Coupling of lactose molecules to the carrier protein hinders the spleen and bone marrow uptake of doxorubicin conjugated with human albumin.

Several attempts have been made to enhance doxorubicin (DOXO) concentrations in tumour cells by drug conjugation with human albumin (HSA). HSA-DOXO has the drawback of causing DOXO accumulation in spleen and bone marrow, with a consequent leucopoenia not produced when lactose molecules are coupled to the carrier protein. In the present experiments we demonstrated that the effect of HSA lactosamination is not a consequence of a more rapid disappearance from the bloodstream of the lactosaminated conjugate (L-HSA-DOXO), which is rapidly internalized by the liver through the asialoglycoprotein receptor, but is due to a hindered uptake by spleen and bone marrow cells caused by the coupled lactose molecules. Experiments in vitro showed that HSA-DOXO produced an inhibition of murine macrophage proliferation not caused by L-HSA-DOXO. This result can be explained by higher amounts of the former conjugate entering in these cells and suggests macrophages as the cell type responsible for the spleen and bone marrow internalization of HSA-DOXO hindered by lactose coupling. Importantly, lactosamination of HSA did not reduce the marked uptake of HSA-DOXO by chemically induced rat hepatocellular carcinoma. L-HSA-DOXO, by avoiding DOXO accumulation in bone marrow is an attractive candidate for clinical trials against tumors which were found to actively internalize this conjugate in laboratory animals, such as hepatocellular carcinoma.     

Nasal septal perforations: our surgical technique.

OBJECTIVE: The aim of this paper was to describe our surgical technique for the treatment of nasal septal perforations. STUDY AND DESIGN: We studied 31 patients with nasal septal perforation treated with an endoscope-assisted technique, based on a bilateral dissection of monopedicled mucosal flaps from the nasal fossa floor, sutured at the edge of the perforation previously unstuck, without any graft interposed between the two mucosal layers. RESULTS: In our experience with 31 patients, the use of this technique led to the persistent closing (with follow-up for at least one year) of 96.3% of the perforations smaller than 3 cm. CONCLUSIONS: Our technique has the advantage of an endonasal approach, without any external incision, and the use of monopedicled flaps from the nasal fossa floor without any graft interposition, avoiding any other surgical procedure and morbidity in the donor site of the graft. The use of nasal endoscopy permits superior precision in all surgical steps. SIGNIFICANCE: The high success rate in perforations smaller than 3 cm seems to confirm the effectiveness of this technique.     

Magnesium salts in the treatment of ventricular tachycardia

We report the results of magnesium sulphate (MgSO4) infusion in 10 patients with different ventricular arrhythmias: 6 torsade de pointes (2 with total A-V block, 1 with acute myocardial infarction and 3 with lengthening of the Q-Tc due to antiarrhythmic and/or diuretic treatment), 1 bidirectional ventricular tachycardia (on chronic treatment with digoxin (0.5 mg/day) and diuretics), and 3 polymorphic ventricular ectopic beats plus ventricular tachycardia runs (2 with hypertensive and 1 with ischemic cardiomyopathy). MgSO4 in normal saline was given at low rate (50 mg/min) and continued 2 hours after disappearance of arrhythmia, and the infusion was repeated at the same rate for 60-90 min twice daily for the next 3-4 days. In all patients the drug was effective and no side effects were observed. The heart rate and Q-Tc interval remained unchanged from baseline values. Serum creatinine concentration was normal. Serum Mg++, 60 minutes after the beginning of the infusion, was comparable to control values in all the patients, except 2 with hypomagnesemia. Finally, we can conclude that MgSO4 is an useful therapeutic tool for the treatment of various ventricular tachycardias.     

Transabdominal repair of cystocele by wedge colpectomy during combined abdominal-vaginal surgery

The aim of the study was to evaluate the effectiveness of transabdominal wedge colpectomy as surgical treatment for cystocele. One hundred and sixty-three women with either first or second-degree cystocele (Beecham classification), rectocele and concomitant stress urinary incontinence or benign pelvic masses were submitted for a combined operation. Transabdominal repair of the cystocele was performed by wedge colpectomy employing two different absorbable sutures, Vicryl and PDS. The choice of suture was not random but depended on the period at which surgery was performed. Data obtained were analyzed with Student’st-test and Fisher’s exact test. The cystocele cure rate was 90.2% (110 out of 122) at 3-year follow-up and was significantly associated with the preoperative degree, being 95.5% and 76.5% in first and in second degree, respectively (P=0.003). At 1-year follow-up the cure rate was significantly associated with the type of the suture employed (P=0.01). At 2-year follow-up rectocele cure rate was 97.2% and vaginal vault prolapse appeared in 3.5% of cases. Stress urinary incontinence relapsed in 10% of patients after Burch colposuspension. After the operation 94.1% of the women declared normal coitus. In the present series wedge colpectomy was found to be effective in repairing first-degree cystocele, whereas a high incidence of relapse was observed when second-degree cystocele was present preoperatively. The suture material employed influenced the cure rate. EDITORIAL COMMENT: Wedge colpectomy of the anterior vaginal wall has been described by Weinstein and Roberts (1949), Macer (1978) and Drutz (1991) as a means of abdominally correcting anterior vaginal wall relaxation. Although the present authors did not find as high a success rate with the procedure as the previous investigators, they do show that an abdominal approach to cystocele repair is feasible. There are instances when such an approach would be advantageous to avoid repositioning for a vaginal anterior wall repair. The danger of abdominal anterior wedge colpectomy lies in the dissection of the bladder base from the underlying vaginal wall. Dissection in this area must proceed carefully to avoid trauma to the bladder, ureters and, more distally, to the urethrovesical junction. Performed carefully, with attention directed at avoiding these structures, the abdominal wedge colpectomy is a potentially useful procedure to add to the armamentarium of the urogynecologic surgeon.     

Abdominal aortic aneurysm and horseshoe kidney. Clinical cases

The concomitance of horseshoe kidney and abdominal aortic aneurysm is rare but represents an interesting challenge for vascular surgeons. The trouble is greater if the diagnosis is formulated intraoperatively and specially if it is an emergency operation for aortic rupture or fissuration. The surgeon's aim is to get to the aneurysm collar without damaging the kidney, the renal arteries or the urinary tract that often have an anomalous development. The authors make a review of the literature and describe three cases occurred out of 2558 prosthetic reconstructions due to abdominal aortic aneurysm.     

T stages of tumors of the tongue and floor of the mouth: correlation between MR with gadopentetate dimeglumine and pathologic data.

PURPOSETo define MR accuracy in the evaluation of the T stages of tumors of the tongue and floor of the mouth.METHODSFifty-two patients affected by squamous cell carcinoma were studied with a superconductive system at 1.5 T. The study was performed with spin-echo T1- and T2-weighted images before contrast and short spin-echo T1-weighted and gradient-echo sequences after gadopentetate dimeglumine administration. The results obtained with MR were compared with pathologic data.RESULTSGood correlation of T stages (TNM system) was obtained in 45 of 52 cases. MR did not show four superficial lesions. In one case, infiltration of the cortical bone of the mandible was not demonstrated (MR, T2; pathologic, T4), and in another the lesion was classified as T2 instead of T3, as it was pathologically. One lesion was classified as T4 on MR because of infiltration of the alveolar ridge but was classified as T2 at surgery. In 46 patients who underwent surgery, the accuracy of MR was excellent for predicting the relationship of tumor to midline and oral floor musculature. The results obtained with gadopentetate dimeglumine were better than those obtained in noncontrast studies in 32 (62%) of 53 cases.CONCLUSIONMR showed high accuracy in the study of tumors of the tongue and floor of the mouth.     

Micronuclei frequencies in hospital workers occupationally exposed to low levels of ionizing radiation: influence of smoking status and other factors

In the context of a medical surveillance program aimed at preventing cancer risk from exposure to ionizing radiation, we investigated chromosomal damage in peripheral lymphocytes from 37 hospital workers exposed to low levels of ionizing radiation and 37 controls. The micronuleus (MN) assay was used as a biomarker of genetic damage. The influence of confounding factors like smoking status, age and gender was investigated by multiple regression analysis. The results indicated that, overall, MN frequency was higher in exposed workers than in controls, although the difference was not statistically significant. Interestingly, smoking status significantly raised MN frequency among the exposed workers but not among controls. This suggests that smoking can influence chromosomal damage induced in humans by ionizing radiation. Among both exposed workers and controls, MN frequency was found to increase with age. Female gender influenced the increase in MN frequency in the exposed group. Our results suggest that the effect of cigarette smoking should be carefully factored into genetic monitoring studies assessing the risks associated with low level radiation exposure.     

Differences in lectin binding of malignant pleural mesothelioma and adenocarcinoma of the lung.

In order to differentiate between malignant pleural mesothelioma and adenocarcinoma of the lung, the glycoconjugate profiles of 6 reactive mesothelial lesions, 23 mesotheliomas (17 epithelial, 1 desmoplastic, 2 biphasic, and 3 fibrous types), and 28 well-differentiated pulmonary adenocarcinomas were evaluated with the use of 8 lectins in addition to anti-carcinoembryonic, anti-keratin and anti-epithelial membrane antigen. Formalin-fixed, paraffin-embedded tissues were stained with the avidin-biotin peroxidase complex method. Reactions of wheat germ (WGA) and peanut (PNA) agglutinin with neuraminidase treatment lectins were positive in 5 of 6 (83%) and 3 of 6 (50%) cases, respectively, in reactive mesothelial lesions. Thirteen of 23 (57%) malignant mesotheliomas of the pleura showed a positive reaction for WGA and PNA with neuraminidase treatment; other lectins were low-positive, below 9%. In contrast, pulmonary adenocarcinomas showed positive reactions in 27 of 28 cases (96%) for PNA, 26 of 28 (93%) for Ricinus communis (RCA-I), 25 of 28 (89%) for WGA, and 22 of 28 (79%) for succinylated WGA (SucWGA). The findings suggest that malignant pleural mesothelioma and pulmonary adenocarcinoma have consistent and distinct glycoconjugate profiles, and that stains for RCA-I and SucWGA may be useful for differential diagnosis.