Therapy of human cervical carcinoma with monoclonal antibody-Pseudomonas exotoxin conjugates.

Pseudomonas exotoxin A (PE) linked to the F(ab')2 fragment of 1H10, a murine monoclonal antibody recognizing a carbohydrate epitope of a glycoconjugate expressed on the surface of human cervical carcinoma tumor cells, was evaluated for in vitro and in vivo activity. PE can kill cells by ADP-ribosylating elongation factor 2 thus inhibiting protein synthesis. Disulfide- as well as thioether-linked immunotoxins (1H10-PE) killed cervical carcinoma cells in vitro and were 20-160 times more inhibitory to target than to control cells. Cell killing was antibody mediated as demonstrated by the reduction of 1H10-PE growth inhibition to target CaSki cells by free 1H10 F(ab')2. In addition, a control antibody immunotoxin was nontoxic to CaSki cells. Thioether-linked 1H10-PE administered either i.v. or i.p. suppressed the growth of established solid s.c. cervical carcinoma tumors xenografted in nude mice for over 30 days. Treatment with antibody alone or a control immunotoxin had no significant effect on tumor growth. Administration of immunotoxin i.p. was associated with less toxicity than administration i.v., but i.v. injections were more effective at suppressing the growth of established solid tumors.     

Conjunctival involvement of lymphomatoid granulomatosis

Lymphomatoid granulomatosis is an angiocentric and angiodestructive lympho-proliferative disorder involving multisystems but rarely conjunctiva. We present a 62-year-old Chinese female with lymphomatoid granulomatosis who had an ulcerative conjunctival nodule. Conjunctival biopsy revealed pathological findings important for diagnosis and indicating progression of disease severity. To our knowledge, this is the first report to demonstrate pathological findings characteristic of lymphomatoid granulomatosis with conjunctival involvement.     

Differential risks of subsequent vascular events for transient ischaemic attack and minor ischaemic stroke.

Using a prospective hospital-based registry, 146 patients with transient ischaemic attack (TIA) were compared with 376 patients with minor first-ever ischaemic stroke with respect to the 3-month risk of subsequent vascular events, in order to clarify the distinctions between the disease entities. All patients were enrolled within 48 h of onset. The risk factor distribution for the two groups was comparable, except that the TIA patients had more previous TIAs. Large artery atherosclerosis (34%) and small vessel occlusion (32%) were the main aetiologies in the TIA group, whereas small vessel occlusion (49%) was the major cause in the stroke group. The 3-month risk of combined endpoints of stroke, myocardial infarction, and vascular death for TIA patients was higher than that for the minor stroke group (15.1% vs. 3.2%; hazard ratio 4.6, 95% confidence interval 2.3-9.3 in multivariate analysis). Large artery atherosclerosis and male sex were the other significant predictors. TIA may demand more urgent management than minor stroke. The fact that aetiology is a predictor, highlights the need for rapid diagnostic tests to establish pathogenesis.     

Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.     

The effect of atherogenic infusions of the triglyceride-rich, lipid emulsion, Lipofundin-S, on the in vitro growth characteristics of rat aortic smooth muscle cells.

This study shows that arterial smooth muscle cells (SMC) isolated from rats receiving atherogenic doses of the lipid emulsion, Lipofundin-S, alter their in vitro growth properties. Compared to cells from control animals, SMC isolated from Lipofundin-S-infused rats show a reduction in both saturation density and response to increasing serum concentrations, without a change in the baseline proliferation. Also, SMC isolated from lipid-treated animals and grown for five days in the presence of 30, 150, or 300 pg/ml estradiol show a 30% increase in growth vs. cells from controls. Epinephrine at 1 microM stimulates growth in SMC from control rats, while causing no growth enhancement over five days in cells from lipid-infused animals. Thus, atherogenic infusions of Lipofundin-S into rats cause phenotypic changes in arterial SMC which can be passed to successive cell generations in vitro.     

Differential analgesic effect of tenoxicam on post-cesarean uterine cramping pain between primiparous and multiparous women.

BACKGROUND AND PURPOSE: Uterine cramping pain is related to prostaglandins, which are mediated by cyclooxygenase. However, it is unknown whether the analgesic effects of the non-selective cyclooxygenase inhibitor tenoxicam are different between primiparous and multiparous women. This placebo-controlled, double-blind study compared the analgesic effect of tenoxicam on post-cesarean uterine cramping pain in primiparous and multiparous women. METHODS: Forty primiparous women and 40 multiparous women who were scheduled for elective cesarean delivery were allocated into the following 4 groups: saline-primipara (SP) group, tenoxicam-primipara (TP) group, saline-multipara (SM) group, and tenoxicam-multipara (TM) group. Saline or 20 mg tenoxicam was intravenously injected immediately after clamping of the umbilical cord. All patients received patient-controlled analgesia for postoperative pain control. Resting wound pain, uterine cramping pain, morphine consumption, and morphine-related side effects were evaluated at 4 and 24 hours after surgery. RESULTS: At 24 hours after surgery, tenoxicam-related relief of uterine cramping pain was 2.1 in primiparous women (visual analog scale: SP 5.6 (4.4-6.8) minus TP 3.5 (2.2-4.9); p < 0.01). The tenoxicam-related morphine-sparing effect was 14 mg (45%) in primiparous women (SP 31.4 mg (23.9-38.8) minus TP 17.4 mg (11.6-23.2); p < 0.01). The tenoxicam-related relief of uterine cramping pain and tenoxicam-related morphine-sparing effect were not significant in multiparous women. CONCLUSIONS: This study revealed that the analgesic effect of tenoxicam on post-cesarean uterine cramping pain is greater in primiparous women than in multiparous women. Further studies are required to determine whether a higher dosage of tenoxicam is beneficial to reduce uterine cramping pain in multiparous women.     

The effects of hyperthyroidism on oesophageal motility.

This study, evaluating the effects of hyperthyroidism (HT) in oesophageal motility, depended on an oesophageal radionuclide transit test. A modified standard method was used to calculate: (a) total mean transit time (MTT), (b) residual fraction (RF) and (c) retrograde index (RI) in a supine position. Eighteen untreated patients with HT and 25 normal volunteers (NV) with a similar age distribution were included in this study. The results showed that oesophageal motility in patients with HT was worse than in the normal controls (P < 0.05 by Student's t-test). The correlation of MTT, RF and RI with size and function of thyroid glands in the patients with HT were calculated to explain the effects of HT in oesophageal motility. The results showed that neither the size nor the function of the thyroid glands in HT affected oesophageal motility.     

Subclinical neurotoxicity of mercury vapor revealed by a multimodality evoked potential study of chloralkali workers

Pattern visual, brainstem auditory, and somatosensory evoked potential (EP) studies were performed on 26 chloralkali workers. The intensity of mercury vapor exposure in these workers was estimated from the individual working history. Mercury levels in blood, urine, and hair were determined with atomic absorption spectrometry. The EP findings were compared with those from individually matched normal subjects. In brainstem auditory and somatosensory EP studies, prolonged neural conduction times in the central nervous system (CNS) were found in workers exposed to mercury vapor. In the pattern visual EP study, mercury workers had higher interpeak amplitudes. Findings of this study suggested that chronic exposure to mercury vapor would affect the CNS functions. A multimodality EP study is a useful adjunct in evaluation of chronic mercury neurotoxicity, especially in an epidemiological study.