Airway management in obesity hypoventilation syndrome.

The role of tracheostomy is limited in the obesity hypoventilation syndrome unless severe upper airway obstruction exists. If it is performed, special techniques must be applied to overcome the problems associated with tracheostomy in the morbidly obese patient. If attention is paid to these details, however, tracheostomy provides clinically important benefits in this difficult clinical situation.

Free flap reconstruction of recalcitrant hypopharyngeal stricture.

A case report is presented of the use of a jejunal microvascular free flap for the reconstruction of a hypopharyngeal stricture caused by caustic ingestion. Although the airway was reestablished, there was aspiration and diplophonia. This case is discussed as an example of an effective treatment of a difficult problem, but one posing secondary problems arising from the use of jejunum.

Cutaneous photoprotection using a hydroxyl radical scavenger in photodynamic therapy.

Photodynamic therapy (PDT) is emerging as an effective therapy for a variety of malignant diseases, including head and neck cancer. Prolonged cutaneous photosensitivity following therapy, however, remains the most significant side effect. The biochemical mechanism of this sensitivity, and indeed of the tumoricidal effect of PDT, is uncertain, but is believed to involve formation of singlet oxygen and possibly other oxygen-derived free radicals. This laboratory recently reported that a singlet oxygen scavenger, diphenylisobenzofuran (DPIBF), afforded cutaneous photoprotection to 67% of animals treated with PDT. Those results, the first from an in vivo study, supported the idea that singlet oxygen plays a significant role in PDT and its associated toxicity. They also, however, suggested that it is not the sole intermediate. The current study looks at the photoprotective effects of the hydroxyl radical scavenger dimethyl thiourea, alone and in conjunction with DPIBF. Our results strongly support a role for the hydroxyl radical in producing the cutaneous phototoxicity associated with PDT.

Verdins in photodynamic therapy of squamous cell carcinoma.

Photodynamic therapy (PDT) is a relatively new treatment modality employing photoactive drugs in combination with light to destroy malignant tissue. Porphyrins (ie, hematoporphyrin derivative and dihematoporphyrin ether) have been the most thoroughly investigated photoactive drugs. The primary limitation of the use of porphyrins in PDT is the shallow depth of effective tumor kill. Each photoactive drug is activated maximally by light of a particular wavelength, and longer wavelengths are able to penetrate tissue to a greater depth. Hematoporphyrin derivative and its semipurified form, dihematoporphyrin ether, are activated by light at 630 nm, which penetrates tissue to a maximum of 8 mm. The search for more effective photosensitizers is under way. Verdins, photoactive compounds in the class of chlorins, have recently been synthesized with activating wavelengths near 700 nm. This longer activation wavelength should theoretically allow a greater depth of tumor kill. Verdins have been shown to be effective photosensitizers in a urothelial carcinoma model in rats. In this study, we investigated the effectiveness of these compounds on squamous cell carcinoma in the hamster cheek pouch model.

Prevention of cutaneous phototoxicity in photodynamic therapy.

Photodynamic therapy using hematoporphyrin derivative (Hpd), or its semipurified form, dihematoporphyrin ether (DHE), in combination with light, has proven effective in the treatment of several types of neoplasms including squamous cell carcinoma. A major disadvantage of this therapy is the long-term retention of these drugs in skin, which may result in cutaneous phototoxicity for weeks after treatment. Singlet oxygen has been identified as the primary cytotoxic product in the reaction of Hpd and light in vitro. This study demonstrates the protective effect in vivo of the singlet oxygen scavengers 1,3 diphenylisobenzofuran and L-tryptophan on the skin of young rats exposed to light after receiving DHE.

Thrombolysis with systemically administered t-PA in a new venous thrombosis model.

Early thrombosis of either the arterial or venous supply of a free flap or island pedicle flap results in total flap necrosis. Until very recently, the only option for flap salvage was surgical intervention and, often, revision of the vascular pedicle. Current advances in the pharmacologic treatment of coronary artery and deep leg vein thrombosis have kindled interest in the field of reconstructive surgery for pharmacologic treatment of thromboses that compromise flaps. In the past, there has been research on the local and systemic administration of thrombolytic agents for lysis of experimentally induced thrombi in various animal models. A new venous inversion graft thrombosis model is presented here, which possesses many advantages over previously employed research models. This study demonstrates thrombolysis with systemically administered tissue plasminogen activator (t-PA) in this model.

Real time multivariable laser Doppler analysis of arterial and venous compromise.

Laser Doppler perfusion monitoring was used to assess microcirculatory blood flow, volume, and velocity before and after total arterial or total venous occlusion in 18 buttock island flaps. Critical analysis of these three laser Doppler perfusion values was found to be useful in differentiating adequately perfused skin from inadequately perfused skin, as well as in distinguishing arterial from venous compromise. Multivariable laser Doppler analysis demonstrated that arterial occlusion produced a more rapid and greater percentage decrease in flow and volume values than did venous occlusion. Arterial occlusion produced an insignificant percentage change in velocity values, whereas venous occlusion produced a substantial percentage decrease in velocity values. The substantial intrasubject and intersubject variability in absolute laser Doppler perfusion values suggests that normalized or percentage change values are more revealing than absolute values, although they require the acquisition of reliable baseline data.

Leeches. Objective monitoring of altered perfusion in congested flaps.

In plastic and reconstructive surgery, there has been new interest in the use of the medicinal leech (Hirudo medicinalis) for the treatment of venous congestion. To the best of our knowledge, no study has been performed to objectively demonstrate the benefits of leeching a congested flap. Doppler laser perfusion monitoring (DLPM) was used to record blood flow changes in pig rump flaps compromised by venous occlusion. With the application of leeches to nine congested pig rump flaps, significant increases in blood flow were demonstrated both clinically and by DLPM. It is concluded from this study that DLPM can demonstrate objective improvement in microcirculatory perfusion with leeching.

ATP dependence of vesicular stomatitis virus transcription initiation and modulation by mutation in the nucleocapsid protein.

We recently reported that vesicular stomatitis virus pol R mutants contain a template-associated N-protein alteration which allows for efficient readthrough of leader RNA termination sites in vitro (Perrault et al., Cell 35:175-185, 1983). We show here that in vitro RNA synthesis mediated by pol R virions is much more resistant to replacement of ATP by the analog beta,gamma-imido ATP than by wild-type virus (approximately 50% inhibition versus approximately 95%). Characterization of beta,gamma-imido ATP-resistant and control products by size, polyadenylic acid content, frequency of initiation at the 3' end of the template, and readthrough of the leader-N gene junction leads us to conclude the following: (i) most likely, the ATP dependence of the transcription process primarily reflects a requirement for initiation or entry of the polymerase at the 3' end of the template; (ii) this requirement is largely bypassed in the mutant pol R viruses; (iii) the synthesis of small, internally initiated transcripts by wild-type virus is less dependent on ATP than that of leader RNA; and (iv) termination at leader RNA sites is not directly affected when beta,gamma-imido ATP is added before initiation of synthesis. These results are discussed in terms of the possible roles of ATP and the nucleocapsid protein in initiation and termination of vesicular stomatitis virus RNA synthesis.