Sarcoplasmic body myopathy--a rare hereditary myopathy with characteristic inclusions.

OBJECTIVES: To characterise a Swedish family with a rare hereditary myopathy with unique sarcoplasmic inclusion bodies in the muscle biopsy. MATERIALS AND METHODS: Part of the pedigree was described in 1980. Nine new members of the included and the phenotype further characterised through clinical, neurophysiological and radiological investigations. RESULTS: Six of the nine subjects displayed clinical and/or laboratory evidence of myopathy with sarcoplasmic inclusions. CONCLUSIONS: Sarcoplasmic body myopathy is distinguished from other distal myopathies by a more malignant course and early involvement of thenar muscles and hand flexors. Five to ten years after onset the affected subjects develop distal, as well as proximal, weakness and atrophy and the majority require a wheelchair after ten to fifteen years of disease. The disorder is manifested through elevated creatine kinase levels and the presence of the pathognomonic sarcoplasmic inclusions prior to clinical signs and symptoms.

Intestinal pHi studied with continuous saline tonometry during ischaemia and reperfusion in the pig.

OBJECTIVE: To evaluate continuous saline tonometry for detection of progressive intestinal ischaemia and reperfusion in a porcine model. DESIGN: In eight anaesthetised pigs, small bowel mucosal pCO2 was recorded by means of two identical equipments for continuous saline tonometry and a standard tonometry balloon during ischaemia and reperfusion. RESULTS: Both systems of saline tonometry functioned stably during the four hour protocol ischaemia, although not significant until after 45 min for one of the tonometers. CONCLUSION: The equipment for continuous saline tonometry has a good reactivity, an accuracy comparable with standard tonometry.

Validation of a novel method for continuous saline tonometry in a porcine model.

Only intermittent and semi-continuous tonometric measurement of gastric and intestinal pHi is possible with the equipment available today. Earlier we developed a system for continuous saline tonometry and tested it in vitro. To assess the in vivo reliability of this method for continuous gastrointestinal saline tonometry, a standard tonometer for measurement of intestinal pCO2 and corresponding pHi was modified to allow continuous perfusion of physiological saline in a closed system and tested in a porcine model. In 11 anaesthetized and haemodynamically stable pigs, two continuous tonometry balloons were inserted into the distal small bowel, and a standard tonometry balloon was used as reference. To test long-term function of the continuous tonometers the research protocol lasted for eight hours. The two continuous saline tonometers performed well, and after an equilibration time of three hours the mean pHi values were stable between 7.35 and 7.43 and between 7.32 and 7.39 respectively. The standard tonometer measured stable pHi values. These preliminary studies indicate that continuous saline tonometry performs well over eight hours with a small bias and a good precision.

Decreased DMPK transcript levels in myotonic dystrophy 1 type IIA muscle fibers.

Myotonic dystrophy 1 is caused by the expansion of a CTG trinucleotide repeat on chromosome 19q13.3. The repeat lies in the 3' untranslated region of the myotonic dystrophy protein kinase gene (DMPK), and it has been hypothesised that the expansion alters the expression levels of DMPK and/or its neighbouring genes, DMWD and SIX5. Published data remain controversial, partly due to the mixed cell populations found in most tissues examined. We have microdissected human skeletal muscle biopsies from myotonic dystrophy 1 patients and controls and analysed gene expression at this locus for type I and type IIA fibres, using quantitative real-time reverse transcription-polymerase chain reaction. Levels of DMPK expression were specifically decreased in the type IIA fibres of myotonic dystrophy patients, below the levels found in controls. This suggests that DMPK expression is altered in this disease, suggesting significant pathological consequences.

[Intestinal ischemia after abdominal aorta surgery. A dreaded complication surveyed by a combination of different methods]. / Tarmischemi efter bukaortakirurgi. Fruktad komplikation kartlagd med en kombination av olika metoder.

The article consists of a review of findings in previously published reports on intestinal ischaemia after abdominal aortic surgery. In a combined cohort and case-control study of 2,824 patients from the Swedish vascular registry, the incidence of intestinal ischaemia was 2.8%. The independent risk factors identified were preoperative shock, emergency surgery, renal insufficiency, advanced age, operation at a regional hospital, aortabifemoral grafting, ligation of one or both internal iliac arteries, bleeding > 10 litres, and operating and cross-clamping time. Cardinal symptoms were unreliable predictors. Sigmoidoscopy was potentially diagnostic in 95 per cent of cases. In a clinical study of 34 patients, sigmoid colon pHi was highly predictive of ischaemic colitis and other life-threatening complications. In a por-cine model of ischaemic colitis, blood flow in the superior mesenteric artery, colonic pHi and histological mucosal damage were unaffected by dobutamine.

Diabetes mellitus as a risk factor for early outcome after carotid endarterectomy--a population-based study.

BACKGROUND AND PURPOSE: to determine if diabetes mellitus is a risk factor for outcome after carotid endarterectomy (CEA). METHODS: the outcome and complications of all vascular procedures performed in Sweden are registered prospectively in the Swedish Vascular Registry (Swedvasc) and form the basis of this report. During the 10-year period 1987-96 2622 CEAs were analysed for notified complications. RESULTS: of the 2622 CEAs, 341 (13%) were performed on diabetics and 2281 (87%) on non-diabetics. Patients with diabetes presented at a younger age (67.1+/-8.3 years vs. 68.2+/-8.3 years p =0.028), were more likely to have a history of hypertension (61.9% vs. 50% p =0.001) and were less often smokers (34.9% vs. 43.2% p =0.001). Diabetics presented more often with minor stroke (41.3% vs. 30.8% p =0.002) and non-diabetics more often with amaurosis fugax (18.9% vs. 14.4% p =0.04). Diabetics had a higher 30-day mortality (3.2% vs. 1. 4% p =0.02). The 30-day neurologic and cardiac morbidity did not differ. The 1-year mortality was 7.9% in diabetics and 4.4% in non-diabetics (p =0.008). Non-diabetics operated on in 1992-96 compared to those operated on in 1987-91 had a significantly lower combined permanent stroke and death rate (3.7% vs. 5.7% p =0.05), a difference not found in diabetics (6.3% for 1987-92 and 6.8% for 1992-96; N.S). CONCLUSIONS: diabetics had both a higher 30-day and 1-year mortality after CEA compared to non-diabetics, mainly because of cardiac complications. However, postoperative neurologic morbidity did not differ.

A new method for continuous tonometric pCO2 measurement--in vitro studies.

The available methods for tonometric pCO2 measurement only provide the possibility of performing intermittent registrations. A new method allowing continuous tonometric pCO2 measurement has been developed and tested in an in vitro model. A standard tonometer for intestinal pCO2 measurement was modified to allow continuous perfusion of the balloon with physiological saline solution in a closed system. The pCO2 in the system was determined in a specially constructed measurement chamber with a TCM20 percutaneous pCO2 monitor. In this in vitro model the tonometer balloon was placed in a saline bath with a constant pCO2 concentration and the measurements from the closed circulating system were compared with those obtained from a standard tonometer placed in the same bath. In 8 and 24 h experiments the circulating system measured the pCO2 value as accurately and reliably as traditional tonometry. This study indicates that the new method makes continuous monitoring of pCO2 possible.

CTG-repeat length in distal and proximal leg muscles of symptomatic and non-symptomatic patients with myotonic dystrophy: relation to muscle strength and degree of histopathological abnormalities.

Myotonic dystrophy (DM) is an autosomal dominant, multisystemic disorder with a variable phenotypic expression including muscle weakness and myotonia. The muscle wasting is most marked in distal limbs and in facial and neck muscles, although proximal limb muscles become affected as the disease progresses. The CTG-trinucleotide-repeat expansion associated with myotonic dystrophy is usually larger in muscle tissue than in leukocytes. It is unclear whether the repeat length itself bears any relation to the differences in the degree of weakness and atrophy between different muscles. We therefore analysed CTG-repeat lengths in blood and in proximal (m. vastus lateralis) and distal (m. tibialis anterior) muscles of patients with DM (n = 4) and non-symptomatic carriers of the mutant DM allele (n = 2) using conventional Southern blot hybridization. Muscle strength and histopathological abnormalities were evaluated for each muscle. In patients with clinical symptoms, the degree of paresis and morphological abnormalities was markedly more pronounced in m. tibialis anterior than in m. vastus lateralis. In these individuals, the CTG-repeat length was larger in muscles than in leukocytes, whereas in the two non-symptomatic carriers no difference could be detected. Furthermore, there was no clear difference in the repeat length between the two muscles in any of the patients. In conclusion, the selective muscular weakness and atrophy in DM do not seem to be related to differences in CTG-repeat length between different muscles.

Pentafuside (Trimeris).

Pentafuside (T-20) is a 36 amino acid peptide compound under development by Trimeris for the potential treatment of HIV infection, for which it received US FDA fast track designation in February 1999 [313596,182694]. It corresponds to amino acids 638 to 673 of HIV-1(LA1) transmembrane protein, gp41 [238873]. Pentafuside blocks HIV infection, uniquely, by preventing membrane fusion, an essential process in viral replication. In preclinical studies it blocked infection of cells by HIV and prevented the fusion of one HIV-infected cell with another [171217]. In March 1998, Trimeris signed a letter of intent with DuPont Merck Pharm Co to conduct trials of Merck's efavirenz in combination with pentafuside. The trial planned to enroll up to 48 HIV-infected individuals at three sites in the US, who have begun to fail their existing triple combination therapy. Prior exposure to non-nucleoside reverse transcriptase inhibitors and protease inhibitors, other than indinavir, will be among the exclusion criteria for the study. The first 10 days of the study is a dose-optimization period that will assess the safety, pharmacokinetics and antiviral activity of multiple ascending doses of pentafuside. After completion of this period, subjects will be eligible to participate in an extension period of at least six months, during which pentafuside will be administered in combination with efavirenz and two protease inhibitors [281696]. The use of pentafuside and truncated peptides in combination with other antiviral agents is claimed in WO-09640191.

Deltoid muscle in patients with polymyalgia rheumatica.

OBJECTIVE: To investigate muscle tissue in patients with polymyalgia rheumatica (PMR). METHODS: Deltoid muscle biopsies obtained from 10 female patients with PMR before corticosteroid therapy and from 5 healthy female controls of similar age were studied using light microscopy. Serial cryosections were stained for the activity of myofibrillar ATPases at various pH and for oxidative and glycolytic enzymes. Sections were also incubated with antibodies against different myosin heavy chain (MyHC) isoforms, and the laminin alpha1 chain, identifying capillaries and cell borders, and against ligands for selected adhesion molecules. RESULTS: The muscle fibers in patients and controls were mainly of type I containing slow MyHC, or type II AB containing both fast A and fast B MyHC isoforms. The oxidative capacity of the muscle fibers was in general low. In the patients with PMR the numbers of capillaries per unit area of type I and type II fibers were higher than in controls (p = 0.05 and p < 0.5, respectively). No accumulation of inflammatory cells or increased expression of adhesion molecules in the muscle sections from patients with PMR was found. CONCLUSION: There is increased microvascularization of the deltoid muscle fibers in patients with PMR. Whether this is directly associated with the systemic inflammation and the musculoskeletal symptoms or is mainly due to muscle fiber atrophy could not be determined.

Variation of CTG-repeat number of the DMPK gene in muscle tissue.

Myotonic dystrophy (DM) is associated with an unstable expansion of CTG repeats located in the 3' untranslated region of a protein kinase-encoding gene (DMPK) on chromosome 19 (19q13.3). The CTG repeat number varies between 5 and 37 in lymphocytes of normal individuals, whereas DM patients may have expansions from 50 to several thousand copies. Although the CTG expansions related to myotonic dystrophy (DM) are usually larger in muscle compared to peripheral blood, the variation in repeat number in non-dystrophic muscle is not known. In order to investigate if there is a variation, the CTG-repeat number was determined in percutaneous muscle biopsies obtained from 86 individuals without any muscle disorder or with a neuromuscular disorder without any clinical or histopathological signs of DM. The number of CTG repeats varied between 5 and 28, this being within the normal range reported for peripheral blood. A major sharp peak at n = 5 (27%) and a broader peak at n = 8-17 (56%) with peak values at n = 12 and 14 (11 and 14%, respectively) were observed. Alleles with 19 or more repeats amounted to 17% with a small peak at n = 20 and 21 (6 and 4%, respectively). It is concluded that the normal variation of CTG-repeat number in skeletal muscle is within the range found in peripheral blood, although there is a slight shift in the overall frequency distribution towards alleles with CTG repeat numbers in the higher range.

Early detection of major complications after abdominal aortic surgery: predictive value of sigmoid colon and gastric intramucosal pH monitoring.

The early detection and reversal of gastrointestinal ischaemia is thought to play a key role in minimizing the incidence of complications after abdominal aortic surgery. In an open prospective non-selective study intramucosal pH (pHi) was monitored in 27 patients undergoing elective aortic surgery and in seven submitted to emergency procedures. The pHi was monitored in the sigmoid colon in all 34 patients and in the stomach in 26. Eight patients developed major complications, four of whom had ischaemic colitis, and five died. Sigmoid acidosis (pHi below 7.10) served as an early warning; if acidosis was reversed within 2 h no major complication developed, if prolonged it was predictive of major morbidity (sensitivity 100 per cent, specificity 92 per cent). A colonic pHi below 6.86 predicted endoscopically detectable ischaemic colitis. A gastric pHi below 7.20 predicted major complications with a sensitivity of 100 per cent and specificity of 81 per cent. Both monitoring procedures were considered feasible, although monitoring in the sigmoid colon was found to be superior for the patients studied.

Larger expansions of the CTG repeat in muscle compared to lymphocytes from patients with myotonic dystrophy.

The discovery that there is an expansion of a CTG repeat underlying myotonic dystrophy has led to new approaches in diagnosis and genetic counselling for this disorder. The size of the expansion correlates to a reasonable degree with the clinical symptoms within a given family. We report comparisons of the length of the expansion seen in lymphocytes and muscle samples from eight patients. In all cases the length of the expansion seen in DNA isolated from muscle was larger than that seen in lymphocytes from the same patient. There was no progression of the expansion over a period of 10-15 years in muscle samples from two of these patients even though there had been significant progression of the severity of symptoms during that time.

Muscle fibre degeneration in distal myopathy (Welander)--ultrastructure related to immunohistochemical observations on cytoskeletal proteins and Leu-19 antigen.

In seven patients with long-standing and six patients with early symptoms of Welander distal myopathy (WDM), monoclonal antibodies directed against such cytoskeletal proteins as dystrophin, spectrin and desmin and against Leu-19, a myoblast and satellite cell related antigen, were applied to muscle biopsies from the anterior tibial and soleus muscles. In addition, ultrastructural studies were carried out on biopsies from the soleus muscle. In muscle fibres from patients with early symptoms there was normal immunostaining for dystrophin, spectrin, desmin and Leu-19. In the patients with long-standing symptoms, there was also a normal expression of dystrophin, and a normal staining for spectrin and desmin was found in normal sized muscle fibres. Occasionally normal sized muscle fibres showed staining for Leu-19. Increased staining for spectrin and desmin and a strong Leu-19 staining was seen in normal sized muscle fibres with rimmed vacuoles and in atrophic fibres. Increased staining for spectrin, desmin and Leu-19 has been described in denervated muscle fibres and, thus, the present findings may support earlier findings of a neurogenic component in Welander distal myopathy. In the soleus muscle, ultrastructural muscle fibre abnormalities conformed to those in the anterior tibial muscle. Many rimmed vacuoles were observed which corresponded, at the ultrastructural level, to autophagic vacuoles. Intranuclear and cytoplasmic filamentous inclusions of the same shape and diameter as in inclusion body myositis were observed.

Surgical management of intestinal complications of radiotherapy for gynecological malignancies.

Sixty patients treated for gynecological malignancies with radiation therapy and operated upon because of late intestinal complications of the treatment were studied. Among patients irradiated for cervical carcinoma an incidence of 3.2% of operated intestinal lesions was encountered. Fifty-nine per cent of the women had a history of previous pelvic inflammatory disease on pelvic surgery. The most common symptoms leading to surgery were mechanical subileus/ileus, pain and fistulas. The majority of patients (53%) were operated upon within 2 years after irradiation, but an interval up to 20 years was recorded. 50% were operated upon within 2 years after irradiation, but an interval up to 20 years was recorded. 50% were reoperated during follow-up. Intestinal resections (38%) and by-passes (15%) were the most frequent surgical procedures at first operation. 57% of the patients were operated upon due to acute conditions and 31% were due to chronic problems, 12% due to tumour suspicion. An operation mortality rate of 5% was found. No obvious correlation could be seen between accumulated irradiation dose and severity of complications. The results of surgical intervention and complications are analysed and different strategies in handling these patients discussed.

Hepatic portal vein gas following endoscopic retrograde cholangiography with sphincterotomy. Case report.

In a 60-year-old woman, endoscopic retrograde choledochography with sphincterotomy was followed by appearance of gas in the portal venous system. Venous bleeding was seen immediately after completion of sphincterotomy. The patient recovered well. Even in the absence of duodenal perforation, sphincterotomy may be complicated by hepatic portal venous gas.