Showing papers by "Mayo Clinic published in 1990"

Levamisole and Fluorouracil for Adjuvant Therapy of Resected Colon Carcinoma

Abstract: Twelve hundred ninety-six patients with resected colon cancer that either was locally invasive (Stage B2) or had regional nodal involvement (Stage C) were randomly assigned to observation or to treatment for one year with levamisole combined with fluorouracil. Patients with Stage C disease could also be randomly assigned to treatment with levamisole alone. The median follow-up time at this writing is 3 years (range, 2 to 5 1/2). Among the patients with Stage C disease, therapy with levamisole plus fluorouracil reduced the risk of cancer recurrence by 41 percent (P<0.0001). The overall death rate was reduced by 33 percent (P ≈ 0.006). Treatment with levamisole alone had no detectable effect. The results in the patients with Stage B2 disease were equivocal and too preliminary to allow firm conclusions. Toxic effects of levamisole alone were infrequent, usually consisting of mild nausea with occasional dermatitis or leukopenia, and those of levamisole plus fluorouracil were essentially the same as t...

The "megaprimer" method of site-directed mutagenesis.

Abstract: We describe a simple and efficient method of mutagenesis which we term the "megaprimer" method. The method utilizes three oligonucleotide primers to perform two rounds of polymerase chain reaction. In the method, the product of the first polymerase chain reaction is used as one of the polymerase chain reaction primers (a "megaprimer") for the second polymerase chain reaction. When a phage promoter and a translational initiation signal are attached to the appropriate oligonucleotide primer, the mutant protein can be generated without any in vivo manipulations. To illustrate the method, two mutations in the catalytic domain of the human factor IX gene have been generated. The substitution of megaprimers for oligonucleotide primers may have utility in other polymerase chain reaction-based methods.

Effect of femoral head size on wear of the polyethylene acetabular component.

Abstract: A technique was developed to determine the wear of the acetabular component of a total hip replacement by examination of standardized initial and follow-up radiographs. Three hundred and eighty-five hips were followed for at least 9.5 years after replacement. The least amount and rate of linear wear were associated with use of a femoral head that had a diameter of twenty-eight millimeters (p less than 0.001). The greatest amount and mean rate of linear wear occurred with twenty-two-millimeter components, but these differences were not statistically significant. The greatest volumetric wear and mean rate rate of volumetric wear were seen with thirty-two-millimeter components (p less than 0.001). A wider radiolucent line in acetabular Zone 1 was associated with use of the thirty-two-millimeter head. The amounts of resorption of the proximal part of the femoral neck and of lysis of the proximal part of the femur both correlated positively with the extent of linear and volumetric wear; this suggests an association between the amount of debris from wear and these changes in the femoral neck and proximal part of the femur.

Martingale-based residuals for survival models

Abstract: SUMMARY Graphical methods based on the analysis of residuals are considered for the setting of the highly-used Cox (1972) regression model and for the Andersen-Gill (1982) generalization of that model. We start with a class of martingale-based residuals as proposed by Barlow & Prentice (1988). These residuals and/or their transforms are useful for investigating the functional form of a covariate, the proportional hazards assumption, the leverage of each subject upon the estimates of 13, and the lack of model fit to a given subject. 1 1. Model Consider a set of n independent subjects such that the counting process Ni {Ni(t), t } O} for the ith subject in the set indicates the number of observed events experienced over time t. The sample paths of the Ni are step functions with jumps of size +1 and with Ni(0) =0. We assume that the intensity function for Ni(t) is given by Yi(t)dA{t, Zi(t)} = Yi(t) eP'Z(t) dAO(t), (1) where Yi(t) is a 0-1 process indicating whether the ith subject is a risk at time t, 13 is a vector of regression coefficients, Zi(t) is a p dimensional vector of covariate processes, and Ao is the baseline cumulative hazard function. Several familar survival models fit into this framework. The Andersen & Gill (1982) generalization of the Cox (1972) model arises when AO(t) is completely unspecified. The further restriction that Yi(t) = 1 until the first event or censoring, and is 0 thereafter yields the Cox model. The parametric form AO(t) = t yields a Poisson model, or an exponential if restricted to a single event per subject, and AO(t) = tP a Weibull model. Our attention will focus primarily on the Andersen-Gill and Cox models; however, the

Validity of self-reported waist and hip circumferences in men and women.

Abstract: Recent epidemiologic evidence indicates an association between fat distribution and many diseases. To assess the validity of circumference measurements obtained by self-report, the authors analyzed data from 123 men aged 4C75 years and 140 women aged 41–65 years, drawn from two large ongoing prospec

Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis.

Abstract: Although fluoride increases bone mass, the newly formed bone may have reduced strength. To assess the effect of fluoride treatment on the fracture rate in osteoporosis, we conducted a four-year prospective clinical trial in 202 postmenopausal women with osteoporosis and vertebral fractures who were randomly assigned to receive sodium fluoride (75 mg per day) or placebo. All received a calcium supplement (1500 mg per day). Sixty-six women in the fluoride group and 69 women in the placebo group completed the trial. As compared with the placebo group, the treatment group had increases in median bone mineral density of 35 percent (P less than 0.0001) in the lumbar spine (predominantly cancellous bone), 12 percent (P less than 0.0001) in the femoral neck, and 10 percent (P less than 0.0001) in the femoral trochanter (sites of mixed cortical and cancellous bone), but the bone mineral density decreased by 4 percent (P less than 0.02) in the shaft of the radius (predominantly cortical bone). The number of new vertebral fractures was similar in the treatment and placebo groups (163 and 136, respectively; P not significant), but the number of nonvertebral fractures was higher in the treatment group (72 vs. 24; P less than 0.01). Fifty-four women in the fluoride group and 24 in the placebo group had side effects sufficiently severe to warrant dose reduction; the major side effects were gastrointestinal symptoms and lower-extremity pain. We conclude that fluoride therapy increases cancellous but decreases cortical bone mineral density and increases skeletal fragility. Thus, under the conditions of this study, the fluoride-calcium regimen was not effective treatment for postmenopausal osteoporosis.

Eosinophilic gastroenteritis: a clinicopathological study of patients with disease of the mucosa, muscle layer, and subserosal tissues.

Abstract: The aim of this study was to evaluate the clinicopathological spectrum of eosinophilic gastroenteritis and identify possible difficulties in establishing the diagnosis. All patients with a diagnosis of eosinophilic gastroenteritis, defined by the presence of gastrointestinal symptoms and eosinophilic infiltration of the gut (38), or a radiological diagnosis with peripheral eosinophilia (two), were identified from the Mayo Clinic records; in none was there evidence of extraintestinal disease. Patients were divided into three groups according to the Klein classification: predominant mucosal (23), muscular (12), or subserosal disease (five). A fourth group of patients (10) for comparison had abdominal symptoms and unexplained peripheral eosinophilia but no proven eosinophilic infiltration of the gut. It was found that a history of allergy was reported by 20 of 40 patients with eosinophilic gastroenteritis. Peripheral eosinophilia was absent in nine of 40. The patients with subserosal disease were distinct from the other groups in presentation (abdominal bloating, ascites), higher eosinophil counts and in their dramatic responses to steroid therapy. Otherwise the patients were similar regarding demographic factors, presenting symptoms (abdominal pain, nausea, weight loss, diarrhoea), and laboratory parameters. The ESR was moderately raised in 10 of 40 patients. The disease may affect any area of the gastrointestinal tract; eosinophilic infiltration was documented in the oesophagus in one patient and in the colon in two cases. Endoscopic biopsies missed the diagnosis in five of 40 presumably because of patchy disease. Eosinophilic gastroenteritis should be considered in the differential diagnosis of unexplained gastrointestinal symptoms even in the absence of peripheral eosinophilia.

Long-term outcome after surgical repair of isolated atrial septal defect. Follow-up at 27 to 32 years

Abstract: Background. Atrial septal defects have been surgically correctable for more than 30 years. The long-term survival rates among patients treated in the early era of cardiac surgery are poorly documented, but such data are of critical importance to the future medical care, employability, and insurability of these patients. Methods. To determine the natural history of surgically corrected atrial septal defects, we studied all 123 patients who underwent repair of an isolated defect (ostium secundum or sinus venosus) at the Mayo Clinic between 1956 and 1960, 27 to 32 years after the procedure. The follow-up status of all patients was determined by written questionnaires and telephone interviews. Hospital records and death certificates were obtained if interim hospitalization or death had occurred. Results. The overall 30-year actuarial survival rate among survivors of the perioperative period was 74 percent, as compared with 85 percent among controls matched for age and sex. The perioperative mortality...

Normal axial alignment of the lower extremity and load-bearing distribution at the knee

Abstract: Based on a series of 120 normal subjects of different gender and age, the geometry of the knee joint was analyzed using a full-length weight-bearing roentgenogram of the lower extremity. A special computer program based on the theory of a rigid body spring model was applied to calculate the important anatomic and biomechanical factors of the knee joint. The tibiofemoral mechanical angle was 1.2 degrees varus. Hence, it is difficult to rationalize the 3 degree varus placement of the tibial component in total knee arthroplasty suggested by some authors. The distal femoral anatomic valgus (measured from the lower one-half of the femur) was 4.2 degrees in reference to its mechanical axis. This angle became 4.9 degrees when the full-length femoral anatomic axis was used. When simulating a one-legged weight-bearing stance by shifting the upper-body gravity closer to the knee joint, 75% of the knee joint load passed through the medial tibial plateau. The knee joint-line obliquity was more varus in male subjects. The female subjects had a higher peak joint pressure and a greater patello-tibial Q angle. Age had little effect on the factors relating to axial alignment of the lower extremity and load transmission through the knee joint.

The eosinophil and bronchial asthma: Current understanding

Abstract: Article synthese au sujet des effets physiologiques et pathologiques des eosinophiles dans les asthmes bronchiques. des proteines majeures basiques (MBP) dont la concentration est elevee dans les lavages bronchoalveolaires des patients, ont ete etudiees

Incidence and clinical features of trigeminal neuralgia, Rochester, Minnesota, 1945-1984.

Abstract: The overall crude incidence rate of trigeminal neuralgia per 100,000 population in Rochester, Minnesota, for 1945 through 1984 was 4.3 for both sexes combined. The age-adjusted (to total 1980 US population) rate for women (5.9) was significantly higher than that for men (3.4). Annual incidence rates increased significantly with age in both women and men. Data based on evidence in the medical records suggest that trigeminal neuralgia is a rather rare and unpredictable disease: The number of episodes varies from 1 to 11, and length of episode from 1 day to 4 years. This study indicates an elevated relative risk associated with hypertension (both overall and among women in the cohort). Also, prevalence of multiple sclerosis was significantly greater among the group of 75 patients who had trigeminal neuralgia. Since the data on treatment in this study do not correspond to a randomized clinical trial, they are presented as empirical results only and show no single treatment of choice for trigeminal neuralgia.

Relation of pulmonary vein to mitral flow velocities by transesophageal Doppler echocardiography. Effect of different loading conditions.

Abstract: It has previously been demonstrated that predictable changes occur in mitral flow velocities under different loading conditions. The purpose of this study was to relate changes in pulmonary venous and mitral flow velocities during different loading conditions as assessed by transesophageal echocardiography in the operating room. Nineteen patients had measurements of hemodynamics, that is, mitral and pulmonary vein flow velocities during the control situation, a decrease in preload by administration of nitroglycerin, an increase in preload by administration of fluids, and an increase in afterload by infusion of phenylephrine. There was a direct correlation between the changes in the mitral E velocity and the early peak diastolic velocity in the pulmonary vein curves (r = 0.61) as well as a direct correlation between the deceleration time of the mitral and pulmonary venous flow velocities in early diastole (r = 0.84). This indicates that diastolic flow velocity in the pulmonary vein is determined by the same factors that influence the mitral flow velocity curves. A decrease in preload caused a significant reduction in the initial E velocity and prolongation of deceleration time, and an increase in preload caused an increase in E velocity and shortening of deceleration time. An increase in afterload produced a variable effect on the initial E velocity and deceleration time and was dependent on the left ventricular filling pressure. The change in systolic forward flow velocity in the pulmonary vein was directly proportional to the change in cardiac output (r = 0.60). The pulmonary capillary wedge pressure correlated best with the flow velocity reversal in the pulmonary vein at atrial contraction (r = 0.81). Use of pulmonary vein velocities in conjunction with mitral flow velocities can help in understanding left ventricular filling.

Temporal lobe seizures: lateralization with MR volume measurements of the hippocampal formation.

Abstract: A retrospective magnetic resonance (MR) imaging study was performed in 41 right-handed patients with presumed mesial sclerosis who underwent surgery for medically intractable, complex partial seizures of temporal lobe origin. The ability of each of five different MR imaging-based tests to lateralize the seizure disorder was determined. In order of decreasing usefulness the tests were (a) hippocampal formation (HF) volume measurements, (b) visual grading of MR images for unilateral HF atrophy, (c) anterior temporal lobe (ATL) volume measurements, (d) visual grading of MR images for unilateral ATL atrophy, and (e) evidence of unilateral medial temporal lobe signal intensity abnormalities on long repetition time MR images. A right-side minus left-side volume (designated DHF) was obtained to quantify unilateral HF atrophy with a single number. Patients with right-sided seizures had a median DHF of -0.4 cm3, while those with left-sided seizures had a median DHF of 0.8 cm3, consistent with atrophy of the HF ips...

Restenosis after balloon angioplasty. A practical proliferative model in porcine coronary arteries.

Abstract: A model of proliferative human restenosis was developed in domestic pigs by using deep injury to the coronary arterial media. Metal wire coils were delivered percutaneously to the coronary arteries of 11 pigs with an oversized, high-pressure (14 atm) balloon and were left in place for times ranging from 28 to 70 days. During placement, the balloon expanded the coils and delivered them securely within the arterial lumen. Light microscopic examination of the vessels confirmed fracture of the internal elastic lamina by the coil. An extensive proliferative response occurred in 10 of the 11 pigs and was associated with a luminal area narrowing of at least 50% in all but one pig. The histopathologic features of the proliferative response were identical to those observed in human cases of restenosis after angioplasty. Immunohistochemical studies confirmed the prominence of smooth muscle cells in the proliferative tissue. A similar response was obtained in two of five porcine coronary arteries in which balloon inflation only was performed, without coil implant. This model is practical and inexpensive and closely mimics the proliferative portion of human restenosis both grossly and microscopically. Thus, it may be useful for understanding human restenosis and for testing therapies aimed at preventing restenosis after balloon angioplasty or other coronary interventional procedures.

Post-traumatic contracture of the elbow: operative treatment, including distraction arthroplasty

Abstract: Twenty-six consecutive patients who had post-traumatic contracture of the elbow were treated by operative release alone or by release and distraction arthroplasty, with or without fascial interposition. The type of operative procedure was determined by whether the factors limiting motion were purely extra-articular (extrinsic) or whether they included intra-articular (intrinsic) elements as well. The mean preoperative arc of total motion was 30 degrees (from 63 to 93 degrees of flexion). At follow-up examination, twenty-two to ninety-four months post-operatively, of twenty-five patients, the mean arc of total motion was 96 degrees (from 30 to 126 degrees). There were eight complications in seven (27 per cent) of the patients. Of these, four (avulsion of the triceps tendon, deep infection, and two ulnar-nerve paresthesias) were managed by subsequent operative treatment. The other four complications included drainage from a pin site, which resolved after removal of the pin: a three by two-centimeter skin slough, which spontaneously epithelialized; aseptic resorption of the distal end of the humerus and proximal end of the ulna, which stopped after immobilization and subsequent bracing of the elbow but resulted in moderate instability; and ulnar-nerve paresthesia, which was not operatively treated and persisted. Twenty-four (96 per cent) of the twenty-five patients who were followed for twenty-two months or more were satisfied with the results of the procedure because of the improved facility in carrying out activities of daily living. No patient had increased pain, but two had moderate instability. It was concluded that the results of distraction arthroplasty can be gratifying, but the technique is demanding and the rate of complications is high.

Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis

Abstract: Although fluoride increases bone mass, the newly formed bone may have reduced strength. To assess the effect of fluoride treatment on the fracture rate in osteoporosis, we conducted a four-year prospective clinical trial in 202 postmenopausal women with osteoporosis and vertebral fractures who were randomly assigned to receive sodium fluoride (75 mg per day) or placebo. All received a calcium supplement (1500 mg per day). Sixty-six women in the fluoride group and 69 women in the placebo group completed the trial. As compared with the placebo group, the treatment group had increases in median bone mineral density of 35 percent (P less than 0.0001) in the lumbar spine (predominantly cancellous bone), 12 percent (P less than 0.0001) in the femoral neck, and 10 percent (P less than 0.0001) in the femoral trochanter (sites of mixed cortical and cancellous bone), but the bone mineral density decreased by 4 percent (P less than 0.02) in the shaft of the radius (predominantly cortical bone). The number of new vertebral fractures was similar in the treatment and placebo groups (163 and 136, respectively; P not significant), but the number of nonvertebral fractures was higher in the treatment group (72 vs. 24; P less than 0.01). Fifty-four women in the fluoride group and 24 in the placebo group had side effects sufficiently severe to warrant dose reduction; the major side effects were gastrointestinal symptoms and lower-extremity pain. We conclude that fluoride therapy increases cancellous but decreases cortical bone mineral density and increases skeletal fragility. Thus, under the conditions of this study, the fluoride-calcium regimen was not effective treatment for postmenopausal osteoporosis.

Tracheobronchial Foreign Bodies in Adults

Abstract: Study Objective:To define the clinical spectrum of tracheobronchial foreign body aspiration in adults, assess predisposing conditions, evaluate the efficacy of bronchoscopy, and determine ...

Human growth hormone prevents the protein catabolic side effects of prednisone in humans.

Abstract: Prednisone treatment causes protein wasting and adds additional risks to a patient, whereas human growth hormone (hGH) treatment causes positive nitrogen balance. To determine whether concomitant administration of hGH prevents the protein catabolic effects of prednisone, four groups of eight healthy volunteers each were studied using isotope dilution and nitrogen balance techniques after 7 d of placebo, hGH alone (0.1 mg.kg-1.d-1), prednisone alone (0.8 mg.kg-1.d-1), or prednisone plus hGH (n = 8 in each group). Whether protein balance was calculated from the leucine kinetic data or nitrogen balance values, prednisone alone induced protein wasting (P less than 0.001), whereas hGH alone resulted in positive (P less than 0.001) protein balance, when compared to the placebo-treated subjects. When hGH was added to prednisone therapy, the glucocorticoid-induced protein catabolism was prevented. Using leucine kinetic data, negative protein balance during prednisone was due to increased (P less than 0.05) proteolysis, whereas hGH had no effect on proteolysis and increased (P less than 0.01) whole body protein synthesis. During combined treatment, estimates of proteolysis and protein synthesis were similar to those observed in the placebo treated control group. In conclusion, human growth hormone may have a distinct role in preventing the protein losses associated with the administration of pharmacologic doses of glucocorticosteroids in humans.

Ataxic sensory neuropathy and dorsal root ganglionitis associated with Sjögren's syndrome.

Abstract: Thirteen patients, 11 women and 2 men, developed sensory and autonomic neuronopathies in association with features of primary Sjogren's syndrome. In 11, Sjogren's syndrome had not been previously diagnosed at the time of neurological presentation. All had prominent loss of kinesthesia and proprioception. Pain and thermal sensibility were less severely affected. Most had evidence of autonomic insufficiency. In some this was severe, with Adie's pupils, fixed tachycardia, and orthostatic hypotension. The course ranged from an abrupt, devastating onset to indolent progression over years. Stabilization or functional improvement occurred in 6 patients, 2 of whom received no drug therapy. Sensory nerve conduction studies and examination of nerve biopsy specimens demonstrated a wide spectrum in the severity of loss of large myelinated fibers. The cutaneous nerves of 6 patients had perivascular mononuclear infiltrates without necrotizing arteritis. Examination of biopsy specimens of dorsal root ganglia in 3 patients revealed lymphocytic (T-cell) infiltration in the dorsal roots and ganglia, with focal clusters around neurons. In the more mildly affected ganglia, individual sensory neurons were undergoing degeneration. In the most advanced case, very few neurons remained. The possibility of Sjogren's syndrome should be considered in patients, especially women, who develop acute, subacute, or chronic sensory and autonomic neuropathies, with ataxia and kinesthetic loss.

Pouchitis and extraintestinal manifestations of inflammatory bowel disease after ileal pouch-anal anastomosis.

Abstract: Although the etiology of pouchitis after ileal pouch-anal anastomosis (IPAA) is unknown, its manifestations resemble those of nonspecific inflammatory bowel disease, including, anecdotally, the apparent ability to evoke extraintestinal manifestations (EIM) of inflammatory bowel disease (IBD). Our aim was to determine in what manner pouchitis and EIMs were associated. The computerized records of 819 consecutive patients who underwent IPAA between January 1981 and December 1988 were reviewed. Eighty-five patients were excluded (because of incomplete follow-up, death, or permanent ileostomy). Follow-up of the remaining 734 patients was complete (mean, 41 months). The mean age was 32 years and the ratio of men to women was 1:1. Ileal pouch-anal anastomosis was performed for chronic ulcerative colitis in 91% of patients and for familial adenomatous polyposis in 9%. Pouchitis occurred in 31% of chronic ulcerative colitis patients and 6% of familial adenomatous polyposis patients (p less than 0.01). The mean time to first occurrence was 17 months. Pouchitis recurred in 61% of patients at risk. Patients with preoperative and postoperative EIMs had significantly higher rates of pouchitis than did patients without EIMs (39% preoperative EIMs versus 26% with no EIMs, p less than 0.001; 53% postoperative EIMs versus 25% with no EIMs, p less than 0.001). Of patients with pouchitis in whom EIMs resolved after IPAA but then recurred (n = 12), EIMs recurred when pouchitis occurred and abated when pouchitis was treated in seven patients. We concluded that pouchitis occurred frequently after IPAA and that patients with EIMs were at higher risk of developing pouchitis than were patients who never had EIMs. Furthermore some patients experienced a temporal relationship between flares of EIMs and pouchitis. These results imply that pouchitis may be a novel manifestation of inflammatory bowel disease persisting after operation.

Detection of Somatostatin Receptors in Surgical and Percutaneous Needle Biopsy Samples of Carcinoids and Islet Cell Carcinomas

Abstract: Somatostatin (SS) receptor status was investigated in the tumor tissues from 62 patients with carcinoid tumors and 15 patients with islet cell carcinomas using receptor autoradiography techniques with two different iodinated somatostatin analogues as radioligands, a [Leu8, DTrp22, Tyr25]somatostatin-28 and a somatostatin octapeptide, Tyr3-octreotide. The carcinoid tumors were either primaries (n = 32) or metastases (n = 43), sampled as surgical specimens or as small needle liver biopsies. Fifty-four of 62 carcinoid patients had SS receptor-positive tumors (87%). All 15 islet cell carcinoma patients had positive tumors (4 primaries, 11 metastases), i.e., 3 vipomas, 3 insulinomas, 2 glucagonomas, 1 gastrinoma, 2 polyfunctional tumors, and 4 nonfunctioning tumors. Saturation and competition experiments on tissue sections revealed saturable, high affinity binding sites pharmacologically specific for bioactive SS analogues. In a majority of the tumors, the receptors were densely distributed and were always homogeneously found in the whole tumor. All except two tumors were labeled with both radioligands. Multiple liver metastases (n = 16) from three different patients were all shown to contain a comparable amount of receptors. SS receptors could be demonstrated even in very small tissue samples of liver metastases obtained by percutaneous liver biopsies (mean weight, 6.8 mg). The majority of the eight SS receptor-negative carcinoids were mainly bronchial carcinoids (n = 5), usually poorly differentiated. On the contrary, SS receptor-positive cases were never found to be anaplastic. All tumors except one from patients pretreated with octreotide (3 days to 3.8 years) were SS receptor positive. In the majority of carcinoids or islet cell carcinomas, the SS receptor status correlated with the in vivo biochemical response (hormone inhibition) to octreotide. These data demonstrate (a) the high prevalence of SS receptors in the primary tumors of both carcinoids and islet cell carcinomas, (b) their presence in metastases as well, (c) their continuous expression even during long term octreotide therapy, (d) the possibility of measuring SS receptors in percutaneous needle liver biopsies, and (e) the evidence of their functionality. This study therefore suggests that tumoral SS receptors may be the likely molecular basis for octreotide action and may be an important parameter for predicting the therapeutic efficacy of SS analogues in carcinoids and islet cell carcinomas.

Microvascular changes in early and advanced dermatomyositis: A quantitative study

Abstract: In adult dermatomyositis 10 muscle specimens with no or minimal histological alterations were compared with 7 that showed typical alterations. Five specimens from patients with inclusion body myositis, 5 from patients with polymyositis, and 8 from normal subjects served as controls. Vascular endothelium, visualized with the lectin Ulex europaeus agglutinin I, and complement membrane attack complex were demonstrated in the same cryostat sections by paired immunofluorescence. Large randomly selected fields were analyzed to determine the number of capillaries per square millimeter of fiber area (capillary density), per 1,000-microns 2 area of each muscle fiber (capillary index), and in 100 x 100-microns grid squares. In dermatomyositis specimens with minimal structural alterations there was focal capillary depletion, the capillary density was significantly reduced, and the frequency distributions of the capillary index and grid count were shifted to the left. In advanced dermatomyositis specimens, the findings were similar but more severe. In both kinds of specimens, clusters of capillaries reacted for complement membrane attack complex. The 2 patients with the highest proportion of vessels positive for membrane attack complex had a fulminant and fatal course. In polymyositis and inclusion body myositis specimens, the capillaries had a normal overall density and none reacted for membrane attack complex. The findings imply that the capillaries are an early and specific target of the disease process in dermatomyositis.

Cancellous bone remodeling in type i (postmenopausal) osteoporosis: Quantitative assessment of rates of formation, resorption, and bone loss at tissue and cellular levels

Abstract: The cellular mechanisms for bone loss in type I (postmenopausal) osteoporosis are highly controversial. We attempted to resolve this by assessing rates of formation and resorption of iliac cancellous bone by a new histomorphometric method in 89 women with osteoporosis (mean age +/- SD, 66 +/- 6 years) and in 32 carefully selected normal postmenopausal women (64 +/- 6 years). In the osteoporotic women, bone resorption rate was increased by 39% (P less than 0.05) at the cellular level and by 67% (P less than 0.05) at the tissue level, whereas bone formation was unchanged at the tissue level but decreased by 14% (P less than 0.01) at the cellular (osteoblast) level. This pronounced remodeling imbalance (P less than 0.001) was probably exacerbated by a 45% increase (P less than 0.1) in activation frequency of new remodeling foci. These abnormalities were associated with a high rate of cancellous bone loss (median, 5.8%/year versus 0.1% year in controls). Thus, accelerated loss of cancellous bone in type I osteoporosis results from the combination of increased bone resorption and inadequate compensation by bone formation.