Prevention of heterotopic bone formation after total hip arthroplasty: a prospective randomised study comparing postoperative radiation therapy with indomethacin medication.

Heterotopic ossification (HO) after total hip arthroplasty is known to be a major complication with an impact on the functional outcome. Efforts have been made to prevent the occurrence of HO by means of either radiation therapy or pharmacotherapy. To date, there are no data available regarding the relative benefit of radiation versus medication with non-steroidal anti-inflammatory drugs. The objective of this study was to compare single-dose 600-cGy radiation therapy with indomethacin medication for their effect on the prevention of heterotopic bone formation after total hip arthroplasty. In all, 154 patients were included in the study. All patients underwent primary total hip arthroplasty due to osteoarthritis. Patients were randomly assigned to three different therapeutic groups. (a) The radiation group received a single radiation dose of 600 cGy between the 2nd and 4th postoperative day. (b) The indomethacin group received an oral application of indomethacin 2 x 50 mg per day from the 1st to 42nd postoperative day. (c) The control group received neither radiation nor indomethacin medication. There were significant group differences (P < 0.001). A least significant difference test (LSD) revealed that the mean of the control group was significantly different from that of the radiation and indomethacin groups. The 13 patients (8.4%) classified Brooker 3 or 4 were all in the control group. Again, this effect was statistically significant (chi-square, P < 0.001). In conclusion, this study demonstrated that both radiation and indomethacin therapy are effective in the prevention of postoperative HO. The choice for either one of the treatments has to be based on availability, contraindications, side-effects, practicability, standardisation and cost. Based on these considerations together with the results of this study, we currently use postoperative radiation with 600 cGy for all patients undergoing primary total hip arthroplasty.

Severe lymphocytopenia and interstitial pneumonia in patients treated with paclitaxel and simultaneous radiotherapy for non-small-cell lung cancer.

PURPOSE: In a phase II trial with paclitaxel and simultaneous radiotherapy in non-small-cell lung cancer (NSCLC) patients, an unexpected high incidence of interstitial pneumonias was observed. The type of immunodeficiency associated with this treatment approach is characterized. PATIENTS AND METHODS: Fifteen patients with inoperable stage IIIA/B NSCLC were treated with paclitaxel as a 3-hour infusion on day 1 in weeks 1 to 3 and 6 to 8 at dose levels between 50 mg/m2 and 86 mg/m2 and with simultaneous radiotherapy in daily doses of 2 Gy, 5 days per week, in weeks 1 to 3 and 6 to 8 up to a total dose of 56 Gy. Hematologic parameters and lymphocyte subsets were monitored. RESULTS: Fourteen patients are assessable for response. The overall response rate was 78%, with four major responses, six partial remissions, and four minor responses. The major toxic effect observed was a moderate to severe protracted lymphocytopenia (380 +/- 310/microL) in all patients. Seven patients developed moderate to severe interstitial pneumonia; one had an additional herpes zoster infection, while an eighth patient had a cytomegalovirus infection. During treatment, all lymphocyte subsets were reduced, as follows (n = 9, mean +/- SD): CD4+ T cells (100 +/- 90/microL), CD8+ T cells (130 +/- 160/microL), natural killer (NK) cells (70 +/- 80/microL), and B cells (20 +/- 10/microL). Thus, the most pronounced toxicity was seen in CD4+ T and B cells. There was no recovery of lymphocyte subsets during a 3-month follow-up period. CONCLUSION: Paclitaxel with simultaneous radiation induces lymphocytopenia and promotes opportunistic infections. Long-term antibiotic and antimycotic prophylaxis is recommended. Whether the lymphocytopenia is an additive effect of paclitaxel and radiation or whether it can be induced by low-dose weekly paclitaxel alone remains to be determined.

[Radiotherapy for prevention of postoperative periarticular calcinosis. Using fractionated irradiation after total endoprosthesis of the hip joint]. / Strahlentherapie zur Prophylaxe von postoperativen periartikulären Verkalkungen. Nutzen einer fraktionierten Bestrahlung nach Totalendoprothese des Hüftgelenks.

According to the Literature, and confirmed by our own experience, fractionated postoperative radiation administered after total hip replacement can, with a high degree of reliability (13 out of 14 patients), prevent postoperative ossification. At least in the case of elderly patients beyond the age of procreation, it is superior to alternative therapeutic measures (biphosphonates, prostaglandin synthesis inhibitors).

[The inhibition of the proliferation and energy metabolism of Cloudman melanoma cells in vitro by aphidicolin and gamma radiation]. / Hemmung der Proliferation und des Energiestoffwechsels von Cloudman-Melanomzellen in vitro durch Aphidicolin und Gammastrahlung.

PURPOSE: The present investigation is concerned with the effect of aphidicolin (a tetracyclic diterpenoid) and gamma-ray [correction of X-ray] irradiation--alone or in combination--on cell proliferation, protein production, glucose consumption and lactate production of in vitro cultured Cloudman melanoma cells. METHODS: Monolayer cultures of Cloudman melanoma cells in exponential growth phase were irradiated with 2, 4 or 6 Gy (cobalt-60) or treated for 96 h with 0.1, 0.2 or 1.0 microgram/ml aphidicolin. Further, the combination of 0.1 or 0.2 micrograms/ml aphidicolin with the above mentioned radiation doses were investigated. Measurements were performed in regard to changes of cell number, protein content, glucose consumption and lactate production. RESULTS: Single treatments resulted in a dose-dependent inhibition of cell proliferation, protein production, glucose consumption and lactate production. Combined treatment with aphidicolin and irradiation caused an augmentation of the respective single effects. The inhibitory effects were more pronounced under serum-free than serum-containing culture conditions. Influence of aphidicolin and irradiation did not result in an immediate cell death, but in a state of unbalanced growth with enlarged cells (in part with an increased number of nuclei) and an increased cellular protein content. CONCLUSIONS: The combination of aphidicolin with gamma-ray [correction of X-ray] irradiation caused a stronger effect than the respective single treatments.

[Optimization of verification photographs in thoracic wall irradiations (so-called tangential field technique) in breast carcinoma. A short technical-methodical report]. / Optimierung von Verifikationsaufnahmen bei Thoraxwandbestrahlungen (sogenannte tangentiale Zangenfelder) beim Mammakarzinom. Kurze technisch-methodische Mitteilung.

When irradiating under high voltage condition, verification photographs prove to be difficult to take if the Gantry position is not aligned to 0 degree respectively 180 degrees, since the patient is being irradiated diagonally. Under these conditions it is extremely difficult to align the X-ray-cartridge vertically to the central beam of the therapeutic radiation. This results in, amongst others, misprojections, so that definite dimensions of portrayed organ structures become practical impossible to determine. This paper presented describes how we have solved these problems on our high voltage units (tele-gamma cobalt unit and linear-accelerator). By using simple accessories, determination of dimensions of organ structures, as shown on the verification photographs, are made possible. We illustrate our method by using the so-called tangential fields technique when irradiating mamma carcinoma.

[A new topical carbonic anhydrase inhibitor (MK-927). Tolerance comparison with betaxolol in healthy probands]. / Ein neuer, lokal anwendbarer Carboanhydrasehemmer (MK-927). Toleranzvergleich mit Betaxolol bei gesunden Probanden.

MK-927 is a new topical carboanhydrase inhibitor with proven ability to lower intraocular pressure in glaucoma patients. Subjective and objective symptoms following topical application of MK-927 were evaluated in a randomized, double-blind, placebo-controlled study in which 24 healthy male volunteers took part. Symptoms were rated according to a visual analog scale by the volunteers and according to a grading scale by the examiner. The study showed good local tolerance of MK-927, comparable to that of Betaxolol.

[Oculo-oscillodynamography findings in glaucoma without hypertension]. / Okulooszillodynamographische Befunde bei Glaukom ohne Hochdruck.

Oculo-oscillodynamography after Ulrich was performed in 27 patients suffering from glaucoma without hypertension (so-called low-tension glaucoma). Patients who had severe systemic disease or were receiving systemic medication which might influence IOP, and patients with narrow angle and an IOP higher than 22 mm Hg were excluded. In 85% of the patients a severe decrease in systolic ciliary perfusion pressure was found, whereas the systolic retinal and diastolic ocular perfusion pressures were significantly lower in almost 30% of the cases. Glaucoma without hypertension appears to be caused by the vascular change at the disk.

[Ulrich oculo-oscillodynamography in carotid artery stenosis and temporal arteritis]. / Okulooszillodynamographie nach Ulrich bei Carotisstenose und Arteriitis temporalis.

Oculo-oscillodynamography (OODG) after Ulrich was performed on 21 patients suffering from unilateral hemodynamically relevant carotid stenosis. In ten patients the perfusion pressure was low on the affected side. In the other eleven patients there was no difference between the two sides and these patients were thought to have well-developed collateral anastomoses. In nine patients with temporal arteriitis low perfusion pressure was found by OODG on the side with the lower visual acuity. After systemic therapy with corticosteroids the perfusion pressure normalized on both sides.

[Effectiveness and tolerance of an active combination of timolol and pilocarpine--a pilot project]. / Wirksamkeit und Verträglichkeit einer Wirkstoffkombination von Timolol und Pilocarpin--Eine Pilotstudie.

A pilot study was conducted to find out whether it is possible to achieve a further drop in intraocular pressure in eyes with glaucoma, which is about 22 mmHg after treatment with 0.5% timolol, by employing a combination preparation of timolol 0.5% and pilocarpine 2% or timolol 0.5% and pilocarpine 4% respectively, administered as eyedrops. This resulted in an average additional lowering of 1.9 mmHg after 2 hrs and by 2.1 mmHg after 6 hours (TP2) or by 3.0 mmHg after 2 and 3.5 mmHg after 6 and by 2.7 mmHg after 12 hours (TP4), the therapeutically relevant duration of effectivity being 6 (TP2) or 12 (TP4) hours, respectively.

Significance of histamine formation and release in the development of endotoxic shock: proof of current concepts by randomized controlled studies in rats.

The significance of histamine in the initiation and progression of septic (endotoxic) shock is still uncertain. Increased new formation and increased release of histamine are the two hypotheses currently considered as the basis for a causal relationship. Both hypotheses were tested in a standardized rat model of endotoxic shock. Several randomized controlled studies were performed with inhibitors of histamine formation (histidine decarboxylase inhibitors) and of its action via receptors (H1 and H2 receptor antagonists). Two inhibitors of histamine formation (alpha-methylhistidine and alpha-fluoromethylhistidine) in a wide range of doses exerted no significant effects on survival curves for rats in endotoxic shock, despite enzyme inhibition in vitro and in homogenates of liver obtained from rats immediately after death. In addition, three H1 and three H2 receptor antagonists, which were selected on the basis of markedly different antihistaminic efficacies and of defined non-antihistaminic (nonspecific) efficacies, gave no indications of specific histamine-mediated effects on survival parameters in these studies when tested either singly or in various combinations. Thus, histamine cannot be shown to be a predominant factor in the lethal outcome of endotoxic shock in rats.

[Vascular effect and intraocular pressure-reducing effect of beta blockers]. / Gefässwirksamkeit und augendrucksenkender Effekt von Betablockern.

A study was conducted to investigate the influence of a vasodilating beta receptor blocking substance on IOP in eyes with open-angle glaucoma. The study proceeded from the hypothesis that throttling of the production of aqueous humor by beta blockers and reduction of intraocular pressure is caused by vasoconstriction of the afferent vessels. The authors found that the degree of reduction of intraocular pressure corresponded to the effect of beta blockers routinely applied in glaucoma therapy. However, the duration of the effect was shorter. The above-mentioned hypothesis would thus seem to be disproved.

Induced histidine decarboxylase in endotoxic shock: identification of the enzyme in rat liver and influence of its inhibitors on survival parameters.

The hypothesis of a causal relationship between a progressive and unrestrained increase of tissue histamine formation by activation of an inducible histidine decarboxylase (HDC) and lethality in endotoxic shock (Schayer's 'induced histamine concept') was tested in a standardized rat endotoxic shock model. Initial enzyme identification studies in the rat shock liver (8 hrs after endotoxin challenge) clearly demonstrate that the 'induced' histidine decarboxylase is an acid (specific) HDC. The succeeding randomized, controlled study with appropriate inhibitors of the enzyme, alpha-methyl-histidine (competitive inhibitor) and alpha-fluoromethyl-histidine (irreversible inhibitor) using doses of 2, 20 or 100 mg/kg showed no significant effect on the survival rate of rats in endotoxin shock. The survival rate of the non-treated endotoxin control group (NaCl) was 25%; all methylprednisolone treated rats (50 mg/kg) survived. Thus, the 'induced' histamine is not a predominant factor (necessary or sufficient determinant) for the lethal outcome in rat endotoxic shock. The protective effect of MP is not predominantly due to the inhibition of the 'induced' histidine decarboxylase. The use of HDC-inhibitors as the appropriate instruments for evaluation of the significance of this mechanism is discussed.