Efficacy of chymopapain in chemonucleolysis. A review.

STUDY DESIGN: This study was designed to determine the current experience in the use of chymopapain injection in the treatment of herniated intervertebral discs by analyzing reports appearing between 1985 and 1993. Forty-five clinical studies included 7,335 patients treated worldwide, some including comparisons to open laminectomy/discectomy and others to percutaneous discectomy. OBJECTIVES: Because controversy persists after 30 years of clinical use of chymopapain, the results of current experience should establish the efficacy for those who want to consider chemonucleolysis as a treatment for a herniated nucleus pulposus. SUMMARY OF BACKGROUND DATA: There is the suggestion that use of other than conservative treatment is made only to achieve a better result in the short term. The selection of type of treatment will depend on contraindications, with failures of chemonucleolysis found largely in those having spinal stenosis or sequestrated discs. Worker compensation patients respond less successfully than those with better motivation. METHODS: The 45 studies were analyzed for determination of successful outcome and divided into 16 with more than 100 patients, 13 with less than 100 patients and 16 with comparison to other treatments. RESULTS: Individual success rates exceeded 60% whereas cohort total averaged 76%. In studies comparing chemonucleolysis with open discectomy, success rate averaged 76.2% as compared with 88% for open surgery. In two other studies, percutaneous discectomy was less successful than chemonucleolysis. Where included, duration of hospitalization showed less time and thus less costs for chemonucleolysis. Return to work complications showed time off slightly less for chemonucleolysis than for laminectomy. CONCLUSIONS: Chemonucleolysis, though somewhat less effective than open discectomy, can be successfully and safely used in about four of five carefully selected patients without the trauma, risks, and subsequent fibrosis associated with lumbar disc surgery.

Safety of chemonucleolysis. Adverse effects reported in the United States, 1982-1991.

This survey covers 121 "serious" and "unexpected" adverse events after treatment with chymodiactin (chymopapain for injection) among approximately 135,000 patients in the United States. They were reported to the Food and Drug Administration (FDA) within 15 days of notification of the manufacturer between 1982 and the end of 1991. They included fatal anaphylaxis (seven cases), infections (24 cases), hemorrhage (32 cases), and neurologic (32 cases) and miscellaneous (15 cases) events, with a mortality rate of 0.019%. Anaphylactic reactions reported in a postmarketing survey can be attributed to chymopapain itself and infections to lack of asepsis during its administration. The causes of other adverse reactions cannot be as clearly defined, but many are unlikely to have been due to chymopapain or its administration. More careful selection of patients and closer attention to technique during chemonucleolysis have dramatically reduced the incidence of these adverse events, which occur far less frequently than after diskectomy.

Biomechanics of Ender rods, compression screw, and Zickel nail in the fixation of stable subtrochanteric femur osteotomies.

Compression screws, Ender rods, and Zickel nails were evaluated mechanically to determine their resulting stability in the fixation of experimental subtrochanteric femur osteotomies. Twenty-five pairs of human cadaver femurs were used. Experimental osteotomies were created and a random member of each pair was fixed with a compression screw (AMBI system, Richards Mfg. Co). The other member was fixed with either Ender rods or a Zickel nail. The specimens were oriented in a direction to approximate the in vivo position of maximum resultant force on the femur and then subjected to a single progressive load to failure on a materials testing machine. The ultimate strength of fixation with the compression screw was approximately 4.6 times greater than with the Ender rods and 1.8 times greater than that with the Zickel nail. Ender rods and Zickel nails failed primarily in external rotation, whereas the compression screw failed by bone fracturing and varus bending.

Measuring codependents' close relationships: a preliminary study.

A survey of clinical literature and input from addiction counselors yielded eight commonly assumed characteristics of codependents' relationships. These were defined in a manner amenable to measurement by the Acquaintance Description Form (Wright, 1985), and added to the standard form to provide a codependent version (ADF-C2). Forty-one women and 19 men awaiting or beginning codependent counseling responded to the ADF-C2, and to Friel's Codependency Assessment Inventory and forms soliciting background information. Thirty-nine women and 30 men from the general population provided a comparison group. Although tentative, results were encouraging concerning progress toward measuring codependents' relationships. Broad profiles for both women and men supported the foundational observation that codependents maintain strong commitments to their partners notwithstanding stress and unrewardingness. Specifically, codependent women showed five expected characteristics: Control, Exaggerated Responsibility, Worth Dependency, Rescue Orientation, and Change Orientation. Codependent men showed two: Control and Exaggerated Responsibility.

A comparison of the effects of streptozotocin, N-methylnitrosourea and alloxan on isolated islets of Langerhans.

Isolated normal rat islets were pre-incubated with Streptozotocin (STZ), N-methylnitrosourea (MNU) or alloxan for 5, 10, 30 or 60 minutes at 0 degree C or 37 degrees C, and then were washed and incubated at 37 degrees C for 60 minutes with glucose (16.7 mM). Suppression of the insulinotropic response to glucose during incubation required 10 minutes of pre-incubation with the nitrosoureas whose effects were directly related to concentration and were temperature dependent. The suppressive effects of both nitrosoureas could be reduced or abolished by simultaneous addition to the pre-incubation media of nicotinamide, 2-deoxyglucose or 3-0-methyl-glucose, but were unaffected by reduced glutathione, glucosamine, N-acetylglucosamine or mannoheptulose. Unlike the nitrosoureas, alloxan was B-cytotoxic at 0 degree C. The effect of alloxan at 0 degree C was blocked by glutathione but not by glucose. The evidence in this study is inconsistent with the concept that the glucose moiety of STZ promotes entry and action of this nitrosourea in pancreatic islet cells. Secondly, it shows that the immediate B-cytotoxic action of alloxan differ from that of STZ or MNU and is not abolished by decrease in temperature.

The characterization of phenazine methosulfate stimulated insulin secretion.

This investigation was initiated to characterize the stimulation of insulin secretion by phenazine methosulfate (PMS). Islets of Langerhans, isolated by the collagenase method from normal rats and rats pre-injected with either streptozotocin or 6-aminonicotinamide, were exposed to PMS under various experimental conditions and insulin secretion in response to PMS, glucose and pyridine nucleotides was determined. Insulin releasing action of PMS was dose-, time- and temperature-related, occurred in the absence of glucose, and was inhibited by epinephrine, but not by mannoheptulose. In the perifusion system, the pattern of response induced by PMS was spike-like release reaching a maximum in 5 min and declining rapidly to half-maximal value in 10 min. After exposure of islets to beta-cytotoxin either in vivo or in vitro, complete reversal of the cytotoxic effect was obtained with PMS which induced release of insulin in both normal and beta-cytotoxin islets pre-treated. It is concluded that islets depleted of coenzymes could still secrete insulin in response to a reactive proton donor, which might act by substituting for coenzymes and that the immediate action of beta-cytotoxins does not completely arrest the secretory mechanisms in islets of Langerhans.

Cryptogenic fibrosing alveolitis: pattern of disease in the lung.

The distribution of disease has been studied in 10 patients with histologically confirmed cryptogenic fibrosing alveolitis by means of computed tomography of the lungs, gallium 67 uptake scintigraphy, and ventilation and perfusion scintigraphy. The findings of computed tomography and scintigraphy showed no correlation with the UICC/Cincinnati grades of the plain chest radiographs, even when these were supplemented with information from lateral and oblique chest films. Computed tomography showed subpleural shadowing in every patient except one who had responded well to corticosteroid treatment. Subpleural shadowing was commoner in the inferior and posterior parts of the lung lobes and was commonest in the posterior lower subpleural areas. The central lung showed three types of change--firstly, a dense shadowing, which was sometimes associated with much increased gallium uptake; secondly, dilated smaller airways with small bullae, suggesting airway disease; and, thirdly, gross bullous change.

Late complications of total hip replacement from bone cement within the pelvis. A review of the literature and a case report involving dyspareunia.

It is not uncommon to observe bone cement in the pelvis on radiographs after total hip replacement, a finding which is generally considered to be benign. This paper reviews some catastrophic late complications from intrapelvic methylmethacrylate. We also describe a case of progressive, unbearable dyspareunia beginning three years after total hip replacement. A possible explanation of the pathophysiology is suggested. Recommendations for prevention, diagnosis, and treatment of these late complications are offered.

Adult idiopathic pulmonary haemosiderosis: a comparison of lung function changes and the distribution of pulmonary disease in patients with and without coeliac disease.

Seven patients with idiopathic pulmonary haemosiderosis were investigated with chest radiographs, pulmonary function tests, computed axial tomograms, and isotope ventilation and perfusion scans. Three of the patients had coeliac disease (CD) and a fourth an abnormal small bowel mucosa under the dissecting microscope which was normal histologically. Five patients showed airflow limitation with a low transfer coefficient. Three of these had air trapping, two of whom had hyperinflation of the lungs, and the third a total lung capacity at the upper limit of normal. Two patients showed a central distribution of radiographic opacities, and the other five had changes throughout the lung fields. The presence or absence of CD showed no relationship to these findings.

Effect of diabetogenic nitrosourea on the activity of the pentose phosphate hunt in isolated islets.

The effect of streptozotocin (STZ) on the activity of the pentose phosphate shunt in islets was studied. Isolated rat islets were pre-incubated with glucose (1.7 mM) alone or with streptozotocin (STZ) or N-methyl-N-nitrosourea (MNU). The effects of these pretreatments on glucose metabolism and insulin secretion were assessed during subsequent incubation with either (1.14C), (6.14C). or (U.14C). glucose (16.7 mM) alone or plus phenazine methosulfate (PMS). Islets pretreated with STZ (1.5 mM) metabolized less (1.14C) and (U.14C). glucose. The order of inhibition by STZ of (14C)-glucose metabolism by islets was: (1.14C). greater than (U.14C). greater than (6.14C)-glucose. Whereas PMS (0.5 mM) increased the metabolism of both (U.14C). and (1.14C)-glucose, the metabolism of (6.14C)-glucose by STZ-pretreated islets was not increased by PMS. In a separate series of experiments, the total NADP+ + NADPH, but not the NAD content of the islets decreased after 2 min exposure of islets of STZ. At 30-min exposure, the levels of both pyridine coenzymes and that of 6-phosphogluconate were significantly decreased. The level of NADP+ + NADPH in islets was decreased more than the level of NAD. Insulin secretion was suppressed by the nitrosoureas. PMS (0.5 mM) increased the level of NADP+ + NADPH content of islets and augmented insulin secretion. It is concluded that the pentose phosphate pathway is inhibited on brief exposure of islets to STZ or MNU. Such inhibition may contribute to the suppression of insulin secretion caused by these nitrosoureas.

Synovial sarcoma.

One hundred and eighty-five patients, whose ages ranged from two to seventy years (mean, thirty years), have been treated at the Mayo Clinic for synovial sarcoma. Sixty-nine per cent of the tumors occurred in the lower extremity: 25 per cent, in the upper extremity; and 6 per cent, in the trunk. Histological characteristics included a predominant bimorphic pattern in 33 per cent of the tumors, a monomorphic pattern in 31 per cent, and a mixed pattern in 36 per cent. For all patients, the five-year survival rate was 38 per cent and the ten-year rate was 23 per cent, with a median survival time of thiry-nine months. However, for those patients treated since 1960, the five-year survival rate was 55 per cent and the ten-year rate was 38 per cent. Female patients had a significantly better survival time than did male patients. Younger patients had a better survival rate, and the prognosis was better for those patients whose tumor were either less than five centimeters in diameter or located in the lower extremity. Survival rates were best for those patients who had wide local excision, but this type of surgery was performed for the lesions that had a more favorable prognosis. A regression study indicated that the size of the tumor was the single most important prognostic variable for survival. Second in importance was the extent of disease on initial presentation, followed by the chronological time of treatment, the age of the patient, and the anatomical site of the tumor.

Adult idiopathic pulmonary haemosiderosis and coeliac disease.

Small bowel biopsies were performed in seven patients in whom a diagnosis of idiopathic pulmonary haemosiderosis had been made. Villous atrophy was present in three patients and convoluted villi in one. There was no correlation between gastrointestinal symptoms or routine blood tests and abnormality of the small bowel mucosa. Three of the four patients with abnormal mucosa had HLA B8 antigen and the three patients with villous atrophy responded to gluten withdrawal.

Effects of halothane on glucose-stimulated insulin secretion and glucose oxidation in isolated rat pancreatic islets.

Previous studies have shown that halothane inhibits glucose-stimulated insulin secretion. This study was designed to determine whether the mechanism of inhibition involves a reduction in glucose metabolism. The effects of halothane on glucose (16.7 mM)-stimulated insulin secretion and glucose oxidation were studied in isolated rat pancreatic islets. Halothane, 0.11 mM (0.5 MAC), 0.22 mM (1.0 MAC), and 0.33 mM (1.5 MAC), inhibited glucose-stimulated insulin release in a dose-related manner by 5.2 per cent (NS), 21.0 per cent (P < 0.05), and 32.6 per cent (P < 0.01), respectively. At the 0.33 mM (1.5 MAC) concentration, halothane did not significantly inhibit the oxidation of 6-14C-glucose to 14CO2, although higher concentrations of halothane did result in significant inhibition. The data suggest that halothane's inhibitory effect on glucose-stimulated insulin secretion is not due to interference with glucose oxidation.

Respiratory function changes after asbestos pleurisy.

Six patients with radiographic evidence of diffuse pleural thickening after industrial asbestos exposure are described. Five had computed tomography of the thorax. All the scans showed marked circumferential pleural thickening often with calcification, and four showed no significant evidence of intrapulmonary fibrosis (asbestosis). Lung function testing showed reduction of the inspiratory capacity and the single-breath carbon monoxide transfer factor (TLCO). The transfer coefficient, calculated as the TLCO divided by the alveolar volume determined by helium dilution during the measurement of TLCO, was increased. Pseudo-static compliance curves showed markedly more negative intrapleural pressures at all lung volumes than found in normal people. These results suggest that the circumferential pleural thickening was preventing normal lung expansion despite abnormally great distending pressures. The pattern of lung function tests is sufficiently distinctive for it to be recognised in clinical practice, and suggests that the lungs are held rigidly within an abnormal pleura. The pleural thickening in our patients may have been related to the condition described as "benign asbestos pleurisy" rather than the interstitial fibrosis of asbestosis.

Inhibition by ether of glucose-stimulated insulin secretion in isolated pieces of rat pancreas.

Addition of glucose (16.7 mM) to isolated pieces of rat pancreas increased insulin secretion 5.4-fold over basal secretion rates. Ether at 1, 1.5 and 2 MAC inhibited this insulinogenic effect of glucose in a dose-related manner by 5, 18 (P less than 0.01) and 29 (P less than 0.01) per cent, respectively.