The walking dead: sequential nuclear and organelle destruction during hair development.

BACKGROUND: Transition of hair shaft keratinocytes from actively respiring, nucleated cells to structural cells devoid of nucleus and cytoplasm is key to hair production. This form of cell 'death', or cornification, requires cellular organelle removal to allow the cytoplasm to become packed with keratin filament bundles that further require cross-linking to create a strong hair fibre. Although these processes are well described in epidermal keratinocytes, there is a lack of understanding of such mechanisms, specifically in the hair follicle. OBJECTIVES: To gain insights into cornification mechanisms within the hair follicle and thus improve our understanding of normal hair physiology. METHODS: Scalp biopsies and hair-pluck samples were obtained from healthy human donors and analysed microscopically after immunohistochemical staining. RESULTS: A focal point of respiratory activity was evident in keratogenous zone cells within the hair shaft, which also exhibited nuclear damage. Nuclear degradation occurred via both caspase-dependent and caspase-independent pathways. Conversely, mitophagy was driven by Bnip3L and restricted to the boundary of the keratogenous zone at Adamson's Fringe. CONCLUSIONS: We propose a model of stepwise living-dead transition within the first 1 mm of hair formation, whereby fully functional, nucleated cells first consolidate required functions by degrading nuclear DNA, yet continue to respire and provide the source of reactive oxygen species required for keratin cross-linking. Finally, as the cells become packed with keratin bundles, Bnip3L expression triggers mitophagy to rid the cells of the last remaining 'living' characteristic, thus completing the march from 'living' to 'dead' within the hair follicle.

Laser-assisted thermal angioplasty in human peripheral artery occlusions: mechanism of recanalization.

Recanalization of completely occluded superficial femoral or popliteal arteries was attempted in 18 patients with use of an Argon laser-mediated thermal probe. The length of the occluded segments varied between 0.5 and 26.0 cm, but 67% of the occlusions were greater than 9 cm long. The initial success rate was 67%. Arterial perforation occurred in six patients but was not associated with major complications. To study the mechanism of the laser-mediated thermal probe, thermal recanalization was performed on 11 human arterial segments in vitro obtained after amputation, and mechanical recanalization was performed in vitro in 10 human peripheral arteries with use of a guide wire and catheter technique. An additional four arteries were studied with the laser probe as a non-heated mechanical device. Both the mechanical and thermal devices appear to follow a similar pathway through a complete obstruction. These studies suggest that the thermal probe burns through soft fibrous tissue but is mechanically deflected away from hard fibrocalcific plaque. The probe then advances along the plane between the intimal plaque and the media for a variable length before perforating through the adventitia. These observations suggest that the major mechanism of thermal probe recanalization may be a mechanical process. It appears that thermal probe devices do not inherently seek the true lumen of an occluded artery and that better guidance systems need to be developed.

The current status of surgery for bullous emphysema.

The great majority of cases of emphysema are generalized with diffuse involvement of all portions of the lung: Clearly, surgery has little to offer in such cases. In contrast, there is an uncommon variant involving primarily the upper lobes and the superior portions of the lingula and lower lobes, which spares the relatively normally functioning lower lobes. A number of diagnostic tests are available to identify compression of uninvolved lower lobe tissue, the most reliable of which identify pulmonary vasculature that is crowded together. We suggest that whole lung tomograms or pulmonary angiograms provide the most convincing evidence of compression of normal tissue. In properly selected patients with compression or displacement of normal lung, thoracotomy with simple excision of the bullae is tolerated by even the most ill patients if care is taken to carefully support the patient postoperatively with assisted ventilation and prolonged chest tube suction. There were no deaths in 19 patients and the results were rewarding, often spectacular, and surprisingly enduring. It is likely that some patients with operable bullous emphysema are not being studied or offered operation because of a lack of knowledge about the benefits possible with bullectomy.

Successful prolonged heparinless venoarterial bypass in sheep.

In order to investigate the safety of prolonged heparinless venoarterial bypass (HL-VAB), we subjected 18 sheep to prolonged HL-VAB for up to 6 days. Three animals died of granulomatous lung abscess and one died from intra-abdominal abscess. One animal died of generalized thromboembolism secondary to mechanical damage of the nonthrombogenic coating occurring at the time of cannulation. HL-VAB was successfully carried out in 13 sheep. Although clots were found at all tubing connections where blood turbulence occurred, only the previously mentioned animal showed evidence of thromboembolism. Damage to the nonthrombogenic tubing exposed to the roller pump head was seen in all animals, and its severity appeared to be related to the duration of bypass. Scanning electron microscopic examination revealed scattered platelet aggregates on the nonthrombogenic coated surfaces without clinical evidence of embolization. Hematocrit values, leukocyte counts, platelet counts, prothrombin time (PT), activated partial thromboplastin time (PTT), thrombin time (TT), plasma fibrinogen levels, and factor V and VIII levels remained unchanged, whereas free plasma hemoglobin levels rose slightly during 6 days of HL-VAB. HL-VAB for up to 6 days appears to have little adverse effect on blood cells and blood coagulation factors. For current clinical use, the nonthrombogenic coated tubing circuit should be changed every 48 hours because of time-related trauma to the coated tubing from the roller pump.

Experimental evaluation of hypothermic intermittent coronary perfusion.

The recovery of the myocardial contractility of blood-perfused papillary muscle from the rabbit hearts was used to determine if hypothermia would minimize the myocardial injury associated with intermittent aortic cross-clamping (IACC). Continuous normothermic coronary perfusion for 2 hours with either cross circulation or a membrane oxygenator had only minimal adverse effects on contractility. None of the hearts tolerated normothermic IACC (45 minutes of anoxia and 10 minutes of reperfusion, repeated twice), When the myocardial temperature was reduced to 32 degrees C., the recovery following IACC was 41.25 +/- 11.21 percent (n=8). With hypothermia of 28 degrees C., it was 70.43 +/- 13.03 percent (cross circulation group, n=7) or 68.36 +/- 13.11 percent (membrane oxygenator group, n=7). If the hearts were cooled to 24 degrees C., the recovery of the myocardial contractility following IACC was 90.95 +/- 5.42 percent (n=11). The improvement of the degree of recovery by hypothermia was statistically highly significant (p less than 0.005). Creatine phosphokinase (CPK) and isoenzymes (CPK-MB) were also measured in some groups, but the results warrrant further studies before they can be correlated with the myocardial function.

Oxygen consumption of the normal and failing heart during left heart bypass.

In order to determine whether myocardial oxygen consumption (MOC) is decreased during left heart bypass (LHB), two groups of 6 dogs each were subjected to 2 hours of heparinless LHB. Group 2 differed from Group 1 in that cardiogenic shock was induced by temporary coronary artery occlusion prior to LHB. In Group 1 animals (normal dogs), MOC decreased significantly during the surgical preparation but did not change appreciably during subsequent LHB. Upon completion of LHB, MOC increased slightly in all animals. This increase in MOC was insignificant, however, when adjusted to changes in mean aortic blood pressure (MAP). A highly positive linear correlation between MOC and MAP was noted regardless of whether the animals were on or off bypass. In Group 2 animals, MOC was markedly decreased after the iduction of cardiogenic shock but gradually increased during the 2 hours of LHB. Upon completion of bypass, MOC of the damaged heart increased to a remarkable degree, but not to initial control levels. However, the linear correlation between MOC and MAP, noted before the induction of cardiogenic shock, disappeared after shock and was not restored after 2 hours of apparently successful bypass. We have concluded that MOC is decreased surgical stress and is further decreased by temporary coronary artery occlusion. MOC is not, however, reduced by nearly total or total LHB in normal hearts. MOC is markedly decreased by cardiac damage but gradually increases in damaged hearts by the use of LHB.

Preservation of myocardial ultrastructure.

This study compares the effects of 2 hour periods of normothermic anoxic arrest, continuous normothermic coronary perfusion, continuous cold coronary perfusion, and topical cooling of the ischemic myocardium on survival and ultramicroscopic structure of the canine myocardium. No animal survived 2 hours of normothermic anoxic arrest. Severe ultrastructural damage was observed in the nuclei, mitochondria, and myofibrils. Topical cooling of the ischemic myocardium to 15 degrees C. markedly improved survival and preservation of the myocardial fine structure. Continuous perfusion of the coronary arteries with cold blood resulted in 100 per cent survival through the experimental period, with preservation of the normal myocardial ultrastructure. The technique of cold coronary perfusion should be particularly useful in cardiac surgical patients in whom maximal preservation of myocardial function is essential for survival.

Functional evaluation of normothermic intermittent coronary perfusion.

The myocardial contractility of papillary muscle from rabbit hearts was used to evaluate various techniques of normothermic intermittent coronary perfusion. A progressive decline of the myocardial contractility was noted as aortic cross-clamping and coronary reperfusion were repeated. After a net anoxic period of 90 minutes, the contractility fell to 58.67, 60.2, and 40 percent of the base line when single aortic cross-clamping time was 5, 10, and 15 minutes, respectively, interrupted by 5 minutes of reperfusion. Repeated application of single cross-clamping of 20 minutes or longer was not tolerated by the rabbit hearts. When the heart was reperfused for 10 minutes, between 15 minute periods of anoxia, the final recovery of contractility was 62 percent. Normothermic intermittent coronary perfusion has a significant adverse effect on the myocardial contractility. If this technique is to be used, single anoxic times should not be longer than 15 minutes and the heart must be reperfused for at least 10 minutes.

Extrapleural and extraperitoneal staged technique in successful management of complicated thoracic anastomotic aneurysm.

A simplified, staged technique was employed in the management of a descending thoracic aortic pseudoaneurysm occurring in a thoracic aortobifemoral graft that had been placed 10 years earlier. Our initial procedure comprised ligature of the femoral limbs of the functional thoracic aortobifemoral graft together with a right axilloinfrarenal aortobifemoral bypass. This was followed by definitive descending thoracic pseudoaneurysm management 2 weeks later via a thoracoabdominal extrapleural-extraperitoneal approach. This staged approach provided by a preformed shunt, eliminated the disadvantages of heparinization, hemolysis, or trauma of cannulation during the definitive thoracic aneurysmectomy procedure. Ligature and defunctionization of the original thoracic aortofemoral graft simplified the operative dissection, and the extrapleural and extraperitoneal approach minimized postoperative complications.

Simplified technique for the management of refractory varicose ulcers.

A technique of accurately visualizing incompetent perforating veins with the use of intraosseous venography following muscle stimulation is described. The procedure was employed in 55 patients with recurrent stasis ulcers who had had previous operations. Surgical management incorporating our venographic technique yielded extremely satisfactory results in this selected group.

Peripheral embolism resulting from unsuspected atheromatous aortic plaques.

Three cases of peripheral embolism resulting from atheromatous aortic plaques are reported. Although the majority of arterial thromboemboli are believed to have originated from mural thrombi within one of the cardiac chambers, there is reason to believe that embolism from atheromatous material within a major artery may occur more often than is represented in current literature. Successful management of this condition will necessitate (1) clinical awareness, (2) careful scrutinization of material recovered from embolectomy, (3) angiography to demonstrate the embolic source in the aorta or its main braches, and (4) appropriate remedy by either endarterectomy or graft replacement of the diseased artery segment. The pitfalls in the diagnosis of this condition are discussed.

Successful management of prosthetic graft infection with continuous povidone-iodine irrigation.

In ten consecutive patients, prosthetic graft infections were managed by a continuous povidone-iodine irrigation technique supplemented by intravenous administration of an appropriate antibiotic. A colostomy bag apparatus was used to ensure constant soaking and immersion of the infected wound. Wound healing occurred in all patients either by secondary intention, direct suturing, or rotation graft technique, and all grafts except one have remained patent and functional over a follow-up period of one to four years. The effectiveness of this management modality permits control of infection without the necessity of prosthetic graft removal and eliminates the need for other intricate bypass operations in these patients with sepsis who are often critically ill.

Extended axillopopliteal-axillotibial bypass. Valuable adjunct to limb revascularization.

Although axillofemoral bypass is now widely used, little has been reported of its more distal extension. Our experience in 12 patients with axillopopliteal (nine) and axillopopliteal-tibial (APT) (three) bypass form the basis of this report. Indications for these extended bypasses included suppurative groin infections and obliterated common and profunda femoris arteries. These procedures were rapidly performed in poor-risk and often critically ill patients. One patient died of recurrent aortoduodenal hemorrhage three weeks following successful APT bypass. The other 11 patients enjoyed patent grafts for periods ranging from six months to two years, although four of these patients successfully underwent a declotting procedure during this period. The early results of these extended APT grafts have been gratifying. This technique would seem to be especially promising for the management of limb ischemia or for rerouting in patients with infected aortic prosthesis.

Peripheral atheroembolism: an enigma.

Fifteen patients with peripheral atheroembolism were studied and followed up for from one to three years. Clinical recognition of this condition is often masked by its elusive presentation. Foot pain may be the very earliest symptom. Transient presentation is an important feature. Eventually, gangrene develops in the toes. Ankle pulses are present on physical examinations. Both aortography showing proximal ulcerative plaques and digital arteriograms revealing the sharp cutoff pattern of an arterial embolus provide diagnostic confirmation. The results of treatment were satisfactory in all instances following aortoiliac endarterectomy or Dacron graft interposition. In five patients wiht gangrenous changes, toe amputation was necessary.

Prevention of paraplegia associated with resection of extensive thoracic aneurysms.

A review of the literature suggests that paraplegia associated with thoracic aortic surgery is preventable if intraoperative hypotension is eliminated, the distal aorta perfused adequately, and the intercostal arteries below T-8 level preserved. A surgical technique has been developed that leaves the posterior aortic wall, preserving the intercostal arteries below the level of T-8, and interspersing a diagonally tailored prosthesis with the aid of left atrial-to-femoral arterial bypass without heparinization. Seven patients with extensive aneurysms involving the entire descending thoracic aorta were operated on successfully by this technique without neurological complications.

In situ saphenous vein bypass.

Our 20-year results with in situ saphenous vein grafting in the lower extremity were reviewed and compared wih those where reversed saphenous veins were employed. The ten-year patency rates for both types of grafts terminating at the popliteal artery ranged from 41% to 43% and showed no statistical difference. The reversed saphenous vein performed well in the femoropopliteal position because the vein is usually of the same size at the knee as in the groin and thus does not taper when reversed. We have identified from our study specific indications for the in situ operation. These indications are the presence of small or substantially tapering or bifurcating great saphenous veins that otherwise would be unsatisfactory for conventional reversed vein grafting. We believe that the in situ saphenous vein operation should be considered before resorting to prosthetic leg grafts that carry a lower long-term patency, particularly when carried below the knee.

Management of lymph fistula in the groin after arterial reconstruction.

Leakage of lymph from the inguinal incision is a rare but disturbing complication of arterial surgery. This article describes our experience in the management of 12 patients in whom lymphorrhea developed following arterial reconstruction. Seven patients were treated with pressure dressings, antibiotics, and immobilization. In this group, fistula healing was delayed up to four weeks, and wound infection occurred in three of seven patients. One patient eventually required removal of the prosthetic graft and below-knee amputation. Early groin reexploration and direct ligature of ruptured lymphatics was performed in the remaining five patients. Hospitalization was shortened and wound infection prevented in all patients in this group. We recommend prompt operative closure as the preferred approach in the management of lymph fistula following vascular reconstruction, especially when synthetic graft material is present.

Stump pressure: an unreliable guide for shunting during carotid endarterectomy.

A correlative analysis was made between the neurological status of the awake patient and the internal carotid artery stump pressure in 125 consecutive patients undergoing carotid endarterectomy. There was no mortality in this series. Twenty-four patients lost consciousness immediately after carotid cross-clamping, even though stump pressures were above 50 mm Hg in more than one third of the cases. The majority (80.8%) of the patients tolerated cross-clamping (stump pressures were between 20 and 90 mm Hg). This study demonstrated the variability of cerebral tolerance relative to absolute stump pressure guidelines, such as 25 or 50 mm Hg; reliance on these values to determine the need for intraoperative shunting could lead to stroke at operation. Our experience also showed that assessment of the awake but tranquil patient continues to be the safest and most reliable guide to selective shunting during carotid endarterectomy.

Total body washout for the treatment of endotoxin shock. An experimental study.

In order to study the therapeutic effects of total body washout (TBW) in experimental endotoxin shock, we used the following procedure. Seventeen rabbits (controls) received Escherichia coli endotoxin (5 mg/kg) intravenously and were observed for 12 hours. Shock developed in 14 rabbits; they died in 5.2 +/- 1.0 (mean +/- SD) hours, with a survival rate of 18%. Seventeen rabbits were subjected to TBW only. Muscle temperature was lowered to 25 C with a pump oxygenator circuit and the animals were exsanguinated. After residual blood was flushed out with cold, lactated Ringer solution, the animals were rewarmed with another circuit that was primed with homologous blood. Fourteen animals survived (82%). Two hours after E. coli endotoxin was injected intravenously 17 animals were treated with TBW. The survival rate (53%) of this group was significantly higher than in the control group (18%) (P less than .005). Eight nonsurvivors showed hypotension and acidosis even after TBW treatment, thus indicating the irreversibility of their endotoxin shock. This study indicates that endotoxin shock may be reversed by TBW if it is instituted before irreversible cellular damage.

Retinal artery emboli. Indications for angiography and carotid endarterectomy.

Six patients with ocular symptoms were referred by the Eye Service to the Vascular Service because of the presence of cholesterol emboli on fundoscopic examination of the retinal arteries. None of the six patients had classic intermittent retinal or cerebral ischemic attacks. Four-vessel aortic arch arteriogram was suggested and significant ipsilateral carotid disease was found in all patients. Four patients underwent carotid endarterectomy, with removal of ulcerated plaques from the carotid bifurcation. Two patients had total occlusion of the ipsilateral internal carotid artery and therefore were not operative candidates. The presence of retinal cholesterol emboli is an indication for extracranial arteriography. When ipsilateral ulcerative disease is found, carotid endarterectomy is indicated regardless of the symptoms.