Apoptosis of skeletal muscle myofibers and interstitial cells in experimental heart failure

Congestive heart failure (CHF) is characterized by a limb skeletal muscle myopathy with shift from the slow aerobic, fatigue resistant fibers, to the fast, anaerobic ones, and muscle bulk loss. Apoptosis (A) has been recently demonstrated to play a role in several cardiovascular diseases. AIM OF THE STUDY: we have investigated the role of A in the skeletal muscle of the hindlimbs in an experimental model of CHF. ANIMALS AND METHODS: CHF was induced in 7 males 80-100 g Sprague-Dawley rats with 30 mg/kg monocrotaline. Five age and diet matched controls were also studied. The time course of A was also studied in additional animals at day 0, 17, 24 and 30 days. RESULTS: At day 27 the electrophoretic analysis of myosin heavy chains (MHCs) demonstrated in the CHF rats the occurrence of a myopathy, with disappearance of slow MHC1 in the Tibialis Anterior (TA), and a significant shift from the slow to the fast isoforms in the soleus and EDL. With in situ DNA nick-end labelling (TUNEL) we found in the TA of CHF animals a significantly higher number of TUNEL positive nuclei (0.43 +/- 0.24 v 0.08 +/- 0.02, P<0.02 and TUNEL positive myonuclei (0.031 +/- 0.012 v 0.0025 +/- 0.005, P<0.02). The time course of A showed a progressive rise in interstitial and myocyte A, accompanied by a drop in fibers cross-sectional area and muscle weight/body weight, that came out to be significant at 30 days. Western blot showed a lower expression of Bcl-2 at 27 days and a further drop at 30 days in the CHF rats. Double staining for TUNEL and antibody against anti-MHC2a and anti MHC2b + 2x showed that A occurs non-selectively in all the myofiber types. BetaANP and Right Ventricle Mass/Volume (RVM/V) correlated significantly with total apoptotic nuclei. CONCLUSIONS: In CHF myofibers A can lead to muscle atrophy. Endothelial cells A may produce an imbalance in myofibres nutrition with relative ischemia that triggers the preferential synthesis of fast anaerobic myosin as an adaptive mechanism or alternatively induce myofibres death.     

Decreased proportion of type I myofibers in skeletal muscle of dogs with chronic heart failure

BACKGROUND: Whether biochemical and histological abnormalities of skeletal muscle (SM) develop in patients with chronic heart failure (HF) remains controversial. In the present study, dogs with chronic HF were used to examine potential alterations of SM fiber type, fiber size, number of capillaries per fiber (C/F), beta-adrenergic receptor density (Bmax), and fiber ultrastructural integrity. METHODS AND RESULTS: HF was produced in 17 dogs by sequential intracoronary microembolizations. Biopsies of the lateral head of the triceps muscle were used in all studies. Type I and type II fibers were differentiated by myofibrillar ATPase (pH 9.4 or 4.2). Bmax was assessed by radioligand binding and SM ultrastructure by transmission electron microscopy. Comparisons were made with biopsies obtained from nine control dogs. The percentage of SM type I fibers was reduced in HF dogs compared with control dogs (19 +/- 2% versus 32 +/- 5%) (p < 0.001), whereas the percentage of SM type II fibers was increased (81 +/- 2% versus 68 +/- 5%) (p < 0.001). The change in fiber type composition was not associated with a preferential atrophy or hypertrophy of either fiber type. There was no difference in SM Bmax (198.9 +/- 14.3 versus 186.8 +/- 17.3 fmol/mg protein) or in C/F (5.37 +/- 0.26 versus 5.84 +/- 0.21) between HF dogs and control dogs. No ultrastructural abnormalities were present in SM fibers of HF dogs. CONCLUSIONS: In dogs with HF, there is a decrease in the relative composition of the slow-twitch type I SM fibers and an increase in fast-twitch type II fibers. The shift in fiber type composition is not associated with preferential atrophy of either fiber type or with a reduction in C/F, beta-adrenergic receptor density, or structural abnormalities of the myofibers.     

Diagnostic laparoscopy in primary and secondary infertility

PURPOSE: Our purpose was to compare the diagnostic efficacy of laparoscopy between primary and secondary infertility and to define a subgroup in which the positive findings are low. METHODS: A retrospective review of the cases of 206 infertile women who underwent laparoscopy was conducted. RESULTS: Eighty-two (39.8%) patients were found to have evidence of pelvic disease--20 (22.2%) with primary infertility and 62 (54.3%) with secondary infertility. The ratio of positive findings in secondary infertility was significant in comparison with the positive findings in primary infertility. In only 3 of the 20 patients with primary infertility was there no history of an abdominal operation, pelvic inflammatory disease, or an abnormal hysterosalpingography. Of the 62 women who suffered secondary infertility and had positive findings in laparoscopy, 15 had no history of suspect findings. CONCLUSIONS: The diagnostic yield of laparoscopy for primary infertility in the absence of indications of mechanical factors is low. Therefore the need for diagnostic laparoscopy in these cases should be reconsidered.     

Genetic alterations in primary and secondary hyperparathyroidism

OBJECTIVE: To evaluate treatment of patients with primary liver cancer. DESIGN: Prospective protocol including subsets of randomised studies. SETTING: University hospital, Sweden. SUBJECTS: 123 patients with primary liver cancer. INTERVENTIONS: 64 patients underwent hepatic resection, 25 were included in a trial of adjuvant chemotherapy. 24 further patients whose tumours were not resectable were included in a trial of intra-arterial infusion of doxorubicin. MAIN OUTCOME MEASURES: Survival and postoperative morbidity. RESULTS: The median survival time for patients who had had resections was 11 months (range 0-111). Twelve per cent survived more than 5 years. No prognostic factor had any significant effect on outcome. The postoperative mortality was 11% (7/64). The patients allocated to adjuvant chemotherapy survived a median of 10 months (range 1-47) and the controls 29 months (range 8-111) (p=0.04). Patients with unresectable liver cancer treated with intra-arterial doxorubicin lived no longer than untreated controls (median 8 months (range 1-56) compared with 7 months (range 1-28)). CONCLUSIONS: Treatment of patients with primary liver cancer is still an unsolved problem. Adjuvant chemotherapy with doxorubicin had no beneficial effect on survival.     

Contraction of developing avian heart muscle

26 patients with at least one clinical symptom that could indicate a tear of the scapho-lunate interosseous ligament but normal static and dynamic radiographs were examined by arthroscopy. We found that a diagnosis of scapho-lunate instability could be established by dynamic manoeuvres during radio-carpal and mid-carpal arthroscopy. Five patients were found to have true scapholunate instability. Six tears of the interosseous ligament without instability were also detected but it was doubtful if the tear was the origin of the painful symptomatology. This experience suggests that dynamic manoeuvres during arthroscopy are superior to other methods in diagnosing scapholunate instabilities at the pre-radiographic stage.     

Management of trauma to primary and developing teeth

Traumatic dental injuries to the young child can present both diagnostic and therapeutic challenges. Luxation injuries to the primary dentition are the most common injuries. Yet, they are the most controversial with regard to definitive treatment, prognosis, and sequelae. Damage to the developing teeth subsequent to primary tooth injury is often unavoidable and has permanent effects on the dentition. Diagnostic criteria, treatment options, and outcomes are presented in this article; however, treatment decisions are often based on patient behavior.     

Sensorimotor integration in human primary and secondary somatosensory cortices

We measured somatosensory evoked fields (SEFs) to electric median nerve stimuli from eight healthy subjects with a whole-scalp 122-channel neuromagnetometer in two different conditions: (i) 'rest', with stimuli producing clear tactile sensation without any motor movement, and (ii) 'contraction' with exactly the same stimuli as in 'rest', but with the subjects maintaining sub-maximal isometric contraction in thenar muscles of the stimulated hand. The aim was to study the role of the primary (SI) and secondary somatosensory (SII) cortices in sensorimotor integration. The amplitude of the SI response N20m did not change with coincident isometric contraction, whereas P35m was significantly reduced. On the contrary, activation of contra- and ipsilateral SII cortices was significantly enhanced during the contraction. We suggest that isometric contraction facilitates activation of SII cortices to tactile stimuli, possibly by decreasing inhibition from the SI cortex. The enhanced SII activation may be related to tuning of SII neurons towards relevant tactile input arising from the region of the body where the muscle activation occurs.     

Clinical features of primary and secondary atypical mycobacteriosis

A clinical investigation was carried out in 39 patients with atypical mycobacteriosis (AM). The patients at our hospital diagnosed as having AM during an 11-year period from 1981 to 1991 were reviewed in this study. The incidence of AM among all of mycobacterial infections has been increasing since 1988. The atypical mycobacteria detected included M. avium complex (MAC) in 79%, M. kansasii in 26%, and other organisms in 5%. Patients who had primary infection without underlying respiratory disease were compared with those who had secondary infection. In secondary infection, MAC was detected in the sputum of a high percentage of patients and was positive for more than 6 months despite therapy. Gamma globulin levels were also increased in patients with secondary infection. Cell mediated immunity was examined by the DNCB reaction and the detection of CD4- and CD8- positive T lymphocytes. The DNCB skin reaction was positive in 6 out of 26 patients with secondary infection. The percentage of CD8- positive T lymphocytes was higher in patients with secondary disease. Fischer's ratio (indicating the balance of plasma amino acids) was also examined as an index of the nutritional status. It was significantly lower in secondary infection compared with primary infection. Moreover, secondary infection was associated with a lower positive rate for the DNCB skin reaction and a lower Fischer's ratio when compared with pulmonary tuberculosis. Thus impairment of cell-mediated immunity, malnutrition, and a poor prognosis were significantly more common in secondary infection compared with primary infection.     

Optimal management of primary and secondary mitral regurgitation

Systemic lupus erythematosus and antiphospholipid antibody syndrome are associated with an increased risk of intrauterine growth restriction, miscarriage, stillbirth and premature delivery. Recent advances in therapy during pregnancy have improved the outcome but there is still significant fetal and maternal morbidity and mortality. Treatment of patients failing conventional therapy during the second half of pregnancy is difficult and may be complicated by the development of preeclampsia. The addition of intravenous immunoglobulin therapy offers a low risk strategy for reducing autoantibody mediated disease and improving placental function in severely compromised, growth restricted pregnancies.     

Carboxyhemoglobin levels in primary and secondary cigar and pipe smokers

This study of 130 subjects was performed to obtain more data about the smoking habits and levels of carboxyhemoglobin in various types of pipe and cigar smokers. These smokers may be divided by history into primary or secondary smokers and also into current inhalers and noninhalers. Prior studies of carboxyhemoglobin levels have yielded conflicting results, presumably due to differences in current habits of inhalation, which were often not taken into account. Cigarette, primary pipe, and secondary pipe inhalers had similar carboxyhemoglobin levels that were significantly higher than nonsmokers (5.6, 5.0, 5.4, and 1.0 percent, respectively). Cigar inhalers had markedly elevated concentrations of carboxyhemoglobin (13.8 and 11.8 percent in primary and secondary inhalers, respectively). Most secondary cigar and pipe smokers inhaled, whereas most primary smokers did not. Intentional inhalation, rather than past smoking history, is the most important factor in determining the carboxyhemoglobin level for each type of smoke.     

Purification of a novel muscle cell growth factor S-myotrophin from porcine skeletal muscle

A comparison of muscle weight between denerved and control rabbit hind legs revealed that a water-soluble 12 kDa substance was reduced in atrophied muscles after denervation. We hypothesised that a water-soluble growth factor exists which mediates a signal from motor nerves to muscles. To isolate this factor we modified the purification procedures of Sen et al. [S. Sen, G. Kundu, N. Mekhail, J. Castel, K. Misono, B. Healy, Myotrophin: purification of a novel peptide from spontaneously hypertensive rat heart that influences myocardial growth, J. Biol. Chem. 265 (1990) 16635-16643.], who originally purified a water-soluble growth factor from cardiac muscles. Four additional purification steps were added to the method. Using this technique, a novel muscle cell growth factor, named s-myotrophin, was purified from porcine skeletal muscle (M. longissimus thoracis). Purified s-myotrophin appeared as a single band (12 kDa) on SDS-PAGE and had a strong growth promoting activity (increase of protein synthesis) of cultured primary skeletal muscle cells. Almost no loss of growth promoting activity was observed after trypsin and chymotrypsin digestion. No fragmentation of s-myotrophin was observed after exposure to lysylendopeptidase, thermolysin, trypsin and chymotrypsin. Crude preparation of this molecule could be detected by periodic acid/Schiff (PAS) staining. Deglycosylation of s-myotrophin produced a smaller molecule having an approximately 7 kDa mass. These data indicate a novel 12 kDa protein has been isolated which has growth promoting properties on skeletal muscle cells.     

Factor XIIIa immunoreactivity in primary and secondary tumours of the meninges

Occasionally variants of meningeal hemangiopericytomas (HPC) may be confused with primary and secondary tumours of the meninges by virtue of their features and patterns of growth. Until now, a specific immunohistochemical marker for HPC could not be identified. HPC are reported to express factor XIIIa (F XIIIa) in the cytoplasm of the tumour cells. In an effort to assess the diagnostic value of F XIIIa for meningeal HPC, we investigated 38 primary meningeal tumours (6 HPC, 28 meningiomas of various subtypes, 4 meningeal sarcomas) and 23 secondary meningeal tumors (8 metastatic carcinomas, 6 gliosarcomas, 9 anaplastic gliomas) with anti-F XIIIa antibody. All HPC revealed 5%-20% of F-XIIIa-positive neoplastic cells. Malignant fibrous histiocytomas and gliosarcomas with MFH-like structures also exhibited multiple F-XIIIa-positive cells. Most of the F-XIIIa-positive cells in meningiomas were identified as macrophages. Furthermore, there was a population of small dark cells of uncertain histogenesis. Cells with positive immunoreactivity for F-XIIIa in metastatic carcinomas and gliomas apparently were of macrophage lineage. Though, in some cases, it would have been difficult to distinguish reactive from neoplastic cells without simultaneous immunohistochemical investigation with antibodies for macrophages, cytokeratin, EMA and GFAP. Because of these uncertainties, wo believe that the potential of F XIIIa-antibody in obtaining precise differential diagnostic information is limited.     

The comparative histopathology of primary and secondary lesions in murine salmonellosis

In a primary infection, Swiss-Webster mice were injected i.p. with 10(2) or 10(3) virulent Salmonella typhimurium. Multiple microscopic acute abscesses with predominantly polymorphonuclear leucocytes (PMNs) were seen in the liver and the spleen beginning on the 4th day after infection. By the 7th day, these lesions had become enlarged and were gradually transformed into granulomas with central necrosis and peripheral mononuclear cells. The animals usually died within 12 days with massive systemic infection and degeneration of the tissues. In contrast, it was necessary to inoculate 10(6) virulent salmonella i.v. into mice immunized with avirulent S. thphimurium in order to initiate microscopically observable lesions in the liver and the spleen. These secondary lesions were characterized by the early appearance of minute granulomas composed almost entirely of histiocytic cells. They remained small and isolated, usually without central necrosis. Subsequent regression of the lesions and regeneration of normal tissue occurred after the 2nd week following infection. The animals usually survived such a challenge infection.     

Spatial accuracy of primary and secondary memory-guided saccades in schizophrenic patients

A reusable cone suitable for use with existing laparoscopy cannulas was designed to provide means for sealing and stabilizing the operative site throughout the procedure, and for repairing the surgical site after the surgery is completed. The device consists of a moveable laparoscopic cannula cone fitted with suture holders. The cone contains tunnels terminating at its distal end that serve as passages for sutures loaded on a special needle to traverse the abdominal wall. When sutures are pulled into suture holders they stabilize the cannula and seal the puncture site. When sutures are tied at the end of the procedure, they achieve full-thickness closure of the operative site. The laparoscopic cannula cone stabilizes the cannula on the abdominal wall, maintains an air-tight seal, controls potential hemorrhage from the cannula puncture site, and achieves satisfactory closure of the surgical defect. Preliminary experience with the instrument and method has been most satisfactory.     

Therapeutic approaches to primary and secondary brain tumours

INTRODUCTION: This study examined the long-term effects of hysterectomy, with and without bilateral oophorectomy, and treatment with estrogen replacement on bone mineral density in older hysterectomized women. METHODS: Subjects were 346 women 60-89 years of age, who were participants in the Rancho Bernardo Study and attended a follow-up clinic visit in 1988-1991. Bone density was measured at the ultradistal wrist, midshaft radius, lumbar spine and hip. RESULTS: Of these women, 182 had a hysterectomy with conservation of one or both ovaries and 164 had a hysterectomy with bilateral oophorectomy. Current estrogen users had the highest bone densities; those who never used estrogen replacement had the lowest. Only 9.1% of oophorectomized women, compared to 19.2% of those with ovarian conservation had never used estrogen (P < .01). After adjustment for covariates including estrogen replacement therapy, hysterectomized women with ovarian conservation had marginally higher bone densities at the wrist (P < .09) and spine (P < .06) than oophorectomized women. We found significant differences only among women currently using estrogen (P < .05 for wrist and P < .01 for spine densities, respectively). Bone density did not differ at any site by oophorectomy status among past or never users of estrogen. CONCLUSIONS: Hysterectomized women who use estrogen replacement therapy have better bone density, regardless of a bilateral oophorectomy. In addition, bilateral oophorectomy may not have a long-term negative effect on bone density; hysterectomized women who do not use estrogen appear to have equivalent bone density whether or not they had a bilateral oophorectomy.     

Polyneural innervation in the psoas muscle of the developing rat

Polyneural innervation was studied in the psoas muscle in developing rats from P4 till P25 and at adult age, with the combined silver-acetylcholinesterase technique. Nerve endings were counted, and end-plates were measured. These data were compared with such data in the human. The end of polyneural innervation in the rat (around P20) and in the human (around 12 weeks postterm age) in both cases coincides with a transformation in motor behavior and postural control. The rat's psoas muscle at early stages is less heavily innervated than this muscle in the human. Up to three axons per motor end-plate were counted at P4, but in the human up to five axons at 25 weeks of post menstrual age. This difference might be related to the lower percentage of type I muscle fibers in the rat.