Action of Calloselasma rhodostoma (Malayan pit viper) venom on human blood coagulation and fibrinolysis using computerized thromboelastography (CTEG)

The effects of Malayan pit viper (Calloselasma rhodostoma) venom on human blood coagulation and fibrinolysis were studied in vitro using computerized thromboelastography. At low concentrations the venom had a coagulant effect shown by faster onset of the coagulation process (shortened SP and R), faster progress of the clot (increased angle and shortened K), and increased coagulation (TEG) index. The maximum amplitude (MA) was not affected, suggesting that the venom had no apparent effect on platelet function; and clot lysis was similar to that in the controls, suggesting that there was no primary fibrinolytic activity. At higher concentrations the venom had anticoagulant effects, SP and R were progressively shortened, but there was poor/no progress in the clot formed, evident from prolonged or absent K, diminished MA and reduced angle. These results show that C. rhodostoma venom has both coagulant and anticoagulant actions. The coagulant action may be due to Factor X activator predominance at low concentrations, while the anticoagulant action could be due to ancrod action. TEG is able to demonstrate the dual effect of this venom, previously described as a paradox, and may be a useful tool in the diagnosis and monitoring of envenomation patients.     

The role of office hysteroscopy in in vitro fertilization.

Twenty-eight patients participated prospectively in a study to evaluate the impact of hysteroscopically detected uterine and cervical anomalies on the success rate of ET in an IVF-ET program. All participants had a normal intrauterine cavity by standard HSG. All the patients had a diagnostic office hysteroscopy under paracervical block before commencing COH. Because our IVF program does not include hysteroscopy as a requirement before undergoing IVF and because the significance of mild intrauterine abnormalities is not yet known, the hysteroscopic findings were not relayed to the personnel involved in the IVF-ET procedure. Sixteen patients (group I) had a normal hysteroscopic evaluation. Twelve patients (group II) had abnormal hysteroscopic findings including small uterine septa, small submucous fibroids, uterine hypoplasia and cervical ridges. Although no difference in patients or cycle characteristics was present, there was a significant difference in the clinical PR between patients in groups I and II. In conclusion, in an IVF-ET program patients with normal hysterography but abnormal hysteroscopic findings had a significantly lower clinical PR, demonstrating the importance of performing hysteroscopy before IVF-ET.     

Down-regulation of muscarinic receptors in the striatum of organophosphate-treated swine

Subacute (daily) administration of diisopropylfluorophosphate (DFP) to male swine (Yorkshire white) resulted in a 97% inhibition of cholinesterase and a decrease of [3H]quinuclidinyl benzilate [( 3H]QNB) binding sites in homogenates of striata by approximately 50% after 14 days. The maximal density of receptors (Bmax) decreased from 2.1 +/- 0.3 to 1.0 +/- 0.2 pmole/mg protein. There was no significant change in the dissociation constant (Kd) for [3H]QNB binding (control: 52.6 +/- 10.7 pM; 7-day: 57 +/- 2.8 pM). Carbachol displacement of [3H]QNB binding yielded data best fit by a two-binding site model. The dissociation constants were KiL = 115 +/- 62 microM (55 +/- 3%) and KiH = 1.8 +/- 0.7 microM (45 +/- 3%), respectively, for the low- and high-affinity states. Seven-Day treatment with DFP reduced the percentage of high-affinity receptors to 22 +/- 8.6%, but affected neither the low- nor the high-affinity Kd (100 +/- 20 and 2 +/- 0.6 microM). With the addition of Mg2+, striatal homogenates had low- and high-affinity receptors in the proportion of approximately 1 to 1. In the presence of Gpp(NH)p + Mg2+ the ratio of high- to low-affinity receptors was 3:1 in homogenates of control tissue (to 26 +/- 5%). This treatment had no effect on this ratio in homogenates of tissue from 7-day DFP-treated swine (3:1) since it was already 3:1. Pirenzepine displacement of [3H]QNB binding was best described by a two-binding site model, with Ki values of 38 +/- 14 and 201 +/- 78 nM, which represent 74 and 26% of the binding sites, respectively. The high affinity Kd value was unchanged following 7 days of DFP treatment (24 +/- 5 nM). There appears to be little change in the displacement curves for pirenzepine inhibition of [3H]QNB binding. This suggests that about 75% of the receptors are of the M1 subtype. Thus, subacute administration of DFP causes not only a decrease in the number of receptors, but also a change in the proportion of agonist affinity states which is related to the interaction of the guanine nucleotide binding protein and the muscarinic receptor.     

Partial tolerance in rat renal allograft recipients following multiple blood transfusions and concomitant cyclosporine

Multiple prior administrations of donor-strain blood while under limited cyclosporine cover, consistently induce extensive rat renal allograft survival and transplantation tolerance. Yet it was hypothesized that some chronic rejection mechanisms were nevertheless operative since consistent but nonprogressive minor renal dysfunction was observed long-term. A histopathologic study on these putative tolerant rats was undertaken to test this hypothesis. Twenty long-term LEW recipients of BN renal allografts receiving the blood-CsA regimen were examined histopathologically at day 100 post-transplant. Sixteen control LEW recipients receiving only a BN renal allograft were studied acutely at day 7 posttransplant. The control recipients demonstrated a range of lesions consistent with previous studies on acute renal allograft rejection in the rat. However, tolerant recipients demonstrated mild-to-moderate lesions consistent with chronic mechanisms of rejection including the following: moderate focal interstitial mononuclear inflammatory cellular infiltration, with periglomerular and perivascular accumulation; occasional arteriolar luminal obliteration and glomerular atrophy; focal areas of moderate interstitial fibrosis; mild interstitial hemorrhage; mild-to-moderate tubular atrophy; and focal tubular necrosis. Previously our laboratory has documented that tissue-specific renal basement membrane antigens may be responsible for inciting this pattern of focal chronic interstitial inflammation. However, from the present histopathologic studies, it would appear likely that chronic rejection mechanisms in these recipients, which were defined as tolerant by immunologic criteria, involve both tissue-specific and MHC determinants. Therefore, induction of transplantation tolerance in these indefinite survivors is partial or incomplete.     

Isolation and identification of chondroitin sulfates from the mud snail

Chondroitin sulfates were isolated from the mud snail. For the quantitative analysis of enzymatic digestion products of isolated chondroitin sulfates, strong anion exchange-high performance liquid chromatography (SAX-HPLC) was performed. By the action of chondroitinase ABC, three unsaturated disaccharides 2-acetamide-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-D-galactose (ΔDi-OS), 2-acetamide-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose (ΔDi-6S) and 2-acetamide-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose (ΔDi-4S) were produced from the mud snail chondroitin sulfates. The analysis showed that relative proportion of ΔDi-OS/ΔDi-6S/ΔDi-4S was 58.7/3.1/38.2. The immunomodulating activity of chondroitin sulfate was examined by cell proliferation assay and these results suggest that it might be a immunosuppressant.     

Efficacy of radical neck dissection for the control of cervical metastasis after radiotherapy for nasopharyngeal carcinoma

Fifty-one patients who had persistent or recurrent neck disease from nasopharyngeal carcinoma after radiotherapy underwent radical neck dissection. The follow-up period ranged from 0.5 to 9 years (median: 2 years). Multiple cervical lymph node involvement was present in 51% of the patients (26 of 51). Malignant cells were detected in 88% of the resected specimens (45 of 51). The clinical sign of fixation of lymph node is the only factor that affects the successful control of neck disease (p = 0.04). Extracapsular extension of the nodal disease was present, and 35% of the lymph nodes were adherent to surrounding structures at operation (18 of 51). There was one hospital mortality and the overall morbidity was minimal. The actuarial survival at 5 years was 38%, and the probability of control of neck disease was 66%. Radical neck dissection is effective in controlling post-irradiation cervical metastasis from nasopharyngeal carcinoma.     

Isolation and analysis of nephritic-producing immune complexes in Plasmodium berghei-infected mice.

A nephritic condition was developed by infecting Swiss Webster albino mice with the malarial parasite Plasmodium berghei NK 65. These animals were tested for urinary protein and the presence of circulating immune complexes using reagent strips and a polyethylene glycol (PEG) precipitation assay. The circulating immune complexes were isolated from the sera using both affinity chromatography and PEG precipitation and from the kidney by acid elution. The isolated complexes were dissociated into their individual components and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The components of the complexes were transferred to nitrocellulose sheets and probed for the presence of malarial antigens using a rabbit anti-P berghei antisera. The overall humoral response to the malarial parasite was evaluated using a radial immunodiffusion assay. The present study confirmed that the malarial-infected animals not only developed the nephritic condition (as evident by the high levels of proteinuria) but also, as indicated by the PEG assay, have the presence of high levels of circulating immune complexes in their serum. The apparent absence in the SDS gels of any abnormal protein bands followed by the inability of the Western blot to reveal any malarial antigens provides some of the strongest evidence to date that these malarial proteins are not directly involved in the circulating immune complexes believed to be responsible for producing this nephritic condition.     

Evaluation and treatment of a male factor component to unexplained infertility

The standard semen analysis frequently fails to identify subfertile males even when findings are normal and conversely often fails to identify fertile males with subnormal semen analyses. This has created the need to produce other tests of sperm physiology that will better distinguish a fertile from a subfertile specimen. Understanding more about the nature of the sperm defect should lead to the establishment of more specific and effective therapies. Until that time, it would still be reasonable to try some of the available empirical therapies even though they may work merely by a placebo mechanism.     

Gastrointestinal dysfunction among intensive care unit patients

This study used the Acute Physiological and Chronic Health Evaluation (APACHE II) system to select two groups of ICU patients with comparable risk of hospital death to evaluate the importance of GI dysfunction, defined as failure to tolerate enteral nutrition (EN), as a prognostic factor. In our ICU, patients who have not undergone recent bowel surgery are treated by EN. Those patients who cannot tolerate EN are treated by total parenteral nutrition (TPN). One hundred and eleven patients who tolerated EN (functioning gut) and 97 TPN patients who failed to tolerate EN (GI dysfunction) were studied. The mean APACHE II scores of the two groups were 17.7 +/- 6.5 (SD) and 17.7 +/- 5.1, respectively. The observed mortality of patients with GI dysfunction (51%) was significantly higher (p less than .0005) than that of patients with a functioning gut (25%). This was associated with significantly poorer APACHE II mean BP, oxygenation, and creatinine scores among the GI dysfunction patients. Our results suggest that shock, ischemia, and hypoxemia, in addition to causing impairment of renal function, may bring about changes in the GI tract, evident clinically only as a failure to tolerate EN, which have an adverse effect on the prognosis of ICU patients so affected.