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Biomedical subjects

R Hoffmann

Publications and source records attributed to R Hoffmann.

At least 127 records · Page 7Linked to original sources
PubMed2000

Comparison of three different plating techniques for the dorsum of the distal radius: a biomechanical study.

Three different plating techniques were used on experimentally produced dorsally displaced distal radius fractures in cadavers and were tested in 4-point bending: a AO 3.5-mm T plate (group 1), two 2. 0-mm titanium plates 60 degrees to each other (group 2), and the AO pi plate (group 3). A metaphyseal defect was simulated by a dorsally open wedge osteotomy. The tests show that the 2-mm double-plating technique has superior stiffness and statistically equivalent bending and bone gap to failure compared with the AO 3.5-mm T plate or the pi plate when applied to the unstable distal radius fracture model. (J Hand Surg 2000; 25A:29-33.

Biomechanical Phenomena↗
PubMed2000

Capecitabine in the treatment of metastatic renal cell carcinoma.

To evaluate the therapeutic effects and systemic toxicities of a capecitabine-based home therapy regimen in patients with metastatic renal cell carcinoma, 30 patients were enrolled in a phase II clinical trial. Treatment consisted of oral capecitabine combined with subcutaneous recombinant human interferon-alpha 2a, recombinant human interleukin-2 and oral 13-cis-retinoic acid. There were two (7%) complete responses (CRs) and eight (27%) partial remissions (PRs), for an overall objective response rate of 34% (95% CI 17-53%). Except one, all responses are ongoing, with a median duration of 9+ and 8+ months for CRs and PRs, respectively. Additionally, 12 patients (40%) reached stable disease. Eight patients (27%) showed continued disease progression despite treatment. Therapy was well tolerated and was given in the outpatient setting. Capecitabine-related World Health Organization (WHO) grade 2 and 3 toxicities were observed in five and two patients respectively, and were limited to fatigue, nausea/vomiting, diarrhoea, stomatitis, dermatitis and hand-and-foot syndrome. The substitution of capecitabine for 5-FU in the pre-existing biochemotherapy regimen did not result in a reduced therapeutic efficacy and showed significant anti-tumour activity in patients with advanced renal cell carcinoma.

Administration, Oral↗
PubMed2000

Coping strategies and emotional wellbeing among HIV-infected men and women experiencing AIDS-related bereavement.

AIDS influences the psychological coping not only of the person with the disease but also those close to that individual. Following a death from AIDS, family members and friends may experience atypical bereavement. Bereavement coping challenges can be especially difficult and pronounced for persons who are themselves HIV-positive. The prevalence of AIDS-related bereavement and psychosocial predictors of grief severity were examined in an ethnically diverse sample of 199 HIV-infected men and women. Eighty per cent of HIV-positive respondents had experienced the loss of someone close to AIDS, the majority of whom had sustained multiple and repetitive losses. Two-thirds of the participants who had experienced an AIDS-related loss reported grief symptoms in the past month. Hierarchical regression analyses revealed that grief was most closely associated with emotional suppression and avoiding coping strategies, with residual variance related to depression. Interventions for AIDS-related bereavement that reduce distress and maladaptive ways of coping are needed in order to meet the secondary prevention needs of bereaved people living with HIV/AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Insect peptides with improved protease-resistance protect mice against bacterial infection.

At a time of the emergence of drug-resistant bacterial strains, the development of antimicrobial compounds with novel mechanisms of action is of considerable interest. Perhaps the most promising among these is a family of antibacterial peptides originally isolated from insects. These were shown to act in a stereospecific manner on an as-yet unidentified target bacterial protein. One of these peptides, drosocin, is inactive in vivo due to the rapid decomposition in mammalian sera. However, another family member, pyrrhocoricin, is significantly more stable, has increased in vitro efficacy against gram-negative bacterial strains, and if administered alone, as we show here, is devoid of in vitro or in vivo toxicity. At low doses, pyrrhocoricin protected mice against Escherichia coli infection, but at a higher dose augmented the infection of compromised animals. Analogs of pyrrhocoricin were, therefore, synthesized to further improve protease resistance and reduce toxicity. A linear derivative containing unnatural amino acids at both termini showed high potency and lack of toxicity in vivo and an expanded cyclic analog displayed broad activity spectrum in vitro. The bioactive conformation of native pyrrhocoricin was determined by nuclear magnetic resonance spectroscopy, and similar to drosocin, reverse turns were identified as pharmacologically important elements at the termini, bridged by an extended peptide domain. Knowledge of the primary and secondary structural requirements for in vivo activity of these peptides allows the design of novel antibacterial drug leads.

Amino Acid Sequence↗
PubMed2000

Non-contrast second harmonic imaging improves interobserver agreement and accuracy of dobutamine stress echocardiography in patients with impaired image quality.

OBJECTIVE: To examine the influence of second harmonic imaging during dobutamine echocardiography on regional endocardial visibility, interobserver agreement in the interpretation of wall motion abnormalities, and diagnostic accuracy in patients with reduced image quality. DESIGN: Blinded comparison. SETTING: Tertiary care centre. PATIENTS: 103 consecutive patients with suspected coronary artery disease and impaired transthoracic image quality (>/= 2 segments with poor endocardial delineation). METHODS: Fundamental and second harmonic imaging were performed at each stage of a dobutamine stress echocardiography. Coronary angiography was undertaken within three weeks of dobutamine echocardiography in 75 patients. MAIN OUTCOME MEASURES: Evaluation of regional endocardial visibility (scoring from 0 = poor to 2 = good) and of segmental wall motion abnormalities for both modalities separately. A second blinded examiner analysed 70 studies to determine interobserver agreement. RESULTS: Mean (SD) visibility score for all segments was 1.2 (0.4) using fundamental imaging and 1.7 (0.2) using second harmonic imaging at rest (p < 0.001), and 1.1 (0.4) v 1.6 (0.3), respectively, at peak dobutamine dose (p < 0.001). The average number of segments with poor endocardial visibility was lower for second harmonic than for fundamental imaging (0.6 (1.1) v 3.8 (2.6) at rest, p < 0.001; 0.9 (1.3) v 4.3 (2.9) at peak dose, p < 0.001). Improvement was most pronounced in all lateral and anterior segments. The kappa value for identical study interpretation increased from 0. 40 to 0.69 (p < 0.05). Sensitivity for the diagnosis of coronary artery disease was 64% using fundamental imaging versus 92% using harmonic imaging (p < 0.001), while specificity remained unchanged at 75% for both imaging modalities. CONCLUSIONS: Second harmonic imaging enhances endocardial visibility during dobutamine echocardiography. Consequently, interobserver agreement on stress echocardiography interpretation and diagnostic accuracy are significantly improved compared to fundamental imaging. Thus, in difficult to image patients, dobutamine echocardiography should be performed using second harmonic imaging.

Cardiotonic Agents↗
PubMed2000

An X-linked gene involved in androgenetic alopecia: a lesson to be learned from adrenoleukodystrophy.

BACKGROUND: Adrenoleukodystrophy (ALD), including its adult variant adrenomyeloneuropathy (AMN), is an X-linked recessive trait characterized by progressive demyelinization of the nervous system. The gene defect involves a peroxisomal transporter protein, resulting in accumulation of very-long-chain fatty acids in the brain and other organs such as the adrenal glands. Affected men show various endocrine disorders. Moreover, disturbances of hair growth are frequently mentioned in reports on ALD/AMN. OBJECTIVE: This study was performed to delineate further the hair status and type of hair loss in men with AMN. METHODS: We examined and documented the status of hair growth in 16 men suffering from AMN. A meticulous history with particular regard to hair changes was taken from all patients and their family members. RESULTS: The age of the patients varied between 27 and 62 years, their mean age was 39.8 years. Twelve men showed male-pattern androgenetic alopecia (AGA), Hamilton grades IV-VIII, 3 men had a female-pattern AGA (Ludwig grade I or II). Ten of the patients with male-pattern AGA had reached Hamilton stage VII or VIII. The remaining scalp hair was unusually scarce and thin in 11 cases, regardless of the grade of AGA. Moreover, in 10 of 16 patients the eyelids showed pronounced madarosis. The remaining body hair was found to be normal. If present, endocrine manifestations had started prior to the onset of alopecia, and in 11 of 12 patients hair loss was apparent before neurological symptoms were noted. CONCLUSION: ALD/AMN gives rise to two different types of hair loss. Firstly, affected men show diffuse hair loss involving the entire scalp and the eyelashes. Secondly, they tend to develop AGA more frequently and earlier and in a severer form. Paradoxically, pronounced AGA is present although the patients may simultaneously show some degree of hypogonadism. Hence, the X-linked ALD mutation can be taken as a well-defined gene within the polygenic spectrum of genes responsible for AGA. This may be of theoretical importance for the elucidation of the pathogenetic pathways of AGA.

Adrenoleukodystrophy↗
PubMed2000

Ferrocene: Ironclad History or Rashomon Tale?

What really happened? To recount a pivotal 20th century chemical discovery, the assignment of its structure to ferrocene, ain't easy! One might have thought that telling the story would be straightforward, from published papers and correspondence with some of their authors. Not so. One emerges with a good bit of sympathy for historians of science-who did just what and why is pretty hard to determine, even when less than fifty years have elapsed.

Journal Article↗
PubMed2000

Transesophageal 3-dimensional echocardiography: in vivo determination of left ventricular mass in comparison with magnetic resonance imaging.

The objective of this study was to assess the accuracy and reproducibility of transesophageal 3-dimensional echocardiography (3DE) in comparison with magnetic resonance imaging (MRI) for the in vivo calculation of left ventricular mass (LVM). In addition, mass values obtained by M-mode echocardiography were compared with those calculated by MRI. Three-dimensional reconstruction of the left ventricle was performed from a transesophageal and transgastric transducer position with a multiplane transducer in 20 patients. Left ventricular mass was calculated from both transducer positions by using slices of various thicknesses, ranging from 5 to 20 mm. Reproducibility was determined by 5 repeated measurements of mass in each of 5 randomly selected left ventricles. M-mode echocardiography was performed according to the method described by Devereux. For MRI, multiple short-axis views with 10-mm slice thickness were acquired in inspiration hold. Correlation was high for mass determined by 3DE and MRI (for 10-mm slice thickness: r = 0.99; y = 0.99 x - 0.7 g; standard error of estimate = 8.5 g; P <.001). There was no statistical bias, and the limits of agreement ranged from +/-16.4 g to +/-27.2 g, depending on the slice thickness. Variability was lowest for a slice thickness of 10 mm (SD +/- 8.2 g). The reproducibility of mass determination was excellent (mean width of the 95% CI 12.8 g). Left ventricular mass values calculated from the transgastric and transesophageal transducer position were not different from each other (mean bias 0.6 +/- 9.1 g; P = ns). M-mode-based LVM calculations showed systematic overestimation and large measurement variability (bias 23.7 g; 95% CI +/- 92.8 g). Compared with MRI, transesophageal 3DE is an accurate and reproducible method for the determination of LVM and clearly superior to M-mode echocardiography.

Adult↗
PubMed2000

Current understanding of androgenetic alopecia. Part I: etiopathogenesis.

Androgenetic alopecia (AGA) is the most common type of hair loss in men and women. This continuous process results in a type of alopecia that follows a definite pattern in those individuals who are genetically predisposed. At present the predisposing genes are unknown but the relatively strong concordance of the degree of baldness in fathers and sons is not consistent with a simple Mendelian trait and a polygenic basis is therefore most likely. AGA can be defined as a DHT-dependent process with continuous miniaturization of sensitive HF. Today we do not understand the molecular steps involved in androgen-dependent beard growth versus androgen-dependent hair loss in AGA. However, recent experimental and clinical advances enable us to explain some pathogenetic steps leading to androgenetic hair loss. Among other steroidogenic isoenzymes such as 17b- and 3b- hydroxysteroid dehydrogenases, the type 2 5a-reductase within the dermal papilla plays a central role by the intrafollicular conversion of T to DHT.

17-Hydroxysteroid Dehydrogenases↗
PubMed2000

Normalisation of hair follicle morphology in C3H/HeJ alopecia areata mice after treatment with squaric acid dibutylester.

Alopecia areata is a non-scarring, reversible disorder, presumably caused by an autoimmune attack on anagen hair follicles. Treatments are numerous, and most of these are ineffective. However, the elicitation of contact dermatitis on the affected skin is commonly associated with hair regrowth. A major advance in the study of alopecia areata has been the introduction and characterisation of the C3H/HeJ mouse model that exhibits many features of the human disease. In this study we examined the effects of squaric acid dibutylester treatment on hair follicles and the associated leukocyte infiltrate in alopecia areata mice by light and transmission electron microscopic analysis. This was compared with unaffected normal mice and alopecic untreated mice. Experimental mice were treated unilaterally with the contact allergen squaric acid dibutylester and the skin was assessed after hair regrowth. The characteristic pathological picture of alopecia areata was observed in alopecic but not normal mice. Nine of eleven experimental mice regrew hair on the treated side only and this was associated with a reduction in peri/intrafollicular inflammatory cell infiltrates, hair follicle dystrophy, melanin incontinence/clumping, and an increase in the numbers of hair follicles in full anagen. This normalisation of hair follicle status after treatment reflects the successful reversal of disease in these mice. The mechanism of action of topical immunotherapy with a potent contact allergen such as squaric acid dibutylester still needs to be elucidated, but an altered immune milieu is suspected. This study further validates the C3H/HeJ mouse model of alopecia areata in the search for therapeutic interventions in this common hair follicle disorder.

Adjuvants, Immunologic↗
PubMed2000

The novel drug CS-891 inhibits 5alpha-reductase activity in freshly isolated dermal papilla of human hair follicles.

The local conversion of testosterone (T) to the more potent androgen dihydrotestosterone (DHT) by 5alpha-reductase (5aR) is implicated in the pathogenesis of androgenetic alopecia (AGA). Recently, the clinical effectiveness of finasteride, a selective type II 5aR inhibitor, in treating AGA has been documented, and these clinical studies have shown that circulating DHT is lowered by 60-70% in men taking finasteride. The source of the residual circulating DHT is presumed to be due to type I 5aR activity which is not affected by finasteride. Several novel compounds with potent dual inhibitory activity on both isoenzymes have been described and CS-891 is one of them. This compound may be likewise effective in the prevention or treatment of AGA. As a prerequisite for such an action CS-891 should be able to inhibit 5aR activity in its target tissue: the hair follicles (HF). Here we report on the capability of CS-891 to inhibit 5aR activity in dermal papillae (DP) of human HF.

Adult↗
PubMed1999

Intravascular ultrasound comparison of chronic recoil among different stent designs.

Intravascular ultrasound studies were acquired in 70 native coronary artery lesions after implantation and at follow-up of Palmaz-Schatz, GFX, NIR, and CrossFlex stents. Chronic stent recoil was minimal in the Palmaz-Schatz, GFX, and NIR stents; however, there was small, but significant chronic recoil of the CrossFlex stent.

Coronary Disease↗
PubMed1999

Transthoracic echocardiography using second harmonic imaging: diagnostic alternative to transesophageal echocardiography for the detection of atrial right to left shunt in patients with cerebral embolic events.

OBJECTIVES: We sought to evaluate whether transthoracic contrast echocardiography using second harmonic imaging (SHI) is a diagnostic alternative to transesophageal contrast echocardiography (TEE) for the detection of atrial right to left shunt. BACKGROUND: Paradoxic embolism is considered to be the major cause of cerebral ischemic events in young patients. Contrast echocardiography using TEE has proven to be superior to transthoracic echocardiography (TTE) for the detection of atrial shunting, SHI is a new imaging modality that enhances the visualization of echocardiographic contrast agents. METHODS: We evaluated 111 patients with an ischemic cerebral embolic event for the presence of atrial right to left shunt using an intravenous (IV) contrast agent in combination with three different echocardiographic imaging modalities: 1) TTE using fundamental imaging (FI); 2) TTE using SHI; and 3) TEE. The severity of atrial shunting and the duration of contrast visibility within the left heart chambers were evaluated for each imaging modality. Image quality was assessed separately for each modality by semiquantitative scoring (0 = poor to 3 = excellent). Presence of atrial right to left shunt was defined as detection of contrast bubbles in the left atrium within the first three cardiac cycles after contrast appearance in the right atrium either spontaneously or after the Valsalva maneuver. RESULTS: A total of 57 patients showed evidence of atrial right to left shunt with either imaging modality. Fifty-one studies were positive with TEE, 52 studies were positive with SHI, and 32 were positive with FI (p<0.001 for FI vs. SHI and TEE). The severity of contrast passage was significantly larger using SHI (61.6+/-80.2 bubbles) compared to FI (53.7+/-69.6 bubbles; p<0.005 vs. SHI) but was not different compared to TEE (43.9+/-54.3 bubbles; p = NS vs. SHI). The duration of contrast visibility was significantly longer for SHI (17.4+/-12.4 s) compared to FI (13.1+/-9.7 s; p<0.001) and TEE (11.9+/-9.6 s; p<0.02). Mean image quality improved significantly from FI (1.5+/-0.8) to SHI (2.0+/-0.8; p<0.001 vs. FI) and TEE (2.5+/-0.7; p<0.001 vs. SHI). CONCLUSIONS: In combination with IV contrast injections, TEE and SHI have a comparable yield for the detection of atrial right to left shunt. Both modalities may miss patients with atrial shunting. In young patients with an unexplained cerebrovascular event and no clinical evidence of cardiac disease, a positive SHI study may obviate the need to perform a TEE study to search for cardiac sources of emboli.

Adult↗
PubMed1999

Virus-specific lymphokine production differs quantitatively but not qualitatively in acute and chronic hepatitis B infection.

Cytokines that are secreted as a response to viral antigen not only have direct antiviral properties but also crucially influence immune reactions determining the outcome of infection. As an advantageous alternative to the study of cytokines present in the supernatants of antigen-specific T cell clones and lines, we have used ELISPOT assays to determine the number of interferon-gamma (IFN-gamma)- and IL4-producing cells generated by peripheral blood mononuclear cells from patients with acute hepatitis B (AHB) and chronic hepatitis B (CHB) infection in response to HBcAg in a short-term culture (48 h). In response to HBcAg IFN-gamma was predominantly produced. In contrast to the results obtained in acute hepatitis B, the typical lymphokine pattern in CHB was characterized by a weak or absent antigen-specific IFN-gamma production. A predominance of IL-4-producing cells was not observed in either AHB or CHB. A significant number of IFN-gamma-producing cells was usually detectable during phases of viral elimination and the quality of the lymphokine response seemed to be epitope independent. Comparison of the results obtained in proliferation assays and ELISPOT assays clearly shows that lymphokine production upon stimulation with viral protein is totally independent of T cell proliferation and more sensitively reflects antiviral reactivity.

Acute Disease↗
PubMed1999

The development of circadian rhythms in a human infant.

STUDY OBJECTIVES: This study examines the ontogeny and interaction of circadian rhythms of sleep, wake, temperature, melatonin, and feeding in the human newborn, and the influence of photic and non-photic factors on the initiation of entrainment. DESIGN: An infant's sleep-wake state, temperature, and salivary melatonin were monitored from birth to 6 months. Temperature was obtained every hour, and the infant's sleep/eating onset/termination were observed continuously and recorded until day 182. Salivary melatonin was obtained weekly for a 24-hour period, starting at week 3. SETTING: The infant slept in his parents' bedroom. All household members awakened, retired, and ate meals according to a fixed schedule during the study, while the infant ate, slept, and woke on demand. PARTICIPANTS: A healthy male infant was the subject. Biological parents gathered data continuously for six months. INTERVENTIONS: The infant's schedule was on-demand; the household's was fixed. Illumination was restricted to sunlight. MEASUREMENTS AND RESULTS: The circadian rhythm of temperature appeared first, soon after birth, and became statistically significant within one week. The wake circadian rhythm appeared second, attaining significance at day 45; approximately the same time that increased melatonin concentration began to occur at sunset. The sleep circadian rhythm appeared last, attaining significance after day 56. Ninety to 120 minute zones of sustained wakefulness first appeared in the second month of life subsequent to awakening and prior to sleep onset. The infant's nocturnal sleep-onset was coupled to sunset before day 60 and subsequently to family bedtime, giving evidence of initial photic entrainment followed by social entrainment. CONCLUSIONS: Circadian rhythms appeared much more rapidly in this infant than previously reported; their rapid appearance was probably facilitated by maximal exposure to sunlight, and regular social cues. These lighting conditions replicate universal infant experience prior to the invention of artificial light.

Brain↗
PubMed1999

Tissue proliferation within and surrounding Palmaz-Schatz stents is dependent on the aggressiveness of stent implantation technique.

In-stent restenosis is entirely due to intimal hyperplasia. Histologic studies have indicated that intimal hyperplasia is related to the arterial injury induced during stent implantation. We used intravascular ultrasound (IVUS) imaging to study whether tissue proliferation inside and surrounding stents is related to the aggressiveness of the implantation technique. After intervention and follow-up (mean 5.6 +/- 3.7 months), serial IVUS imaging was performed in 102 native artery stented stenoses in 91 patients. Measurements at 5 predetermined segments within each stented lesion included external elastic membrane, stent, and lumen cross-sectional areas (CSAs). Calculations included mean plaque CSA growth outside of the stent (external elastic membrane-stent) and mean neointimal hyperplasia CSA and thickness within the stent (stent-lumen). Stenoses were categorized depending on the aggressiveness of stent placement (group 1, adjunct percutaneous transluminal coronary angioplasty pressure < 16 atm and/or balloon/artery ratio < 1.1; group 2, adjunct percutaneous transluminal coronary angioplasty pressure > or = 16 atm and balloon/artery ratio > or = 1.1). An aggressiveness score was calculated as balloon/artery ratio x inflation pressure. Mean intimal hyperplasia CSA (2.9 +/- 1.5 vs 2.2 +/- 1.6 mm2, p = 0.028), mean intimal hyperplasia thickness (0.34 +/- 0.19 vs 0.25 +/- 0.19 mm, p = 0.012), and mean peristent tissue growth CSA (2.5 +/- 1.0 vs 1.1 +/- 1.4 mm2, p = 0.003) were significantly greater in group 2 stenoses. In addition, intimal hyperplasia CSA and thickness correlated significantly with balloon/artery ratio x inflation pressures: r = 0.305, p = 0.002 and r = 0.329, p = 0.0007, respectively, as did peristent tissue proliferation CSA (r = 0.466, p = 0.001). Tissue proliferation inside and surrounding stents may be related to aggressiveness of the stent implantation technique.

Angioplasty, Balloon, Coronary↗