Cardiovascular disease and obstructive sleep apnea: implications for physicians.

Obstructive sleep apnea (OSA) has been strongly associated with several cardiovascular disorders during the past decade, and studies suggested that there might be a causal relationship. Recent studies have described several pathophysiologic mechanisms that are active in OSA and may participate in the development of cardiovascular disorders. Primarily, the repetitive respiratory events that occur in OSA cause hypoxia, hypercapnea, arousals, or disrupted sleep singly or in combination. These abnormal physiologic events result in increased sympathetic outflow, alterations in blood pressure control mechanisms, dysfunctional ventilatory regulation, and vascular alterations. As a consequence of the relative impact and the genetic predisposition, these pathophysiologic alterations may lead to or complicate a wide variety of cardiovascular disorders. Frequently, patients who have OSA present with complaints of excessive daytime sleepiness, chronic fatigue, snoring, morning headache, and nocturnal arousals. Difficult-to-control hypertension, recurrent exacerbations of congestive heart failure, and nocturnal angina are common cardiovascular manifestations of undiagnosed OSA. This article reviews the major cardiovascular disorders associated with OSA and the pathophysiologic mechanisms associated with their development.

Murine laminin binds to Histoplasma capsulatum. A possible mechanism of dissemination.

Histoplasmosis, an increasingly important opportunistic infection in immunosuppressed subjects, is characterized by hematogenous dissemination of the yeast from the lung. The mechanism of this dissemination is not fully understood. Laminin, the major glycoprotein of the extracellular matrix, is known to mediate the attachment of various invasive pathogens to host tissues. In the current study, laminin is demonstrated to bind to Histoplasma capsulatum in a rapid, specific, and saturable manner. Scatchard analysis with 125I-labeled laminin revealed an estimated 3.0 x 10(4) binding sites per yeast with an apparent Kd for laminin binding of 1.6 x 10(-9) M. Laminin binding to H. capsulatum was decreased from 62 +/- 1 to 17 +/- 1 ng (P < 0.001) in the presence of 3,000 nM of Ile-Lys-Val-Ala-Val, a pentapeptide within one major cell attachment site of laminin. A 50-kD H. capsulatum laminin-binding protein was demonstrated using an 125I-Ln blot of H. capsulatum cell wall proteins. The 50-kD protein is also recognized by antibodies directed at the 67-kD laminin receptor, suggesting they are related. This study proposes a possible mechanism for H. capsulatum attachment to laminin, an important first step required for the yeast to recognize and traverse the basement membrane.

Comparative study of cerebral cortical potentials associated with voluntary movements in monkey and man.

Eight monkeys (Macaca mulatta) were taught to squeeze and release a handgrip. The movement simulated the brisk squeeze of a hand dynamometer performed by 7 human subjects. Monkey. During the performance of the voluntary movements, slow cortical potentials (motor potentials or MPs) were studied with monopolar, surface bipolar, transcortical and intracortical recordings. A survey of the dorsal expanse of cerebral cortex showed that the contralateral motor hand area, somatosensory hand area and area 6 adjacent to the supplementary motor area became active with movement. MPs also were seen in the motor and somatosensory cortex medial to the hand area, but we concluded that those potentials were probably related to adventitious movements in the arm and leg. That area 6 became active with movement was further verified with extracellular unit recording; the behavior of area 6 units was compared with that recorded from units in the motor hand area. Using simultaneous transcortical recordings a sequence of cortical activation was observed in those areas generating an MP. The motor hand area became active first, followed in turn by area 6 and the somatosensory hand area. The monosynaptic cortico-cortical connections of the motor hand area were studied with autoradiographic and horseradish peroxidase techniques and compared to the distribution of the MP. The hand area demonstrated reciprocal connectivity with portions of the somatosensory hand area, the supplementary motor area in area 6 and the cortex adjacent to the intraparietal sulcus. The distribution of the MPs correlated with the connectivity to the supplementary motor and somatosensory areas. Our physiologic studies did not adequately investigate the area adjacent to the intraparietal sulcus. Man. Motor potentials were studied using surface bipolar recordings with closely spaced electrodes (inter-electrode distances 1 cm or 2 cm). Recordings were made directly from the cortex in one subject studied under local anesthesia during an operation for epilepsy, and epidurally in 6 subjects in whom epidural electrode arrays had been inserted for the purpose of localizing an epileptogenic focus. Similar to the findings in the animals, MPs were recorded from the contralateral motor and somatosensory hand area with activity in motor cortex appearing first; area 6 just anterior to the motor hand area probably also generated a response. In addition, a locally generated potential not seen in monkey was recorded anterior to area 6. This difference in response distribution is viewed as possibly relating to the different significance which the seemingly comparable hand movements have for the animal and human subjects. No response was seen in motor and somatosensory hand area with ipsilateral movements. We have no information for the anteriorly recorded response with ipsilateral movement.

Artificial feeding of Simulium vectors of human and bovine onchoceriasis.

A technique for feeding simuliids artificially in a feeding-tube containing blood covered by a membrane has been developed with a view to studying the development of Onchocerca volvulus of man and O. gutturosa of cattle in their respective vectors. A number of different kinds of membranes were tested, but skin from 2-day-old chicks was found to be most satisfactory. S. ornatum, the vector of O. gutturosa in England, fed readily on human and ox blood. The trials were carried out in a constant-temperature room with artificial lighting supplied by 60- or 100-watt clear blue-glass lamps illuminating the feeding-tube with 20 lumens per ft(2). Ultraviolet illumination was not satisfactory but light filtered through coloured screens gave good results in the middle of the spectrum. The flies fed well up to a temperature of 21 degrees C (70 degrees F) and a relative humidity of 65%-75%. The over-all feeding rate was 24.5%.The work was extended to trials with the vectors of human onchocerciasis at Kumba in West Cameroon and Amani in Tanzania. Successful membrane-feeding was achieved with the anthropophilic strains of S. damnosum from West and East Africa and with S. woodi, the main vector of O. volvulus in the Amani region. S. vorax, which is a good laboratory host for O. volvulus also, fed readily. S. nyasalandicum could be induced, but not readily, to feed through membranes. Once again, skin from 2-day-old chicks was the best membrane and human or ox blood, defibrinated or heparinized, either fresh or deep-frozen, was accepted by the flies. Wild and laboratory-bred S. damnosum also fed on a chimpanzee in a dark-room with artificial illumination at Kumba.

A review of the control of Simulium vectors of onchocerciasis.

The purpose of this paper is to bring together all the available information concerning the control of Simulium vectors of onchocerciasis in Africa and Central and South America.Some of the larger control schemes are described in detail. Insecticidal formulations, rates of dosage, and methods of application are given when available, and costs per square mile (or square kilometre) are quoted where possible as a guide to future operations.The efficacy of ground application (larviciding) as compared with aerial application (larviciding and adulticiding) is discussed and it is concluded that ground larviciding is likely to achieve the best results, at less cost, in onchocercal foci where the vectors usually breed in small, densely wooded streams.Data in connexion with fly densities, prior and subsequent to control schemes, are quoted when available.