GGCX mutations in a patient with overlapping pseudoxanthoma elasticum/cutis laxa-like phenotype.

Pseudoxanthoma elasticum (PXE) is a multisystem disorder characterized by ectopic mineralization of connective tissues with primary manifestations in the skin, eyes and the cardiovascular system. The classic forms of PXE are caused by mutations in the ABCC6 gene encoding the ABCC6 protein, expressed primarily in the liver. Cutis laxa (CL) manifests with loose and sagging skin with loss of recoil. In 2009 we investigated a 19-year-old patient with overlapping cutaneous features of PXE and CL, together with alpha thalassaemia. Genetic analysis failed to identify pathogenic mutations in ABCC6. More recently we developed a gene-targeted panel of next-generation sequencing technology. This panel has 29 genes, 22 of which, including ABCC6 and GGCX, are associated with ectopic mineralization phenotypes. Mutation analysis in the patient identified two heterozygous GGCX mutations: c.200_201delTT in exon 2 and c.763G>A, p.V255M in exon 7. The GGCX gene encodes a γ-glutamyl carboxylase necessary for activation of blood coagulation factors in the liver. The p.V255M mutation was previously reported to result in reduced γ-glutamyl carboxylase activity in vitro, while the c.200_201delTT mutation is novel. Previous studies reported that mutations in GGCX cause overlapping PXE/CL skin phenotypes in association with or without multiple vitamin K-dependent coagulation factor deficiency. Our patient had loose redundant skin, moderate-to-severe angioid streaks and characteristic calcification of elastic structures in the mid dermis, consistent with PXE/CL overlap, but no coagulation abnormalities. Our studies expand the GGCX mutation landscape in patients with PXE-like phenotypes.

Performance of growing cattle grazing stockpiled Jesup tall fescue with varying endophyte status.

The objective of this study was to evaluate the performance of growing cattle when intensively grazing stockpiled endophyte-infected (E+), endophyte-free (E-), and nontoxic endophyte-infected (EN) tall fescue during the winter. The experiment was conducted over 5 consecutive winters. In each year, plots (1 ha each, 4 per treatment) were harvested for hay in August, fertilized in September, and forage was allowed to accumulate until grazing was initiated in early December. Each year, 48 Angus-cross tester cattle (4 per plot) were given a daily allotment of forage, under strip-grazing (frontal grazing) management, with a target residual height of 5 cm. Steers were used the first year, and heifers were used in subsequent years. The grazing periods for determination of pasture ADG were 86 d (yr 1), 70 d (yr 2), 86 d (yr 3), 72 d (yr 4), and 56 d (yr 5). Pasture ADG of cattle did not differ among treatments (P = 0.13) and were 0.51, 0.59, and 0.56 kg/d (SEM 0.03) for E+, E-, and EN, respectively. Serum prolactin concentrations of heifers grazing E+ were less (P < 0.05) than those grazing E- and EN during all years except yr 2. In yr 2, E+ and E- did not differ (P = 0.11). Serum prolactin of heifers grazing E- and EN did not differ (P > 0.20) except in yr 4. During yr 4, serum prolactin of heifers grazing E- was greater (P = 0.05) than that of heifers grazing EN. Serum urea-N concentrations (SUN) tended to differ among treatments (P = 0.10) and there was a treatment x year interaction (P = 0.05). During yr 1 through 3, SUN did not differ (P > 0.15) among treatments. However, as the stands aged, E- had a greater invasion of other plant species, which increased the CP content of the sward, thus causing heifers grazing E- during yr 5 to have greater (P < 0.01) SUN than heifers grazing E+ and EN, which did not differ (P = 0.89). Forage disappearance (DM basis) did not differ (P = 0.75) among treatments and was 4.7, 4.7, and 5.0 kg/animal daily (SEM 0.27) for E+, E-, and EN, respectively. Body weight gain per hectare was greater (P = 0.04) for E+ (257 kg) than for E- (220 kg) or EN (228 kg). In most years, animal grazing days on E+ were greater than those on E- or EN. However, in yr 5, animal grazing days did not differ (P > 0.20) among treatments. The use of stockpiled E+ as a source of low-cost winter feed is a viable option for producers, whereas grazing of EN may be more beneficial during the spring and fall, when more severe negative effects of ergot alkaloids have been observed.

Families of schizophrenics: a movement in jeopardy.

The family self-help movement in schizophrenia is in danger of losing its effectiveness, the authors believe. Many in the movement seem overly concerned with being accepted by professionals and others, which means that they become less single-minded in their advocacy for their relatives and for their own needs. Family groups are having difficulty maintaining their separate and unique identity and are including others who tend to undermine their efforts. The family movement in schizophrenia would do well to follow the example of the parents of the developmentally disabled in their unswerving devotion to their cause, which appears to be the key to their success in achieving greatly increased services and funding.

Schizophrenia through the eyes of families.

The authors contend that families of schizophrenics have received too little help from mental health professionals, even though in many cases families are the real primary care agents for long-term patients released from mental hospitals. They discuss some of the problems that occur in living with a long-term patient and describe mutual-support and advocacy groups that relatives have formed. They emphasize that mental health professionals can help families of schizophrenics by providing practical, realistic advice on how to deal with the illness, by offering empathy and support rather than placing blame, and by working to ensure that there are adequate treatment and rehabilitation services available.