Normosmic idiopathic hypogonadotrophic hypogonadism due to a rare KISS1R gene mutation.

Hypogonadotrophic hypogonadism is due to impaired or reduced gonadotrophin secretion from the pituitary gland. In the absence of any anatomical or functional lesions of the pituitary or hypothalamic gland, the hypogonadotrophic hypogonadism is referred to as idiopathic hypogonadotrophic hypogonadism (IHH). We present a case of a young lady born to consanguineous parents who was found to have IHH due to a rare gene mutation. Learning points: The genetic basis of a majority of cases of IHH remains unknown.IHH can have different clinical endocrine manifestations.Patients can present late to the healthcare service because of unawareness and stigmata associated with the clinical features.Family members of affected individuals can be affected to varying degrees.

The use of Fourier-transform infrared spectroscopy for the quantitative determination of glucose concentration in whole blood.

Fourier-transform infrared transmission spectroscopy has been used for the determination of glucose concentration in whole blood samples from 28 patients. A 4-vector partial least-squares calibration model, using the spectral range 950-1200 cm(-1), yielded a standard-error-of-prediction of 0.59 mM for an independent test set. For blood samples from a single patient, we found that the glucose concentration was proportional to the difference between the values of the second derivative spectrum at 1082 cm(-1) and 1093 cm(-1). This indicates that spectroscopy at these two specific wavenumbers alone could be used to determine the glucose concentration in blood plasma samples from a single patient, with a prediction error of 0.95 mM.

Determination of Glucose Concentration in Whole Blood using Fourier-Transform Infrared Spectroscopy.

Fourier-transform infrared(FTIR) transmission spectroscopy has beenused for the determination of glucoseconcentrations in whole blood samples fromtwenty-eight patients. A four-vectorpartial least squares calibration model,using the spectral range 950-1200 cm(-1),yielded a standard error of prediction of0.59 mM for an independent test set. Forblood samples from a single patient, wefound that the glucose concentration wasproportional to the difference between thevalues of the second derivative spectrum at1082 cm(-1) and 1093 cm(-1), suggestingthat these two specific wavelengths can beused for determining glucose concentrationsin blood.

Metachromatic leucodystrophy: a newly identified mutation in arylsulphatase A, D281Y, found as a compound heterozygote with I179L in an adult onset case.

The majority of mutations identified in patients with Metachromatic leucodystrophy are unique to individual families. We report here a new mutation in the arylsulphatase A gene (D281Y) identified in a patient with late-onset Metachromatic leucodystrophy. This mutation was inherited in cis with the common pseudo-deficiency allele and in trans with the previously described I179S (250100.0008) mutation which complicated the enzymatic diagnosis of this condition. Sequence comparison shows D281 to be highly conserved amongst the arylsulphatases. The clinical features of this patient which are predominantly of a slowly progressive psychiatric and intellectual deterioration rather than rapid neurological impairment are typical of I179S compound heterozygotes.

Incidence, character and clinical relevance of mixed cryoglobulinaemia in patients with chronic hepatitis C virus infection.

Hepatitis C virus (HCV) infection has been implicated in the pathogenesis of mixed cryoglobulinaemia. Several studies have shown the presence of anti-HCV antibodies and HCV-RNA in both sera and cryoglobulins of such patients. However, the prevalence and clinical significance of cryoglobulins remain uncertain in patients with chronic HCV infection. We have studied 113 consecutive patients referred for assessment because of the presence of anti-HCV antibody in serum for the presence of cryoglobulinaemia and ascertained their clinical relevance and immunochemical properties. Twenty-one of 113 (19%) had detectable cryoglobulins with a mean protein concentration of 0.38 g/l (range 0.15-3.34 g/l). Most of these patients were asymptomatic. The cryoglobulins were of type III in 19 (91%) and of type II in two patients (9%). The latter two patients had the highest concentration of cryoglobulins, subnormal C4 and C1q levels suggesting classical pathway activation and vasculitis with renal impairment. The cryoglobulin IgG subclasses were mainly IgG1 and IgG3. HCV-RNA was detected more frequently in the sera of cryoglobulin-positive patients than in cryoglobulin-negative patients. This study showed that mixed cryoglobulinaemia is common in chronic HCV infection, and is predominantly type III. Evidence of systemic or renal disease was rare except in those with type II cryoglobulinaemia, and this may reflect either the concentration of the cryoprecipitate or the presence of a monoclonal complement-activating IgM paraprotein. The detection of HCV-RNA in the majority of the cryoprecipitates further supports the important role of HCV in the etiopathogenesis of essential mixed cryoglobulinaemia, although the mechanism is at present unclear.

A novel capillary collection method for obtaining current glycosylated haemoglobin levels in diabetic children.

A simple method for collecting capillary blood for measurement of glycosylated haemoglobin (HbA1c) was developed that allows samples to be obtained at home and then mailed to the laboratory 2 weeks before a hospital visit. A single drop of blood is collected into a 2 ml plastic tube and sent for HbA1c assay on the Diamat HPLC system which has inter- and intra-assay coefficients of variation < 2.6 and < 1.2%, respectively. Results of simultaneously obtained venous and capillary samples in 32 diabetic children agreed well with each other. A separate study of 25 patients was performed to determine whether transport conditions affected the samples. Posted samples were compared with venous samples; again the values were in good agreement. This method is now used routinely in the diabetic clinic. Its value was determined by questionnaire in 40 children with age range 4-17 years. No family experienced difficulty collecting samples and all samples received were suitable for analysis. Children preferred this method to blood collection in the clinic as they felt it was less traumatic and more convenient. Seventy-nine percent of them understood its value in the long-term control of diabetes. In 40.5% of visits changes to management were made at the clinic due to the availability of the results.

The effect of antioxidants on the production of volatile nitrosamines during the frying of bacon.

In model system studies simulating the frying of bacon a considerable variation in the production of N-nitrosopyrrolidine (NOPyr) has been observed, as occurs in sliced bacon fried conventionally. The inclusion of ascorbate or erythorbate (isoacorbate) has led consistently to a fall in or an elimination of NOPyr production up to an addition of 300 ppm (1,5 mM). Above this concentration of ascorbate, the elimination of NOPyr formation persisted in some instances but in others an increased production of the nitrosamine occurred. Using alpha-tocopherol, a fall of NOPyr production during the simulated frying of bacon was obtained with increase of concentration of the antioxidant, there being a consistent elimination of the volatile nitrosamine following an additionof 500 ppm (1.16 mM). Whilst ascorbyl palmitate had a similar action in reducing or eliminating NOPyr production, no synergistic effect between it and alpha-tocopherol was noted in an experiment combining the two antioxidants. When bacon was fried in fat containing 400 or 800 ppm alpha-tocopherol, the total production of NOPyr and DMN in the fried bacon, cooked out fat and condensate was markedly reduced but not completely eliminated as in the model system studies. Similarly, the curing of bacon with a brine containing a mixture of alpha-tocopherol, ascorbyl palmitate and citric acid has led to considerable reductions in NOPyr and DMN output on frying when the combined concentrations of the two anti-oxidants were calculated to be 800 ppm.