Glomerular epithelial cell endocytosis in puromycin-induced glomerulopathy.

Glomerulopathy and nephrotic syndrome were induced in rats by intravenous puromycin aminonucleoside. Ten days after the injection of puromycin, the animals have developed heavy proteinuria. During this phase, glomerular epithelial cell endocytosis was studied by injecting a conjugate of horseradish peroxidase and poly-L-lysine. This conjugate has been shown to be endocytosed by glomerular epithelial cells. The rats were serially sacrificed from 1 min to 24 h after this injection. Peroxidase was localised cytochemically and observed at light and electron microscopy. The early events of endocytosis in glomerulopathy (namely the binding to the plasma membrane, the membrane invagination and the formation of the early vesicles) were qualitatively similar to those in the normal. The later events (the fusion of the vesicles and their movement within the cells) were inhibited. The results show that puromycin aminonucleoside damages epithelial cell endocytotic activity and affects the later processing of the conjugate within the cells.     

A longitudinal study of cholinesterase changes in pregnancy

Serum cholinesterase activity was measured at intervals before, during, and after 44 pregnancies in 43 women. Three patterns of change were seen: (a) A decline in activity after conception, with no return towards pre-conception values before delivery (20 pregnancies). (b) A decline in activity accompanied by a partial or complete return to pre-conception values before delivery (19 pregnancies). (c) Either no discernible decline or increased activity during gestation (five pregnancies). We saw no association between these patterns and either the sex of the child, parity, smoking history, or alcohol intake. However, the continuous decrease in cholinesterase activity occurred in the youngest group of women, a decrease followed by an increase in the intermediate age group, and no decrease at all in the oldest group. Although not all the age-related differences quite reached statistical significance, these findings suggest that the patterns of change may be determined by some aspect of maternal physical maturity.     

Pulse-generated runoff: a new method of determining calf vessel patency

A non-invasive method of determining calf vessel patency before femorodistal bypass has been developed. This pulse-generated runoff (PGR) system generates blood flow in patent calf arteries by means of a pulsatile cuff even if the existing Doppler signal is inaudible. PGR was compared with pre-operative arteriography in 95 ischaemic limbs and both were compared with the peripheral resistance measured at operation in 62 limbs. There was a highly significant correlation between the PGR and arteriogram scores (rs = 0.74, P less than 0.001) but PGR tended to detect more patent vessels than arteriography. The peripheral resistance correlated better with PGR than arteriography (rs = -0.71 and -0.54 respectively, P less than 0.001). PGR is a simple, non-invasive method of determining calf and foot vessel patency pre-operatively.     

L-Dopa-responsive Parkinson's syndrome in association with phenylketonuria: In vivo dopamine transporter and D2 receptor findings.

Reports of parkinsonism in phenylketonuria are exceedingly rare. We report on a patient who had received a delayed diagnosis of phenylketonuria as an infant and subsequently developed levodopa-responsive parkinsonism at the age of 33. Single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123))I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) used to measure dopamine transporter levels on two occasions, 7 and 9 years after the onset of neurological symptoms, were normal. Iodine-123-iodo-lisuride SPECT (IBZM) imaging, however, showed reduced caudate over putamen binding. This combination of imaging findings indicates a possible upregulation of postsynaptic D2 receptors in the context of intact presynaptic dopamine nerve terminal density.     

Germline mutations in the neurofibromatosis type 2 tumour suppressor gene

The recent identification of the NF2 tumour suppressor genehas enabled large scale screening for pathological mutationsin the gene. We have sought germline mutations In the NF2 geneby SSCP and heteroduplex analysis of cDNA and genomic DNA samplesfollowed by cloning and sequencing of mutant alleles. In thepresent report we describe 11 putative pathological mutations,including five nonsense mutations, three short insertions ordeletions cauing frameshifts and three missense mutations. Moststop mutations and frameshift mutations were found In Individualsexpressing a severe phenotype while one of the three missensemutations was associated with a mild phenotype. Four unrelatedNF2 patients of the 93 tested were found to have identical nonsensemutations caused by a C to T transition (C169) in a CpG dinucleotide,which is a potential mutational hotspot in the NF2 tumour suppressorgene.     

Intergenerational studies of human birthweight from the 1958 birth cohort. II. Do parents who were twins have babies as heavy as those born to singletons?

OBJECTIVE: To ascertain whether maternal twinning influences the previously described association between the birthweight of singleton mothers and their infants. DESIGN AND SUBJECTS: The association between the birthweight of singleton parents and their offspring and that between twin parents and their offspring was compared using data from the 23-year-old sample of the 1958 British national birth cohort. The numbers available for full comparison were 1027 female and 611 male singleton cohort members, and 26 female and 17 male twin cohort members and their first singleton livebirths. RESULTS: Of the mothers who had been twins, half had been of low birthweight, and overall their mean weight was 700 g less than that of their singleton counterparts. Nevertheless, the mean birthweight of babies of twin mothers was 133 g, and of twin fathers 94 g, greater than of babies of corresponding singletons. For female, but not male, parents this difference persisted after adjustment for confounding variables. CONCLUSIONS: We suggest two possible reasons for the difference between the weight of babies of twin and singleton mothers. Firstly, the growth of twins becomes retarded late in pregnancy, possibly after a period critical in determining long-term reproductive effects. Secondly, the twin survivors were of higher birthweight than the original twin cohort, whilst the singleton survivors were more representative of all singleton births, thus introducing a possible bias.     

Post-herpetic neuralgia and topical capsaicin

Topical 0.025% capsaicin was used to treat 33 patients with post-herpetic neuralgia (PHN). Thirty-nine percent of those entering the trial achieved at least a good result and 55% were improved or better. Fifty-six percent of the 23 patients completing the study had good or excellent pain relief after 4 weeks. Seventy-eight percent of the 23 noted at least some improvement in pain. Post-capsaicin burning was a common, untoward effect in most patients and in about one-third was so unbearable that the trial was terminated prematurely. This treatment appears to be a useful modality in PHN, particularly in the elderly in whom oral medications are often poorly tolerated; however, it does require supervision. A double-blind, controlled trial is now necessary.     

Validation of a modified one-step rebreathing technique for measuring exercise cardiac output

A modification of the Farhi one-step rebreathing technique (1) is described for determining submaximal exercise cardiac output (Q). Factors critical in the estimation of Q are initial rebreathing bag volume and constant bag volume during the maneuver. By substituting a high flow rate analyzer (500 ml.min-1) for the recommended low flow rate mass spectrometer (60 ml.min-1), adding a recirculation circuit from the outlet of the analyzer to an inlet at the base of the rebreathing bag, and reducing the length of sample tubing to the analyzer, we were able to recirculate the subject's expired gas and achieve no loss of bag volume. No statistically significant differences in estimate of cardiac output were noted between the mass spectrometer and LB-2 analyzer with recirculation circuit during submaximal cycling. Heart rate and oxygen uptake were highly correlated with cardiac output and agreed well with the literature, irrespective of the CO2 analyzer system used. A unique feature of our method is that the subject's tidal volume is measured prior to the maneuver and then used as the initial rebreathing bag volume. Varying the bag volume by +/- 0.2 L from the tidal volume had no significant effect on the estimate of cardiac output during exercise. Now quick, reliable, and noninvasive measurements of cardiac output are feasible in subjects--not only in the laboratory but also in the field where a mass spectrometer is not readily portable.     

Service needs of youths released from a state psychiatric facility as perceived by service providers and families

The following article reports on the results of service needs assessments of a cohort of youths released from a state psychiatric facility as perceived by service providers and families/caregivers. Families as well as service providers consistently agreed on three service areas of high need—psychotherapy for the child, family therapy and parent skill training. However, families perceived a need for a number of other services that are not traditionally provided by the mental health system such as after school recreation activities and self-help and support groups for the child. The discrepancies between service providers and families' perceptions of assessed needs may lead to families dropping out of service due to the unresponsiveness of the services in meeting their perceived needs. Steps that service providers need to take to be more responsive to the needs of families are discussed.This study was funded by a grant from the Office of Program Evaluation and Research, Ohio Department of Mental Health.