Human Papilloma Virus Positive Oropharyngeal Squamous Cell Carcinoma and the Immune System: Pathogenesis, Immunotherapy and Future Perspectives.

Oropharyngeal squamous cell carcinoma (OPSCC), a subset of head and neck squamous cell carcinoma (HNSCC), involves the palatine tonsils, soft palate, base of tongue, and uvula, with the ability to spread to adjacent subsites. Personalized treatment strategies for Human Papillomavirus-associated squamous cell carcinoma of the oropharynx (HPV+OPSCC) are yet to be established. In this article, we summarise our current understanding of the pathogenesis of HPV+OPSCC, the intrinsic role of the immune system, current ICI clinical trials, and the potential role of small molecule immunotherapy in HPV+OPSCC.

Meiotic recombination and sporulation in repair-deficient strains of yeast.

A genetic system designed to monitor recombination and sporulation in various repair-deficient yeast strains was constructed. Variously heterozygous at seven or eight sites distributed across the genome, the system facilitated sensitive detection of changes in frequency or pattern of meiotic recombination. Ten rad mutants sensitive primarily to UV-irradiation and without terminal blocks in the sporulation process were studied. Seven were defective in excision repair (rad1, rad2, rad3, rad4, rad10, rad14 and rad16), and three were defective in mutagenic repair (rad5, rad9 and rad18). Individually, each mutant displayed behavior consistent with an orthodox meiosis including a wild-type meiotic recombination profile with respect to gene conversion, PMS and intergenic map distances. Accordingly, we conclude that these mutants are without major effect on meiotic heteroduplex formation or correction. However, certain combinations of excision-defective mutants with rad18 exhibited marked ascosporal inviability. Tetraploids homozygous for rad1 and rad18 produce a large proportion of diploid spores containing a recessive lethal.

Flank mass and pain in a 72-year-old man.

This patient had retroperitoneal multiseptated masses, which extensively invaded the right flank and thigh musculature. The radiologic, pathologic, and clinical findings were consistent with a retroperitoneal pseudomyxoma from an appendiceal mucocele.

Effects of acute caffeine withdrawal on habituated male runners.

This study investigated the effects of caffeine withdrawal on six trained caffeine-habituated male runners: age 29.8 +/- 5.8 (SD) yr, height 180.4 +/- 5.4 cm, weight 77.3 +/- 6.7 kg, maximal O2 uptake 63.0 +/- 5.4 ml.kg-1.min-1, and daily caffeine intake 674 +/- 128 mg. The subjects received a loading dose (5 mg/kg body wt) of caffeine 48 h before each testing session. They were then given (using a repeated-measures double-blind design) additional doses of caffeine (5 mg/kg body wt) or a placebo 36, 24, 12, and 2 h before testing. They ran at a velocity corresponding to their lactate threshold for 60 min in a caffeine withdrawal or caffeinated condition. Caffeine withdrawal resulted in no significant differences in absolute O2 uptake, O2 uptake relative to maximal O2 uptake, respiratory exchange ratios, or free fatty acid concentrations. Glycerol concentrations were significantly attenuated in the withdrawal condition. No significant differences were revealed in calculated substrate utilization. It was concluded that caffeine withdrawal significantly affects lipolysis but not substrate utilization during prolonged running.

Durability of the reproductive axis in eumenorrheic women during 1 yr of endurance training.

Menstrual cycle (MC) alterations occur in some endurance-training women. We hypothesized that a prospective running program would evoke alterations in MC phase lengths and in the physiological frequency of pulses of luteinizing hormone (LH) and/or diminish 24-h integrated serum LH concentrations in some women. In addition, we postulated that women who train more intensively (above the lactate threshold) would show alterations in gonadotropin release earlier in the training program or to a greater degree. To test these hypotheses, we examined the effects of different exercise intensities on physiological and endocrine responses. Twenty-three healthy eumenorrheic gynecologically mature (postmenarchal age 17.8 +/- 0.9 yr) untrained women undertook a 1-yr training program at one of two exercise intensities, one at a velocity corresponding to the lactate threshold (LT) and the other halfway between that of LT and peak running velocity, or served as controls. Training distance was the same in each exercise group. Physiological measurements were repeated every four MC to track changes in fitness and readjust training velocities. The lengths of the MC and the follicular and luteal phases were determined from hormonal concentrations. Body composition, nutritional intake, and pulsatile release of LH were determined. The women ran approximately 790 miles. Each group improved physiologically, with the greater than LT group improving to a greater degree. A less than 2-day decrease in the luteal phase length was observed only in the greater than LT group. No significant changes for any parameter of pulsatile LH release were noted between exercise groups. No significant changes in nutritional intake and only small changes in body composition were noted in either exercise group despite the added energy expenditure of exercise. We conclude that a progressive exercise program of moderate distance and intensity does not adversely affect the robust reproductive system of gynecologically mature eumenorrheic women.

Reproductive hormones and bone mineral density in women runners.

We examined the relationships among reproductive hormone concentrations and bone mineral density (BMD) in 43 women runners classified as eumenorrheic (n = 24), oligomenorrheic (n = 8), or amenorrheic (n = 11). Results were compared with a eumenorrheic nonrunner control group (n = 11). Serum 17 beta-estradiol, progesterone, and dehydroepiandrosterone sulfate concentrations were determined in daily blood samples for 21 days, and integrated concentrations (areas under the curve) were calculated. BMD was assessed at the lumbar spine and proximal femur by dual-photon absorptiometry. As expected, 17 beta-estradiol, progesterone, and lumbar spine BMD were higher in the control and eumenorrheic runner groups than in the oligomenorrheic and amenorrheic runner groups (P less than 0.05). Progesterone concentration was significantly correlated with lumbar spine BMD in the eumenorrheic runners (r = 0.61). None of the steroid hormones was significantly related to BMD in the oligomenorrheic/amenorrheic group. The present data suggest that circulating levels of gonadal steroid hormones affect axial BMD in eumenorrheic runners.

Cardiovascular effects of H2-receptor antagonists.

The type II histamine receptor antagonists, cimetidine and ranitidine, widely used in treatment of peptic ulcer disease have been reported to cause bradycardia. To evaluate the cardiovascular effects of H2 antagonists nineteen healthy volunteers were entered into a double-blind crossover comparison of cimetidine 300 mg qid, ranitidine 150 mg bid, and placebo. Subjects ingested study medicine for 7 days prior to being tested by the Bruce Exercise Test. Heart rate, blood pressure, oxygen consumption, expiratory volume, and fractional expiration of CO2 and O2 were measured at rest, exercise and recovery. A plasma sample for determination of cimetidine and ranitidine levels were obtained prior to the exercise period. Multivariate analysis and paired t test revealed no significant differences for the cardiovascular or pulmonary variables. However, in 5 subjects, the heart rate at 25% maximum VO2 was depressed 8% (P less than or equal to 0.03). This effect in a small percentage of the population suggests that further studies are needed to determine if subpopulations are affected.

Effect of Eleutherococcus senticosus on submaximal and maximal exercise performance.

We investigated the effect of Eleutherococcus senticosus Maxim L (ESML) on performance during submaximal and maximal aerobic exercise. Twenty highly trained distance runners randomly assigned in matched pairs to either an experimental (ESML) or placebo (PL) group, participated in an 8-wk double-blind study during which they completed five trails of a 10-min treadmill run at their 10 km (10K) race pace and a maximal treadmill test (T(max)). Following a baseline trail, ESML and PL consumed, respectively, 3.4 ml of ESML extract or placebo daily for 6 wk. Subjects were tested every 2 wk during supplementation and 2 wk following withdrawal. Heart rate (HR), oxygen consumption (VO2), expired minute volume (VE), ventilatory equivalent for oxygen (VE/VO2), respiratory exchange ratio (RER), and rating of perceived exertion (RPE) were measured during the 10K and T(max) tests. Resting, post-10K and post-T(max) blood samples were analyzed for serum lactate. No significant differences were observed between ESML and PL for: HR, VO2, VE, VE/VO2, RER, or RPE; T(max) time to exhaustion; or serum lactate. The data do not support an ergogenic effect of ESML supplementation on selected metabolic, performance, or psychologic parameters associated with submaximal and maximal aerobic exercise tasks.

Oxidants, joint inflammation and anti-inflammatory strategies.

In summary, we support the hypothesis that the rheumatoid knee is subjected to repeated hypoxic reperfusion injury. Moreover, we speculate that oxidative damage induced as a consequence of hypoxic reperfusion injury leads to the synthesis of intracellular stress proteins. In certain individuals this triggers an autoimmune response which might explain the persistance of the rheumatoid disease process. This gives scope for novel therapeutic approaches in the future development of anti-inflammatory agents.

Osteoclastic giant cell tumor of the pancreas. Aspiration cytology, light microscopy, and ultrastructure with review of the literature.

The osteoclastic giant cell tumor of the pancreas is a rare primary neoplasm that by light and electron microscopy mimics giant cell tumor of bone. In the proper clinical setting, this lesion can be diagnosed by fine needle aspiration. Review of 10 cases reveals a female predominance, a median survival of 12 months, and a tendency for local invasion, rather than lymphatic or distant metastasis, and for invasion of large veins. An epithelial origin is favored for this malignant neoplasm, which expresses varying degrees of mesenchymal differentiation.

The prevalence of actinomycetes-like organisms found in cervicovaginal smears of 300 IUD wearers.

The association of Actinomyces with IUD wearers has been widely documented and the possibility of the recognition of actinomycetes-like organisms in routine Papanicolaou-stained cervicovaginal smears has been reported. We conducted a retrospective study of IUD wearers to determine the prevalence and significance of actinomycetes-like organisms found in such smears. Three hundred smears from current IUD wearers were rescreened for actinomycetes-like organisms. Of this group, 200 patients were from a public health family planning clinic, and 100 were private patients. The incidence for the public health group was 25.5% and for the private patient group, 8%. A case history of actinomycosis is included. Findings such as other infectious agents, abnormal cytology and symptoms are also discussed. Although the presence of Actinomyces probably represents an opportunistic infection, the threat of pelvic actinomycosis with serious complications poses a management problem to the clinician when Actinomyces is reported in a routine Papanicolaou smear. Our findings lead us to question the practicality of the earlier recommendations of IUD removal and antibiotic therapy.

PIP: 300 Papanicolaou smears from current IUD wearers were rescreened to determine the prevalence of actinomycetes. Of the 300 patients, 59 showed actinomycetes-like organisms in cervicovaginal smears. Of the 59 positive cases, 51 (of 200, 25%) were from public health clinics and 8 (of 100, 8%) were from private patients. Of 21 patients complaining of irregular bleeding, only 4 had positive actinomycete cultures. In cases positive for the organisms there was no correlation of prevalence found with the phase of the menstrual cycle or with menstruation itself. A case history of actinomycosis is included. Although the presence of Actinomyces probably represents an opportunitistic pathogenic infection, management of this infection is important to eradicate the threat of pelvic actinomycosis. In the case history described, however, antibiotic therapy failed, and a complete abdominal hysterectomy was performed.

The ex vivo measurement of malondialdehyde and chemiluminescence as possible indices for anti-inflammatory drug evaluation.

A well-established model of foot-pad oedema in the rat, an example of a cell-mediated hypersensitivity reaction, was used in this study. Male rats were immunized on day 0 with Freund's complete adjuvant (FCA) and then challenged 6 days later with FCA in one hind paw. Within 4 h of the initiation of this acute inflammatory reaction, the presence of free radicals was detected as luminol-amplified chemiluminescence (LAC) directly from the inflamed paws. In addition, an increase in malondialdehyde (MDA), an end product of lipid peroxidation, was measured in both inflamed tissue and plasma. Groups of animals were treated with either diclofenac sodium, indomethacin, piroxicam or prednisolone either 1 h before or 6 h after challenge, oedema, LAC and MDA being measured at various times after challenge. The three non-steroidal anti-inflammatory drugs (NSAIDs) and prednisolone, given 1 h before challenge, significantly inhibited LAC and plasma MDA levels at 4 h post challenge. When given 6 h after challenge all drugs significantly inhibited oedema at 24 h. Furthermore, all the drugs inhibited tissue MDA and LAC but only indomethacin and piroxicam reached significance. The data suggest a role for lipid peroxidation and free-radical generation in inflammation and provide possible indices for in vivo drug activity and evaluation.

How exercise affects lipid profiles in women: what to recommend for patients.

After menopause, women have less favorable lipid profiles than before menopause. While regular exercise improves lipid metabolism in men, the specifics for doing so in pre- and postmenopausal women are not fully understood. Literature review suggests that higher-volume aerobic exercise programs increase high-density lipoprotein cholesterol (HDL-C) levels in both pre- and postmenopausal women. Although longitudinal studies of resistance training did not reveal increases in HDL-C levels in women, other favorable benefits observed included decreases in low-density lipoprotein-cholesterol, total cholesterol, and body fat. Cross-sectional studies, however, seem to favor high-volume exercise for increasing HDL-C levels.