Prognostic role of screening tests of haemostasis and underlying diseases in acute disseminated intra-vascular coagulation in adults

Summary. The significance of precipitating causes of acute disseminated intra-vascular coagulation (DIC) and the severity of derangement of haemostasis based on laboratory investigations carried out initially were evaluated in 98 patients and was related to the fatal outcome in them. It was seen that septicaemia was the commonest precipating cause. Survival was better in patients in whom DIC was precipitated by obstetric causes compared with those with septicaemia (P < 0.01). Death was also more frequently associated in patients with higher prothrombin time (PPT) ratio (> 1.5) and/or higher activated partial thromboplastin time (APTT) ratio (> 2.5) as compared to their lower values (P < 0.01 each). Death occurred in all the seventeen patients in whom septicaemia was present along with PPT ratio of > 1.5. It is concluded that deranged haemostasis and presence of septicaemia both independent of each other, contribute to the fatal outcome in acute DIC. Combination of both is associated with poorest prognosis.     

Antibodies Against the β-Subunit of Ovine Luteinizing Hormone Can Decrease the Clearance of Human Chorionic Gonadotropin in Rhesus Monkeys*

ABSTRACT: Contraceptive vaccines based on active immunization against gonadotropic hormones are being investigated in humans and other primates. Immunization against the β-subunit of ovine luteinizing hormone (oLHβ) reduces fertility in rhesus monkeys by inducing inadequate luteal phases and preventing corpus luteum rescue by rhesus chorionic gonadotropin (rhCG). These effects result from the cross-reactions of the oLHβ-antibodies with rhCG and rhLH. We used human CG (hCG), which also cross-reacts strongly with anti-oLHβ to examine how the circulating oLHβ-antibodies affect the metabolic clearance rates (MCR) of hCG in rhesus monkeys. ¹²⁵I-hCG was injected into four nonimmunized and seven immunized monkeys and blood was collected at frequent intervals over 7 days. Total and immunoprecipitable radioactivity did not differ significantly, suggesting that the radioactivity in the plasma consisted almost entirely of ¹²⁵I-hCG. This was confirmed by column chromatography. The MCR (mean ± SE) was significantly lower (p < 0.001) in six immunized monkeys (0.35 ± 0.06 liters/day) as compared to controls (1.19 ± 0.09 liters/day). The hCG disappearance curve in control monkeys was best described by a two-compartmental system (slow and fast) while an additional third (intermediate) compartment of distribution was typical for immunized animals. The half-lives of hCG for the two exponentials corresponding to the slow and fast components of distribution were not significantly different between the two groups. One immunized monkey had a MCR (1.44 liters/day) that was much greater than the MCR of the other six. This monkey cleared a significantly smaller proportion of hCG in the slow and a higher proportion in the intermediate compartment and unlike the others, formed a circulating immune complex capable of binding hCG that was significantly larger than the antibody-hCG complexes found in the other six immunized animals. We conclude that circulating antibodies to oLHβ reduced the MCR of hCG in six of seven monkeys. The decreased MCR found in immunized monkeys is associated with a shift in clearance from the “fast” to the “slow” compartment as well as the addition of an intermediate compartment of distribution. Plasma disappearance rates of hCG depend on the size of the antibody hCG complex.     

Diagnosing fibrotic lung disease: When is high‐resolution computed tomography sufficient to make a diagnosis of idiopathic pulmonary fibrosis?

Idiopathic pulmonary fibrosis (IPF), a progressive and fatal diffuse parenchymal lung disease, is defined pathologically by the pattern of usual interstitial pneumonia (UIP). Unfortunately, a surgical lung biopsy cannot be performed in all patients due to comorbidities that may significantly increase the morbidity and mortality of the procedure. High-resolution computed tomography (HRCT) has been put forth as a surrogate to recognize pathological UIP. The quality of the HRCT impacts the ability to make a diagnosis of UIP and varies based on the centre performing the study and patient factors. The evaluation of the HRCT includes assessing the distribution and predominance of key radiographical findings, such as honeycomb, septal thickening, traction bronchiectasis and ground glass attenuation lesions. The combination of the pattern and distribution is what leads to a diagnosis and associated confidence level. HRCT features of definite UIP (subpleural, basal predominant honeycomb with septal thickening, traction bronchiectasis and ground glass attenuation lesions) have a high specificity for the UIP pathological pattern. In such cases, surgical lung biopsy can be avoided. There are caveats to using the HRCT to diagnose IPF in isolation as a variety of chronic pulmonary interstitial diseases may progress to a UIP pattern. Referral centres with experience in diffuse parenchymal lung disease that have multidisciplinary teams encompassing clinicians, radiologists and pathologists have the highest level of agreement in diagnosing IPF.     

MISSED ANTERIOR CROSSING VESSELS DURING OPEN RETROPERITONEAL PYELOPLASTY: LAPAROSCOPIC TRANSPERITONEAL DISCOVERY AND REPAIR

PURPOSE: Extrinsic ureteropelvic junction obstruction due to anterior crossing segmental renal vessels is present in more than 50% of patients in adulthood. In this situation the ureter must usually be dismembered and transposed anterior to the crossing vascular structures, where it is anastomosed to the renal pelvis. Via the open retroperitoneal approach there may be a limited view of the anterior surface of the ureteropelvic junction and, hence, anterior crossing vessels may possibly be missed. We describe 2 patients with ureteropelvic junction obstruction in whom anterior vessels were missed during open retroperitoneal repair. Laparoscopic transperitoneal secondary pyeloplasty with posterior displacement of the crossing renal vessel was performed in each case. MATERIALS AND METHODS: Two patients presented with symptomatic congenital ureteropelvic junction obstruction after failed endopyelotomy in 1 and failed open retroperitoneal procedures in both. Preoperatively spiral computerized tomography angiography with a ureteropelvic junction protocol revealed crossing vessels in the 2 cases. This finding was confirmed at transperitoneal laparoscopic pyeloplasty. The ureter and renal pelvis were transposed anterior to the crossing vessels and 2 rows of running sutures were placed to complete the anastomosis. RESULTS: The 2 laparoscopic procedures were completed successfully. The anterior crossing vessels were preserved in each case. Currently the patients are asymptomatic and furosemide washout renal scan was normal. CONCLUSIONS: Spiral CT angiography reliably delineates the renal vascular anatomy in patients with ureteropelvic junction obstruction. This study may be valuable before planned open retroperitoneal ureteropelvic junction obstruction repair. Laparoscopic pyeloplasty may successfully manage anterior crossing vessels associated with secondary ureteropelvic junction obstruction.     

A 90-Day Subcutaneous Toxicity and Fertility Study of a LHRH Antagonist in Rats

A 90-Day Subcutaneous Toxicity and Fertility Study of a LHRHAntagonist in Rats. SUNDARAM, K., DIDOLKAR, A. K., KEIZER-ZUCKER,A., DEJESUS, W., RIVIER, J., VALE, W., AND BARDIN, C. W. (1990).Fundam. Appl. Toxicol. 14, 734–744. [Ac-D2Nal¹,4Cl-DPhe²,D3Pal³,Arg⁵,DGlu⁶(anisole adduct),DAla¹⁰]-GnRH (Nal-Glu) is an antagonist ofLHRH and has the potential to be utilized as an antigonadalagent. A study was undertaken to evaluate the toxicologicaleffects of Nal-Glu in rats. Nal-Glu, dissolved in 5% mannitolin water containing 9 ml/liter benzyl alcohol, was administeredsubcutaneously. In subchronic studies, groups of 12 male and12 female rats received 0, 50, 250, or 1250 µg/kg bodyweight (BW) Nal-Glu for 90 days and were killed on Day 91. Additionalgroups of male and female rats were given the high dose of Nal-Glu(1250 µ/kg BW) or vehicle for either 30 or 90 days. Theirfertility was assessed by mating them with normal animals. Unlikesome other LHRH antagonists, Nal-Glu exhibited a low potencyfor causing in vitro histamine release from rat peritoneal mastcells. Furthermore, in acute In vivo studies, Nal-Glu was lessactive in the induction of peripheral edema. In the subchronicstudy, all doses of Nal-Glu were well tolerated and there wereno apparent systemic toxic effects. The pharmacological effectsof Nal-Glu were quite evident, however. Nal-Glu treatment ledto a significantly decreased body weight gain in the males anda significantly increased body weight gain in the females. Therewas a dose-dependent decrease in weights of gonads and reproductiveorgans in both the sexes. Some of the hematological and serologicalparameters were significantly different in Nal-Glu-treated animals.However, most of the values were within the normal range andare considered to be of no toxicological significance. Histopathologicalevaluations were made in the control and high-dose groups only.In the male, a seminiferous tubular degeneration and atrophyof the interstitial cells was seen. The prostate and seminalvesicles were also atrophied and the epididymides were devoidof spermatozoa. In the females, the ovaries and uteri were atrophic.The injection site of Nal-Glu-treated rats had inflammatorychanges indicative of a local irritating action of the drug.All other tissues had normal histomorphology. Both male andfemale rats became infertile when 1250 MgAg Nal-Glu was administeredfor 30 days. Normal fertility was restored 8 weeks after cessationof 90-day treatment. It is concluded that repeated administrationof Nal-Glu leads to reversible infertility in both male andfemale rats. Although it was irritating at the site of injection,Nal-Glu had no systemic toxicological effects.     

Chain phase trajectory of a protein molecule

This paper presents the profile map of a protein conformation as a three-dimensional e-ø plot, where the third dimension is the residue number. The trajectories of some proteins of known crystalline structure, a few super-secondary structures in proteins and valinomycin in conformational space are presented and examined. A graphic code for amino acids based on physico-chemical considerations is devised as part of the present scheme. The representation presented here is useful in correlating primary structure with tertiary fold, intricate sequentially correlated structural features and for the comparison of different conformations of the same or similar polymers.     

Long-Term Immunization Against the β-Subunit of Ovine Luteinizing Hormone (oLHβ) Has No Adverse Effects on Pituitary Function in Rhesus Monkeys

ABSTRACT: One postulated safety hazard of contraceptive methods based on immunization against gonadotropic hormones is the possibility that circulating antibodies which crossreact with pituitary hormones may impair pituitary function through the deposition of immunoglobulin and/or complement suggesting immune complexes. In order to evaluate this possibility in rhesus monkeys actively immunized against the β-sub-unit of ovine luteinizing hormone (oLHβ), we used three approaches to study the effects of long-term immunization on pituitary function: a) evaluation of pituitary responsiveness to challenge with a GnRH-agonist; b) examination of pituitary histology and immunostaining with gonadotropin antisera; and c) examination of pituitary cells for deposition of immune complexes. Our results indicate that circulating anti-oLHβ antibodies did not result in significant impairment of pituitary function in rhesus monkeys.     

Specificity of spatial clustering of amino acid residues as an evolutionary trend in proteins

Three-dimensional structures of cytochrome c and myoglobin molecules together with amino acid substitution data on these proteins from a close range of taxa highlight an interesting evolutionary trend. Assuming three-dimensional structures of homologous proteins to be largely similar, the distribution of amino acid residue types around one another was studied. The application of information theory to three dimensional arrangement of amino acid residues revealed that in general, the higher the taxonomic order, the more specific is the clustering of residue types with one another.