Preservation of Bile Ductules Mitigates Bile Duct Loss

The finer branches of the biliary tree (FBBT) contain a regenerative compartment. We hypothesized that preservation of the FBBT together with its microvasculature will lead to recovery of biliary damage and prolonged preservation of bile ductules during the development of chronic liver allograft rejection. The interlobular bile ducts, portal bile ductules and extraportal biliary cells with and without microvessels were studied in sequential biopsies in five patients who fulfilled the Banff criteria of early chronic rejection (CR) (imminence group). Biopsies of CR patients (n = 12) served as controls. Biopsies were double immunostained with CD34 (microvessels) and cytokeratin 7 (biliary structures). Proliferation and proangiogenic activity were assessed with Ki67 and VEGF-A immunostaining. Severe damage of bile ducts in the imminence group did not progress to significant bile duct loss. This was associated with a high proliferative activity in all biliary structures and preservation of the microvascular compartment. VEGF-A expression was increased in all but the reperfusion biopsies. In conclusion, both regenerative activity of the FBBT and an intact microvascular compartment are associated with less damage of the biliary tree and could therefore be prerequisites for biliary regeneration.     

Treatment of dysfunctional uterine bleeding in the perimenopause: the effects of adding combined estradiol/norethisterone acetate therapy to goserelin acetate treatment--a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: To assess the effects of adding combined estradiol/norethisterone acetate therapy (CENT) to goserelin acetate treatment (GA) of dysfunctional uterine bleeding (DUB) in perimenopausal women. METHODS: In a randomized, placebo-controlled, double-blind trial followed by an open follow-up study, 31 perimenopausal women with DUB were recruited from gynecological outpatient departments of two Dutch hospitals and randomized for treatment with either GA/placebo or GA/CENT for 6 months followed by 18 months of GA/CENT for all. The main outcome measures were abdominal pain, number of bleeding days, double-layer endometrial thickness (DET), Greene climacteric score (GCS), visual analog scale for well-being, bone mineral density (BMD) and mammographic density (BI-RAD score). RESULTS: Abdominal pain, number of bleeding days and DET decreased in both groups, the between-group difference in decrease not being statistically significant. GCS initially showed significant improvement in the GA/CENT group. BMD decreased significantly in the GA/placebo group (-4.1%) compared with the GA/CENT group (-0.3%). Another 18 months of GA/CENT did not result in a lasting difference in BMD between groups. BI-RAD scores did not differ significantly between or within the two groups. CONCLUSIONS: Adding CENT to GA treatment for DUB in perimenopausal women initially prevented BMD loss and improved climacteric complaints, while having no negative impact on vaginal bleeding, abdominal pain or BI-RAD scores. However, prolonged treatment did not result in a lasting prevention of bone loss.     

Determination of 3,4-dihydroxyphenylalanine (DOPA) in plasma and cerebrospinal fluid by high performance liquid chromatography with electrochemical detection

We report a reliable method for determining DOPA levels in plasma and cerebrospinal fluid. The method is based on complete conversion of DOPA to dopamine and quantification by HPLC-ECD of the dopamine formed. Lower limit of detection was 0.5 nmol/l. No differences in plasma DOPA levels were found between normal children (0-15 yr, n = 60), normal adults (n = 39) and patients with essential hypertension (n = 40) or Parkinson's disease (no DOPA therapy, n = 30). In normal individuals and in patients with essential hypertension venous plasma levels were higher than arterial levels (10.2 vs 9.3 nmol/l, p less than 0.001, V/A ratio 1.11 (SD 0.08), n = 15). Sympathetic stimuli (standing, tilting, bicycle exercise, tyramine) did not influence DOPA levels. In untreated depressed patients (n = 10) and in non-parkinsonian neurological patients (n = 12) cerebrospinal fluid levels of DOPA were 4.5 (SD 2.4) and 5.2 (SD 1.3) nmol/l respectively. A direct method for the measurement of DOPA by HPLC-ECD after deproteinization of plasma is also described and compared with the conversion method. Good agreement was found when plasma DOPA levels exceeded 0.25 mumol/l (y(conversion method) = 0.943x (direct method) + 0.118; n = 60; r = 0.985). The direct method, because of greater simplicity and the possibility of simultaneous measurement of the DOPA metabolite 3-O-methyldopa, is the method of choice with plasma samples from DOPA-treated patients. In non-DOPA treated individuals the conversion method is superior and has proved to be an accurate and sensitive method for the determination of DOPA levels in plasma and cerebrospinal fluid.     

Is additional epidural sympathetic block in microvascular surgery contraindicated? A preliminary report

The use of additional epidural sympathetic block during and after microvascular surgery in the lower extremities to prevent vasospasm is generally agreed on. However, a significant fall in the perfusion rate of the transplants was seen after application of bupivacaine (Marcain) via the epidural catheter. This effect has, to our knowledge, not been described before and is probably caused by the sympathectomy effect of this type of analgesia.     

Estimating Potency for the E max-Model Without Attaining Maximal Effects

The most widely applied model relating drug concentrations to effects is the E_max model. In practice, concentration–effect relationships often deviate from a simple linear relationship but without reaching a clear maximum because a further increase in concentration might be associated with unacceptable or distorting side effects. The parameters for the E_max model can only be estimated with reasonable precision if the curve shows sign of reaching a maximum, otherwise both EC₅₀ and E_max estimates may be extremely imprecise. This paper provides a solution by introducing a new parameter (S₀ ) equal to E_max/EC₅₀ that can be used to characterize potency adequately even if there are no signs of a clear maximum. Simulations are presented to investigate the nature of the new parameter and published examples are used as illustration.     

Mitotic and meiotic detection of radiation-induced translocations in mouse stem cell spermatogonia using fluorescencein situ hybridization

The efficiency of two methods of detection of translocations induced in mouse stem cell spermatogonia by X-ray doses of 2, 5 and 7 Gy was compared: classical multivalent analysis at diakinesis-metaphase I of meiosis and observation via fluorescencein situ hybridization analysis of mitotic or meiotic stages. Specific DNA libraries for chromosomes 1, 11 and 13 were used. The results obtained indicate that (a) chromosomes 1, 11 and 13 are more involved in multivalent formation than expected on the basis of DNA content and (b) if the mitotic FISH analysis data are corrected for the observed over-representation, the frequencies of induced translocations are similar to those recorded in the classical multivalent studies, suggesting equal scoring efficiencies in both systems.     

The in vitro fertilisation programme at Tygerberg Hospital and the University of Stellenbosch. Five years' experience, April 1983-January 1988

The results of the in vitro fertilisation programme at Tygerberg Hospital for the period April 1983 to January 1988 are presented. Of the 1117 laparoscopies performed, 825 patients reached the transfer stage. A live-birth rate of 9.3% was achieved. The pregnancy rate after transfer of 4 embryos was 25.9% compared with 15.4% after 2 embryos and 10.8% after 3 embryos (P = less than 0.0001). The multiple pregnancy rate was 2.8% in the group receiving 2 embryos and 11.7% and 10.4% in those receiving 3 and 4 embryos, respectively. Of the 77 successful pregnancies (90 babies), 1 baby died at 34 weeks' gestation as the result of abruptio placentae due to preeclampsia and 1 cot death occurred. The only congenital abnormality encountered was a cleft palate.     

Diagnosis of ligament rupture of the ankle joint: Physical examination, arthrography, stress radiography and sonography compared in 160 patients after inversion trauma

We prospectively enrolled 160 consecutive patients with inversion trauma of the ankle in a diagnostic protocol that included physical examination within 2 days and at 5 days after trauma, arthrography, stress radiography, and ultrasonography. 135 patients had pathological lateral ligament laxity on the later physical examination or lateral ligament rupture diagnosed on arthrography and they were operated on. 122 of these patients had ligament ruptures.

At clinical follow-up after a minimum of half a year, all of the patients who were not operated on had stable joints without signs of previous ligament ruptures.

Delayed physical examination at 5 days after the injury led to the highest overall sensitivity (96%) and specificity (84%) for the detection of a ligament rupture. Additional diagnostic procedures, at a considerable cost, yielded little additional information.     

Allografted keratinocytes used to accelerate the treatment of burn wounds are replaced by recipient cells

Cultured keratinocytes were used as allografts on burn wounds in two patients. In both patients successful covering of the wounds was obtained. DNA fingerprinting of the epidermis covering the wounds 21 days later showed that the cultured keratinocytes were replaced by the patients' cells.     

The range of minimum provoking doses in hazelnut-allergic patients as determined by double-blind, placebo-controlled food challenges

BACKGROUND: The risk for allergic reactions depends on the sensitivity of individuals and the quantities of offending food ingested. The sensitivity varies among allergic individuals, as does the threshold dose of a food allergen capable of inducing an allergic reaction. OBJECTIVE: This study aimed at determining the distribution of minimum provoking doses of hazelnut in a hazelnut-allergic population. METHODS: Thirty-one patients with a history of hazelnut-related allergic symptoms, a positive skin prick test to hazelnut and/or an elevated specific IgE level, were included. Double-blind, placebo-controlled food challenges (DBPCFC) were performed with seven increasing doses of dried hazelnut (1 mg to 1 g hazelnut protein) randomly interspersed with seven placebo doses. RESULTS: Twenty-nine patients had a positive challenge. Itching of the oral cavity and/or lips was the first symptom in all cases. Additional gastrointestinal symptoms were reported in five patients and difficulty in swallowing in one patient. Lip swelling was observed in two patients, followed by generalized urticaria in one of these. Threshold doses for eliciting subjective reactions varied from a dose of 1 mg up to 100 mg hazelnut protein (equivalent to 6.4-640 mg hazelnut meal). Extrapolation of the dose-response curve showed that 50% of our hazelnut-allergic population will suffer from an allergic reaction after ingestion of 6 mg (95% CI, 2-11 mg) of hazelnut protein. Objective symptoms were observed in two patients after 1 and 1,000 mg, respectively. CONCLUSION: DBPCFCs demonstrated threshold doses in half of the hazelnut-allergic patients similar to doses previously described to be hidden in consumer products. This stresses the need for careful labelling and strategies to prevent and detect contamination of food products with hazelnut residues.