TP53 mutation analyses on breast carcinomas: a study of paraffin-embedded archival material.

The aim of this investigation was to examine the possibility of analysing TP53 mutations in archival paraffin-embedded material with the constant denaturant gel electrophoresis (CDGE) method. We extracted DNA from 193 archival primary breast carcinoma samples, diagnosed in 1981-83; further analysis was possible for 186 of these. TP53 mutations in exons 5-8 were detected with CDGE in 30 samples (16.1%) and 17 of these mutations were confirmed by sequencing. Immunohistochemistry demonstrated TP53 nuclear accumulation in 58 tumours (31%). A strong association between the presence of TP53 mutations and TP53 immunostaining was observed (P < 0.001). Our mutation and immunohistochemistry results are in agreement with other findings based on fresh tumour tissue. TP53 abnormalities were significantly related to high S-phase fraction, low oestrogen receptor (ER) content and high tumour grade. Survival of patients with TP53 abnormalities, in the group as a whole, did not differ from patients with normal TP53. Our study did, however, show that patients with abnormal TP53 had a significantly shorter post-recurrence survival (P = 0.005) than patients with normal TP53.     

The effect of burn wound size on ureagenesis and nitrogen balance.

Hypermetabolic burn patients are frequently in negative nitrogen balance despite provision of estimated caloric needs. We studied 18 thermally injured adult patients in order to evaluate the relationship of burn wound size to urea production and nitrogen balance. We selected data from 147 patient-days when the patients received 100 +/- 25% of their estimated caloric needs. Three significantly different burn size groups (by body surface area [BSA]) were identified by calculation of the catabolic index (CI): group 1, 0-10% BSA (CI = -0.1); group 2, 11-30% BSA (CI = 6.4); and group 3,31-60% BSA (CI = 10.5). The urine urea nitrogen (UUN) for groups 1,2, and 3 was 11.1, 18.9, and 25.3 gm/day, and nitrogen balance was 1.0, -3.9, and -5.8 gm/day, respectively. When nitrogen was given in a calorie:nitrogen ratio of 150:1, only those patients in group I were able to achieve positive balance. We conclude that large burn wounds are associated with increased ureagenesis and impaired nitrogen retention. The protein intake, at the customary calorie:nitrogen ratio of 150:1, may not provide adequate nitrogen to achieve equilibrium, even when energy demands have been met, in patients with burn wounds greater than 10% BSA.     

Second primary cancers among 109 000 cases of non-Hodgkin's lymphoma

An analysis of other primary cancers in individuals with non-Hodgkin's lymphoma (NHL) can help to elucidate this cancer aetiology. In all, 109 451 first primary NHL were included in a pooled analysis of 13 cancer registries. The observed numbers of second cancers were compared to the expected numbers derived from the age-, sex-, calendar period- and registry-specific incidence rates. We also calculated the standardised incidence ratios for NHL as a second primary after other cancers. There was a 47% (95% confidence interval 43-51%) overall increase in the risk of a primary cancer after NHL. A strongly significant (P<0.001) increase was observed for cancers of the lip, tongue, oropharynx*, stomach, small intestine, colon*, liver, nasal cavity*, lung, soft tissues*, skin melanoma*, nonmelanoma skin*, bladder*, kidney*, thyroid*, Hodgkin's lymphoma*, lymphoid leukaemia* and myeloid leukaemia. Non-Hodgkin's lymphoma as a second primary was increased after cancers marked with an asterisk. Patterns of risk indicate a treatment effect for lung, bladder, stomach, Hodgkin's lymphoma and myeloid leukaemia. Common risk factors may be involved for cancers of the lung, bladder, nasal cavity and for soft tissues, such as pesticides. Bidirectional effects for several cancer sites of potential viral origin argue strongly for a role for immune suppression in NHL.     

Markers of collagen synthesis and degradation in urogenital tissue from women with and without stress urinary incontinence

AIMS: Multiparity and obesity are risk factors for stress urinary incontinence (SUI), but collagen synthesis and metabolism in the urogenital tissue itself may also affect its function and control of micturition. Whether changes in synthesis or degradation of collagen are part of the etiology of SUI is not known and published studies show diverging results. The aims of the present study was to investigate collagen turnover in urogenital tissue in women with SUI (n=71) and in urologically healthy women (n=31). METHODS: Markers of collagen synthesis and breakdown, the carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of type I collagen (ICTP), and the amino-terminal propeptide of procollagen III (PIIINP) were assayed in urogenital tissue homogenates and peripheral serum. RESULTS: In the total clinical material SUI patients were significantly older, had a significantly higher body mass index (BMI) and significantly lower serum PICP and tissue ICTP levels than the controls. When healthy controls were compared with SUI patients matched for age, BMI, parity, and hormonal/menopausal status (31 women in each group), the SUI patients had significantly lower serum concentrations of PICP and significantly lower tissue concentrations of PIIINP and ICTP than the controls. Within the total material of SUI patients, post-menopausal women with weak and strong HRT and pre-menopausal women had significantly lower S-ICTP concentrations than untreated post-menopausal patients. Significant negative correlations to parity were found for T-PIIINP and T-PICP and to BMI for T-ICTP. CONCLUSIONS: The low tissue collagen marker levels in women with SUI suggest a reduced collagen turnover, which may negatively affect tissue strength and elasticity.     

Multicentre study of validity and interrater reliability of the modified Nursing Care Recording System (NCR11) for assessment of workload in the ICU

BACKGROUND: Reliable assessment of nursing workload is necessary for the quantitative approach to staffing of intensive care units. The Nursing Care Recording System (NCR11) scores both the nursing contribution to patient care and those related to medical procedures. The purpose of the present work was to compare NCR11 scoring with the Therapeutic Intervention Scoring System (TISS) and Nine Equivalents of Nurse Manpower use Score (NEMS) and to examine the interrater reliability of NCR11 scoring. METHODS: Bias and precision of workload scores (NCR11 vs. TISS or NEMS) were assessed for 6126 consecutive admissions (23910 ICU-days) at three intensive care units. Inter-rater reliability was analyzed by having nurses at nine ICUs score workload using NCR11 for three dummy intensive care patient cases presented over a 3-year period. Variability in scoring was analyzed using the coefficient of variation. RESULTS: Agreement between NCR11 and TISS or NEMS was poor and limits of agreement were wide. Linear relationships between NCR11 and TISS or NEMS scores differed between units. Variability in NCR11 scoring decreased significantly from 10.4% to 5.9% between dummy cases 1 and 2 and remained low for patient case 3. CONCLUSION: The NCR11 does not measure the same elements of workload in the ICU as do TISS and NEMS. Inter-rater reliability with NCR11 is good, showing little variation in scoring between nurses.     

Preserved anterograde and retrograde memory of rapidly acquired olfactory discrminations after neurotoxic hippocampal lesions

A forced-choice discrimination paradigm was used in two experiments, to evaluate retrograde and anterograde amnesia in rats after hippocampal ablation. In a within-subjects design (Experiment 1), rats were trained on a set of 10 olfactory discriminations 4 weeks before surgery and on a separate set of 10 discriminations 1 week before surgery. In a mixed design (Experiment 2), rats were trained on olfactory discriminations in one of three conditions: condition 1 (10 discriminations at 4 weeks before surgery); condition 2 (10 discriminations at 1 week before surgery); or condition 3 (10 discriminations at 4 weeks before surgery and 10 discriminations at 1 week before surgery). Discriminations in both experiments were rapidly learned, requiring 7-10 trials to reach criterion. After training, half of the rats in each condition received bilateral neurotoxic lesions of the hippocampus, and the other half received sham surgery. One week after surgery, all rats were given a retention test, consisting of a single critical trial for each discrimination. In both experiments, rats with selective hippocampal lesions exhibited preserved retention of these olfactory discriminations with no observable retention gradient. A postoperative acquisition test for two new discriminations indicated that anterograde memory was also preserved, while a postoperative test of spatial learning in the Morris water maze confirmed that the hippocampal lesions impaired spatial learning. Together, these experiments refute the contention that the hippocampus is requisite for (non-spatial) olfactory memory consolidation, storage, or access, despite the condition that the information be rapidly acquired.     

Racial differences of lens transparency properties with aging and prevalence of age-related cataract applying a WHO classification system

PURPOSE: To investigate racial differences of lens transparency properties and the prevalence of lens opacification by age. METHODS: Lenses of randomly selected Asian (1,038 Japanese and 517 Singaporeans) and Caucasian (1,045 Icelanders) subjects were evaluated for their lens transparency property (LTP). The prevalence of lens opacification was determined with a newly proposed WHO cataract classification system. RESULTS: LTP increased with aging for all nationalities. Light scattering intensity was significantly higher in the Singaporeans followed by the Icelandic subjects. The prevalence of cortical opacification in Singaporeans was significantly higher than those of the other nationalities up to the age of 60, and the prevalence in Asians was significantly higher than that in Caucasians aged 60-69. Cortical opacification was more prevalent than the other types for both Japanese and Icelanders in their 50s, 60s and 70s. Regarding the central optical zone, the prevalence in the Singaporeans was significantly higher than in the other two groups in their 50s and 60s. The prevalence of nuclear opacification in Singaporeans was markedly higher than those of the two other groups for all ages. Subcapsular cataract was the least prevalent type for all age groups and nationalities; however, the highest prevalence was observed in Singaporeans. CONCLUSIONS: Lens transparency decreased with age in the Singaporeans more markedly than in the other two groups. The high prevalence of nuclear opacification in Singaporeans is considered to be due to environmental rather than race-specific factors.