration of the lesions and thereby added to the ultrasonographic findings. RESULTS: All three patients demonstrated a similar pattern of lesions, consisting of (1) unilateral germinal matrix hemorrhage with cystic resorption, (2) residual blood in the cerebrospinal fluid with a "granular" ependymal reaction, (3) asymmetric ventriculomegaly predominating on the side of the hemorrhage with mild atrophy and periventricular cysts, and (4) partial hypoplasia of the ipsilateral thalamus. On the basis of two cases in which information about the pregnancy was available and in which fetal oligohydramnios without ruptured membranes was detected, we assume that this pattern of lesions may have resulted from a hypoxic-ischemic episode followed by intraventricular hemorrhage. CONCLUSIONS: Because these three infants with congenital hydrocephalus were born during a period of only 18 months in a perinatal center serving a region with 16,000 live births per year, we speculate that a posthemorrhagic cause for congenital hydrocephalus underestimated.

Adult↗