Initial experiences with isolated limb perfusion for unresectable melanoma of the limb.

AIMS: Our initial results with isolated limb perfusion (ILP) using melphalan ± TNF alpha in patients with unresectable melanoma of the limb were analyzed. METHODS: 15 ILPs were performed between 2001 and 2006. Indications for ILP were stage III or IV metastatic melanoma. Complete and partial response rates, time to local and systemic tumour progression rates, disease free and overall survival rates were retrospectively analyzed. RESULTS: Overall response rate was 93%, with a 67% complete response and a 26% partial response rate. In eight cases grade II, while in six cases grade III local toxicity was detected. However, one mortality was detected in the early postoperative phase due to a grade V complication. With a mean follow-up period of 2.7 years, eight patients had local progression and in four of those, systemic progression was detected. CONCLUSIONS: ILP was generally well tolerated and limb salvage was achieved in all cases.

Early prediction of cardiac allograft vasculopathy and heart transplant failure.

Early risk-prediction is essential to prevent cardiac allograft vasculopathy (CAV) and graft failure in heart transplant patients. We developed multivariate models to identify patients likely to experience CAV, severe CAV, and failure due to CAV, at 1, 5 and 10 years. A cohort of 172 patients was followed prospectively for 6.7 ± 3.9 years. Logistic regression models were developed and cross-validated using bootstrap resampling. Predictive markers of atherothrombosis (myocardial fibrin deposition, and loss of vascular antithrombin and tissue plasminogen activator) and arterial endothelial activation (intercellular adhesion molecule-1 expression) were measured in serial biopsies obtained within 3 months posttransplant. Most markers were univariately associated with outcome. Multivariate models showed that loss of tissue plasminogen activator was the dominant and, in most cases, only predictor of long-term CAV (p < 0.001), severe CAV (p < 0.001), and graft failure due to CAV (p < 0.001). The models discriminated patients having adverse outcomes, had particularly high negative predictive values (graft failure due to CAV: 99%, 99% and 95% at 1, 5 and 10 years) and predicted event incidence and time to event. Early absence of atherothrombotic risk identifies a patient subgroup that rarely develops CAV or graft failure, implying that this low-risk subgroup could possibly be followed with fewer invasive procedures.

Effect of desensitization in solid organ transplant recipients depends on some cytokines genes polymorphism.

Desensitization (DS) is widely used to decrease PRA in solid organs transplant candidates (TC). Various numbers of cycles of DS are required to reduce or eliminate donor specific antibodies (DSA). The goal of this study was to investigate if there was a correlation between polymorphism (PM) of some cytokine genes and intensity of DS required to make the recipient/donor cross match compatible. Thirty-one TCs were included in the study. Antibody specificity, percent of reactive antibodies (PRA) and serum concentration of cytokines were analyzed using the LUMINEX platform. PCR-SSP method was used for IL-1alpha, IL-1beta, IL-1R, IL-1Ralpha, IL-4Ralpha, IL-12, IFNgamma, TGFbeta1, TNFalpha, IL-2, IL-4, IL-6 and IL-10 gene PM analysis. Significant relationship between PM of genes encoding IL-4Ralpha, IFNgamma and IL-12 (p70) and susceptibility to DS was demonstrated (p=0.04, p=0.01 and p=0.05 respectively). Correlation between elevated serum level of IL-12 (p70) and A/A or C/A genotype at -1188 position was found in resistant to DS TCs (p=0.015). These results indicate that analysis PM of genes encoding IL-4R, IFNgamma and IL-12 enables to define the DS strategy in TCs more accurately regarding the number of plasmapheresis (PP) cycles and dose of intravenous immunoglobulin (IVIG).

Lysine requirement of kittens given purified diets for maximal growth.

Three experiments were conducted using a total of 15 male and 15 female weaned specific pathogen-free kittens given amino acid-based purified diets containing varying concentrations of lysine (from 4.0 to 11.3 g/kg diet) in a Latin square design of 10 day periods. In experiment 1, the predicted lysine requirement was 7.7 g/kg diet, and in experiments 2 and 3, maximal weight gain occurred at 8.0 g lysine/kg diet. In experiment 3, nitrogen balance was not different for kittens given diets containing 8.0 and 9.0 g lysine/kg. These experiments support a requirement of 8.0 g lysine (free base)/kg diet, in a diet with a calculated metabolizable energy value of 4.7 kcal/g.

Skin and soft tissues. Management of four common infections in the nursing home patient.

Common skin and soft tissue infections in nursing home patients include herpes zoster, cellulitis, pressure ulcer infections, and scables. Treatment of shingles with an oral antiviral should be started within 24 hours of symptom onset. Dissemination and bacterial superinfection require antibiotic therapy. Use of corticosteroids to prevent post-herpetic neuralgia remains controversial. Cellulitis is most often caused by Staphylococcus aureus and beta-hemolytic streptococci (groups A and B). Therapy for cellulitis is empiric; gram-negative bacilli should be covered in diabetic patients. Most pressure ulcers never become infected; for those that do, empiric therapy should cover S aureus, gram-negative bacilli, and anaerobes. Topical treatment of scables with 5% permethrin cream or 1% lindane lotion is recommended.

Treatment of vascular thrombosis with enoxaparin in orthotopic heart transplant patients during the early postoperative period.

Management of anti-coagulation in the early period after orthotopic heart transplantation, when the frequency of invasive procedures to assess for graft rejection is high, presents a difficult clinical problem in which the need for effective therapy must be weighed against the desire for outpatient treatment. In this report, we summarize the clinical course and long-term outcome of 6 patients from our center in whom vascular thrombosis was treated on an outpatient basis with enoxaparin. We conclude that the use of enoxaparin may provide a safe and reasonable alternative to conventional anti-coagulation therapy during this period.

Clinical manifestations of early syphilis by HIV status and gender: results of the syphilis and HIV study.

BACKGROUND: Despite reports of unusual clinical presentations and therapeutic responses among HIV-infected patients with syphilis, syphilis has not been regarded as a serious opportunistic infection that predictably progresses among most HIV-coinfected patients. GOAL: To define and describe differences in the presentation and response to treatment of early syphilis among HIV-infected and HIV-uninfected patients, to describe any differences by gender, and to determine if clinical presentation of central nervous system involvement predicted serologic failure. DESIGN: A prospective, multicenter, randomized, controlled trial of enhanced versus standard therapy to compare the benefit of enhanced therapy, the clinical importance of central nervous system involvement, and the clinical manifestations of early syphilis infection among HIV-infected and HIV-uninfected patients. RESULTS: The median number of ulcers was significantly greater among HIV-infected and HIV-uninfected patients, as was the percent of HIV-infected patients with multiple ulcers. Among patients diagnosed with secondary syphilis, a higher percentage of HIV-infected patients presented with genital ulcers [13/53 (25%)] than did HIV-uninfected patients [27/200 (14%)]. No differences between HIV-infected and HIV-uninfected patients were detected for other secondary syphilis manifestations. Although women presented more frequently with secondary syphilis than did men, no other gender differences in clinical manifestations were noted. Neurologic complaints were reported most frequently among patients with secondary syphilis [103/248 patients (42%)] compared with patients with primary syphilis [32/136 (24%)] and early latent syphilis [48/ 142, (34%)] (P < 0.05), but no differences in neurologic complaints were apparent by HIV status or CSF abnormalities. No neurologic complaints were significantly associated with serologic treatment failures at 6 months. CONCLUSIONS: Overall, HIV infection had a small effect on the clinical manifestations of primary and secondary syphilis. Compared with HIV-uninfected patients, HIV-infected patients with primary syphilis tended to present more frequently with multiple ulcers, and HIV-infected patients with secondary syphilis presented with concomitant genitals ulcers more frequently.

A prospective comparison of pedal ergometry with conventional treadmill testing in the investigation of lower extremity pain.

BACKGROUND: Investigation of lower extremity pain is compromised by comorbid disorders that may interfere with conventional testing. AIMS: To compare pedal ergometry with conventional treadmill testing. METHODS: A prospective study was performed where patients presenting with a diagnosis of intermittent claudication were assessed by both methods of testing. RESULTS: Of 78 patients studied with both tests, no exercise-induced ankle pressure changes occurred in 26, two were unable to complete either test despite normal pressure measurements, while 24 had exercise-induced pressure drop detected by both tests. Of patients who completed pedal ergometry, 21 were unable to complete the treadmill test, 14 of whom had negative ergometry, while seven had a pressure drop detected by pedal ergometry. Three had pressure changes with pedal ergometry, but not with treadmill testing and two had pressure changes on the treadmill not reproduced by pedal ergometry. CONCLUSIONS: Pedal ergometer is more sensitive than treadmill testing in detecting arterial insufficiency, as indicated by a 20% or greater fall in ankle pressure, and more suitable in a subgroup of patients unable to tolerate conventional treadmill testing.

Fluoroquinolones.

The fluoroquinolone class of antimicrobial agents has expanded dramatically in the last 5 years and will continue to grow over the next decade. This article discusses the newer fluoroquinolones in detail, including pharmacokinetics, pharmacodynamics, safety, and drug interactions, and the spectrum of in vitro activity. Newer agents are compared and contrasted with the older ones, particularly ciprofloxacin and ofloxacin, and problems with liver toxicity and trovafloxacin are described. Finally, appropriate use of the fluoroquinolones is discussed, including their role in the treatment of urinary tract infections, sexually transmitted diseases, gastrointestinal infections, osteomyelitis, and respiratory tract infections.

Bacteroides fragilis bacteremia and infected aortic aneurysm presenting as fever of unknown origin: diagnostic delay without routine anaerobic blood cultures.

We report the case of a 71-year-old male with Bacteroides fragilis bactermia and infected aortic aneurysm that went undiagnosed, in part, because routine anaerobic blood cultures were not obtained. Bacteremia caused by anaerobes has been reported to be declining, and recommendations to discontinue routine anaerobic blood cultures have been implemented in some hospitals. To our knowledge, this is the first report of an anaerobic bacteremia and infection that had a delay in diagnosis due to this change in blood-culturing protocol. The potential impact of deleting anaerobic blood cultures from routine protocols is discussed.

Long term results of polytetrafluoroethylene in above knee femoropopliteal bypass for critical ischaemia.

Ninety-six consecutive above-knee femoropopliteal bypasses, using polytetrafluoroethylene (PTFE) preferentially, were performed for limb-threatening ischaemia. Cumulative primary graft patency was 68 per cent, 49 per cent and 36 per cent and limb salvage 93 per cent, 85 per cent and 75 per cent at 1, 3 and 5 yr respectively. As a result of poor long term survival (51 per cent at 5 yr), and the healing of remedial lesions before graft occlusion, 68 patients (72 per cent) required no further intervention. Eighteen secondary bypasses were undertaken, 12 using ipsilateral saphenous vein. In this group of elderly patients with poor life expectancy, where a limited operation is desirable, the use of PTFE provided excellent limb salvage with low morbidity. Although we can no longer justify our continued use of PTFE in every case of critical ischaemia because of its inferior patency to autogenous vein, we continue to use it preferentially in patients whose lifespan is likely to be short and in cases where a remedial lesion is present.

Etiology of genital ulcers and prevalence of human immunodeficiency virus coinfection in 10 US cities. The Genital Ulcer Disease Surveillance Group.

To determine the etiology of genital ulcers and to assess the prevalence of human immunodeficiency virus (HIV) infection in ulcer patients in 10 US cities, ulcer and serum specimens were collected from approximately 50 ulcer patients at a sexually transmitted disease clinic in each city. Ulcer specimens were tested using a multiplex polymerase chain reaction assay to detect Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV); sera were tested for antibody to HIV. H. ducreyi was detected in ulcer specimens from patients in Memphis (20% of specimens) and Chicago (12%). T. pallidum was detected in ulcer specimens from every city except Los Angeles (median, 9% of specimens; range, 0%-46%). HSV was detected in >/=50% of specimens from all cities except Memphis (42%). HIV seroprevalence in ulcer patients was 6% (range by city, 0%-18%). These data suggest that chancroid is prevalent in some US cities and that persons with genital ulcers should be a focus of HIV prevention activities.

Exercise echocardiography, angiography, and intracoronary ultrasound after cardiac transplantation.

Fifty-one consecutive patients underwent exercise echocardiography, angiography, and intracoronary ultrasound (ICUS) 2.5 years (range from 1 to 6) after cardiac transplantation. The average age of the donor was 29 years (range 13 to 50), and the average age of the recipient was 49 +/- 12 years. In total, 78 studies were performed, as 25 patients had >1 annual evaluation and 2 patients had 3 consecutive annual evaluations. Of the 78 angiographic studies, 40 (26 patients) had evidence of coronary artery disease, defined as a focal stenosis (>20%, n=4) or luminal irregularities (n=36). However, by ICUS all 51 patients had intimal thickening at some point, with 34 patients possessing diffuse disease and 17 focal intimal thickening only. Of the 25 serial studies, 12 progressed by at least 1 Stanford class. The sensitivity of angiography for determination of class III to IV intimal thickening was 64% and the specificity was 76%. On exercise echocardiography, 6 examinations revealed resting wall motions abnormalities, whereas 6 had inducible wall motion abnormalities with exercise. The sensitivity of exercise echocardiography to determine class III to IV intimal thickening was 15%, and the specificity was 85%. In conclusion, exercise echocardiography is an insensitive method for predicting transplant-mediated coronary artery disease, whereas luminal irregularities on angiography may predict the presence of Stanford grade III to IV intimal thickening.

Infantile hypertrophic pyloric stenosis: long-term audit from a general surgical unit.

This article describes a 22 year experience of a general surgical unit in the treatment of infantile hypertrophic pyloric stenosis (IHPS). The hospital course of 229 IHPS patients is reviewed. The male:female ratio was 3.6:1, median age 6 weeks (range 2-26 weeks) with a positive family history in 8.3%. The diagnosis of IHPS was established clinically by palpation of a "pyloric tumour" during a pre operative test meal/clinical examination in 92.6%; in the remainder, the diagnosis was made radiologically. Ramstedt's pyloromyotomy was performed within 5 days of admission in 74% of patients and within 10 days of admission in 89%. The median post-operative hospital stay was 10 days (range 3-60 days). Wound morbidity occurred in 10.0% wound infection (7.3%) and wound dehiscence (2.6%). However, wound morbidity was reduced in the second half of the series, partly by greater utililisation of non-absorbable suture in place of chromic catgut for wound closure. Mucosal penetration was suspected in 14.8% of cases. Repeat pyloromyotomy was necessary in 1.3%. One baby died (0.4%)- this was in the early part of the series and was directly attributable to fluid and electrolyte disorder. We conclude that Ramstedt's pyloromyotomy for infantile hypertrophic pyloric stenosis can be performed with acceptable morbidity and minimal mortality in a general surgical unit.

Spinal claudication versus arterial claudication.

Ninety-three consecutive treadmill exercise stress test were performed for the assessment of peripheral vascular function. Thirty-one were for atypical claudication-like symptoms including pain on standing, relief on sitting and back pain. Pedal pulses were palpable in 24 patients. Twenty-five patients (81%) had a negative stress test, suggesting a non-vascular aetiology and this finding was subsequently confirmed in 24 of the 25. The final diagnoses were spinal stenosis 13, [CT = 3, myelogram = 5, neurosurgeon opinion = 4, MRI = 1], myositis 2, restless leg syndrome 2 and osteoarthritis 7. Four patients had symptoms due to a combination of peripheral occlusive arterial disease and spinal stenosis; the latter was considered the predominant disorder in all four. Of the original 31 patients with atypical symptoms, spinal stenosis was present in 13 (42%). Atypia- in the common syndrome of intermittent claudication should alert the surgeon to the possibility of spinal canal disorders. Further investigation may identify significant pathology spinal stenosis in particular.

Institutional variation in hemotherapy for solid organ transplantation.

BACKGROUND: Solid organ allograft recipients may require large amounts of blood components. The modification of components to make them safer for iatrogenically immunosuppressed transplant patients increases workload demands on blood banks and transfusion services. STUDY DESIGN AND METHODS: Institutions within the United States and Canada providing hemotherapy as support for transplant recipients were surveyed for their transfusion practices. RESULTS: Responses from 25 institutions provide the data for this report. In 1991, the mean intraoperative red cell requirements ranged from <1 unit for renal allograft recipients to 17.3 units for liver transplant recipients. The latter group also required the greatest amounts of platelets, fresh-frozen plasma, and cryoprecipitate. More than 75 percent of responding institutions provided either cytomegalovirus-seronegative or white cell-reduced cellular components to pediatric recipients of liver allografts and to both adult and pediatric recipients of heart, lung, and heart-lung allografts. The use of irradiated cellular blood components, although uncommon, was greatest in heart transplant recipients. The use of pretransplantation transfusions for immunomodulation was generally limited to patients awaiting a living-donor renal transplant. CONCLUSION: Transfusion practices varied among the institutions, but the majority provide cytomegalovirus-safe cellular blood components to heart and lung allograft recipients and to pediatric transplant patients. Gamma-radiated cellular components are not routinely provided to patients undergoing solid organ transplantation. Liver allograft recipients require the greatest amount of hemotherapeutic support.

An exploratory study of the pattern of consent for autopsy in a regional hospital setting.

A prospective study of the pattern of responses to requests for autopsy in a general surgical unit was performed. Information on the characteristics of the deceased, of the requestee and of the requester was documented in the case of 66 patients who died while in hospital. Permission to perform autopsy was not requested in 39 out of 66 cases and this was the most frequent contributory factor to the low rate of autopsy. Once a decision to grant or refuse autopsy is made by relatives of the deceased, the decision is unlikely to be reversed. Permission to perform autopsy was more likely to be sought when the deceased was male than when deceased was female. The relatives of patients who had recently undergone surgery were more likely to refuse permission for autopsy than were those of patients who had not had recent surgery.