Effects of physical conditioning on fibrinolytic variables and fibrinogen in young and old healthy adults

BACKGROUND. The effects of 6 months of intensive endurance exercise training on resting tissue-type plasminogen activator (t-PA) activity, plasminogen activator inhibitor type 1 (PAI-1) activity, t-PA antigen, and fibrinogen were studied in 10 young (24-30 years) and in 13 old male subjects (60-82 years). METHODS AND RESULTS. After training, maximum oxygen consumption was increased in the young group by 18% (44.9 +/- 5.0 to 52.9 +/- 6.6 ml/kg/min, p less than 0.001), whereas it was increased in the old group by 22% (29.0 +/- 4.2 to 35.5 +/- 3.6 ml/kg/min, p less than 0.001). The young group had no significant changes in any of the measured variables, whereas the old group had a 39% increase in t-PA activity (0.82 +/- 0.47 to 1.14 +/- 0.42 IU/ml, p less than 0.03), a 141% increase in the percentage of t-PA in the active form (11.1 +/- 7.7 to 26.8 +/- 15.1%, p less than 0.01), a 58% decrease in PAI-1 activity (8.4 +/- 4.9 to 3.5 +/- 1.7 AU/ml, p less than 0.01), and a 13% decrease in fibrinogen (3.57 +/- 0.79 to 3.11 +/- 0.52 g/l, p less than 0.01). CONCLUSIONS. We conclude that intensive exercise training enhances resting t-PA activity and reduces fibrinogen and PAI-1 activity in older men. These effects are potential mechanisms by which habitual physical activity might reduce the risk of cardiovascular disease.     

Maternal obesity and pregnancy outcome: a study of 287,213 pregnancies in London

OBJECTIVE: To examine the maternal and foetal risks of adverse pregnancy outcome in relation to maternal obesity, expressed as body mass index (BMI, kg/m(2)) in a large unselected geographical population. DESIGN: Retrospective analysis of data from a validated maternity database system which includes all but one of the maternity units in the North West Thames Region. A comparison of pregnancy outcomes was made on the basis of maternal BMI at booking. SUBJECTS: A total of 287,213 completed singleton pregnancies were studied including 176,923 (61.6%) normal weight (BMI 20--24.9), 79 014 (27.5%) moderately obese (BMI 25--29.9) and 31,276 (10.9%) very obese (BMI> or =30) women. MEASUREMENTS: Ante-natal complications, intervention in labour, maternal morbidity and neonatal outcome were examined and data presented as raw frequencies and adjusted odds ratios with 99% confidence intervals following logistic regression analysis to account for confounding variables. RESULTS: Compared to women with normal BMI, the following outcomes were significantly more common in obese pregnant women (odds ratio (99% confidence interval) for BMI 25--30 and BMI> or =30 respectively): gestational diabetes mellitus (1.68 (1.53--1.84), 3.6 (3.25--3.98)); proteinuric pre-eclampsia (1.44 (1.28--1.62), 2.14 (1.85--2.47)); induction of labour (2.14 (1.85--2.47), 1.70 (1.64--1.76)); delivery by emergency caesarian section (1.30 (1.25--1.34), 1.83 (1.74--1.93)); postpartum haemorrhage (1.16 (1.12--1.21), 1.39 (1.32--1.46)); genital tract infection (1.24 (1.09--1.41), 1.30 (1.07--1.56)); urinary tract infection (1.17 (1.04-1.33), 1.39 (1.18--1.63)); wound infection (1.27 (1.09--1.48), 2.24 (1.91--2.64)); birthweight above the 90th centile (1.57 (1.50--1.64), 2.36 (2.23--2.50)), and intrauterine death (1.10 (0.94--1.28), 1.40 (1.14--1.71)). However, delivery before 32 weeks' gestation (0.73 (0.65--0.82), 0.81 (0.69--0.95)) and breastfeeding at discharge (0.86 (0.84--0.88), 0.58 (0.56--0.60)) were significantly less likely in the overweight groups. In all cases, increasing maternal BMI was associated with increased magnitude of risk. CONCLUSION: Maternal obesity carries significant risks for the mother and foetus. The risk increases with the degree of obesity and persists after accounting for other confounding demographic factors. The basis of many of the complications is likely to be related to the altered metabolic state associated with morbid obesity.     

Essential thrombocythaemia and the Philadelphia chromosome

Six adult patients presented with clinical features of essential thrombocythaemia. Five of the patients, although Ph-positive, have maintained these features without evidence of leukaemia; in one case for 9 years. A sixth patient developed leukaemic blast crisis following a persistently high platelet count over 4 years. Her cells were Ph-negative, but hybridization of gene probes to chromosomes in situ and to leukaemic DNA showed that the abl oncogene had moved to the breakpoint cluster region (bcr) on the normal chromosome 22. This patient has the same molecular gene change as occurs in some cases of Ph-negative chronic myeloid leukaemia (CML) whose leukaemic cells likewise show no evidence of chromosomal translocation. Molecular studies are essential for the correct diagnosis of these patients. The Ph genomic lesion appears to have a range of leukaemic expression which includes thrombocythaemia as well as chronic myeloid leukaemia and acute lymphatic leukaemia.     

Ph-negative chronic myeloid leukaemia

An analysis of five patients with Philadelphia chromosome (Ph) negative chronic myeloid leukaemia (CML) revealed that two were clinically and haematologically identical to Ph-positive CML whereas three should be reclassified as chronic myelomonocytic leukaemia (CMML). At a molecular level the first two patients showed the same juxtaposition of c-abl and bcr genes as is seen in Ph-positive CML. These genomic changes were not seen in the other three patients. Observations on these five patients suggest that the clinical course and prognosis of the rare patient who carries the Ph 'molecular defect' but lacks the Philadelphia chromosome is no different from Ph-positive CML.     

Uncertainties surrounding the choice of surgical treatment for ‘bone on bone’ medial compartment osteoarthritis of the knee

A number of different surgical interventions can be used for treating antero-medial osteoarthritis (AMOA) of the knee and this choice can present challenges for patient's decision-making. Patients with AMOA can undergo Total Knee Replacement (TKR), Unicompartmental Knee Replacement (UKR) or High Tibial Osteotomy (HTO) for the same pathology. However many uncertainties still exist as to deciding which operation is best for individual patients and the Orthopaedic community has failed to systematically compare treatment options. The relative lack of scientifically based evidence has impacted on the ability to provide clear guidelines on treatment choice, patient suitability and direct patient preference for treatment. This paper, using available evidence, discusses the issue and offers some suggestions for future development.     

Diagnostic testing for galactose-alpha-1,3-galactose,United States, 2010 to 2018

BackgroundAlpha-gal syndrome (AGS) is an emerging immunoglobulin E (IgE)–mediated allergy to galactose-alpha-1,3-galactose (alpha-gal). The geographic distribution and burden of AGS in the United States are unknown.ObjectiveTo characterize alpha-gal IgE testing patterns and describe the trends and distribution from 2010 to 2018 in the United States.MethodsThis retrospective analysis included all persons tested for alpha-gal IgE antibodies by Viracor-IBT Laboratories (Lee’s Summit, Missouri), the primary site of testing in the United States. Data included age and sex of person tested, specimen state of origin, collection date, and result value; persons with at least 1 positive test result (≥0.1 kU/L) were compared with negatives. Proportions tested and with positive test results were calculated using the US Census population estimates.ResultsOverall, 122,068 specimens from 105,674 persons were tested for alpha-gal IgE during July 1, 2010, to December 31, 2018. Nearly one-third (34,256, 32.4%) had at least 1 positive result. The number of persons receiving positive test results increased 6-fold from 1110 in 2011 to 7798 in 2018. Of those receiving positive test results, mean [SD] age was 46.9 (19.8) years; men were more likely to test positive than women (43.3% vs 26.0%). Arkansas, Virginia, Kentucky, Oklahoma, and Missouri had the highest number of persons who were tested and had a positive result per 100,000 population.ConclusionMore than 34,000 persons, most presumably symptomatic, have received positive test results for IgE antibodies to alpha-gal, suggesting AGS is an increasingly recognized public health problem. The geographic distribution of persons who tested positive is consistent with exposure to Amblyomma americanum ticks.     

Cervical lymph node metastasis in squamous cell carcinoma of the buccal mucosa: a retrospective study on pattern of involvement and clinical analysis

Background The study was performed with an aim to map the pattern of metastasis of squamous cell carcinomas of buccal mucosa to various cervical lymph node levels and analyze its correlation with primary tumor size and histo-pathological grading. Material and Methods 254 patients with squamous cell carcinoma of the buccal mucosa treated with surgery first approach were analyzed retrospectively. The tumor size was noted from pre-operative CT Scans and were divided into early and advanced tumors. The resected specimen was studied to note the histo-pathological grading of the squamous cell carcinoma and the metastatic deposits at various lymph node levels. Results Out of 254 patients (149 females, 105 males), 145 patients showed histo-pathologically proven metastatic deposits in one or more lymph nodes out of which there were 56 patients showing occult metastasis. 78/145 patients showed metastatic involvement of level IB and/or IA lymph nodes, 31 showed involvement of level II and/or I lymph nodes, 27 showed involvement of level III with or without involvement of level I and II and 9 showed metastasis to level IV and V lymph nodes with or without level I, II or III lymph nodes. Cervical lymph node metastasis had statistically significant association with tumor size with advanced tumors showing worse pattern of metastatic spread beyond level I and II lymph nodes. As the degree of differentiation of squamous cell carcinoma reduced, they were more prone for cervical metastasis with moderately and poorly differentiated squamous cell carcinoma showing higher involvement of level III, IV and V lymph nodes. Conclusions The majority of buccal mucosa cases showed metastasis to level I, II and III lymph nodes out of which level IB and/or IA was most frequently involved. Metastasis to level IV and V lymph nodes was rare and was seen especially in patients with advanced primary tumor and poor histo-pathologic differentiation. Key words:Oral squamous cell carcinoma (OSCC), cervical lymph node metastasis, histologic differentiation, locally advanced disease.     

A Complex Ph1 Translocation in a Patient with Primary Thrombocythaemia

S ummary . Routine blood examination of a 27-year-old female revealed a platelet count of 2000 10⁹/1. Bone marrow cells showed the Philadelphia chromosome which was one product of a complex rearrangement of chromosomes 9, 22 and X. Her platelet count was lowered by plateletphoresis and chemotherapy. She remains in good health 19 months later, but her thrombocythaemia is considered to be an early manifestation of chronic myeloid leukaemia.