The ultrastructural changes in the skin in dermatitis herpetiformis after withdrawal of dapsone

The development of skin lesions in patients with dermatitis herpetiformis after the withdrawal of their dapsone therapy was studied with the electron microscope. In control biopsies from patients prior to cessation of treatment, membrane-bound vacuoles were found beneath the basal lamina of the epidermis as previously described. After dapsone withdrawal, there was an apparent increase in the number of vacuoles and occasionally several vacuoles appeared to have coalesced forming an early blister. At this stage, the basal lamina and associated hemidesmosomes were normal although in places there were small discontinuities in the basal lamina. Where the reaction was more intense, vacuoles and cells, mainly eosinophils, were embedded in fibrin de posits. Above this, the basal lamina was usually disrupted with involvement of the basal epidermal cells. These results suggest that the vacuoles do play a part in the formation of the pathological lesion in dermatitis herpetiformis. In addition, the basal lamina is shown to be only secondarily involved. The nature of the vacuoles has still to be elucidated.     

THE ACTION OF CHEMOTHERAPEUTIC AGENTS ON PSORIATIC EPIDERMIS

SUMMARY. —Mitotic counts and histological features have been studied in 35 psoriatic patients prior to treatment, and during treatment with topically applied fluocinolone acetonide, methotrexate, dithranol and coal tar.
Prior to treatment there was considerable variation in the mitotic counts in the 35 biopsies. The granular layer was absent in 10 biopsy specimens, partially formed in small areas in 21, well formed in most areas in 2, and normal in 2. There was no correlation between the mitotic counts and state of the granular layer.
With methotrexate and dithranol treatment the granular layer showed improvement prior to a significant fall in the mitotic counts. With fluocinolone acetonide the improvement in the granular layer appeared at the same time as a significant fall in the mean mitotic count, but the granular layer had completely reformed in 7 of the 9 patients while the mitotic count was still considerably raised compared to uninvolved psoriatic skin. With coal tar the results were not uniform; some patients showed a significant fall in mitotic counts prior to improvement in the granular layer and others first showed improvement in the granular layer.
It is suggested that in clearing psoriasis these drugs have an action other than, or in addition to, inhibiting mitosis.     

Pegfilgrastim and daily granulocyte colony-stimulating factor: patterns of use and neutropenia-related outcomes in cancer patients in Spain – results of the LEARN Study

Daily granulocyte colony-stimulating factors [(G-CSFs); e.g. filgrastim, lenograstim] are frequently used to reduce the duration of chemotherapy-induced neutropenia (CIN) and the incidence of febrile neutropenia (FN) in cancer patients. A pegylated formulation of filgrastim, pegfilgrastim, which is administered once per cycle, was introduced in Spain in 2003. LEARN was a multi-centre, retrospective, observational study in Spain comparing patterns of use of daily G-CSF and pegfilgrastim, and CIN-related outcomes in adults with non-myeloid malignancies receiving myelosuppressive chemotherapy. Outcome measures were the percentage of patients receiving G-CSF for primary prophylaxis versus secondary prophylaxis/treatment, duration of treatment with G-CSF and incidence of CIN-related complications. Medical records from consecutive patients with documented pegfilgrastim ( n  = 75) or daily G-CSF ( n  = 111) use during 2003 were included. The proportion of patients receiving primary or secondary prophylaxis was comparable between the pegfilgrastim (39 and 48% respectively) and daily G-CSF (40 and 48% respectively) groups. However, there was a trend towards less frequent use to treat a neutropenic event such as FN or neutropenia in the pegfilgrastim group (17 versus 30% with daily G-CSF). Chemotherapy-induced neutropenia-related complications were less frequent in patients receiving pegfilgrastim (e.g. FN 11 versus 24% with daily G-CSF). This is the first study to show the potential benefits of pegfilgrastim over daily G-CSF in Spanish clinical practice.     

Calcium Antagonists. Mechanisms, Therapeutic Indications and Reservations: A Review

The chief site of action of the calcium antagonist drugs isthe slow calcium channel in two tissues: the atrioventricularnode and vascular smooth muscle. The exact mode whereby theseagents work is still unknown, but recently studies withradioligandssuggest that the binding site for the dihydropyridines suchas nifedipine is different from the site for theverapamil group(including diltiazem). In some way these agents ‘close’or ‘block’ the calcium channels. Verapamil and diltiazemare active against the calcium channel of the atrioventricularnode which nifedipine in clinical doses is not; in contrast,nifedipine is more active on peripheral vascular arterial muscle,presumably inhibiting the calcium channel more strongly. Anintracellular site of action of these agents on calmodulin invascular smooth muscle cannot be excluded. Clinically, the chiefcalcium antagonists (verapamil, nifedipine, diltiazem) constitutea powerful group of cardioactive agents with a spectrum of therapeuticactions rather similar to beta-adrenoceptor blockade, beingeffectivein angina of effort and rest, and hypertension. Critical differencesare dependent on the individual propertiesof the calcium antagonists.Thus only verapamil and diltiazem are effective in inhibitingthe AV node while the dihydropyridines such as nifedipine areonly vasodilators in clinical doses. As a group, calcium antagonistscause vascular dilation and do not cause bronchial constriction,in contrast to the beta-adrenoceptor blocking agents. In manypatients these diverse properties allow safe combination ofcalcium antagonists and beta-adrenoceptor blockers if due careis observed.     

INHIBITION OF THE COLONIC MOTOR RESPONSE TO EATING BY PINAVERIUM BROMIDE IN IRRITABLE BOWEL SYNDROME PATIENTS

The effect of pinaverium bromide on the colonic motor response to eating was investigated in 10 irritable bowel syndrome patients, by means of an intraluminal probe supporting 8 groups of electrodes. At each site examined from transverse to sigmoid colon, the electromyograms exhibited 2 kinds of spike bursts: short spike bursts (SSB) localized at one electrode, and long spike bursts (LSB), isolated, propagated orally or aborally over a few centimeters, or aborally propagated over the whole length of the colon investigated (migrating long spike bursts, MLSB). Recordings were continuously performed over 24 hr. Each patient received at 7.00 p.m. on day 1 and at noon on day 2 an 800-1000 Kcal meal preceded by IV administration of pinaverium bromide (4 mg) or placebo. After placebo administration, the duration of LSB activity and the number of MLSB were significantly increased over 3 postprandial hr by comparison with the 2 hr preceding the meal. After pinaverium injection no significant postprandial change in LSB and MLSB activity was noted. The SSB activity was not modified after the meals preceded by placebo or pinaverium injection. These results suggest that the inhibitory action of pinaverium bromide on postprandial colonic motility may support the clinical efficacy of this agent in the treatment of the irritable bowel syndrome.     

Gastrointestinal Effects of Diazepam-withdrawal are Linked to Activation of Central Cholecystokinin-ergic Pathways in Rats

Abstract— The influence of flumazenil-precipitated diazepam withdrawal on intestinal myoelectric activity and colonic transit was evaluated, in diazepam-dependent rats. Administered intraperitoneally, flumazenil (15 mg kg^?1) induced a strong stimulation of the duodenal spiking activity lasting 197 ± 20 min, and accelerated colonic transit corresponding to a significantly (P < 0·05) increased value of the geometric centre (3.52 ± 0.23 vs 2·44 ± 0·1 for the control). Both devazepide and L365260 administered intracerebroventricularly at a dose of 10 μg kg^?1 abolished the flumazenil-induced withdrawal effect on the duodenum, whereas at a lower dose (1 μg kg^?1) only L365260 was able to antagonize this effect. In the same way, devazepide, loxiglumide and L365260 suppressed the effect of precipitated withdrawal on colonic transit when administered intracerebroventricularly at a dose of 10 μg kg^?1, whereas similar blockade was obtained at a dose of 5 μg kg^?I with L365260, and 10 ng kg^?1 with PD135–158. It is concluded that in rats precipitated diazepam-withdrawal altered intestinal motility and colonic transit and that these effects are mediated by central release of cholecystokinin (CCK) or activation of CCK-ergic neurons.     

Is the Potential of Teenage Consultations Being Missed?: a Study of Consultation Times in Primary Care

There is a paucity of knowlege regarding teenage health eventhough it features as one of the priority areas in the government'shealth plans. There have been few reports of adolescent contactswith primary care teams, although there are impressions of asuboptimal service. As a prelude to understanding more aboutcommunication between general practitioners and teenage patients,this study aimed to look at the time spent on teenage consultations,which can be used as one method of describing the quality ofcare provided to teenage patients. Nine-hundred consultationsinvolving six doctors in one surgery were timed over a 3 monthperiod by one observer using a validated method. One-hundredand nineteen consultations with patients aged 11–19 werecompared with the 781 consultations for other age groups andshowed a statistically significant mean shortfall of nearly2 minutes (23%). This trend was confirmed for all six doctors,despite a broad range of average consulting times. The studyalso demonstrated some other characteristics of teenage consultations.Several implications of these results are discussed as wellas possible reasons for these findings. The study emphasizesthe need for further research in this area.