Healing of the aponeurosis during recovery from aponeurotomy: morphological and histological adaptation and related changes in mechanical properties.

Aponeurotomy, which is the transection of an aponeurosis perpendicular to its length, is performed to lengthen spastic and/or short muscles. During recovery, the cut ends of the aponeurosis are reconnected by new connective tissue bridging both ends. The aim of this study is to investigate the histological features of this new connective tissue as well as its mechanical properties after recovery from aponeurotomy. For this purpose, aponeurotomy was performed on the proximal aponeurosis of rat m. gastrocnemius medialis (GM), which was followed by six weeks of recovery. The lengths of aponeurotic tissues were measured as a function of active muscle length. The results are compared to a control group as well as to the acute effects and a sham operated group. Activation of the muscle at increasing lengths after aponeurotomy caused a gap between the cut ends of the aponeurosis. However, after recovery, new connective tissue is formed bridging the aponeurotic ends, consisting of thin collagen fibres, which are densely packed and generally arranged in the direction of the aponeurosis. The number of fibroblasts was three to five times higher than that of aponeurotic tissue of the intact parts as well as that of the acute and sham operated muscles. The strain of the new connective tissue as a function of active muscle length was shown to be about three times higher than that of the aponeurosis. It is concluded that the inserted new aponeurotic tissue is more compliant and that the aponeurosis becomes 10-15% longer than in untreated muscle. As a consequence, the muscle fibres located distally to the new aponeurotic tissue will become shorter than prior to aponeurotomy. This explains a shift of the length-force curve, which favours the restoration of the range of joint motion.

Development of granulomatous common variable immunodeficiency subsequent to infection with Toxoplasma gondii.

Common variable immunodeficiency (CVID) is a heterogeneous immunodeficiency that is accompanied by granulomatous lesions in 5-10% of cases. Why some patients develop granulomatous disease remains unclear. Here we describe a 12-year-old previously healthy girl who presented with pancytopenia and granulomatous lymphoproliferation subsequent to infection with Toxoplasma gondii. Loosely arranged non-fibrosing granulomas were observed in the liver, lymph nodes and lung, but no Toxoplasma tachyzoites could be demonstrated and polymerase chain reaction (PCR) and culture were negative for Toxoplasma and a wide range of other pathogens. While the patient had a normal peripheral B cell status at presentation, the development of CVID could be observed during the following months, leading to a loss of memory B cells. This was accompanied by an increasingly activated CD4(+) T cell compartment and high serum levels of angiotensin-converting enzyme (ACE), tumour necrosis factor (TNF) and sCD25. Steroid therapy reduced pancytopenia, granulomatous lymphoproliferation and cytokine elevations, but did not improve the B cell status. This is the first report of an association of Toxoplasma infection with granulomatous CVID and provides one of the rare examples where the onset of CVID could be documented subsequent to an infectious disease.

Dieulafoy lesion in a one-year-old child.

The Dieulafoy lesion is a rare cause of severe upper gastrointestinal bleeding associated with a significant mortality. Rebleeding from undiscovered lesions is frequent and often fatal. The outcome depends on a high degree of suspicion for the condition. In any age group, the entity may be underdiagnosed rather than truly rare. It is particularly uncommon in infants. The authors report the case of the youngest patient so far to suffer from a Dieulafoy lesion.

Experimental use of an albumin-glutaraldehyde tissue adhesive for sealing tracheal anastomoses.

AIM: The purpose of this study was to test the performance of an albumin-glutaraldehyde tissue adhesive (BioGlue, manufactured by CryoLife Inc., Kennesaw, GA, USA) when used on tracheal resections in rabbits, which is a sensitive model to investigate the biocompatibility of the glue. METHODS: The 24 animals were anesthetized and underwent cervicotomy with resection of a 10 mm long tracheal segment. The experimental group (18 animals with 2, 4 and 12 week endpoints) had a tracheal anastomosis performed with a maximum of 4 sutures for the approximation of the tissue margins. The anastomotic line was then circumferentially covered with the adhesive. Control animals (6 animals, 4 week endpoint) had a tracheal anastomosis performed with the use of twice interrupted, airtight running suture. The experiments were conducted after approval by the Institutional Ethics Committee and in accordance with the European Convention on Animal Care. RESULTS: Macroscopic evaluation revealed a tight closure of the anastomosis in 23 animals. One rabbit developed tracheo-cutaneous fistula, 2 rabbits experienced intraluminal granulations due to infection, and 1 rabbit developed tracheal stenosis due to insufficient sutures with axis-displacement of the anastomosed tracheal lumina. On microscopic examination, after 2 weeks an inflammatory tissue response consisting of neutrophils, macrophages and foreign body giant cells was found surrounding the glued area. After 4 weeks the tissue was granulomatous in character with an increasing number of multinucleated giant cells. In general, persistent granulomatous inflammation and fibrous scar tissue was seen after 12 weeks. Both, macroscopically and microscopically, fibroangioblastic tissue responses were found in the control group after 4 weeks. CONCLUSIONS: Despite secondary healing disruptions such as granuloma formation, our investigations suggest that the results of albumin-glutaraldehyde tissue adhesive sealed tracheal anastomoses with a few approximating sutures are comparable with those using suture technique. Short term results demonstrated good biocompatibility of the glue.

Toxic epidermal necrolysis: differential diagnosis of an epidermolytic dermopathy in a hematopoietic stem cell transplant recipient.

Toxic epidermal necrolysis (TEN) is an epidermolytic skin disorder associated with drug administration. It is associated with an erythematous rash with full thickness epidermal loss and characteristic histology. A 35-year-old woman underwent allogeneic hematopoietic stem cell transplantation (HSCT) for severe aplastic anemia (SAA). She developed an acute epidermolytic rash and TEN was diagnosed on the basis of skin biopsy. In the HSCT setting, TEN should be thought of as an important differential diagnosis of epidermolytic dermopathies. The most distinctive diagnostic test in the differential diagnosis of these disorders is skin biopsy

Experimental use of an albumin-glutaraldehyde tissue adhesive for sealing pulmonary parenchyma and bronchial anastomoses.

OBJECTIVE: Despite advanced surgical techniques, major complications of bronchial anastomoses and parenchymal repair, including early leak, fistula formation and granulations still occur. The purpose of this study was to test the performance of an albumin-glutaraldehyde tissue adhesive (BioGlue), CryoLife Inc., Kennesaw, GA) as a sealant for bronchial anastomoses and parenchyma lesions. METHODS: Twenty-four sheep were split into two surgical groups. The first group consisted of six control sheep receiving standard sutured bronchial anastomosis with a 4-week end-point. The second group included 18 sheep receiving both a bronchial anastomosis and parenchymal defect repair using the adhesive with 2, 4, and 12 week end-point. Histopathologic evaluation was conducted at the study end-points. RESULTS: Bronchial anastomosis and parenchymal tissue repair can be sealed successfully against air leakage with adhesive. Macroscopic evaluation revealed a tight closure of the anastomosis and parenchyma defect in all postoperative stages, initially by the adhesive layer, and later by connective tissue. On microscopic examination, an inflammatory tissue response consisting of polymorphonuclear neutrophils, macrophages, granulation tissue and foreign body giant cells were found surrounding the glued area after 2 weeks. After 4 weeks the tissue response presented a granulomatous character. No granulomatous or foreign body reaction was present in the hand sutured group. After 12 weeks few remnants of adhesive surrounded by fibrous scar tissue were detectable in bronchial anastomosis and parenchymal repair. Healing was not considerably complicated by foreign body reaction or tissue granulation. CONCLUSION: This study supports BioGlue to be effective as an adjunct in sealing bronchial anastomosis and lung parenchyma defects in sheep, with minimal secondary healing disruptions such as granuloma formation. The results of this study indicate that the use of BioGlue in human pulmonary surgery should be effective.

Pathomorphological and histological analysis of the indirect revascularization method.

OBJECTIVE: This experimental study was initiated to determine whether TMLR may prevent porcine myocardium from ischemia and necrosis after acute myocardial infarction. In addition, the influence of TMLR on healthy myocardium was analyzed. METHODS: The short-term effectiveness of TMLR was evaluated in 38 open-chest anesthetized pigs with (n = 18) or without (n = 20) acute LAD occlusion (observation period 6 hours): Six pigs served as controls (thoracotomy only). An additional six pigs had LAD occlusion only (ischemic group). A subsequent 12 pigs were treated by TMLR (CO2) prior to LAD occlusion: Six pigs received one laser channel/cm2 (group 1) and in six pigs two channels/cm2 in the LAD territory (group 2) were performed. In addition, 14 pigs underwent TMLR without ischemia: Seven pigs received 1 channel/cm2 (group 3) and seven pigs 2 channels/cm2 (group 4). Pathomorphological assessment and histology were performed. RESULTS: TMLR limits the expansion of the myocardial infarction zone: laser group 2 demonstrated a significantly smaller area of necrosis in the area at risk (ischemic group (32%) vs. laser group 1 (18%, p = ns) and 2 (8%, p = 0.0076); laser group 1 vs. 2, p = 0.0056). The amount of the area of necrosis of laser groups 3 (0.4%) and 4 (0.04%) compared to control (0%) did not differ significantly (p = ns). Furthermore, in the lased territories of laser groups 3 and 4 microscopic analysis revealed signs of ischemia in 10 +/- 30.9% of all examined histological samples (p = ns vs. control). During a short coronary occlusion the laser-induced tracks were partially filled with blue dye in 94.8 +/- 27.0/85.9 +/- 34.3/94.85 +/- 22.0%/70.21 +/- 47.0% (laser groups 1 - 4 respectively p = ns) The myocardial water content-measurements (MWC) of the ischemia and laser group 1 were not different at the end of the experiment (p = ns). In contrast, laser groups 2, 3 and 4 revealed significantly higher MWC values compared to control (p = 0.036, p < 0.001, p < 0.001; respectively). CONCLUSIONS: This prolonged acute study demonstrates that preventive CO2-laser revascularization significantly reduces the amount of necrosis in the area at risk. Histological examination supported the idea that some pigment gained access to the ischemic tissue via patent channels. In healthy myocardium, TMLR significantly increases myocardial water content and induces non-significant small ischemic and very small necrotic areas surrounding open laser channels.

[Penetrating stab injury to the heart with unusually long survival]. / Penetrierende Herzstichverletzung mit ungewöhnlich langer Uberlebenszeit.

A 19-year-old man was injured with a kitchen knife by a singular stab to the left anterior thoracic wall. Initial medical treatment was limited to the extrathoracic soft tissue wound and volume replacement by infusion. Subsequently the circulatory situation stabilized and the patient seemed to be out of danger. 3 1/2 hours after treatment a hemorrhagic shock developed, which resulted in the death of the patient while an emergency thoracotomy was still being performed. At autopsy a penetrating stab wound was detected in the left ventricle with the wound track being partially blocked by thrombotic material. The pathophysiological causes of the atypical clinical course are described and discussed with reference to the relevant literature.

[Late spreading of tuberculosis in tubercular spondylitis]. / Tuberkulöse Spätstreuung bei Spondylitis tuberculosa.

HISTORY AND ADMISSION DIAGNOSIS: A 65-year-old man, known to have had a gastric ulcer and chronic rheumatoid arthritis as well as alcohol and nicotine abuse, was admitted because of suspected endocarditis. Physical examination revealed marked pain on pressure over the throacic spine. Vesicular breath sounds were reduced over the entire thorax and there was a systolic murmur over Erb's point (above the right clavicle). There was a purulent bursitis over the olecranon. INVESTIGATIONS: Abnormal laboratory tests were: elevated C-reactive protein, elevated leucocyte count (up to 33 thousand during the hospital stay). Smears from the bursitis and blood cultures revealed Staph. aureus. Computed tomography demonstrated a fracture of the 7th thoracic vertebra with a paravertebral abscess. Echocardiography showed anatherosclerotic aortic valve with floating particles. DIAGNOSIS, TREATMENT AND COURSE: Treatment of the suspected staphylococcal bacteraemia with purulent bursitis, spondylitis and aortic valvar endocarditis was begun with broad-spectrum antibiotics, but the patient soon developed a severe acute respiratory distress syndrome and he died of multi-organ failure. Autopsy revealed as cause of death left heart failure with aortic valvar endocarditis and gelatinour pneumonia caused by late tubercular dissemination from the tubercular spondylitis. CONCLUSION: Tuberculosis can be a life-threatening infection. Uncharacteristic history and extrapulmonary manifestations can make it very difficult to arrive at the correct diagnosis.

Inducible nitric oxide synthase in skeletal muscle of patients with chronic heart failure.

OBJECTIVES: The expression and localization of inducible nitric oxide (NO) synthase (NOS II) was evaluated as a source of NO which has been shown to affect muscle contraction. BACKGROUND: Advanced stages of chronic heart failure are associated with systemic activation of cytokines which have been shown to stimulate the expression of NOS II in various cell types, including myocytes. We hypothesized that systemic cytokine activation could lead to expression of NOS II in skeletal muscle of patients with chronic heart failure. METHODS: Skeletal muscle specimens were obtained by percutaneous needle biopsy in six normal volunteers and eight patients with heart failure (New York Heart Association class III). Electron microscopy immunocytochemistry (immunogold labeling) with specific anti-NOS antibodies was utilized to elucidate the intracellular localization of NOS II and neuronal NO synthase (NOS I) in myocytes of skeletal muscle. Reverse transcriptase, competitive polymerase chain reaction (PCR) was applied to quantify NOS II mRNA in skeletal muscle. RESULTS: Inducible nitric oxide synthase was readily expressed in the cytosol of skeletal muscle myocytes; NOS I expression was sparse. Polymerase chain reaction results indicated that NOS II gene expression is increased in patients with chronic heart failure. CONCLUSIONS: Inducible NO synthase is expressed in human skeletal muscle and its gene expression is increased in patients with severe heart failure. Given the experimental evidence that NO can attenuate contractile performance of skeletal muscle and can mediate muscle wasting, an increased local production of NO in skeletal muscle by NOS II may have important implications for patients with severe heart failure.

Clinical implication of screening p53 gene mutations in head and neck squamous cell carcinomas.

The role of the tumour-suppressor gene p53 in the tumorigenesis of head and neck cancer has been well established, but the clinical significance of p53 alteration is still unclear. A group of 50 patients with head and neck squamous cell carcinoma (HNSCC) were investigated for p53 alterations. DNA was extracted from fresh tumour samples and polymerase chain reaction/single-strand conformation polymorphism analysis was used to detect p53 gene mutations in the region from exon 5 to exon 9. In addition, p53 protein overexpression was assessed by immunohistochemistry using the monoclonal antibody DO-7 on paraffin-embedded tissue sections. p53 gene mutations were found in 45% and p53 protein expression was detected in 61.2% of tumour samples. While p53 protein expression was not correlated with any clinical factors, p53 gene mutations indicated local regional recurrences of HNSCC. The risk of locoregional recurrence was significantly greater in patients with a p53 gene mutation than in patients with the wild-type p53 gene (P = 0.001). Multivariate analysis confirmed p53 gene mutation to be an independently predictive factor for the tumour recurrence (P = 0.0064). When we analysed p53 gene mutation in 12 patients with primary and recurrent tumours, we found that 4 patients (33.3%) had a different p53 gene mutation in the recurrent tumour from that in the original primary tumour. The results indicate that p53 gene mutations and not protein overexpression are valuable predictors for tumour recurrences and for differential diagnosis of a second primary HNSCC.

The effect of a calcium hydroxide paste on wound healing and osseointegration of dental implants. A pilot study in beagle dogs.

The aim of this investigation was to evaluate the effect of a new calcium hydroxide suspension (Osteoinductal) on the healing process of endosseous dental implants after placement. The material, composed of 25% calcium hydroxide, 25% Oleum pedum tauri and 50% vaselinum album, was developed with the intention to accelerate and to increase the mineralized bone to implant contact during the healing phase. Eight adult beagle dogs were used in this study. Prior to the beginning of the study the dogs had all mandibular premolars extracted. After the extraction sites had healed for 3 months, implant osteotomies were performed. On one side of the mandibular premolars extracted. After the extraction sites had healed for 3 months, implant osteotomies were performed. On one side of the mandible Osteoinductal was applied into the osteotomies before placement of the implants, whereas the other side did not receive Osteoinductal. A total of 48 implants were placed with two losses during the entire study period. Two dogs were sacrificed 1 week, 2 weeks, 4 weeks and 3 months after implant placement. The specimens were evaluated histologically and histomorphometrically. In the histological evaluation an intense inflammatory reaction towards the calcium hydroxide suspension was found leading to a destruction of the bone surrounding the implants after 1 and 2 weeks. A giant cell reaction against the test material was visible at 4 weeks. At 3 months no inflammatory and no giant cell reaction could be depicted in the test group. The mean direct bone to implant contact or inflammatory tissue to implant contact showed no differences between test and control group for 1 and 2 weeks. Although statistically not significant, there was a clinical significant difference in the mineralized bone to implant contact between test and control group for the last two timepoints (i.e. 4-week specimens: test group 2.3 +/- 0.9%, control group 26.8 +/- 11.1%; 3-month specimens: test group 10.5 +/- 12.7%, control group 60.7 +/- 13.7%). This study indicates that the use of the calcium hydroxide suspension Osteoinductal has a detrimental effect on wound healing and osseointegration of dental implants and cannot be recommended for use with dental implants.

Early detection of metastasis by alterations in the cellular immune system in the murine liver and blood.

We investigated the reaction of the cellular immune system of liver and blood in the C57BL/6 mouse to a metastasizing Lewis lung carcinoma. The cellular immune system of the liver consists of mature and immature macrophages, B-cells, T-cells including their subpopulations, and natural killer cells, and their percentage frequencies differ significantly from those in the corresponding mononuclear blood cell (MBC) compartment. This suggests that the hepatic immune cells represent a system with autonomous function showing a typical homing of its members. Imminent metastasis to the liver is signalled by impressive alterations in the percentage frequencies of nonparenchymal liver cells (NPLC). There are a dramatic loss of mature macrophages, an increase in immature macrophages, a reduction of T-helper cells leading to a low CD4/CD8 ratio, and an increase in natural killer cells. In the blood, the corresponding precursor cells show comparable changes with a delay of at least 2 days. Early metastasis is accompanied by a significant increase in mononuclear NPLC producing tumour necrosis factor alpha. The alterations in percentage frequencies of the NPLC during tumour metastasis differ markedly from the changes in these cells in the liver during endotoxinaemia.

Inhibition of HIV-1 in cell culture by synthetic humate analogues derived from hydroquinone: mechanism of inhibition.

Humic acids are natural constituents of soil and ground water and mainly consist of mixtures of polycyclic phenolic compounds. A similar complex of compounds with a mean size of about 1000 Da, designated HS-1500, was synthesized by oxidation of hydroquinone. HS-1500 inhibited HIV-1 infection of MT-2 cells with an IC50 of 50-300 ng/ml and showed a mean cell toxicity of about 600 micrograms/ml. Inhibition of HIV-induced syncytium formation was observed at 10-50 micrograms/ml. Treatment of free and cell-attached HIV with HS-1500 irreversibly reduced its infectivity, whereas the susceptibility of target cells for the virus was not impaired by treatment prior to infection. The HIV envelope protein gp120SU bound to sepharose-coupled HS-1500 and could be eluted by high salt and detergent. HS-1500 interfered with the CD4-induced proteolytic cleavage of the V3 loop of virion gp120SU. Furthermore, binding of V3 loop-specific antibodies was irreversibly inhibited, whereas binding of soluble CD4 to gp120SU on virus and infected cells was not affected. In conclusion, our data suggest, that the synthetic humic acid analogue inhibits the infectivity of HIV particles by interference with a V3 loop-mediated step of virus entry.

Development and prevention of skeletal muscle structural alterations after experimental myocardial infarction.

The present study was designed to assess whether structural alterations develop within skeletal muscle 1 yr after myocardial infarction (MI) and failure and, if so, whether these structural alterations can be prevented by angiotensin-converting enzyme (ACE) inhibition. Infarcted rats were randomized and treated for 1 yr with either placebo (MI-IP, n = 9), a low dose of lisinopril (MI-LL, 0.5 mg.kg-1.day-1, n = 12), or a high dose of lisinopril (MI-LH, 5 mg.kg-1.day-1, n = 9). Sham-operated animals served as controls (SH, n = 14). One year after MI, in situ fixation of rat hindlimb was performed to investigate interstitial collagen volume fraction (CVF), capillary density, and media thickness of resistance vessels (80-200 microns) of musculus quadriceps femoris muscle. Infarct size was similar in all infarct groups and averaged 26 +/- 4%. Right ventricular weight was increased in MI-IP compared with SH, MI-LL, and MI-LH. Both left ventricular (LV) CVF and skeletal muscle CVF were increased in MI-IP. LV CVF and skeletal muscle CVF were closely related to each other (n = 44, r = 0.5377, P < 0.002). In infarcted rats, high-dose ACE inhibition significantly reduced skeletal muscle and LV CVF. Skeletal muscle capillary density and capillary-to-muscle fiber ratio were significantly decreased in infarcted rats but were restored by low- and high-dose ACE inhibition. Media thickness of intramuscular resistance vessels was increased in the MI-IP group and significantly reduced by high-dose ACE inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatoid adenocarcinoma of the stomach: a case report.

A case of primarily inoperable hepatoid adenocarcinoma of the stomach is reported, which, after chemotherapy with farmorubicin, 5-fluorouracil and leucovorin, showed an impressive regression resulting in an improvement of the overall condition of the patient and a decrease of the serum AFP level from initially 79.120 ng/ml to 3.728 ng/ml. In a second operation the tumor was removed and intraoperative radiation therapy was applied to the head of the pancreas and intraabdominal lymph nodes. Furthermore, we discuss the main pathologic features of this rare tumor entity and give a short review of the literature.

Mechanisms of human eosinophil activation by complement protein C5a and platelet-activating factor: similar functional responses are accompanied by different morphologic alterations.

The complement system is an important amplification system for the propagation of allergic as well as pseudoallergic inflammatory reactions. In the present study, the effect of the major anaphylatoxin C5a was compared with that of platelet-activating factor (PAF) on highly purified eosinophils (> or = 95%) by functional as well as morphologic criteria. Upon stimulation with C5a, eosinophils maintained their spheric structure, developing short, pseudopodia-like protrusions, whereas PAF induced the generation of a number of digitating protrusions. As shown by functional and ultrastructural assay systems, both stimuli provoked significant extracellular and intracellular H2O2 production in eosinophils, which was inhibited by cytochalasin B. With C5a, a pronounced H2O2 production was detected within the small cytoplasmic vesicles, whereas PAF-induced H2O2 production was observed on the outer surface of the plasma membrane in the contact zones between adjacent cells. Morphologic signs of degranulation induced by C5a and PAF were accompanied by the significantly increased release of eosinophil cationic protein and eosinophil peroxidase in the presence of cytochalasin B. Like PAF, C5a induced a significant production of reactive oxygen species in eosinophils, as measured by lucigenin-dependent chemiluminescence (CL) responses in eosinophils. Maximal responses, comparable with those of interleukin-5 (100 U/ml), were observed at concentrations of 10(-5)-10(-6) and 10(-7)-10(-8) M for PAF and C5a, respectively. Separation of eosinophils by discontinuous density gradients revealed the existence of two hypodense eosinophil populations, one of them showing significantly reduced CL responses upon stimulation with C5a and PAF. In addition, CL responses upon stimulation with C5a and PAF were abrogated by cytochalasin B, staurosporine, and wortmannin, and were almost completely blocked by pertussis toxin. In conclusion, these data indicate that C5a induces events in human eosinophils comparable to those induced by PAF in the assay systems tested. Thus, C5a, generated after activation of the complement system, may be of major importance for the eosinophil activation observed in eosinophil-related disease.

Comparative effects of chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on cardiac remodeling after myocardial infarction in the rat.

BACKGROUND: After myocardial infarction, the noninfarcted left ventricle develops reactive hypertrophy associated with a depressed coronary flow reserve, myocardial interstitial fibrosis, and reduced capillary density. The present study investigated the comparative cardiac effects of chronic angiotensin-converting enzyme (ACE) inhibition and selective angiotensin II type 1 receptor (AT1) blockade in the rat model of myocardial infarction and failure. METHODS AND RESULTS: Seven days after coronary ligation (MI), rats were randomized to enalapril (n = 8; 500 micrograms.kg-1.d-1), losartan (n = 9; 3 mg.kg-1.d-1), or placebo (n = 8) and treated for 6 weeks. Sham-operated rats (n = 10) served as controls. Coronary blood flow was measured with radiolabeled microspheres during baseline and maximal coronary dilation induced by dipyridamole (2 mg.kg-1.min-1 over 10 minutes). Right and left ventricular (LV) weight was increased in infarcted rats compared with sham-operated animals and enalapril- and losartan-treated MI rats. Minimal LV and right ventricular coronary vascular resistance was increased in MI rats but normalized with enalapril and losartan (LV:sham, 8.9; MI-placebo, 12.7; MI-enalapril, 9.2; MI-losartan, 8.8 mm Hg.mL-1.min-1.g-1, all P < .05 versus MI-placebo). Interstitial fibrosis determined from perfusion-fixed hearts was increased in infarcted rats but reduced by both enalapril and losartan. Myocardial capillary density improved with enalapril and losartan. In separate groups treated as above, plasma and tissue ACE activity was determined and demonstrated significantly higher ACE activity in noninfarcted LV tissue of MI-placebo rats compared with sham (0.64 vs 0.27 nmol.mg protein-1.min-1, P < .05). Enalapril and losartan reduced LV ACE activity (0.39 and 0.29 nmol.mg protein-1.min-1, P < .05 versus MI-placebo). CONCLUSIONS: The present study demonstrates that both chronic ACE inhibition and AT1 receptor blockade (1) reduces cardiac hypertrophy, (2) restores minimal coronary vascular resistance in postinfarction reactive hypertrophy, and (3) attenuates the development of myocardial interstitial fibrosis in the noninfarcted LV. These results suggest that inhibition of generation of angiotensin II and AT1 receptor blockade are equally effective in preventing important features of ventricular remodeling after myocardial infarction.

Carcinosarcomas of the lung. Three case reports and literature review.

Therapy and course of pulmonary manifestations of carcinosarcomas in three patients are described. For this rare mixed tumor there is a prevalence among men between the ages of forty and seventy. Operative therapy should be employed whenever possible, because of the poor results achieved thus far using radiotherapy or chemotherapy. Carcinosarcomas were thought to have a worse prognosis than other non-small-cell bronchial carcinomas but an increasing number of reports indicate a similar clinical course and prognosis. Pneumonectomy was required for two of our patients and lobectomy was performed in the third. The period of observation extended over two years. One patient, tumor stage T4N0M0 died of his disease after seven months. The two other patients, tumor stages T3N0M0 and T2N1M0, were operated on thirty-three and thirty-five months ago respectively and are clinically disease-free and in good health.

Influence of humate on calcium hydroxyapatite implants.

Implanted bovine apatite is highly osteoconductive, since it serves the host tissue as a "guide-line" for the deposition of newly developing bone tissue. It is well tolerated, but it showed no signs of being resorbed during the course of the experiment. Previous impregnation of the bovine hydroxyapatite with a low molecular humate substance obviously encourages its resorption. This is most easily explained by the known ability of humate to induce the activation of leucocytes. The occasional over-resorption of the apatite is dependent (1) upon the preparation of the implant (granulate) and (2) the local concentration of the humate. Future research is being directed towards the production of a satisfactorily usable form of humate and apatite and the investigation of its HIV blocking action on heterologous cancellous bone.