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.

The evolution of extracranial carotid artery surgery as seen by one surgeon over the past 40 years.

Carotid endarterectomy is one of the most common vascular and neurosurgical operations. Controversies regarding its indications and safety have required several decades before general resolution, while its methodology is still debated. The first operations are described with particular emphasis on the epic successful procedure in 1954 by Eastcott and Rob. Early procedures were on patients with frank strokes with poor results. The development of carotid endarterectomy was slow because neurologists were unsure of its effectiveness and safety as the mortality and stroke results recorded by untrained surgeons were unacceptable. It was not until some 35 years after its introduction that randomised controlled trials, both in North America and Europe, defined its indications and demonstrated its benefits for both symptomatic and asymptomatic carotid stenosis. Clamping of the carotid vessels, required during endarterectomy, may result in various degrees of cerebral ischaemia. Methods to determine which patients need shunting are compared. The author has employed local neck block anesthesia since 1972, which is the only method that provides constant neurological assessment for selective shunting during carotid cross clamping. Evidence is presented showing that local anaesthesia also reduces complications of general anaesthesia, especially myocardial infarction. The technique of neck block, conventional endarterectomy and two varieties of eversion endarterectomy for carotid disease are described. Each of these techniques of endarterectomy is advantageous in certain circumstances, suggesting that vascular surgeons should ideally be proficient in each. Likewise, the management of early stroke after operation, stenotic or occluded external carotid the presence of retinal Hollenhorst plaques, and the totally occluded internal carotid, is presented. Finally, observations on some famous figures who suffered from cerebrovascular complications secondary to carotid disease and what effect it may have had on world history is discussed.

Primary closure of infected diabetic foot wounds. A report of closed instillation in 30 cases.

Multiple surgical strategies are available for managing the infected diabetic foot at risk for amputation. The authors present their experience with the closed instillation system in the management of 30 such cases in 29 patients over a 5-year period. Data were collected from the hospital records of neuropathic patients presenting with deep-plantar-space infections or presumed acute osteomyelitis. All 29 patients were male; 57% had marginal or poor vascular supply, and 83% were nutritionally compromised or had proteinuria. At the conclusion of the study, 34% of the patients were dead, reflecting the severity of comorbid conditions found in this population. Despite the marginal healing capacity of these patients, the procedure had a 90% success rate, as defined by expeditious return to prior level of functioning and residential living situation without need for re-operation or higher-level amputation.

Solitary pulmonary nodules: Part I. Morphologic evaluation for differentiation of benign and malignant lesions.

The solitary pulmonary nodule is a common radiologic abnormality that is often detected incidentally. Although most solitary pulmonary nodules have benign causes, many represent stage I lung cancers and must be distinguished from benign nodules in an expeditious and cost-effective manner. Evaluation of specific morphologic features of a solitary pulmonary nodule with conventional imaging techniques can help differentiate benign from malignant nodules and obviate further costly assessment. Small size and smooth, well-defined margins are suggestive of but not diagnostic for benignity. Lobulated contour as well as an irregular or spiculated margin with distortion of adjacent vessels are typically associated with malignancy. There is considerable overlap in the internal characteristics (eg, attenuation, cavitation, wall thickness) of benign and malignant nodules. The presence of intranodular fat is a reliable indicator of a hamartoma. The presence and pattern of calcification can also help differentiate benign from malignant nodules. Computed tomography (CT) (particularly thin-section CT) is 10-20 times more sensitive than standard radiography and allows objective, quantitative assessment of calcification. Initial evaluation often results in nonspecific findings, in which case nodules are classified as indeterminate and require further evaluation to exclude malignancy. Growth rate assessment, Bayesian analysis, contrast material-enhanced CT, positron emission tomography, and transthoracic needle aspiration biopsy can be useful in this regard.

Solitary pulmonary nodules: Part II. Evaluation of the indeterminate nodule.

Various strategies may be used to evaluate indeterminate solitary pulmonary nodules. Growth rate assessment is an important and cost-effective step in the evaluation of these nodules. Clinical features (eg, patient age, history of prior malignancy, presenting symptoms, smoking history) can be useful in suggesting the diagnosis and aiding in management planning. Bayesian analysis allows more precise determination of the probability of malignancy (pCa). Decision analysis models suggest that the most cost-effective management strategy depends on the pCa for a given nodule. At contrast material-enhanced computed tomography, nodular enhancement of less than 15 HU is strongly predictive of a benign lesion, whereas enhancement of more than 20 HU typically indicates malignancy. At 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography, lesions with low FDG uptake are typically benign, whereas those with increased FDG uptake are typically malignant. Results of transthoracic needle aspiration biopsy influence management in approximately 50% of cases and, in indeterminate lesions with a pCa between 0.05 and 0.6, is the best initial diagnostic procedure. It is optimally used in peripheral nodules and has been reported to establish a benign diagnosis in up to 91% of cases. Although there is no one correct management approach, the ability to distinguish benign from malignant solitary pulmonary lesions has improved with the use of these strategies.

Thoracic manifestations of breast carcinoma: metastatic disease and complications of treatment.

Breast cancer, a common malignancy in women, is a major cause of cancer-related deaths. Metastases to the thorax are common in patients with breast cancer. Metastases can manifest radiographically as pulmonary nodules, lymphangitis carcinomatosa, endobronchial masses, intrathoracic adenopathy, pericardial or myocardial masses and pleural effusions. Additionally, pulmonary abnormalities occur after radiotherapy, chemotherapy and autologous bone marrow transplantation. Knowledge of the various intrathoracic manifestations of metastases and complications of therapy is important in staging and evaluating patients with breast cancer and deciding on the most appropriate treatment.

Lung cancer staging and management: comparison of contrast-enhanced and nonenhanced helical CT of the thorax.

PURPOSE: To determine whether contrast material-enhanced helical computed tomography (CT) of the thorax and upper abdomen changes the tumor stage and management compared with nonenhanced helical CT in patients with newly diagnosed lung cancer. MATERIALS AND METHODS: During 15 months, any patient in whom lung cancer was strongly suspected or newly diagnosed and who was scheduled for thoracic CT was considered eligible for the study. All patients underwent nonenhanced thoracic helical CT from the lung apices through the adrenal glands and then contrast-enhanced thoracic helical CT from the lung apices through the entire liver. Each study was read independently, and the thoracic radiologic stage was determined. Tissue sampling was performed and the final pathologic stage assigned. RESULTS: Ninety-six patients had a final pathologic diagnosis of lung cancer. There was agreement in stage between the nonenhanced and contrast-enhanced examinations in 92 of the 96 patients. In three patients, the tumor stage at nonehanced CT increased at contrast-enhanced CT, from IA to IIA (n = 1), IIB to IV (n = 1), and IIIB to IV (n = 1). In one patient, the tumor stage decreased from IIIB to IIB. There was no substantial change in management of any patient. CONCLUSION: The results suggest that contrast-enhanced thoracic CT through the liver for staging lung cancer rarely changes the tumor stage determined with nonenhanced CT through the adrenal glands and does not substantially influence management decisions.

Opportunistic fungal pneumonia.

Opportunistic fungal infection is a common cause of serious morbidity and mortality in immunocompromised patients. These infections occur primarily in patients with chemotherapy-induced neutropenia, acquired immunodeficiency syndrome. or immunosuppression after solid organ or bone marrow transplantation. The most important opportunistic fungal pathogens include Cryptococcus neoformans, Candida and Aspergillus species, and the fungi that cause mucormycosis. Opportunistic pneumonia caused by previously unrecognized pathogens, such as Fusarium, Penicillium, and the dematiaceous fungi, are increasingly reported. The clinical and radiologic features of opportunistic fungal pneumonia are highly variable and often nonspecific. Diagnosis requires knowledge of the various modes of presentation, radiologic manifestations, and epidemiology of these infections. Because many of these organisms can colonize the upper airway, sputum cultures are considered diagnostically unreliable. Instead, definitive diagnosis requires culture of the fungus from infected tissue or demonstration of the organism on microscopic examination.

Bronchial anastomotic complications in lung transplant recipients: virtual bronchoscopy for noninvasive assessment.

PURPOSE: To compare the accuracy of virtual bronchoscopy (VB) with that of axial computed tomography (CT) in the assessment of bronchial anastomotic complications in lung transplant recipients. MATERIALS AND METHODS: Twenty-seven bronchial anastomoses in 17 patients were evaluated with helical CT. Axial CT and VB images were evaluated for surface irregularity and the presence, length, and severity of stenosis. Findings were correlated with the results of fiberoptic bronchoscopy (FOB). RESULTS: There were 12 anastomotic stenoses at FOB. Pooled accuracy (among all four readers) of VB and axial CT for diagnosis of clinically relevant stenosis was 97% and 80%, respectively, at the right bronchial anastomoses and 92% and 75%, respectively, at the left bronchial anastomoses. Pooled accuracy of VB and Axial CT for stenosis length was 72% and 62%, respectively, at the right anastomoses and 81% and 69%, respectively, at the left anastomoses. These differences were not statistically significant. Both the VB and axial CT images showed surface irregularities when anastomotic infection (n = 2) or dehiscence (n = 1) was present but resulted in an overdiagnosis of mucosal abnormalities when anastomoses were normal. CONCLUSION: VB was slightly more accurate than axial CT for diagnosis of clinically relevant stenoses at bronchial anastomoses in lung transplant recipients. However, because VB is not 100% accurate and has no role in the diagnosis of infection or dehiscence, it probably will not replace FOB for assessment of bronchial anastomotic complications in this population.

Hume Memorial lecture. Prevention of spinal cord complications in aortic surgery.

Paraplegia or paraparesis after operations on the thoracic and abdominal aorta is a devastating event, both for the patient and the surgeon. While its incidence varies from under 1% with operations at the top and bottom of the aorta, its occurrence in the midportion of the aorta, just above the diaphragm, even in the best of hands exceeds 10%. Over a decade ago, Crawford et al (J Vasc Surg. 1986;3:389-404) introduced the use of inclusion and sequential clamping techniques for thoracoabdominal aneurysmectomy, lowering both morbidity and neurologic sequelae. Although these techniques have been widely adopted, newer ancillary adjuncts have been recommended by a number of investigators. This paper summarizes the possible causes of paraplegia secondary to the various operations on the aorta and analyzes the status and value of the various ancillary techniques in its prevention.

Making the diagnosis of osteomyelitis. The role of prevalence.

Clinicians may have poor sensitivity in determining whether a given diabetic patient with a foot ulcer has osteomyelitis. Thus many turn to diagnostic tests. The literature was reviewed and data on the sensitivity and specificity of five commonly used diagnostic tests were compiled. Using Bayes' theorem, the authors' analysis suggests that pretest probability may be more important in the decision-making process than individual test characteristics. Also, a positive probe-to-bone test is as predictive of osteomyelitis as the other four tests. A negative magnetic resonance imaging test most likely rules out osteomyelitis. Interpretation of any test result is greatly influenced by the pretest probability of disease. Future work needs to focus on aiding the clinician in determining the patient's probability of disease prior to testing in order to optimize patient care.

Preservation of the pelvic circulation during infrarenal aortic surgery.

Paraplegia, ischemia of the colon, and gluteal necrosis are uncommon but devastating sequelae of surgery of the infrarenal aorta. These complications are ischemic in nature, secondary to the following technical maneuvers, individually or in combination: bilateral occlusion of the hypogastric arteries; division of a patent inferior mesenteric artery; or proximal end-to-end aortic to common femoral artery bypass grafting accompanied by stenosis of the external iliac arteries. The etiology of paraplegia after infrarenal aortic surgery is of particular interest since it now appears that it is more likely due to interruption of flow to lumbosacral branches of the hypogastric arteries supplying the conus of the spinal cord and/or to division of a low-lying 'conus medullaris artery' rather than to occlusion of the higher-lying great radicularis artery of Adamkiewicz. Knowledge of the pelvic circulation to the colon, buttocks, and terminal spinal cord allows the surgeon prophylactically to avoid or reconstruct critical branches during operations on the infrarenal aorta. While rare, severe complications cannot be completely eliminated; hopefully their incidence can be reduced by an understanding of their etiology.

Bilateral popliteal artery injury from bumper crush injury.

Blunt trauma to the knee of sufficient force to result in knee dislocation or fracture is commonly associated with popliteal artery injury. The challenging problem of bilateral popliteal artery injury has been rarely reported. We describe a case of bilateral popliteal artery injury after bumper crush injury between two automobiles that illustrates a successful method of management. Expeditious revascularization with minimum ischemia time was obtained by using the posterior approach, rather than the conventional medial approach, allowing two surgical teams to work simultaneously.

Results of bullectomy.

Bullous emphysema patients with severe dyspnea or repeated pneumothorax who demonstrate compression or crowding of relatively normal underlying lung can benefit significantly from surgical intervention. As much of the normal lung should be preserved as possible by excision only of the bullae. Buttressing of the stapled bases of the bullae may minimize postoperative air leak, allowing even simultaneous bilateral operation. Further experience and follow-up of the thoracoscopic approach to bullectomy may establish it as the approach of choice rather than thoracotomy.

Detection of the Staphylococcal mecA gene by chemiluminescent DNA hybridization.

A new solution-phase DNA hybridization capture assay for the rapid detection of the mecA gene in clinical isolates of Staphylococcus was compared with multiplex PCR and disk diffusion methods. The assay uses a DNA capture probe immobilized on paramagnetic particles and a second DNA probe labeled with an acridinium ester. Bacteria from 24-h cultures are lysed, and the lysates are hybridized with the DNA probes. After magnetic separation to remove unhybridized labeled probe, the mecA gene is detected by the chemiluminescence of the hybridized probe. Four hundred consecutive staphylococcal isolates were assayed, including 147 S. aureus and 253 coagulase-negative Staphylococcus isolates. Among the S. aureus isolates, 14 of 147 were MecA+ by both the hybridization capture assay and PCR; 133 of 147 were MecA negative by both assays (positive and negative predictive values, 100%). Comparison of disk diffusion results with those obtained by genotypic methods indicated that 14 of 147 S. aureus isolates judged to be resistant were positive by both methods; 119 of 147 were Oxs and negative by both genotypic methods (positive and negative predictive values, 50 and 100%, respectively). The remaining 14 S. aureus isolates were MecA- Oxr; among these, 13 were beta-lactamase hyperproducers. For coagulase-negative staphylococci, 130 of 253 were MecA+ by the hybridization capture assay; 129 of 130 of these isolates were positive by PCR (positive and negative predictive values, 99.2 and 100%, respectively). Comparison with the disk diffusion assay showed that 128 of the coagulase-negative MecA+ isolates were Oxr; 111 of 253 were MecA- and Oxs (positive and negative predictive values, 90.8 and 99.1%, respectively). Thirteen coagulase-negative isolates were MecA-Oxr; among these, three were beta-lactamase hyperproducers. Comparison of the hybridization capture assay results with PCR indicates that the DNA hybridization assay is a sensitive and specific test for the detection of the mecA gene in clinical isolates of Staphylococcus.

Inguinal wound fluid collections after vascular surgery: management by early reoperation.

Inguinal wounds complicated by significant fluid collections after vascular grafting procedures were managed by exploration soon after recognition in 14 patients. Within 24 hours, incisions were reexplored, fluid collections were evacuated and cultured, and closed suction drains were placed. The wound was reapproximated, and broad spectrum antibiotics were given intravenously until 24 hours after removal of the drain. Variables evaluated included spontaneous drainage before exploration, positive intraoperative wound cultures, exposure of graft when the wound was opened, and type of graft used. On careful follow-up, from 5 months to 3.5 years, averaging 14 months, only one patient had an infected graft, occurring 6 months after the wound exploration. There were no complications in wound healing from the inguinal explorations. These results suggest that early exploration and reclosure of clinically significant postoperative fluid collections is safe, results in primary healing, and has a low rate of subsequent graft infection.

Vascular access surgery as an outpatient procedure.

Construction of a vascular access site for hemodialysis has traditionally been done on an inpatient basis or more recently in a hospital operating room as a 1-day admission. Over 18 months we performed 49 vascular access procedures on 45 patients in a freestanding ambulatory surgical center. Four patients had an arteriovenous radiocephalic autogenous fistula constructed, 30 patients had a polytetrafluoroethylene (PTFE) prosthesis inserted as an arteriovenous bridge graft, 11 patients had a planned reconstruction of a previously placed graft, 1 patient had a false aneurysm corrected, 1 patient had a chronically infected graft removed, and 2 patients had a thrombectomy. All procedures were in the upper extremities except for one femorosaphenous PTFE graft and one excision of a false aneurysm in a thigh prosthesis. Only one patient, an 84-year-old woman, required hospitalization following the outpatient procedure because she was unable to care for herself. No postoperative infection had occurred at 1 month follow-up. A left upper extremity graft performed at another inpatient facility was removed because of infection. The protocol for outpatient vascular access surgery includes preoperative evaluation of the patient for determination of the access site within a week of operation; duplex scan of subclavian veins if central venous lines have been in place for more than 2 weeks; scheduling surgery for the afternoon or morning following routine hemodialysis; obtaining a hemoglobin level, serum/electrolyte study, and an ECG following the last hemodialysis; parenteral antimicrobial prophylaxis; local infiltration anesthesia with standby; a minimum of 1 hour of observation in the recovery room; and a repeat hematocrit study prior to discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

An objective method for the assessment of psychosocial problems in adolescents with epilepsy.

Psychosocial problems in adolescents with epilepsy have been of concern for many years, but have been difficult to assess. This article presents the multicenter development of the Adolescent Psychosocial Seizure Inventory (APSI), an empirically based self-report test patterned after the Washington Psychosocial Seizure Inventory, which is used to evaluate psychosocial problems in adults. After pilot work, 120 adolescents with epilepsy from five centers in North America took the APSI and were interviewed by professionals with respect to adequacy of adjustment in eight psychosocial areas. At least one parent or guardian was also interviewed. Interrater reliability of professional ratings in each area was established. Using an item-by-item, empirically based technique, eight psychosocial scales were developed as well as three validity scales. Reliability of the scales was established by both internal consistency and test-retest procedures. Results for each adolescent are presented in profile form. These results give a visual display of the types and extent of problems that likely would be identified in a detailed professional assessment. It is anticipated that the APSI will be of value in a variety of treatment and research contexts.

Cytologic assessment of tumor cell kinetics: applications of monoclonal antibody Ki-67 to fine-needle aspiration smears.

Rates of tumor-cell proliferation often provide prognostic information about a given neoplasm. Previously available methods for accessing cell kinetics are time consuming and expensive, and often require special equipment or radioactive reagents. Monoclonal antibody Ki-67 binds a nuclear antigen expressed in proliferating but not in resting cells. We studied Ki-67 immunostaining of fine-needle aspiration smears from 40 benign and malignant masses. Labeling indices ranged from 0 (thyroid follicular adenoma) to 75 percent (pulmonary oat-cell carcinoma). Frozen section immunostaining (11 cases) and flow cytometric assessment of cell proliferation (8 cases) were in good agreement with Ki-67 labeling indices on smear material. We suggest that this method provides a rapid, inexpensive, and dependable means of assessing tumor-cell kinetics in cytologic preparations.