U.K. guidelines for the management of cutaneous melanoma

These guidelines for management of cutaneous melanoma present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation. To reflect the collaborative process for the U.K., they are subject to dual publication in the British Journal of Dermatology and the British Journal of Plastic Surgery.     

Staging of colorectal cancer

CT, MR, and TRUS play complementary roles in staging CRC. Further improvements in these techniques will improve the accuracy of preoperative stating and thereby help optimize patient treatment and outcome⁴⁹.     

Skinfold thickness varies directly with spring coefficient and inversely with jaw pressure

PURPOSE: The main aims of this study were to: 1) determine whether heavy use of Harpenden calipers caused deterioration of the spring coefficient (force per unit length), 2) to quantify the change in skinfold thickness per unit change in jaw closing (downscale) pressure, and 3) to develop a calibration range for these calipers. METHODS: Part a) The change in spring force per unit length after at least 100,000 cycles of opening and closing five different springs was measured on a load cell. Part b) The dynamic downscale jaw pressure exerted by six pairs of Harpenden springs was measured on one caliper. Two were new pairs of springs (N1 and N2), two were 25-yr-old springs (O1 and O2), and two pairs (S1 and S2) had been used for less 1 yr. The six spring pairs were used to measure skinfold thicknesses at nine sites, in triplicate, on 20 subjects with the order of springs randomized and counterbalanced. Part c) The downscale jaw pressure of 78 Harpenden calipers was measured at eight jaw gaps. RESULTS: Part a) The springs did not change their characteristics after >100,000 cycles. Part b) At each skinfold site, the lowest thickness was recorded for S2 which exerted the highest jaw pressure (9.04 g x mm(-2)) and conversely the highest thickness was for N1 which exerted the lowest jaw pressure (8.02 g x mm(-2)). Increasing the downscale jaw closing pressure from 8.0 to 9.0 g x mm(-2) reduced a skinfold thickness by approximately 10%. Part c) The mean downscale jaw pressure was 7.82 +/- 0.25 g x mm(-2). CONCLUSIONS: In summary, it is suggested that if accurate skinfold measures between different Harpenden calipers are required, the downscale jaw pressure should be in the range of 7.40-7.82 and 7.85-8.21 g x mm(-2), at jaw gaps of 5 and 40 mm, respectively. These jaw pressures can be achieved by servicing the caliper pivot and indicator gauge to minimize frictional losses, adjusting the caliper jaw alignment, and by selecting springs that have a spring coefficient in the range 1.10-1.15 N x mm(-1).     

Severe bilateral internal tibial torsion in an adult, corrected by O'Donoghue's derotation osteotomy

A case report of an adult with severe bilateral internal tibial torsion is presented. The deformities were corrected by a modification of the tibial osteotomy described by O'Donoghue in 1939. The osteotomies healed well, and the deformities were completely corrected.     

Vertebral osteomyelitis in paraplegia: incidence, risk factors, clinical picture

PURPOSE: Because vertebral osteomyelitis (VOM) appears to be relatively common among patients paralyzed due to myelopathy, a population of these patients was surveyed to A) estimate the incidence of VOM, B) identify risk factors, and C) review clinical features. METHOD: The cohort of 537 patients with myelopathy paralyzed prior to January 1, 1989 and subsequently hospitalized at the authors' facility over an 11-year survey period was surveyed. All were male, 93% had a traumatic etiology of paralysis, 50% were > or = 50 years of age, 53% were paraplegic, 54% were motor and sensory complete, and 56% had been paralyzed for 15 years or more. VOM was diagnosed by computerized tomographic demonstration of intervertebral end plate destruction and a positive culture of that site. The relative incidences of VOM were calculated as cases per spinal cord injury (SCI) and general hospitalizations; potential risk factors were assessed by rates of VOM in the myelopathy cohort and clinical features of VOM in these patients were noted. RESULTS: Ten patients with myelopathy developed VOM, an incidence of 20.9 cases/10,000 SCI versus 1.8 cases/10,000 general hospitalizations. The risk ratio was 7.1 (p = .05) for paraplegia, 7.9 (p = .04) for motor and sensory completeness, and 4.4 (p = .06) for diabetes mellitus. The risk ratio for the 3 factors combined was 14.5 (p = .001). Initial clinical presentations were notable for back pain and plain radiographic films revealing paraspinal masses and pleural effusion. CONCLUSIONS: Patients with myelopathy are uniquely at risk for VOM if their paralysis is at the paraplegic level and is motor and sensory complete.     

Impact of prolonged infusions of the putative differentiating agent sodium phenylbutyrate on myelodysplastic syndromes and acute myeloid leukemia.

The aromatic fatty acid sodium phenylbutyrate (PB) promotes cytostasis and differentiation in a wide variety of tumor types; among several molecular activities, inhibition of histone deacetylase (HDAC) may account for many of its pharmacodynamic effects. A Phase I study demonstrated promising preliminary evidence of clinical activity in acute myeloid leukemia and myelodysplastic syndrome; however, plasma concentrations achieved at the maximum tolerated dose were less than those targeted based on in vitro studies. Because prolonged exposure to suboptimal concentrations of PB in vitro led to pharmacodynamic changes similar to a more brief exposure to higher concentrations, a study of the feasibility of prolonged administration of sodium PB was performed. Selected patients with acute myeloid leukemia and myelodysplastic syndrome were treated with sodium PB as a continuous i.v. infusion via ambulatory infusion pump. Sequential cohorts were treated for 7 consecutive days out of 14 or with 21 consecutive days out of 28. Prolonged infusions were well tolerated; dose-limiting central nervous system toxicity developed in 1 of 23 patients treated. End-of-infusion plasma concentrations were maintained within a range sufficient to inhibit HDAC. Two patients on the 21/28 schedule developed hematological improvement. Prolonged infusions of PB are well tolerated making this an attractive platform for the clinical investigation of HDAC inhibition.     

Complementary roles of laparoscopic abdominal exploration and diagnostic peritoneal lavage for evaluating abdominal stab wounds: a prospective study

PURPOSE: To determine the roles of laparoscopic abdominal exploration (LE) and diagnostic peritoneal lavage (DPL) in the evaluation of abdominal stab wounds, we prospectively compared LE with mandatory celiotomy (MC) in 76 patients having anterior abdominal stab wounds penetrating the fascia over a 22-month period. PATIENTS AND METHODS: Twenty-two patients underwent emergency celiotomy. The remaining patients were subjected to DPL and assigned to treatment by either celiotomy or initial LE with subsequent conversion to open exploration at the discretion of the attending surgeon. Results: Laparotomy was avoided in 55% of the 31 patients undergoing initial laparoscopy, and this group demonstrated a significant decrease in the incidence of nontherapeutic celiotomy, from 19% to 57% (P < 0.05), as well as decreased length of hospital stay (4 +/- 0.6 v 5.9 +/- 0.4 days; P < 0.05), and total hospital cost ($6119 +/- 756 v $8312 +/- 627; P < 0.05). There were no missed intraabdominal injuries or morbidity from laparoscopy identified in follow-up. The DPL (N = 36) was positive in 11 of the 12 patients with injury requiring surgical repair and was negative in 16 of the 25 patients not requiring repair. The sensitivity and specificity of DPL were 0.91 and 0.64 compared with 1.0 and 0.74 for laparoscopy. CONCLUSIONS: An algorithm to evaluate stable patients with anterior abdominal stab wounds and minimize overall costs of care, incidence of nontherapeutic celiotomy, and rate of missed injuries is suggested consisting of DPL followed by observation in patients with negative DPL and by laparoscopy in patients with positive DPL. Wounds to the thoracoabdominal region may be best evaluated by initial LE, as diaphragmatic wounds may result in a false-negative DPL.     

Length of postovariectomy interval and age, but not estrogen replacement, regulate N-methyl-D-aspartate receptor mRNA levels in the hippocampus of female rats

Estrogens and N-methyl-D-aspartate (NMDA) receptors regulate multiple aspects of morphological and functional plasticity in young animals. For example, estrogens increase spine density in the hippocampus, and NMDA antagonists block these effects. Few studies have examined the effects of age, postovariectomy interval, and duration of estrogen replacement in the hippocampus and more specifically on NMDA receptor subunits. Therefore, the present study was designed to investigate the effects of short- and long-term estrogen replacement or deprivation on mRNA levels of three NMDA receptor subunits, NR1, NR2A, and NR2B, in the hippocampus of aging female Sprague-Dawley rats. Young (3- to 4-month-old) and middle-aged (12- to 13-month-old) rats were ovariectomized for 1 month and then treated with estrogen or vehicle for either 2 days or 2 weeks. Another set of middle-aged and aged (24-to 25-month-old) animals were ovariectomized for 6 months and treated with estrogen or vehicle for 2 days or 2 weeks. RNase protection assay was used to assess changes in the NMDA receptor subunit mRNA levels. Our results demonstrated significant effects of age and length of ovariectomy on NMDA receptor mRNA levels, with little effect of the estrogen status of the animals on these parameters. The largest effect was seen for the length of the postovariectomy interval, with the results demonstrating that rats with a short-term ovariectomy have substantially higher NMDA receptor subunit mRNA levels than animals with long-term ovariectomy. The most dramatic effects of aging were seen for NR1 and NR2B mRNAs in ventral hippocampus, with large age-related increases. These data suggest that age and duration of ovariectomy impact NMDA receptor mRNA levels in the hippocampus, potentially affecting the stoichiometry and/or function of these receptors. These findings have important implications for postmenopausal or hysterectomy/oophorectomy estrogen depletion and replacement in humans.     

Association of hyperglycemia with increased mortality after severe burn injury

OBJECTIVE: To assess results of exchange nailing in nonunion after intramedullary (IM) nailing of humeral shaft fractures. METHODS: This was a retrospective study; 24 patients with nonunion after IM nailing of humeral shaft fractures were reviewed. In 13 cases, nonunion was treated using exchange nailing, and 11 patients were treated nonoperatively. Union was assessed from radiographs. Shoulder joint symptoms and function were assessed after a mean 4.7 years' follow-up using Constant-Murley scoring and self-administered questionnaires devised by L'Insalata et al. RESULTS: Single or repeated exchange nailing resulted in union in 6 of 13 patients. Shoulder joint function was satisfactory (mean Constant-Murley score of 72) for those patients whose fracture eventually united and poor (mean Constant-Murley score of 39) for those left with nonunion. CONCLUSION: Exchange nailing results in a poor union rate in nonunion after IM nailing of humeral shaft fractures. Permanent nonunion of the humeral shaft leaves the patient with severe disability.