Sex differences in the effects of early neocortical injury on neuronal size distribution of the medial geniculate nucleus in the rat are mediated by perinatal gonadal steroids.
Freezing injury to the cortical plate of rats induces cerebrocortical microgyria and, in males but not females, a shift toward greater numbers of small neurons in the medial geniculate nucleus (MGN). The purpose of the current study was to examine a hormonal basis for this sex difference. Cross-sectional neuronal areas of the MGN were measured in male rats, untreated female rats and female rats treated perinatally with testosterone propionate, all of which had received either neonatal cortical freezing or sham injury. Both male and androgenized female rats with microgyria had significantly smaller MGN neurons when compared to their sham-operated counterparts, whereas untreated females with microgyria did not. These differences were also reflected in MGN neuronal size distribution: both male and androgenized female rats with microgyria had more small and fewer large neurons in their MGN in comparison to shams, while there was no difference in MGN neuronal size distribution between lesioned and sham females. These findings suggest that perinatal gonadal steroids mediate the sex difference in thalamic response to induction of microgyria in the rat cortex. (+info)
Natural history of dysplasia of the uterine cervix.
BACKGROUND: A historical cohort of Toronto (Ontario, Canada) women whose Pap smear histories were recorded at a major cytopathology laboratory provided the opportunity to study progression and regression of cervical dysplasia in an era (1962-1980) during which cervical squamous lesions were managed conservatively. METHODS: Actuarial and Cox's survival analyses were used to estimate the rates and relative risks of progression and regression of mild (cervical intraepithelial neoplasia 1 [CIN1]) and moderate (CIN2) dysplasias. In addition, more than 17,000 women with a history of Pap smears between 1970 and 1980 inclusive and who were diagnosed as having mild, moderate, or severe dysplasia were linked to the Ontario Cancer Registry for the outcome of any subsequent cervical cancers occurring through 1989. RESULTS: Both mild and moderate dysplasias were more likely to regress than to progress. The risk of progression from mild to severe dysplasia or worse was only 1% per year, but the risk of progression from moderate dysplasia was 16% within 2 years and 25% within 5 years. Most of the excess risk of cervical cancer for severe and moderate dysplasias occurred within 2 years of the initial dysplastic smear. After 2 years, in comparison with mild dysplasia, the relative risks for progression from severe or moderate dysplasia to cervical cancer in situ or worse was 4.2 (95% confidence interval [CI] = 3.0-5.7) and 2.5 (95% CI = 2.2-3.0), respectively. CONCLUSION: The risk of progression for moderate dysplasia was intermediate between the risks for mild and severe dysplasia; thus, the moderate category may represent a clinically useful distinction. The majority of untreated mild dysplasias were recorded as regressing to yield a normal smear within 2 years. (+info)
Low-dose combination therapy as first-line hypertension treatment for blacks and nonblacks.
To assess the efficacy and safety of bisoprolol/6.25-mg hydrochlorothiazide (HCTZ), amlodipine, and enalapril in black and nonblack patients, data from two comparative studies were pooled and subgroup analyses performed. Both studies had similar designs and included all three active treatments. The second study also included a placebo group. Subjects (n = 541) with a sitting diastolic blood pressure of 95-114 mmHg were titrated to achieve a diastolic blood pressure < or = 90 mmHg. The studies included 114 blacks and 427 nonblacks. Results of an intention-to-treat analysis of mean change from baseline after 12 weeks of treatment showed the following: 1) blood pressure was significantly lowered by all three active drugs compared with baseline or placebo; 2) in blacks, bisoprolol/6.25-mg HCTZ resulted in significantly greater reductions of systolic and diastolic blood pressure than enalapril or placebo, but was not significantly different from amlodipine; 3) in nonblacks, bisoprolol/6.25-mg HCTZ resulted in significantly greater reduction of diastolic blood pressure than amlodipine, enalapril, or placebo. The placebo-corrected change in blood pressure was greater for blacks than whites on the bisoprolol/6.25-mg HCTZ combination, but this was not statistically significant. Bisoprolol/6.25-mg HCTZ controlled diastolic blood pressure to < or = 90 mmHg in significantly more patients than enalapril or placebo in blacks and nonblacks. The difference in control rates was not significant versus amlodipine. The incidence of drug-related adverse events was similar between treatments; however, bisoprolol/6.25-mg HCTZ had a lower discontinuation rate due to lack of blood pressure control or adverse experiences in both blacks and nonblacks. (+info)
Extent and severity of atherosclerotic involvement of the aortic valve and root in familial hypercholesterolaemia.
OBJECTIVE: To compare the frequency of valvar and supravalvar aortic stenosis in homozygous and heterozygous familial hypercholesterolaemia (FH). DESIGN: Analysis of life time cholesterol exposure and prevalence of aortic atherosclerosis in 84 consecutive cases attending a lipid clinic. SETTING: A tertiary referral centre in London. PATIENTS: Outpatients with FH (six homozygous, 78 heterozygous). INTERVENTIONS: Maintenance of lipid lowering treatment. MAIN OUTCOME MEASURES: Calculated cholesterol x years score (CYS) and echocardiographic measurement of aortic root diameter, aortic valve thickness, and transaortic gradient. RESULTS: Four homozygotes with a mean (SD) CYS of 387 (124) mmol/1 x years had severe aortic stenosis (treatment started after seven years of age), whereas the other two had echocardiographic evidence of supravalvar thickening but no aortic valve stenosis (treatment started before three years of age). On multivariate analysis, mean transaortic gradient correlated significantly with CYS (mean = 523 (175) mmol/1 x years) in heterozygotes (p = 0.0001), but only two had severe aortic valve and root involvement. CONCLUSIONS: In patients with familial hypercholesterolaemia, aortic stenosis is common in homozygotes, and aortic root involvement is always present despite the lower CYS than in heterozygotes. It appears to be determined by short term exposure to high cholesterol concentrations in early life. Conversely, aortic root and valve involvement are rare in heterozygotes and occur only with severe, prolonged hypercholesterolaemia, possibly accelerating age related degenerative effects. (+info)
Amino acid composition of protein termini are biased in different manners.
An exhaustive statistical analysis of the amino acid sequences at the carboxyl (C) and amino (N) termini of proteins and of coding nucleic acid sequences at the 5' side of the stop codons was undertaken. At the N ends, Met and Ala residues are over-represented at the first (+1) position whereas at positions 2 and 5 Thr is preferred. These peculiarities at N-termini are most probably related to the mechanism of initiation of translation (for Met) and to the mechanisms governing the life-span of proteins via regulation of their degradation (for Ala and Thr). We assume that the C-terminal bias facilitates fixation of the C ends on the protein globule by a preference for charged and Cys residues. The terminal biases, a novel feature of protein structure, have to be taken into account when molecular evolution, three-dimensional structure, initiation and termination of translation, protein folding and life-span are concerned. In addition, the bias of protein termini composition is an important feature which should be considered in protein engineering experiments. (+info)
Prevalence of true vein graft aneurysms: implications for aneurysm pathogenesis.
BACKGROUND: Circumstantial evidence suggests that arterial aneurysms have a different cause than atherosclerosis and may form part of a generalized dilating diathesis. The aim of this study was to compare the rates of spontaneous aneurysm formation in vein grafts performed either for popliteal aneurysms or for occlusive disease. The hypothesis was that if arterial aneurysms form a part of a systemic process, then the rates of vein graft aneurysms should be higher for patients with popliteal aneurysms than for patients with lower limb ischemia caused by atherosclerosis. METHODS: Infrainguinal vein grafting procedures performed from 1990 to 1995 were entered into a prospective audit and graft surveillance program. Aneurysmal change was defined as a focal increase in the graft diameter of 1.5 cm or greater, excluding false aneurysms and dilatations after graft angioplasty. RESULTS: During the study period, 221 grafting procedures were performed in 200 patients with occlusive disease and 24 grafting procedures were performed in 21 patients with popliteal aneurysms. Graft surveillance revealed spontaneous aneurysm formation in 10 of the 24 bypass grafts (42%) for popliteal aneurysms but in only 4 of the 221 grafting procedures (2%) that were performed for chronic lower limb ischemia. CONCLUSION: This study provides further evidence that aneurysmal disease is a systemic process, and this finding has clinical implications for the treatment of popliteal aneurysms. (+info)
Cryoglobulinaemia and rheumatic manifestations in patients with hepatitis C virus infection.
OBJECTIVES: To investigate the association of cryoglobulinaemia and rheumatic manifestations in Korean patients with hepatitis C virus (HCV) infection. METHODS: Forty nine Korean patients with HCV infection were recruited. The prevalence, concentration, and type of cryoglobulin (by immunofixation), rheumatoid factor (RF), antinuclear antibody (ANA), and various rheumatological symptoms were investigated and HCV genotype was determined by polymerase chain reaction with genotype specific primer. RESULTS: The prevalence of cryoglobulin was 59% in Korean HCV patients and the concentration of cryoglobulin was 9.8 (7.9) g/l (mean (SD)). The type of cryoglobulinaemia was identified in 23 (80%) of 29 HCV patients with cryoglobulinaemia and they were all type III. There were no differences in age, sex, history of operation and transfusion, proportion of liver cirrhosis between the patients with cryoglobulinaemia and those without cryoglobulinaemia. The frequencies of RF and ANA were 14% and 3.4% respectively in HCV patients with cryoglobulinaemia. There was no difference in HCV genotype between the patients with cryoglobulinaemia and those without cryoglobulinaemia. Clinical features of HCV patients were as follows: arthralgia/arthritis (35%), cutaneous manifestation (37%), Raynaud's phenomenon (8%), paresthesia (44%), dry eyes (22%), dry mouth (10%), oral ulcer (33%), and abdominal pain (14%). However, these rheumatological symptoms did not differ between the two groups. CONCLUSION: Although the rheumatological symptoms were not different between HCV patients with and without cryoglobulinaemia, HCV patients showed various rheumatological manifestations. These result suggests that HCV infection could be included as one of the causes in patients with unexplained rheumatological symptoms. (+info)
Fetal tachycardias: management and outcome of 127 consecutive cases.
OBJECTIVE: To review the management and outcome of fetal tachycardia, and to determine the problems encountered with various treatment protocols. STUDY DESIGN: Retrospective analysis. SUBJECTS: 127 consecutive fetuses with a tachycardia presenting between 1980 and 1996 to a single tertiary centre for fetal cardiology. The median gestational age at presentation was 32 weeks (range 18 to 42). RESULTS: 105 fetuses had a supraventricular tachycardia and 22 had atrial flutter. Overall, 52 fetuses were hydropic and 75 non-hydropic. Prenatal control of the tachycardia was achieved in 83% of treated non-hydropic fetuses compared with 66% of the treated hydropic fetuses. Digoxin monotherapy converted most (62%) of the treated non-hydropic fetuses, and 96% survived through the neonatal period. First line drug treatment for hydropic fetuses was more diverse, including digoxin (n = 5), digoxin plus verapamil (n = 14), and flecainide (n = 27). The response rates to these drugs were 20%, 57%, and 59%, respectively, confirming that digoxin monotherapy is a poor choice for the hydropic fetus. Response to flecainide was faster than to the other drugs. Direct fetal treatment was used in four fetuses, of whom two survived. Overall, 73% (n = 38) of the hydropic fetuses survived. Postnatally, 4% of the non-hydropic group had ECG evidence of pre-excitation, compared with 16% of the hydropic group; 57% of non-hydropic fetuses were treated with long term anti-arrhythmics compared with 79% of hydropic fetuses. CONCLUSIONS: Non-hydropic fetuses with tachycardias have a very good prognosis with transplacental treatment. Most arrhythmias associated with fetal hydrops can be controlled with transplacental treatment, but the mortality in this group is 27%. At present, there is no ideal treatment protocol for these fetuses and a large prospective multicentre trial is required to optimise treatment of both hydropic and non-hydropic fetuses. (+info)