Quantification of concordance and discordance between apolipoprotein-B and the currently recommended non-HDL-cholesterol goals for cardiovascular risk assessment in patients with diabetes and hypertriglyceridemia.

AIMS: In patients with diabetes and hypertriglyceridemia, LDL-cholesterol (LDL-C) provides an inaccurate reflection of LDL particle burden. The relative value of non-HDL-cholesterol (non-HDL-C) and apolipoprotein-B (Apo-B) in estimating cardiovascular risk is controversial. We assessed the discordance between non-HDL-C and Apo-B targets in patients with diabetes with TG 200-499 mg/dl. METHODS: Data from 1430 determinations of LDL-C, non-HDL-C, and Apo-B in ambulatory patients with diabetes were analyzed. Rates of discordance were calculated, based on the currently recommended LDL-C, non-HDL-C, and Apo-B goals. RESULTS: In patients with non-HDL-C goal of <130 mg/dl, there was a discordance with Apo-B level goal of <90 mg/dl, in 31% of samples. In patients with non-HDL-C goal of <100 mg/dl, 6% of samples had Apo-B ≥80 and 18% had Apo-B <80 mg/dl. Using the Apo-B goal of <70 mg/dl, these numbers were 37% and 3.5% respectively. There was also a significant gender difference, i.e. under-estimation of risk by suggested non-HDL-C cut-offs, in females, compared to males. CONCLUSIONS: In patients with diabetes and hypertriglyceridemia, a considerable discordance exists between non-HDL-C and Apo-B. Our data suggest a need for prospective studies to compare the relative merits of non-HDL-C and Apo-B targets in the assessment of cardiovascular risk.

Medicare coverage for patients with diabetes. A national plan with individual consequences.

The prevalence of diabetes in the U.S. Medicare population is growing at an alarming rate. From 1980 to 2004, the number of people aged 65 or older with diagnosed diabetes increased from 2.3 million to 5.8 million. According to the Centers for Medicare and Medicaid (CMS), 32% of Medicare spending is attributed to the diabetes population. Since its inception, Medicare has expanded medical coverage of monitoring devices, screening tests and visits, educational efforts, and preventive medical services for its diabetic enrollees. However, oral antidiabetic agents and insulin were excluded from reimbursement. In 2003, Congress passed the Medicare Modernization Act that includes a drug benefit to be administered either through Medicare Advantage drug plans or privately sponsored prescription drug plans for implementation in January 2006. In this article we highlight key patient and drug plan characteristics and resources that providers may focus upon to assist their patients choose a coverage plan. Using a case example, we illustrate the variable financial impact the adoption of Medicare part D may have on beneficiaries with diabetes due to their economic status. We further discuss the potential consequences the legislation will have on diabetic patients enrolled in Medicare, their providers, prescribing strategies, and the diabetes market.

Do "so-called" normal growth hormone concentrations (2-5 micrograms/l) indicate cure in acromegaly?

The study was undertaken to determine whether acromegalic patients with mean growth hormone (GH) concentrations of 2-5 micrograms/l have biochemically active disease following pituitary surgery or radiotherapy. 22 patients with acromegaly, 22 post surgery, 19 post radiotherapy had GH concentrations estimated during: (i) an oral glucose tolerance test (OGTT), (ii) a standard TRH test and (iii) 20 minute sampling for 8 hours. IGF-1 concentrations were measured. 6 normal subjects were also studied. Patients were divided into 3 groups on the basis of their mean GH concentration during the 8 hour sampling, > 5 micrograms/l, 2-5 micrograms/l, < 2 micrograms/l. Patients with mean GH concentrations of 2-5 micrograms/l (n = 6) had biochemically active disease: all had inadequate suppression of GH after OGTT, 5 had elevated IGF-1 concentrations, 4 had a paradoxical response to TRH. Patients with mean GH concentrations > 5 micrograms/l (n = 6) all had inadequate suppression after OGTT, 5 of 6 had increased IGF-1 concentrations, and 5 had abnormal responses to TRH. Of patients with mean GH concentrations < 2 micrograms/l (n = 10), 2 had elevated IGF-1 levels, 5 had abnormal responses to TRH and 4 inadequate GH suppression after OGTT. GH pulse number was similar in the three groups and GH pulse amplitude was significantly higher in those with GH > 5 micrograms/l compared to the other groups. In conclusion patients with GH concentrations of 2-5 micrograms/l have biochemically active disease and should be considered for further therapy after hypophysectomy.

Prolactin-inhibiting activity of GnRH associated peptide in cultured human pituitary cells.

The 56-amino-acid extension of GnRH in the human GnRH precursor (pHGnRH 14-69 or GAP) has previously been shown to inhibit PRL secretion from cultured rat pituitary cells. We have studied the effect of GAP and shorter sequences on prolactin secretion from human and rat pituitary cells. Bacterially synthesized GAP inhibited PRL secretion from human pituitary cells. At 10(-6) M GAP inhibition of prolactin release was 67.7% which was similar to that observed in rat pituitary cells (65.5%). A series of shorter peptide sequences (pHGnRH 14-26, pHGnRH 14-36, pHGnRH 14-37.NH2, pHGnRH 28-36, pHGnRH 38-49 and pHGnRH 51-66) which are potentially processed from GAP at basic amino acid residues had no effect on prolactin secretion from human or rat pituitary cells at doses up to 10(-5) M.

Euthyroid hyperthyroxinaemia due to endogenous antibodies to thyroxine and tri-iodothyronine. A case report.

A case of euthyroid hyperthyroxinaemia caused by auto-antibodies to thyroxine and tri-iodothyronine is presented. Gel filtration chromatography of the patient's serum showed increased binding of radio-labelled thyroxine analogue to a macromolecular component, which migrated in the gammaglobulin region on electrophoresis. Precipitation by protein A confirmed that this was an immunoglobulin. The importance of recognising this condition so that inappropriate therapy can be avoided is stressed.

Culture of functionally active human pituitary cells: investigation of gonadotropin regulation.

A method for culturing cells from human pituitaries obtained at autopsy for studies of the secretion of gonadotropins and other hormones is described. The EC50 of GnRH-stimulated LH secretion from human pituitary cells was 1.25 nmol/L, similar to that found with rat pituitary cells (2.45 nmol/L). The GnRH agonist (D-Ala6, N alpha MeLeu7, Pro9-NEt)GnRH was 10-fold more active in stimulating LH release from both human and rat pituitary cells (EC50, 0.21 and 0.35 nmol/L, respectively). The GnRH antagonists (Ac-D-Nal(2)1,D-alpha-Me-4-ClPhe2,D-3-Pal3,D-Arg6,D-Ala10 )GnRH and (D-pGlu1,D-Phe2,D-Trp3,6)GnRH both inhibited 3 nmol/L GnRH-stimulated LH release from human pituitary cells (IC50, 2.40 and 78.6 nmol/L, respectively) with potencies similar to those observed in the rat (IC50, 0.68 and 33.0 nmol/L, respectively). Stimulation of the human pituitary cells with 100 nmol/L GnRH for 44 min resulted in biphasic release of LH and FSH. The initial phase occurred during the first 4 min of stimulation, and the second protracted plateau phase continued for at least the ensuing 40 min. The kinetics of LH and FSH release were identical, with no evidence of differential release at any stage. GnRH-stimulated LH and FSH secretion was Ca2+ dependent. The presence of 3 mmol/L EGTA prevented the gonadotropin response to GnRH, and the Ca2+ ionophore A23187 stimulated release of both LH and FSH. The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate also stimulated gonadotropin secretion, indicating that activation of protein kinase-C is able to elicit LH release. GnRH desensitized the cells to subsequent stimulation with GnRH. After initial 2-h incubation with 0.1-100 nmol/L GnRH, LH release during a second 2-h incubation with the same doses was reduced by 50-100%. The reduction in FSH ranged from 63-92%. Depletion of gonadotropin pools may contribute to desensitization, since total LH and FSH cell content decreased 48% and 49%, respectively, after 100 nmol/L GnRH stimulation for 4 h. We conclude that functionally active cells can be cultured from human pituitaries obtained postmortem and that the mechanism of GnRH action and the relative potencies of GnRH analogs closely parallel those in the rat.

Neuroendocrine regulation of thyrotropin release in cultured human pituitary cells.

The regulation of TSH release in man was investigated using cell cultures derived from human pituitaries obtained within 24 h of accidental death. TRH stimulated TSH release in a dose-dependent manner. The ED50 was 2.9 +/- 0.6 (+/- SEM) nmol/L, similar to that reported for rat pituitary cell cultures. The release of TSH was calcium dependent, since the calcium channel antagonist verapamil inhibited TRH-stimulated TSH release, and the calcium ionophore A23187 stimulated TSH release. 12-O-Tetradecanoyl-phorbol-13-acetate stimulated TSH secretion, while dibuytryl cAMP had no effect. Epinephrine and serotonin stimulated TSH release, and dopamine and somatostatin inhibited TRH-stimulated TSH release. These findings have directly demonstrated that the regulation of TSH secretion by hypothalamic neuropeptides and biogenic amines in the human pituitary is similar to that in the rat. The development of a tissue culture system to study thyrotrophs from postmortem human pituitaries provides the means for detailed studies of the regulation of TSH secretion in man.

The effect of an intensive education programme on the glycaemic control of type I diabetic patients.

The effect of patient education on glycaemic control in insulin-dependent diabetes mellitus was assessed in 20 patients selected from the Diabetes Clinic, Groote Schuur Hospital. Education in all aspects of self-care was given to small groups of between 5 and 7 patients. Biochemical tests including measurement of fasting blood glucose (FBG) and glycosylated haemoglobin (HbA1c), were performed during a 6-week 'control' period before the educational course, and again during a 6-week 'test' period after it. The mean HbA1c fell from 10.05 +/- 0.43% at the end of the control period to 8.47 +/- 0.25% at the end of the test period (P less than 0.001). FBG levels dropped from 13.53 +/- 0.84 mmol/l at the commencement of the study to 10.83 +/- 1.29 mmol/l before the educational course, and to 9.41 +/- 0.72 mmol/l at the completion of the study. We therefore conclude that intensive education of this nature is of benefit in improving glycaemic control, at least in the short term.

Fatal hyperparathyroid crisis.

A case of hyperparathyroid crisis presenting with a serum calcium level of 7.6 mmol/l is presented. The rarity and importance of recognizing the condition early is emphasized.

Regulation of thyrotrophin secretion.

Substantial advances in understanding the regulation of thyrotrophin (TSH) secretion have been made during the past decade. The hypothalamic tripeptide, thyrotrophin-releasing hormone, is the major stimulator of TSH secretion, and thyroid hormones exert the major inhibitory influences on TSH secretion. Other hypothalamic peptides, biogenic amines and steroid hormones modulate TSH secretion. Basal serum TSH measurement is mainly of value in diagnosing primary hypothyroidism, but because the lower limit of the normal range of TSH is not clearly defined, dynamic measurements of TSH secretion are used in preference to basal measurements in assessing other disorders of the hypothalamopituitary-thyroid axis.

Cushing's syndrome in pregnancy. A case report.

A case of Cushing's syndrome caused by a right adrenal adenoma in a 16-week gravid patient is reported. After right adrenalectomy she was maintained on replacement doses of hydrocortisone, and at 38 weeks' gestation a healthy but small-for-gestational age infant was delivered vaginally.

Live abdominal pregnancy presenting as massive rectal bleeding.

A case of massive rectal bleeding resulting from the placental attachment of an abdominal pregnancy to the sigmoid colon is reported. Both mother and infant survived this rare complication which should be considered when abdominal colic and major gastrointestinal haemorrhage occur in a pregnant patient.