Using HIV-1 sequence variability to explore virus biology.

Human immunodeficiency virus type 1 (HIV-1) only recently established an epidemic world-wide infection in the human population. The virus persists in the human host through active replication and is able to avoid clearance by the immune system. Active replication is an important component of the rapid evolutionary potential of HIV-1, a potential which manifests itself in the evolution of immune escape variants, drug resistant variants, and variants with the ability to use different cell surface coreceptors in conjunction with CD4. Multiple zoonotic introductions, compartmentalization of virus replication in the body, and genetic bottlenecks associated with sampling during transmission, antiretroviral therapy, and geographic and/or host population isolation further contribute to the range of sequences present in extant viruses. The sum of the history of all of these phenomena is reflected in HIV-1 sequence variability, and most of these phenomena are ongoing today. Here we review the use of HIV-1 sequence variability to explore its underlying biology.     

Organization of central hyperthermic mechanisms in helium-cold hypothermic hamsters

We have investigated the ability of three hyperthermic stimuli (PGE2, 5-HT and ACh) to elicit hyperthermia in the Helium-Cold (He-Cold) hypothermic hamster. Hamsters in these conditions are poikilothermic and will passively follow room temperature in a regulated cold room. Animals were injected centrally at AH/POA sites via an indwelling guide tube at body temperatures maintained between 9-12 degrees C. Active sites in the AH/POA were determined prior to the experiment by PGE2 injection. PGE2 injection at an effective AH/POA site immediately reversed the anesthetic induced hypothermia in warm air. Hamsters were induced into hypothermia by the He-Cold induction method and body temperatures were maintained in a 9 degrees C cold room. Colonic temperatures were monitored at 5 minute intervals by a YSI thermistor probe and telethermometer. Central injections of 5-HT (2 micrograms/microliter) and ACh (50 micrograms/microliter) at effective AH/POA sites evoked significant increases in colonic temperature in He-Cold hamsters. PGE2 injections were not different from saline control injections and did not elicit pronounced temperature changes in these animals. Specific blockade of the 5-HT and ACh temperature increases was demonstrated with specific antagonist injections. The results suggest that the central organization of heat-gain mechanisms in the AH/POA is the same as normothermic animals even at temperatures well below those previously investigated.     

Vergleichende Ergebnisse komprimierender und nicht komprimierender Operationsmethoden nach medialer Schenkelhalsfraktur

This is a personal clinical and radiological follow-up of 65 patients with fractures of the femoral neck who were treated in 1973 to 1984 at our hospital. 30 patients were oparated by nailing according to Smith-Petersen and in 35 patients osteosynthesis was performed by means of three or four lag screws. A comparative study between these two methods was done. The two main complications of femoral neck fracture, a vascular head necrosis and pseudarthrosis, were of special interest. The mean follow-up time was 7.2 years with the fracture fixed by nailing and 4.1 years, with the fractures operated by lag screws. Out of the 65 patients the total rate of femoral head necroses was 21.5% and 10.7% of pseudarthrosis. In the fractures treated by the nailing method the rate of necrosis was 23.3% and the rate of pseudarthrosis 13.3%. In the fractures operated by lag screws the incidence of head necrosis was 20% and 8.5% by pseudarthrosis. Fracture displacement was primarily responsible for the development of aseptic necrosis, but we could see also a relation between head necrosis and the inclination of the fracture line. Fractures of the type PIII/GIII/IV are those with the highest rate of avascular necrosis. Furthermore, the development of both, aseptic necrosis and pseudarthrosis, is strongly influenced by incomplete reduction.     

Transosseous arthroscopic repair of partial articular-surface supraspinatus tendon tears

Partial articular-surface tendon avulsion (PASTA) lesions of the supraspinatus muscle represent a common cause for shoulder impairment and a preceding pathology for full-thickness tendon tears. Arthroscopic tendon repair is a possible surgical method of treatment. The purposes of cuff repair are anatomical tendon healing, prevention of tear size progression to completion and reduction of shoulder pain. In this report, we describe a transtendon arthroscopic technique of transosseous refixation of articular-side partial tears leaving the bursal layer of the supraspinatus tendon intact. A curved hollow needle is used to perform an all arthroscopic transosseous mattress suture. Thus, anatomical tendon-to-bone contact of the rotator cuff to the footprint is restored. Preliminary clinical results of 16 patients are convincing with significant pain relief and functional improvement.     

Long-term results (10 years) of intensive breast conserving therapy including a high-dose and large-volume interstitial brachytherapy boost (LDR/HDR) for T1/T2 breast cancer.

BACKGROUND AND PURPOSE: During the past 15 years many retrospective studies and prospective randomized trials have been published supporting the use of breast conserving treatment (BCT) including surgery and radiotherapy. However, there are still many controversies on the necessary amount of resection, the width of the resection margins and the optimal radiation technique, dose and volume, in particular of the boost. In this retrospective study a large cohort of 410 women with early breast cancer treated with BCT including an interstitial brachytherapy (BT) boost is evaluated after a long follow-up period. MATERIAL AND METHODS: In order to clarify the impact of the different treatment-related factors on local control, these were carefully discriminated, based on widely accepted classification and reporting systems for surgery as well as for radiotherapy. The surgical approach was classified according to EORTC criteria and a high rate of quadrantectomies (60%) was found. Dose and volume of interstitial BT is reported according to recommendations of ICRU 58, and reveals a significant radiation dose and volume: minimum target dose, mean central dose (MCD) and '85% of MCD' for low-dose rate (LDR) BT was mean 20, 28 and 24 Gy, for high-dose rate (HDR) BT it was mean '10, 15 and 13 Gy, respectively; the treated volume was 104 cc for LDR BT and 83 cc for HDR BT. RESULTS: The actuarial rates for overall survival, disease-free survival and disease-specific survival were 97, 90 and 98% at 5 years and 85, 79 and 92% at 10 years. There have been only 16 breast recurrences in 410 treated patients resulting in a 5- and 10-year actuarial local recurrence rate of 2 and 3.9%, respectively; six recurrences (1.5%) were in the original quadrant. Except age and menopausal status, all tumour- and patient-related risk factors had no significant impact on local control. CONCLUSIONS: Our data confirm that intensive BCT leads to excellent long-term results in terms of local control, masking classical risk factors. This high-dose and large-volume interstitial BT seems to be superior to classical BCT without BT.     

Early and intermediate results of conservatively and surgically treated lateral clavicular fractures]

Between 1986 and 1988 67 patients with distal clavicular fracture were treated at the trauma hospital in Innsbruck. Depending on type of fracture conservative treatment (using a spica or other bandages) was performed in those cases without dislocation. Operation was necessary if coracoclavicular ligament was ruptured and dislocation of the distal clavicular end was found in X-rays. The most common practice was the use of K-wires and wire-loops. Plate fixation was necessary in one case of delayed fracture healing. No pseudarthrosis was seen in X-rays, mobility of the shoulder girdle was good and symptoms of pain were rare.     

Effects of Kneippism, a standardized complex therapy, on pain, quality of life and use of medicines: cohort study with a one-year follow-up]

BACKGROUND: Inpatient as well as outpatient cure in a spa environment with commonly 3- to 4-week duration features a combination of different treatments customized according to the needs of the individual patient. The physiological rationale and the mode of action are widely accepted. However, firm quantitative evidence of the clinical effectiveness is incomplete. OBJECTIVE: To document the effects of a well standardized complex therapeutic regimen (Kneippism) on pain, quality of life, and drug consumption during therapy and with 1-year follow up. STUDY DESIGN: Prospective cohort study with assessments at the beginning, during, and at the end of treatment and with follow-up investigations 3, 6, and 12 months thereafter. SETTING: Four spa clinics in Bad W?rishofen, Southern Bavaria. PATIENTS: 363 patients (248 outpatients, mean duration of therapy 23.3 days, and 115 inpatients, mean duration of therapy 27.4 days), one half between 40 and 60 years old above 60 years of age, predominantly suffering from musculoskeletal and/or cardiovascular diseases. INTERVENTION: Custom-tailored combination of therapies comprising of hydro-, kinesi-, and phytotherapy, dietetics, 'ordnungstherapie', and continued disease-specific standard treatment, if necessary. MAIN OUTCOME MEASURE: Pain, patients' self-rating, (IRES questionnaire), medication. RESULTS: The monitored dimensions of pain improved significantly during treatment and remained at that level essentially for the complete follow up interval. The same was true for various dimensions of reported subjective complaints as well as for drug consumption. CONCLUSION: When estimating the clinical relevance of a complex therapeutic regimen such as a cure of 3- to 4-week duration, the question of the impact of the specific effect of single components is secondary to the question of the overall relevance of that therapeutic concept. The findings of this study point at potential long-term effects of at least 1-year duration.