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.     

Open rhinoplasty for treatment of nasal tip haemangioma

Haemangiomas are the most common tumours of infancy. They typically proliferate then involute with considerable variation as regards to their rates of proliferation and involution. Haemangioma of the nasal tip is a lesion of special characteristics. During proliferation, it expands, contracts and deviates the nasal cartilages. Particularly, it regresses slowly and frequently involutes incompletely. That is why excision of the lesion is frequently suggested. The present study was conducted to evaluate open rhinoplasty after initial non-excision treatment modalities namely, intra-lesional corticosteroid injections and laser treatment, as a protocol of treatment for nasal tip haemangiomas. Twelve patients with nasal tip haemangiomas were included in the present study. Patients of both sexes, of different ages, with deep and mixed haemangiomas were studied. Disfigurement was the constant presenting symptom. Initial non-excision treatment reported different responses as denoted by the regression of the lesions’ size. Haemangiomas constantly extended between the medial crura of the alar cartilages as noted by the constant widening of the columella pre-operatively and the obvious separation of the nasal cartilages intra-operatively. This separation was constantly found to require approximation by sutures. The results of the present study concluded that whenever an early presentation with nasal tip haemangioma could be established, initial non-excision treatment followed by open rhinoplasty could be a useful protocol of treatment. Within the limitations of the present study, this protocol could achieve an early, safe and effective treatment for nasal tip haemangiomas with provisionally acceptable cosmetic outcomes so far.     

In vitro cytotoxicity and phototoxicity of N-piperazinyl quinolone derivatives with a 2-thienyl group.

We examined the cytotoxic potential of nine N-[2-substituted-2-(2-thienyl)ethyl] piperazinyl quinolone derivatives on human oral epithelial mouth carcinoma (KB) and human squamous carcinoma (A431) cell lines. Phototoxic properties of these compounds were also evaluated by mouse 3T3 fibroblast under ultraviolet-A (UVA) irradiation. The percent of cell viability was evaluated by MTT assay. Compound 6 having a 4-[2-(phenylmethoxyimino)-2-(2-thienyl)ethyl] group attached to N4 position of piperazine ring of enoxacin showed the highest cytotoxicity potential on both A431 and KB cell lines (IC50 of 3.11+/-0.52 and 4.91+/-1.94 microg/ml, respectively). While some of the other tested compounds exhibited clear phototoxic potential in 3T3 cell line, compound 6 showed only a minor potential of phototoxicity. These findings suggest the high potential of 4-[2-(phenylmethoxyimino)-2-(2-thienyl)ethyl] derivative of enoxacin as a cytotoxic compound with low potency of phototoxic reactions. The mentioned chemical was identified to be of special interest for further characterization.     

Intravenous magnesium sulphate effect on maternal serum and amniotic fluid cytokines levels in preterm labour patients.

Our objective was to evaluate the effect of intravenous magnesium sulphate administration to patients with preterm labour on maternal serum and amniotic fluid IL-1beta, IL-6, IL-10 and TNFalpha concentrations. Thirty-six patients at 24-34 weeks of singleton gestation, who presented with contractions (> or = 8 in 60 min) had amniocentesis to rule out intrauterine infection. The patients received intravenous MgSO4 for tocolysis. Twenty-six patients had amniocentesis performed before initiation of MgSO4 (controls) while 10 others had the procedure during tocolytic therapy (study patients). Magnesium, IL-1beta, IL-6, TNFalpha and IL-10 concentrations were measured. Study and control groups were statistically compared using Student t test. Mean magnesium levels were significantly higher in the study group (P < 0.01). There were no significant differences between the cytokines levels in maternal serum and in amniotic fluid between the groups. Our results suggest that the mechanism of magnesium as a tocolytic agent may not be mediated via the examined cytokines.     

Hypocholesterolemic effect of khellin and methoxsalen in male albino rats.

Khellin (CAS 82-02-0) and methoxsalen (CAS 298-81-7) were examined in male albino rats to evaluate their ability to modify serum lipoprotein cholesterol. Clinical chemistry parameters were also measured to obtain information indicative of possible drug toxicity. The drugs were evaluated in four-week double dose studies. After four weeks at 0.45 mg/100 mg b.wt. for khellin and 0.27 mg/100 g b.wt. for methoxsalen, per day, both drugs significantly lowered low density lipoprotein cholesterol, high density lipoprotein cholesterol and total cholesterol. Very low density lipoprotein cholesterol and triglycerides were not changed. No apparent toxicity was observed as clinical chemistry parameters and body weights were not different compared to control values. Similar results were observed with a lower dose of khellin (0.23 mg/100 g b.wt./d). A dose of 0.13 mg/100 g b.wt./d of methoxsalen had no observable effect in this study. Confirmation of the hypocholesterolemic activity of khellin and methoxsalen in this study enhances the therapeutic potential of these compounds against atherosclerosis.     

Comparative value of prostaglandin E1 and papaverine in treatment of erectile failure: double-blind crossover study among Egyptian patients.

In a double-blind, crossover designation penile intracavernous prostaglandin E1 and papaverine hydrochloride were compared in regard to effectiveness and safety in 52 patients investigated and treated for sexual erectile dysfunction. In evidence of the reliable effectiveness, prostaglandin E1 (20 micrograms/ml.) induced significant positive erectile response in 42 of 52 patients (81%). This rate reached 100% with neurogenic, hyperprolactinemic and/or psychogenic impotence. However, with papaverine hydrochloride (30 mg./ml.) and exclusively in cases of vasculogenic (most probably arteriogenic) impotence, negative erectile response was revealed as absent erection in 6 of 52 patients (11.5%) and nonrigid tumescence in 13 (25%) versus 2 (3.8%) and 8 (15.4%), respectively, with prostaglandin E1. Moreover, with prostaglandin E1 the regional pain was tolerable and transient, and the positive erectile response was not attended by priapism even in patients who formerly had priapism with papaverine hydrochloride. However, presently with prostaglandin E1 the relatively higher cost and shorter expiration period would probably limit its diagnostic and therapeutic use in Egypt, and probably in other developing countries.     

Direct toxic effect of iodide in excess on iodine-deficient thyroid glands: epithelial necrosis and inflammation associated with lipofuscin accumulation

Involution of thyroid hyperplasia (induced by a low iodine diet and a goitrogen, propylthiouracil, PTU) was obtained in mice by administering a high or a moderate dose of iodide (HID or MID, respectively). In HID involuting glands, vasoconstriction was observed after 12 hr whereas necrosis and inflammation were very abundant as early as after 6 hr and maximal after 48 hr. They were not prevented by papaverine by which vasoconstriction was inhibited, but were inhibited by the continuation of PTU by which iodide oxidation and organification were inhibited. Lipofuscin inclusions in thyroid and inflammatory cells were always associated with necrosis. On the contrary, when involution was induced by MID or by HID + triiodothyronine (T3), or by T3 alone, neither necrosis nor inflammation occurred and apoptosis was the only mode of cell deletion. No lipofuscin inclusion occurred. Our results demonstrate that iodide in excess, after being oxidized or organified, is directly toxic for iodine-deficient thyroid cells. The presence of lipofuscin suggests that its toxicity is mediated by lipid peroxidation, a consequence of production of free radicals in excess.     

Mechanism of fluconazole resistance in Candida albicans biofilms: phase-specific role of efflux pumps and membrane sterols

Candida albicans biofilms are formed through three distinct developmental phases and are associated with high fluconazole (FLU) resistance. In the present study, we used a set of isogenic Candida strains lacking one or more of the drug efflux pumps Cdr1p, Cdr2p, and Mdr1p to determine their role in FLU resistance of biofilms. Additionally, variation in sterol profile as a possible mechanism of drug resistance was investigated. Our results indicate that parent and mutant strains formed similar biofilms. However, biofilms formed by double and triple mutants were more susceptible to FLU at 6 h (MIC = 64 and 16 microg/ml, respectively) than the wild-type strain (MIC > 256 microg/ml). At later time points (12 and 48 h), all the strains became resistant to this azole (MIC > or = 256 microg/ml), indicating lack of involvement of efflux pumps in resistance at late stages of biofilm formation. Northern blot analyses revealed that Candida biofilms expressed CDR and MDR1 genes in all the developmental phases, while planktonic cells expressed these genes only at the 12- and 48-h time points. Functionality of efflux pumps was assayed by rhodamine (Rh123) efflux assays, which revealed significant differences in Rh123 retention between biofilm and planktonic cells at the early phase (P = 0.0006) but not at later stages (12 and 48 h). Sterol analyses showed that ergosterol levels were significantly decreased (P < 0.001) at intermediate and mature phases, compared to those in early-phase biofilms. These studies suggest that multicomponent, phase-specific mechanisms are operative in antifungal resistance of fungal biofilms.