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Hermansky-Pudlak syndrome (HPS) is an autosomal recessive condition characterized by a bleeding diathesis and hypopigmentation of the skin, hair, and eyes. Some HPS patients develop other complications such as granulomatous colitis and/or fatal pulmonary fibrosis. Eight genes have been associated with this condition, resulting in subtypes HPS-1 through HPS-8. The HPS gene products are involved in the biogenesis of specialized lysosome-related organelles such as melanosomes and platelet delta granules. HPS1 and HPS4 form a stable complex named biogenesis of lysosome-related organelles complex (BLOC)-3, and patients with BLOC-3 or AP-3 deficiency develop pulmonary fibrosis. Therefore, it is important to subtype each HPS patient. HPS type 1 (HPS-1) occurs frequently on the island of Puerto Rico because of a founder mutation. Here, we describe seven mutations, six of which, to our knowledge, are previously unreported in the HPS1, HPS4, and HPS5 genes among patients of Mexican, Uruguayan, Honduran, Cuban, Venezuelan, and Salvadoran ancestries. Our findings demonstrate that the diagnosis of HPS should be considered in Hispanic patients with oculocutaneous albinism and bleeding symptoms. Moreover, such patients should not be assumed to have the HPS-1 subtype typical of northwest Puerto Rican patients. We recommend molecular HPS subtyping in such cases, as it may have significant implications for prognosis and intervention.

Questions: Does inspiratory muscle training improve maximal inspiratory pressure in intubated older people? Does it improve breathing pattern and time to wean from mechanical ventilation?, Design: Randomised trial with concealed allocation and intention-to-treat analysis., Participants: 41 elderly, intubated adults who had been mechanically ventilated for at least 48 hr in an intensive care unit., Intervention: The experimental group received usual care plus inspiratory muscle training using a threshold device, with an initial load of 30% of their maximal inspiratory pressure, increased by 10% (absolute) daily. Training was administered for 5 min, twice a day, 7 days a week from the commencement of weaning until extubation. The control group received usual care only., Outcome Measures: The primary outcome was the change in maximal inspiratory pressure during the weaning period. Secondary outcomes were the weaning time (ie, from commencement of pressure support ventilation to successful extubation), and the index of Tobin (ie, respiratory rate divided by tidal volume during a 1-min spontaneous breathing trial)., Results: Maximal inspiratory pressure increased significantly more in the experimental group than in the control group (MD 7.6 cmH(2)0, 95% CI 5.8 to 9.4). The index of Tobin decreased significantly more in the experimental group than in the control group (MD 8.3 br/min/L, 95% CI 2.9 to 13.7). In those who did not die or receive a tracheostomy, time to weaning was significantly shorter in the experimental group than in the control group (MD 1.7 days, 95% CI 0.4 to 3.0)., Conclusions: In intubated older people, inspiratory muscle training improves maximal inspiratory pressure and the index of Tobin, with a reduced weaning time in some patients., Trial Registration: NCT00922493.