Faculty Bibliography

STUDY OBJECTIVE: Intermittent positive pressure ventilation (IPPV) can be delivered via various oral, nasal, or oronasal interfaces as an alternative to tracheostomy for up to 24 h of ventilatory support. Nocturnal nasal IPPV is often associated with frequent transient but at times severe oxyhemoglobin desaturations (dSaO2s) and sleep fragmentation. The purpose of this study was to determine if nocturnal mouthpiece IPPV is also associated with dSaO2s and sleep disruption. DESIGN: Twenty-seven postpolio ventilator-assisted individuals (VAIs) using mouthpiece IPPV with little or no ventilator-free breathing time (VFBT) underwent nocturnal oxyhemoglobin saturation (SaO2) monitoring. In addition, 15 underwent nocturnal capnography and 13 underwent polysomnography. RESULTS: Mean nocturnal SaO2 was normal in 22 of 27 and maximum end-tidal PCO2 was normal in 12 of 15 VAIs. Use of lipseal retention for nocturnal mouthpiece IPPV significantly improved blood gas values during sleep. The polysomnography results demonstrated relatively normal sleep efficiency. CONCLUSIONS: Nocturnal mouthpiece IPPV is most effective with lipseal retention. It can provide normal alveolar ventilation and SaO2 during sleep for VAIs with little or no measurable vital capacity or VFBT. Because transient dSaO2s can be eliminated with lipseal retention, it may disrupt sleep less than nasal IPPV

Osteogenesis imperfecta, a rare connective tissue disorder, is known to be associated sometimes with the invagination of the basilar skull. This deformity may disturb respiratory function secondary to brain stem compression and hydrocephalus. In addition, the deformed thoracic cage and fragile ribs make pulmonary care more complicated. A case of 24-year-old man is presented with brain stem compression syndrome secondary to osteogenesis imperfecta congenita with basilar impression. He developed respiratory failure and became tracheostomy positive-pressure ventilator dependent at the age of 21 years. He also suffered multiple skeletal abnormalities and mental retardation, and following the brain stem compression, severe quadriparesis. The patient's condition is stable since he has been using the ventilator and he is currently living in the community

Six ventilator-assisted individuals (VAIs) with spinal muscular atrophy (SMA) are described. All six survived by using intermittent positive pressure ventilation via an indwelling tracheostomy for a mean of 11.7 +/- 17.7 yr despite frequent episodes of mucus plugging and pneumonia. Four of the VAIs also received all nutrition via indwelling gastrostomy tubes because of severe bulbar muscle weakness. Four VAIs used tracheostomy intermittent positive pressure ventilation with their tracheostomy cuffs deflated and could communicate verbally. Five of the six VAIs remained institutionalized from the onset of ventilatory use. Two SMA VAIs survived for 15 and 4 yr, respectively, despite need for ventilatory support since early infancy. All four SMA VAIs who could communicate remained socially active and one, gainfully employed. We conclude that for patients with advanced SMA markedly prolonged survival is possible with ventilatory assistance despite severe respiratory and bulbar muscle dysfunction

In Drosophila, as in mammalian cells, the Raf serine/threonine kinase appears to act as a common transducer of signals from several different receptor tyrosine kinases. We describe a new role for Raf in Drosophila development, showing that Raf acts in the somatic follicle cells to specify the dorsoventral polarity of the egg. Targeted expression of activated Raf (Rafgof) within follicle cells is sufficient to dorsalize both the eggshell and the embryo, whereas reduced Raf activity ventralizes the eggshell. We show that Raf functions downstream of the EGF receptor to instruct the dorsal follicle cell fate. In this assay, human and Drosophila Rafgof are functionally similar, in that either can induce ventral follicle cells to assume a dorsal fate.

We have designed a system for targeted gene expression that allows the selective activation of any cloned gene in a wide variety of tissue- and cell-specific patterns. The gene encoding the yeast transcriptional activator GAL4 is inserted randomly into the Drosophila genome to drive GAL4 expression from one of a diverse array of genomic enhancers. It is then possible to introduce a gene containing GAL4 binding sites within its promoter, to activate it in those cells where GAL4 is expressed, and to observe the effect of this directed misexpression on development. We have used GAL4-directed transcription to expand the domain of embryonic expression of the homeobox protein even-skipped. We show that even-skipped represses wingless and transforms cells that would normally secrete naked cuticle into denticle secreting cells. The GAL4 system can thus be used to study regulatory interactions during embryonic development. In adults, targeted expression can be used to generate dominant phenotypes for use in genetic screens. We have directed expression of an activated form of the Dras2 protein, resulting in dominant eye and wing defects that can be used in screens to identify other members of the Dras2 signal transduction pathway.

Pulmonary complications from impaired airway secretion clearance mechanisms are major causes of morbidity and mortality for post-poliomyelitis individuals. The purpose of this study was to review the long-term use of manually assisted coughing and mechanical insufflation-exsufflation (MI-E) by post-poliomyelitis ventilator-assisted individuals (PVAIs) and to compare the peak cough expiratory flows (PCEF) created during unassisted and assisted coughing. Twenty-four PVAIs who have used noninvasive methods of ventilatory support for an average of 27 years, relied on methods of manually assisted coughing and/or MI-E without complications during intercurrent respiratory tract infections (RTIs). Nine of the 24 individuals were studied for PCEF. They had a mean forced vital capacity (FVC) of 0.54 +/- 0.47L and a mean maximum insufflation capacity achieved by air stacking of ventilator insufflations and glossopharyngeal breathing of 1.7L. The PCEF were as follows: unassisted, 1.78 +/- 1.16L/sec; following a maximum assisted insufflation, 3.75 +/- 0.73L/sec; with manual assistance by abdominal compression following a maximum assisted insufflation, 4.64 +/- 1.42L/sec; and with MI-E, 6.97 +/- 0.89L/sec. We conclude that manually assisted coughing and MI-E are effective and safe methods of airway secretion clearance for PVAIs with impaired expiratory muscle function who would otherwise be managed by endotracheal suctioning. Severely decreased maximum insufflation capacity but not vital capacity indicate need for a tracheostomy

Despite wider application of the use of nocturnal intermittent positive pressure ventilation (IPPV) via nasal access for the management of nocturnal hypoventilation, there continues to be a lack of familiarity with the use of IPPV via the mouth for ventilatory support. Unlike nasal IPPV, which is generally practical only for nocturnal use, up to 24-h mouth IPPV was the key method of noninvasive ventilatory support that permitted the avoidance or elimination of tracheostomy for 257 individuals with acute or chronic ventilatory failure. Mouth IPPV was delivered via commercially available mouthpieces for daytime aid and mouthpiece with lip seal or custom orthodontic interfaces for nocturnal support. The use of mouth IPPV alone or in a regimen with other noninvasive ventilatory aids was reviewed for these 257 individuals. Mouth IPPV was used for nocturnal aid by 163 individuals, 61 of whom had little or no measurable vital capacity or significant ventilator-free breathing time, for more than 1,560 patient-years with few complications. It was also the predominant method of daytime ventilatory support for 228 individuals for more than 2,350 patient-years. We conclude that for individuals with adequate bulbar muscle function but chronic respiratory muscle insufficiency, mouth IPPV can be an effective alternative to tracheostomy. It can significantly prolong survival while optimizing convenience, safety, and communication

The purpose of this article is to present a cost analysis of in-home vs institutionalization for severely physically disabled ventilator-assisted individuals (VAIs). Following rehabilitation and adaptation to noninvasive methods of ventilatory support, 30 VAIs were maintained in the community for 12.9 +/- 1.1 years with personal care attendants organized by a home care vendor reimbursed by New York City Medicaid. The program permitted self-directed severely disabled clients, including these 30 exclusively nontracheostomized VAIs, to live in the community and direct their attendant care and personal affairs. Prior to discharge home, the 30 patients resided in the respiratory unit of a long-term care facility for a mean of 8.9 +/- 10.1 years. The unit is currently reimbursed at a mean rate of $718.80 per patient per day. The current mean total cost of maintaining these VAIs in the community is $235.13 +/- 56.73 per patient per day. The conversion to and/or maintenance on 24-h nontracheostomy ventilatory support permitted discharge to the community by allowing the VAI to be attended by trained but uncredentialed home care attendants, thus avoiding prohibitively expensive in-home nursing for tracheostomy care. This created a savings to the public of 77 percent or $176,137 per year per client. We conclude that conversion to and/or use of noninvasive methods of ventilatory aid can be a reasonable and cost-saving goal. More respiratory rehabilitation centers are needed to free up hospital beds and facilitate discharge of VAIs to the community. There is also evidence that trained attendants should be permitted to suction tracheostomized VAIs in the home

The purpose of this work is to present 640 patient-years of experience using the intermittent abdominal pressure ventilator (IAPV) in a regimen of noninvasive ventilatory support for patients with paralytic/restrictive respiratory insufficiency. Fifty-two of the 54 patients who used the IAPV used 24-hour noninvasive ventilatory support. Thirty-eight of the 52 patients could tolerate less than 15 minutes of free time off their ventilators except by the successful use of glossopharyngeal breathing (GPB). No patient, however, retained an indwelling tracheostomy and none required or used supplemental oxygen therapy. Forty-eight of the 54 patients used the IAPV for daytime support for a mean of 12.9 +/- 11.5 years (3 months to 39 years) while using other forms of noninvasive support overnight. All 48 patients maintained normal minute ventilation and end-tidal PCO2 on the IAPV. One patient used the IAPV only for nocturnal ventilatory support for six months. Five patients relied on the IAPV as their sole method of ventilatory support 24 hours a day for a mean of 13.4 +/- 11.2 years (range, 2 to 31 years). Three of these five patients had no free time and were studied by nocturnal SaO2 monitoring that demonstrated a mean SaO2 of 95 percent or greater and a minimum SaO2 of 86 percent. The maximum end-tidal PCO2 was 49 mm Hg during sleep on the IAPV. The 48 patients receiving daytime IAPV support reported few difficulties. However, two of the five patients using the IAPV 24 hours a day had development of sacral decubiti. The IAPV became ineffective for 12 patients after 12.3 +/- 9.5 years of use. These patients then switched to daytime mouth IPPV. We conclude that the IAPV is a safe and effective method of long-term daytime ventilatory support for patients with paralytic/restrictive respiratory insufficiency. Its use is optimized when employed in combination with other noninvasive methods of ventilatory support, thus eliminating the need for tracheostomy, and optimizing the use of GPB. Regular follow-up is important because the IAPV can become less effective with time