Cyclical behavior of bone remodeling and bone loss in healthy women after menopause: results of a prospective study

Annual changes in lumbar bone mineral density (LBMD) and bone remodeling markers were measured in 238 healthy pre- and postmenopausal women, aged 45–74 years. The subjects were divided into groups according to their menstrual status and years since menopause. The results obtained indicate that bone loss is not a constant process over time but rather exhibits cyclical damping oscillations. When the log-linear trend of LBMD decrement was transformed into a constant by considering annual percentage changes, the presence of a cyclical component of 7 years was evident. By employing a harmonic regression model, the cyclical component was also statistically significant on baseline data. The cyclical behavior of LBMD decrement corresponded to an analogous behavior of the bone remodeling markers. These results suggest that a lack of estrogen acts as a synchronizer on bone remodeling by triggering a latent cyclical rhythm of bone loss that persists throughout life after menopause. The existence of a chronobiological rhythm of bone loss starting after menopause, if confirmed, could have important clinical implications.     

Acetylcholine-mediated modulation of striatal function

Striatal spiny neurones serve as a major anatomical locus for the relay of cortical information flow through the basal ganglia. these projection neurones also represent the main synaptic target of cholinergic interneurones, whose physiological role in striatal activity still remains largely enigmatic. The striatal cholinergic system has been implicated in the pathophysiology of movement disorders such as Parkinson's disease, but the cellular mechanisms underlying cholinergic-neurone function are still unknown. On the basis of in vitro electrophysiological evidence, obtained from a rat corticostriatal-slice preparation, we propose that endogenous ACh exerts a complex modulation of striatal synaptic transmission, which produces both short-term and long-term effects. ACh-mediated mechanisms might be of crucial importance in processing the cortical inputs to the striatum.     

Endometrial carcinoma with laparotomy wound recurrence: complete remission following surgery and chemotherapy consisting of paclitaxel and carboplatin

We present a patient with surgical stage I endometrial cancer who experienced laparotomy wound recurrence 4 years after primary treatment. She was treated successfully by complete surgical resection of recurrent tumors and chemotherapy. A 62-year-old white female with laparotomy wound recurrence of endometrial carcinoma with small-bowel involvement and concomitant subcutaneous metastasis in the abdominal wall underwent complete surgical resection of metastatic tumors followed by six cycles of chemotherapy consisting of paclitaxel (175 mg/m2) and carboplatin (area under the curve 5). Since 24 months after resection of recurrence, she has no evidence of disease recurrence. Endometrial carcinoma with laparotomy wound recurrences, especially those with concomitant metastases, can be successfully treated by complete surgical resection followed by chemotherapy consisting of paclitaxel and carboplatin.     

Estimates of the world-wide prevalence of cancer for 25 sites in the adult population.

In health services planning, in addition to the basic measures of disease occurrence incidence and mortality, other indexes expressing the demand of care are also required to develop strategies for service provision. One of these is prevalence of the disease, which measures the absolute number, and relative proportion in the population, of individuals affected by the disease and that require some form of medical attention. For most cancer sites, cases surviving 5 years from diagnosis experience thereafter the same survival as the general population, so most of the workload is therefore due to medical acts within these first 5 years. This article reports world-wide estimates of 1-, 2-3- and 4-5-year point prevalence in 1990 in the population aged 15 years or over, and hence describes the number of cancer cases diagnosed between 1986 and 1990 who were still alive at the end of 1990. These estimates of prevalence at 1, 2-3 and 4-5 years are applicable to the evaluation of initial treatment, clinical follow-up and point of cure, respectively, for the majority of cancers. We describe the computational procedure and data sources utilised to obtain these figures and compare them with data published by 2 cancer registries. The highest prevalence of cancer is in North America with 1.5% of the population affected and diagnosed in the previous 5 years (about 0.5% of the population in years 4-5 and 2-3 of follow-up and 0.4% within the first year of diagnosis). This corresponds to over 3.2 million individuals. Western Europe and Australia and New Zealand show very similar percentages with 1.2% and 1.1% of the population affected (about 3.9 and 0.2 million cases respectively). Japan and Eastern Europe form the next batch with 1.0% and 0.7%, followed by Latin America and the Caribbean (overall prevalence of 0.4%), and all remaining regions are around 0.2%. Cancer prevalence in developed countries is very similar in men and women, 1.1% of the sex-specific population, while in developing countries the prevalence is some 25% greater in women than men, reflecting a preponderance of cancer sites with poor survival such as liver, oesophagus and stomach in males. The magnitude of disease incidence is the primary determinant of crude prevalence of cases diagnosed within 1 year so that differences by region mainly reflect variation in risk. In the long-term period however different demographic patterns with long-life expectancy in high-income countries determine a higher prevalence in these areas even for relatively uncommon cancer sites such as the cervix.     

Neurofibromatosis type 1 and precocious puberty

Since neurofibromatosis type 1 (NF1) is a well known cause of precocious puberty (PP), we reviewed 412 NF1 pediatric patients to evaluate the prevalence of PP, the association with optic pathway tumors (OPT), and other clinical, auxological and hormonal data. Thirty-one of 412 patients had OPT (7.5%), 10/412 PP (2.4%), and in seven of these PP was associated with OPT (7/31, 22.6%). OPT in patients with PP involved the chiasm in four patients, and the optic nerves alone in three patients. The age at the onset of puberty (or better at diagnosis) ranged from 5.2 to 7.5 yr in girls (n=6) and from 7.9 to 8.9 yr in boys (n=4). LHRH agonist therapy was used in only three children because in the others the predicted height at diagnosis was good, treatment was refused or the patients were referred to us too late. The three treated patients attained a final height within the familial range. In the untreated patients the progression of puberty was not too rapid and final height was slightly below the genetic target in four patients; however, three patients had a final height markedly below the familial range. In conclusion, the prevalence of PP is increased in children with NF1, and frequently but not exclusively is associated with OPT. Moreover, sexual precocity does not seem to be necessarily bound to chiasmatic OPT. Treatment seems to be useful in the children with younger age at the onset of puberty or with a progressive decline in predicted final height.     

Hydrogenated fat diet intake during pregnancy and lactation modifies the PAI-1 gene expression in white adipose tissue of offspring in adult life

We examine whether feeding pregnant and lactating rats hydrogenated fats rich in trans fatty acids modifies the plasma lipid profiles and the expression of adipokines involved with insulin resistance and cardiovascular disease in their 90-day-old offspring. Pregnant and lactating Wistar rats were fed with either a control diet (C group) or one enriched with hydrogenated vegetable fat (T group). Upon weaning, the male pups were sorted into four groups: CC, mothers were receiving C and pups were kept on C; CT, mothers were receiving C and pups were fed with T; TT, mothers were receiving T and pups were kept on T; TC, mothers were receiving T and pups were fed with C. Pups' food intake and body weight were quantified weekly and the pups were killed at day 90 of life by decapitation. Blood and carcass as well as retroperitoneal, epididymal, and subcutaneous white adipose tissues were collected. Food intake and body weight were lower in TC and TT, and metabolic efficiency was reduced in TT. Offspring of TT and TC rats had increased white adipose tissue PAI-1 gene expression. Insulin receptor was higher in TT than other groups. Ingestion of hydrogenated vegetable fat by the mother during gestation and lactation could promote deleterious consequences, even after the withdrawal of the causal factor.     

Early findings from a community-based, cluster-randomized, controlled oral cancer screening trial in Kerala, India. The Trivandrum Oral Cancer Screening Study Group

BACKGROUND: Oral cancer satisfies the criteria for a suitable disease for screening, and oral visual inspection is a suitable test for oral cancer screening. The efficacy of screening in reducing mortality from oral cancer has not yet been evaluated. The authors describe a cluster-randomized, controlled oral cancer screening trial in southern India and its early results. METHODS: Apparently healthy subjects age 35 years or older in 13 clusters called panchayaths were randomized to either an intervention group (n = 7) or a control group (n = 6). Subjects in the intervention group will receive 3 rounds of screening consisting of oral visual inspection by trained health workers at 3-year intervals. The first round of screening was carried out between October 1995 and May 1998. Participants were visited in their homes and interviewed for sociodemographic details, tobacco-smoking and alcohol-drinking habits, and personal medical history. Those with tobacco or alcohol habits were advised to stop those habits. Subjects in the intervention group were offered screening, and those with lesions suggestive of oral leukoplakia, submucous fibrosis, or oral cancer were referred for examination by physicians. Confirmed leukoplakias were excised whenever possible, others were kept on follow-up, and those with confirmed oral cancers were referred for treatment. Data on oral cancer incidence, stage distribution, survival, and mortality in the study groups are obtained by record linkage with the Trivandrum population-based cancer registry and municipal death registration systems. RESULTS: There were 59,894 eligible subjects in the intervention group and 54,707 in the control group; 31.4% of the former group reported no tobacco or alcohol habits, compared with 44.1% of the latter. The distribution of age, education, occupation, income, and socioeconomic status were similar in the two groups. Of 3585 subjects in the intervention group referred, 52.4% were examined by physicians; 36 subjects with oral cancers and 1310 with oral precancers were diagnosed. Of the 63 oral cancers recorded in the cancer registry, 47 were in the intervention group and 16 were in the control group, yielding incidence rates of 56.1 and 20.3 per 100,000 person-years in the intervention and control groups, respectively. The program sensitivity for detection of oral cancer was 76.6% and the specificity 76.2%; the positive predictive value was 1.0% for oral cancer. In the intervention group, 72.3% of the cases were in Stages I-II, as opposed to 12.5% in the control group. The 3-year case fatality rates were 14.9% (7 of 47 patients) in the intervention group and 56.3% (9 of 16 patients) in the control group. CONCLUSIONS: Though compliance with referral for confirmatory examination in the first round was lower than the 70% anticipated, intermediate end points, such as stage at diagnosis and case fatality, indicate that the trial is making fairly satisfactory progress.     

Protective effect of n-acetylcysteine in a model of influenza infection in mice

Reactive oxygen intermediates (ROI) and cytokines, particularly tumor necrosis factor (TNF) have been implicated in the pathogenesis of influenza. Using a murine model of influenza, we have studied the levels of TNF, interleukin 6 (IL-6) and of superoxide-generating xanthine oxidase (XO). Mice infected intranasally with influenza virus APR/8 had high levels of XO, TNF and IL-6 in the broncoalveolar lavage, as early as 3 d after infection. XO was elevated also in serum and lung tissue. Administration of the antioxidant N-acetylcysteine (NAC,1 g/kg per day, orally) significantly decreased the mortality in infected mice, indicating a role for RO1 in the lethality associated with influenza infection.     

Desmoplastic malignant mesothelioma masquerading as sclerosing mediastinitis: a diagnostic dilemma.

A 48-year-old woman presented with dyspnea, chest discomfort, and left vocal cord paralysis that developed 2 months after a flu-like illness. Radiographic examination showed prominence of mediastinal soft tissues and an ill-defined left upper lobe infiltrate. Dense mediastinal sclerosis was found at thoracotomy, and biopsy samples taken from the sclerotic areas showed densely hyalinized fibrotic tissue. Necrotizing granulomas containing organisms resembling Histoplasma capsulatum were present within mediastinal lymph nodes. Based on these findings, a diagnosis of sclerosing mediastinitis was made. During the next year, the patient's respiratory function deteriorated, and biopsy samples taken during a second thoracotomy 1 year later were again interpreted as sclerosing mediastinitis. The patient died postoperatively; at autopsy, the sclerotic mass involving the mediastinum was composed of a mixture of dense fibrosis and sarcomatous tissue. The final diagnosis was localized mediastinal desmoplastic malignant mesothelioma. We report it here because of its unusual clinical presentation, which mimicked sclerosing mediastinitis.     

Relationship Between Spine Bone Mineral Density and Vertebral Body Heights

The aim of this study was to investigate the correlation between lumbar spine bone mineral density (LS-BMD) and the vertebral body heights with advancing age and years since menopause. One hundred and sixty-three women ages 39–74 years (77 normal premenopausal, ages 39–54, and 86 normal postmenopausal, ages 46–74 years) were studied. LS-BMD was measured by dual energy X-ray absorptiometry. Vertebral heights were evaluated, using morphometry, as the sum of anterior (AHs), middle (MHs), and posterior (PHs) vertebral body heights from T₄ to L₅. The AHs/PHs ratio at the same level was also calculated. AHs, MHs, PHs, and AHs/PHs ratio directly correlated with LS-BMD; the correlations are AHs r = 0.80, P < 0.0001, MHs r = 0.75, P < 0.0001, PHs r = 0.76, P < 0.0001, and AHs/PHs r = 0.66, P < 0.001. Both LS-BMD and AHs are inversely correlated with age, and the regressions fit with both linear and cubic curves. The statistical significance of the correlations persists while maintaining age constant. The linear regression curve of AHs with age indicates that the spine height decrement rate is 2.12 mm/year, corresponding to 7.4 cm in 35 years. AHs decreases immediately after menopause fitting with a cubic curve model, with a decrement rate of about 3 cm in the first 5 years after menopause. We conclude that the measurement of the sum of vertebral body heights could usefully integrate LS-BMD evaluation in the clinical and epidemiological investigation of osteoporosis. Received: 30 May 1997 / Accepted: 14 November 1997