Clinicopathological features of melanocytic skin lesions in Egypt.

Although melanocytic skin lesions have been recognized since antiquity, their literature was limited to Caucasians. To date, the clinicopathologic features of these lesions in Egyptians are still unknown. To define these features, diagnostic records of the melanocytic skin lesions received at the Pathology Department, Assuit University Hospitals (1989-2004) were reviewed. The lesions examined included 12 benign naevi (BN), 10 dysplastic naevi (DN), and 21 cutaneous malignant melanomas (CMMs). The DN and CMMs were more common in men than in women (2 : 1 and 1.5 : 1, respectively) while BN were more common in women (2 : 1). The average age incidence was 33+/-5, 38+/-7 and 54+/-3 years, for BN, DN and CMM, respectively. The lower limb (13/21, 62%), head and neck (7/21, 33%) were the most common sites for CMMs. The average size (mm) was 2+/-0.3, 4+/-0.6 and 21+/-0.3 for BN, DN and CMMs, respectively. Recurrence occurred in 10% of CMMs. Histologically, CMMs were of nodular type and composed of epithelioid (7/21, 33%), spindle cells (1/21, 5%), or mixed cells (13/21, 62%). The mean tumour thickness (Breslow) was 6+/-0.5 mm. CMMs included two of 21(9%), three of 21(14%), six of 21(38%), and 10 of 21(38%) with Clark level II, III, IV and V. In Egypt, CMM is the third most common cutaneous neoplasm following squamous and basal cell carcinomas. Compared with Western societies, melanoma has a male sex predilection, similar histological features but different topographical distribution and rare incidence. The striking difference from Western series is the incidence of nodular melanoma - in the West this represents 15-30% of melanomas, with superficial spreading being the majority. Another key difference from the West is the 'sun-bed' culture of the West and the desire to have suntans. This is the first study that reports the clinicopathologic features of melanocytic skin lesions in Egypt.     

Fontan completion without surgery.

OBJECTIVE: There are several modifications introduced in the preparation for a subsequent non-surgical transcatheter completion of the Fontan procedure. We report our experience with one type of the modification and the short-term results following its implementation. METHODS: During bidirectional cavopulmonary connection (BCPC) an intra-atrial lateral tunnel is additionally created, as intended for a Fontan procedure but fenestrated with a 10-14 mm aperture. The cardiac end of the superior vena cava (SVC) is then patched to maintain the physiology of BCPC. During the interventional transcatheter completion procedure, the SVC patch is perforated using radio-frequency (RF) energy, balloon-dilated, and stented as well. The aperture is closed with a device when required. Paired t-test was used to compare data before and after the Fontan completion. RESULTS: From June 2003 to February 2006, 16 patients (9 boys and 7 girls, mean age 12 months) underwent the surgical procedure described. The mean bypass time was 137 min and the mean ischemic time was 77 min. There were no operative deaths. One patient with bilateral SVC required a take down due to recurrent effusions. Ten months later, nine patients underwent completion (mean age 20 months, mean weight 10.6 kg). The stents were dilated to a mean diameter of 14.4mm. All except one aperture was closed with a device. The mean fluoroscopy time was 41 min. Oxygen saturation increased from 85 to 94% (p=0.001). Pulmonary artery pressures remained normal (16 mmHg before and 19 mmHg after, p=0.12). No patients required mechanical ventilation and none developed pleural effusions or arrhythmias. All were discharged from hospital within 6 days of the Fontan completion. Twenty-two months after Fontan, all were well. Echocardiography revealed no gradients across the stents. Two patients had minor leaks across the aperture. One underwent further stent dilatation a year later. CONCLUSIONS: Fontan completion without surgery is suitable in patients with single ventricles with lower mortality and morbidity, avoids multiple surgical interventions while maintaining the staged approach and allows for successive dilatation of the Fontan pathway to accommodate for growth.     

Morbidity, mortality, and long-term survival after sleeve lobectomy for non-small cell lung cancer.

OBJECTIVE: Sleeve lobectomy is a widely accepted procedure for central tumors for which the alternative is pneumonectomy. The purpose of this study is to assess operative mortality, morbidity, and long-term results of sleeve lobectomies performed for non-small cell lung carcinoma (NSCLC). METHODS: A retrospective review of 218 patients who underwent sleeve lobectomy for NSCLC between 1981 and 2005 was undertaken. There were 186 (85%) men and 32 women with a mean age of 61.9 years (range, 19-82 years). Eighty patients (36.6%) had a preoperative contraindication to pneumonectomy. Right upper lobectomy was the most common operation (45.4%). Vascular sleeve resection was performed in 28 patients (12.8%) and was commonly associated with left upper lobectomy (n=20; 9.1%; p=0.0001). The histologic type was predominantly squamous cell carcinoma (n=164; 75%), followed by adenocarcinoma (n=46; 21%). Resection was incomplete in nine (4.1%) patients. RESULTS: There were nine operative deaths; the operative mortality and the morbidity rates were 4.1% and 22.9%, respectively. A total of 14 (6.4%) patients presented with bronchial anastomotic complications: two were fatal postoperatively, seven patients required reoperation, three required a stent insertion, and two were managed conservatively. Multivariate analysis showed that compromised patients (p=0.001), current smoking (p=0.01), right sided resections (p=0.003), bilobectomy (p=0.03), squamous cell carcinoma (p=0.03), and presence of N1 or N2 disease (p=0.01) were risk factors for mortality and morbidity. Follow-up was complete in 208 patients (95.4%). Overall 5-year and 10-year survival rates were 53% and 28.6%, respectively. After complete resection, recurrence was local in 10 patients, mediastinal in 20, and distant in 25. By multivariate analysis, two factors significantly and independently influenced survival: nodal status (N0-N1 vs N2; p=0.01) and the stage of the lung cancer (stage I-II vs III, p=0.02). CONCLUSIONS: For patients with NSCLC, sleeve lobectomy achieves local tumor control, even in patients with preoperative contraindication to pneumonectomy and is associated with low mortality and bronchial anastomotic complication rates. Postoperative complications are higher in compromised patients, smokers, N disease, right sided resections, bilobectomies, and squamous cell cancers. The presence of N2 disease and stage III significantly worsen the prognosis.     

Assessment of sublingual immunotherapy efficacy in children with house dust mite-induced allergic asthma optimally controlled by pharmacologic treatment and mite-avoidance measures

Although several studies have demonstrated the efficacy of subcutaneous immunotherapy in allergic asthma, few have shown the same benefit using sublingual immunotherapy (SLIT) in asthmatic patients. This study was conducted to assess the efficacy of house dust mite (HDM) SLIT in addition to allergen avoidance and standard pharmacologic treatment. A double-blind, placebo-controlled trial was performed in 111 children (aged 5-15 yr) with HDM-induced mild-to-moderate asthma. After a 4-week baseline phase, patients were randomly assigned to receive SLIT with tablets of HDM extract (n = 55) or placebo (n = 56) for 18 months. Pharmacologic treatment was adjusted every 3 months following a step-down approach. Asthma symptom scores, reduction in use of inhaled corticosteroids and inhaled beta(2)-agonists, rhinitis symptoms, lung function tests, skin sensitivity to HDM, dust mite-specific immunoglobulin (Ig) E and IgG(4), and quality of life (QoL) were assessed during the study. After 18 months of treatment, diurnal and nocturnal asthma symptoms scores did not show significant differences between SLIT and placebo groups. Inhaled corticosteroids and inhaled beta(2)-agonists use was reduced in both groups without significant differences between groups. There were no significant differences in lung function (forced expiratory volume in 1 s and peak flow rate variations) between groups. Rhinitis symptom score decreased in both groups, with no difference between the two groups. The severity dimension of QoL was significantly improved in the SLIT group (age 6-12 yr). SLIT induced a significant reduction of skin sensitivity to HDM (p < 0.01) and a significant increase in HDM-specific IgE and IgG(4) antibodies (p < 0.001) in the SLIT group compared with the placebo group. SLIT was well tolerated with mild/moderate local adverse events. No severe systemic reactions were reported. This study indicates that, when mild-moderate asthmatic children are optimally controlled by pharmacologic treatment and HDM avoidance, SLIT does not provide additional benefit, despite a significant reduction in allergic response to HDM. Under such conditions, only a complete, but ethically unfeasible, discontinuation of inhaled corticosteroid would have demonstrated a possible benefit of SLIT.     

Extracardiac Right Atrium-to-Right Ventricle Homograft for Uncorrectable Tricuspid Valve Disease

Surgically uncorrectable tricuspid valve disease in children is rare. However, when it happens the surgical options are very limited. Tricuspid valve replacement using a mechanical valve or stented bioprosthesis is impractical. Use of homografts in the “anatomic position” has its limitations. We report here the use of an extracardiac homograft connection between the right atrium and right ventricle in a 16-month-old boy in whom severe tricuspid valve stenosis developed after surgical repair of a complex ventricular septal defect associated with dextrocardia and anomalous systemic venous drainage. The patient remains well receiving no cardiac medication 12 months after the procedure.     

Factors affecting early and long-term outcomes after completion pneumonectomy

Objective: To identify factors that affect operative mortality and morbidity and long-term survival after completion pneumonectomy. Methods: We retrospectively reviewed the charts of consecutive patients who underwent completion pneumonectomy at our cardiothoracic surgery department from January 1996 to December 2005. Results: We identified 69 patients, who accounted for 17.8% of all pneumonectomies during the study period; 22 had benign disease and 47 malignant disease (second primary lung cancer, n = 19; local recurrence, n = 17; or metastasis, n = 11). There were 50 males and 19 females with a mean age of 60 years (range, 29–80 years). Postoperative mortality was 12% and postoperative morbidity 41%. Factors associated with postoperative mortality included obesity (p = 0.005), coronary artery disease (p = 0.03), removal of the right lung (p = 0.02), advanced age (p = 0.02), and renal failure (p < 0.0001). Preoperative renal failure was the only significant risk factor for mortality by multivariate analysis (p = 0.036). Bronchopleural fistula developed in seven patients (10%), with risk factors being removal of the right lung (p = 0.04) and mechanical stump closure (p = 0.03). Overall survival was 65% after 3 years and 46% after 5 years. Long-term survival was not affected by the reason for completion pneumonectomy. Conclusion: Although long-term survival was acceptable, postoperative mortality and morbidity rates remained high, confirming the reputation of completion pneumonectomy as a challenging procedure. Significant comorbidities and removal of the right lung were the main risk factors for postoperative mortality. Improved patient selection and better management of preoperative renal failure may improve the postoperative outcomes of this procedure, which offers a chance for prolonged survival.     

Stimulation of cortical acetylcholine release by orexin A

The basal forebrain cholinergic system is a critical component of the neurobiological substrates underlying attentional function. Orexin neurons are important for arousal and maintenance of wakefulness and are found in the area of the hypothalamus previously shown to project to the basal forebrain. We used dual-probe in vivo microdialysis in rats to test the hypothesis that orexin A (OxA) increases cortical acetylcholine (ACh) release. Intrabasalis administration of OxA (0, 0.1, 10.0 microM via reverse dialysis) dose-dependently increased ACh release within the prefrontal cortex (PFC). In a separate group of animals, local (intra-PFC) administration of OxA via reverse dialysis was found to have no significant effect on ACh release. In order to obtain anatomical corroboration of the basal forebrain as a site of orexin modulation of corticopetal cholinergic activity, we used immunohistochemistry to examine the relationship between orexin fibers and cholinergic neurons in the basal forebrain. We observed widespread distribution of orexin-immunoreactive fibers in cholinergic regions of the basal forebrain, particularly in more rostral areas where frequent instances of apparent appositional contact were observed between orexin fibers and choline acetyltransferase-positive cell bodies. Collectively, these data suggest that orexin projections to the basal forebrain form an important link between hypothalamic arousal and forebrain attentional systems.     

The significance of 'anti-HBc only' in the clinical virology laboratory.

BACKGROUND: Isolated detection of hepatitis B core antibody (anti-HBc) in the absence of surface antigen (HBsAg) or antibody (anti-HBs) has been reported, particularly among individuals infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). The significance of this phenomenon is unknown and it is unclear whether all individuals with such serological pattern need further molecular investigations. OBJECTIVES: To determine the prevalence of 'anti-HBc only' in samples referred to a clinical virology laboratory and to evaluate its significance and possible mechanisms. STUDY DESIGN: Samples identified as anti-HBc positive (389/4359, 8.9%) during an 11-month period were investigated for HBsAg, anti-HBs, anti-HCV and anti-HIV. 'Anti-HBc only' samples were tested for HBV DNA using a nested qualitative PCR. Viral loads were measured in samples with detectable HBV DNA and the DNA sequences were analysed. RESULTS: Of 379 samples with detectable anti-HBc, 155 (40.9%) were 'anti-HBc only'. HBV DNA was detected in 6/151 (4%), all of which had a viral load <400 copies per ml. Anti-HIV was found in 50/151 (33.1%) and anti-HCV in 14/151 (9.3%). Of these, only one of the HIV infected patients had detectable HBV DNA. Phylogenetic analysis of the HBV surface gene from three patients showed a variety of genotypes (A, E and G). One sequence had a mutation in codon 144, which has previously been reported to give false negative HBsAg results. CONCLUSIONS: 'Anti-HBc only' is a common phenomenon in the clinical virology laboratory but only a small proportion of samples had detectable HBV DNA. The presence of HBsAg mutants with possible false negative HBsAg test result is of concern. Samples with 'anti-HBc only' could be used to monitor the emergence of these mutants.     

Safety of various dosage regimens during induction of sublingual immunotherapy. A preliminary study

BACKGROUND: Sublingual immunotherapy (SLIT) has been demonstrated to be a viable alternative to injection immunotherapy. Administration of high doses of allergens to ensure efficacy has been shown to be well tolerated. The aim of the present study was the first step to address the issue of fast-induction regimens using various induction SLIT regimens in paediatric and adult patients. METHODS: Sixty-four patients (age range 5-46 years) with grass pollen rhinoconjunctivitis were enrolled in an 8-month double-blind, placebo-controlled trial of SLIT. Sixty-three patients were randomized to four groups and evaluated at the end of the study. One group received placebo (n = 16) and the other three groups (n = 47) received five grass pollen extracts according to three different induction regimens: regimen 1 starting with 3 IR tablets (n = 15), regimen 2 starting with 10 IR (n = 16) and regimen 3 starting with 30 IR (n = 16). The maintenance phase was made with sublingual-swallow drops at the same concentration of 300 IR/ml for all the patients. Adverse events were recorded on diary cards. RESULTS: During induction phase, 25/47 patients in the SLIT groups had adverse reactions in comparison to 2/16 patients in the placebo group (p < 0.05). The rate of adverse reactions was 33.3% (11.8-61.6) (95% CI) for regimen 1, 31.3% (11.0-58.7) for regimen 2, 43.8% (19.8-70.1) for regimen 3 and 12.5% (1.6-38.3) for placebo. Fifty-seven reactions were local reactions involving the oral region (54 SLIT, 3 placebo) and 13 were systemic reactions (all in the SLIT groups). 11/13 reactions were mild (gastrointestinal disorders, rhinoconjunctivitis), 1/13 consisted of moderate asthma and 1/13 consisted of severe abdominal pain. No urticaria, angioedema or life-threatening events were observed. CONCLUSIONS: These preliminary data showed that various induction regimens for SLIT are generally well tolerated and could allow a fast build-up phase of SLIT.