Diffusion-weighted MRI in the follow-up of chronic periaortitis.

OBJECTIVE: To evaluate the usefulness of diffusion-weighted MRI (DWI) for the assessment of the intraindividual follow-up in patients with chronic periaortitis (CP) under medication. METHODS: MRI data of 21 consecutive patients with newly diagnosed untreated disease were retrospectively examined before and after medical therapy, with a median follow-up of 16 weeks. DWI parameters [b800 signal, apparent diffusion coefficient (ADC) values] of the CP and psoas muscle were analysed together with the extent and contrast enhancement. Pre- and post-treatment laboratory inflammation markers were acquired parallel to each MR examination. RESULTS: Statistically significant lower b800 signal intensities (p ≤ 0.0001) and higher ADC values (p ≤ 0.0001) were observed after medical treatment within the fibrous periaortic tissue. Extent and contrast enhancement of the CP showed also a statistically significant decrease (p ≤ 0.0001) in the follow-up examinations, while the control parameters within the psoas muscle showed no differences. CONCLUSION: DWI seems to be a useful method for the evaluation of response to treatment without contrast agents. The technique may be helpful in the assessment of disease activity to guide further therapeutic strategies. ADVANCES IN KNOWLEDGE: DWI detects significant differences in the intraindividual follow-up of CP under medical therapy.

Diffusion-weighted MRI in the follow-up of chronic periaortitis.

OBJECTIVE:: To evaluate the usefulness of diffusion-weighted MRI (DWI) for the assessment of the intraindividual follow-up in patients with chronic periaortitis (CP) under medication. METHODS:: MRI data of 21 consecutive patients with newly diagnosed untreated disease were retrospectively examined before and after medical therapy, with a median follow-up of 16 weeks. DWI parameters [b800 signal, apparent diffusion coefficient (ADC) values] of the CP and psoas muscle were analysed together with the extent and contrast enhancement. Pre- and post-treatment laboratory inflammation markers were acquired parallel to each MR examination. RESULTS:: Statistically significant lower b800 signal intensities (p ≤ 0.0001) and higher ADC values (p ≤ 0.0001) were observed after medical treatment within the fibrous periaortic tissue. Extent and contrast enhancement of the CP showed also a statistically significant decrease (p ≤ 0.0001) in the follow-up examinations, while the control parameters within the psoas muscle showed no differences. CONCLUSION:: DWI seems to be a useful method for the evaluation of response to treatment without contrast agents. The technique may be helpful in the assessment of disease activity to guide further therapeutic strategies. ADVANCES IN KNOWLEDGE:: DWI detects significant differences in the intraindividual follow-up of CP under medical therapy.

[Subcutaneous mass as initial manifestation of an osteolytic metastasis]. / Subkutane Weichteilschwellung als Erstmanifestation einer osteolytischen Knochenmetastase.

HISTORY AND CLINICAL FINDINGS: A 69-year-old woman was admitted for evaluation of a left occipital subcutaneous tumour which had grown during the preceding eight weeks from 2 × 2 cm to 4 × 4 cm. INVESTIGATIONS: Sonography revealed a pressure-sensitive subcutaneous mass with osteolytic destruction in the occipital bone. Cranial magnetic resonance imaging confirmed the osteolytic lesion. Thoracic computed tomography showed a lesion in the upper left lobe of the lung with metastases in the hilar lymph nodes. DIAGNOSIS, TREATMENT AND COURSE: Transbronchial biopsy revealed a bronchial carcinoma. After resection of the osteolytic lesion its histology was confirmed to be an osseous metastasis of the carcinoma. Palliative chemotherapy and cranial irradiation were initiated. CONCLUSION: Solitary osteolytic lesions of the skull occur in the context of osseous metastases. Other possible causes include solitary plasmocytoma and eosinophilic granuloma.

MR evaluation of retroperitoneal fibrosis.

PURPOSE: Retroperitoneal fibrosis (RPF) is a rare fibrosing process. The relation of contrast enhancement within the fibrosis and the psoas muscle was suggested for the evaluation of disease activity and response to treatment, but no standardized method for the quantification of the disease activity is currently available. We introduce an MR parameter for the evaluation of RPF. MATERIALS AND METHODS: 29 patients with untreated idiopathic RPF were examined before medical therapy and after three months of treatment. MR analyses included quotients of T 1 and T 2-signal intensities between the RPF and the psoas muscle. Furthermore, we examined the dynamic contrast enhancement of the fibrous tissue. The respective data were compared with the extent of the RPF after 3 months. RESULTS: In the follow-up examinations we observed a significant regression in 37.9 % (n = 11) of cases, a mild regression in 48.3 % (n = 14) and a stable extent in 13.8 % (n = 4). Patients with a significantly reduced extent showed the highest mean values for the applied MR quotients in the initial examination. The lowest mean values for the respective parameters were found for the group with a stable extent. Only dynamic enhancement quotients showed statistically significant differences (p = 0.011) between the groups of response. CONCLUSION: We observed a significant reduction in the fibrous tissue after pharmacological treatment in patients with an elevated dynamic enhancement quotient in the initial examination.

[Fournier gangrene (necrotizing fasciitis) in a woman with diabetes mellitus]. / Fournier-Gangrän mit letalem Verlauf bei einer Patientin mit Diabetes mellitus.

HISTORY AND CLINICAL FINDINGS: A 67-year-old woman with insuline-dependent diabetes mellitus and chronic alcohol abuse was admitted with impaired consciousness and fever. Physical examination showed a livid induration of the perineal and vaginal soft tissues with crepitations. INVESTIGATIONS: Laboratory tests showed greatly elevated infection parameters. Abdominal computed tomography revealed perineal and vaginal subcutaneous gas accumulation extending into the ventral abdominal wall. TREATMENT AND COURSE: The combination of an obscure infection and subcutaneous genital gas accumulation suggested the diagnosis of Fournier gangrene, a necrotizing fasciitis. In spite of administration of broad-spectrum antibiotics and repeated surgical removal of necrotic tissue the patient died of multiple organ failure. CONCLUSION: Successful treatment of Fournier gangrene critically depends on immediate treatment. Administration of broad-spectrum antibiotics and aggressive surgical resection of the necrotic tissue may prevent continuing spreading of the infection. Computed tomography provides an early diagnosis and guides the presurgical evaluation of the subcutaneous spread.

Phase-inversion tissue harmonic imaging compared to fundamental B-mode ultrasound in the evaluation of the pathology of large and small bowel.

Our purpose was to compare phase-inversion harmonic imaging (PIHI) with conventional B-mode ultrasound (US) regarding image quality in the evaluation of bowel pathology. Forty-one patients prospectively underwent intestinal ultrasound scans with US and PIHI in randomly chosen order. Crucial technical parameters were standardized. Bowel morphology as well as perienteric pathology and complications were documented. In 24 cases, the ultrasound results were compared to those of other imaging modalities. Three radiologists evaluated (1) overall image quality, (2) lesion conspicuity and diagnostic confidence, and (3) detection of free fluid on hardcopy films. The ratings for image quality were compared using the two-sample paired t test for means and Bowker's test for symmetry (p=0.05). Compared to US, PIHI provided significantly better overall image quality, lesion conspicuity and diagnostic confidence, as well as better detection of free fluid (p< 0.05). Bowel wall pathology, detected by both modalities, showed good correlation to additional imaging modalities. In 12 patients (29.3%), a gain of crucial diagnostic information was observed with PIHI when compared to US. PIHI significantly enhances sonography of the intestine by offering better overall image quality, better visualization of bowel pathology and associated changes. Additionally, PIHI adds crucial diagnostic information in several patients.

Transient osteoporosis of the navicular bone in a runner.

INTRODUCTION: Transient osteoporosis or the bone marrow oedema syndrome is described as a self-limiting disorder. Transient osteoporosis usually affects only one bone, predominantly the proximal femur. Involvement of the foot is rare and often overlooked. A disorder of the navicular bone of the foot can be found twice in the literature. MATERIALS AND METHODS: We report a case of transient osteoporosis of the navicular bone of the foot in a 20-year-old, female, top-level track athlete (400 m sprinter) treated with alendronate, and a review of the literature. RESULTS: The therapeutic options are limited, frequently consisting of non-specific, symptomatic therapy. Some authors report favourable results with core decompression, while others have reported good results with a conservative regime of symptomatic treatment and avoidance of weight-bearing until the clinical and radiological changes have resolved. In the described case, the patient had a favourable result after a short course of treatment with alendronate. She experienced almost immediate pain reduction and presented a complete resolution of the abnormal signal intensity on MRI. CONCLUSION: This rapid result makes the use of alendronate seem promising in athletes with transient osteoporosis, permitting an early return to high-level activities.

Aneurysmal bone cyst: value of MR imaging and conventional radiography.

Our objective was to investigate the accuracy and the diagnostic value of different imaging features of primary aneurysmal bone cysts (ABC) in conventional radiographs and MRI. Conventional radiographs and MR images of 34 patients with a suspected aneurysmal bone cyst were reevaluated by six independent radiologists in a blinded fashion. Morphological features, MR signal characteristics, and contrast enhancement patterns were assessed. Diagnoses were correlated with histology. Sensitivity and specificity of the different imaging findings for each imaging technique were calculated. In 24 patients ABC was histologically proven. In 10 cases diagnoses other than ABC were established. Conventional radiography and MRI each demonstrated a sensitivity of 76.4 and 77.8% with a specificity of 55.0 and 66.7%, respectively. With combined use of both imaging modalities sensitivity and specificity increased to 82.6 and 70%, respectively. The ABC was significantly more often seen as circumscribed lesion with bone expansion, lobulation, septa, and pathological cortical bone reaction than those cases with different diagnoses. Septal contrast enhancement proved to be a useful MR imaging finding in suspected ABC. The combined use of conventional radiographs and MRI revealed the highest sensitivity in the diagnosis of ABC in relation to histology. Magnetic resonance imaging provides improved diagnostic specificity and valuable information on soft tissue changes.

Vascular capsule for telemetric monitoring of blood pressure.

PURPOSE: Development and experimental evaluation of an intravascular monitoring system for telemetric measurement of blood pressure and heart rate. MATERIALS AND METHODS: The monitoring system consists of an implantable silicone capsule (diameter 2.3 mm), containing a dedicated microchip with pressure sensors and signal-processing circuits as well as an antenna for wireless data and energy transfer using 6.78 MHz transponder technology. Three self-expanding legs at one end of the capsule served as a mechanism to lock the capsule at an arterial branch. A flow model, driven by a ventricular assist system, was used for testing and optimizing the implantation equipment, for checking the anchoring mechanism and for ensuring transmission of the measured pressure to the readout unit. In-vivo experiments were performed in 8 minipigs (weight 25 to 30 kg), with three capsules placed in each minipig via the femoral artery using a dedicated 8-F sheath/pusher system. Follow-up was by CT angiography for up to 6 months after implantation. RESULTS: Flow model tests revealed a maximum deviation of pressure and heart rate measurements of 5% from the reference measurements. Signal transmission was reliable over a distance of 3 to 4 cm. Fluoroscopically guided in-vivo implantation of the capsules was simple and straightforward. In arteries with a diameter of 5 to 6 mm, the capsules were permanently fixed with one or two legs interlocked in side branches and without occlusion within 6 months. Three capsules developed a small non-occlusive appositional thrombus attached to the downstream (leg) part of the capsule. CONCLUSION: Our in-vitro and in-vivo experiments demonstrate the feasibility of wireless transmission from a capsule with a sufficient resolution of the sensor output signals to determine blood pressure and pulse rate. As long as the vessel diameter is wide enough, arterial fixation of the capsule does not induce thrombotic occlusion of the parent artery. With respect to future clinical applications, further refinements of the transmission technology are needed to extend the transmission distance between capsule and reader antenna. The technology of intelligent implants has further implications, such as monitoring of other physiological parameters, and the design of a control loop, which may be used for therapeutic feedback.

Multiple aseptic pulmonary nodules with central necrosis in association with pyoderma gangrenosum.

Pulmonary manifestations of pyoderma gangrenosum are relatively rare. We report the case of a 45-year-old patient with multiple pulmonary nodules with central necrosis as assessed by CT scan. The patient had a 4-year history of pyoderma gangrenosum with only minor skin manifestations. A CT-guided, fine-needle biopsy of the lung revealed a nonspecific, inflammatory, aseptic necrotic process, which was comparable to the skin biopsy of one pyoderma lesion. Following the initiation of oral prednisolone therapy, a rapid resolution of the pulmonary nodules occurred. We conclude that pulmonary nodules represent a rare pulmonary manifestation of pyoderma gangrenosum.

[Mono-contrast distension study of the small intestine. Comparison of conventional small bowel follow-through with enteroclysis]. / Monokontrast-Distensionsuntersuchung des Dünndarms. Vergleich mit der konventionellen MDP und dem Enteroklysma.

PURPOSE: Development of a new monocontrast examination of the small bowel. MATERIAL AND METHODS: The new examination was applied to 20 patients with suspected bowel obstruction or inflammatory bowel disease. A contrast mixture, containing gelatin, a water-soluble contrast medium (Peritrast) and water (GPW-mixture) was given over an intestinal tube. The viscosity of the new contrast mixture was measured by rotation and flow viscosimetry. The diagnostic value and the degree of small bowel distension were determined independently by 3 examiners. By comparison 20 randomized selected small bowel follow-through examinations (SBFT) and 20 small bowel enemas were examined. Special questionnaires were used to determine subjective compatibility and discomfort. RESULTS: Due to the viscosity of the new contrast medium and the administration over an intestinal tube, a good bowel distension was achieved with the GPW mixture. The bowel distension (p: < 0.01) and the diagnostic value (p: < 0.01) of the new examination in comparison to the SBFT was characterized as being significantly better. In comparison to the small bowel enema, distension was not significantly better (p: 0.31-1.0). The diagnostic value of the small bowel enema was characterized as significantly better by one of the three examiners in comparison to the new monocontrast-distenson examination (p-level < 0.01). CONCLUSION: The monocontrast-distension examination is a potential alternative in patients in whom a small bowel enema with barium sulfate is contraindicated.

Reduction of contrast material dose and artifacts by a saline flush using a double power injector in helical CT of the thorax.

OBJECTIVE: Our objective was to evaluate a combined method of contrast material bolus followed by saline solution flush for thoracic helical CT and statistical comparison with a uniphasic injection protocol. MATERIALS AND METHODS: Fifty patients underwent helical CT of the thorax using 60 ml of contrast material (370 mg I/ml) followed by flushing with 30 ml of physiologic saline solution. These 50 patients had been examined before using our previous protocol, 75 ml of the same contrast material without a subsequent saline solution. Mean attenuation values for both protocols were measured in the superior vena cava, the pulmonary trunk, and the ascending aorta. Image artifacts and mediastinal and hilar depiction were graded and compared. RESULTS: Mean attenuation values in the superior vena cava were considerably higher in the regimen without saline solution flush (459 H versus 352 H) and in the pulmonary trunk and the ascending aorta were almost identical for both protocols. Injection of saline solution diminished surrounding artifacts (p = 0.001). Grading results for the evaluation of mediastinal and hilar structures were not significantly different in the two protocols (p = 0.564). CONCLUSION: Injection of contrast material followed by a saline solution bolus using a double power injector when performing thoracic helical CT allows a 20% reduction of contrast material volume to 60 ml with a similar degree of enhancement. In addition, perivenous artifacts in the superior vena cava are significantly reduced.

Percutaneous treatment of thrombosed primary arteriovenous hemodialysis access fistulae.

BACKGROUND: We reviewed the efficacy of percutaneous intervention in acute thrombotic occlusion of native arteriovenous (AV) fistulae for hemodialysis. METHODS: Eight-one percutaneous procedures were performed in 54 patients presenting with a clotted native dialysis fistula. There were 60 cases of a long-segment thrombosis of the fistula. In 20 cases, a small thrombus usually caused by an underlying severe stenosis was observed. A proximal arterial occlusion was seen in one case. Treatment depended on clot size and included balloon dilation (N = 20), mechanical thrombectomy with various devices (N = 58), as well as pharmacomechanical thrombolysis (N = 3). RESULTS: Full restoration of flow was established in 72 cases (88.9%). Early reobstruction within 14 days occurred in eight cases (11.1%). Primary patency rates after a 1-, 3-, 6-, and 12-month period were 74, 63, 52, and 27%, respectively. Overall fistula patency was 75% after 3 months, 65% after 6 months, 51% after 12 months, and 22% after 24 months. CONCLUSIONS: Acute thrombotic occlusion of native AV fistulae is a major complication of hemodialysis. The results of treatment are believed to be less successful than thrombosis treatment in synthetic grafts. Our results, however, indicate the efficacy of percutaneous treatment in native fistulae, and demonstrate comparable technical results and patency rates.

[Diagnosis and visualization of renal artery stenosis by color-coded Doppler ultrasonography. Comparison of central and peripheral flow patterns]. / Diagnostik und Darstellung von Stenosen der Arteria renalis mittels Farbkodierter Dopplersonographie. Vergleich von zentraler und peripherer Flussableitung.

PURPOSE: Comparison between central and peripheral flow patterns with color-coded duplex sonography in the diagnosis of renal artery stenosis. MATERIALS AND METHODS: In a prospective study with sixty-six patients systolic velocity (central examination) and acceleration index (peripheral examination) were determined using color-coded duplex sonography examination in order to detect and visualize renal artery stenosis. If the central and peripheral measurements were negative, no angiography was performed. In contrast, if one of the methods yielded a pathological finding, catheter angiography was performed to verify the results (21 patients), as well as in two other unclear cases. RESULTS: An agreement between central and peripheral measuring was seen in 49 of 66 patients. In ten patients central and peripheral measurements showed different results. In seven cases the peripheral measurements were not clear. Compared to angiography, peripheral measurement showed a sensitivity of 60%, a specificity of 75% and a positive predictive value of 81.8%. In contrast, central examination had a sensitivity of 100%, a specificity of 75% and a positive predictive value of 88.2%. CONCLUSIONS: Based on our preliminary results, the measurement of the systolic velocity peak seems to be an effective method to detect renal artery stenosis.

Magnetic resonance angiography of nonferromagnetic iliac artery stents and stent-grafts: A comparative study in sheep.

PURPOSE: To compare nonferromagnetic iliac artery prostheses in their suitability for patency monitoring with magnetic resonance angiography (MRA) using conventional angiography as a reference. METHODS: In experiment 1, three Memotherm stents were inserted into the iliac arteries of each of six sheep: two "tandem" stents on one side and a single stent on the other side. In experiment 2, four prostheses (normal and low-porosity Corvita stent-grafts, Memotherm, ZA-stent) were inserted in each of 11 sheep. Patency was monitored before and 1, 3, and 6 months after insertion with 3D phase-contrast and two 2D time-of-flight sequences (TOF-1: TR/TE = 18/6.9, TOF-2: 13/2.5) with and without contrast at 1.5 T. On 206 coronal MIP images (72 pre-, 134 post-stenting), three readers analyzed 824 iliac segments (206 x 4) for patency and artifacts. RESULTS: There was no difference in the number of artifacts between tandem and single iliac Memotherm stents. The ZA-stent induced significantly fewer artifacts than the other prostheses (p < 0.00001). With MRA, patency of the ZA-stent was correctly diagnosed in 88% of cases, which was almost comparable to nonstented iliac segments (95%), patency of the Memotherm stent in 59%, and of the Corvita stent-grafts in 57% and 55%. The TOF-2 sequence with contrast yielded the best images. CONCLUSION: MRA compatibility of nonferromagnetic prostheses depends strongly on the design of the device. MRA may be used to monitor the patency of iliac ZA-stents, whereas iliac Memotherm stents and Corvita stent-grafts appear to be less suited for follow-up with MRA.

[CT-guided percutaneous biopsies for the classification of focal liver lesions: a comparison between 14 G and 18 G puncture biopsy needles]. / CT-gesteuerte perkutane Biopsien zur Klassifizierung von fokalen Leberläsionen: Vergleich zwischen 14 G- und 18 G-Stanzbiopsienadeln.

PURPOSE: Analysis and comparison of CT-guided 14- and 18-gauge cutting needle biopsies to accurately assess focal liver disease. METHODS: The data of 272 CT-guided biopsies in 268 patients were evaluated retrospectively with regard to sensitivity, specificity and complication rate of the chosen needle caliber in differentiating between benign and malignant disease as well as in the ability to determine specific cell types in the various disorders. A 14-gauge (G) needle was used in 101 (37.1%) cases, an 18-g needle biopsy was performed in 171 (62.9%) cases. The Fisher exact test was employed for statistical analysis. RESULTS: Cutting needle biopsy yielded sufficient histologic material in 267 of 272 (98.2%) cases. Correct diagnosis of malignancy was established in 178 of 191 (93.2%) lesions, 73 of 76 (96.1%) disorders were accurately defined as benign, resulting in an overall value of 94.0% (251 of 267). Of these 251 biopsies a definite histological diagnosis could be determined in 90.6% of the cases employing a 14 G needle and in 90.3% using an 18-g needle. The sensitivity, specificity and rate of complications were 94.8%, 92.0%, 3.0% for the 14-g needle and 92.7%, 97.6%, 0.6% for the 18-g needle, respectively. There were no statistically significant differences with regard to the needle size. CONCLUSIONS: CT-guided biopsy of hepatic lesions with the 18-g biopsy needle is of equivalent diagnostic accuracy when compared with the 14-g needle.

Treatment of hemodialysis-related central venous stenosis or occlusion: results of primary Wallstent placement and follow-up in 50 patients.

PURPOSE: To analyze the effectiveness of stent placement as the primary treatment for central venous obstruction in patients undergoing hemodialysis. MATERIAL AND METHODS: Fifty-seven Wallstents were placed in 50 patients with symptomatic shunt dysfunction and arm swelling due to central venous obstruction. Technical success, complication, and patency rates were evaluated. RESULTS: Stent deployment was successful in all patients, and early rethrombosis (within 1 week) was noted in one patient (2%). Seventy-three episodes of reobstruction occurred and were treated percutaneously with angioplasty alone in 54 cases (74%). Nineteen cases (26%) necessitated additional stent placement. The 3-, 6-, 12-, and 24-month primary patency rates were 92%, 84%, 56%, and 28%, respectively. Cumulative overall stent patency was 97% after 6 and 12 months, 89% after 24 months, and 81% after 36 and 48 months. CONCLUSION: In the treatment of brachiocephalic and subclavian venous obstruction, stent placement shows excellent technical results and helps preserve vascular access for a substantial period. Multiple repeat interventions are, however, frequently required to maintain patency.

Bedside testing (SimpliRED) in the diagnosis of deep vein thrombosis. Evaluation of 250 patients.

RATIONALE AND OBJECTIVES: The authors evaluate the sensitivity and specificity of a bedside test (SimpliRED) in the diagnosis of deep vein thrombosis compared with contrast phlebography. METHODS: Two hundred fifty patients, referred for phlebography, underwent bedside testing for detection of deep vein thrombosis. Contrast phlebography was performed immediately afterward. SimpliRED provides a clearly visible agglutination of the patient's red blood cells in the presence of elevated levels of cross-linked fibrin derivative (D-dimer), which is specific for fibrin breakdown. RESULTS: In 82 (32.8%) patients, deep vein thrombosis was confirmed venographically. An abnormal D-Dimer test was found in 79 of the 82 patients with thrombosis (sensitivity: 96.3%). The three patients who were diagnosed falsely as normal on agglutinin testing, had venograms which showed only an isolated calf thrombosis in small muscle veins (< 2 cm in diameter) not requiring treatment. One hundred of 168 patients without venographic thrombosis were diagnosed correctly by SimpliRED (specificity: 59.5%). The positive predictive value was 53.7%; the negative predictive value was 96.8%. CONCLUSIONS: All thrombotic disorders in the leg that required further treatment were identified correctly. SimpliRED is a very sensitive test with moderate specificity in the diagnosis of deep vein thrombosis. Therefore, further invasive testing is needed only in those patients in whom the D-dimer test is abnormal. A false-positive result of the bedside test may be nonspecific or due to elevated levels of fibrin split products, which can occur whenever the coagulation system has been activated by any of several conditions.

Nuclear and mitochondrial changes of co-cultivated spinal cord, spinal ganglia and muscle fibers following treatment with various doses of zidovudine.

Long-term zidovudine (also termed azidothymidine, AZT) treatment of AIDS patients may cause severe myopathy characterized by conspicuous mitochondrial and nuclear changes. The mitochondrial changes are attributed to an inhibitory effect of AZT on the mitochondrial gamma-polymerase in a variety of cells. Inhibition of the nuclear alpha-polymerase is another well-known side effect of AZT, whereas the (nuclear) beta-polymerase appears to be rather insensitive. The nuclear changes seen in AIDS patients are usually considered secondary to the human immunodeficiency virus infection. To eliminate the influence of the virus on the nuclei, we studied the effect of AZT on non-infected, organotypic co-cultures of spinal ganglia, spinal cord, and skeletal muscle from fetal rats. We noted significant changes not only in the mitochondria but also in the nuclei of spinal ganglia, spinal cord, and muscle cells, which depended more on the duration of AZT application (1, 3, 5, and 8 days) than on the concentration (0.1, 1, 10, 100 and 1000 microM). The alterations of the mitochondria consisted mainly of swelling, loss of cristae and, finally, disappearance. The nuclei showed nucleolar segregation, marginal condensation of heterochromatin, formation of interchromatin and perichromatin granules, nuclear protrusions and pseudoinclusions and, finally, disintegration. The changes were not as pleomorphic as those seen in biopsy specimens from AIDS patients who had received long-term treatment with AZT. However, this difference can easily be attributed to the short duration of drug application in tissue culture compared to the long-term medication in patients.