Biomechanical strength and failure mechanism of different tubercula refixation methods within the framework of an arthroplasty for shoulder fracture.

BACKGROUND: Tuberosity repair in shoulder fracture prosthesis implantation still remains a challenge often leading to poor functional outcomes, despite a variety of materials and suggested suture patterns. We aimed to evaluate, which forces currently used suture and cerclage materials withstand and to assess whether they are useful with regard to stability of reconstruction of tuberosities and which failure modes they display. MATERIAL AND METHODS: Using sheep infraspinatus tendons with attached tuberosities three different suture materials (suture 1: Ethibond size 2; suture 2: Orthocord size 2; suture 3: Fiberwire size 5) and a 0.8mm titanium cerclage wire were investigated. For each suture material as well as the cerclage wire 6 tests were carried out. A material testing machine was used to perform cyclic loading tests (20mm/min, Fmin=50N, Fmax=100N, respectively after 50 cycles: Fmax+50N until failure). Outcome measures and thus comparison criteria were the maximum holding force, number of cycles reached, total elongation of the system (tendon and suture) and qualitative appraisal and documentation of the mechanism of failure. RESULTS: Overall average maximum forces between the fixation materials differed significantly (P=0.003), especially suture 3 (braided polyethylene coating, non-resorbable polyfile UHMW core) displayed superior results in comparison to the cerclage wire (P=0.016). Although, primary elongation of the cerclage technique was significantly lower compared to the suture materials (P=0.002). All tests showed a high initial lengthening and caused incision-like defects in the bone or tendon and led to failure and huge displacement of the tuberosities. DISCUSSION: Currently used suture and cerclage materials have a limited usefulness for refixation of tuberosities due to an increased risk of obstruction for bony consolidation. LEVEL OF EVIDENCE: Basic science, Biomechanics.

Impact of early detection and treatment of diabetes on the 6-year prevalence of cardiac autonomic neuropathy in people with screen-detected diabetes: ADDITION-Denmark, a cluster-randomised study.

AIMS/HYPOTHESIS: There is limited evidence on how multifactorial treatment improves outcomes of diabetes when initiated in the lead time between detection by screening and diagnosis in routine clinical practice. Cardiac autonomic neuropathy (CAN) in people with diabetes indicates widespread damage to the autonomic nervous system, which may severely affect health and quality of life. We examined effects of early detection and subsequent intensive treatment of type 2 diabetes in primary care on the prevalence of CAN at the 6-year follow-up examination in a pragmatic cluster-randomised parallel group trial. METHODS: One hundred and ninety general practices were randomised to deliver either intensive multifactorial treatment (IT) or routine care (RC) as recommended by national guidelines to patients with type 2 diabetes, identified through a stepwise screening programme in the primary care setting. 1533 people (IT, n = 910; RC, n = 623) were identified and included. At the 6-year follow-up examination, measures of CAN were applied in an unselected subsample of 777 participants using heart rate variability analysis and standard tests of CAN. RESULTS: At the 6-year follow-up examination, the prevalence of early CAN was 15.1% in the RC group and 15.5% in the IT group, while manifest CAN was present in 7.1% and 7.3%, respectively. We found no statistically significant effect of intensive treatment on the prevalence of CAN compared with routine care. CONCLUSIONS/INTERPRETATION: In the Danish arm of the ADDITION Study, signs of CAN were highly prevalent 6 years after a screening-based diagnosis of type 2 diabetes. Intensive multifactorial treatment did not significantly affect the prevalence of CAN compared with routine care. However, at follow-up the level of medication was also high in the RC group.

Cardiac structure and diastolic function in mild primary hyperparathyroidism.

CONTEXT: Data on the presence, extent, and reversibility of cardiovascular disease in primary hyperparathyroidism (PHPT) are conflicting. OBJECTIVE: To evaluate the heart in PHPT, we assessed cardiac structure and diastolic function in patients with mild PHPT compared with age- and sex-matched controls. DESIGN: This was a case-control study. SETTINGS: The study was conducted in a university hospital Metabolic Bone Diseases Unit. PARTICIPANTS: Fifty-four men and women with PHPT and 76 controls without PHPT participated in the study. OUTCOME MEASURES: We measured left ventricular mass index (LVMI), the presence of mitral annular calcification, the ratio of early to late diastolic mitral inflow velocities (E/A), and early diastolic velocity of the lateral mitral annulus using Doppler tissue imaging (tissue Doppler e'). RESULTS: Patients had mild disease with mean (+/-sd) serum calcium 10.5 +/- 0.5 mg/dl and PTH 96 +/- 45 pg/ml. LVMI and diastolic function were normal in PHPT. There was no difference in LVMI (98 +/- 23 vs. 96 +/- 24 g/m(2), P = 0.69) or the frequency of mitral annular calcification between PHPT cases and controls. Diastolic function variables (E/A and tissue Doppler e') were higher (better) in cases compared with controls, although both were within the reference range. PHPT patients with low E/A had higher serum PTH (121 +/- 36 vs. 89 +/- 46 pg/ml, P = 0.03) and calcium (10.8 +/- 0.4 vs. 10.5 +/- 0.5 mg/dl, P = 0.05) than those with normal values. Finally, we found LVMI to be inversely associated with serum 25-hydroxyvitamin D in PHPT (r = -0.29, P < 0.05). All findings persisted after adjustment for group differences in cardiovascular risk factors. CONCLUSIONS: Patients with biochemically mild PHPT do not have evidence of increased left ventricular mass, diastolic dysfunction, or increased valvular calcifications. However, the data support an association between low vitamin D levels and the development of left ventricular hypertrophy in this disorder. Finally, the increased serum calcium and PTH levels in those with diastolic dysfunction suggest that disease severity may determine the presence of cardiac manifestations in PHPT.

The decline in hip bone density after gastric bypass surgery is associated with extent of weight loss.

CONTEXT: Bariatric surgery is common and may be associated with deleterious effects on the skeleton. OBJECTIVE: Our objective was to assess bone metabolism and bone mineral density (BMD) after Roux-en-Y gastric bypass. DESIGN AND SETTING: We conducted a 1-yr prospective longitudinal study at a university hospital bariatric surgery practice and metabolic bone disease unit. PARTICIPANTS: Participants included 23 obese (mean body mass index 47 kg/m(2)) men and women, aged 20-64 yr. MAIN OUTCOME MEASURES: Serum PTH, 25-hydroxyvitamin D, osteocalcin, and urinary N-telopeptide, and BMD were assessed. RESULTS: Patients lost 45 +/- 2 kg 1 yr postoperatively (P < 0.01). PTH increased early (3 months, 43-50 pg/ml; P < 0.001) and urinary calcium dropped (161-92 mg/24 h; P < 0.01), despite doubling of calcium intake (1318-2488 mg/d; P < 0.001). Serum 25-hydroxyvitamin D concentrations were unchanged (23-26 ng/ml), although vitamin D intake increased by 260% (658 IU/d at baseline to 1698 IU/d at 12 months; P < 0.05). Markers of bone remodeling rose (P < 0.01 for both urinary N-telopeptide and osteocalcin), whereas BMD decreased at the femoral neck (9.2%, P < 0.005) and at the total hip (8.0%, P < 0.005). These declines were strongly associated with the extent of weight loss (femoral neck: r = 0.90, P < 0.0001; and total hip: r = 0.65, P = 0.02). Lumbar spine and distal radius sites did not change. CONCLUSIONS: After Roux-en-Y gastric bypass, there was evidence of calcium and vitamin D malabsorption. Bone turnover increased, and hip bone density rapidly declined. The decline in hip BMD was strongly associated with weight loss itself. Vigilance for nutritional deficiencies and bone loss in patients both before and after bariatric surgery is crucial.

Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.

Identification of a nonmammalian Golf subtype: functional role in olfactory signaling of airborne odorants in Xenopus laevis.

Attempts to identify the Galpha subtypes in the two compartments of the olfactory system from Xenopus, which are supposed to be specialized for detecting aquatic and volatile odorous compounds, revealed that a Galpha(o1) subtype is characteristic for the "water nose," the lateral diverticulum, whereas a novel Galpha(s) subtype predominates in the "air nose," the medial diverticulum. The newly identified Galpha(s)-type is more closely related to Galpha(olf) of rat and human than to the known Galpha(s)-isoform of Xenopus; it is therefore considered the first identified nonmammalian Galpha(olf) subtype. Sequence comparison of Galpha(olf) from amphibia and mammals revealed a particular conservation within the alpha-helical domains, which are supposed to control the GDP/GTP-exchange rate. The selective expression of different Galpha subtypes in the two anatomically separated and functionally specialized nasal compartments parallels the expression of distinct classes of olfactory receptors. Moreover, biochemical analysis revealed that stimulation with appropriate odorous compounds elicits the formation of inositol trisphosphate in the lateral diverticulum. In contrast, cyclic adenosine monophosphate signals were induced in the medial diverticulum, and this response appears to be mediated by the novel Galpha(olf) subtype. The data indicate that olfactory sensory neurons in each of the nasal cavities are equipped not only with defined sets of receptor types but also with a distinct molecular machinery for the chemo-electrical transduction process.

Radiology report production times: voice recognition vs. transcription.

Computer-based voice-recognition software has many potential advantages in producing reports of radiology procedures. Using voice-recognition systems, however, necessitates increased involvement of the radiologist in the process of producing the report. The radiologist, previously responsible only for recording a report onto tape and ensuring the integrity of the final report now becomes obligated to interact with the computer and to ensure the integrity of the transcription process as well as the accuracy of the final report. Two attending radiologists and one first-year radiology resident at an academic medical center timed the production of reports using both the voice recognition system and tape transcription of reports of plain films (n = 27), mammograms (n = 25), and GI/GU exams (n = 17). In addition, the taped dictations were transcribed and then corrected by the physicians. The additional correction time (determined as an average) was added to the tape times to produce a "corrected" tape time. Paired T-Test procedures were used to determine if pairs of readings (voice recognition vs. corrected tape transcription) differed in length of time. In addition, the data was stratified into three groupings--plain film, mammography, and GI/GU--in order to assess for differences between modalities. The length of time required to produce a radiology report using the commercial radiology voice recognition system employed at our center is significantly longer than that required by the traditional corrected tape transcription system. One motivation to use a voice recognition system is the cost savings achieved by eliminating transcriptionists and replacing them with the radiologist using the voice recognition system. In our institution this cost savings is estimated to be $100,000 annually. This apparent cost savings is reduced by the cost of the lost productivity of the radiologist. Compared to tape transcription, our data demonstrate a significant increase in the amount of time necessary for radiologists to produce a radiology report when using the voice recognition system currently employed in our hospital. While it is likely that future systems will require less extra time, this factor needs to be accounted for when departments consider using such systems to replace transcriptionists with radiologists.

A possible role for caveolin as a signaling organizer in olfactory sensory membranes.

Fast kinetics and sensitivity of olfactory signaling raise the question of whether the participating proteins may be associated in supramolecular transduction complexes. We found evidence that caveolin proteins could play an important role in organizing signaling elements in olfactory sensory neurons. Western blot analysis indicated that caveolins are highly enriched in olfactory sensory membranes, where they co-localize in detergent-insoluble complexes with key components of the signaling pathways. Furthermore, the results of immunoprecipitation experiments suggest that G proteins and effector enzyme form preassembled subcellular complexes with caveolins. Since anti-caveolin antibodies and synthetic peptides derived from the scaffolding domains of caveolin-1 and caveolin-2 effectively attenuated second messenger responses in sensory cilia preparations in a characteristic manner, the data led to the suggestion that caveolins could mediate the assembly of signaling complexes within specialized membrane microdomains of olfactory sensory neurons.

The CXC-chemokine platelet factor 4 promotes monocyte survival and induces monocyte differentiation into macrophages.

Unstimulated monocytes rapidly undergo physiological changes resulting in programmed cell death (apoptosis) while stimuli promoting differentiation of these cells into macrophages were shown to inhibit apoptotic processes. In the present study, we report that the platelet-derived alpha-chemokine platelet factor 4 (PF4) induces the differentiation of monocytes into macrophages, as is evident from morphological changes as well as from the up-regulation of differentiation markers (carboxypeptidase M/MAX1 and CD71). Significant alterations of the phenotype were observed after 72 hours of culture in the presence of the chemokine and required a minimal concentration of 625 nmol/L PF4. PF4-induced macrophages were characterized by a lack of HLA-DR antigen on their surface but showed a strong increase in the expression of the CD28 ligand B7-2. Furthermore, PF4 stimulation prevented monocytes from undergoing spontaneous apoptosis during 72 hours of culture as determined in an annexin-V-binding assay. Although PF4 induced the secretion of relevant amounts of TNF-alpha, neutralizing antibodies directed against TNF-alpha or granulocyte-macrophage colony-stimulating factor (GM-CSF) did not revert PF4-induced rescue from programmed cell death, suggesting that PF4 exerts its antiapoptotic effects in a TNF-alpha- or GM-CSF-independent fashion. On the basis of these results, we propose a novel role for PF4 in the control of monocyte differentiation during an inflammatory process in vivo. (Blood. 2000;95:1158-1166)

[Surveillance of group illnesses with Norwalk-like viruses (NLV) in Baden-Württemberg. Isolation and detection of Norwalk-like viral RNA from fecal samples with RT-PCR]. / Verfolgung von Gruppenerkrankungen mit Norwalk-like-Viren (NLV) in Baden-Württemberg. Isolierung und Detektion von Norwalk-like-Virus-RNA aus Stuhlproben mittels RT-PCR.

Between the turn of the years 98/99 and 99/2000, stool samples from various health departments in the south of Germany were sent to the LGA (Landesgesundheitsamt Baden-Württemberg). Different testings as bacteriological routines for enterobacteriaceae and virological antigen screenings of the stool samples for adeno-, astro- and rotaviruses lead to negative results. Additional RT-PCR tests for the presence of Norwalk-RNA showed nearly 40% of positive samples. From 14 group infections between december 98 and january 2000, 286 samples in total were sent to the LGA, 118 of them gave positive results for the norwalk agent. For the verification of the analysis, some random samples were sent to the Robert-Koch-Institut, div. of molecular virology at Berlin, where the results were confirmed.

[Sentinel lymph nodes in breast carcinoma]. / Sentinel Lymphknoten beim Mammakarzinom.

Aim of the experiment is to select patients with positive axillary lymph nodes by means of the sentinel lymph node concept. In this way all other patients who would not benefit from a lymph node dissection are spared from this procedure and its morbidity. Till now the sentinel lymphadenectomy is, however, still an experimental technic with yet unproven utility.

[Surgical procedures in therapy of breast carcinoma with reference to the value of axillary endoscopy techniques]. / Chirurgische Strategien zur Therapie des Mammakarzinoms unter Berücksichtigung des Stellenwertes axilloskopischer Techniken.

During the last decades the surgical treatment of breast cancer has been dramatically changed. Today breast conservative treatment represents a therapeutic option applicable to nearly 70% of the women. In contrast to this, the technic of axillary dissection remained unchanged. Suzanne et al. proposed an axilloscopic technic to reduce this morbidity. The sometimes unacceptable low lymph node count in the specimen induced us to modify this procedure. In the future the sentinel lymph node concept perhaps offers the possibility to select NO-patients and to spare the axillary dissection completely to this sub-group.

Differential expression and function of CD80 (B7-1) and CD86 (B7-2) on human peripheral blood monocytes.

The interaction of CD28 with its ligands is important for T-cell activation. Recent studies demonstrated the existence of at least two ligands on accessory cells, CD80 (B7-1) and CD86 (B7-2). In this study we demonstrate that, although CD80 and CD86 are both expressed on monocytes, they seem to have different functions. Freshly isolated monocytes express CD86 but are CD80-negative. CD80 expression is weakly induced after 6-8 hr of in vitro culture and is enhanced by stimulation. CD86 expression is enhanced faster than CD80 expression and reaches the peak level after 4-6 hr in stimulated cells. Reverse transcription-polymerase chain reaction studies demonstrate that freshly isolated monocytes contain no CD80-mRNA. The mRNA of CD80 is induced after 4-6 hr of culture, which matches with the expression of the protein. Inhibition studies using different antibodies against both molecules and the fusion protein CTLA4Ig show that only anti-CD80 and CTLA4Ig could partially inhibit antigen-specific (tuberculin) and polyclonal (anti-CD3) lymphoproliferation and interferon-gamma (IFN-gamma) secretion of T cells cocultured with autologous monocytes. IFN-gamma secretion was more sensitive to blocking costimulation than proliferation. The antibody BB-1 did not inhibit proliferation and cytokine secretion, nor did the anti-CD86 clone IT2.2. CTLA4Ig, which binds both CD80 and CD86, has the same inhibitory capacity as the anti-CD80 antibody tested. From those findings we conclude that human monocytes use CD80 as a costimulatory ligand for CD28 and utilize other costimulatory mechanisms besides those mediated via molecules of the B7 family.

No dantrolene protection in a dog model of complete cerebral ischaemia.

Intracellular free calcium is believed to play a major role in the ischaemic cascade which leads to cell death. Calcium channel blockers, which in part inhibit the influx of extracellular calcium, have been shown to be neuroprotective in both complete and focal cerebral ischaemia models. Dantrolene, an agent used in the treatment of malignant hyperthermia, is known to inhibit the release of stored intracellular calcium. Assuming that reduced levels of intracellular free calcium would improve neurologic outcome, we studied the neuroprotective potential of dantrolene. A complete cerebral ischaemia model was used to examine ten anesthetized dogs. Five were given intravenous dantrolene and five were given equal volumes of saline prior to the ischaemic event. Simultaneous occlusion of the venae cavae and ascending aorta provided eleven minutes of complete cerebral ischaemia as monitored by electroencephalography. Arterial blood gases and serum glucose levels were drawn prior to ischaemia, 5 and 20 minutes post-ischaemia, and following extubation. Forty-eight hours following the ischaemic event, neurologic outcomes were scored. No significant differences were observed between the two groups. All ten dogs had equally significant increases in serum glucose levels at 5 and 20 minutes post-ischaemia. The average neurologic outcome of the five dantrolene-treated dogs equalled the average of the five controls. These results suggest that dantrolene, alone, is not neuroprotective during complete cerebral ischaemia.

Non-Hodgkin's lymphomas--prognostic analysis and therapeutic recommendations.

The total non-Hodgkin's lymphoma-population between 1960 and 1985 treated by means of radiotherapy or combined radio-chemotherapy in the Medical Academy Dresden was analysed prognostically. 247 patients were classified according to previous scheme, 79 were subdivided on the basis of the recommendations of the Kiel-classification. The remission rates and survival curves achieved bear comparison with international literature (remission rates for the low-malignancy group = 85.3% and for the high-malignancy group = 80.0%; 5-year survival rates for the low-malignancy group = 61.9% and for the high-malignancy group = 41.7%). The influence of histology, clinical stage and involvement of organs is discussed according to our results and information from appropriate reference sources. Our analysis confirms the high importance of a common radiologic-internal outpatient department for coordination of the diagnostic and therapeutic programme. Principles of treatment are presented with special respect to polychemotherapy.