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Biomedical subjects

S Weller

Publications and source records attributed to S Weller.

At least 55 records · Page 3Linked to original sources
PubMed1994

Phase I trial of valaciclovir, the L-valyl ester of acyclovir, in patients with advanced human immunodeficiency virus disease.

Valaciclovir, the L-valyl ester of acyclovir, is rapidly and extensively converted in humans to acyclovir after oral administration by first-pass metabolism. A phase I study was conducted in two cohorts of volunteers with advanced human immunodeficiency virus (HIV) disease (absolute CD4 lymphocyte count of < 150 cells per microliters) who received oral valaciclovir at dosages of 1,000 or 2,000 mg four times daily for 30 days. All patients were clinically stable without any changes in underlying HIV-related medications for > or = 6 weeks prior to entry in study; these medications were continued throughout the study. Multiple-dose administration of valaciclovir showed a generally favorable safety profile. Nausea, vomiting, diarrhea, and abdominal pain each were reported in < or = 31% of the patients; of these symptoms, only one episode of diarrhea was considered causally related to valaciclovir exposure. Four patients developed neutropenia (two at each dose level) which was not clinically significant. There were no renal or neurologic adverse events. Valaciclovir was rapidly absorbed and converted to acyclovir, with plasma valaciclovir levels generally undetectable or levels of < or = 0.4 microgram/ml. After 3 h postdosing, valaciclovir was not detectable in plasma. Acyclovir was measurable in plasma as early as 15 min following valaciclovir dosing, and plasma concentrations of acyclovir greatly exceeded those of valaciclovir. The mean values for the maximum concentration of drug in plasma, time to maximum concentration of drug in plasma, area under the concentration-time curve from 0 h to infinity, and apparent half-life of acyclovir obtained after single- and multiple-dose valaciclovir administration in HIV-infected patients were similar to those reported in normal healthy volunteers. The time to maximum concentration in serum and half-life of acyclovir after valaciclovir administration were approximately 2 and 3 h, respectively, which were similar to those reported after oral administration of acyclovir itself. The mean trough and peak acyclovir concentrations and the daily area under the concentration-time curve acyclovir values at steady state were 2.5 and 8.4 micrograms/ml and 120 h micrograms/ml, respectively, after a dosage of 2,000 mg of valaciclovir four times daily. These values were approximately fivefold greater than those achieved with high dosages of oral acyclovir (800 mg, five times daily) and were not affected by continued use of medications necessary for management of advanced HIV disease. Thus, 2,000 mg of valaciclovir given orally four times daily should be evaluated for its potential efficacy in suppressing cytomegalovirus and other herpes group virus infections not optimally managed with current oral acyclovir therapy.

Acyclovir↗
PubMed1994

[Indications, technique and results of muscle flaps in decubitus ulcers of the pelvic region in paraplegic patients].

Over a period of 10 years 57 pelvic pressure sores of 47 para- and tetraplegic patients were covered operatively with a muscle flap at the Co-Operative Trade Association Hospital for Accidents, at Tübingen, Germany. 39 patients with 49 muscle flap-covered decubiti were seen in a follow-up examination. Despite many postoperative complications--not uncommon for septic patients--there was a high rate of complete healing (94%) of the pressure sores within a short period of rehabilitation. Indeed one cannot prove the superiority of the muscle flaps over cutaneous and fasciocutaneous flaps because of the missing statistical comparability and correlation capability of the results with other studies. In our opinion muscle flaps in the pelvic area seem to be advantageous to cutaneous and fasciocutaneous flaps.

Adult↗
PubMed1994

[Results of "expanded" arthrolysis of the knee joint].

This report shows the results of 20 patients, suffering on severe knee stiffness, who were treated between 1980-1989 at the Berufsgenossenschaftliche Unfallklinik in Tübingen with an expanded knee arthrolysis. The knee stiffness of all patients was caused by trauma (65% polytrauma) or infection. More than 2/3 of the patients (70%) had a preoperative degree of motion which was less than 60 degrees. In average 9 months after the initial trauma the expanded knee arthrolysis was performed. The arthrolysis was in most of the cases (n = 15) combined with a supracondylar correction osteotomy. The average preoperative range of motion from (ext./flex.) 0-15-62 degrees has postoperatively been increased to (ext./flex.) 0-5-92 degrees which corresponds to a relative improvement of motion of 43%. Eleven patients showed good or fair results. The prognosis of knee stiffness is influenced by the etiology, the pre-operative loss of motion and the period of time between initial trauma and arthrolysis, and as well by the intraoperatively achieved range of motion and the post-operative application of continuous passive motion. The expanded arthrolysis of the knee is a usefull instrument in the therapy of severe posttraumatic knee stiffness.

Adolescent↗
PubMed1994

Effects of flupirtine coadministration on phenprocoumon plasma concentrations and prothrombin time.

The influence of flupirtine, a non-opioid, centrally acting analgesic agent on phenprocoumon plasma levels and protein binding as well as prolongation of prothrombin time has been investigated in 12 healthy male volunteers. Subjects received phenprocoumon 1.5 mg od over 28 days. From day 15 to 28 oral flupirtine 100mg tid was added. Phenprocoumon plasma levels and prothrombin time (Quick time), measured at trough before the morning drug intake, were chosen as primary pharmacokinetic and pharmacodynamic variables. In addition, phenprocoumon protein binding and the eudismic ratio of phenprocoumon were determined. The mean values from data obtained on day 12 to 15 (i.e. measurements under phenprocoumon alone) and the mean values from those data obtained from day 25 to 28 (i.e. under comedication with flupirtine) were subject to subsequent statistical procedures. Phenprocoumon plasma concentrations came to 1.38 +/- 0.28 micrograms/ml on day 12 to 15 and were not significantly altered under flupirtine coadministration with 1.48 +/- 0.36 micrograms/ml on day 25 to 28 (95% confidence interval: 1.02-1.11, point estimator: 1.06). The average Quick time came to 68 +/- 10% on day 12-15 and 73 +/- 15% on day 25-28. The nonparametric 95%-confidence interval for the ratio ranged between 0.96 and 1.14, the point estimator was determined to 1.04. Protein binding of phenprocoumon was determined to 88.8% +/- 0.5 on day 14 and to 88.9 +/- 0.5% on day 28. The ratio of S/R-phenprocoumon was 1:0.84 on day 14 and 1:0.84 on day 28. These results do not provide any evidence for a pharmacokinetic and/or pharmacodynamic interaction between flupirtine and phenprocoumon.

Administration, Oral↗
PubMed1994

[Long-term results of arthrodesis of the upper ankle joint].

From 1985 to 1987 a total of 95 ankle arthrodesis were performed. The retrospective study showed in most cases a bony healing within 14 weeks with a complication rate of 20%, due to reduced conditions of the soft tissue. The follow up examination of 52 patients showed a good to very good result in 48 cases. Nearly 70% of the patients did not use orthopaedic made-to-measure shoes at the time of follow up. Only 4% were dissatisfied with this procedure. Therefore the arthrodesis of the ankle should be preferred in comparison to the arthroplastik.

Adult↗
PubMed1994

[Bone repair in pseudarthrosis after arthrodesis of the upper ankle joint].

Delayed union or non-union of ankle arthrodesis is a common problem and revision arthrodesis is necessary in those difficult cases. Three cases are presented, in which a non-union after tibiotalar or tibiacalcanear fusion could be treated effectively with a bone graft taken from the anterior cortex of the distal tibia or from the anterior iliacal spine. The bone graft was fixed proximally with a screw. Distally the graft was inserted in an slot gouged into the talus or the calcaneus respectively with or without screw fixation. Postoperative care included short-time external fixation and immobilisation with a shortleg weight bearing cast. We conclude that the technique of a sliding tibiotalar graft can be used for effective treatment of non-union following ankle arthrodesis.

Adult↗
PubMed1994

[Correction of post-traumatic deformity after femoral intramedullary nailing].

Posttraumatic deformities of the femoral shaft secondary to intramedullary nailing of femoral shaft fractures consist in rotation deformities, leg shortening or axis deformities, which are either single deformities or combined with each other. The most common deformity is external rotation with or without posttraumatic length discrepancies. 16 cases, in which corrective osteotomies have been performed in the years 1985 to 90 in the Berufsgenossenschaftliche Unfallklinik Tübingen are analyzed; indications, techniques and results are discussed.

Adolescent↗
PubMed1993

Combination therapy with zidovudine and didanosine compared with zidovudine alone in HIV-1 infection.

OBJECTIVE: To assess safety, pharmacokinetics, and in-vivo virologic activity of five different combination regimens of zidovudine and didanosine compared with zidovudine alone in patients with human immunodeficiency virus type 1 (HIV-1) infection. DESIGN: Open-label, partially randomized, dose-ranging study. SETTING: University-affiliated, medical center clinics. PATIENTS: A total of 69 patients with HIV-1 infection, CD4+ cell counts fewer than 400 cells/mm3, and fewer than 121 days of previous zidovudine treatment. INTERVENTIONS: Fifty-five patients received combination therapy with zidovudine and didanosine, and 14 received zidovudine therapy alone (600 mg/d). Daily dosages in milligrams of zidovudine and didanosine, respectively, in the five combination groups were 150 and 90 mg, 300 and 334 mg, 600 and 334 mg, 300 and 500 mg, and 600 and 500 mg. MEASUREMENTS: CD4+ cell counts, HIV-1 RNA titers in plasma, and toxic effects. RESULTS: The combination regimens were associated with higher and more sustained increases in CD4+ cells than zidovudine alone, even after adjustment for initial CD4+ counts and previous zidovudine therapy (P < 0.001). The median increase in CD4+ cell counts was 166 cells/mm3 with combination therapy and 77 cells/mm3 with zidovudine alone (P = 0.001) and did not differ statistically among the five combination regimens. Human immunodeficiency virus type 1 RNA titers in plasma decreased in 15 (83%) of 18 combination-therapy recipients compared with 2 of 7 zidovudine-alone recipients (P = 0.017). No pharmacokinetic interactions were seen between zidovudine and didanosine. Toxicity rates were low among all treatment groups. A greater decrease in hemoglobin levels was seen with the regimen using zidovudine alone (-8 g/L) compared with combination regimens using the same zidovudine dose (-1.5 g/L, P = 0.03). CONCLUSIONS: Combination therapy with zidovudine and didanosine produced larger and more sustained increases in CD4+ cell counts, more frequent decreases in plasma HIV-1 RNA titers, and more stable hematologic status than zidovudine therapy alone. The effects of this combination on the progression of HIV disease merit further study, to provide information about clinical outcome, because this was a relatively small study based on surrogate markers of HIV-1 infection.

Adult↗
PubMed1993

Intramedullary pressure, strain on the diaphysis and increase in cortical temperature when reaming the femoral medullary cavity--a comparison of blunt and sharp reamers.

Clinical application has shown intramedullary nailing to be a safe therapeutic procedure, although damage to the vascular system and fat embolism have been demonstrated in animal experiments. The main negative factors were presumed to be the increase in intramedullary pressure and the increase in cortical temperature. In this study, the effect of the blunting of the reamers on the increase in intramedullary pressure, the tangential strain on the diaphysis and the increase in cortical temperature was to be clarified. The measurements were carried out on pairs of human femora reamed with sharp and blunt AO reamers. The pressure was measured in the middle of the diaphysis and in the metaphysis, the strain in the middle of the femur and the temperature on four aspects of the femur. The femora were reamed with identical compression and traction forces in a water bath at 37 degrees C. In comparison with the sharp reamer, the blunt reamer develops 2.1 times the positive diaphyseal pressure, 1.7 times the positive metaphyseal pressure, 1.6 times the negative diaphyseal pressure, 1.5 times the positive tangential strain, 55 times the negative tangential strain and 2.8 times the increase in cortical temperature. There is no difference in the negative metaphyseal pressure. Since blunt reamers produce greater intramedullary pressure values, greater tangential strain on the diaphysis and a greater increase in cortical temperature, the attention of surgeons and operating staff must be drawn to the fact that they should treat the reamers gently and replace them whenever necessary.

Equipment Failure↗
PubMed1993

Extent of bluntness and damage to reamers from hospitals.

The negative effects of intramedullary nailing, such as aseptic cortical necroses and fat embolisms, are mainly caused by an increase in intramedullary pressure and an increase in cortical temperature during the reaming process. The degree of bluntness of the reamers has a negative influence on these two parameters. The objective of this study was to examine the degree of bluntness and damage to intramedullary reamers in clinical use. 10 sets of intramedullary reamers returned from Swiss clinics were examined with regard to the radius of the cutting edge and the degree of damage. The following results were established (MN = medullary nailings): Sharpest reamers: hospitals with 300-400 beds. Hospitals with < 5 MN per year. Bluntest reamers: hospitals with > 1000 beds. Hospitals with 40-60 MN/year. Least damaged reamers: hospitals with 300-400 beds. Hospitals with 40-60 MN/year Most damaged reamers: hospitals with > 1000 beds. Hospitals with 40-60 MN/year Due to the fact that some of the reamers in clinical use are of inadequate quality both with regard to the sharpness of the milling lips and the degree of damage, doctors and operating staff should be instructed to check the quality of cutting tools before using them, to treat them carefully and to replace them if necessary.

Equipment Failure↗
PubMed1993

Influence of the compression force on the intramedullary pressure development in reaming of the femoral medullary cavity.

The reaming process is considered the main damage factor in intramedullary nailing, as there are repeated increases in intramedullary pressure and cortical temperature, which can lead to aseptic cortex necroses and fat embolisms. In this study, the influence of the compression force on the increase in pressure is to be examined. The intramedullary pressure was measured in the middle of the diaphysis and in the metaphysis of human femora reamed under various compression forces. The compression force exerted by the surgeon was measured on polyurethane femora. It was observed that an increase in the compression force of 1.8 times led to an increase in the diaphyseal pressure of 4.7 times and of the metaphyseal pressure of 3.1 times. As surgeons exert high compression forces, peak pressures of 970 mmHg diaphyseally and 1150 mmHg metaphyseally must be expected in the hospital. If reaming is carried out with less compression force, the intramedullary pressure can easily be reduced by 79% in the area of the diaphysis and by 68% in the metaphysis.

Femoral Fractures↗
PubMed1993

The pharmacokinetics and safety of zidovudine in the third trimester of pregnancy for women infected with human immunodeficiency virus and their infants: phase I acquired immunodeficiency syndrome clinical trials group study (protocol 082). Zidovudine Collaborative Working Group.

OBJECTIVES: We measured the pharmacokinetics and safety of zidovudine in pregnant women infected with human immunodeficiency virus and their offspring. STUDY DESIGN: Asymptomatic human immunodeficiency virus-infected women with uncomplicated singleton gestations (28 to 36 weeks) underwent parenteral and oral zidovudine treatment during pregnancy and labor. Maternal and neonatal drug levels were measured at delivery and sequentially for 48 hours. Infants were followed up for 18 months. RESULTS: The total body clearance (26.3 +/- 10.1 ml/min/kg), mean terminal elimination phase zidovudine half-life (1.3 +/- 0.2 hours), and urinary zidovudine recovery were similar to values in nonpregnant adults. Essentially equivalent zidovudine levels in the mother and neonate at delivery implied little, if any, fetal zidovudine metabolism. The half-life of zidovudine in the neonates was tenfold that of the mother. No significant adverse effects were noted in the infant at birth or on follow-up. CONCLUSIONS: In both mothers and infants the drug appeared safe and well tolerated with no significant hematologic abnormalities.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Phase I evaluation of zidovudine administered to infants exposed at birth to the human immunodeficiency virus.

This study evaluated the safety, tolerability, and pharmacokinetics of zidovudine administered intravenously and orally to infants born to women infected with the human immunodeficiency virus. Thirty-two symptom-free infants were enrolled before 3 months of age. The pharmacokinetics of zidovudine were evaluated in each infant after single intravenously and orally administered doses of zidovudine on consecutive days, and during long-term oral administration of the drug for 4 to 6 weeks. As new patients were enrolled, doses of zidovudine were progressively increased from 2 to 4 mg/kg. Therapy was continued for up to 12 months in 7 of the infants proved to be infected with human immunodeficiency virus. Zidovudine was generally well tolerated; 20 children (62.5%) had anemia (hemoglobin level < 10.0 gm/dl) during therapy and 9 (28.1%) had neutropenia (neutrophil count < or = 750 cells/mm3); these hematologic abnormalities usually resolved spontaneously. The total body clearance of zidovudine increased significantly with age, from an average of 10.9 ml/min per kilogram in infants < or = 14 days of age to 19.0 ml/min per kilogram in older infants (p < 0.0001). Concurrently, there was a significant decrease in serum half-life from 3.12 hours in infants < or = 14 days to 1.87 hours in older infants (p = 0.0002). Oral absorption was satisfactory and bioavailability decreased significantly with age, from 89% in infants < or = 14 days to 61% in those > 14 days of age (p = 0.0002). Plasma concentrations of zidovudine were calculated to be in excess of 1 mumol/L (0.267 micrograms/ml) for 4.12 +/- 1.86 hours and 2.25 +/- 0.78 hours after oral doses of 2 mg/kg in infants younger than 2 weeks and 3 mg/kg in older infants, respectively. We conclude that zidovudine administered at oral doses of 2 mg/kg every 6 hours to infants aged less than 2 weeks and 3 mg/kg every 6 hours to infants older than 2 weeks resulted in plasma concentrations that are considered virustatic against human immunodeficiency virus. Zidovudine was well tolerated by infants at these doses.

Administration, Oral↗
PubMed1993

Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single- and multiple-dose administration to normal volunteers.

The pharmacokinetics and safety of the L-valyl ester pro-drug of acyclovir, valaciclovir (256U87), were investigated in two phase I, placebo-controlled trials in normal volunteers. These included a single-dose study with doses from 100 to 1000 mg (single cohort) and a multiple-dose investigation with doses from 250 to 2000 mg (five separate cohorts). In each cohort, eight subjects received valaciclovir and four subjects received placebo. Pharmacokinetic findings for valaciclovir and acyclovir were consistent in the two studies. Valaciclovir was rapidly and extensively converted to acyclovir, resulting in significantly greater acyclovir bioavailability (approximately threefold to fivefold) compared with that historically observed with high-dose (800 mg) oral acyclovir. At the higher valaciclovir doses, acyclovir maximum concentration and daily area under the concentration-time curve approximated those obtained with intravenous acyclovir. The favorable safety profile and enhanced acyclovir bioavailability from valaciclovir administration has prompted additional clinical evaluations for zoster and herpes simplex virus treatment, as well as cytomegalovirus suppression in immunocompromised patients.

Acyclovir↗
PubMed1993

Permethrin-impregnated bed nets for malaria control in northern Guatemala: epidemiologic impact and community acceptance.

Permethrin-impregnated bed nets were evaluated as a control measure for malaria in northern Guatemala. Twelve hundred forty participants were allocated to one of three experimental groups (impregnated bed nets [IBN], untreated bed nets [UBN], and controls) and followed up for a period of 13 months. The incidence density of malaria was significantly lower in both IBN (86 cases/1,000 person-years) and UBN groups (106/1,000) compared with that in controls (200/1,000). No difference in malaria incidence was noted between the IBN and UBN groups. Complaints of fever and chills were less frequent in the IBN group compared with controls. The participants were enthusiastic about the nets, which they saw as a means for avoiding nuisance insects more than for preventing malaria. Most (85%) wanted to wash their nets every 4-12 weeks, a practice known to shorten the duration of residual insecticide action. Larger studies are needed to determine whether or not impregnated bed nets offer an advantage over untreated nets in this setting.

Adult↗
PubMed1993

[Tibio-calcaneus fusion].

From January 1977 to August 1992 22 tibiocalcaneal fusions were performed at the Co-Operative Trade Association Hospital for Accidents, at Tübingen, Germany. 21 of these fusions healed both clinically and roentgenologically, the quality of the effected healing being stable. In more than two-thirds of the cases the indication for performing the fusion had been a fracture of the talus of the Weber/Marti IV or Hawkins III type with its associated complications. Hence, bony fusion between tibia and calcaneus is a commendably reliable treatment possibility in severe diseases of the talus and its adjacent articulations. The result can of course be only as good as the indication arrived at by the physician. In traumatology, this indication is mainly prompted by aseptic necrosis of the talus following talus fractures of maximum severity. A large number of relevant publications mentions an almost 100 per cent rate of necrosis associated with this lesion. This raises the very important question whether in case of such most severe forms of talus fracture it would not be better to aim at a primary tibio-calcaneal fusion straightway to save the patient the trouble of an otherwise prolonged course of the disease with doubtful outcome.

Adult↗
PubMed1993

[Change in treatment procedure after primary external fixator osteosynthesis in polytrauma patients].

In polytrauma patients stabilisation of fractures is of minor importance compared with life-saving surgical interventions concerning the body cavities. Because of persisting instability especially of long bones with disadvantageous effects on the state of shock and the respiratory system (fat embolism, ARDS) early stabilisation of fractures should be achieved. In our experience the majority of cases allows external fixation of long bone fractures simultaneously with or following the life-saving operations. Postoperative positioning and nursing as well as additional diagnostic procedures are considerably facilitated. An early change of the stabilisation method should be performed as soon as possible if tolerated by the general and soft tissue conditions. Follow-up of 54 patients with 76 fractures stabilised primarily by external fixator demonstrates our experiences with planning and realisation of the change of stabilisation method. The functional and radiological results after an average of 28 months are pointed out.

Adolescent↗