Chronic subdural haematoma after endoscopic treatment of a supracellar arachnoid cyst.

Neuroendoscopy is considered a safe treatment option for intracranial arachnoid cysts. However a variety of complications has been reported after such interventions. Here we present the first case of a chronic subdural hematoma two months after the combined treatment of a supracellar arachnoid cyst with endoscopic third ventriculostomy and cyst fenestration.

Pressure dressing in breast surgery: is this the solution for seroma formation?

PURPOSE: Pressure dressing (PD) after modified radical mastectomy (MRM) for breast cancer is investigated here as an easy-to-apply method to reduce seroma formation and subsequent need for clinical care. PATIENTS AND METHODS: Two hundred mastectomized patients who were treated with PD on the skin flaps and the axilla immediately postoperatively (group A) were compared with a similar non-PD group (B). Surgical technique and perioperative care were the same. Drains were removed when drain output was reduced to 30 ml per day, or on postoperative day 8 regardless of output. RESULTS: Mean time with drains kept in situ was 4.9 and 5.5 days in group A and B, respectively. Five (2.5%) patients in group A and 16 (8%) in group B developed seromas after the removal of the drains. In total, 9 seroma needle aspirations were performed in group A and 26 in group B. Differences were statistically significant. CONCLUSION: Our findings are supportive of PD as an effective, cheap and easy-to-apply method for the reduction (a) of the time with drains in situ after MRM, (b) of the number of patients developing seromas and (c) of the seroma aspirations. This can potentially reduce further complications, needed medical care and cut expenditure.

Optimal treatment of a recurrent giant craniopharyngioma: lessons from a case.

A case of a 33-year-old man presented with symptoms of dramatic deterioration of the level of consciousness because of a recurrence of a previously aspirated and irradiated craniopharyngioma is described. The tumor had grown enormously in dimensions and was extending in the region of hypothalamus, third ventricle and brain stem, with signs of local compression and obstructive hydrocephalus. Radical surgical excision, despite the size and the location of the lesion, was the therapy of choice. The surgical technique is described. We conclude that in expert hands, microsurgery aiming at total removal should be the therapeutic option for the treatment of recurrent as well as primary craniopharyngiomas.

A preclinical survey on the efficacy of lactandrate in the treatment of colon carcinoma.

PURPOSE: There has been a recent and dramatic increase in the pace of drug development for colorectal cancer which holds promise to further improve curative therapy. We tested lactandrate, an alkylating ester of D-lactam androsterone, for antineoplastic activity against colon adenocarcinoma in vitro and in vivo. MATERIALS AND METHODS: The cytostatic and cytotoxic activity of lactandrate were evaluated in vitro against 9 human colon adenocarcinoma cell lines. The in vitro testing was performed with the sulforhodamine B (SRB) colorimetric assay and the mean concentrations of each drug that generated 50% (GI50) or total (100%) growth inhibition (TGI), as well as the drug concentrations that produced cytotoxicity against 50% of the cultured cells (IC50) were calculated. The in vivo antitumour effect was determined against two rodent colon carcinomas, the Colon 26 and the relatively chemoresistant Colon 38 carcinoma, as well as against the human xenograft CX-1 colon carcinoma. RESULTS: Lactandrate displayed a satisfactory activity against the 9 human colon cancer cell lines, inducing significant growth inhibition and cytotoxicity. Lactandrate induced antiproliferative activity against colon cancer cell lines linearly correlated with the carcinoembryonic antigen (CEA) production. There was a non-linear polynomial correlation between CEA production and the cytotoxic effect of lactandrate. The more differentiated cell lines DLD-1 and HCC2998 appeared more resistant to the cytostatic effect of lactandrate. In vivo, the compound produced a significant antitumour activity against Colon 26 and Colon 38, as well as a moderate antitumour effect against CX-1 colon carcinoma. CONCLUSION: Preclinical research supports the high in vitro and in vivo antitumour potential of lactandrate against colon carcinoma. Therefore, lactandrate represents an important candidate drug for further clinical development.

Antitumour effect of a- and d- lactam androgen nitrogen mustards on non-small cell lung carcinoma.

PURPOSE: We tested 3 alkylating esters of D-lactam androsterone, 3 alkylating esters of A-lactam testosterone and the alkylating nitrogen mustard components of these esters, for antineoplastic activity on non-small cell lung carcinoma (NSCLC) in vitro and in vivo. MATERIALS AND METHODS: Cytostatic and cytotoxic activity was evaluated in vitro against 10 human NSCLC cell lines. The in vitro testing was performed with the MTT metabolic-colorimetric assay and the mean concentrations of each drug that generated 50% or total (100%) growth inhibition (GI50 and TGI, respectively) as well as the drug concentrations that produced cytotoxicity against 50% of the cultured cells (IC50) were calculated. Furthermore, the in vivo antitumour effect was determined against the relatively chemo-resistant Lewis lung carcinoma (LLC) on mice. The acute toxicity of the tested compounds was appointed in C57BL mice and the antitumor effect on LLC was assessed from the percent increase in median lifespan of the treated animals over the untreated (control) (T/C%). RESULTS: The lactam steroidal esters presented lower toxicity and increased antineoplastic activity in vitro and in vivo compared to their respective alkylating components. An A-lactam testosterone ester namely: 17beta-hydroxy- 3-aza-A-homo-4alpha-androsten-4-one-p-N,N-bis (2chloroethyl) amino phenoxy acetate (ALT-CAPOA) performed significantly higher anticancer activity in vitro and in vivo. This compound generated 37.5% 90-day disease free survivors (cures) against LLC. CONCLUSION: These results indicate a high antitumor potential of lactam steroid alkylating esters depended on the alkylating moiety as well as on the modified steroidal carrier. Preclinical research supports that ALT-CAPOA generates well-tolerated toxicity as well as superior antitumor activity against NSCLC. These significant results call for further clinical development.

Preclinical evaluation of the homo-aza-steroid ester 13beta-hydroxy-13alpha-amino-13,17- seco-5alpha-androstan-17-oic-13,17-lactam-p-bis(2-chloroethyl)aminophenoxy acetate for the treatment of malignant melanoma.

PURPOSE: To investigate the in vitro and in vivo activity of an homo-aza-steroid alkylating ester, namely 13beta-hydroxy- 13alpha-amino-13,17-seco-5alpha-androstan-17-oic-13,17- lactam-p-bis (2-chloro ethyl) aminophenoxy acetate (HASE), in comparison with dacarbazine (DTIC) in the treatment of malignant melanoma. MATERIALS AND METHODS: Cytotoxicity was assessed in vitro by the MTT assay using a panel of 6 malignant melanoma human cell lines, with or without the presence of rat liver microsome assay. B16 melanoma-bearing mice were used to evaluate in vivo the antitumor activity of the tested compounds. RESULTS: In all cases of in vitro screening, HASE displayed significantly higher (p <0.0001) cytostatic and cytotoxic activity than DTIC. Moreover, the antitumor activity of HASE in B16 melanoma-bearing mice was satisfactory, prolonging the mice lifespan at 67%, compared to 43% achieved by DTIC. Furthermore, HASE significantly inhibited the tumor growth (tumor growth rate: <42%) as this was defined by tumor volume and weight differences, presenting higher antitumor effect than DTIC. CONCLUSION: HASE displayed superior in vitro and in vivo activity than DTIC in the treatment of melanoma. Thus, HASE may be considered as a significant candidate anticancer agent for further development.

Phenobarbital inducibility and differences in protein expression of an animal model.

Aldehyde dehydrogenases (ALDHs) are a group of enzymes which catalyze the conversion of aldehydes to the corresponding carboxylic acids in a NAD(P)(+)-dependent reaction. In mammals, different ALDHs are constitutively expressed in liver, stomach, eye and skin. In addition, inducible ALDH-isoenzymes are detectable in many tissues; apart from other physico- and immuno-chemical differences, two cytosolic ALDHs (ALDH1A3 and ALDH3A1) are known to be activated in rat liver, by different types of inducers of drug metabolism. Phenobarbital-type inducers increase the ALDH1A3, while polycyclic hydrocarbons (such as BaP and TCDD) increase the expression of the two members of ALDH3A subfamily (3A1 and 3A2). In this study, we used two Wistar rat substrains which have been well-characterized for different inducibility of ALDH1A3 enzyme activity after treatment with phenobarbital. Animals that respond (RR) or do not respond (rr) to treatment have been inbred for almost 25 years, offering a useful experimental model. Apart from the level of ALDH1A3 induced enzyme expression after phenobarbital treatment, no other differences between the two substrains have been noticed, as far as drug metabolizing enzyme activities (like the pentoxy- and ethoxy-O-dealkylation rate) are concerned. According to the present results, the ALDH1A3 expression is still the only difference between the two substrains. Immunoblotting experiments with polyclonal antibodies raised against CYP2B1 or/and CYP1A1/1A2 showed no differences between the two substrains. Additionally, data concerning time- and dose-response induction of ALDH1A3 after phenobarbital and griseofulvin treatment are presented. It is concluded that these two Wistar rat substrains represent a unique animal model for studying what seems to be the only difference between these substrains - the genetic basis of the phenobarbital induction.

Differentiation of disulfiram effects on central catecholamines and hepatic ethanol metabolism.

Disulfiram is used in the treatment of chronic alcoholism, because of the unpleasant symptoms it provokes after ethanol intake. The underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the liver aldehyde dehydrogenases. In addition, it is known that disulfiram also has some neurotoxic properties. The aim of our study was to investigate the relationship between the pharmacological and neurotoxicological properties of disulfiram with respect to the doses applied. Increasing doses of disulfiram (25, 50, 75, 100 and 150 mg/kg) were administered intraperitoneally to Wistar rats and the hepatic enzyme activities of alcohol and aldehyde dehydrogenases were measured. Also, in two brain subregions (midbrain and hypothalamus) the levels of noradrenaline, dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid were determined. The higher dose of disulfiram (150 mg/kg) produced lethal effects in all treated animals. Aldehyde dehydrogenase activities were inhibited by disulfiram in a dose-dependent way, while alcohol dehydrogenase was not affected at all. Concerning the levels of brain biogenic amines, disulfiram produced a significant reduction in noradrenaline and an increase in dopamine levels in both structures of the brain, in a dose-dependent way. However, the lowest dose applied (25 mg/kg) had no effects on brain catecholamines. It is known that high doses of disulfiram may cause severe encephalopathy and peripheral neuropathy in humans, which could be attributed to the impairment of the metabolism of brain biogenic amines, due to inhibition of dopamine-beta-hydroxylase. Our experimental data show that disulfiram affects the level of brain biogenic amines at dose levels higher than those inhibiting the activity of aldehyde dehydrogenase. Therefore, in clinical practice 'disulfiram reaction' could still be achieved with a low dosage regimen not producing neurotoxicity

Mutagenicity, developmental toxicity and carcinogenicity of cannabis.

Data on the mutagenicity, developmental toxicity and carcinogenicity of cannabis are reviewed in this article. The available evidence on the possible mutagenic effects of cannabinoids is still inconclusive. There is no consensus on the induction of point mutations, while some experimental results suggest that cannabinoids may cause chromosomal damage. Concerning the developmental effects of cannabis, an increased embryolethality and somatic growth retardation have been observed in animals, as well as changes in motor behaviour, after perinatal exposure to cannabinoids. An elevated risk for infertility has been suggested for women smoking marijuana. On the other hand, intrauterine exposure to cannabinoids may be followed by changes of behaviour later in childhood. Finally, the experimental work concerning the possible carcinogenic action of cannabinoids has shown that cannabis acts as a tumour promotor in animals. Epidemiological studies have incriminated cannabis smoking for the development of head and neck carcinomas and for carcinomas of the respiratory tract in humans, but several confounding factors have rendered this evidence inconclusive. At least part of the great popularity of cannabis smoking is due to the widespread belief that it is harmless. However, the studies presented in this review show that, despite their low acute toxicity profile, cannabinoids represent several risks in terms of chronic toxicity.

Immunohistochemical detection of oestrogen receptors in ductal carcinoma in situ of the breast.

The expression of oestrogen receptor (ER) protein in invasive carcinoma of the breast and its clinical significance has been extensively evaluated. Little information is available regarding ER expression in ductal carcinoma in situ (DCIS). In this study, 46 formalin-fixed, paraffin-embedded tissue specimens of mammographically detected DCIS were evaluated immunohistochemically for the presence of ER using specific monoclonal antibodies against ER (ER-ICA Abbott Lab). The associations between ER expression and histological type, degree of differentiation and patient menopausal status were evaluated. Positive ER staining was present in 72% of cases. Non-comedo types of DCIS were more frequently ER-positive than comedocarcinoma. ER-positive tumours were inversely correlated with the presence of nuclear pleomorphism. The incidence of ER in pre-menopausal and post-menopausal women was similar. In conclusion, ER expression is present in a considerable percentage of DCIS, and ER-positivity is associated with the degree of differentiation and non-comedo carcinoma variants.

Acute arterial thrombosis of the lower extremities due to prolonged intestinal obstruction.

A case of a female patient who was admitted urgently with intestinal obstruction, peripheral shock, hypovolemia and acute ischemia of the lower extremities is presented. The ischemia of the lower extremities had developed due to low cardiac output following extensive dehydration caused by a prolonged intestinal obstruction from a cholelith. Although this pathogenetic mechanism of acute ischemia of the lower extremities is well known, this characteristic case is, nevertheless, presented to alert the clinician of this situation.

Early surgical results on acute arterial occlusion of the extremities.

Although the earliest possible embolectomy is still correlated with best rates of limb salvage, we consider, as do most other authors, that the only critical criterion for operability must be the viability of the ischemic limb. Even in the presence of gangrene of the foot relief of arterial occlusion is recommended in order to secure a more distal amputation. Arterial embolectomy seems to be a simple surgical procedure; however, in the presence of atherosclerotic arteries or in the cases of acute arterial thrombosis the operative procedure needs considerable experience in vascular surgical techniques to secure a successful outcome. Finally, the prevention and early treatment of the revascularization syndrome together with appropriate cardiopulmonary management in a strict intensive-care unit can improve the mortality significantly in cases of acute arterial occlusion of the extremities.

Lymphedema of the upper limb after surgery for breast cancer.

Radical mastectomy is followed by swelling of the arm, and although the number of surgeons employing the operation is decreasing, postmastectomy lymphedema continues to be a serious complication. In the present report based on 158 women who underwent modified radical (126) or simple (32) mastectomy and occasionally radiation for histologically proved adenocarcinoma of the breast, the pathogenesis and treatment of postmastectomy lymphedema are discussed. The following conclusions can be drawn: (1) The occurrence of postmastectomy lymphedema diminishes the less extensive the operation. (2) Mild lymphedema that develops early postoperatively tends to subside. (3) Conservative treatment in the majority of cases is effective in controlling postmastectomy lymphedema of a mild to moderate degree. (4) Modified radical mastectomy, which is as radical as Halsted's operation, is rarely followed by lymphedema.