Phenotype, genotype and glycaemic variability in people with activating mutations in the ABCC8 gene: response to appropriate therapy.

AIMS: To examine the phenotypic features of people identified with ABCC8-maturity-onset diabetes of the young (MODY) who were included in the adult 'Mater MODY' cohort and to establish their response to sulfonylurea therapy. METHODS: Ten participants with activating ABCC8 mutations were phenotyped in detail. A 2-hour oral glucose tolerance test was performed to establish glycaemic tolerance, with glucose, insulin and C-peptide measurements taken at baseline and 30-min intervals. Insulin was discontinued and sulfonylurea therapy initiated after genetic diagnosis of ABCC8-MODY. A blinded continuous glucose monitoring sensor was used to establish glycaemic control on insulin vs a sulfonylurea. RESULTS: The mean age at diagnosis of diabetes was 33.8 ± 11.1 years, with fasting glucose of 18.9 ± 11.5 mmol/l and a mean (range) HbA1c of 86 (51,126) mmol/mol [10.0 (6.8,13.7)%]. Following a genetic diagnosis of ABCC8-MODY three out of four participants discontinued insulin (mean duration 10.6 ± 1.69 years) and started sulfonylurea treatment. The mean (range) HbA1c prior to genetic diagnosis was 52 (43,74) mmol/mol (6.9%) and the post-treatment change was 44 (30,57) mmol/mol (6.2%; P=0.16). Retinopathy was the most common microvascular complication in this cohort, occurring in five out of 10 participants. CONCLUSIONS: Low-dose sulfonylurea therapy resulted in stable glycaemic control and the elimination of hypoglycaemic episodes attributable to insulin therapy. The use of appropriate therapy at the early stages of diabetes may decrease the incidence of complications and reduce the risks of hypoglycaemia associated with insulin therapy.

An audit of waiting times at a district general hospital sexual health department--how far are we from the 48 hours target?

The Government has stated that by 2008, anyone who wants an appointment at a genitourinary medicine clinic should be able to get one within 48 hours. We have performed an audit of waiting times for appointments in our clinic and compared this to the most recent Health Protection Agency (HPA) audit. Our audit showed that 75% of people were offered an appointment within 48 hours, but only 62% accepted - the rest wanted to be seen later. In contrast, the HPA audit suggests that only 63% of patients were offered an appointment within 48 hours, and 59% were seen within this time frame. Our audit highlights the fact that many people do not want to be seen within 48 hours and call in to question the validity of this as a target for all patients.

Acceptability and compliance with daily injections of procaine penicillin in the outpatient treatment of syphilis-treponemal infection.

BACKGROUND: In the United Kingdom, it is recommended that syphilis should be treated with intramuscular daily procaine penicillin with or without oral probenecid for 8 to 21 days. However, it has been argued that this regimen would be unacceptable to patients in terms of daily attendance and volume of drug administered, resulting in poor compliance. GOAL: To assess the acceptability of and compliance with daily procaine penicillin for 10 to 17 days in patients attending an East London Genito-Urinary Medicine Clinic with a diagnosis of syphilis-treponemal infection. STUDY DESIGN: The notes of 210 consecutive patients attending with syphilis-treponemal infection who had been offered treatment with daily procaine penicillin, with or without oral probenecid for 10 to 17 days, were reviewed retrospectively. RESULTS: Of 210 patients who were offered daily procaine penicillin, 42 (20%) declined and were given oral doxycycline, amoxicillin, or depot penicillin injections. Of 168 patients who accepted daily procaine penicillin, depending on the stage of infection, 90 (54%) had 1.8 g of daily procaine penicillin together with oral probenecid 500 mg every 6 hours for 17 days (high-dose regimen), 57 (34%) had 0.6 g of daily procaine penicillin for 10 to 17 days (low-dose regimen), and 21 (12%) had mixed-dose regimens ranging from 0.5 to 2.4 g. Of the 90 who had high-dose regimen, 76 (84%) complied with treatment compared with 50 (88%) of 57 who had low-dose regimen. All 21 patients who had mixed-dose regimens complied fully. CONCLUSIONS: Daily procaine penicillin is a well-accepted out-patient regimen with excellent compliance (88% overall) and minimal side effects. Because the high-dose regimen has been shown to achieve treponemicidal levels of penicillin in the cerebrospinal fluid, it is recommended for patients with neurosyphilis or those in whom neurosyphilis cannot be excluded. It also could be considered for patients with concomitant human immunodeficiency virus infection in view of the possible progression to neurosyphilis in those treated with depot penicillin.

Incidence of microvascular complications in type 1 diabetic subjects with limited joint mobility: a 10-year prospective study.

Previous cross-sectional studies have shown a significant correlation between limited joint mobility (LJM) and the microvascular complications of Type 1 diabetes, but whether LJM precedes and, therefore, may be regarded as an early marker for complications is unknown. Twenty-two Type 1 diabetic patients (10 male/12 female; diabetes duration at follow-up 20.1 +/- 1.3 (SEM) years) with LJM, and 22 subjects matched for age, sex, and duration of diabetes, without LJM were observed over a 10-year period. Both groups were free of retinopathy and negative for 'dipstick' proteinuria at baseline. After 10 years, of 22 patients with LJM, 10 had developed background and 3 proliferative retinopathy compared with 9 and 1 control subjects, respectively. Microalbuminuria (20 < or = albumin excretion rate < 200 micrograms min-1) was present in 3 and macroalbuminuria (albumin excretion rate > or = 200 micrograms min-1) in 2 of LJM patients compared with 6 and 1 control subjects, respectively. Ankle and toe vibration perception thresholds, HbA1, mean HbA1 (a mean of serial HbA1 measurements obtained during the 10-year follow-up period), and arterial blood pressure did not differ between the two groups (p > 0.05). At 10-year review, 9 of the control subjects had developed LJM of whom 4 had retinopathy and 4 microalbuminuria. Thus, while LJM may be another 'chronic complication' of diabetes, its presence does not appear to predict those at increased risk of developing microvascular complications.

The gene responsible for familial hypocalciuric hypercalcemia maps to chromosome 3q in four unrelated families.

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant syndrome of unknown aetiology characterized by lifelong elevation in serum calcium concentration and low urinary calcium excretion. These features suggest that the causal gene is important for maintenance of extracellular calcium homeostasis by the parathyroid gland and kidney. To identify the chromosomal location of FHH gene(s), we clinically evaluated 114 individuals in four unrelated affected families and performed linkage analyses. The disease gene mapped to the long arm of chromosome 3 in each family (combined maximum multipoint lod score = 20.67). We suggest that this is the predominant FHH locus and anticipate that identification of the FHH gene will improve our understanding of the molecular basis for physiologic and pathologic regulation of calcium.

Severe hypercalcaemia four months after acute oliguric renal failure--successful treatment with intravenous clodronate.

A 33 year old man developed acute oliguric failure lasting 66 days, eight days after admission with multiple gun shot wounds. On day 99 after admission, serum calcium was elevated mildly at 2.54 mmol/l (normal range 2.1-2.5 mmol/l). Serum parathormone was undetectable. He was discharged soon afterwards. He presented again on day 164 with nausea, vomiting and blurred vision. Fundoscopy revealed an ischaemic retinopathy and extensive keratopathy. Serum calcium was 3.48 mmol/l and serum creatinine 262 umol/l (normal range 40-110 umol/l). Repeat parathormone was undetectable and there was no evidence of myeloma, sarcoidosis or malignancy. Following treatment with intravenous saline and frusemide, serum calcium fell to a nadir of 3.05 mmol/l. On day 168 an infusion of sodium clodronate 300 mg was given. Twenty-four hours later serum calcium was 2.65 mmol/l and 48 hours later calcium was 2.26 mmol/l. Normocalcaemia was maintained for 17 days and severe hypercalcaemia never recurred. This is the first report in which biphosphonates have been successfully used to treat hypercalcaemia following acute renal failure thus obviating the need for further dialysis.

Distribution of Oriental and German cockroaches, Blatta orientalis and Blattella germanica (Dictyoptera), in the United Kingdom.

Results are presented of a survey carried out by Rentokil Ltd on the distribution of the Oriental cockroach Blatta orientalis L. and the German cockroach Blattella germanica L. in the United Kingdom. The known ranges of both species are increased considerably by the findings of the survey, with several new vice-county records for Scotland (including the Western Isles), England and Wales. The frequency at which Blatta orientalis was observed in outdoor habitats may indicate that this species sometimes spreads to new areas without human assistance.

Envenomation by the inland taipan, Oxyuranus microlepidotus.

A case of envenomation by a three-week-old inland taipan (Oxyuranus microlepidotus)-the second recorded case of a bite by possibly the most venomous snake in the world - is reported. Evidence which supports the use of the term "inland taipan", and confirms the effectiveness of taipan antivenom in the treatment of bites by this snake, is presented.