Chorioretinal neovascular membranes complicating contusional eye injuries with indirect choroidal ruptures.

Chorioretinal neovascular membranes are a recognised but rare cause of late visual loss in eyes suffering contusional injuries. A series of eight cases is presented all with indirect choroidal ruptures involving the perifoveal region. Two main patterns of 'at risk' rupture were noted: a temporally situated rupture passing almost directly through the fovea, and a rupture which curves inferior or superior to the optic disc stopping just short of the fovea. In six of eight cases there was only a partial thickness rupture of the choroid. These neovascular membranes may present at any time after the original injury, either early (within six months of the injury), which could be related to persistence of the normal reparative neovascular response, or late (at least one year after the injury), which are more likely to have resulted from a secondary breakdown of the outer blood-retina barrier.     

Subcortical white matter lesions in osmotic demyelination syndrome.

We describe a case of histologically proved osmotic demyelination syndrome. In addition to abnormal T2 signal within the pons and thalami, MR showed linear enhancing lesions at the cortical medullary junction.     

Inter-NICU variation in rates and management of thrombocytopenia among very low birth-weight infants.

OBJECTIVES: To investigate variation among neonatal intensive care units (NICUs) in prevalence and management of thrombocytopenia in infants <1500 g. STUDY DESIGN: In total 1283 infants &<1500 g admitted to six NICUs over 21 months were prospectively analyzed. Illness severity was measured by the Score for Neonatal Acute Physiology (SNAP). Platelet counts in the first 12 hours after birth and on day 3 of life were abstracted from the infants' medical records. Thrombocytopenia was determined from the lowest platelet count in each of these time periods. RESULTS: There was variability in rates of thrombocytopenia among NICUs, even after controlling for risk factors (e.g., SNAP, small for gestational (SGA) age and maternal hypertension). One site had a high prevalence of thrombocytopenia, but the lowest percentage of infants with thrombocytopenia who received platelet transfusions. After controlling for SNAP, GA, SGA, Apgar score and incidence of thrombocytopenia, the odds of receiving platelets at this site, relative to the site with the highest transfusion rate, was 0.10 (95% CI 0.02 to 0.43). CONCLUSIONS: This multicenter study finds a 10-fold variation among NICU in the administration of platelets to their thrombocytopenic infants that cannot be explained by presence of thrombocytopenia or illness severity.     

Novel therapeutic approaches for multiple myeloma

Summary: Multiple myeloma (MM) affects 15 000 new patients annually in the US, with 50 000 total patients, and remains incurable. Our preliminary in vitro and animal studies suggest a role for MM–host interactions in regulating MM cell growth, drug resistance, and migration in the bone marrow. Importantly, treatment strategies which target mechanisms whereby MM cells grow and survive in the bone marrow, including thalidomide and its potent immunomodulatory derivatives and proteasome inhibitor PS‐341, can overcome classical drug resistance in preclinical and early clinical studies.     

Cultured human granulosa cells as a model for corpus luteum function: relative roles of gonadotrophin and low density lipoprotein studied under defined culture conditions.

In primates, corpus luteum development involves both gonadotrophin stimulation and exposure to low density lipoprotein (LDL) delivered through vascularization of the granulosa cell-derived layer. These regulatory influences were modelled in vitro using granulosa cells obtained during in-vitro fertilization (IVF) cycles controlled with gonadotrophin releasing hormone (GnRH) analogue, human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG). Granulosa cells were cultured in defined medium on extracellular matrix. Without gonadotrophin or LDL in the medium, progesterone production declined progressively. With LDL alone, there was a short-lived elevation of progesterone output which subsequently declined. Culture with HCG alone resulted in a relatively unchanged rate of steroid production over 5 days despite morphological development. This contrasted with a marked and sustained increase in progesterone output over the same time when granulosa cells were cultured with combined HCG/LDL. Cultures were challenged with combined HCG/LDL on day 5. Where initial incubation included HCG, the challenge resulted in a recovery of progesterone output to values comparable to those of granulosa cells exposed to continuous HCG/LDL. Initial incubation without gonadotrophin led to a reduced response. Results suggest that LDL delivery to granulosa cells of the early corpus luteum causes a short-lived period of progesterone production. Sustained luteinization of granulosa cells and maintenance of gonadotrophin responsiveness requires continued exposure to gonadotrophin in the luteal phase.     

Serum IgG and IgM levels in new and regular long-term plasmapheresis donors.

This Australian study monitored the effects of monthly plasmapheresis on donor serum IgG and IgM levels in 127 new and 124 established plasma donors who donated 1014 units over a five-month period. Of the 251 donors, 3% had reduced total serum protein (TSP) levels, 7% had low IgG levels and 12% had low IgM levels prior to donation on at least one occasion over the study period. Statistical analysis showed that the TSP, IgG and IgM levels of new donors who had donated plasma on less than 10 occasions were no more likely to fall below normal than those of old donors. However, new and old donors whose IgG or IgM levels fell below normal at any time during the study had significantly lower levels of the relevant parameter on entry to the study. Followed longitudinally, IgG and IgM levels in old and new donors tended to fall, although levels fluctuated throughout the study. Statistical analysis failed to show any correlation between TSP levels and IgG or IgM levels. These parameters did not correlate significantly with the number of previous plasmaphereses, donor weight, volume collected or history of infection. This study highlighted the need for regular, specific quantitation of IgG and IgM levels as well as TSP in regular plasmapheresis donors. The frequency of testing is yet to be determined, in view of the high materials and labour costs of such a programme.     

Tubulin and microtubules in cochlear hair cells: comparative immunocytochemistry and ultrastructure

The distribution of tubulin has been investigated in surface preparations of the guinea pig organ of Corti using indirect immunofluorescence microscopy. Two different monoclonal antibodies to tubulin produce similar distinct patterns of labelling in hair cells. Labelling is greater in inner hair cells than outer hair cells. It occurs in rings around the cell apex, and in a meshwork below and channels through, the cuticular plate. In outer hair cells from the apical region of the cochlea, labelling occurs around the location of a basalward protrusion of the cuticular plate. These patterns correlate with the location of microtubules observed using transmission electron microscopy. A large patch of labelling occurs on the strial side of the cell corresponding to the largest channel through the cuticular plate and the kinociliary basal body. Strands of labelling are seen running parallel to the long axis of the cell between the subcuticular and synaptic region. Many more of these strands are seen in the inner hair cell than the outer hair cell and may correspond to tracks of microtubules transporting neurotransmitter vesicles or other organelles. In outer hair cells, intense labelling and many microtubules are seen in the subnuclear region. The possible roles of the different microtubule arrangements are discussed.     

The first t-test

The data with which Student illustrated the application of his famous distribution are examined from a number of aspects. Central to the discussion is the within-patient clinical trial at Kalamazoo whose results were published by Cushny and Peebles and misquoted by Student and Fisher. This trial is discussed from historical, pharmacological and statistical perspectives. Student's and Fisher's analyses and a more modern analysis by Preece are considered as is Cushny's and Peebles's interpretation. Brief biographies of the five physicians involved in running the trial are presented.