We screened for PDHA1 mutations in 40 patients with biochemically demonstrated PDHc deficiency or strong clinical suspicion, and found changes with probable pathological significance in 20. Five patients presented new mutations: p.A169V, c.932_938del, c.1143_1144 ins24, c.1146_1159dup and c.510-30G> A, this latter is a new undescribed cause of exon 6 skipping. Another four mutations have been found, and previously reported, in our patients: p.H113D, p.P172L, p.Y243del and p.Y369Q. Eleven patients presented seven known mutations: p.R127Q, p.I166I, p.A198T, p.R263G, p.R302C, p.R378C and c.1142_1145dup. The latter three were found in more than one unrelated patient: p.R302C was detected in a heterozygous girl and a mosaic male, p.R378C in two males and finally, c.1142_1145dup in three females; only one in 20 mothers was found to be a carrier (p.R263G). Apart from those 20 patients, the only alteration detected in one girl with clear PDHc and PDH-E1 deficiency was the silent change c.396A> C (p.R132R), and other eight PDHc deficient patients carry combinations of known infrequent polymorphisms that are overrepresented among our 20 unsolved patients. The importance of these changes on PDH activity is unclear. Investigations in the other PDHc genes are in course in order to elucidate the genetic defect in the unresolved patients.

1. The aim of the study was to detect differences between salt-sensitive and salt-resistant hypertensive patients in the response of the renin—aldosterone axis, plasma noradrenaline and atrial natriuretic peptide to high salt intake. 2. Fifty essential hypertensive patients followed 2 weeks of a standard diet with 20 mmol of NaCl daily, supplemented by placebo tablets for the first 7 days and by NaCl tablets for the last 7 days, in a single-blind fashion. Salt sensitivity was defined as a significant rise (P < 0.05) in 24 h mean blood pressure obtained by ambulatory blood pressure monitoring from the low- to the high-salt period. Biochemical and hormonal measurements were performed on the last day of both periods. 3. Twenty-two (44%) patients fulfilled criteria of salt-sensitive hypertension, whereas the remaining 28 (56%) were considered salt-resistant. High salt intake promoted a significant decrease (P < 0.05) in plasma creatinine, potassium, glucose, cholesterol, low-density lipoprotein-cholesterol, triacylglycerols, uric acid and plasma renin activity, and a significant increase in plasma atrial natriuretic peptide and 24 h urinary calcium excretion. The direction of these changes did not differ between salt-sensitive and salt-resistant patients. Salt-resistant hypertensive patients exhibited a significant decrease in plasma aldosterone induced by high salt intake (from 446 ∓ 35 to 226 ± 35 pmol/l; P < 0.001), whereas this parameter was not significantly modified in salt-sensitive patients (from 485 ± 76 to 364 ± 83 pmol/l; P not significant). Salt-sensitive patients showed an increase in plasma noradrenaline after high salt intake (from 1.15 ± 0.11 to 1.56 ± 0.14 nmol/l; P < 0.05), whereas salt-resistant patients presented a decrease in this parameter (from 1.48 ± 0.08 to 1.12 ± 0.08 nmol/l; P < 0.05). The change in plasma noradrenaline was directly correlated with the change in mean blood pressure induced by high salt intake (r = 0.479; P = 0.003). 4. We conclude that the increase in blood pressure induced by high salt intake in salt-sensitive patients is associated with a stimulation of the sympathetic nervous system and a blunted decrease in plasma aldosterone. Conversely, changes in renal function, electrolyte excretion and plasma concentrations of atrial natriuretic peptide induced by high salt intake seem to be similar in both salt-sensitive and salt-resistant patients.

The higher mortality rate in men than in women after hip fracture may in part be explained by the poor nutritional status in men.

In a prospective study, nine patients with osteoid osteoma were treated with a selective cyclooxygenase-2 inhibitor (rofecoxib). Patient pain perception with no treatment, with conventional nonsteroidal anti-inflammatory drug (NSAID) treatment, and with rofecoxib therapy was compared using a visual analog scale. Tumor response was also monitored by radiographs, computed tomography, and bone scintigraphy. In all cases, pain diminished on administration of rofecoxib in comparison to conventional NSAIDs (P<.05). Four patients underwent surgery whereas in the remaining five patients, bone scintigraphy showed reduced uptake after 6 months. In four patients who were retested at 12 months, scintigraphy values were normal. These four patients are currently asymptomatic and are not receiving any treatment, whereas the fifth patient is still receiving therapy.

We used ambulatory blood pressure monitoring (ABPM) in the assessment of salt sensitivity in 40 essential hypertensive patients, comparing 24-h mean blood pressure during 7 days of low salt (20 mmol NaCl/day) and high salt (260 mmol NaCl/day) intake. Salt sensitivity was diagnosed in 18 essential hypertensive patients (45%), each of them showing a significant increase in mean blood pressure (P< .05) from low to high salt diet. Salt-sensitive patients exhibited a high-salt-dependent increase in all blood pressure parameters including 24-h systolic, mean, diastolic blood pressure, blood pressure load, area under the curve, and awake and asleep blood pressure values. These patients exhibited a nondipper profile on both low-salt and high-salt diets. Salt-resistant patients (55%) showed a decrease in awake, and an increase in asleep blood pressure values after high salt intake, thus tending to flatten the circadian blood pressure profile. We conclude that ABPM is a useful method to assess salt sensitivity. In salt-resistant patients high salt intake induces a significant increase in asleep blood pressure with no significant changes in 24-h blood pressure, promoting a flattened blood pressure curve and tending to transform a dipper into a nondipper profile, which could have important implications in end-organ damage.