Antiproliferative potential of sarcophine and its semisynthetic sulfur-containing derivatives against human mammary carcinoma cell lines

The marine-derived cembranoid sarcophine (1) and its sulfur-containing semisynthetic derivatives (2–6) were evaluated for anticancer potential using cell cycle progression markers. No effect on MCF-7 cell viability or apoptosis was seen with these derivatives at concentrations of up to 100 μM after 72 h of incubation. At 100 μM, sarcophine and its derivatives 2–5 arrested the MCF-7 cells in G0/G1 phase, with concomitant decrease in the cell populations at S and G2+M phases. MDA-MB-231 cells were not responsive to any of the derivatives. Our preliminary results suggest that the sulfur-containing derivatives of sarcophine, especially 2 and 3, show potent and cell-specific antiproliferative activity.     

Chronic granulomatous disease 100% corrected by displacement bone marrow transplantation from a volunteer unrelated donor

A boy whose chronic granulomatous disease (CGD) manifested in infancy, and whose elder brother had died at 7 years of age, had phagocytes with complete lack of functional cytochrome B-245 and which could not be induced by interferon gamma to achieve adequate staphylococcal killing. He underwent an elective displacement bone marrow transplant from a volunteer unrelated donor at the age of 8 months. This has achieved 100% replacement of the CGD granulocytes by those of the normal volunteer and the boy has since had a normal childhood for 3 years. Six previous transplants for CGD are briefly reviewed and illustrate that the host abnormal marrow must be completely displaced using an adequate dose of busulphan to ensure 100% stable engraftment of the donor's marrow and that this is best done under elective conditions before septic foci and irreversible organ damage have occurred. Criteria need to be developed to identify early those patients likely to have severe morbidity.     

Determinants of case fatality rates of meningococcal disease during outbreaks in Makkah, Saudi Arabia, 1987-97

We studied case-fatality rates (CFRs) among cases of meningococcal disease (MCD) admitted to Makkah (Saudi Arabia) hospitals during the period 1988-97. Of 483 cases, 431 (89.2%) were due to strains of serogroup A, 31 (6.4%) to serogroup W135, 16 (3.3%) to serogroup C, and 5 (10%) to serogroup B. Eighty-one patients died (case fatality rate (CFR)) 16.8%, 95% CI 13.5%, 20.4%). The CFR in infections due to serogroup A strains was 14.8%, and for other serogroups it was 32.7% (95% CI 20.3%, 47.1%). The CFR of MCD due to N. meningitidis serogroup A increased steadily with age (P<0.05). Seeking first medical help at a foreign Hajj medical mission and being treated in a non-specialized hospital were associated with a higher case fatality rate.     

Urinary trypsin inhibitor suppresses premature cervical ripening

Unknown signals from the fetus are thought to be involved in the onset of parturition. We recently discovered that urinary trypsin inhibitor (UTI) from fetal urine inhibits uterine muscle contraction. Objectives: The aim of this research was to elucidate the mechanism of action of UTI in suppressing cervical maturation. Study design: Non-pregnant and pregnant rabbits pretreated with and without UTI suppositories containing 1000 U (400 μg) for 3 days were treated for 2 days with vaginal suppositories containing 100 ng of interleukin-8 (IL-8). Results: IL-8 induced softening and dilatation of the rabbit cervices. In contrast UTI inhibited IL-8 induced cervical softening and dilatation. Water content, collagen content, neutrophil counts, elastase activity and collagenase activity of the cervix were increased by IL-8, but they did not increase by IL-8 with UTI. Conclusion: These results suggest that UTI inhibits cervical maturation induced by IL-8.     

Mortality in 504 infants weighing less than 1501 g at birth and treated in four neonatal intensive care units of South-Belgium between 1976 and 1980

Mortality was studied in 504 infants weighing less than 1501 g at birth and treated in four neonatal intensive care units of South-Belgium between 1976 and 1980. Two hundred and twenty-one babies died during their stay at the hospital, a mortality rate of 438 per 1000 live births. The neonatal mortality rate (mortality during the first 28 days of life) was 373 per 1000 live-births. Thirty-three infants died after the neonatal period, which is 15% of the total number of deaths. Twothirds of these post-neonatal deaths were related to complications of diseases associated with pre-term delivery. Mortality rates were higher in infants of less than 1001 g than in those of 1001–1250 g or 1251–1500 birth weight. In each birth weight category, patients born in their own obstetrical departments and referred infants had similar mortality rates. Longitudinal analysis showed improving mortality rates between 1976 and 1977 in the total population of VLBW infants, between 1977 and 1978 in infants of <1001 g and in 1980 compared to 1976 in the 1251–1500 g group. There were higher incidences of need for ventilatory assistance, patent ductus arteriosus, necrotising enterocolitis and septicaemia in referred patients of <1001 g than in patients born in their own obstetrical departments with comparable birth weight. Artification ventilation was more often required in referred infants of 1251–1500 g. This study confirms the importance of considering at least the complete hospital stay when analysing mortality in VLBW infants. Infants of <1001 g had high mortality, particularly after the neonatal period. This phenomenon was asscciated with complications of morbid conditions related to extreme prematurity.Abbreviations VLBW very low birth weight - PDA patent ductus areeriosus - NEC necrotising enterocolitis     

Gyrate atrophy of the choroid and retina: a case report

BACKGROUND: Gyrate atrophy of the retina and choroid is a rare disease, with recessive autosomal transmission, characterized by progressive chorioretinal atrophy causing blindness. It results from a congenital deficit in aminotransferase ornithine. Case report:The authors present the case of a young patient aged 15 years old consulting for a progressive fall of visual acuity with hemeralopia. Eye funduscopy showed regions of confluent rounded chorioretinal atrophy. The visual field, the electroretinogram and the retinal angiography were all alterated. Gyrate atrophy of the retina and choroid was evocated. DISCUSSION: It is a systemic and rare metabolic disease where ocular features are dominating. Differencial diagnosis are pigmentary retinopathies. Cataract and/or myopia are often joined to the retinal lesions. General signs could consist in muscular weakness, thin and rare hairs and mental retardation. More than; visual fields, electroretinogram, retinal angiography that are alterated; the plasmatic dosage of the ornithine is often high. The treatment is based on the dietetics with uncertain results. The genic therapy would be the treatment of future.     

Acquired oculomotor paralysis: a new therapeutic approach. Apropos of 10 cases

PURPOSE: The aim of this work is to report our rehabilitation scheme and outcome in patients with acquired oculomotor palsy. PATIENTS AND METHODS: We cared for 10 patients with oculomotor palsy between January 1996 and March 1998 at the Casablanca University Hospital. Our orthoptic rehabilitation scheme was based on reinforcing the patient's sensorial potential using a prism dioper and motor capacities by soliciting vergency and version movements. RESULTS: The 10 patients (7 males, 3 females, mean age 39.5 years) had unilateral IV palsy (n =3), bilateral IV palsy (n= 1), unilateral VI palsy (n= 2), bilateral VI palsy (n= 1), partial unilateral III palsy (n= 1) and dissociated bilateral III palsy (n= 2). Mean delay to initiation of rehabilitation was 49 days and mean duration for treatment was 3 months. We achieved total recovery in 50% of the cases and partial recovery in 40%. Intermittent diplopia persisted in 10 per thousand of the cases. These results differ slightly from those in the literature where total regression is reported in about 50% of the patients after therapeutic abstention. CONCLUSION: This small series is insufficient to validate our method. The results obtained do however show that rehabilitation is safe and should be applied more widely in patients with oculomotor palsy.     

Medulloepithelioma of the ciliary body. A case report

Medulloepithelioma of the ciliary body is an uncommon intraocular tumor occurring during the first year of life. Malignant degeneration may occur. We report the case of a 4-year-old child who presented medulloepithelioma of the left eye disclosed by oesotropia at 2 years of age. Clinically, there was oesotropia, positive light perception and cataract with vascular membrane spreading to the nasal side of the irido-corneal angle. CT scan and ultrasound B revealed a ciliary body tumor involving the sclera and orbital fat. After exenteration, the pathology study reported malignant medulloepithelioma of the ciliary body with scleral extension. No local recurrence or metastasis has been observed at 8 months follow-up. We discuss the clinical, radiological and therapeutic features of this uncommon tumor.     

ACCELERATED PAPER: Formation and accumulation of DNA ethenobases in adult Sprague-Dawley rats exposed to vinyl chloride

DNA ethenbases are promutagenic lesions formed by carcinogenssuch as vinyl chloride (VC). Their formation was investigatedin 9-week old, male Sprague-Dawley rats exposed to 500 p.p.m.VC by inhalation (4 h/day, 5 days/ week) for 1, 2, 4 or 8 weeksand in 7- and 14-week old, matched control animals. 1, N⁶Ethenoadenine(A) and 3, N⁴-ethenocytosine (eC) deoxyribonucleotides wereanalysed by immunoaffinity Purification and 32P-postlabelling.This postabelling method was compared with a radio-immunoassaymethod, which yielded similar results. Back-ground levels ofethenobases were found in DNA from the liver, lungs, kidneysand circulating lymphocytes of unexposed, control rats. In theliver, the following back-ground molar ratios of ethenobaseto parent base in DNA were detected (mean valuesx10–8):A/A, 0.04–0.05; C/C, 0.06–0.07. In the lungs, kidneysand circluating lympho-cytes, background levels of A and C rangedfrom 1.7 to 4.2x10–8 and from respectively. Followinga 5-day exposure to VC, a significant increase of A and D wasmeasured in hepatic DNA from rats sacrificed immediately aftertreatment. Further, a dose-dependent increase of both ethenoadducts was observed in liver DNA of VC-treated rats. Comparedto the 5-day exposure, 4-fold higher levels of A and C wereobserved in the liver of animals after 8 weeks of exposure.In contrast, there was an accumulation of C but not of A inlungs and kidneys. In circulating lymphocytes, no significantincrease of ethenobase levels above control values was observedafter 2 months of exposure to VC. Both etheno adducts were foundto be pesistent in liver DNA, after 2 months following the terminationof VC exposure. These results further support the notion thatDNA ethenogenesis. are critical lesions in VC-induced carcinogenesis.The possible contribution of lipid peroxidation products thatalso yield ethenobases, on the formation and persistence ofthese DNA adducts, remains to be clarified.