Whole-Brain Atrophy Rate in Idiopathic Parkinson's Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy.

In multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), the absence of surrogate endpoints makes clinical trials long and expensive. We aim to determine annualized whole-brain atrophy rates (a-WBAR) in idiopathic Parkinson's disease (IPD), MSA, and PSP. Ten healthy controls, 20 IPD, 12 PSP, and 8 MSA patients were studied using a volumetric MRI technique (SIENA). In controls, the a-WBAR was 0.37% ± 0.28 (CI 95% 0.17-0.57), while in IPD a-WBAR was 0.54% ± 0.38 (CI 95% 0.32-0.68). The IPD patients did not differ from the controls. In PSP, the a-WBAR was 1.26% ± 0.51 (CI 95%: 0.95-1.58). In MSA, a-WBAR was 1.65% ± 1.12 (CI 95%: 0.71-2.59). MSA did not differ from PSP. The a-WBAR in PSP and MSA were significantly higher than in the IPD group (p = 0.004 and p < 0.001, resp.). In PSP, the use of a-WBAR required one-half of the patients needed for clinical scales to detect a 50% reduction in their progression. In MSA, one-quarter of the patients would be needed to detect the same effect. a-WBAR is a reasonable candidate to consider as a surrogate endpoint in short clinical trials using smaller sample sizes. The confidence intervals for a-WBAR may add a potential retrospective application for a-WBAR to improve the diagnostic accuracy of MSA and PSP versus IPD.

Attempted isolation of the gene encoding the 21 Kd Plasmodium berghei ookinete transmission blocking antigen from Plasmodium yoelli and Plasmodium vivax.

The 21kD ookinete antigen of Plasmodium berghei (Pbs 21) has been shown to elicit an effective and long lasting transmission blocking immune response in mice. Having cloned and sequenced this antigen (Paton et al. 1993) the sequence was compared to the genes of the same family previously identified in P. falciparum, P. gallinaceum (Kaslow et al. 1989) and P. reichenowi (Lal et al. 1990). Four conserved areas were identified in this comparison, to which degenerate oligonucleotides were designed. PCR amplification and screening of genomic libraries was then carried out using these oligonucleotides. The P. yoelii gene was successfully cloned and a number of novel P. vivax genes identified but the P. vivax homologue of Pbs21 remains elusive.

Attempted isolation of the gene encoding the 21 Kd Plasmodium berghei ookinete transmission blocking antigen from Plasmodium yoelli and Plasmodium vivax

The 21kD ookinete antigen of Plasmodium berghei (Pbs 21) has been shown to elicit an effective and long lasting transmission blocking immune response in mice. Having cloned and sequenced this antigen (Paton et al. 1993) the sequence was compared to the genes of the same family previously identified in P. falciparum, P. gallinaceum (Kaslow et al. 1989) and P. reichenowi (Lal et al. 1990). Four conserved areas were identified in this comparison, to which degenerate oligonucleotides were designed. PCR amplification and screening of genomic libraries was then carried out using these oligonucleotides. The P. yoelii gene was successfully cloned and a number of novel P. vivax genes identified but the P. vivax homologue of Pbs21 remains elusive.

Research on AIDS: knowledge, attitudes and practices among street youth.

PIP: CHILDHOPE (with funding from the United Nations Children's Fund and the aid of nongovernmental organizations in the Philippines, Thailand, Colombia, and Kenya) conducted surveys of street youth in order to ascertain their knowledge, attitudes, and practices in regard to sex and the prevention of human immunodeficiency virus (HIV) infections and other sexually transmitted diseases (STDs). The youth also participated in acquired immunodeficiency syndrome (AIDS) prevention and sex education activities. Youth from all 4 sites reported early sexual activity and multiple partners. Sex was used in all 4 sites to obtain pleasure (recreation), income (prostitution), food or shelter (survival sex), and power (gang rape). Philippine youth reported prostitution and survival sex, including homosexual sex, with foreigners and locals. Kenyan girls reported both prostitution (their main occupation) and survival sex. Kenyan males reported prostitution with foreigners and locals, and rapes of girls. In Bogota, males reported rapes of girls, and gang rapes of females for punishment or initiation. They also reported using sex workers and exchanging sex with men or women for food and shelter. Females from Bogota reported that their "friends" sometimes used survival sex to support their children; nearly all had been previously involved in survival sex on the street. Sexual abuse was common in Kenya and the Philippines; some youth in Manila were abused at shelters. In all 4 sites, there was a high awareness of AIDS and STDs, but information was often incorrect, especially in regard to transmission and treatment of STDs. Although nearly all of the youth knew about modes of transmission of HIV, those from the Philippines and Colombia did not have a personal realization or fear that they could contract it, while those from Kenya and Thailand believed they were at high risk and wanted assistance. 20/21 Kenyan girls were tested by the Undugu Society for HIV after detection of current STD infections in 7 of them; 4 were HIV positive. 2 of these have returned home, and 2 are being provided shelter, counseling and support by the Society. Without changing the problems that create a need for survival sex among youth, little can be done about promoting safe sex and healthy lifestyles.^ieng

Effect of surgical repair on respiratory mechanics in congenital diaphragmatic hernia.

To determine whether surgical repair of congenital diaphragmatic hernia (CHD) results in improvement in respiratory mechanics, we measured respiratory system compliance in nine patients (five survivors and four nonsurvivors) before and after operation. In all nine infants, CHD was diagnosed within 6 hours of life, and surgical repair was through an abdominal approach after a period of stabilization. Measurements were made noninvasively, using the passive expiratory flow-volume technique. In only one of the nine infants did compliance immediately improve after surgical repair, and in another it showed no change. Both of these infants survived, with an uneventful postoperative course. In the remaining seven infants, however, postoperative compliance immediately decreased to 10% to 77% from the preoperative value. The four infants with more than 50% decrease in compliance died with increasing hypoxemia and acidosis. These results suggest that respiratory mechanics in CHD, far from improving, frequently deteriorate as a result of repair of the hernia. The role of urgent surgery in this malformation should be reevaluated.

Ventilatory predictors of pulmonary hypoplasia in congenital diaphragmatic hernia, confirmed by morphologic assessment.

We carried out a prospective study in 66 infants with congenital diaphragmatic hernia within the first 6 hours of life to determine whether outcome is related to the degree of underlying pulmonary hypoplasia, as predicted by preoperative PaCO2, when correlated with an index of ventilation (VI = mean airway pressure X respiratory rate) and confirmed by postmortem analysis of the lung. Those infants with PaCO2 greater than 40 mm Hg before surgery had a 77% mortality; when PaCO2 reduction could be achieved only with VI greater than 1000, the mortality was still greater than 50%. After repair, however, the ability to hyperventilate to PaCO2 less than 40 mm Hg proved to be an important determinant of survival; only one of 31 infants in this group died, whereas only two of 27 infants with PaCO2 greater than 40 mm Hg survived. In 16 infants with PaCO2 greater than 40 mm Hg despite hyperventilation, high-frequency oscillatory ventilation was started. This resulted in a rapid fall in PaCO2, but 14 of the 16 infants had only temporary improvement in oxygenation, and died. In five of the infants who died, alveolar number was assessed by postmortem morphometric analysis; there was a severe reduction to less than 10% of published normal neonatal values. Pulmonary vascular changes of increased muscularization were less remarkable than those observed in infants with persistent pulmonary hypertension. Our findings suggest that the degree of pulmonary hypoplasia (which would not be influenced by surgical repair), rather than the pulmonary vascular abnormality, mainly determines survival. Consideration could therefore be given to an initial nonsurgical approach to congenital diaphragmatic hernia, with the expectation that pulmonary function might improve and pulmonary vascular resistance decrease.

Pulse oximetry in pediatric intensive care: comparison with measured saturations and transcutaneous oxygen tension.

We evaluated a new pulse oximeter designed to monitor beat-to-beat arterial oxygen saturation (SaO2) and compared the monitored SaO2 with arterial samples measured by co-oximetry. In 40 critically ill children (112 data sets) with a mean age of 3.9 years (range 1 day to 19 years), SaO2 ranged from 57% to 100%, and PaO2 from 27 to 128 mm Hg, heart rates from 85 to 210 beats per minute, hematocrit from 20% to 67%, and fetal hemoglobin levels from 1.3% to 60%; peripheral temperatures varied between 26.5 degrees and 36.5 degrees C. Linear correlation analysis revealed a good agreement between simultaneous pulse oximeter values and both directly measured SaO2 (r = 0.95) and that calculated from measured arterial PaO2 (r = 0.95). The device detected several otherwise unrecognized drops in SaO2 but failed to function in four patients with poor peripheral perfusion secondary to low cardiac output. Simultaneous measurements with a tcPO2 electrode showed a similarly good correlation with PaO22 (r = 0.91), but the differences between the two measurements were much wider (mean 7.1 +/- 10.3 mm Hg, range -14 to +49 mm Hg) than the differences between pulse oximeter SaO2 and measured SaO2 (1.5% +/- 3.5%, range -7.5% to -9%) and were not predictable. We conclude that pulse oximetry is a reliable and accurate noninvasive device for measuring saturation, which because of its rapid response time may be an important advance in monitoring changes in oxygenation and guiding oxygen therapy.