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.

Clinical experience with exenatide in a routine secondary care diabetes clinic.

Exenatide use in type 2 diabetes is limited in routine clinical practice. We examined a cross-section of 90 patients. Mean weight and HBA(1c) were 114.9+/-20.6 kg, 10.3+/-2.1% at initiation; 108.0+/-15.3 kg (p<0.0001), 9.0+/-2.1% (p<0.001) at 3 months; 109.2+/-18.2 kg (p<0.0001), 9.5+/-2.3% (p=0.08) at 6 months. Exenatide appears effective in reducing HBA(1c) and weight.

Use of a patient linked data warehouse to facilitate diabetes trial recruitment from primary care.

Recruitment into clinical trials from primary care may be difficult. Our aim was to use the Secure Anonymised Information Linkage (SAIL) databank to identify potential participants for two factitious trials. We identified 284 and 711 participants for each study (population=250,086). This method appears promising in identifying trial participants.

The role of endothelial dysfunction in the pathophysiology of erectile dysfunction in diabetes and in determining response to treatment.

BACKGROUND: Erectile dysfunction (ED) in diabetes is related to autonomic neuropathy and endothelial dysfunction. We studied the relative importance of these factors in diabetic and non-diabetic men with ED and determined if they predict responses to treatment with sildenafil. METHODS: Thirty-three men, aged 35-65 years, with ED (20 diabetic, 13 non-diabetic), 15 of whom were sildenafil responders and 18 non-responders, were compared with 30 age and risk-matched control subjects (15 diabetic, 15 non-diabetic). Subjects with ED completed the International Index of Erectile Function (IIEF) questionnaire. Endothelial function was assessed by changes in brachio-radial and femoro-tibial arterial pulse-wave velocity (pulse-wave velocity) during reactive hyperaemia, expressed as percentage endothelium-dependent dilatation. Autonomic function was assessed by heart rate variation during expiration and inspiration (E/I ratio) and during the valsalva manoeuvre. RESULTS: The respective changes in pulse-wave velocity, in the arm and leg [mean (sd)] were 0.71 (6.5)% and 3.5 (6.4)% in the impotent diabetic men, 0.7 (7.6)% and 2.4 (5.9)% in the non-diabetic impotent men, -0.68 (5.7)% and -1.31 (7.2)% in the non-impotent diabetic men and 7.7 (3.7)% and 7.6 (3.4)% in the control subjects. There was a significant interaction between ED and diabetic status such that there was significantly impaired vascular response in the diabetic group (both with and without ED) and in the non-diabetic group with ED compared with the non-diabetic control group (P = 0.01 and P = 0.001 for brachio-radial and femoro-tibial measures, respectively). The E/I ratios of the diabetic men were significantly lower than those of the control subjects [1.17 (0.14) vs. 1.33 (0.16), P < 0.02), but there were no differences in the measures of autonomic neuropathy between the groups with ED and those with normal erectile function. Amongst diabetic men, the initial IIEF scores (maximum score 30, low score indicates more severe ED) were significantly higher in sildenafil-responders than non-responders [16.3 (8.4), vs. 6.8 (7 1), P < 0.02]. The rate of sildenafil response was not significantly affected by the measures of endothelial or autonomic function. CONCLUSIONS: ED in both diabetic and non-diabetic men is characterized by marked endothelial dysfunction in comparison with non-diabetic control subjects. Response to sildenafil is not predicted by either endothelial function or autonomic function, but in diabetic men appears to be related to the initial degree of erectile dysfunction.

Androgen status in healthy premenopausal women with loss of libido.

Androgen deficiency may contribute to female sexual dysfunction and loss of libido. The role of the active metabolite of testosterone, dihydrotestosterone (DHT), in these conditions is uncertain. The aim of this study was to determine the role of androgens and DHT in the etiology of loss of libido in healthy women. We studied 29 premenopausal women with reduced libido (subjects) and 12 healthy females (controls). They were aged 18 to 45 years and in a stable heterosexual relationship. At 9 a.m. we took venous blood in the follicular phase for serum estradiol, total testosterone, and DHT, dehydroepiandrosterone sulfate (DHEAS), and SHBG levels. Subjects were interviewed by a psychosexual counsellor. Using the modified Wilson's sexual fantasy questionnaire (Baumgartner, Scalora, & Huss, 2002) and sexual satisfaction by Golombok-Rust Inventory of Sexual Satisfaction (GRISS Rust & Golombok, 1985, 1986) we assessed sexual drive. The total testosterone and DHT levels (mean +/- SD) were respectively 0.97 +/- 0.38 mmol/L and 0.76 +/- 0.37 nmol/L in subjects and 0.97 +/- 0.41 mmol/L and 0.77 +/- 0.15 nmol/L in controls. The SHBG and DHEAS were respectively 65 +/- 42 mmol/L and 3.76 +/- 1.0 umol/L in subjects and 65 +/- 29 mmol/L and 3.67 +/- 2.6 in controls. The scores of the Wilson questionnaire and GRISS were respectively 21 +/- 14.1 and 5 +/- 2.1 in subjects and 35 +/- 14.8 & 2 +/- 1.2 in controls. Subjects were more likely than controls to have low income (48% versus 8%, p < 0.02), a minor illnesses (57% versus 17%, p < 0.02), a history of depression (57% versus 8%, p = 0.025) and to report sexual problems in their partners (24% versus 0%, p = 0.053). Loss of libido in otherwise healthy women may be related to relationship problem, depression, psychosocial factors, and sexual dysfunction in the partner but do not appear to be related to androgen status.

Clinical guidelines online: do they improve compliance?

BACKGROUND: The introduction of intranet services in a district general hospital provided an opportunity to put evidence based national guidelines online to facilitate access and promote application of best practice in acute medical care. This study evaluated the effectiveness of this approach. METHOD: Local guidelines were made available online at ward terminals after they had been distributed in paper form. An interrupted time series design was used to evaluate the impact on compliance with three preselected guidelines, which addressed the management of suspected deep vein thrombosis, upper gastrointestinal bleeding, and stroke. This was supplemented by a qualitative assessment of the views of medical staff. RESULTS: There was a significant increase in the adherence to the guidelines for stroke when they were made available online, but this was not demonstrable for deep vein thrombosis or upper gastrointestinal bleeding. Qualitative interviews with junior medical staff and consultants after the study was completed revealed that there was confusion regarding the application of the guidelines for deep vein thrombosis and little active support from the gastroenterologists for the guidelines for upper gastrointestinal bleeding. The stroke guidelines were actively promoted by their author and widely supported. CONCLUSION: Making guidelines available online will not be effective unless they are actively promoted and represent a consensus view.

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.

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.

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.

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.