John J. Grayhack

Incidence and severity of sexual adverse experiences in finasteride and placebo-treated men with benign prostatic hyperplasia.

OBJECTIVES To evaluate the incidence and resolution of sexual adverse experiences (AEs) in men with benign prostatic hyperplasia treated with finasteride 5 mg compared with placebo. METHODS The Proscar Long-term Efficacy and Safety Study (PLESS) was a 4-year, randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of finasteride 5 mg in 3040 men, aged 45 to 78 years, with symptomatic benign prostatic hyperplasia, enlarged prostates, and no evidence of prostate cancer. Patients completed a questionnaire at screening regarding their history of sexual dysfunction. During treatment, spontaneously self-reported sexual AEs were recorded. RESULTS At screening, 46% of patients in each treatment group reported some history of sexual dysfunction. During year 1 of the study, 15% of finasteride-treated patients and 7% of placebo-treated patients had sexual AEs that were considered drug related by the investigator (P <0.001). During years 2 to 4, no between-group difference was noted in the incidence of new sexual AEs (7% in each group). The drug-related sexual AE profile for finasteride was similar for men with or without a history of sexual dysfunction. Sexual AEs resolved while continuing therapy in 12% of finasteride patients and 19% of placebo patients. Only 4% of finasteride and 2% of placebo patients discontinued the study because of sexual AEs. In men who discontinued with a sexual AE, 50% and 41% experienced resolution of their sexual AE after discontinuing finasteride or placebo therapy, respectively. CONCLUSIONS Compared with placebo, men treated with finasteride experienced new drug-related sexual AEs with an increased incidence only during the first year of therapy.

A cholinergic receptor site on murine lymphocytes with novel binding characteristics.

To further analyze functionally important cholinergic receptors on lymphocytes, we studied the binding of the muscarinic antagonist Quinuclidinyl benzilate (QNB) to murine splenic lymphocytes. Studies of displacement of [3H]QNB by unlabeled QNB on lymphocytes revealed at least two binding sites. Scatchard analysis of equilibrium binding isotherms also distinguished two sites with apparent Kds of 480 nM and 16 microM. There was greater specific QNB binding to B cell-enriched lymphocyte fractions than to T cell fractions. Lymphocyte binding demonstrated temperature-dependent dissociability, and specific binding occurred on isolated lymphocyte membranes as well. Both muscarinic and nicotinic ligands competed for QNB binding to lymphocytes with low and nearly equal affinity. Therefore, QNB binding sites on lymphocytes appear to be of low affinity and of mixed muscarinic and nicotinic character.

A kyphectomy technique with reduced perioperative morbidity for myelomeningocele kyphosis.

Study Design. The lumbar sacropelvis in 11 patients with myelomeningocele and kyphosis was treated with a subtraction kyphectomy technique and posterior instrumentation. The results of this procedure in the 11 patients were evaluated and compared with previous results. Objective. To examine critically their experience using the subtraction (decancellation) vertebrectomy technique combined with posterior instrumentation for myelomeningocele kyphosis, the authors reviewed the charts of 18 myelomeningocele patients who underwent surgery for lumbar kyphosis between 1994 and 1998. Summary of Background. The benefits of restoring sagittal spinal alignment in myelomeningocele patients with severe lumbar kyphosis deformity to achieve postural stability and improved sitting balance generally are accepted. The optimal method of deformity correction, the extent of instrumentation, and the role of limited arthrodesis remain undefined. Methods. Of the 18 patients considered, 11 met the inclusion criteria of having undergone reconstruction using a subtraction (decancellation) vertebrectomy technique, preservation of the thecal sac, limited arthrodesis with posterior transpedicular lumbosacral instrumentation, and a minimum follow-up evaluation of 2 years. The study considered the age of the patient, number of levels fused, estimated blood loss, preoperative deformity, immediate postoperative correction, magnitude of correction, and maintenance of correction at latest follow-up assessment. Results. The average age at the time of the index procedure was 6 years (range, 3–12 years). The average preoperative kyphosis was 88° (range, 50–149°). Immediately after surgery, the average curve measurement was 3° lordosis (range, 50° to 50°). The average magnitude of postoperative sagittal plane deformity correction was 91° (range, 43–126°). Finally, the magnitude of correction maintained at the final follow-up assessment averaged 66° (range, 22–114°). This represented an average loss of correction at 2 years of 24° (range, 0–84°). There were no deaths, episodes of acute-onset hydrocephalus, vascular complications, or chronic deep wound infections. Conclusions. The subtraction (decancellation) vertebrectomy technique with preservation of the dural sac is a safe and efficacious technique for correction and stabilization of myelomeningocele kyphosis in young patients. Morbidity is reduced, as compared with that of excision techniques. Restoration of sagittal alignment at the time of initial correction and stabilization to achieve a balanced spine led to acceptable results.

Long-term outcome of patients with intraspinal neuroblastoma

BACKGROUND Chemotherapy, radiotherapy, and surgical decompression with laminectomy are effective therapeutic options in the treatment of cord compression from neuroblastoma (NB). We report the long-term outcome of patients with intraspinal NB treated with or without laminectomy at two large pediatric oncology centers. PROCEDURE We reviewed the medical records and radiographs of 26 children with intraspinal NB treated at Childrens Memorial Hospital in Chicago, Illinois, between 1985 and 1994 or at St. Jude Childrens Research Hospital in Memphis, Tennessee, between 1967 and 1992. RESULTS Twenty-four of the 26 patients are alive and disease-free (follow-up of 2-29 years; median, 10 years 2 months). Fifteen of the 23 patients with neurologic impairment underwent initial laminectomy. Nine of these 15 patients recovered neurologic function, including 3 patients who presented with paraplegia. Eleven of the 15 patients who underwent laminectomy have developed mild to severe spinal deformities. Eight patients with neurologic symptoms consequent to cord compression were treated with initial chemotherapy and/or surgery, but did not undergo laminectomy. Three patients with mild to moderate deficits recovered neurologic function. Four of 11 patients with intraspinal NB who did not undergo laminectomy have mild to severe scoliosis. CONCLUSIONS A low incidence of neurologic recovery was seen in patients with long-standing severe cord compression regardless of treatment modality. For patients with partial neurologic deficits, recovery was seen in most patients following chemotherapy or surgical decompression with laminectomy. A higher incidence of spinal deformities was seen in the patients treated with initial laminectomy.

Standards in anterior spine surgery in pediatric patients with neuromuscular scoliosis

The authors reviewed 111 patients with neuromuscular disease who underwent anterior spine surgery for correction of scoliosis. An overall complication rate of 44.1% was found, 21.6% major and 22.5% minor. Pulmonary complications were the most common major complications, urinary tract infections the most common minor complications. The rate of complications was greater in patients with cerebral palsy, thoracoabdominal and transthoracic approaches, staged procedures, operative blood loss >1,000 mL, or previous spine surgery. In addition, statistical analysis confirmed that curve magnitude >100° degrees was a risk factor for complications.

Management of late-onset tibia vara in the obese patient by using circular external fixation

Previously published series of surgery for late-onset tibia vara reported a significant number of complications and fair or poor results. Obesity in many of these patients makes surgical intervention an even more daunting prospect. Circular external fixation is applicable to almost any limb size and allows weight bearing as tolerated, with gradual adjustment of alignment. Twenty-five tibiae in 17 patients who exceeded their ideal body weight by > or =50% underwent correction of late-onset tibia vara with the Ilizarov technique. Average age at surgery was 11 years 7 months (range, 7 years 8 months to 15 years 11 months). Mean varus deformity was 27 degrees (range, 10-55 degrees). Treatment time averaged 12 weeks in patients without lengthening and 16.9 weeks in those requiring lengthening (mean, 3.5 cm). All patients achieved alignment within 5 degrees of normal. Complications included one delayed union, premature consolidation in one, and two residual limb-length inequalities. There were no cases of osteomyelitis, compartment syndrome, or nerve palsy. These results are a significant improvement over reports of traditional methods in these difficult patients.

Do latex precautions in children with myelodysplasia reduce intraoperative allergic reactions

Children with myelodysplasia have an increased incidence of latex allergy, which can lead to severe intraoperative allergic reactions. Despite widespread recommendations to avoid intraoperative latex exposure, little evidence exists to support the efficacy of this practice. We examined the incidence of intraoperative allergic reactions in children with myelodysplasia who underwent 1,025 operations in a 36-month period before and after institution of a standardized latex-avoidance protocol. Risk factors for an intraoperative reaction were found to be a history of latex allergy (p = 0.001) and surgery performed before institution of the latex-avoidance protocol (p = 0.01). The estimate of increased risk for allergic reaction was 3.09 times higher in cases performed without latex avoidance. Recognized violation of the protocol after its institution led to severe allergic reactions in three patients. Our experience suggests that a latex-avoidance protocol reduces intraoperative allergic reactions in children with myelodysplasia. Development of severe allergic reactions with violation of the protocol reinforces the importance of vigilance on the part of all operating room personnel in its implementation.

Clinical Dilemmas and Problems in Assessing Prostatic Metastasis to Bone: The Scientific Challenge

Metastatic spread to bone by carcinoma of the prostate has long been a focus of attention in this increasingly recognized malignancy. Early series of patients with carcinoma of the prostate were made up predominantly of individuals with symptoms from their disease; predominant among these were those relating to bladder neck obstruction (65–96%) and bone pain (15–40%) (Grayhack and Wendel, 1977). Despite increasing efforts to diagnose prostatic malignancy early, the data generated by the American College of Surgeons survey in the past decade (Murphy and associates, 1982) indicated that metastatic carcinoma of the prostate (Stage D) was recognizably present in about one-fourth of patients at the time of their initial diagnosis and suggest the recognized site of dissemination was most commonly bone. Failure to achieve a disease-free state by surgical excision or radiation treatment of the primary prostatic neoplasm has provided evidence to support the presumption that the incidence of dissemination to bone at diagnosis or possibly subsequently is far more common than initial diagnostic evaluation indicates (Gervasi and associates, 1989; Kozlowski and Grayhack, 1991; Paulson and associates, 1990). The problems posed by understanding the factors leading to bone metastasis, recognizing the metastasis when they are present, and altering the metastasis and their consequences continue to present major challenges in our patient care efforts.

Toxic shock syndrome complicating orthopaedic manipulation of bone. A report of two cases.

In 1978, Todd and Fishaut described toxic shock syndrome, a multisystem disorder usually associated with toxic shock syndrome toxin-1, a toxin elaborated by Staphylococcus aureus . Most cases occur during menstruation and are associated with vaginal colonization by strains of this bacterium that elaborate the toxin. Other risk factors include the use of tampons, a young age, and a low serum concentration of anti-toxic shock syndrome toxin-1 antibody8. Toxic shock syndrome can also occur in patients who are not menstruating; the risk factors are less certain but include nasal operations and the presence of a non-operative or operative wound. Toxic shock syndrome that is not related to menstruation is less often associated with the isolation of Staphylococcus aureus that produces toxic shock syndrome toxin-1; only 40 to 60 per cent of isolates from such patients produce the toxin, compared with 90 to 100 per cent of isolates from patients who are menstruating4,6,14. Other toxins, most notably staphylococcal enterotoxin-B, have been implicated in toxic shock syndrome in non-menstruating patients. Orthopaedic procedures have not been considered a risk factor for toxic shock syndrome, and there have been few reports of toxic shock syndrome associated with bone manipulation and implants. One report described two patients who survived after insertion of an external fixator18 and one, a patient who died after removal of a metallic internal-fixation device from the healed site of a right femoral varus derotational osteotomy combined with a right arthrodesis of the wrist with iliac-crest bone graft and fixation with two Kirschner wires13. Staphylococcus aureus grew on culture of specimens obtained during incision and drainage of the iliac crest and the wrist13. Additionally, Irvine et al. reported a death due to toxic shock syndrome after removal of three …

Pediatric Scoliosis and Kyphosis: An Overview of Diagnosis, Management, and Surgical Treatment

Evaluation of pediatric spinal deformity requires knowledge of special orthopaedic testing and radiographic interpretation. The determination of recommendations for treatment of spinal abnormalities in children can be challenging and at times complex, as treatment options are dependent upon a variety of factors. The etiology of scoliosis or kyphosis, presence or absence of vertebral anomalies, symptoms, magnitude of the curve, physiologic/skeletal age, and evidence of and risk of progression all require consideration and play a role in the shared decision-making process. This article provides an overview of relevant information and includes research outcomes to support the care of pediatric patients with spinal deformities. [Pediatr Ann. 2017;46(12):e472-e480.].