Patient perceptions of symptoms and concerns during cancer chemotherapy: 'affects my family' is the most important.

BACKGROUND: Cancer chemotherapy is associated with a variety of side effects/adverse events. It is very important that patients adhere to the planned chemotherapy regimen, which necessitates a minimum of side effects and that these side effects be kept under control. We have investigated patients' concerns and symptoms during chemotherapy with the aim to seek solutions that will improve patients' quality of life during chemotherapy. METHODS: Forty-nine patients with malignant diseases on parenteral antineoplastic agents were sequentially enrolled in this study. These patients completed a questionnaire consisting of 42 items related to non-physical concerns and 52 items of physical symptoms related to chemotherapy. Each patient was also asked to select the three items among these 94 items which affected him/her the most. RESULTS: The median age of the cancer patients was 62 years and the male-to-female ratio was 18:31. Among the non-physical concerns, the most frequently chosen concern was 'affects my family or partner,' followed by anxiety related to treatment. Regarding the physical symptoms, the most frequent complaints were fatigue, alopecia and constipation, while the most troublesome symptoms were nausea, poor taste and paresthesia. Overall, the most frequently expressed concerns were 'affects my family or partner' and anxiety related to treatment. Male patients suffered most from fever, fatigue and nausea, and female patients complained more of poor taste and gastrointestinal problems. CONCLUSION: Patient perceptions of adverse events associated with cancer chemotherapy apparently have changed from physical symptoms to non-physical concerns. In our patient cohort 'affects my family or partner' was the most important concern. One important point to note is that female patients often complained of poor taste because this meant they were unable to cook well.

Associations of Buccal Cell Telomere Length with Daily Intake of ß-Carotene or α-Tocopherol Are Dependent on Carotenoid Metabolism-related Gene Polymorphisms in Healthy Japanese Adults.

OBJECTIVE: Telomere length shortening is modulated not only by aging, but also by both genetic and environmental factors. The aim of this study was to investigate the interactions between antioxidant nutrient metabolism-related gene single nucleotide polymorphisms (the genetic factors) and nutrient intake (the environmental factors) in their effects on telomere length shortening. SETTING AND PARTICIPANTS: Data were collected on the relative telomere lengths (RTLs) of buccal cells and the habitual food intake of 70 healthy Japanese adults. MEASUREMENTS: All subjects were genotyped for two common single nucleotide polymorphisms: rs6564851 in the ß-carotene-15,15'-mono-oxygenase 1 (BCMO1) gene and rs362090 in the intestine-specific homeobox (ISX) gene. RESULTS: Univariate analysis revealed that buccal RTL was not significantly modulated by either age or gender. Then, we subdivided the study population into four groups based on combinations of the rs6564851 and rs362090 genotypes. After this subdivision, we showed a positive effect of daily α- or ß-carotene intake on buccal RTL in the ISX rs362090 G-allele carrier + BCMO1 rs6564851 GG-genotype group (p = 0.026). Additionally, daily intake of another antioxidative fat-soluble vitamin, α-tocopherol, was positively associated with buccal RTL in the ISX rs362090 AA-homozygote + BCMO1 rs6564851 T-allele carrier group (p = 0.037). CONCLUSION: Our study clearly indicates that high dietary intake of the antioxidants α, ß-carotene and α-tocopherol protects buccal cells from RTL shortening, depending on the genetic background of antioxidant vitamin-related genes.

Identification and characterization of functional domains in a mixed lineage kinase LZK.

The mixed lineage kinase (MLK) family is a recently described protein kinase family. The MLKs contain a kinase domain followed by a dual leucine zipper-like motif. We previously reported the molecular cloning of LZK (leucine zipper-bearing kinase), a novel MLK, and that LZK activated the c-Jun NH2 terminal kinase (JNK)/stress-activated protein kinase (SAPK) pathway through MKK7 in cells. Here, we reveal that LZK forms dimers/oligomers through its dual leucine zipper-like motif, and that this is necessary for activation of the JNK/SAPK pathway. We also identify the C-terminal functional region of LZK, which is indispensable for the activation of SEK1, but not that of MKK7.

Effect of iC3b binding to immune complexes upon the phagocytic response of human neutrophils: synergistic functions between Fc gamma R and CR3.

We compared the phagocytosis of immune complexes (IC) and iC3b-opsonized derivatives (iC3b-IC) by human neutrophils. The phagocytosis of iC3b-IC via Fc gamma R and CR3 was much greater than that of IC via Fc gamma R alone. Adding ethanol to the cells decreased iC3b-IC phagocytosis to that of IC, which was not affected by these reagents, suggesting that the enhanced phagocytosis is attributable to CR3-mediated phospholipase D activation. The IC phagocytosis was inhibited more effectively by anti-Fc gamma IIIB, whereas the iC3b-IC phagocytosis was partly inhibited only by anti-Fc gamma RII. The main Fc gamma R might differ in IC and iC3b-IC phagocytosis.

Estimation of absorbed doses in humans due to intravenous administration of fluorine-18-fluorodeoxyglucose in PET studies.

Radiation absorbed doses due to intravenous administration of fluorine-18-fluorodeoxyglucose in positron emission tomography (PET) studies were estimated in normal volunteers. The time-activity curves were obtained for seven human organs (brain, heart, kidney, liver, lung, pancreas, and spleen) by using dynamic PET scans and for bladder content by using a single detector. These time-activity curves were used for the calculation of the cumulative activity in these organs. Absorbed doses were calculated by the MIRD method using the absorbed dose per unit of cumulated activity, "S" value, transformed for the Japanese physique and the organ masses of the Japanese reference man. The bladder wall and the heart were the organs receiving higher doses of 1.2 x 10(-1) and 4.5 x 10(-2) mGy/MBq, respectively. The brain received a dose of 2.9 x 10(-2) mGy/MBq, and other organs received doses between 1.0 x 10(-2) and 3.0 x 10(-2) mGy/MBq. The effective dose equivalent was estimated to be 2.4 x 10(-2) mSv/MBq. These results were comparable to values of absorbed doses reported by other authors on the radiation dosimetry of this radiopharmaceutical.

A new class of potent centrally acting muscle relaxants: pharmacology of oxazolidinones in rat decerebrate rigidity.

The severity of anaemic decerebrate rigidity was quantitatively determined by measuring the frequency of electromyographic potentials in the rat. Some oxazolidinones markedly reduced the severity of this decerebrate rigidity in a dose-dependent manner, (4S,5R)-4-(2-methylpropyl)-3- [3-(perhydroazepin-1-yl)propyl]-5-phenyl-1,3-oxazolidin-2-on e (MLV-6976) being the most potent. In addition to the oxazolidinones, an aminoalcohol derivative, (1RS,2SR)-5-methyl-1-phenyl-2-(3-piperidinopropylamino )hexan-1-ol (MLV-5860) also reduced the rat decerebrate rigidity. In the oxazolidinone series, the optical isomers with absolute configuration (S) at the 4-position were more potent than the corresponding (4R)-isomers, while there was no significant difference in their LD50 values. Normal rats and mice receiving MLV-6976 at doses which reduced decerebrate rigidity showed no behavioural changes, impairment of motor coordination only appearing at extremely high doses. MLV-6976 and its derivatives did not affect spinal reflex potentials in cats. MLV-6976 reduced the severity of harmaline-induced tremor in mice in a dose-dependent manner, but slightly augmented tremorine-induced tremor. The frequency of the spike discharges induced by iontophoretically applied glutamate was reduced by MLV-6976 in a dose-dependent manner in rat cortical neurones. The amplitude of miniature endplate potentials of the rat diaphragm was decreased by MLV-6976 only at concentrations greater than 0.1 mM. It is concluded that MLV-6976 acts on the brainstem or/and higher levels of the brain rather than on the spinal cord or the peripheral nervous system to reduce the excessive activities of the nervous system.

Mixed lineage kinase LZK forms a functional signaling complex with JIP-1, a scaffold protein of the c-Jun NH(2)-terminal kinase pathway.

Leucine zipper-bearing kinase (LZK) is a novel member of the mixed lineage kinase (MLK) protein family, the cDNA of which was first cloned from a human brain cDNA library [Sakuma, H., Ikeda, A., Oka, S., Kozutsumi, Y., Zanetta, J.-P., and Kawasaki, T. (1997) J. Biol. Chem. 272, 28622-28629]. Several MLK family proteins have been proposed to function as MAP kinase kinase kinases in the c-Jun NH(2) terminal kinase (JNK)/stress-activated protein kinase (SAPK) pathway. In the present study, we demonstrated that, like other MLKs, LZK activated the JNK/SAPK pathway but not the ERK pathway. LZK directly phosphorylated and activated MKK7, one of the two MAPKKs in the JNK/SAPK pathway, to a comparable extent to a constitutive active form of MEKK1 (MEKK1DeltaN), suggesting a biological role of LZK as a MAPKKK in the JNK/SAPK pathway. Recent studies have revealed the essential roles of scaffold proteins in intracellular signaling pathways including MAP kinase pathways. JIP-1, one of the scaffold proteins, has been shown to be associated with MLKs, MKK7, and JNK [Whitmarsh, A.J., Cavanagh, J., Tournier, C., Yasuda, J., and Davis, R.J. (1998) Science 281, 1671-1674], suggesting the presence of a selective signaling pathway including LZK, MKK7, and JNK. Consistent with this hypothesis, we provided evidence that LZK is associated with the C-terminal region of JIP-1 through its kinase catalytic domain. In addition, LZK-induced JNK activation was markedly enhanced when LZK and JNK were co-expressed with JIP-1. These results constituted important clues for understanding the molecular mechanisms regulating the signaling specificities of various JNK activators under different cellular conditions.

Dynamic characteristics of the otolithic oculomotor system.

Vertical eye tracking test, up-down test, and running test in the dark and light were carried out to obtain Bode plots of transfer function of the opto-oculomotor, otolithic oculomotor, and opto-otolithic oculomotor systems. 1. The gain and phase of the opto-oculomotor system obtained from the vertical eye tracking test were flat in a frequency range of 0.3 to 1.0 Hz. 2. During the up-down test in the dark, the gain of the otolithic oculomotor system linearly increased at the rate of 20 dB/decade with an increase of frequency from 0.7 to 5 Hz. 3. During the up-down test in the light, the gain and phase were flat in a frequency range of 0.3 to 2.5 Hz. 4. The transfer function calculated with vertical head acceleration as input and vertical eye movement as output in the running test in the dark was similar to that in the light. The gain linearly decreased at the rate of 40 dB/decade with increase of frequency from 0.3 to 3.0 Hz. During running, eye displacement is almost in proportion to the head displacement in both dark and light. In daily, active movement such as running, eye movement proportional to head displacement appears without collaborative action of the opto-oculomotor system. 5. All five patients with bilateral loss of labyrinthine excitability exhibited a similar opto-oculomotor response to that of normal subjects. Three of the five patients did not show any eye movement corresponding to head movement in the up-down test in the dark. However, two patients showed a periodic eye movement in the same test, indicating dispersion of the gain and phase values. 6. These patients exhibited a rhythmic eye movement corresponding to head movement in the running test in the dark and light. However, values of gain and phase obtained in both tests were cultured. The variations in gain obtained from the running test in the light were observed in frequency ranges above and below 1 Hz.

Nasal polyps in the olfactory cleft.

OBJECTIVES: Nasal polyps frequently arise from the middle meatus in patients with nasal polyposis, but caution is required when polyps are seen protruding from the olfactory cleft. The purpose of this study was to evaluate a method to achieve effective and safe access to the olfactory cleft, and to determine the actual incidence of polyps arising from the olfactory cleft in patients with nasal polyposis. PATIENTS: Eighty-four patients with bilateral or unilateral nasal polyps (n = 143) ranging in age from 16 to 72 years underwent endoscopic sinus surgery in the period from January 1994 to December 1996. METHODS: To observe and gain access to the olfactory cleft, septoplasty combined with endoscopic sinus surgery was needed in patients with nasal polyposis. RESULTS: The endoscopy during the combined septoplasty and endoscopic sinus surgery revealed that 36.4% (n = 52) of bilateral or unilateral nasal polyps (n = 143) arose from the olfactory cleft. Of 52 polyps of olfactory cleft origin, 45 (86.5%) arose from the superior turbinate and/or superior meatus, 32 (67.3%) from the medial side of the middle turbinate, 24 (46.2%) from the anterior face of the sphenoid sinus, and 17 (32.7%) from the mucosa of the nasal septum. CONCLUSIONS: These findings suggest that for surgeries of nasal polyposis an approach to the olfactory cleft as well as to the middle meatus is required.

One-eye and locomotor compensation in guinea pigs.

This study was carried out to examine the effect of blindfolding one eye on locomotor compensation after unilateral labyrinthectomy in guinea pigs. A platform runway, designed to examine the locomotion of this species of animals, was used. Eighteen Hartley-strain albino guinea pigs were used. These animals were divided into three groups, with seven in the control group, six whose right eye had been surgically closed in another group, and five whose left eye had been surgically closed in yet another group. After 7 to 11 days of training, a chemical labyrinthectomy by chloroform injection into the middle ear was performed under light ether anesthesia. Animals were checked for locomotion daily by the aforementioned platform method for about a week until regaining preprocedure levels. The locomotor compensation, depicted through the decrement of the deviation count and running time, was observed. Results have shown that the animal's locomotor compensation retarded significantly in the one-eye groups compared to the control group. In addition, those animals whose one eye, ipsilateral to the labyrinthectomy side, was closed required significantly longer time to resume the preprocedure running performance level than the animals whose one eye, contralateral to the lesion side, was closed. Thus, during locomotor compensation, the visual input obtained by animals with one eye ipsilateral to the labyrinthectomy side may be important compared to the visual input of the animals with the contralateral eye.

Ototoxicity of Vasocidin drops applied to the chinchilla middle ear.

Some widely used ototopical preparations are potentially toxic to the middle and inner ear. Vasocidin Ophthalmic Solution (sulfacetamide sodium and prednisolone sodium phosphate) has been advocated as an alternative agent that may have fewer toxic side effects in the treatment of otorrhea. Vasocidin was introduced into the bullae of nine chinchillas to investigate the effects on the middle and inner ear. The organ of Corti and stria vascularis were found to be entirely normal in 17 of the 18 temporal bones studied. Changes observed in the middle ears at one week included inflammation, hemorrhage, and effusion. Examination of specimens at four weeks revealed resolution of most of the inflammatory changes. The results of this experimental study indicate that Vasocidin causes reversible middle ear inflammation with little or no toxic effect on inner ear structures.

Effects of otic drops on chinchilla tympanic membrane.

Experimental studies have shown that if antibiotic otic drops reach the middle ear cavity they produce severe inflammation. However, the effects of these preparations on the tympanic membrane have not been thoroughly investigated. This study was designed to assess morphological changes in the chinchilla tympanic membrane two to 21 days after a single 0.2-mL application of an antibiotic otic preparation (Cortisporin Otic Suspension) to the middle ear cavity. At two days, the epidermal and the mucosal layers were destroyed. By four days, reepithelialization had occurred and all layers of the tympanic membrane subsequently became markedly hyperplastic. Disruption of the fibrous layer, invasion of keratinizing epidermis to the medial surface, and perforation were observed at three weeks. These findings indicate that tympanic membrane damage is a potentially significant aspect of the ototoxic properties of topical otic preparations.

Increase in life expectancy at birth in Japan: some implications for variable patterns of decrease in mortality.

The characteristics of the increase in life expectancy at birth (eo) in Japan were analyzed using the life tables of developed countries in which the values of eo were almost the same. When the decrease in age-specific probability of dying (qx) and its contribution to total gain in eo in Japan were compared to those of other developed countries, the decline in qx in prime, middle and old age groups accounts for much of the change; the decrease in this variable for males aged 50 years and over accounted for 35% of the recent increase in eo. Well-organized medical care and public services are discussed in relation to this unique and unusually rapid increase in eo for the Japanese population.

Experimental cholesteatoma. Epidermal ingrowth through tympanic membrane following middle ear application of propylene glycol.

This study was designed to investigate morphological changes in the tympanic membrane (TM) associated with cholesteatoma formation in experimental animals following application of propylene glycol to the middle ear. A 50% solution of propylene glycol was applied bilaterally to the middle ear cavities of 30 young-adult chinchillas. The animals were sacrificed for light and electron microscopic study at intervals of 2 days to 6 weeks after a single application of 0.2 ml of the propylene glycol solution. At 2 days there was complete destruction of the epidermal and mucosal layers of the TM. The denuded lateral surface rapidly became re-epithelialized by hyperplastic epidermal cells and by 2-3 weeks, keratinizing epidermis penetrated damaged areas of the fibrous layer of the lamina propria to reach the medial surface of the TM. These epidermal cells proliferated in the middle ear cavity, forming cholesteatomas. Our observations indicate that invasion of the intact, but structurally altered, tympanic membrane by hyperplastic epidermis is a primary mechanism of cholesteatoma formation in the animal model.