Observational evidence of the seasonal and demographic variation in experienced temperature from 77 743 UK Biobank participants.

BACKGROUND: Exposure to cold is known to be associated with severe health impacts. The primary epidemiological evidence for this is the seasonal variation in mortality. However, there is a paucity of directly measured data for personal cold temperature exposure. This paper develops the concept of experienced temperature, and reports how it varies with season, demographics and housing factors. METHODS: This study uses data from 77 743 UK Biobank participants. A novel method to directly measure participant's exposure to low temperatures using a thermistor in a wrist-worn activity monitor is described. These readings are combined with demographic and housing factor variables in a multiple regression model to understand underlying relationships. RESULTS: The study reveals a significant difference in experienced temperature of ~1.8°C between the periods of coldest and hottest external temperature. A number of demographic differences were also observed-such as people of Chinese ethnic background experiencing 0.65°C lower temperatures than other groups. CONCLUSIONS: This paper presents primary evidence for a seasonal variation in experienced temperature. This variation likely contributes to cold related mortality and morbidity. It is hypothesized that this relationship would be less strong in countries which suffer fewer impacts of cold winter temperatures.

Randomized, double-blind phase II study to compare nitroglycerin plus oral vinorelbine plus cisplatin with oral vinorelbine plus cisplatin alone in patients with stage IIIB/IV non-small cell lung cancer (NSCLC).

OBJECTIVES: Adding nitroglycerin to the combination of vinorelbine plus cisplatin has been reported to improve the overall survival (OS) of Asian patients with stage IIIB/IV non-small cell lung cancer (NSCLC) probably due to better drug delivery based on changed vascular tonus. The main objective of our study was to evaluate the effect of adding nitroglycerin to vinorelbine and cisplatin in a Caucasian population. METHODS: 66 chemonaïve patients with stage IIIB/IV NSCLC received oral vinorelbine (first cycle 60 mg/m(2), subsequent cycles: 80 mg/m(2) in the absence of any hematological toxicity ≥ grade 3 in cycle 1) once daily on days 1 and 8 of each cycle and cisplatin (80 mg/m(2) i.v.) on day 1 of each cycle (q3w). Nitroglycerin (arm A, n=34) or placebo patches (arm B, n=32) were administered once daily from day -3 to day 2 of each cycle and were removed about 12h after administration. One nitroglycerin patch contained 25mg nitroglycerin. RESULTS: Median age was 62.5 (33-82) years. In the overall population (n=66), the objective response rate (ORR) was 27.3% (all PR; 95%CI: 17.0-39.6), with a disease control rate (DCR) of 57.6% (95%CI: 44.8-69.7), a median time to progression (TTP) of 4.8 months (n=58; 95%CI: 3.4-5.9) and a median overall survival (OS) of 11.5 months (95%CI: 7.9-13.6). ORR and DCR were numerically higher in arm A than in arm B (35.3% vs. 18.8% and 61.8% vs. 53.1%, respectively), whereas TTP and OS were comparable. The main hematological and non-hematological toxicities grade ≥ 3 were moderate with no significant differences between the two treatment arms. CONCLUSIONS: Overall, oral vinorelbine plus cisplatin showed a high level of efficacy and adequate tolerability in first line treatment of NSCLC. Despite the low sample size per group the results seem to confirm the previous results reported in Asian patients.

[Comparing immunohistochemical diagnosis of cancer of unknown primary with gene expression-based tumor classification]. / Vergleich immunhistologischer mit genexpressionsbasierter Diagnostik: von Karzinomen mit unbekanntem Primarius.

Five percent of cancer cases present as metastases. If the primary tumor cannot be identified after diagnostic workup, the disease is referred to as cancer of unknown primary (CUP) and is classified as C80.9 according to ICD-10. In Germany, CUP is among the ten most common causes of tumor-related death, with mortality similar to mortality in gastric or pancreatic cancer. Biopsies of the tumor manifestation are generally examined histopathologically and by immunohistochemistry (IHC). Gene expression profiling (GEP) is a new diagnostic technique that might further contribute to tumor specification.In a retrospective study, 43 CUP cases underwent central immunohistochemical review and centrally performed GEP using a classifier based on 495 genes. There was concordance between IHC, GEP and clinical picture in 54% of cases. In four cases, the combination of methods led to an unequivocal identification of the primary tumor.In conclusion, we regard detailed IHC workup and complementary GEP advisable for the purposes of targeted therapy, as well as to identify or exclude specific tumors in a CUP situation.

Paclitaxel and carboplatin vs gemcitabine and vinorelbine in patients with adeno- or undifferentiated carcinoma of unknown primary: a randomised prospective phase II trial.

Platinum/taxane combinations are widely used in patients with carcinoma of unknown primary (CUP), yielding response rates of 30% and median overall survival of 9-11 months in selected patients. Yet these combinations have not been subject to a randomised trial to overcome selection bias, a major problem in CUP. We randomised 92 patients to either paclitaxel/carboplatin (arm A) or the non-platinum non-taxane regimen gemcitabine/vinorelbine (arm B). The primary endpoint was rate of practicability as defined: application of >or=2 cycles of therapy (1) with a maximal delay of 1 week (2) and survival of >or=8 months (3). Practicability was shown in 52.4% (95% CI 36-68%) in arm A and in 42.2% (95% CI 28-58%) in arm B, respectively. The median overall survival, 1-year survival -rate and response rate of patients treated in arm A was 11.0 months, 38, and 23.8%, arm B 7.0 months, 29, and 20%. In conclusion, the paclitaxel/carboplatin regimen showed clinically meaningful activity in this randomised trial (Clinical trial registration number 219, 'Deutsches KrebsStudienRegister', German Cancer Society.)

Myelodysplastic syndrome and acute myelogenous leukemia secondary to heart transplantation.

Myelodysplastic syndrome and acute myelogenous leukemia secondary to radiotherapy, radiation exposure, and chemotherapy is a well-documented malignant stem cell disorder. The incidence and natural course of myelodysplastic syndrome and acute myelogenous leukemia after organ transplantation remains less thoroughly investigated. In our institution, 631 heart transplantations have been performed between 1983 and 1998. We report five patients (age, 22-63 years) with myelodysplastic syndrome (MDS) (n=1) or acute myelogenous leukemia (AML) (n=4) occuring 4-8 years after transplantation. Immunosuppression consisted uniformly of a combination of prednisone, cyclosporine, and azathioprine. Successful cytogenetic analysis was performed in three patients, showing typical cytogenetic abnormalities in each case. The course of AML was uniformly fatal. One patient with MDS, refractory anemia with excess of blasts according to the FAB criteria, is alive with transfusion dependency 32 months after diagnosis. MDS and AML may occur during immunosuppression after heart transplantation. Treatment results are poor in this subgroup of patients with secondary leukemia.

Effect of topical oral G-CSF on oral mucositis: a randomised placebo-controlled trial.

Oral mucositis is a dose-limiting toxicity of intensive chemotherapy. It is caused directly by the cytotoxic effect of chemotherapeutic agents and indirectly by sustained neutropenia. Severe oral mucositis is an important predisposing factor for life-threatening septic complications during aplasia. It also reduces quality of life. At present, no effective causal prophylaxis or treatment against oral mucositis is established. We performed a prospective randomised placebo-controlled trial using topical oral r-metHuG-CSF (filgrastim) in high-grade lymphoma patients treated according to the B-NHL protocol, which contains high-dose methotrexate and causes severe oral mucositis (WHO grades I-IV) in >50% of patients. Between August 1996 and July 1997, a total of 32 chemotherapy cycles were documented in eight patients (four male, four female). Mucosal erythema and ulceration were recorded. All patients assessed their oral pain and impact on swallowing daily, using a subjective scale from no to maximal discomfort (1-10). In addition, oral mucositis was assessed according to the WHO score. Filgrastim was administered in 16 cycles as a viscous mouthrinse (carboxymethylcellulose 2%, oleum citrii) 4 x 120 microg/day from days 10 to 16. Sixteen cycles were given to control patients, of these 14 with placebo, and another two cycles with no treatment. Severe mucositis (WHO grade III/IV) was documented in 21 of 32 cycles (65.5%). A difference of borderline significance was observed for the reduction of maximum severity of oral mucositis between G-CSF vs placebo (P = 0.058), with a reduction of WHO grade IV of 50% (four G-CSF vs eight control). The number of days in hospital was reduced significantly in the G-CSF group (P = 0.02). In conclusion, topical oral G-CSF mouthrinses may be beneficial to reduce oral mucositis.

Early detection of chronic disseminated Candida infection in leukemia patients with febrile neutropenia: value of computer-assisted serial ultrasound documentation.

Computer tomography (CT) is known to be as sensitive as magnetic resonance imaging (MRI) in detecting fungal microabscesses in chronic disseminated candidiasis. However, all imaging techniques have to be repeated in cases of suspected fungal infection. Therefore, use of the CT or MRI scan is limited. Only ultrasound (US) examinations can be repeated as often as needed. The disadvantage of US is a lack of sufficient documentation. We analyzed the value of computer-assisted documentation in serial ultrasonography of leukemia patients with suspected chronic disseminated candidiasis. From November 1996 until October 1997, a total of 220 ultrasound examinations (Kranzbühler Logiq 500, 3.5 MHz convex array) were performed in 58 patients undergoing intensive chemotherapy. Initial US pictures were stored on a personal computer and compared with the live US at the time of reevaluation in cases of persistent fever. Ultrasound detected microabscesses in liver and/or spleen in eight of the 58 patients. Diagnosis was confirmed by autopsy/biopsy (n = 6), blood culture (n = 1), and a significant Candida antibody titer (n = 1). Focal lesions occurred only after neutrophil recovery. However, a newly evolving nonhomogeneous, micronodular pattern of liver and spleen occurred during febrile neutropenia in three patients, and two of these developed focal lesions subsequently. Follow-up was easy, since US pictures could be compared directly with stored examinations on screen. We conclude that serial US is sensitive in detecting microabscesses in the liver or the spleen. Computer-assisted US documentation proved to be a helpful tool for detection as well as in the follow-up of patients with chronic disseminated candidiasis.

Placement and restoration of implants by predoctoral students: the Creighton experience.

Teaching of implant dentistry in the predoctoral dental curriculum has evolved dramatically over the past 20 years. In 1974, only one third of American dental schools addressed the topic of implants. Today, 48 of the 54 American dental schools have predoctoral curricula. The Creighton University experience offers some unique and instructive insights into a 10-year process of developing and implementing a predoctoral implant dentistry curriculum. All interested students may perform both the surgical placement and restoration of implant prostheses. Clinical instruction involves all restorative and surgical faculty members. Favorable 3-year (91%) and 5-year (87%) surgical success rates have been maintained. This article presents one university's program for examination and discussion.

A simple and rapid method for the determination of D-sorbitol in plasma using the Cobas Mira S.

The standard enzymatic assay for quantification of D-sorbitol in plasma was adapted to the automatic analyzer Cobas Mira S. In the assay, NAD (reagent) in the presence of sorbitoldehydrogenase (SDH; start reagent) converts D-sorbitol to fructose with formation of NADH, which was detected automatically as the difference between the first and last readings at 340 nm. The sample blank values for each specimen were subtracted to exclude both endogenous D-sorbitol and sugars, which also react as substrates for SDH. The method is simple, rapid (40 samples/h), precise down to endogenous concentrations (coefficient of variation < 5%; limit of determination: 0.38 mg/L) and linear up to 100 mg/L. Samples with higher D-sorbitol concentrations were estimated after dilution. The method was used to measure disposition curves of sorbitol in volunteers after a single intravenous dose of 0.8 g sorbitol.

Central ossifying fibroma of the anterior maxilla: report of case.

Central ossifying fibromas are well-documented, benign lesions usually found on the mandible and posterior maxilla. These lesions are differentiated from other fibro-osseous proliferations by specific clinical, radiographic, and histopathological criteria. An unusual case involving the anterior maxilla is described, including a review of the diagnostic features of the lesion as well as a discussion of its relationship to other fibro-osseous lesions.

The role of dental disease in fever of unknown origin.

The case presented emphasizes the need for evaluation of the oral cavity in the diagnostic workup of fever of unknown origin. Hurley stated, "Protracted fever of obscure cause remains one of the more daunting clinical challenges facing the physician. It calls for mobilization of all the physician's own skills and the expertise of colleagues as well as maintenance of an open mind to the patient's complaints and observations. Dogged determination and a systematic approach are the keys to solving the problem." When the possibility of dental disease is overlooked, the resulting search is sometimes long, tedious, and expensive. Early examination of the oral cavity by qualified personnel should be done even though pain is not present.

Stress reduction prior to oral surgery.

Patients about to undergo oral surgical procedures may be fearful and anxious. It is thought that stress reduction can be attained by relaxation and reassurance. One time stress reduction techniques were tested on 100 patients prior to oral surgery and measurements of stress were made prior to and during the procedures. Patients were divided randomly into four groups: group one patients received general surgical information about tooth removal; group two patients listened to a relaxation tape; group three patients listened to a combination of surgical information and relaxation information tape; and group four patients had no intervention. The day of oral surgery, patients were administered Corah's Dental Anxiety Scale. In addition, measurements of peripheral skin temperature, frontalis EMG for facial muscle tension and blood pressure recordings were made. The measurements were taken prior to and after the patients listened to the information mentioned above on audio tapes, (groups 1-3) or relaxed in their own way (group 4). Self assessment of anxiety reduction was recorded and evaluation of relaxation was made by the oral surgeon during the surgical procedure. Observations were made relating to age, sex, degree of surgical difficulty and presence or absence of preoperative pain. A significant decrease in blood pressure (p_.01 was noted between the experimental and control group. Reduction of anxiety was notably seen with group three patients, where EMG and temperature differences varied from the control group. It was also noted that all patients perceived some degree of relaxation.

Wood fiber contamination of reusable cotton laparotomy pads.

If the thesis that disposable fabrics are responsible for granulomatous peritonitis is correct, surgeons who operate within the abdominal cavity and use these products would be reporting instances of granulomatous peritonitis in epidemic proportions. Such is not so. Consequently, there can be valid concern expressed as to implied medicolegal problems. While the observations and conclusions were made in obvious good faith, nevertheless, there appears to be sufficient grounds for questioning this apparent cause and effect conclusion and for focusing interest on a more important consideration, the indiscriminate collection, sorting and laundering of the reusable cotton laparotomy pad. Certainly, attention should be directed to the more rigidly controlled use and disposition of these pads by the individual hospital.