Intranasal verrucous carcinoma: relationship to inverting papilloma and human papillomavirus.

OBJECTIVES: To establish the incidence, appearance, behavior, and appropriate treatment of intranasal verrucous carcinoma and determine its relationship to inverting papilloma and human papillomavirus (HPV). STUDY DESIGN: Retrospective review of all cases of intranasal verrucous carcinoma seen at the Mayo Clinic from 1960 through May 1996. METHODS: Retrospective chart review and data collection for age, sex, smoking history, location, association with inverting papilloma, treatment, recurrence, and follow-up. Polymerase chain reaction (PCR) testing for the presence of HPV DNA was performed on all specimens. RESULTS: Of the 13 patients identified, most presented with nasal obstruction (10) or a noticeable intranasal lesion (8). The maxillary sinus was the extranasal site most often involved. Five patients had verrucous cancer develop in an inverting papilloma, and one had squamous cell carcinoma with the verrucous component (a hybrid tumor). All but one patient underwent surgery as initial treatment; only one patient had preoperative radiation therapy. Surgical procedures ranged from local excision to a craniofacial resection. Follow-up ranged from 2 months to 32 years (mean, 6.5 y). Four patients had a single recurrence and two tumors recurred a second time. No metastases developed and no one died from the tumor. In seven patients (10 specimens), DNA was successfully amplified for PCR testing, and no HPV DNA was detected. CONCLUSIONS: When verrucous tumors are discovered early, they can be treated effectively with wide local excision. In some cases, a more extensive procedure may be required. A possible role for HPV in the etiology of these tumors was not found.

Relationship of human papillomavirus to Schneiderian papillomas.

OBJECTIVES/HYPOTHESIS: To classify a large group of Schneiderian papillomas (SPs) into their histologic subtypes and to determine the incidence of human papillomavirus (HPV) in each subtype. STUDY DESIGN: Pathologic review and polymerase chain reaction-based (PCR-based) examination of archived tissue. METHODS: Slides of 114 tumors diagnosed as Schneiderian, inverting, fungiform, or cylindric cell papillomas, or any associated carcinomas, were examined by a head and neck pathologist. Using PCR, consensus primers for the L1 region of HPV were used to determine the presence of HPV in the tumors. This was also performed on normal turbinate control specimens. RESULTS: Eighty-two (78%) were the inverting subtype, 21 (20%) the fungiform subtype, and 2 (2%) the cylindric cell type. Nine tumors were diagnosed as either verrucous or squamous cell carcinoma. Eighty-eight percent of the tumors had DNA of sufficient quality to be amplified using PCR. Of these, 5 of 69 (6.8%) inverting, 17 of 17 (100%) fungiform, and 0 of 2 cylindric cell papillomas were positive for HPV. One of nine (11.1%) cancers was positive for HPV. No normal turbinate tissue contained HPV. HPV types 6b and 11 accounted for all cases of fungiform papillomas. Of the five HPV-positive inverting papillomas, three had HPV type 11 and two had HPV type 16. The single carcinoma containing HPV contained HPV type 18. CONCLUSIONS: The histologic subtype of SPs is important, as their etiologies appear to be different. HPV 6b and 11 appear to be involved in all cases of fungiform papillomas but are only rarely involved in cases of inverting or cylindric cell papillomas. HPV 16 may rarely play a role in cases of inverting papillomas, and HPV 16 and 18 may be involved in a subset of cases of carcinomas originating in an inverting papilloma.

Polarization contrast in near-field scanning optical microscopy.

Recent advances in probe design have led to enhanced resolution (currently as significant as ~ 12 nm) in optical microscopes based on near-field imaging. We demonstrate that the polarization of emitted and detected light in such microscopes can be manipulated sensitively to generate contrast. We show that the contrast on certain patterns is consistent with a simple interpretation of the requisite boundary conditions, whereas in other cases a more complicated interaction between the probe and the sample is involved. Finally application of the technique to near-filed magneto-optic imaging is demonstrated.

Breaking the diffraction barrier: optical microscopy on a nanometric scale.

In near-field scanning optical microscopy, a light source or detector with dimensions less than the wavelength (lambda) is placed in close proximity (lambda/50) to a sample to generate images with resolution better than the diffraction limit. A near-field probe has been developed that yields a resolution of approximately 12 nm ( approximately lambda/43) and signals approximately 10(4)- to 10(6)-fold larger than those reported previously. In addition, image contrast is demonstrated to be highly polarization dependent. With these probes, near-field microscopy appears poised to fulfill its promise by combining the power of optical characterization methods with nanometric spatial resolution.

Effects of detergent on the binding of solubilized sodium channels to immobilized wheat germ agglutinin: structural implications.

The binding of the solubilized voltage-dependent sodium channel from rat brain to immobilized wheat germ agglutinin (WGA) is detergent-dependent. When solubilized in sodium cholate, only 11% of total recovered channels bound to a WGA-Sepharose column. When solubilized in Triton X-100 or CHAPS, however, 80% and 60% could bind, respectively. The effect of cholate on sodium channel binding is relatively specific: the major rat brain glycoproteins which bind to immobilized WGA are roughly the same in either Triton or cholate, as analyzed by SDS gel electrophoresis. The structural implications for the channel are discussed.

The clinical pharmacology of vancomycin in seriously ill preterm infants.

The first dose and steady state pharmacokinetics of vancomycin were studied in 16 seriously ill preterm infants (less than or equal to 34 wk gestational age) with documented Staphylococcus epidermidis infections. One infant was dropped from the study due to peripheral flushing occurring during administration of the first dose. Individual vancomycin doses ranged from 9.8 to 17.8 mg/kg and were infused intravenously over 15-37 min. Fifteen infants were studied after the first dose of vancomycin, whereas only 12 of these 15 were able to be studied under steady state conditions. Vancomycin half-life, steady-state volume of distribution, and body clearance averaged 6.0 h, 0.53 liter/kg, and 1.22 ml/min after the first dose and only slight differences were observed in these parameter estimates under steady state conditions. However, substantial accumulation of vancomycin in serum was observed with multiple dosing. Complete 8-h urine collections were possible in 12 of 15 premature infants after the first dose of vancomycin. Overall, 44.6% of the dose was recovered in the urine with a corresponding vancomycin renal ClR averaging 0.88 ml/min. Vancomycin body Cl correlated directly with renal ClR (r = 0.88, p less than 0.001) and body weight (r = 0.8, p less than 0.001). Vancomycin pharmacokinetic parameter estimates Vdss and Cl correlated directly with body weight, surface area, and postconceptional age. No significant relationships were observed between these parameter estimates and gestational age or postnatal age. Fourteen of 15 infants were treated successfully for their underlying infectious process. These data support the use of lower doses of vancomycin than previously recommended for the treatment of preterm infants.

Multicenter evaluation of six methods for predicting warfarin maintenance-dose requirements from initial response.

Warfarin maintenance-dose requirements predicted by six mathematical methods based on initial response to therapy were compared with patients' actual dose requirements in a multicenter trial. Data were collected for patients who had received an initial regimen of warfarin sodium 10 mg orally every 24 hours for three days and for whom a prothrombin time (PT) had been determined 16-20 hours after the third dose. Patients' individual dose requirements and PT values were recorded during one to three follow-up visits after discharge from one of seven medical centers. Prothrombin ratios (patient PT divided by control PT) calculated on day 4 were used for maintenance-dose prediction by five methods; a sixth method was based on the cumulative warfarin dose-PT response curve up to a PT value of 20 seconds. For 54 men and 30 women who qualified for the study, 197 maintenance-dose-PT response measurements were recorded; 95 in the first four weeks of therapy, 76 during weeks 5-12, and 26 at 6-12 months after initial treatment. Prothrombin ratios were within the therapeutic range (PT 1.5-2.5 times the control value) in 154 observations, and the mean actual warfarin sodium maintenance dose associated with therapeutic response was 7.6 mg/day. For patients with therapeutic prothrombin ratios, dose predictions by the five methods using prothrombin ratios (PRs) correlated significantly with actual dose requirements. The formula that predicted doses numerically closest to the actual dose is as follows: Dose = 11.17 - 21.08 (log PR). Only 45 observations were obtained for the sixth prediction method, and the correlation between actual and predicted doses was not significant. Initial warfarin maintenance-dose requirements can be predicted effectively based on one PT determination after administration of three daily 10-mg doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of H1- and H2-receptor blockade on the inhibition of immediate cutaneous reactions.

The effects of cyproheptadine, cimetidine, and their combination on the wheal-and-flare skin-test response was evaluated using an intradermal skin-test technique in a double-blind, placebo-controlled study. Sixteen volunteers with known positive skin-test reactions to at least two antigens were divided into four treatment groups in a four-way crossover design. The patients received baseline intradermal skin tests on the back consisting of dilutions of mixed grasses and weeds, histamine diphosphate and codeine phosphate, and buffered-saline control. Following the baseline testing, the patients received cyproheptadine (4 mg q.i.d.), cimetidine (300 mg q.i.d.), the combination, and placebo in a double-blind trial. Of the 16 patients, 12 completed all treatment courses. Following pretreatment with cyproheptadine, cimetidine, and the combination, areas of wheal-and-flare response for each test substance were significantly suppressed. Although it appeared that the combination augmented wheal-and-flare suppression, the observed difference, compared with the cyproheptadine pretreatment sequence, was not statistically significant. The administration of H1 and H2 antagonists should be discontinued before the diagnostic use of immediate skin tests.

Heat stroke: report on 18 cases.

Eighteen hyperpyrexial patients with a mean rectal temperature of 42.3 degrees (range 41.2-43.1 degrees C) were rapidly cooled in a unit producing evaporative cooling from a warm skin. Sixteen patients recovered, and two, who were diabetic, died. The time taken for the core temperature to drop to 38 degrees C varied from 26 min to 5 h. The success of a treatment which maintained vasodilatation by warming the skin accords with the hypothesis that peripheral vasoconstriction combined with a high metabolic heat output is a major factor in the pathogenesis of heat stroke.

A physiological body-cooling unit for treatment of heat stroke.

The high incidence of heat stroke during the Mecca pilgrimage in hot weather prompted the development of a new method of rapidly cooling hyperpyrexial patients. A cooling bed was devised which achieved a high rate of evaporative cooling by spraying patients with water at 15 degrees C and warm air, which reached the body surface at 30-35 degrees C. The cooling bed also made possible the administration of ancillary treatment both efficiently and hygienically.

The blood groups, serum groups, red-cell isoenzymes and haemoglobins of the Sandawe and Nyaturu of Tanzania.

Blood specimens from members of the click-speaking Sandawe tribe of Tanzania and of the adjacent Bantu-speaking Nyaturu tribe have been tested for antigens of 11 blood group systems, for variants of 3 plasma-protein systems and 9 red-cell-enzyme systems, for haemoglobin variants. The results are tabulated and gene frequencies computed. For most systems, the frequencies in the two tribes are similar to one another and, in so far as data are available, similar to the neighbouring Bantu-speaking tribes. The principal genetic difference between the Sandawe and the Nyaturu is in their frequencies of haemoglobin S and of glucose-6-phosphate dehydrogenase deficiency, both of which characters are several times higher in the Nyaturu than in the Sandawe; both characters are protective against falciparum malaria, and this suggests that the Nyaturu have in the past been much more strongly exposed to this infection than the Sandawe.

Energy expenditure and physiological performance of Sudanese cane cutters.

The thermal and exercise tolerances of 165 Sudanese cane cutters were measured in the laboratory and related to work performance and productivity in the cane fields. The results showed that the amount of cane cut per minute in the field was significantly correlated with changes in body weight (r = +0-53) during the third hour of work, aerobic energy expenditure (r = + 0-43), and cardiac frequency during work. These variables in turn were associated with predicted maximal power output (VO2 max) measured in the laboratory. The average energy expenditure during cane cutting was 1-66 +/- 0-33 1/min-1 (34-9 kJ/min-1) which represents approximately 60% of the workers predicted VO2 max. This rate of energy expenditure was sustained in the cane fields for at least three hours without significant pauses for rest. The sweat losses measured in 32 cane cutters during the two and three hours of work averaged 637 +/- 221 and 770 +/- 282 g/h-1 respectively, while the mean urine temperature immediately on cessation of effort was 37-74 +/- 0-46 degrees C. Despite the additional environmental heat load of the tropics, it would seem that cane cutters performing a self-paced task demanding heavy physical effort, are able to sustain work levels well in excess of those recommended for most European factory workers without obvious signs of fatigue or heat stress.

Work capacity, thermal responses and lung function: united kingdom studies in the L.B.P.

Results of physiological studies from some ten U.K. Human Adaptability projects are presented. U.K. investigators made major contributions in developing and adapting techniques for the assussment under field conditions of work capacity, heat tolerance and respiratory function. The various ethnic studies of work capacity revealed the special role of body size and muscularity, as well as training, in determining the observed inter- and intra-population variance. The results on samples from U.K., New Guinea, the Caribbean, Israel, West and East Africa and the Ethiopian highlands gave no indication that genetic difference were significant in determining population differences. Differences in heat tolerance reflect in general the intensity of heat exposure, especially when combined with hard physical work. Indigenous peoples in Africa and New Guinea show some modification in sweating responses which do not appear to be genetically determined but are in some way, as yet not clearly established, attributable to long continued residence in tropical climates. In renal function of some seven ethnic groups were analysed in terms of lung volume bellows function, gas exchange and responses to excercise and carbon dioxide. The relative importance of genetic and non-genetic factors was examined.

Physiological performance and work capacity of Sudanese cane cutters with Schistosoma mansoni infection.

Physiological tests of work performance and measurement of field productivity were made in 194 Sudanese cane cutters in order to study the effect of Schistosoma mansoni infection. The cane cutters were selected from two age ranges (16-24 and 25-45 years) and subdivided into three clinical groups: not infected, infected with, and infected without clinical signs of hepatosplenomegaly. Men infected with Schistosoma haemotobium, malaria (blood film), or with hemoglobin levels less than 10 g/100 ml were excluded. There was a statistically significant (P less than 0.002) higher mean hemoglobin concentration in those not infected but the mean difference was less than 1 g/100 ml. Submaximal responses to exercise on a stationary bicycle ergometer, oxygen intake, ventilation, tidal volume, cardiac frequency and estimated maximal aerobic power output calculated both in absolute terms and relative to lean body mass and leg volume were similar in the six groups of cane cutters. No significant differences were found in physique, body composition or in thermoregulatory function tests. The cane cutters were found to have little natural acclimatization to heat in terms of sweating capacity when compared with a group of fully acclimatized Sudanese soldiers. The mean productivity (mean daily weight of cane cut per man) was significantly correlated with the individual's estimated maximum aerobic capacity determined in the laboratory, but not with the degree of S. mansoni infection. The noninfected group was less "efficient" (mean productivity:oxygen intake) during cutting than the infected groups but a larger proportion of the noninfected were in their first season of cutting. There was a positive correlation between the number of seasons' cutting experience and the individual's age, degree of infection and mean productivity. Cane cutters studied in this investigation were a relatively fit, active population from whom the more seriously ill were excluded. These results do not, therefore necessarily reflect the effects of S. mansoni on physiological work capacity and productivity of more static populations in areas of high endemicity.

Sweat responses in the aged.

The sweating responses to thermal stimulation and to the intradermal injection of acetyl choline or methacholine were measured in 28 men and 18 women aged 70 and over and were compared with the responses in young control subjects of both sexes. There was found to be a marked reduction in the sweating activity of the majority of aged men in comparison with the younger age groups and the body temperature threshold for the onset of sweating was increased. The reduced response and elevated threshold were even more pronounced in aged females. There is considerable variability in response in different subjects and at different bodily sites. Impairment of thermoregulatory function due to diminished or absent sweating is thought to be one of the factors responsible for increased mortality in the elderly population during heat-waves.