In vitro/in vivo functionality of Catapres-TTS

The in vitro and in vivo functionality of Catapres-TTS, a transdermal therapeutic system that delivers the alpha adrenergic receptor agonist clonidine, is discussed in terms of the drug transport kinetics and resultant plasma drug concentration profiles. The design of Catapres-TTS is presented as an optimization by which the best combination of system performance characteristics is obtained within the inherent limitations of the transdermal drug transport properties and the known pharmacokinetic and pharmacodynamic properties of the drug. Clonidine is a potent antihypertensive agent with a relatively low therapeutic index. For Catapres-TTS, the majority of control over the drug input rate resides within the system, rather than within the skin, which significantly reduces the variability in drug input rate and resulting plasma drug concentration both within and between patients. Moreover, the presence of a rate-control element in the system allows for patterning of the drug release rate. An initial bolus of drug is placed in the contact adhesive layer, where its transport into the skin is not inhibited by the rate control element in the system, for reduction in the time needed to achieve steady state drug input. The selection of the loading dose of drug is described as an optimization between the minimization of the lag time and the maintenance of constant plasma drug concentrations during the crossover period between system applications in chronic therapy.     

Infantile Digital Fibroma Treated With Mohs Micrographic Surgery

BACKGROUND: Infantile digital fibroma (IDF) is a rare benign fibrous tumor of childhood that frequently recurs despite local excision. Conservative, nonsurgical management may result in regression and/or joint deformity. OBJECTIVE: To describe the histologic features of IDF and discuss a case excised using Mohs micrographic surgery (MMS). METHODS: Case report and review of the clinical, histologic, and ultrastructural features. RESULTS: Characteristic inclusion bodies of actin were identified with hematoxylin and eosin, Masson's trichrome, and rapid actin immunostain. The tumor was debulked and the majority was removed after one stage of MMS, except where the deep margin approached the joint space. The defect healed by secondary intention. At 2 years the patient had no recurrence or functional joint deformity. CONCLUSION: MMS is a surgical treatment option for IDF.     

Evaluation of the legal risk of a ‘missed’ cancer in two breastscreen services

Variation in opinions of medical experts is a problem for both the legal and medical profession. This is particularly relevant in breast imaging. BreastScreen Queensland and New South Wales have developed a review protocol to assess ‘reasonableness’ of radiological opinions. It is hoped that the protocol will be acceptable to the courts and will result in a fair outcome for all parties involved in a medico-legal dispute.     

Smoking and coffee intake following alcohol withdrawal in alcoholic inpatients

The aim of this study was to assess alcoholic inpatients' smoking and coffee intake variation following withdrawal. Only moderate smokers (less than 30 cigarettes/day) showed a significant increase of cigarette consumption after alcohol withdrawal. However, their urinary cotinine level did not vary, suggesting a behavioral, and not biological, compensation through smoking following alcohol withdrawal. Heavy smokers (30 cigarettes/day or more) showed no significant clinical or biological variation of smoking behavior. Coffee consumption increased after alcohol withdrawal in all patients, irrespective of smoking habits.     

Overexpression/amplification of HER-2/neu is uncommon in hepatocellular carcinoma

BACKGROUND： Hepatocellular carcinoma （HCC） is one of the most prevalent fatal cancers in the world. Despite advances in early diagnosis and improvements in surgical techniques, the survival of patients with HCC even after resection is poor because of the high incidence of recurrences. Therefore, the identification of prognostic factors may be helpful in the development of new treatment protocols. AIMS： To investigate HER-2/neu status in HCC by immunohistochemistry （IHC） and fluorescence in situ hybridisation （FISH）, and to explore the possibility of using trastuzumab in the treatment of HCC. METH ODS： Eight hundred and sixty eight surgical samples from patients with primary HCC were examined for their HER-2/neu status. IHC for HER-2/neu was performed with the HercepTest kit; FISH analysis was performed with the PathVysion HER-2 DNA probe kit. The correlations between HER-2/neu overexpression and clinicopathological characteristics were analysed statistically. RESULTS： HER-2/neu overexpression was detected in 21 （2.42%） of the 868 primary HCCs. Only one specimen showed HER-2/neu gene amplification by FISH. No significant associations were found between HER-2/neu overexpression and the clinicopathological parameters. CONCLUSIONS： There is a low frequency of HER-2/neu overexpression/amplification in HCC. There appears to be no role for HER-2/neu as a prognostic marker and no benefit of anti-HER-2/neu trastuzumab treatment in patients with HCC.     

Acute pustulosis of the legs in diverticulitis with sigmoid stenosis: an overlap between bowel-associated dermatosis–arthritis syndrome and pustular pyoderma gangrenosum

BACKGROUND: Bowel-associated dermatosis-arthritis syndrome denotes the occurrence of diarrhoea with arthritis and skin lesions related to bowel disease with or without bowel bypass. In this condition, the histological finding of cutaneous aseptic neutrophilic cell infiltrate is non-specific and common to a wide spectrum of neutrophilic dermatoses, including pyoderma gangrenosum. OBSERVATION: We describe a 78-year-old woman with fever, abdominal discomfort and arthralgias, who developed grouped pustular lesions on her shins with histologically spongiform pustule formation. Aetiological assessment disclosed diverticular disease with sigmoid stenosis. CONCLUSION: Although clinical and histological features in our case fit the diagnosis of bowel-associated dermatosis-arthritis syndrome, they may also correspond to a pustular variant of pyoderma gangrenosum. Our observation raises the question of the nosological classification of bowel-associated dermatosis-arthritis syndrome within the spectrum of neutrophilic diseases.     

The effect of substance P and other tachykinins on inositol phospholipid hydrolysis in rabbit retina, superior colliculus and retinal cultures

Substance P and eledoisin stimulate the accumulation of inositol phosphates in a dose-dependent manner in retinal and superior colliculus slices of the rabbit. The EC50 values for substance P and eledoisin in both tissues were of the same order (1.5-4.9 microM), suggesting that the receptors in the two tissues were alike with characteristics of the SP-P subtype rather than the SP-E subtype. These data suggest that the SP-immunoreactive material in the retinal ganglion and amacrine cells is identical. The effectiveness for a number of tachykinin substances at 10(-5) M for stimulating inositol phosphates accumulation was as follows: Substance P greater than eledoisin greater than neurokinin A greater than neurokinin B greater than substance P (octapeptide) greater than substance P (pentapeptide). Spantide [(D-Arg1, D-Try7.9, Leu11) substance P] and (D-Pro2, D-Try7.9) substance P did not stimulate inositol phospholipid hydrolysis. However, spantide, at a concentration of 10(-6) M, was an antagonist of the effect produced by substance P, but had no action on the effect produced by neurokinin A or neurokinin B. Substance P and other tachykinins were also effective in stimulating inositol phosphates accumulation in 3-5-day-old rabbit retinal cultures but did not elicit a response in the older (25-30-day-old) cultures which lacked neurones but contained Müller cells. Furthermore, substance P was only active in the younger cultures in stimulating an increase in internal calcium levels. It is therefore concluded that retinal tachykinin receptors linked to phosphoinositide turnover and calcium mobilisation are associated exclusively with neurones and not with Müller cells.