Bilateral macular hemorrhage after laser in situ keratomileusis

· Background: This is the first report of a bilateral submacular hemorrhage after LASIK surgery in an extreme myo pic patient. A 31-year-old man underwent bilateral surgery for correction of –16.75+0.75×70° and –16.50+0.50×55°. · Methods: Case report. · Results: One day after surgery the patient’s uncorrected visual acuity was in the 20/50 range OU and by 17 days after surgery his visual acuity had declined to 20/200 range. Fundus examination showed multifocal subretinal macular and posterior pole hemorrhages. Fluorescein angiography showed some macular lesions compatible with lacquer cracks. · Conclusions: Preoperative and postoperative fundus examination is important to detect this phenomenon. Patients should be informed of this rare complication. Received: 2 June 1998 Revised version received: 16 November 1998 Accepted: 17 November 1998     

Stabilization of rat serum proteins following oral administration of fish oil

The mechanism of action of fish oil (FO), currently used in different chronic inflammatory conditions such as rheumatoid arthritis (RA), is not completely understood, although it is thought that it could alter the metabolism of endogenous autacoids. In addition, we hypothesized that the known capability of fatty acids (FA) of stabilizing serum albumin and perhaps other proteins, may be of pharmacological relevance considering that it is shared by other anti-rheumatic agents (e.g. nonsteroidal antiinflammatory drugs). Thus, we studied the effect of oral administration of FO and corn oil (CO), a vegetable oil with a different composition, on the stability of rat serum proteins, evaluated by a classical in vitro method based on heat-induced protein denaturation. FO, and, to a lower extent, CO inhibited heat-induced denaturation of rat serum (RS): based on the inhibitory activity (EC50) of the major fatty acids against heat-induced denaturation of RS in vitro, it was possible to speculate that in vivo effects of palmitic acid (C16:0) and eicosapentaenoic acid (EPA, C20:5, n-3) may be more relevant than that of linolenic acid (C18:2). To better investigate this phenomenon, we extracted albumin from the serum of animals treated or not with FO with a one-step affinity chromatography technique, obtaining high purity rat serum albumin preparations (RSA-CTRL and RSA-FO), as judged by SDS-PAGE with Coomassie blue staining. When these RSA preparations were heated at 70 degrees C for 30 min, it was noted that RSA-FO was much more stable than RSA-CTRL, presumably due to higher number of long chain fatty acids (FA) such as palmitic acid or EPA. In conclusion, we provided evidences that oral administration of FO in the rat stabilizes serum albumin, due to an increase in the number of protein bound long chain fatty acids (e.g. palmitic acid and EPA). We speculate that the stabilization of serum albumin and perhaps other proteins could prevent changes of antigenicity due to protein denaturation and glycosylation, which may trigger pathological autoimmune responses, suggesting that this action may be involved in the mode of action of FO in RA and other chronic inflammatory diseases.     

Clinicopathological study of familial late infantile Hallervorden-Spatz disease: a particular form of neuroacanthocytosis

The cases of two sisters with late infantile Hallervorden-Spatz disease are reported, one of whom has died. Autopsy of the deceased patient showed typical pallidal lesions, such as axonal spheroids and iron deposits, without involvement of the substantia nigra. Ultrastructural examination revealed that pallidal axonal enlargements consisted of collecition of mitochondria, dense bodies, vesicles and amorphous material. In the living patient, brain MRI showed the classical tiger's eye appearance of the globus pallidus. Retinitis pigmentosa, acanthocytosis and slight neuromuscular involvement with an increase in serum creatine kinase were observed in both subjects. The appearance of the globus pallidus on MRI was in line with the pathological abnormalities. Ultrastructural differences between the principal disorders characterized by neuroaxonal dystrophy are compared and the clinical spectrum and similarities of the different forms of neuroacanthocytosis analysed.     

The effects of cyclosporin A,tamoxifen, and medroxyprogesterone acetate on the enhancement of Adriamycin cytotoxicity in primary cultures of human breast epithelial cells

Summary Adriamycin (Adr), the single most active agent used in the treatment of breast cancer, may become ineffective as treatment progresses due to the development of multidrug resistant (MDR) tumors. A major mechanism associated with MDR is increased P-glycoprotein (Pgp) expression. This study examined the abilities of the anti-estrogen tamoxifen (TAM) and the progestin medroxyprogesterone acetate (MPA) as well as cyclosporin A (CsA), a known resistance modifier, to enhance the cytotoxic effects of Adr on human breast epithelial cells (HBEC) in primary culture. Pgp and estrogen receptor (ER) expression were determined in each of the cultures by immunocytochemical assays using the monoclonal antibodies C219 and H222 Sp, respectively. The Adr-sensitive, Pgp-, ER+ MCF-7 cell line and the Adr-resistant, Pgp+, ER-MCF7-AdrR cell line were used as controls. Primary cultures were categorized as HBEC from tissues with or without previous chemotherapy. Pgp was detected in 1 of the 15 cell cultures from tissues without previous chemotherapy and in 5 of the 6 cell cultures from tissues previously exposed to chemotherapy. Incubation with either CsA or MPA plus Adr enhanced Adr toxicity in Pgp+ but not Pgp- cell cultures, whereas TAM had no effect on the sensitivity of any of the cultures. Of the 21 primary cultures of HBEC, 3 were ER+. There was no correlation between the enhancement of Adr cytotoxicity and ER status. The data suggest that MPA as well as CsA may be useful as modifying agents in overcoming Pgp-associated multidrug resistance.     

Spinal accessory nerve palsy due to neurovascular compression. Report of a case diagnosed by magnetic resonance imaging and magnetic resonance angiography

The case of a young patient with left accessory nerve paralysis is reported. He had slight tilting of the head to the right side, developed over a period of about 6 months. On neurological examination hypotrophy of the left sternocleidomastoid and trapezius muscles was observed. MRI and MR-angiography imaged the presence of a neurovascular compression between the medulla oblungata, at the level of the nerve entry zone, and a vessel loop of an elongated left vertebral artery. In spite of the absence of a surgical demonstration it is our opinion that the neurovascular conflict is the cause of the accessory nerve palsy.     

Caustic ingestion in childhood: current treatment possibilities and their complications

In a review of 15 pediatric patients who had ingested caustic substances, the authors describe the diagnostic and therapeutic procedures to be followed as well as the complications that may occur with their use. The cases reported include 1 esophageal rupture caused by balloon dilatation and 1 recurrent stenosis treated with a silastic tutor.     

Toxin pharmacology of the large-conductance Ca2+-activated K+ channel in the apical membrane of rabbit proximal convoluted tubule in primary culture

The patch-clamp technique was used to study the toxin pharmacology of the large-conductance Ca²⁺-activated K⁺ channel (BKCa) present in the apical membrane of rabbit proximal convoluted tubules (PCT) in primary culture. Experiments were performed with the inside-out configuration. This channel was very selective for K⁺ against Na⁺ and had a conductance of 180 pS with 140 mmol/l in the pipette and the bath. The action of toxins was studied on the extracellular side of the channel by using the pipette perfusion technique. Experimental conditions were 140 mmol/l KCl in the pipette and 140 mmol/l Nad in the bath. Pipette potential was maintained at 0 mV. Perfusion of crude venom from Leiurus quinquestriatus hebraeus inhibited reversibly the open probability (P _o) in a concentration-dependent fashion (IC₅₀=0.8 mg/l; n=3). The following synthetic or purified toxins were tested: synthetic charybdotoxin (ChTX) IC₅₀=7.3×10^–9 M (n=5); iberiotoxin (IbTX) IC₅₀=5.5×10^–7 mol/l (n=3); and kaliotoxin (KTX) IC₅₀=4.8×10^–7 mol/l (n=3). The suppression of the six first N-terminal amino-acids slightly reduced the affinity of ChTX (IC₅₀=1.2×10^–8 mol/l, n=4). Neither Dendroaspis polylepis venom nor purified dendrotoxin modified P _o even at high concentrations (20 mg/l and 10^–6 mol/l respectively). Apamin, which blocked the small-conductance K⁺ channel in cultured PCT, did not act on BKCa. These results indicate that ChTX is the most efficient known toxin against the epithelial BKCa in primary cultures of PCT. In spite of there being considerable homology of sequence between ChTX, IbTX and KTX, ChTX was about 100 times more effective than the others. Truncated ChTX kept a high affinity for this channel and could be used to obtain a labelled probe.     

Serum esterase inhibition in birds: A nondestructive biomarker to assess organophosphorus and carbamate contamination

With the aim of proposing a nondestructive biomarker for monitoring the toxicological risk to birds of exposure to the organophosphorus insecticide azamethiphos and the carbamate insecticide methomyl, laboratory studies were performed on serum B esterases in Japanese quail (Coturnix coturnix japonica). The birds received two single dose treatments of each compound (azamethiphos and methomyl), i.e., 50 mg/kg and 250 mg/kg respectively. In the first treatment, serum butyrylcholinesterase (BChE) and carboxylesterase (CbE) were drastically inhibited in the azamethiphos-treated group, 24 h after the dose. No inhibition was detected for BChE and CbE activities in the methomyl-treated group, 24 h after the dose. In the second treatment, the birds died or were sacrified 3 h after the dose. Serum BChE and brain acetylcholinesterase (AChE) were strongly inhibited after treatment with both insecticides. Serum CbE, hepatic microsomal CbE and 7-ethoxyresorufin dealkylation activities were also inhibited. A statistically significant correlation between serum BChE and brain AChE was found at lethal and sublethal doses of these xenobiotics. The experimental results indicate that the nondestructive biomarker BChE can give an early qualitative and semi-quantitative warning of the toxic effects of organophosphate and carbamate insecticides in birds.     

Effects of heroin,alone or in combination with other drugs,on the locomotor activity in two inbred strains of mice

The locomotor activity of C57B1/6J and DBA/2J mice was studied, under the influences of heroin, amphetamine, strychnine, or ethanol, and of combinations of the opiate with each one of the other drugs. Heroin treatment was followed by the typical running fit in the C57 mice, while the DBA strain was unaffected. Amphetamine enhanced the activity in the C57 strain only. The combination of heroin with amphetamine or ethanol increased the locomotor activity only in the DBA strain, while heroin + strychnine exerted a clear stimulating effect on the activity of the C57 mice. The strychnine + heroin mixture was more toxic than heroin alone when the lethal doses (LD50) were determined in the 2 strains.