Effects of treatment on fertility in long-term survivors of childhood or adolescent cancer

In a retrospective cohort study of survivors of cancer and of controls, we estimated the risk of infertility after treatment for cancer during childhood or adolescence. We interviewed 2283 long-term survivors of childhood or adolescent cancer diagnosed in the period from 1945 through 1975, who were identified at five cancer centers in the United States. Requirements for admission to the study were diagnosis before the age of 20, survival for at least five years, and attainment of the age of 21. In addition, 3270 controls selected from among the survivors' siblings were interviewed. Cox regression analysis showed that cancer survivors who married and were presumed to be at risk of pregnancy were less likely than their sibling controls to have ever begun a pregnancy (relative fertility, 0.85; 95 percent confidence interval, 0.78 to 0.92). Radiation therapy directed below the diaphragm depressed fertility in both sexes by about 25 percent. Chemotherapy with alkylating agents, with or without radiation to sites below the diaphragm, was associated with a fertility deficit of about 60 percent in the men. Among the women, there was no apparent effect of alkylating-agent therapy administered alone (relative fertility, 1.02) and only a moderate fertility deficit when alkylating-agent therapy was combined with radiation below the diaphragm (relative fertility, 0.81). Relative fertility in the survivors varied considerably according to sex, site of cancer, and type of treatment; these factors should be taken into consideration in counseling survivors about the long-term consequences of disease.     

Paternal mosaicism for a novel PBX1 mutation associated with recurrent perinatal death: Phenotypic expansion of the PBX1‐related syndrome

Autosomal dominant (de novo) mutations in PBX1 are known to cause congenital abnormalities of the kidney and urinary tract (CAKUT), with or without extra‐renal abnormalities. Using trio exome sequencing, we identified a PBX1 p.(Arg107Trp) mutation in a deceased one‐day‐old neonate presenting with CAKUT, asplenia, and severe bilateral diaphragmatic thinning and eventration. Further investigation by droplet digital PCR revealed that the mutation had occurred post‐zygotically in the father, with different variant allele frequencies of the mosaic PBX1 mutation in blood (10%) and sperm (20%). Interestingly, the father had subclinical hydronephrosis in childhood. With an expected recurrence risk of one in five, chorionic villus sampling and prenatal diagnosis for the PBX1 mutation identified recurrence in a subsequent pregnancy. The family opted to continue the pregnancy and the second affected sibling was stillborn at 35 weeks, presenting with similar severe bilateral diaphragmatic eventration, microsplenia, and complete sex reversal (46, XY female). This study highlights the importance of follow‐up studies for presumed de novo and low‐level mosaic variants and broadens the phenotypic spectrum of developmental abnormalities caused by PBX1 mutations.     

Mechanoafferent neurons innervating tail of Aplysia. I. Response properties and synaptic connections

Mechanical, chemical, or electrical stimulation of the tail elicits a short-latency (less than 1 s) tail-withdrawal reflex that is graded with the intensity of the stimulus. The tail-withdrawal reflex is not elicited by stimulation of parts of the body outside of the tail region. Mechanoafferent neurons innervating the tail are located in a small subcluster within a large, homogeneous group of medium-size (40-80 micron) cells on the ventrocaudal (VC) surface of each pleural ganglion. The tail sensory neurons within this large VC cluster are activated by tactile pressure or by electrical stimulation of discrete regions of the tail. They adapt slowly to maintained stimulation and sometimes respond to stimulus offset as well. Both mechanical and electrical stimuli produce responses that are graded with the intensity of the stimulus. Cells in the VC cluster appear to be primary mechanoreceptors because they have axons in peripheral nerves (including nerves innervating the tail), they exhibit action potentials lacking prepotentials in response to tactile stimulation, and these action potentials are still produced by cutaneous stimulation when peripheral and central chemical synaptic transmission is blocked. Stimulation of fields all over the body surface evokes synaptically mediated hyperpolarizing responses in individual mechanoafferent neurons that may represent afferent inhibition. Hyperpolarizing responses lasting many seconds can be produced by brief cutaneous stimuli. The mechanoafferent neurons innervating the tail region make strong monosynaptic connections to tail motor neurons in the ipsilateral pedal ganglion, and through these connections this subpopulation of the VC neurons appears to make a substantial contribution to the short-latency tail-withdrawal reflex. In addition, the combined excitatory receptive fields of these mechanoafferents match the excitatory receptive field of the tail-withdrawal reflex. Mechanoafferent neurons in the VC cluster that have receptive fields on other parts of the body (outside the excitatory receptive field of the tail-withdrawal reflex) have not been observed to make monosynaptic connections to the tail motor neurons. The neurons innervating the tail are reliably found in a discrete region within the larger VC cluster. In addition to this gross somatotopic organization, there is evidence of a finer level of somatotopic organization between the position of the excitatory receptive field on the tail and the position of the cell soma in the tail subcluster.(ABSTRACT TRUNCATED AT 400 WORDS)     

Differential Susceptibility of Chlamydiae to Exogenous Fibroblast Interferon

Mouse fibroblasts (L cells) were incubated for 5 h with 1,000 U of murine fibroblast interferon (MuIFN α+ β) per ml and then were infected with either Chlamydia trachomatis (LGV 440), C. psittaci (6BC), or C. psittaci (Cal 10). Intracellular development of C. trachomatis was reduced 90% in interferon-treated cells 24 h after infection when compared with controls, whereas C. psittaci growth was not affected in interferon-treated cells.     

Housing type,housing location and mental health

A number of studies have suggested a connection between the type of dwellings which people occupy and their mental health. People who live in flats are usually shown to be more prone to mental illness than those who live in houses. Those who live in high-rise accommodation are shown to be particularly vulnerable. These conclusions were examined by comparing rates on an indicator of psychological distress, in different dwelling types located in good and bad council housing areas. The results suggest that psychological distress is more closely associated with the location of a dwelling than with dwelling type. High-rise flats located on inner-city problem estates are associated with high levels of psychological distress, while low levels are found in similar dwelling types located in the suburbs. These findings are consistent when the effect of age, health, sex and household class are taken into consideration.     

Beta-2-adrenoceptor agonists as inhibitors of lung vascular permeability to radiolabelled transferrin in the adult respiratory distress syndrome in man

Increased lung vascular permeability leading to increased plasma protein extravasation and accumulation (PPA) is a characteristic feature of acute lung injury. Using a previously described technique, PPA was monitored in the lungs of patients with the adult respiratory distress syndrome (ARDS) — an extreme example of acute lung injury in man. An external radiation probe detector was used to monitor the pulmonary accumulation of the plasma protein transferrin radiolabelled in-vivo with ^113mIn. Ten patients with ARDS exhibiting increased PPA indices (>1.0x10^-3/min) were given an intravenous infusion of terbutaline (7 g/kg) over 30 min. Of the four patients in whom the post-drug PPA indices remained within the ARDS range, none survived, whilst five of the six patients in whom the post-drug PPA indices were reduced to below 1.0x10^-3/min survived. PPA indices prior to the administration of terbutaline were not significantly different between the survivor (n=5) and non-survivor (n=5) groups. There was a significant decrease in the PPA indices following terbutaline in survivors (p<0.01) but not in non-survivors. Thus beta-2-agonists in therapeutic doses can inhibit increased lung vascular permeability in man. These findings may have prognostic and therapeutic implication for beta-2-agonists in ARDS.