Revascularization and ligamentization of autogenous anterior cruciate ligament grafts in humans.

Forty-eight patients were enrolled in a study to determine the time interval for maturity and remodeling following arthroscopically assisted autogenous anterior cruciate ligament reconstruction (ACLR). Two biopsy specimens, one superficial and one deep, at the same level in the midsubstance of the ACL were obtained. Graft age, time from ACL reconstruction to biopsy, ranged from 3 months to 120 months. The patients were placed into four groups, (1) 3 to 6 months, (2) 7 to 12 months, (3) more than 12 months, and (4) control, in accordance with the time following ACL reconstruction. Each specimen was independently evaluated using light microscopy by two different observers in a blinded design. The biopsy specimens were evaluated for vascularity, cellularity, fiber pattern, and metaplasia when compared with the normal ACL. None of the patients was protected from activity as a result of ligament biopsy and no adverse outcomes were reported as a result of biopsy. Our study showed that fiber pattern, cellularity, vascularity, and degree of metaplasia obtained gross histological similarity with a normal ACL by 12 months after autogenous reconstruction. Unexpectedly, no significant statistical differences were noted for all grafts more than 6 months after ACLR, for two of the histological features studied, vascularity and fiber pattern, P=.05. We conclude that by 12 months after autogenous ACLR, graft maturity resembles a normal ACL. Additionally, because no statistical differences were noted in vascularity and fiber pattern after 6 months following autogenous ACLR, significant graft maturity may occur before 12 months. This may allow early postoperative return to full activity and support proponents of accelerated rehabilitation programs following autogenous ACLR.

Tibial tunnel bone grafting: a new technique for dealing with graft-tunnel mismatch in endoscopic anterior cruciate ligament reconstruction.

A problem that is frequently encountered during endoscopic anterior cruciate ligament reconstruction bone-patellar tendon-bone autograft is that the graft is often too long and protrudes from the tibial tunnel. If less than 20 mm of the bone plug remains in the tibial tunnel, interference screw fixation cannot safely be used, and an alternate form of fixation may have to be employed. A simple technique has been developed to deal with this problem. The technique involves bone-grafting the tibial tunnel with a cancellous core of bone that is removed while creating the tibial tunnel. This not only makes it possible to safely use interference screw fixation in all cases, but it also makes it possible to place the point of graft fixation very near the anatomic anterior cruciate ligament insertion site.

Femoral nerve palsy after arthroscopic surgery with an infusion pump irrigation system. A report of three cases.

One patient developed complete, and two patients, partial, femoral nerve palsy after arthroscopic surgery in which an infusion pump was used to operate an irrigation system. In one case, hip flexor and quadricep function was completely lost after the patient underwent arthroscopic partial medial meniscectomy without the use of a tourniquet. A CT scan of the pelvis demonstrated considerable fluid accumulation in the thigh and inguinal regions. The remaining two patients developed quadriceps weakness, but not complete femoral nerve palsy, after arthroscopic-assisted anterior cruciate ligament reconstructions. Although tourniquets were used in these latter two procedures, the pressures were low (300 to 325 mm Hg) and the tourniquet times not excessive, suggesting that femoral nerve palsy in these two patients resulted from fluid extravasation. In all three cases, muscle function returned within 6 to 7 months, but sensory nerve deficits were still present at that time.

Anterior cruciate ligament reconstruction. Autograft or allograft?

Refinements in arthroscopic techniques have fostered an upsurge in arthroscopically assisted anterior cruciate ligament reconstruction. This article explores the relative merits of autogenous and allogeneic tissue used for this purpose and describes several important technical points in the author's preferred method of surgery.

Characterization of carbon disulfide binding in blood and to other biological substances.

Free and bound forms of CS2 are present in subjects exposed to CS2. In rats exposed to 2 mg/liter (approximately 640 ppm) of CS2 for 4 hr, concentrations of acid-labile CS2 (AL CS2, a form of bound CS2 that can be recovered from biological samples by acid treatment) in plasma and red blood cells (RBCs) increased linearly with exposure time. The majority (90%) of the blood AL CS2 was present in the RBCs. About 95% of the AL CS2 in plasma and in RBCs of exposed rats was found in the precipitates after treatment with ammonium sulfate. Incubation of fractionated human RBC lysates with CS2 showed that CS2 binding in these fractions was proportional to the hemoglobin concentration. These observations show that in blood, CS2 binds (in the form of AL CS2) mainly to hemoglobin and to a small extent to other blood proteins. Binding of CS2 to small molecules, including amino acids, accounted for only a small fraction of blood AL CS2. In in vitro studies, CS2 also bound to human albumin, gamma-globulin, and horse heart myoglobin. It was also found that CS2 binds to amino and sulfhydryl compounds at physiological pH. Plasma incubated with CS2 was found to chelate copper. Chelation of copper-containing enzyme by the reaction products of CS2 and biological amines has been observed and has been proposed as one of the mechanisms by which CS2 induces neurotoxicity (M.J. McKenna and V. DiStefano, 1977b, J. Pharmacol. Exp. Ther. 202, 253-266). Radioisotope studies showed that a substantial portion of the radioactivity could not be released from 14CS2-treated plasma and serum upon acid treatment at elevated temperature. These studies suggest the existence of non-acid-labile bound CS2, besides AL CS2, in plasma and serum treated with CS2.

The role of the red blood cell in the transport of carbon disulfide.

When rats were exposed to 2 mg l-1 (approximately 640 ppm) of carbon disulfide (CS2) for 4 h, the concentration of free CS2 in the red blood cells (RBCs) approached a plateau within 2 h. Free CS2 in plasma reached a steady state concentration within 15 min of exposure. More than 90% of the free CS2 in blood was found in the RBCs regardless of the length of exposure. In vitro studies showed that about 90% of the free CS2 partitioned into the RBCs regardless of whether the CS2 was added first to the plasma or directly to the RBCs. Hence, it appears that the RBC is the major carrier of CS2 in blood. It was found that 98% of the free CS2 in red blood cell lysates was associated with hemoglobin. Free CS2 in RBCs was readily partitioned into olive oil (RBCs/oil = 1/6), less readily into the plasma (RBCs/plasma = 12/1), and only to a small extent into phosphate buffer (RBCs/buffer = 39/1). The extraction of free CS2-loaded RBCs into albumin solution increased with increasing albumin concentrations. CS2 can be extracted with buffer, protein solution, and oil, indicating that CS2 in RBCs can be transferred to the medium in which the RBCs contact. It is proposed that RBCs may also play an important role in the transport of CS2 from lung to tissues and vice versa. The possible role of RBCs in the transport of other organic solvents in the blood is also discussed.

Mechanisms of decreased cerebrospinal fluid production by radiographic contrast media: role of adenylate cyclase activation.

The i.v. administration of radiographic contrast media decreases cerebrospinal fluid (CSF) production as measured by negative pressure collection from the lateral ventricles of anesthetized dogs. Evidence suggests that adrenergic-mediated adenylate cyclase (AC) activity controls CSF production. AC activity was measured in membrane fractions of bovine and canine choroid plexus and rat heart and lung in the presence of various concentrations of the contrast agent sodium diatrizoate. A concentration-dependent inhibition of isoproterenol-stimulated AC activity by the contrast agent was observed in vitro. Specific binding of [3H]dihydroalprenolol to membrane fractions of bovine choroid plexus was also inhibited by sodium diatrizoate. An indication that the inhibition of choroidal AC activity by contrast media is significant in vivo was obtained by measuring CSF production in dogs. The inhibition of CSF production by sodium diatrizoate was reduced 50% when the contrast agent was administered during an i.v. infusion of isoproterenol (100 ng/kg/min). These results indicate that the mechanism of decreased CSF production by contrast media may involve inhibition of beta adrenergic-stimulated AC activity.

How I Manage Osteochondritis Dissecans.

In brief: Knee pain and joint effusion are usually among the earliest symptoms of osteochondritis dissecans, a lesion that occurs most often on the articular surfaces of the femoral condyles. It is seen most frequently among active adolescents but can occur in anyone between the ages of 5 and 50. The principal goal of treatment should be to prevent partial or complete detachment of the lesion and alteration in the articular surface leading to degenerative arthrosis. Treatment may be nonoperative or may involve surgery. For treatment purposes, patients are categorized into three groups: children and young adolescents, adolescents and young adults, and adults.

An investigation of the mechanism of lead-induced relaxation of pigeon crop smooth muscle.

Lead-induced crop dysfunction is probably due to a direct action on the smooth muscle or the neural elements in crop tissue. Strips of crop tissue relax when exposed to lead chloride in vitro. We found that tetrodotoxin and the neurotransmitter antagonists propranolol, sotalol and apamin failed to alter lead-induced relaxation, suggesting that the effect is not neurally mediated. Lead, manganese, cadmium and theophylline inhibited calcium-induced contractions in depolarized crop tissue. However, lead, like the phosphodiesterase inhibitor theophylline and unlike the calcium-influx blocker verapamil, did not inhibit bethanechol- or potassium-stimulated contractions and calcium influx into crop tissue. This suggests that lead does not act by blockade of calcium influx. Lead stimulated cyclic AMP production in cell-free crop membrane preparations. Lead also enhanced manganese stimulation of cyclic AMP production. The results suggest that lead-induced relaxation may be due to stimulation of adenylate cyclase activity resulting in increased intracellular cyclic AMP levels.

Lead induction of crop dysfunction in pigeons through a direct action on neural or smooth muscle components of crop tissue.

Lead acetate solutions administered p.o. to pigeons produce crop stasis. Crop dysfunction may be an indirect effect on crop activity by a direct interaction with the cerebellum or some other site associated with lead-induced ataxia. Alternatively, crop stasis may be due to the direct interaction of lead with sites on the smooth muscle or neural elements in crop tissue. A behavioral test for ataxia was performed on pigeons given lead by crop intubation or i.m. injection. Blood lead concentrations were also monitored. Lead-induced ataxia was separable from lead-induced crop dysfunction depending on the route of lead administration, suggesting that lead-induced crop stasis is not secondary to toxicity at a site associated with ataxia. Intramuscular treatment produced crop stasis more readily than did crop intubation. This probably reflects different mechanisms of absorption and metabolism. A Tris-succinate medium was devised which accommodated the solubility characteristics of lead, permitting studies of crop tissue in vitro. Lead chloride added to crop tissue in tris-succinate medium caused a concentration-related reversible relaxation. Crop circular muscle was more sensitive to Pb++ than was longitudinal muscle, in agreement with the effects of other agonists. The EC30 of crop circular smooth muscle in plasma was 1000 microM PbCl2 compared to 3 microM in Tris-succinate medium. The results suggest that lead induces crop dysfunction by acting either directly on crop smooth muscle or on neural elements in crop tissue.

Pharmacological action of radiographic contrast media reduced cerebrospinal fluid production in the dog.

Intravenous administration of radiographic contrast media (CM) significantly decreases cerebrospinal fluid (CSF) production as measured by negative pressure collection from a lateral ventricle of the anesthetized dog. This effect has been shown with the conventional ionic CM, sodium diatrizoate, and is now reported for the new nonionic agent, iohexol. Continuous infusion of either agent maintains the decrease. The magnitude of the CM-induced decreased CSF production is proportional to the dose in the range of 1 to 4 ml/kg. This action of CM cannot be explained by an osmotic mechanism. Two enzymes involved in the elaboration of CSF, carbonic anhydrase and sodium, potassium-adenosine triphosphatase, are not inhibited by sodium diatrizoate sufficiently in vitro to explain this action of CM. These results indicate a pharmacological action by i.v. CM that may require special attention when reduced CSF production would be deleterious.

Decreased cerebrospinal fluid production by intravenous sodium diatrizoate.

Intravenous administration of the radiographic contrast agent sodium diatrizoate (50%, 2ml/kg) significantly decreased cerebrospinal fluid (CSF) production in dogs for up to 40 minutes as measured from a lateral ventricular cannula. The magnitude of this decrease exceeded the decrease induced by hypertonic saline. Since hypertonicity could not explain the decrease, an enzymatic mechanism was sought. Choroid plexus carbonic anhydrase (CA) has been implicated in the elaboration of CSF. The assay of CA activity was a colorimetric measure of the hydration of CO2 where reaction time is related to the amount of active CA present. The inhibition of dog red blood cell and choroid plexus CA by sodium diatrizoate was compared with that by the known CA inhibitor acetazolamide. Acetazolamide (48 mM) produced almost complete inhibition whereas the inhibition by sodium diatrizoate (84 mM) was not significantly different from control. These results suggest that neither hypertonicity nor CA inhibition is the cause of the reduced CSF production after intravenous injection of sodium diatrizoate in dogs.

Phenylthioalkylamines in experimental tumor treatment in mice.

Two phenylthioalkylamines, phenylthioethylamine (PTEA) and phenylthiopropylamine (PTPA), were prepared and tested for cytotoxicity in vitro and as antitumor agents in (C57BL X DBA/2)F1 (BDF1) mice. Low concentrations of PTEA (median effective concentrations of 8.0, 12.0, and 1.3 micrograms PTEA/ml) inhibited the growth of P388 murine lymphoma, L1210 leukemia, and B16 melanoma cells in culture. PTPA was more effective; concentrations of 0.80, 0.56, and 0.35 micrograms PTPA/ml inhibited the growth of P388, L1210, and B16 in vitro by 50%. PTEA and PTPA treatment increased survival times in BDF1 mice bearing the P388 lymphoma, L1210 leukemia, B16 melanoma, and Lewis lung tumors. Multiple daily administrations of the test compounds were more effective than single daily injections in increasing the life-span in mice bearing the P388 lymphoma and B16 melanoma. Both PTEA and PTPA inhibited the enzyme copper-zinc superoxide dismutase.

Blood-bound carbon disulfide: an indicator of carbon disulfide exposure, and its accumulation in repeatedly exposed rats.

Carbon disulfide is present in exposed subjects in free and bound or acid-labile forms. Sensitivities of the blood acid-labile CS2 (AL CS2) concentration and the modified iodine-azide test (IAT) were compared as indicators of CS2 exposure. Rats were exposed to 15 (approximately 5 ppm), 30, 60, or 120 mg/m3 of CS2. Exposure to 15 or 30 mg/m3 of CS2 could not be detected by the modified IAT. However, a linear relationship between blood CS2 (free or AL CS2) concentrations and these exposure levels was observed. Free CS2 is eliminated rapidly, while AL CS2 is eliminated very slowly from the exposed subjects. Repetitive daily exposures (8 hr/day) to 120 mg/m3 of CS2 were carried out in rats. Blood AL CS2 concentrations in exposed rats increased with each successive exposure while the free CS2 level remained relatively constant. By the sixth or seventh daily exposure the blood AL CS2 concentration was about 2.5 times that of the first 8-hr exposure and about 3 times the level of free CS2. These results indicated an appreciable accumulation of CS2 in subjects repeatedly exposed to low concentrations of the solvent. Rats were also exposed to CS2 8 hr/day for 5 days. After a 2-day nonexposure period (Days 6 and 7), the animals were reexposed on Day 8. The blood AL CS2 concentration in animals exposed on Day 8 was substantially higher than in those that received a single 8-hr exposure (Day 1), despite the hiatus on Days 6 and 7. These results indicated that blood AL CS2 was not totally eliminated during the 2-day nonexposure period. In in vitro experiments, the binding profile of CS2 to human blood was remarkably similar to that of rats exposed to CS2 by inhalation.

A technique of arthroscopic meniscoplasty.

Indications and technique are discussed for arthroscopic repair of meniscal tears by means of mattress sutures delivered by Kirschner wire. Short term results in eight cases are summarized.