Autosomal recessive juvenile parkinsonism (AR-JP, PARK2; OMIM 602544), one of the monogenic forms of Parkinson's disease (PD), was initially described in Japan. It is characterized by early onset (before age 40), marked response to levodopa treatment and levodopa-induced dyskinesias. The gene responsible for AR-JP was recently identified and designated parkin. We have analysed the 12 coding exons of the parkin gene in 35 mostly European families with early onset autosomal recessive parkinsonism. In one family, a homozygous deletion of exon 4 could be demonstrated. By direct sequencing of the exons in the index patients of the remaining 34 families, eight previously undescribed point mutations (homozygous or heterozygous) were detected in eight families that included 20 patients. The mutations segregated with the disease in the families and were not detected on 110-166 control chromosomes. Four mutations caused truncation of the parkin protein. Three were frameshifts (202-203delAG, 255delA and 321-322insGT) and one a nonsense mutation (Trp453Stop). The other four were missense mutations (Lys161Asn, Arg256Cys, Arg275Trp and Thr415Asn) that probably affect amino acids that are important for the function of the parkin protein, since they result in the same phenotype as truncating mutations or homozygous exon deletions. Mean age at onset was 38 +/- 12 years, but onset up to age 58 was observed. Mutations in the parkin gene are therefore not invariably associated with early onset parkinsonism. In many patients, the phenotype is indistinguishable from that of idiopathic PD. This study has shown that a wide variety of different mutations in the parkin gene are a common cause of autosomal recessive parkinsonism in Europe and that different types of point mutations seem to be more frequently responsible for the disease phenotype than are deletions.

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A field experiment of novel systematic design was established on 17 sites in the three years 1988-90 to compare the effect of spray timing on the disease control provided by fungicides. At each site one set of plots received applications of a mixture of fenpropimorph and prochloraz or triadimenol, tridemorph and chlorothalonil fungicides, applied at successively later start dates to produce a series of temporally and spatially related, but discrete, epidemics curtailed at consecutively later stages of development between GS32 and GS75. A second set of plots was treated with a single spray of one of a set of the nine candidate fungicides between GS32 and GS71. Disease developed at each site, with moderate septoria leaf spot (Septoria tritici) at five of the eight sites in 1988 and four of the seven sites in 1989. Erysiphe graminis f.sp. tritici was present at two sites in 1988, four sites in 1989 and one site only in 1990. Puccinia striiformis (four sites only in 1989 and 1990) and brown rust (one site in each year) were less common. The systematic treatments showed consistent relationships between green leaf retention during grain filling and yield. They also provided clear indications that epidemics of foliar disease initiated before flag leaf emergence had the greatest impact on yield. After this stage, yield loss averaged 27·2 kg ha ¹1 for each day that elapsed before fungicide was applied. The sequential single spray treatments showed marked differences between the protectant and eradicant activity of the different fungicides used. Each disease was most effectively controlled on the final leaf by treatment at or immediately after its emergence. Chlorothalonil was as effective as any of the fungicides tested against septoria, when applied before flag leaf emergence, but was inferior when applied after this stage. The fungicides were equally effective against yellow rust when applied just before symptoms were detected, when spray timing appeared to be more important than choice of fungicide. The response of brown rust to fungicides was similar, except that chlorothalonil was the least effective. For mildew, timing seemed to be less important, although sprays applied immediately after leaf emergence provided the best control on each individual leaf layer. Yield was well related to disease and green leaf area late in the season, these factors being more important than which disease was present, which fungicide, and which cultivar were used.

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Two studies carried out in 1982 and 1993 in the city of Pelotas, Southern Brazil, provide a unique opportunity for assessing the impact on maternal and child health of the economic and health care changes, which took place in Brazil in this period. The cohorts of mothers and infants of 1982 and 1993 were studied from the time of delivery. In both years, all mothers identified in the city's maternity hospitals answered a standardised questionnaire and their infants were examined. Over 99% of all children born in the city in each of the 2 years were included in the cohorts. Deaths occurring among these children were monitored prospectively, as well as all hospital admissions in the 1993 cohort. In the 1982 study, attempts were made to locate a 25% sample of the children at the mean age of 12 months using the addresses collected at the hospital (82% of the children were located), and all of the cohort children at the mean age of 20 months and 42 months, through a city census (87% were located in both follow-ups). In the 1993 study, 20% of all children plus all low birthweight infants were sought at 12 months of age, using the addresses collected at the hospital, and 95% were successfully traced. There was a 12% fall in the number of births occurring in 1993 (5,304 births), in comparison with 1982 (6,011 births), in spite of the increase in the population of reproductive age in the city during the decade. There was a marked difference in maternal height and weight at the beginning of pregnancy, with women giving birth in 1993 being, on average, 3.4 cm taller and 2.5 kg heavier than those who gave birth in 1982. The proportion of preterm babies (<37 weeks), measured by the date of last menstrual period, increased from 5.6% in 1982 to 7.5% in 1993. The median duration of breast feeding increased from 3.1 months in 1982 to 4.0 months in 1993. At 12 months of age, the prevalence of deficit of weight for age decreased from 5.4% in 1982 to 3.7% in 1993. The prevalence of deficit of height for age, however, increased from 5.3% to 6.1%. The perinatal mortality rate dropped 31%, from 32.2 per 1,000 births in 1982 to 22.1 deaths per 1,000 births in 1993. There was also a marked reduction in the infant mortality rate, from 36.4 per 1,000 livebirths in 1982 to 21.1 per 1,000 livebirths in 1993. The findings of the study indicate that there were improvements in the decade for most of the indicators evaluated, with the exception of birthweight and gestational age. It appears that improvements in perinatal and infant mortality rates are largely due to improvements in the health care sector.

Vaughan MM, Evans BD, Weitzer MJ. Survival of patients with primary fallopian tube carcinoma. Int J Gynecol Cancer 1998; 8: 16-22. Thirty-seven patients with primary fallopian tube carcinoma (PFTC) presenting between 1952 and 1995 were studied. The mean age was 57 years. Seven patients had stage I disease, 20 stage II, 8 stage III, and 2 stage IV. Actuarial 5-year survivals were 73% for stage I, 33% for stage II and 0% for stage III. Stage was a significant predictor of survival at 5 years (Stage I vs. III, P = 0.0006; stage II vs. III, P = 0.0001), however, the majority of patients, even with early stage disease, died of progressive PFTC within 10 years. Grade appeared highly significant at 5 and 10 years (Grades 1 & 2 vs. 3, P = 0. 0023). Neither age nor lymphocytic infiltrate appeared definitely predictive of survival. Eleven of 22 stage II patients received adjuvant treatment. While their median and 5-year survivals were superior to those not receiving adjuvant treatment (51 vs. 30 months, 47% vs. 22%), the difference was not statistically significant. This retrospective analysis confirms the poor prognosis of patients with PFTC. The majority of patients, even with early stage tumors, eventually succumb to their disease. Larger studies may identify a group of patients potentially curable with surgery alone, and clarify the role of adjuvant therapy.

Combinatorial phage display technology offers a new possibility for making human antibodies which could be used in immune therapy. We explored the use of this technology to make human scFvs specific for crotoxin, the main toxic component of the venom of the South-American rattlesnake Crotalus durissus terrificus. Crotoxin, a phospholipase A2 neurotoxin constituted by the association of two subunits, exerts its lethal action by blocking neuromuscular transmission. This is the first report of human anticrotoxin scFvs (scFv 1, scFv 6 and scFv 8) isolated from a naive library of more than 1010 scFv clones with in vivo neutralizing activity. Nevertheless, differences are observed at the level of biological and immunological effects. Only scFv 8 is able to reduce the myotoxicity induced by crotoxin and scFv 1 is capable of altering the in vitro enzymatic activity of this toxin. All three scFvs recognize a region of one subunit located at the junction with the other one. Moreover these scFvs share strong amino acid homologies at the level of either the heavy or the light chain. Taken together, our results suggest that the use of human anticrotoxin scFvs may lead to a new and less aggressive passive immune therapy against poisoning by the venom of Crotalus durissus terrificus.