CT and MR Imaging Appearance of the Pedicled Submandibular Gland Flap: A Potential Imaging Pitfall in the Posttreatment Head and Neck.

Pedicled locoregional submandibular gland reconstruction flaps are increasingly used in oncologic head and neck surgery and have unique imaging characteristics that can mimic locally recurrent tumor. In this clinical report, 23 posttreatment imaging studies were evaluated in 19 patients who had undergone submandibular gland flap reconstructions after resection of a primary head and neck tumor. Submandibular gland flaps were most commonly mobilized into the parapharyngeal space or parotid bed, with others located inferior to the mandibular body and within marginal mandibulectomy defects. The original shape of the gland was typically not preserved. Identifying the submandibular gland hilum, vascular pedicle, glandular texture, and absence of submandibular gland in the orthotopic location was most useful in recognizing a flap. The interpreting radiologist must be familiar with the unique submandibular gland flap imaging characteristics to accurately differentiate normal postoperative appearance and recurrent tumor.

Molecular Preadaptation to Antimony Resistance in Leishmania donovani on the Indian Subcontinent.

Antimonials (Sb) were used for decades for chemotherapy of visceral leishmaniasis (VL). Now abandoned in the Indian subcontinent (ISC) because of Leishmania donovani resistance, this drug offers a unique model for understanding drug resistance dynamics. In a previous phylogenomic study, we found two distinct populations of L. donovani: the core group (CG) in the Gangetic plains and ISC1 in the Nepalese highlands. Sb resistance was only encountered within the CG, and a series of potential markers were identified. Here, we analyzed the development of resistance to trivalent antimonials (SbIII) upon experimental selection in ISC1 and CG strains. We observed that (i) baseline SbIII susceptibility of parasites was higher in ISC1 than in the CG, (ii) time to SbIII resistance was higher for ISC1 parasites than for CG strains, and (iii) untargeted genomic and metabolomic analyses revealed molecular changes along the selection process: these were more numerous in ISC1 than in the CG. Altogether these observations led to the hypothesis that CG parasites are preadapted to SbIII resistance. This hypothesis was experimentally confirmed by showing that only wild-type CG strains could survive a direct exposure to the maximal concentration of SbIII The main driver of this preadaptation was shown to be MRPA, a gene involved in SbIII sequestration and amplified in an intrachromosomal amplicon in all CG strains characterized so far. This amplicon emerged around 1850 in the CG, well before the implementation of antimonials for VL chemotherapy, and we discuss here several hypotheses of selective pressure that could have accompanied its emergence.IMPORTANCE The "antibiotic resistance crisis" is a major challenge for scientists and medical professionals. This steady rise in drug-resistant pathogens also extends to parasitic diseases, with antimony being the first anti-Leishmania drug that fell in the Indian subcontinent (ISC). Leishmaniasis is a major but neglected infectious disease with limited therapeutic options. Therefore, understanding how parasites became resistant to antimonials is of commanding importance. In this study, we experimentally characterized the dynamics of this resistance acquisition and show for the first time that some Leishmania populations of the ISC were preadapted to antimony resistance, likely driven by environmental factors or by drugs used in the 19th century.

Trochlear Groove and Trochlear Cistern: Useful Anatomic Landmarks for Identifying the Tentorial Segment of Cranial Nerve IV on MRI.

BACKGROUND AND PURPOSE: The trochlear groove and trochlear cistern are anatomic landmarks closely associated with the tentorial segment of cranial nerve IV. The purposes of this study were to describe the MR imaging appearances of the trochlear groove and trochlear cistern and to test our hypothesis that knowledge of these anatomic landmarks facilitates identification of cranial nerve IV in routine clinical practice. MATERIALS AND METHODS: For this retrospective study, consecutive MR imaging examinations of the sinuses performed in 25 patients (50 sides) at our institution were reviewed. Patient characteristics and study indications were recorded. Three readers performed independent assessments of trochlear groove, cistern, and nerve visibility on coronal images obtained by using a T2-weighted driven equilibrium radiofrequency reset pulse sequence. RESULTS: Interobserver agreement was 78% for visibility of the trochlear groove, 56% for the trochlear cistern, and 68% for cranial nerve IV. Following consensus review, the trochlear groove was present in 44/50 sides (88%), the trochlear cistern was present in 25/50 sides (50%), and cranial nerve IV was identified in 36/50 sides (72%). When the trochlear groove was present, cranial nerve IV was identified in 35/44 sides (80%), in contrast to 1/6 sides (17%) with no groove (P = .0013). When the trochlear cistern was present, cranial nerve IV was identified in 23/25 sides (92%), in contrast to 13/25 sides (52%) with no cistern (P = .0016). CONCLUSIONS: The trochlear groove and trochlear cistern are anatomic landmarks that facilitate identification of cranial nerve IV in routine clinical practice.

Successful diagnosis of lymphangioleiomyomatosis with transbronchial lung cryobiopsy.

A 47-year old female was evaluated in our clinic for an incidental discovery of diffuse cystic lung disease on high-resolution computed tomography (CT) scan of the chest. There was no personal or family history of tuberous sclerosis complex (TSC), sicca symptoms, pneumothorax, or skin or renal tumors. Review of her chest CT scan showed bilateral, round, uniform, thin-walled cysts present in a diffuse distribution characteristic of lymphangioleiomyomatosis (LAM). CT scan of the abdomen and pelvis did not reveal angiomyolipomas, lymphangioleiomyomas, abnormal lymphadenopathy, or chylous fluid collections. Serum vascular endothelial growth factor-D was non-diagnostic. In order to achieve diagnostic confirmation, the patient underwent transbronchial cryobiopsy of the lung, revealing changes consistent with LAM. Our case highlights the utility of transbronchial lung cryobiopsy in the evaluation of patients with suspected LAM and suggests that further investigation of this diagnostic technique is warranted in patients presenting with diffuse cystic lung disease.

[Striated muscle microvascular response to implants with sol-gel calcium phosphate coating. A comparative in vivo study]. / Der Einfluss von kalziumphosphatbeschichteten Implantaten auf die Mikrozirkulation des Skelettmuskels. Eine vergleichende In-vivo-Studie.

AIM: Local microvascular perfusion plays an important role in reparative processes and the pathogenesis of infection. The impairment of skeletal muscle microcirculation by a biomaterial may therefore have profound consequences. The aim of our study was to determine whether the biological acceptance of the widely utilised implant material stainless steel can be improved by a coating of sol-gel calcium phosphate. METHODS: Using the hamster dorsal skinfold chamber preparation and intravital microscopy, we quantified nutritive perfusion and leukocyte-endothelium interaction in skeletal muscle after implantation of sol-gel calcium phosphate-coated stainless steel- and commercial pure titanium implants, and compared these results to those obtained with uncoated stainless steel and titanium. RESULTS: Within the first 24 h after implantation, animals with calcium phosphate coated stainless steel showed a significantly lower inflammatory response than did those with an uncoated stainless steel implant. After 24 h the quantified microcirculatory parameters deteriorated for animals with a calcium phosphate-coated stainless steel plate, indicating that, for as yet unknown reasons, the shielding mechanism of the calcium phosphate seems to deteriorate. Although not as inert as pure titanium, we found a relatively low inflammatory response for calcium phosphate coated titanium over the whole observation period, suggesting that the coating as such is well tolerated by the skeletal muscle microcirculation. CONCLUSIONS: Our in vivo results suggest that the biological acceptance of a conventional stainless steel implant can be improved over a short term by a sol-gel coating of calcium phosphate. Concerning tolerance by the local vascular system, commercially pure titanium currently remains unsurpassed.

FDG-PET findings of vertebral compression fractures in osteoporosis: preliminary results.

The aim of this study was to evaluate FDG-PET findings in patients with osteoporosis or preclinical osteoporosis and acute vertebral compression fractures in order to determine whether FDG-PET has a value for distinction of pathological from osteoporotic vertebral fractures. 17 patients with a spontaneous compression fracture of the spine were evaluated by bone scanning with Tc-99m HDP, positron emission tomography with fluorine-18 deoxyglucose (FDG-PET) and magnetic resonance imaging (MRI). Osteoporosis had been established in all cases by X-ray and osteodensitometry. PET and bone scan images were scored independently from 0 (no pathological uptake) to 4 (definitive pathological uptake) by two blinded nuclear medicine physicians. The results of the blinded scoring were compared to MRI findings which served as gold standard. In 13 out of 17 patients, MRI demonstrated a vertebral fracture generating from osteoporosis. In 12 of these 13 cases, PET scans were scored with 0 or 1 and categorized as true negative. Standard uptake values (SUV) ranged between 1.1 and 2.4. In one of the 13 patients, PET was interpreted false positive with an uptake score of 3 (SUV = 2.9). Of the 17 patients, MRI revealed a pathological fracture caused by spondylodiscitis in three patients and by plasmacytoma in one patient. In these patients, all PET scans were highly positive with a score of 3 and 4 and SUV values between 3.8 to 9.8. The bone scans of all 17 patients were positive with scores of 3 or 4 but a differentiation between osteoporotic and pathological fractures was not possible. Our preliminary results indicate that acute vertebral fractures that originated from osteoporosis or preclinical osteoporosis tend to have no pathologically increased FDG uptake. Since a high FDG uptake is characteristic for malignant and inflammatory processes, use of FDG-PET may have potential value for differentiation between osteoporotic and pathological vertebral fractures.

Effects of paramyxoviral infection on airway epithelial cell Foxj1 expression, ciliogenesis, and mucociliary function.

To elucidate molecular mechanisms underlying the association between respiratory viral infection and predisposition to subsequent bacterial infection, we used in vivo and in vitro models and human samples to characterize respiratory virus-induced changes in airway epithelial cell morphology, gene expression, and mucociliary function. Mouse paramyxoviral bronchitis resulted in airway epithelial cell infection and a distinct pattern of epithelial cell morphology changes and altered expression of the differentiation markers beta-tubulin-IV, Clara cell secretory protein, and Foxj1. Furthermore, changes in gene expression were recapitulated using an in vitro epithelial cell culture system and progressed independent of the host inflammatory response. Restoration of mature airway epithelium occurred in a pattern similar to epithelial cell differentiation and ciliogenesis in embryonic lung development characterized by sequential proliferation of undifferentiated cells, basal body production, Foxj1 expression, and beta-tubulin-IV expression. The effects of virus-induced alterations in morphology and gene expression on epithelial cell function were illustrated by decreased airway mucociliary velocity and impaired bacterial clearance. Similar changes in epithelial cell Foxj1 expression were also observed in human paramyxoviral respiratory infection. Taken together, these model systems of paramyxoviral respiratory infection mimic human pathology and identify epithelial cell Foxj1 expression as an early marker of epithelial cell differentiation, recovery, and function.

Pain status of patients with severe haemophilic arthropathy.

Patients with severe haemophilia A growing up before the establishment of prophylactic treatment frequently developed significant haemarthropathies. The goal of the following study was to clarify the role of haemarthropathic pain for haemophilic patients. Furthermore, we aimed to determine to what degree daily activities are influenced by the impairment and which therapeutic modalities are used in pain management. Using a questionnaire we consulted 71 haemophiliacs concerning their complaints and how they were treated in 1999 (average age 43 years; range 21-63 years). The pain in the large joints and spine and the effect of specific treatment was estimated by a visual analogue scale. On average, there were four joints with major pain and 0.5 with minor pain. The most frequent sources of pain were the ankle joints (45%), followed by the knee (39%), spine (14%) and elbow (7%). Fifty percent of all patients complained of pain throughout the day if no treatment was applied. In 29% of patients, pain persisted after application of factor VIII (FVIII), while 12% claimed that pain still remained after use of FVIII and pain killers. Restriction in activities of daily life was reported by 89% of the group and 85% reported on an impact of pain on their mood. Patients primarily used FVIII to decrease pain, followed in frequency by use of anti-inflammatory drugs, orthopaedic footwear, liniments and bandages. Haemophilic patients with haemarthropathy are chronic pain patients. By means of the questionnaire, it is possible to reveal the 'silent' sufferers. Sufficient pain treatment is essential so as to increase the patient's quality of life and avoid inadvertent abnormal postures possibly resulting in increased loading of joints and subsequent bleeding episodes.

Results of a randomized, prospective, multicenter trial of mycophenolate mofetil versus azathioprine in the prevention of acute lung allograft rejection.

BACKGROUND: Although the use of mycophenolate mofetil (MMF) has reduced the incidence of acute rejection in heart and kidney allograft recipients, its role in lung transplantation remains controversial. Therefore, we conducted a randomized, prospective, open-label, multicenter study in lung transplant recipients to determine whether MMF decreases episodes of acute allograft rejection when compared with azathioprine (AZA). METHODS: Between March of 1997 and January of 1999, 81 consecutive lung transplant recipients from two centers were prospectively randomized to receive cyclosporine, corticosteroids, and either 2 mg/kg per day of AZA or 1 g twice daily of MMF. The primary study endpoint was biopsy-proven acute allograft rejection over the first 6 months posttransplant. Secondary endpoints included clinical rejection, cytomegalovirus (CMV) infection, adverse events, and survival. Surveillance bronchoscopies were performed at 1, 3, and 6 months, or if clinically indicated. Pathologists interpreting the biopsy results were blinded to the randomization. Results were analyzed according to intention-to-treat. Between group comparisons of means and proportions were made by using two sample t tests and Fisher's exact tests, respectively. Six-month survival was calculated by the Kaplan-Meier method and compared by the log rank test. RESULTS: Thirty-eight patients were prospectively randomized to receive AZA, and 43 MMF. The incidence of biopsy proven grade II or greater acute allograft rejection at 6 months was 58% in the AZA group and 63% in the MMF group (P=0.82). The 6-month survival rates in the MMF and AZA groups were 86% and 82%, respectively (P=0.57). Rates of CMV infection and adverse events were not significantly different between the two groups. CONCLUSIONS: Acute rejection rates and overall survival at 6 months are similar in lung transplant recipients treated with either MMF- or AZA-based immunosuppression.

Analysis of early deaths after isolated lung transplantation.

STUDY OBJECTIVES: To determine the causes of death in patients dying within 30 days after lung transplantation at the University of Florida, to assess the importance of several diagnostic modalities for determining the causes of their decline, and to construct an algorithm for the evaluation of patients with severe respiratory compromise occurring early after lung transplantation. DESIGN: Retrospective review of medical records and pathology slides from all patients dying within 30 days after lung transplantation, and biopsy specimen diagnoses from all lung allograft recipients at the University of Florida. PATIENTS: Nine deaths occurred during the first 30 days after transplantation among 117 patients undergoing 123 isolated lung transplantation operations. RESULTS: Infections accounted for the greatest number of deaths (bacterial pneumonia, four patients; catheter-related bacteremia, one patient). Persistent pneumonia confirmed by biopsy specimen was usually accompanied by histologic manifestations of acute cellular rejection and was associated with poor patient outcome (ie, death or subsequent development of bronchiolitis obliterans syndrome). In two patients, antibody-mediated rejection either was the immediate cause of death (hyperacute rejection, one patient) or preceded a fatal case of pneumonia (accelerated antibody-mediated rejection, one patient). Other causes of death included hypoxic-ischemic encephalopathy secondary to an intraoperative cardiac arrest (one patient), pulmonary venous thrombosis with bacterial colonization of the thrombotic material (one patient), and ischemic reperfusion injury (one patient). In most patients, more than one type of diagnostic technique was needed to ascertain the cause of the catastrophic decline. CONCLUSIONS: The causes of early posttransplant death in our patient group included infections, antibody-mediated rejection, hypoxic-ischemic encephalopathy secondary to cardiac arrest, pulmonary venous thrombosis, and ischemic reperfusion injury. Because these processes often demonstrate overlapping clinical and morphologic features requiring multiple diagnostic techniques for resolution, a systematic multimodality approach to diagnosis is advantageous for determining the causes of decline in individual patients and for estimating the incidences of the different causes of early graft and patient loss in the lung transplant population.

[Scapula alata as a complication of infection with human parvovirus B19 (erythema infectiosum)]. / Die Scapula alata als Komplikation der Infektion mit dem humanen Parvovirus B19 (Ringelröteln).

This article reports a case of a 38-year-old woman suffering from erythema infectiosum (slap-cheek disease) complicated by arthritis and severe brachial plexus neuritis resulting in scapula winging.

[Surgical outcome of single segment ventral fusion with plate osteosynthesis in therapy refractory chronic cervico-brachialgia]. / Operative Ergebnisse der monosegmentalen ventralen Fusion mit Plattenosteosynthese bei der therapieresistenten chronischen Zervikobrachialgie.

INTRODUCTION: In anterior cervical stabilization, collapses of the grafted bone with resulting localized kyphosis and graft dislocation has been reported. It was the aim of this clinical trial to evaluate the benefit of additional plating while taking specific implant-related complications into account. METHODS: The results of single level anterior cervical spinal fusion were evaluated. In 44 patients suffering from chronic cervical radicular pain with degenerative changes, arthrodesis with iliac-crest bone and plate fixation was performed. Apart from clinical parameters, the pre- and postoperative segmental kyphosis and cervical lordosis were evaluated. RESULTS: The total cervical alignment increased from 15.4 degrees to 18.5 degrees while the alignment of the fused segment increased from 2.6 degrees to 7.7 degrees. Postoperative decrease of correction did not occur. Bony fusion was confirmed in 95% after 12 months and 100% aller 36 months. Our results show that patients had more relief from radicular pain (80%) than from unspecific neck pain (66%). DISCUSSION: In single level anterior cervical fusion, additional plating successfully prevents dislocation of the bone graft and postoperative kyphosis. The clinical results and pseudarthrosis rate do not differ from studies without plating. Long. term follow-up studies are necessary to show the benefit of the reduced postoperative kyphosis.

Durable cure of mucormycosis involving allograft and native lungs.

Among the spectrum of fungi causing disease in lung allograft recipients, fungi in the order Mucorales represent uncommon pathogens. Lung transplant patients, however, often possess more than one risk factor for development of life-threatening mucormycosis. We describe a unique case of pulmonary mucormycosis involving both the allograft and the native lungs, in a single lung transplant recipient with steroid-induced diabetes. Extended intravenous amphotericin B and oral fluconazole therapy, reduction of immunosuppression, and blood glucose control achieved a durable cure without the need for surgical intervention. Early diagnosis with prompt initiation of multiagent antifungal therapy, prolonged continuation of antifungal therapies, and amelioration of contributing conditions are important elements of the treatment strategy that led to successful resolution of the infection.

Complete remission of pulmonary spindle cell carcinoma after treatment with oral germanium sesquioxide.

Spindle cell carcinoma (SCC) is a rare form of lung cancer representing 0.2 to 0.3% of all primary pulmonary malignancies. Even with combined surgery, chemotherapy, and radiation therapy, these tumors are associated with a poor prognosis and only 10% of patients survive 2 years after diagnosis. We describe a patient with an unresectable SCC who, following no response to conventional treatment with combined modality therapy, chose to medicate herself with daily doses of germanium obtained in a health food store. She noted prompt symptomatic improvement and remains clinically and radiographically free of disease 42 months after starting her alternative therapy.

Inhibition of arterial thrombogenesis by quinapril but not losartan.

The cardioprotective effect of angiotensin converting enzyme (ACE) inhibitors and angiotensin type I (AT1) receptor blockers may relate to their antithrombotic effect. We determined the differential effects of the ACE inhibitor quinapril and the AT1 receptor blocker losartan on arterial thrombus formation in the rat. Sprague-Dawley rats were fed regular chow or chow mixed with low-dose quinapril (0. 6 mg/kg/day), high-dose quinapril (1.2 mg/kg/day), or losartan (10 mg/kg/day) for 15 days. Abdominal aorta was exposed and wrapped with Whatman paper impregnated with 29% FeCl(3) (ferric chloride). Time to occlusive thrombus formation and weight of the thrombus were recorded. Aortic superoxide anion generation, platelet aggregation, plasma angiotensin II levels, and morphology of the thrombus were also examined. Both losartan and quinapril caused similar reductions in arterial pressure. Losartan did not affect the time to thrombus formation, whereas quinapril (both low and high doses) delayed the time to thrombus formation (P<.01 vs control). Weight of the thrombus was similar in all groups of rats. Platelet aggregation was inhibited by approximately 50 in both quinapril- and losartan-treated rats. The high-dose quinapril-treated rats showed markedly reduced vascular superoxide anion generation compared with the control rats (P<.05). Plasma angiotensin II levels were unaffected by quinapril treatment but were elevated 7-fold in losartan-treated rats (P <.001 vs. control rats). The thrombi in the control rats consisted of platelet aggregates, fibrin, and red blood cells. The intravascular platelet aggregates were much smaller in the quinapril-treated rats (P<.05 vs. control), but were similar in control and losartan-treated rats. In conclusion, quinapril but not losartan prolongs time to arterial thrombus formation and results in smaller platelet aggregates in the thrombus. Both quinapril and losartan decrease platelet aggregation, but only quinapril decreases superoxide anion generation. This effect on superoxide anion generation as well as mechanisms other than AT1 receptor blockade may underlie the salutary effect of quinapril on arterial thrombogenesis.

[Desmoplastic fibroma of the fibula. A difficult clinical, radiological and histological diagnosis]. / Das desmoplastische Fibrom der Fibula. Die schwierige klinische, radiologische und histologische Diagnose.

Desmoplastic fibroma of bone is a rare benign tumor that is made up of wavy fibroblasts and abundant collagenous tissue. The case of a 18-year-old patient is presented with a two months history of weightbearing pain in the left knee. Neither native x-ray, CT nor MRI could detect the kind of tumor. The histological findings lead finally to the diagnosis of a desmoplastic fibroma. Wide resection prevented recurrence of the tumor for 8 1/2 years until now. Considering the semi-malignant character of the desmoplastic fibroma and the recurrence rate marginal or wide resection for the primary treatment is recommended. The superior imaging quality of MRI facilitates preoperative planning.

[N. thoracicus longus lesion--a rare injury in weight lifting]. / Die N.-thoracicus-longus-Läsion als seltene Verletzung beim Kraftsport.

The case of long thoracic mononeuropathy associated with sport participation a presented. The diagnosis was confirmed with electromyography. It is suggested that the athletic activity caused a stretch injury to the long thoracic nerve. Degenerative changes and infections were excluded. Conservative management, consisting of range of motion exercises for the shoulder and strengthening of the serratus anterior muscle, resulted in a forable outcome. The 12 month follow-up showed only slight changes in EMG and clinical examination.

Susceptibility of lung transplants to preformed donor-specific HLA antibodies as detected by flow cytometry.

BACKGROUND: Preformed anti-HLA antibodies are known to have the potential to induce early graft damage in organ transplant recipients. However, in lung transplant recipients, little information exists about the significance of preformed antibodies directed to either class I or class II HLA antigens. METHODS: A two-color flow cytometry cross-match was performed in 92 consecutive lung transplant recipients using serum obtained immediately before transplantation. The presence of preformed antibodies was correlated with the incidence of severe graft dysfunction manifested as pulmonary infiltrates and severe hypoxemia with onset in the first few hours after transplantation. RESULTS: Six patients (6.5%) had low-level anti-donor IgG antibodies detected by flow cytometry, four against T and two against B lymphocytes. Three patients (50%) developed severe graft dysfunction with pulmonary infiltrates and hypoxemia. Two patients responded to treatment, but the third, who had an antibody highly specific for HLA-DR11, died at 48 hr after transplant. Results of histopathologic studies in this patient are consistent with hyperacute rejection and support a pathogenic role of these antibodies. In contrast, of 86 (93.5%) cases with a negative flow cytometry cross-match, only 4 (5%) had severe but reversible early graft dysfunction with pulmonary infiltrates and hypoxemia, attributed to ischemia-reperfusion injury (P<0.005). CONCLUSIONS: Class II, and perhaps class I HLA antibodies at relatively low concentrations represent a risk factor for severe early pulmonary graft dysfunction, with the potential to progress to hyperacute rejection and death.

Hypoxia-reoxygenation-induced apoptosis in cultured adult rat myocytes and the protective effect of platelets and transforming growth factor-beta(1).

The outcome of myocardial ischemia-reperfusion has been partially attributed to the degree of apoptosis in cardiomyocytes. Aggregating platelets by release of transforming growth factor-beta(1) (TGF-beta(1)) protect the isolated heart against ischemia-reperfusion injury and preserve myocardial TGF-beta(1) content. To gain more insight into the modulation of hypoxia-reoxygenation-induced injury (apoptosis and necrosis) to myocytes by TGF-beta(1) and aggregating platelets, cultured adult rat myocytes were exposed for 48 or 72 h to hypoxia alone, or to hypoxia followed by 3 h of reoxygenation. Apoptosis in the cells was determined by in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining and DNA fragmentation on gel electrophoresis. Hypoxia alone caused a time-dependent increase in myocyte apoptosis (number of apoptotic cells: 19+/-3% at 48 h and 39+/-5% at 72 h compared with 5+/-1% in control cells, based on a 500-cell count). Three hours of reoxygenation after 48 h of hypoxia further increased the number of apoptotic cells (34+/-8 versus 19+/-3% in hypoxia for 48 h), but reoxygenation after 72 h of hypoxia did not additionally increase the number of apoptotic cells, perhaps because of extensive cell necrosis on prolonged hypoxia. Forty-eight hours of hypoxia followed by 3 h of reoxygenation also resulted in a decrease in Bcl-2 and an increase in Fas protein level. Incubation of myocytes with either recombinant TGF-beta(1) (0.5-5 ng/ml) or aggregated platelet supernatant (from 2-3 x10(7) platelets/ml, containing approximately 0.5 ng/ml of TGF-beta(1)) markedly (P<.01) decreased the number of apoptotic cells after hypoxia-reoxygenation. Incubation with TGF-beta(1) also reduced myocyte necrosis as evident from lactate dehydrogenase release and trypan blue dye exclusion. These data demonstrate that hypoxia-reoxygenation results in apoptosis and necrosis in cultured adult rat myocytes; this can be attenuated by TGF-beta(1). Similarity of data with TGF-beta(1) and aggregated platelet supernatant suggests that platelet-mediated cardioprotection during hypoxia-reoxygenation may relate in part to the release of TGF-beta(1).