Mother-to-baby transfer of humoral immunity against retrovirus-induced neurologic disorders and immunodeficiency.

Neonatal FVB/N mice inoculated with ts1, a temperature-sensitive mutant of Moloney murine leukemia virus TB, developed fatal immunodeficiencies and neurologic disorders. In this study, we tested the role of transfer of maternal humoral immunity in preventing ts1-induced disease syndrome in the neonatal mice. We compared the levels of protection provided through maternal antibodies both pre- and postnatally by separating infected neonatal mice into four different groups. The first group was born of and nursed by nonimmune mothers, the second was born of immune mothers but nursed by nonimmune mothers, the third was born of nonimmune mothers but nursed by immune mothers, and the fourth was born of and nursed by immune mothers. Our major findings are: (1) adult mice generate a strong antiviral antibody response; (2) maternal antibody is protective for the newborns and primarily transferred by breast milk; (3) virus titers were cleared in the periphery and the CNS of neonates nursing on immune mothers; and (4) the majority of antiviral antibody generated was specific for the gp70. These results indicate that humoral immunity can be passed efficiently from mother to baby through breast milk and can provide strong protection against neurotropic retrovirus.

Mandible enclosure of upper airway and weight in obstructive sleep apnea.

Although anatomic lesions and obesity can produce obstructive sleep apnea (OSA), most subjects with OSA have no recognizable anatomic lesion. We hypothesized that the occurrence of OSA is related to the size of the region enclosed by the mandible and the degree of obesity. We studied 30 subjects with a range of OSA and obesity with magnetic resonance imaging (MRI). MRI was performed with T-1 weighted sequences. Nocturnal polysomnography was performed in all subjects. Univariate regression analysis indicated there was a significant correlation between the number of apneas and hypopneas per hour of sleep (AH/h) and (1) the area enclosed by the mandible ramus (AMR1) (r = 0.48, p < 0.01) and (2) the distance from the teeth to the posterior mandible ramus (r = 0.39, p < 0.05). Stepwise multiple regression analysis indicated that weight, AMR1, and height explained 69% of the variance of AH/h (r2 = 0.69). We conclude that the occurrence of OSA in these subjects is related to the size of the region enclosed by the mandible as well as to their weight.

Mandible position and activation of submental and masseter muscles during sleep.

Movement of the mandible could influence pharyngeal airway caliber because the mandible is attached to the tongue and to muscles that insert on the hyoid bone. In normal subjects and patients with obstructive sleep apnea (OSA) we measured jaw position during sleep with strain gauges, as well as masseter and submental electromyograms, airflow, esophageal pressure, oximetry, electroencephalograms, and electrooculograms. Jaws of patients with OSA were open more than those of normal subjects at end expiration and opened further at end inspiration, particularly at the termination of apneas when the masseter and submental muscles contracted. Masseter activation occurred only in patients with OSA and in a pattern similar to that of submental muscles. Jaw opening at end expiration could narrow the upper airway, whereas opening at end inspiration could reflect efforts to expand the airway with tracheal tug and with submental muscle activation and efforts to open the mouth to allow mouth breathing. Masseter contraction does not close the jaw but may serve to stabilize it.

Respiratory-related recruitment of the masseter: response to hypercapnia and loading.

To test the hypothesis that a muscle that closes the jaw, the masseter, can be recruited by ventilatory stimuli, we studied the electromyographic activation of the masseter and genioglossus in seven normal awake males who were exposed in random order to progressive hyperoxic hypercapnia, inspiratory threshold loading (-40 cmH2O), and combined hypercapnia and loading. With hypercapnia, the masseter was generally recruited after the genioglossus had been activated. Once recruited, activation of both muscles increased linearly with increasing CO2. Combined hypercapnia and loading produced more activation than either stimulus alone. These data indicate that the masseter is activated by ventilatory stimuli that activate the genioglossus. Earlier recruitment of the genioglossus suggests that activation of the masseter serves to stabilize the mandible and allow the genioglossus to function as a more efficient dilator of the upper airway.

Activation of masseter muscles with inspiratory resistance loading.

Closure of the jaw exerts traction on muscles that insert on the hyoid bone and that may stabilize or expand the pharyngeal airway. We postulated that the masseter muscles, which close the jaw, would be activated when the patency of the pharyngeal airway is threatened. We therefore measured electromyographic activation of the masseters during inspiratory resistance loading and compared it with activation of chin muscles and alae nasi in 10 normal subjects. We observed no masseter activation during quiet unloaded breathing, but as pharyngeal pressure became lower there was a significant increase in masseter activation in all subjects. The change in masseter activation relative to pharyngeal pressure was similar to that of chin muscles and alae nasi. Activation of the masseter preceded the fall in pharyngeal pressure as also occurred in the chin muscles and alae nasi. We conclude that the masseters are activated by inspiratory resistance loading and have respiratory activity similar to pharyngeal airway muscles.

In vitro activity of trimethoprim and sulfamethoxazole against the nontuberculous mycobacteria.

Trimethoprim (TMP) and sulfamethoxazole (SMZ) were studied alone and in combination (TMP-SMZ) against 141 nontuberculous mycobacteria; an agar dilution method was used. All strains of Mycobacterium kansasii (8), Mycobacterium marinum (16), and Mycobacterium scrofulaceum (3); 97% (63 of 65) of strains of Mycobacterium fortuitum; and 27% (3 of 11) of strains of Mycobacterium avium-intracellulare were inhibited by less than or equal to 32 micrograms of SMZ/ml. In contrast, all 38 isolates of Mycobacterium chelonei were resistant to 32 micrograms of SMZ/ml. All species were highly resistant to TMP, with minimal inhibitory concentrations (MICs) of greater than or equal to 64 micrograms/ml. The MICs of TMP-SMZ for these organisms were similar to the MICs of SMZ alone. These results support the use of sulfonamides for treatment of infections due to M. fortuitum and M. marinum and suggest the need for further clinical and laboratory studies of the activity of these drugs against several additional mycobacterial species. TMP-SMZ appears to offer no advantage (in vitro) over SMZ alone against any of these organisms.

Use of trimethoprim-sulfamethoxazole for treatment of infections due to Nocardia.

Trimethoprim-sulfamethoxazole (TMP-SMZ) was used for treatment of 34 patients with pulmonary or cutaneous nocardiosis. Of nine patients with primary cutaneous disease, eight had rapid resolution of their infection after short-term therapy and none have relapsed after a follow-up of more than six months. The 25 patients with pulmonary nocardiosis had a good clinical response, but three of five (60%) who completed less than three months of therapy relapsed within four weeks. Of the 10 patients who completed four to six months of therapy, only one (10%) relapsed and this relapse was due to drug resistance. By the method of serial dilution in agar, 96% of 59 isolates of Nocardia had MICs of SMZ of less than 25 micrograms/ml. Fewer than 20% were susceptible to 2.5 micrograms of TMP/ml. Synergy between TMP and SMZ was usually present with ratios of TMP to SMZ of 1:5, 1:1, or 5:1, but was less common at a ratio of 1:20. Disk susceptibility testing was easy to perform and readily separated sensitive from resistant strains. TMP-SMZ is highly effective for the treatment of nocardiosis, but the question of whether it is more effective clinically than a sulfonamide alone remains unanswered.