Gonadotrophin-releasing hormone agonist therapy for hirsutism is as effective as high dose cyproterone acetate but results in a longer remission

Both cyproterone acetate (CPA) and the gonadotrophin-releasing hormone agonist (GnRHa) have been shown to be effective for the treatment of hirsutism. We wished to compare the effectiveness of CPA in two standard doses with GnRHa and add-back therapy and to compare the length of remission after these treatments. A total of 60 hirsute hyperandrogenic women was assigned to the following treatment groups: CPA 2 mg with 35 microg of ethinylestradiol for 21 days each month (Diane group), CPA 50 mg, days 5-15, and ethinylestradiol 50 microg, days 5-25, each month (CPA group) or Decapeptyl 3.75 mg i.m. every 28 days with the addition of conjugated oestrogen 0.625 mg, days 1-21, and medroxyprogesterone acetate 10 mg, days 12-21 (GnRHa group). Hirsutism was graded by the Ferriman-Gallwey-Lorenzo (FGL) index and anagen hair shaft diameters and serum luteinizing hormone (LH) and testosterone were assessed before and every 3 months during and after treatment. All women were treated for 1 year with 1 year follow-up. At baseline hirsutism and endocrine patterns were similar in all groups. After one year of treatment, hirsutism decreased in all groups but the changes were greater (P <0.05) in the CPA and GnRHa groups than in the Diane group. Serum LH and testosterone were lowest in the GnRHa group. After withdrawal, hirsutism increased rapidly in the Diane and CPA groups and after 6 months, FGL scores and hair shaft diameters were similar to pretreatment values. In the GnRHa group, hirsutism increased more gradually and after 1 year of withdrawal, FGL scores and hair diameters were significantly (P <0.05) less than pretreatment values. Serum LH and testosterone increased rapidly in all three groups reaching pretreatment values by 6 months. These data suggest equal efficacy of the GnRHa and the high dose CPA regimen for the treatment of hirsutism in hyperandrogenic women. GnRHa with add-back treatment appears to result in a longer remission of hirsutism in comparison with CPA.      

Non-steroidal anti-inflammatory drug (NSAID)-induced colonic strictures and perforation: A case report

Although non-steroidal anti-inflammatory drug-induced colopathy is well described, colonic perforations complicating non-steroidal anti-inflammatory drug intake are rare. We report a patient with rheumatoid arthritis who was on long-term diclofenac and presented with early colonic stricture formation and a caecal perforation, which to the best of our knowledge, has only been reported once before. It is important to suspect this diagnosis in patients on non-steroidal anti-inflammatory drug therapy who present with an acute abdomen.     

Effects of REM sleep deprivation of ACTH-induced yawning

Central administration of ACTH in rats induces yawning and stretching. In order to study the effects of REM sleep deprivation on ACTH-induced yawning, the peptide was injected immediately after the REM sleep deprivation period or 24 h later. REM sleep deprivation impaired ACTH-induced yawning, but after a 24-hour recovery period, rats displayed a number of yawns similar to those in control animals. Implications for an involvement of dopaminergic and mainly cholinergic systems are discussed.     

Intensive support to improve clinical decision making in cardiovascular care: a randomised controlled trial in general practice

Objective: To evaluate the effects of feedback reports combined with outreach visits from trained non-physicians on the clinical decision making of general practitioners (GPs) in cardiovascular care.

Design: Pragmatic cluster controlled trial with randomisation of practices to support (intervention group) or no special attention (control group); analysis after 2 years.

Setting: 124 general practices in The Netherlands.

Participants: 185 GPs.

Main outcome measures: Compliance rates for 12 evidence-based indicators for the management of patients with hypertension, hypercholesterolaemia, angina pectoris, or heart failure. The evaluation relied on the prospective recording of patient encounters by the participating GPs.

Results: The GPs reported 30 101 clinical decisions at baseline and 22 454 decisions after the intervention. A significant improvement was seen for five of the 12 indicators: assessment of risk factors in patients with hypercholesterolaemia (odds ratio 2.04; 95% CI 1.44 to 2.88) or angina pectoris (3.07; 1.08 to 8.79), provision of information and advice to patients with hypercholesterolaemia (1.58, 1.17 to 2.13) or hypertension (1.55, 1.35 to 1.77), and checking for clinical signs of deterioration in patients with heart failure (4.11, 2.17 to 7.77). Single handed practices, non-training practices, and practices with older GPs gained particular benefit from the intervention.

Conclusions: Intensive support from trained non-physicians can alter certain aspects of the clinical decision making of GPs in cardiovascular care. The effect is small and the strategy needs further development.

     

Experimental axonopathy induced by immunization with campylobacter jejuni lipopolysaccharide from a patient with guillain‐barré syndrome

Campylobacter jejuni (C. jejunj) infection is the most common antecedent in the axonal variant of Guillain‐Barré syndrome (GBS). Antibodies against nerve gangliosides found in GBS patients recognize cross‐reactive epitopes in the lipopolysaccharide (LPS) of C. jejuni. This led to the molecular mimicry hypothesis of GBS. We immunized eleven rabbits with a LPS extracted from HS:19 C. jejuni strain isolated from a patient with GBS and complete Freund's adjuvant (CFA)(group I). In a second experiment we immunized seven rabbits with LPS, CFA and keyhole limpet hemocyanin (KLH)(group II). All group I rabbits developed high titers of anti‐LPS, anti‐GM1, anti‐GD1b antibodies and lower titers of anti‐GD1a. One rabbit, 50 days after initial inoculation, showed tremor and weakness. All rabbits of group II developed high titres of antiganglioside antibodies and six animals showed weakness 59–113 days after initial inoculation. Two rabbits died. Pathology showed mild to moderate, tendentially grouped, axonal degeneration in sciatic nerves of four out of five animals. Control rabbits of group I (immunized with CFA only) did not develop antibodies, controls of group II (immunized with CFA + KLH) developed low titers of IgG anti‐GM1. None developed neurological signs or showed axonal degeneration. C. jejuni LPS is a potent B‐cell stimulator capable to induce a strong antiganglioside response in rabbits. However, to induce the neuropathy is crucial to employ KLH, a glycoprotein known to stimulate both humoral and cellular responses. This animal model reproduces the pathogenetic process hypothesized in axonal GBS with antiganglioside antibodies post C. jejuni infection.     

Lp(a) lipoprotein: relationship to cardiovascular disease risk factors, exercise, and estrogen.

OBJECTIVE: Lp(a) lipoprotein is a distinct lipoprotein particle that recently has been found to be associated with cardiovascular disease. A study was conducted to assess the influence of cardiovascular disease risk factors on levels of Lp(a) and to evaluate the effects of age, exercise, and estrogen on these levels. STUDY DESIGN: Two studies, a cross-sectional study of older men (n = 105) and women (n = 75) (mean age 76 years) and a prospective study of younger postmenopausal women (mean age 48 years), were carried out. Lp(a) and other lipoproteins were measured in the two studies and differences were sought by statistical analysis. RESULTS: In the cross-sectional study, serum Lp(a) was similar in men and women and was not influenced by age. Lp(a) levels in men and women were higher when there was more than one cardiovascular disease risk factor present (p less than 0.028). We could not demonstrate such a relationship with other lipid and lipoprotein measurements. In the prospective study exercise alone had no influence on Lp(a) levels. Oral estrogen decreased Lp(a) levels marginally (p = 0.08). The decrease in Lp(a) with oral estrogen was associated with increases in triglycerides (p less than 0.01) and very-low-density lipoprotein (p less than 0.06). CONCLUSIONS: These data confirm that elevated Lp(a) levels are an independent risk factor for cardiovascular disease. Lp(a) levels are primarily influenced by genetic factors and it appears estrogen may have a minor influence on its hepatic synthesis.     

Interstitial deletion of 10q: Clinical features and literature review

We report on a patient with interstitial deletion of 10q and compare her to 8 previously described patients, 2 of whom have chromosomal breakpoints similar to our patient. Minor anomalies including broad forehead, hypertelorism, strabismus, prominent philtrum, and “dysplastic” pinnae are present in our patient. Psychomotor retardation and hypotonia are universal findings in 10q interstitial deletion. Growth retardation, not present in our patient, is seen in some. These clinical findings are sufficiently distinct to suggest early chromosome studies. © 1992 Wiley-Liss, Inc.     

Endocrinology: Predictive value of serum oestradiol concentrations and oocyte number in severe ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is a serious complicationof gonadotrophin usage but it is difficult to accurately predictits occurrence. Previous investigators have identified the combinationof high oestradiol concentrations and oocyte number as beingpredictive in 80% of cases. In this study we sought to identifythe incidence of severe OHSS in patients with high oestradiolconcentrations and large numbers of oocytes and to evaluatethe importance of pregnancy in the development of OHSS. Between1990 and 1993, we studied 139 cycles using two assisted reproductivetechniques [oocyte donor, n =72; in-vitro fertilization (IVF),n = 67] in which either oestradiol (>4000 pg/ml), oocytenumber (>25), or both were elevated. OHSS was diagnosed bystandard criteria. There were no cases of severe OHSS in theoocyte donor group and six in the IVF group. Among 10 patientswith oestradiol concentration >6000 pg/ml and >30 oocytes,only one had OHSS (10%). The relative risk of OHSS with pregnancywas 12 (confidence interval 2.18–66.14). We conclude thatthe risk of OHSS even at high levels of stimulation is lowerthan previously believed. Secondly, donors have a very low riskof OHSS, probably because of the absence of pregnancy. As such,cryopreservation of all oocytes in IVF cycles is a reasonablealternative to cycle cancellation or use of adjunctive medication.