Mutations in the glucokinase gene of the fetus result in reduced birth weight.

Low birth weight and fetal thinness have been associated with non-insulin dependent diabetes mellitus (NIDDM) and insulin resistance in childhood and adulthood. It has been proposed that this association results from fetal programming in response to the intrauterine environment. An alternative explanation is that the same genetic influences alter both intrauterine growth and adult glucose tolerance. Fetal insulin secretion in response to maternal glycaemia plays a key role in fetal growth, and adult insulin secretion is a primary determinant of glucose tolerance. We hypothesized that a defect in the sensing of glucose by the pancreas, caused by a heterozygous mutation in the glucokinase gene, could reduce fetal growth and birth weight in addition to causing hyperglycaemia after birth. In 58 offspring, where one parent has a glucokinase mutation, the inheritance of a glucokinase mutation by the fetus resulted in a mean reduction of birth weight of 533 g (P=0.002). In 19 of 21 sibpairs discordant for the presence of a glucokinase mutation, the child with the mutation had a lower birth weight, with a mean difference of 521 g (P=0.0002). Maternal hyperglycaemia due to a glucokinase mutation resulted in a mean increase in birth weight of 601 g (P=0.001). The effects of maternal and fetal glucokinase mutations on birth weight were additive. We propose that these changes in birth weight reflect changes in fetal insulin secretion which are influenced directly by the fetal genotype and indirectly, through maternal hyperglycaemia, by the maternal genotype. This observation suggests that variation in fetal growth could be used in the assessment of the role of genes which modify either insulin secretion or insulin action.

Coexistent trigeminal neuralgia, hemifacial spasm, and hypertension: preoperative imaging of neurovascular compression. Case report.

The case is reported of a 60-year-old woman with left-sided trigeminal neuralgia, hemifacial spasm, and hypertension. Compression of the left trigeminal, facial, and vagus nerves by the anterior and posterior inferior cerebellar arteries and a persistent trigeminal artery variant were demonstrated by magnetic resonance angiography using a novel sequence. At operation the angiographic appearances were confirmed, and decompression was performed with the placement of polyvinyl sponge at all three levels. Postoperatively, the patient had complete relief from the trigeminal neuralgia and hemifacial spasm and has sustained normotension without medication.

Embryonic abnormalities at medical termination of pregnancy with mifepristone and misoprostol during first trimester: observational study.

PIP: The availability of new medical techniques for induced abortion in the first trimester enables observation of the incidence and nature of embryonic and fetal abnormalities in early pregnancy. 506 women, presenting to the Liverpool (England) Women's Hospital in 1994-96 for induced abortion before 9 weeks of gestation, were given oral mifepristone followed by oral misoprostol. Fetal tissue was collected from 206 (44%) of these women. Embryos that appeared structurally abnormal on macroscopic evaluation were examined histologically. There were 39 abnormal embryos, including 10 cases of neural tube defect and 6 abdominal wall defects, and a total of 72 potentially nonviable pregnancies. The potential loss rate for embryos with structural abnormalities or other nonviable conditions was 34%--higher than the widely cited 15% rate of spontaneous abortion for clinical pregnancies. The former figure is likely to reflect the true loss rate in early pregnancy.^ieng

When should patients with bacterial meningitis be referred to a neurosurgical unit?

The case records of 97 patients with proven bacterial meningitis who were referred to a regional neurosurgical unit between 1964 and 1991 were reviewed. Mortality declined from 34% in the first cohort referred between the years 1964-82 to 5% for 1983-91 (X2 = 11.78; p < 0.001). Fewer patients were admitted in coma, (X2 = 4.43; p < 0.05), or with focal neurological signs (X2 = 7.57; p < 0.01) in the second cohort. The rate of referral increased in the later period but the incidence of unsuspected brain abscess (16% and 15%) did not change. There was a strong correlation between coma on admission and death, (X2 = 17.3; p < 0.001) and with brain abscess and death (X2 = 6.73; p < 0.01). In conclusion patients with known or suspected bacterial meningitis coupled with a decreasing level of consciousness or focal neurological signs should be referred to a neurosurgical centre.

Thoracic spinal stenosis in two brothers due to vitamin D-resistant rickets.

X-linked hypophosphataemic vitamin D-resistant rickets is a rare cause of spinal canal stenosis. Two brothers with this condition presented in adulthood with thoracic myelopathy due to spinal canal stenosis. Both were treated by laminectomy using diamond-tipped burrs, with symptomatic improvement.

A high prevalence of glucokinase mutations in gestational diabetic subjects selected by clinical criteria.

AIMS/HYPOTHESIS: Patients with glucokinase mutations are characterised by mild, persistent fasting hyperglycaemia, a small increment in glucose in response to an oral load and a dominant family history. These patients frequently present with gestational diabetes and often require insulin treatment during pregnancy. We assessed whether the selection of gestational diabetic subjects by clinical criteria would result in a high detection rate of glucokinase mutations. METHODS: Caucasian gestational diabetic subjects from the United Kingdom who had fasting hyperglycaemia in pregnancy but did not meet the diagnostic criteria for maturity-onset diabetes of the young (MODY) were selected for direct sequencing of the glucokinase gene if they fulfilled the following four criteria; (1) persisting fasting hyperglycaemia outside pregnancy (5.5-8 mmol/l) (2) a small increment (< 4.6 mmol/l) during a 2-h oral glucose tolerance test (3) insulin treatment during at least one pregnancy but subsequently controlled on diet and (4) a history of Type II (non-insulin-dependent) diabetes mellitus, gestational diabetes or fasting hyperglycaemia (> 5.5 mmol/l) in a first-degree relative. RESULTS: Of the 15 subjects 12 (80%) with all these clinical criteria had glucokinase gene mutations. These included four previously unreported mutations (N180K, R191W, Y215X and L288-1G --> A). CONCLUSION/INTERPRETATION: Phenotypic selection of subjects with gestational diabetes greatly increases the likelihood of detecting a mutation in the glucokinase gene as previous studies have suggested a prevalence of 2.5% (range 0-6%). Our study in gestational diabetes to successfully used clinical criteria to assist in the definition of a genetic subgroup.

Vascular contact with the fifth cranial nerve at the pons in patients with trigeminal neuralgia: detection with 3D FISP imaging.

OBJECTIVE: Vascular contact with the trigeminal nerve at the pons is known to cause trigeminal neuralgia; however, this finding also is present in some asymptomatic subjects. We evaluated the usefulness of high-resolution MR imaging and MR angiography of the posterior fossa to determine the presence or absence of vascular contact with the fifth cranial nerve at the pons in patients with trigeminal neuralgia and in control subjects. SUBJECTS AND METHODS: The trigeminal nerves in 40 symptomatic patients and 114 asymptomatic control subjects were examined for the presence or absence of vascular contact at the pons by using three dimension (3D) fast inflow with steady-state precession (FISP) imaging. Imaging parameters were 35/7/15 degrees (TR/TE/flip angle) with a slab thickness of 55 mm and 64 partitions. Contrast-enhanced imaging was done in 10 of 12 patients with normal findings on an unenhanced scan. Axial, coronal, sagittal, and maximum-intensity-projection images were reviewed by two observers who had no knowledge of the clinical details. The findings on MR images were prospectively compared with the surgical findings in 25 patients. RESULTS: On the unenhanced MR images, vascular contact with the trigeminal nerve at the pons was identified in 70% of 40 nerves in patients with trigeminal neuralgia and in a further 15% following injection of contrast medium. Contact between the nerve and two vessels at the pons was seen in 10% of cases, and deformity of the nerve was present in 30% of cases. In the control group, vascular contact with the nerve was identified in 8% of 114 nerves. Contact between the nerve and two vessels or deformity of the nerve was not identified in any control subject. The difference between the two groups was highly significant regarding the presence or absence of vascular contact with the nerve at the pons (p < 0.001, x2 test), distortion of the nerve (p < .001), and contact between the nerve and two vessels (p < .001). The imaging findings were in agreement with the surgical findings regarding the presence or absence of vascular contact with the nerve in all 25 patients who had surgery. Complete or partial pain relief was achieved following microvascular decompression in all patients who had surgery. CONCLUSION: Despite the fact that vascular contact with the trigeminal nerve at the pons is not specific for trigeminal neuralgia, high-definition unenhanced and enhanced 3D FISP imaging and MR angiography at the posterior fossa are useful in determining the presence or absence of vascular contact with or deformity of, the fifth cranial nerve in patients for whom surgery is planned for treatment of trigeminal neuralgia.