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Biomedical subjects

M Press

Publications and source records attributed to M Press.

61 records · Page 4Linked to original sources

Treating dyslipidaemia in non-insulin-dependent diabetes mellitus -- a special reference to statins.

Patients with non-insulin-dependent diabetes (NIDDM) have an increased incidence of ischaemic heart disease (IHD) when compared with nondiabetic subjects. In addition, they have a worse prognosis after their first myocardial infarction (MI). According to the recent USA recommendations, the threshold for initiation of dietary intervention in diabetic subjects is an LDL greater than 2.6 mmol/l, with the goal to achieve levels less than 2.6 mmol/l (100 mg/dl). This is also the threshold for initiation and treatment goal for pharmacological intervention in diabetic subjects, unless they are completely free of IHD, peripheral vascular disease or cerebrovascular disease and have no other IHD risk factors. In the latter circumstances, the threshold for treatment is an LDL greater than 3.38 mmol/l (130 mg/dl), with the goal to achieve levels less than 3.38 mmol/l. The HMG-CoA reductase inhibitors (statins) can improve the lipid profile effectively and safely in NIDDM. Results from post hoc analyses of diabetic subgroups in the large intervention trials suggest that some statins significantly reduce the risk for IHD-related mortality/morbidity. However, because these results are derived from secondary prevention trials, we cannot be sure if these benefits apply to all diabetic subjects or only to those who already have IHD. Nevertheless, it seems logical to assume that this benefit also applies to NIDDM patients who do not have IHD because they share a similar vascular risk as nondiabetic subjects who have IHD. Intervention trials using statins and fibrates, alone or in combination, in NIDDM are under way. In a few years these trials will provide definitive end-point-based evidence in this high-risk group of patients.

Bezafibrate↗

The effects of transdermal estradiol alone or with cyclical dydrogesterone on markers of cardiovascular disease risk in postmenopausal women with type 2 diabetes: a pilot study.

The objective of this open, longitudinal, controlled study was to assess the effect of transdermal estradiol alone or combined with cyclical dydrogesterone on the markers of cardiovascular disease (CVD) risk in postmenopausal women with type 2 diabetes. The control group consisted of postmenopausal diabetic women who declined menopausal hormone replacement therapy (HRT). Twenty-eight postmenopausal women (19 on HRT and 9 controls) with type 2 diabetes were followed up for 12 months. From the active treatment group 14 women with a uterus in situ had 80 microg/24 hr transdermal estradiol (Fematrix 80; Solvay Healthcare Ltd, Southampton, UK) and oral dydrogesterone 10 mg daily for the first 12 days of the calendar month, whereas 5 women with previous hysterectomy had 80 microg/24 hr transdermal estradiol (Fematrix 80) alone. CVD risk markers were measured before and at regular intervals after starting HRT. The main outcome measures were weight, systolic and diastolic blood pressure, fasting plasma glucose, glycated hemoglobin (HbA1c), glucose/insulin ratio, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, lipoprotein (a), high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and endothelin-1. Transdermal estradiol with or without dydrogesterone in women with type 2 diabetes did not adversely affect any of the measured markers of cardiovascular risk. There was a significant decrease in HbA1c, total cholesterol, and LDL cholesterol at 6 months in women receiving HRT. Some of the cardiovascular disease risk markers may improve in postmenopausal women with type 2 diabetes with transdermal estradiol. This effect may have important clinical implications and it deserves further investigation in appropriately designed trials.

Administration, Cutaneous↗

Standard sperm morphology as a predictor of male fertility potential.

There are many clinicians who believe that standard sperm morphological criteria as determined by the World Health Organization (WHO) may be one of the most reliable indices of male fertility potential. Many previous studies of sperm morphology have lacked meticulous correction of all female infertility factors in forming their conclusions. Other studies may have compared morphological analysis to either the zona-free hamster oocyte penetration test or fertilization rates with in vitro fertilization/embryo transfer (IVF-ET). The former may not be a valid "gold standard" with which to compare, and the latter might not truly reflect the in vivo situation in view of the markedly different type of sperm-oocyte interaction. These data failed to find a strong correlation of abnormal sperm morphology (as determined by WHO criteria) to identify the subnormal male. When motile densities were normal (greater than 10 x 10(6)/ml), 87% of the female partners of men with normal morphology achieved pregnancies within 6 months compared to 82% with subnormal morphology. Even subnormal motile densities and morphology did not predict the subfertile male. These data strongly suggest that the normals established by WHO for morphology are inadequate to distinguish normal from subnormal. Perhaps increasing the percentage of abnormal sperm morphology to be considered subfertile might prove more useful, or perhaps using another type of morphological assessment might be more effective.

Female↗

Effect of shortened exposure time to the critical period for ice crystal formation on subsequent post-thaw semen parameters from cryopreserved sperm.

Cryopreservation of human sperm using present methods leads to a reduced fertility potential of the specimen. In many instances this prevents the successful fertilization of the female partner from the frozen-thawed specimens of males whose semen has been cryopreserved prior to surgery, chemo-therapy, or even vasectomy. Furthermore, even though some donor specimens can be successfully used for achieving pregnancies, one needs to place the sperm intrauterine to approach the same pregnancy rates as those of fresh intracervical insemination. The main mechanism considered for sperm damage by cryopreservation is ice crystal formation. The most critical time for forming ice crystals is from 0 to -10 degrees C. In the present study the effect of a modified rapid cryopreservation technique with reduction of exposure time to the 0 to -10 degrees C temperature range was compared to standard freezing procedures on subsequent semen parameters. Though no significant differences were found on post-thaw motile densities or hypoosmotic swelling test scores, a new, equally effective, but more rapid technique for cryopreservation is reported.

Cryopreservation↗

Male:female sex ratio in births resulting from IVF according to swim-up versus Percoll preparation of inseminated sperm.

Two centers have independently reported a higher rate of male to female births following insemination of sperm prepared by a modified swim-up technique. The principle of the modified swim-up is that a small percentage of the x-bearing sperm are the fastest and travel to the top of the supernatant, followed by the y-bearing sperm; the bulk of the x-bearing sperm remain in the pellet. In this technique, the very top layer is discarded and the resulting supernatant is collected, leaving only the pellet. In contrast, with the conventional swim-up technique, the entire supernatant is collected. The study presented herein retrospectively evaluated the male to female sex ratio of births from in vitro fertilization using standard swim-up technique and compared these results to the ratio obtained from separating with Percoll. There were 53% male births with swim-up vs. 54% with Percoll in singleton pregnancies and 51% males with swim-up vs. 40% with Percoll with multiple births. Thus, conventional swim-up alone does not increase percentage of male births.

Cell Separation↗

Surviving native beta-cells determine outcome of syngeneic intraportal islet transplantation.

In moderately diabetic rats (plasma glucose 20-30 mmol/L), where there is some residual pancreatic islet function, normoglycemia can be restored by transplantation of pancreatic islets into the liver via the portal vein. To examine whether normoglycemia can also be achieved in more severely diabetic animals (which more closely resemble human type I diabetes), we have compared the effect of transplanting 1000 islets intraportally in Lewis rats made moderately diabetic (55 mg/kg streptozotocin injected IP while nonfasting) or severely diabetic (65 mg/kg streptozotocin injected IP while fasting). In the moderately diabetic rats in which residual pancreatic insulin was 128 +/- 40 mU insulin (2.0% of control), plasma glucose stabilized (32 +/- 2.8 mmol/L at 1 week, 34 +/- 2 mmol/L at 3 weeks) as did body weight (falling from 290 +/- 5 to 265 +/- 5 g at 1 week and 253 +/- 6 g at 3 weeks). In contrast, in severely diabetic rats in which residual pancreatic insulin was only 13.5 +/- 4.2 mU insulin (0.21% of control), there was a progressive rise in plasma glucose (30 +/- 1.3 mmol/L at 1 week, 49 +/- 4 mmol/L at 2 weeks, and 67 +/- 7 mmol/L at 3 weeks) and a progressive fall in body weight (from 304 +/- 10 to 260 +/- 5 g by week 1 and to 209 +/- 6 g by week 3). Following islet transplantation, nonfasting plasma glucose normalized in moderately diabetic rats (10.5 +/- 0.6 vs. 9.1 +/- 0.6 mmol/L in nondiabetic controls, NS) after 23 +/- 5 days. In contrast, in the severely diabetic rats plasma glucose stabilized at 32 +/- 5 mmol/L (p < 0.05 compared to moderately diabetic group) but did not normalize. This difference was not attributable to different plasma glucose levels at the time of transplantation (35.1 +/- 1.8 in moderately diabetic vs. 32.5 +/- 2.5 mmol/L in severely diabetic rats). These observations demonstrate that residual native beta-cells (equivalent to only 60-80 islets) contribute to the survival or function of intraportally transplanted islets.

Animals↗

An in vivo technique for screening immunologic factors in the etiology of the unexplained poor postcoital test.

A study was designed to determine the incidence and etiology of the unexplained poor postcoital test. An in vivo comparison of sperm penetration by husband's versus donor sperm in the wife's estrogen-stimulated mucus was performed. The 8 of 30 women showing improvement of husband's penetration in mucus (group 1) were treated with high-dose estrogen (HDE) and hMG, and 4/8 conceived. Anti-sperm antibodies (ASA) were insignificant in this group. In group 2, in which donor sperm penetrated but husband's sperm did not, 8 men of 17 were found to have an ASA level over 50% on the sperm surface; 6/8 treated with high-dose methylprednisolone (MP) had an improved postcoital test, and 5 achieved a pregnancy. Two patients with levels under 50% were still treated with MP, and one achieved a pregnancy. In five group-3 couples, positive ASA were found in the cervical mucus of two women; and one woman improved on the postcoital test and conceived following MP therapy. The 30 unexplained poor postcoital tests occurred in 5,000 couples evaluated. In general, those patients considered to have significant clinical antibody had levels over 50%. Because side effects of MP may be severe, and positive ASA may be found in normal donors, it is important to use a comparison penetration test to help determine if treatment with corticosteroids seems reasonable.

Cervix Mucus↗