Screening for cancers of the head and neck: addressing the problem.

More than 90% of upper aerodigestive tract (UADT) cancers occur in people with specific lifestyle risks, including tobacco and alcohol use. More than 90% of tumors occur in easily examined parts of the head and neck, therefore, there is the possibility of identifying the vast majority of patients through selective screening. Physicians should keep in mind that the mucosa's sojourn from visually suspicious (and possibly malignant) tissue is most likely less than two years, and frequent examination of asymptomatic patients is necessary. When patients wait to bring symptoms to medical attention, their cancers will be advanced 60% of the time when the chance of cure is less than 30%. Given the difficulty of implementing regular examinations in a poorly compliant, high risk population, genetic and molecular screening tools may allow very high risk individuals to be identified.

Avoidance of primary post-tonsillectomy hemorrhage in a teaching program.

OBJECTIVE: To determine the incidence of primary post-tonsillectomy hemorrhage in a teaching institution by using a uniform technique, including a 3-minute relaxation of retraction before case termination and the use of bismuth subgallate. DESIGN: Case series. SETTING: Tertiary care academic pediatric center. PATIENTS: A 7-year retrospective study was performed by using the medical records of 1286 children without a bleeding abnormality who underwent tonsillectomy (with or without adenoidectomy). A uniform technique, proposed to reduce hemorrhage, was used for 705 children and was not used for 581 children. RESULTS: No episodes of primary hemorrhage (onset < or = 24 hours after surgery) occurred, and the incidence of delayed hemorrhage (onset >24 hours after surgery) was 1.1% in the study group. The primary hemorrhage rate of the study group was significantly lower (P = .007) than the rate for the reference group (0.0% vs 1.0%), as was the total hemorrhage rate (1.1% vs 4.1%) and the delayed hemorrhage rate (1.1% vs 3.1%). CONCLUSION: A uniform technique including the use of bismuth subgallate and reassessment of the tonsillar fossae after a 3-minute observation period reduces the incidence of primary tonsillar hemorrhage in a teaching institution setting.

Report of the first case of invasive fungal sinusitis caused by Scopulariopsis acremonium: review of scopulariopsis infections.

Scopulariopsis acremonium is a species of saprophytic fungus not previously reported to cause invasive disease in humans, although invasive infections from other species of Scopulariopsis have been reported and are reviewed. Deep infection with this fungus is associated with a high mortality rate. Invasive fungal sinusitis, in general, is a potentially fatal disease that typically affects immunocompromised patients, such as those receiving intensive chemotherapy or undergoing bone marrow transplantation. We report a case of invasive fungal sinusitis caused by Scopulariopsis acremonium in a patient with leukemia, who was successfully treated with amphotericin B, itraconazole, endoscopic sinus surgery, and granulocyte colony-stimulating factor.

The UNOS OPTN (Organ Procurement and Transplantation Network) waiting list: 1988 through November 30, 1992.

Based on data from the OPTN Waiting List and the Scientific Registry between 1988 and 1992: 1. The number of registrations on the overall waiting list increased by 81% between December 31, 1988 and November 30, 1992. On November 30, 1992, there were 29,047 registrations for a transplant in the United States. Organ-specific waiting lists showing strong increases during the period were lung (1,277%), liver (262%), and heart (162%). The number of heart-lung registrants decreased during the period. 2. Overall, Whites comprised the largest percentage of waiting-list registrants, followed by Blacks and Hispanics. This frequency distribution remained relatively constant between 1988 and 1991. On the organ-specific waiting lists, the percentage of Whites ranged from 80% on the liver waiting list to 90% on the pancreas waiting list. Blacks make up about 12% of the United States population, but about 32% of the kidney waiting list, due to the high incidence of end-stage renal disease among Blacks in the United States. 3. The frequency distribution of age on the waiting lists is shifting toward a greater proportion of potential recipients age 45 or older. This trend was especially true for the liver, lung, and pancreas waiting lists. 4. The percentage of highly sensitized registrants (PRA > or = 80%) on the kidney waiting list decreased by 8% between 1988 and 1991. The percentage of registrants with PRA less than 20% increased by 11.3%, probably as a result of longer waiting times for low-PRA registrants. 5. A result of the growth of the waiting lists was an increase in the median waiting time to transplant during the period. This effect was observed on every waiting list except the heart-lung. The wait for a liver transplant was the shortest (67 days in 1991), whereas the wait for a heart-lung transplant was the longest (543 days in 1990). 6. The overall death rate remained relatively stable, but was up slightly in 1991, when 6.1% of registrants died while waiting for a transplant (compared with 5.6% in 1990). The death rate on the heart-lung waiting list fell from 23.5% in 1988 to 14.8% in 1991, probably because of fewer heart-lung registrations. In 1991, the death rates were highest on the thoracic waiting lists (11.7-14.8%), followed by liver (9.3%), kidney (3.7%), and pancreas (3.0%). 7. The percentage of patients in the most urgent medical status categories remained stable on the heart waiting list and has decreased on the liver waiting list.

Appearance of cytokine-associated central nervous system myelin damage coincides temporally with serum tumor necrosis factor induction after recombinant interleukin-2 infusion in rats.

Endogenous tumor necrosis factor (TNF) activity, assessed by L-929 fibroblast bioassay, was determined in serum samples from rats infused intravenously with recombinant interleukin-2 (rIL-2) or rIL-2 vehicle. Parallel studies of cerebral ultrastructure were conducted in additional rats, comparably infused. Rats received rIL-2 or vehicle either one time only or 3 times daily for 3 days. TNF activity was assessed at 2, 4, and 8 h after the single or final infusion. Rats employed for ultrastructural studies were sacrificed at 4 h after the single or final infusion. Every rIL-2-infused rat exhibited unusual abnormalities of axonal ultrastructure, identical to those previously described after in vitro TNF application to living spinal cord slices. Serum samples drawn during and after the development of axonal changes revealed significantly elevated circulating TNF activity. Controls exhibited neither TNF activity nor altered axons. These studies demonstrate that, following rIL-2 infusion in rats, endogenous TNF circulates at elevated levels during the development of rIL-2-related central nervous system abnormalities similar to those produced in vitro by recombinant TNF. Whether rIL-2-induced circulating TNF is causally-related to the observed myelin damage remains to be determined but merits further investigation, particularly since blood-brain barrier function has been shown to be compromised following rIL-2 infusion.

Cerebral vasomotor responses after recombinant interleukin 2 infusion.

The effects of systemic human recombinant interleukin 2 (rIL-2) infusion upon both the vasoconstrictor effect of hypocapnia and the endothelium-dependent vasodilator effect of acetylcholine (Ach) were examined in anesthetized rats equipped with cranial windows. Prior to the functional studies, each of six animals received an i.v. infusion of rIL-2 (6 x 10(5) IU/kg) every 8 h for 3 days. At the same time, six control animals received infusions of equivalent volumes of sterile water. Eight h after the final infusion, each animal was anesthetized and equipped with a cranial window for the observation of pial arterioles overlying the left frontoparietal cortex. Pial arteriolar diameters were measured before and after the topical application of Ach which in normal cerebral arterioles elicits the release of endothelium-dependent relaxing factor, causing vasodilation. When arteriolar diameters returned to base line, they were measured again both before and during hyperventilation-induced hypocapnia. Following functional assessments, these same pial vessels were processed for study by transmission electron microscopy to determine if any observed functional changes correlated with morphological abnormality. Results of the statistical analyses suggested that normal Ach-induced endothelium-dependent vasodilation was absent in the rIL-2-infused group. Additionally, these animals exhibited reduced reactivity to the vasoconstrictive effects of arterial hypocapnia. The control group exhibited normal responsiveness to both Ach and hyperventilation. Ultrastructural studies revealed occasional morphological alterations of both vascular smooth muscle and endothelial cells in some vessels of rIL-2-infused animals but not in controls. These data suggest that repeated systemic rIL-2 infusion results in altered vasomotor responsiveness within the cerebral microcirculation. The data also suggest that the observed vasomotor changes are not always accompanied by overt morphological alterations of either endothelial or smooth muscle cells.

Immunotherapy for malignant glioma using human recombinant interleukin-2 and activated autologous lymphocytes. A review of pre-clinical and clinical investigations.

Over the past few years, we and a number of other groups have conducted laboratory experiments and clinical trials of human recombinant interleukin-2 (rIL-2) alone or in combination with autologous 'activated' lymphocytes expressing in vitro tumoricidal activity in order to define toxicity and indicate its potential efficacy in patients with high-grade glioma. Because high rIL-2 concentrations can be attained with considerably less toxicity than with a systemic approach, all of the clinical trials, to date, have chosen a direct route; injecting lymphokine and cells into tumor tissue, the cystic cavity remaining after tumor excision, and/or neural parenchyma surrounding the site of tumor excision. While the rIL-2 therapies, as they have been applied in animal glioma models and patients, are safe, cerebral edema around the site of treatment has been a consistent finding. We have also seen, however, that steroid medications used by patients to control their cerebral edema may depress the anti-tumor activity of rIL-2 by depressing the capacity of lymphocytes to develop normal LAK activity. Although none of the immunotherapies involving rIL-2 have produced cures, the fact that sustained clinical responses have been reported, suggests that such therapies may slow a recurrence of tumor at the site of treatment. Efforts to improve outcome from rIL-2--based immunotherapies for malignant glioma are continuing with manipulation of rIL-2 dosing and scheduling and also with combinations of rIL-2 and other recombinant cytokines.

Blood-brain barrier dysfunction in cats following recombinant interleukin-2 infusion.

The effects of systemic human recombinant interleukin-2 (rIL-2) infusion upon blood-brain barrier status and cerebral vascular ultrastructure were examined in cats. Each of eight animals received a single bolus i.v. infusion of rIL-2 (100,000 units/kg). Six control animals were infused with rIL-2 excipient only. Following a 1-h postinfusion survival time, the brain tissue of five rIL-2 infused and three excipient infused animals was processed and examined by light microscopy and electron microscopy for evidence of altered cerebrovascular permeability to systemically circulating horseradish peroxidase. The brain tissue of three additional rIL-2 infused animals and three excipient infused animals, sacrificed 4 h postinfusion, was examined at the light microscopic and electron microscopic levels for the presence of extravasated endogenous IgG. All animals infused with rIL-2 and four of six excipient infused animals showed increased cerebrovascular permeability to the probe used. Altered blood-brain barrier permeability, when present, was recognized in multiple loci throughout the brain, being most prominent within white matter regions. Horseradish peroxidase and IgG were observed within perivascular basal laminae and within the interstices of the brain parenchyma. Numerous endothelial lesions were observed as was flooding of endothelial cytoplasm by horseradish peroxidase or IgG. Every animal studied, regardless of permeability status, showed, within the perivascular brain parenchyma, numerous disrupted neuronal and glial processes as well as expanded intercellular spaces. This study suggests that a single systemic infusion of rIL-2 profoundly alters blood-brain barrier integrity and cerebrovascular morphological integrity. The data also suggest that some of the observed cerebrovascular effects of systemic rIL-2 infusion are due to components of the vehicle for rIL-2.