Effect of aldose reductase inhibition on nerve conduction velocity and resistance to ischemic conduction block in experimental diabetes.

The relationships between nerve polyol levels and both nerve conduction velocity (NCV) and resistance to ischemic conduction block (RICB) in streptozocin-induced diabetic rats were examined in two studies. In the first study, sciatic NCV and RICB of the tail nerve, assessed by measuring the time to disappearance of the nerve action potential after the tail was rendered ischemic, were measured in nondiabetic rats, untreated diabetic rats, and diabetic rats given Statil, an aldose reductase inhibitor (ARI). Sciatic NCV was lower in the untreated diabetic animals than in control animals (P less than .05), and RICB of the tail nerve was greater (P less than .001). Treatment with the ARI completely prevented the slowing of NCV but had no significant effect on the increase in RICB. In the second study, similar groups of rats were treated with either ARI, insulin, or myo-inositol. Sciatic NCV was lower in the untreated diabetic rats than in the nondiabetic rats (P less than .001). In diabetic rats treated with the ARI and in those treated with insulin, NCV was greater than in the untreated diabetic rats (P less than .05 and P less than .001, respectively) and was not significantly different from the nondiabetic rats. NCV in the myo-inositol-treated rats was not significantly different from that in the untreated diabetic rats. RICB was assessed by measuring the decline in sciatic nerve action potential amplitude at minute intervals after death.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth of children before onset of diabetes.

OBJECTIVE: To examine the growth of children before the onset of diabetes. RESEARCH DESIGN AND METHODS: Heights before diagnosis, expressed as SDS, of each diabetic child identified from the diabetes register and of two age- and sex-matched control subjects were obtained from records of routine examinations performed at 3.5, 6, 11, and 13 yr. The heights of their siblings, with control subjects, also were obtained. RESULTS: Diabetic children were considerably taller than control subjects before diagnosis (0-1 yr before diagnosis SDS 0.82 +/- 0.26 vs. 0.16 +/- 0.14, P less than 0.05, n = 24; 1-2 yr before diagnosis SDS 1.02 +/- 0.17 vs. 0.16 +/- 0.14, P less than 0.001, n = 30; 2-3 yr before diagnosis SDS 0.97 +/- 0.23 vs. 0.04 +/- 0.20, P less than 0.005, n = 16). At more than 3 yr before diagnosis, the diabetic children were not significantly taller than control subjects (SDS 0.8 +/- 0.2 vs. 0.27 +/- 0.13, respectively; n = 33). The siblings of the diabetic children were no taller than control subjects. CONCLUSIONS: Diabetic children, but not their siblings, were taller than control subjects before diagnosis, suggesting growth-inducing metabolic changes may precede the onset of clinical diabetes by at least 3 yr.

Effect of aldose reductase inhibition on resistance to ischemic conduction block in diabetic subjects.

OBJECTIVE: To study the effect of aldose reductase inhibition with ponalrestat on resistance to ischemic conduction block (RICB) in diabetic subjects. RESEARCH DESIGN AND METHODS: Twenty-one healthy diabetic subjects without neuropathy were studied. Subjects were randomized to take either a double-blind trial of 600 mg ponalrestat or placebo once daily for 6 wk. The median nerve action potential (MNAP) and conduction velocity (NCV), before and after 20 min of forearm ischemia, were measured at the start and finish of the study. RESULTS: RICB (MNAP remaining after ischemia) decreased from 39.5 to 29.4% in the ponalrestat-treated group (P less than 0.05) and increased from 48.1 +/- 10.2 to 49.5 +/- 6.5% in the placebo-treated group. MNAP and NCV were unchanged in both groups. CONCLUSIONS: Aldose reductase inhibition with ponalrestat partly reverses RICB in diabetes, perhaps by improving nerve hypoxia or reducing nerve energy substrates.

Assessment of the efficacy and safety of Viagra (sildenafil citrate) in men with erectile dysfunction during long-term treatment.

Long-term efficacy and safety of sildenafil was assessed in 1008 patients with erectile dysfunction (ED) enrolled in four flexible-dose (25 - 100 mg), open-label, 36- or 52-week extension studies. After 36 and 52 weeks, 92% and 89% of patients felt that treatment with sildenafil had improved their erections. Responses to a Sexual Function Questionnaire indicated that 52 weeks of sildenafil treatment resulted in clinically significant improvements in the duration and firmness of erections, overall satisfaction with sex life, and the frequency of stimulated erections. Commonly reported adverse events (AEs) were headache, flushing, dyspepsia, and rhinitis, which were generally mild to moderate. Reports of abnormal vision were consistent with previous clinical trials. The occurrence of treatment-related cardiovascular AEs, such as hypertension, tachycardia, and palpitation, was <1%. Discontinuations due to treatment-related AEs were low (2%). Long-term therapy does not diminish the efficacy of sildenafil in patients with ED and remains well tolerated.

Massive hepatosplenomegaly, jaundice and pancytopenia in miliary tuberculosis.

A 29-year-old Caucasian woman presented to hospital with a 2-day history of diarrhoea, anorexia and rigors. Investigations showed abnormal liver function tests, hyponatremia, hypoalbuminaemia and lymphopenia. The initial chest radiograph was normal. A bone marrow trephine biopsy showed non-caseating granulomata and she subsequently developed miliary shadowing on the chest radiograph. A transjugular liver biopsy confirmed the presence of acid-alcohol fast bacilli. Despite starting triple therapy for miliary tuberculosis she remained febrile and developed massive hepatosplenomegaly, jaundice and pancytopenia. Standard triple therapy was substituted with ethambutol, streptomycin and oral prednisolone and the patient made a dramatic recovery. The clinical symptoms of miliary tuberculosis are frequently non-specific and the onset of the illness is often insidious. The liver is involved in almost all patients with miliary tuberculosis, but massive hepatosplenomegaly and jaundice are rare. Standard triple-therapy should be discontinued when there is significant liver dysfunction, and corticosteroids should be considered for patients with miliary tuberculosis who fail to respond to conventional therapy.

Low but detectable serum thyroid-stimulating hormone concentrations in ambulant subjects not receiving thyroxine.

BACKGROUND: In laboratories employing 'front-line' sensitive thyroid-stimulating hormone (TSH) measurement, it is generally accepted that a fully suppressed serum TSH concentration (third-generation assay) alongside normal serum concentrations of free thyroid hormones indicates subclinical hyperthyroidism. However, other explanations are often provided for low but detectable serum TSH concentrations, such as drug effects or non-thyroidal illness. METHODS: We investigated 25 consecutive ambulant individuals, identified over an 18-month period as having low but not fully suppressed TSH concentrations (third-generation assay; sensitivity 0.003 mIU/L) with additional free thyroxine (T(4)), free tri-iodothyronine (T(3)) and thyroid microsomal antibody estimations and thyroid isotope scanning (technetium). RESULTS: Concentrations of serum hormones (median, inter-quartile range) were: TSH, 0.23, 0.17-0.26 mIU/L (reference range 0.34-5.6 mIU/L); free T(4), 14.6, 10.6- 17.6 pmol/L (reference range 10-25 pmol/L); free T(3), 6.1, 5.7-6.6 pmol/L (reference range 4.5-7.5 pmol/L). Thyroid antibodies were negative in all but one individual. On isotope scanning, nine individuals had hot nodules and ten individuals had multinodular goitres (MNG). Of the six with normal scans, ultrasound scanning showed a definite MNG (n = 1) and early MNG (n = 2). CONCLUSIONS: A low but detectable serum TSH concentration, obtained using a third-generation assay, found in an ambulant individual, is frequently a pointer to underlying thyroid disease.

Esthetic restoration of a single-tooth dental implant using a subepithelial connective tissue graft: a case report with 3-year follow-up.

This case report describes the use of a subepithelial connective tissue graft to restore the gingival papillae and augment ridge soft tissues adjacent to a dental implant. The patient was referred for periodontic and prosthodontic evaluation after the placement of an implant--with the implant head 6.5 mm below the adjacent cementoenamel junction--in an area of inadequate bone volume with deficient interproximal papillae and ridge soft tissues. The resulting esthetic defect was restored by means of a combined technique that used a subepithelial connective tissue graft and an emergence profile-contoured crown. A 3-year clinical follow-up with complete regeneration of the gingival papillae is described.

Cutaneous allergy to insulin: could statins and ACE inhibitors play a role? A case report.

Insulin allergy is rare. Both statins and angiotensin converting enzyme (ACE) inhibitors may cause local urticarial skin reactions and have been implicated to precipitate local reactions to insulin. We describe a case of a localised urticarial allergic reaction related to insulin use in a patient co-prescribed an ACE inhibitor and statin.

The causes of hypopituitarism in the absence of abnormal pituitary imaging.

BACKGROUND: Hypopituitarism in the absence of a history of pituitary pathology or abnormal pituitary imaging is rare. AIM: To identify the cause of hypopituitarism in individuals in whom pituitary imaging was normal. DESIGN: Retrospective analysis of electronic patient record. METHOD: A review of the pituitary function in the 506 patients on the Morriston Hospital pituitary database revealed 230 had some degree of hypopituitarism and of these, 21 (9%) had normal pituitary imaging. RESULTS: Of this group, six patients had a past medical history of subarachnoid haemorrhage, head injury or meningitis, and mainly suffered from a deficiency of antidiuretic hormone. One patient had a stroke resulting in multiple anterior hormone deficiencies and six individuals had idiopathic cranial diabetes insipidus (DI). Subsequent investigations of the remaining eight patients with normal pituitary imaging revealed that two had neurosarcoidosis both of whom had panhypopituitarism. Four patients had haemochromatosis which resulted in gonadotropin deficiency in two, DI in one and panhypopituitarism in the other. There were two individuals with confirmed hypopituitarism and multiple hormone deficiencies in which no cause could be identified. CONCLUSION: These results show that hypopituitarism in the absence of pituitary pathology or an identifiable cause is rare. In patients with multiple anterior pituitary hormone deficiencies haemochromatosis and sarcoidosis should be considered.

Adrenal insufficiency following bariatric surgery.

A 35-year-old woman with morbid obesity and amenorrhoea underwent a bilo-pancreatic diversion (BPD). Surgery was successful with good weight loss, restoration of menstruation and almost immediately she conceived for the first time. She was commenced on routine vitamin supplements after surgery but failed to attend follow-up clinic. Five years later, she presented with limb girdle pains, lethargy, night blindness, skin pigmentation, amenorrhoea and dizziness. She had stopped taking supplements prescribed after the surgery. Investigations showed severe vitamin A and D deficiency along with iron and calcium deficiency. Her cholesterol was low at 3.5 mmol L⁻¹. Despite aggressive vitamin replacement, she continued to complain of lethargy and dizziness. Subsequently, three short adrenocorticotropic hormone-stimulation tests were suboptimal (basal cortisol: 196, 185 and 223 nmol L⁻¹; 30 min cortisol: 421, 453 and 435 nmol L⁻¹). She was subsequently commenced on adrenal replacement and her symptoms resolved and she conceived. We describe for the first time in the literature the unexpected finding of adrenal insufficiency following a BPD.

Foot ulceration in a secondary care diabetic clinic population: a 4-year prospective study.

Diabetes guidelines recommend that feet are stratified into low-risk, increased-risk and high-risk. We examined prospective foot ulceration in our secondary care diabetes clinic. At 4-year follow-up, foot ulceration was present in 1/586 (0.17%) in the low-risk, 10/305 (3.3%) in those at increased-risk and 28/236 (11.9%) in the high-risk group.