Role of inter-α-inhibitor and its related proteins in urolithiasis. Purification of an inter-α-inhibitor related protein from the bovine kidney

Urine contains several macromolecules that inhibit calcium oxalate (CaOx) crystallization. Among them is bikunin, the light chain of most of the inter-α-inhibitor (IαI) family of glycoproteins. This study aimed to verify whether bikunin and other members of the IαI family are synthesized in the kidneys or derived exclusively from the plasma. Proteins extracted from homogenized bovine kidney were applied successively to three chromatographic steps on DEAE-Sephacel, Sephacryl S-300, and Mono Q column. The inhibitory activity was assayed using a CaOx crystallization system. The presence of IαI-related proteins was determined by␣electrophoresis and Western blotting. The results showed that kidney extract contained a 125-kDa protein that cross-reacted with anti-IαI antibodies. This protein inhibited CaOx crystallization efficiently. According to its molecular weight and immunoreaction with anti-IαI antibody, the 125-kDa protein could be pre-α-inhibitor. The latter is known to encompass a heavy chain and bikunin, which may explain its inhibitory activity against CaOx crystallization. Consequently, we hypothesize that kidneys may produce some IαI-related proteins that are involved in the inhibition of stone formation. Received: 18 February 1998 / Accepted: 9 July 1998     

Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy.

The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor-derived cell line.     

Acetabular fractures before and after the introduction of seatbelt legislation

Objectives

To compare the incidence and severity of acetabular fractures and associated injuries before and after seatbelt legislation.

Design

A retrospective study.

Setting

Two major trauma centres, which are teaching hospitals.

Patients

Three hundred and ninety-three patients who sustained acetabular fractures during the 5 years before and 5 years after seatbelt legislation was enacted. Of these, the fractures in 198 patients (50.4%) resulted from a motor vehicle accident.

Main Outcome Measures

The number and severity of acetabular fractures and associated injuries.

Results

There has been a significant reduction in the number of acetabular fractures (p = 0.005) since seatbelt use became mandatory, and the complexity of the fractures has decreased. There has also been a marked reduction in associated injuries, such as fractures of other bones, and head, chest and abdominal injuries (p < 0.001).

Conclusion

The seatbelt law has been a useful preventive measure, resulting in a reduction in the incidence of acetabular fractures and associated injuries.     

Grafted fetal suprachiasmatic nucleus cells survive much better in tissue pieces than in suspension

A comparison was made between the survival of fetal suprachiasmatic nucleus (SCN) grafted either in tissue pieces or as tissue suspension. Donor tissue was obtained from day 15, 16 or 17 Wistar fetuses, and stereotaxically placed in the dorsal thalamus of the brain of vasopressin(VP)-deficient Brattleboro adult rats. One month post-grafting, the suspension grafts largely failed to show the immunocytochemical presence of VP- and vasoactive intestinal polypeptide(VIP)-producing SCN cells, but solid piece grafts did. In the suspension grafts only a few tiny clusters of surviving VP SCN neurons were seen and hardly any VIP cells. This suggests that intrinsic contacts are necessary for SCN cells to survive and/or to express their genotype. Efferent VP fiber growth was observed to run from the tissue piece derived SCN grafts towards the periventricular area of the thalamus, a nearby SCN projection area. However, the number of VP efferents was very limited and not consistently present. Surprisingly, magnocellular VP neurons, also present in the fetal SCN grafts, showed an opposite survival pattern. Several of such cells were seen in day 15 suspension grafts, whereas hardly any were found in day 15 tissue piece grafts. These results indicate that the type of graft preparation might be important when survival of particular cells is desired.     

Vertebral artery dissection: warning symptoms, clinical features and prognosis in 26 patients

BACKGROUND AND OBJECTIVES: Internal carotid artery dissection has been extensively studied and well-described. Although there has been a recent increase in the number of reported cases of vertebral artery (VA) dissection, the clinical variety of presentation and the early warning symptoms have not been well-described before. Our objectives in this study include: (1) To determine the early symptoms and warning signs which may help the clinician in the early identification and treatment of patients with VA dissection. (2) To explore the variety of clinical presentation of VA dissection and its relation to prognosis. DESIGN AND SETTING: Retrospective analysis of hospital records in a tertiary academic centre for the period 1989-1999. RESULTS: Twenty-six patients were identified (13 men and 13 women). The mean age was 48. Possible precipitating factors were identified in 14 patients (53%). Sporting activity and chiropractic manipulations were the most common (15% and 11% respectively). Headache and/or neck pain was the prominent feature in 88% of patients and was a warning sign in 53%, preceding onset of stroke by up to 14 days. The most common clinical features included vertigo (57%), unilateral facial paresthesia (46%), cerebellar signs (33%), lateral medullary signs (26%) and visual field defects (15%). Bilateral VA dissection presented in six patients (24%). The most common region of dissection was the C1-C2 level (16 arteries, 51%). Intracranial VA dissection was found in eight arteries (25%). The majority of patients (83%) had favorable outcome. Poor prognosis was associated with (1) bilateral dissection; (2) intracranial VA dissection accompanied by subarachnoid hemorrhage. Only two patients reported stroke recurrence. CONCLUSIONS: Our findings show that VA dissection affects mainly middle age persons and involves both sexes equally. Headache and/or neck pain followed by vertigo or unilateral facial paresthesia is an important warning sign that may precede onset of stroke by several days. Although the majority of patients will have excellent prognosis, this was less likely in patients presenting with subarachnoid hemorrhage or bilateral VA dissection. Recurrence rate was low.     

Cochlear implant outcomes and quality of life in the elderly: Manchester experience over 13 years1

Objectives: To objectively evaluate the clinical and functional outcomes of cochlear implantation in an elderly population. Design: Retrospective comparative study. Setting: Neurotology unit at Manchester Royal Infirmary, a supraregional tertiary referral centre in collaboration with Adult Cochlear Implant Programme at The University of Manchester. Participants: All cochlear implant procedures (38) undertaken on post‐lingually deafened elderly patients (age range at the time of implantation 65–80 years, n = 34) in the period from 1989 to 2002. Main outcome measures: Medical and surgical outcomes. Audiological performance outcomes for isolated words, words in sentences in quiet and noise. Functional outcome measures used are self‐reported measures of the social, psychological and emotional aspects of quality of life, and the differences between expectations for functional outcomes and the realization of functional outcomes. They included expectation profiles, Glasgow Benefit inventory (GBI) and Glasgow Health Status Inventory Questionnaire (GHSI). Results: There was statistically significant improvement post‐implantation of both open and closed set test scores (P < 0.01). Eighty‐two percentage of patients were completely satisfied with their cochlear implants. Patients judged that implantation restored half the loss of quality of life that they had experienced as a result of severe‐profound deafness with a highly significant (P < 0.001) improvement in overall quality of life after implantation. The commonest post‐operative observation was transient mild pyrexia. Conclusions: The age of a cochlear implant candidate should not be a factor in the candidacy decision‐making process. The quality of life of our elderly recipients was significantly improved after cochlear implant.     

The prevalence, classification and treatment of mental disorders among attenders of native faith healers in rural Pakistan

  Background: Although native faith healers are found in all parts of Pakistan, where they practice in harmony with the cultural value system, their practice is poorly understood. This study investigated the prevalence, classification and treatment of mental disorders among attenders at faith healers. Method: The work of faith healers with 139 attenders was observed and recorded. The mental status of attenders was assessed using a two-stage design: screening using the General Health Questionnaire followed by diagnostic interview using the Psychiatric Assessment Schedule. Results: The classification used by faith healers is based on the mystic cause of disorders: saya (27%), jinn possession (16%) or churail (14%). Sixty-one percent of attenders were given a research diagnosis of mental disorder: major depressive episode (24%), generalized anxiety disorder (15%) or epilepsy (9%). There was little agreement between the faith healers' classification and DSM-IIIR diagnosis. Faith healers use powerful techniques of suggestion and cultural psychotherapeutic procedures. Conclusions: Faith healers are a major source of care for people with mental health problems in Pakistan, particularly for women and those with little education. Further research should assess methods of collaboration that will permit people with mental health problems to access effective and culturally appropriate treatment. Accepted: 9 June 2000     

Post‐COVID‐19 splenic infarction in a patient with chronic atrial fibrillation: A case report

We describe splenic infarction (SI), an infrequent condition, in an 82‐year‐old COVID‐19 patient with chronic atrial fibrillation (AF). COVID‐19 may cause thrombosis, and AF is a predisposing factor for splenic infarction. Suspicion of SI may be warranted in COVID‐19 patients with abdominal pain, especially if a predisposing factor exists.     

Synthesis and free radical scavenging activity of coumarin derivatives containing a 2-methylbenzothiazoline motif

Coumarin and benzothiazole scaffolds can be found in a number of natural or synthetic antioxidants. In an effort to develop a novel radical scavenger and potential antioxidant, a series of coumarin derivatives containing 2‐methylbenzothiazoline motif and related compounds was synthesized and evaluated for their DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) and ABTS^?+ (2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) radicals scavenging activities. Among them, 7‐hydroxy‐3‐(2‐methyl‐2,3‐dihydrobenzo[d]thiazol‐2‐yl)‐2H‐chromen‐2‐one ( 3e ) has shown a significant free radical scavenging activity. From the structure–activity point of view, it was found that phenolic coumarin ring and benzothiazoline moiety in target compounds may contribute to the scavenging activity against free radicals.