Autistic symptoms in a child with congenital cytomegaloviras infection

A case of intrauterine cytomegalovirus infection with onset of autistic symptoms apparently after 6 months of age is reported. Physicians who find autistic symptoms in very young children might include cytomegalovirus in their differential to document the presence or absence of a correlation.     

CCK2 gastrin receptor as a potential target for therapy in leukaemia cell lines

The gastrin CCK2 pathway has been implicated in the development of various cancers including leukaemia. An autocrine or intracrine pathway may exist in the leukaemia cell that is involved in stimulating proliferation. We tested four leukaemia cell lines, KU812, ML-1, MOLT-4 and U937 for the existence of the CCK2 receptor and gastrin precursor protein using immunoblotting. We also assessed the effect of CCK2 antagonist PD 135 and both gastrin 17 and glycine-extended gastrin on the proliferation of the cell lines. We found immunoreactive CCK2 and gastrin precursors present in all 4 cell lines. We also observed a stimulatory effect on proliferation by gastrin and glycine-extended gastrin on 2 and 3 of the cell lines respectively and an inhibitory effect of PD 135 on all 4 cell lines. These results demonstrate that the gastrin-gastrin receptor axis is a potential target for new therapeutic strategies.     

Correlation between macroscopic changes of arthrosis and the posterior cruciate ligament histology in the osteoarthritic knee

BACKGROUND: There is ongoing debate about the role of the posterior cruciate ligament (PCL) in total knee arthroplasty. Advocates of PCL retention cite better soft tissue balance and improved proprioception, whereas opponents report late flexion instability. The results of knee replacement are similar whether the PCL is retained or sacrificed. The aim of the present study was to examine the PCL for histological changes that would infer its competence and correlate these with changes easily observed by the operating surgeon. METHODS: A prospective study of 50 osteoarthritic knees was performed. RESULTS: Histology of the PCL showed changes secondary to degeneration and trauma. In most of the ligaments examined, arteriosclerosis and fibrosis were present. Half of the PCL examined showed perineural fibrosis, myxoid change and hyalinization. These changes, although very frequent, did not correlate well to the changes observed in either the anterior or PCL, or in the overall severity of osteoarthrosis. CONCLUSIONS: Posterior cruciate ligaments usually show degenerative and chronic traumatic change of varying degrees on histology. The changes are not predictable from inspection of the knee at surgery. The frequency of these changes suggests that many osteoarthritic PCL are of indifferent quality and the surgeon should consider this when choosing the style of knee replacement.     

Safety and cost benefits of bilateral total knee replacement in an acute hospital

BACKGROUND: Total knee arthroplasty of both knees under the one anaesthetic has become a common procedure. Benefits reported include a shorter overall hospital stay and reduced costs. The published studies come from university associated tertiary referral hospitals with well-established research establishments and a vast experience of joint replacement. This study examines the experience of a small hospital to see if similar benefits can be achieved. METHODS: A retrospective medical record review was performed of the synchronous bilateral knee replacements against a match group of bilateral staged knee replacements. Both groups were compared with a control group of unilateral knee replacements. A prospectively conducted review of the synchronous and staged bilateral knee replacement groups was then carried out to assess the clinical outcome in these two groups. RESULTS: The incidence of surgical and medical complications was not statistically different in any group. The bed stay for bilateral surgery was increased by 2 days compared to unilateral surgery with a net saving of 6 days hospital stay for the patient group having both knees replaced at separate operations within 1 year. At an average of 2.5 years post surgery there was no statistically significant difference in outcome between those patients who had both knees replaced either synchronously or at staged intervals. CONCLUSIONS: Bilateral knee replacement is a good choice for patient and hospital. Bilateral surgery does not increase the risk of perioperative complications to the patient and reduces the overall cost to the hospital. There is no difference in short to medium term clinical outcome between patients who have had both knees replaced synchronously or at staged intervals. Results comparable in safety, as judged by complication rates and efficiency, as judged by length of stay can be achieved in a smaller metropolitan level 2 hospital environment.     

Human galanin (GAL) and galanin 1 receptor (GALR1) variations are not involved in fat intake and early onset obesity

The neuropeptide galanin (GAL) is involved in food intake and in fat ingestion. Presumably, these effects are conveyed via the galanin 1 receptor (GALR1). We screened the coding region of GAL (including 444 bp of its promoter region) and GALR1 for mutations using single-strand conformation polymorphism analysis and denaturing HPLC in up to 191 obese children and adolescents and 106 healthy underweight young adults (students). In GAL, we identified 3 novel single nucleotide polymorphisms (SNPs; silent: g.-419T-->C, g.-244G-->A; missense: g.47C-->T: Ala16Val) and one infrequent missense variation (c.253A-->G: Asn85Asp), and in GALR1 2 novel SNPs (silent: c.150C-->T, missense: c.793A-->T: Ile265Phe). To test for an association with obesity, we genotyped 7 SNPs (GAL: g.-244G-->A, g.47C-->T, rs7101947, rs1042577, rs3136540; GALR1: c.150C-->T, c.793A-->T) in up to 322 obese children and adolescents compared with up to 277 healthy underweight and normal weight young adults. Furthermore, we analyzed these SNPs with respect to potential effects on the percentage of energy consumed as fat in obese children and adolescents. Allele and genotype frequencies did not differ among the groups tested. In addition, we performed a pedigree transmission disequilibrium test (PDT) for one SNP (GAL: g.-244G-->A) in 610 (518 independent) obesity-trios (obese child or adolescent and both of its parents). However, the PDT for SNP GAL g.-244G-->A revealed no transmission disequilibrium. We conclude that the analyzed SNPs in GAL and GALR1 do not play a major role in early onset obesity or dietary fat intake in the obese children and adolescents of our study groups.     

Loss of Insulin Resistance after Roux-en-Y Gastric Bypass Surgery: a Time Course Study

Background: Gastric bypass has repeatedly been shown to improve and even cure type 2 diabetes by substantially improving insulin resistance. The mechanism by which it achieves this is not currently known, but some have hypothesized that there may be important humoral effects brought about by the bypass of the stomach, duodenum or proximal jejunum. A better understanding of the time course of the changes in insulin resistance after surgery might assist our understanding of potential mechanisms. Methods: Intravenous glucose tolerance tests (IVGTT) were performed in 26 severely obese patients on the morning of gastric bypass surgery and again 6 days later. In addition insulin resistance was assessed in 71 patients undergoing gastric bypass surgery by the homeostasis model assessment (HOMA) method before surgery, and again at 6 days, 3, 6, 9, and 12 months. Patients were divided into 3 groups for analysis: diabetics, impaired glucose tolerance and normal glucose tolerance. Results: All 3 groups of patients were noted to have insulin resistance prior to surgery. This was greatest in the diabetic patients, as indicated by HOMA. There was marked loss of/improvement in insulin resistance within 6 days of gastric bypass by both IVGTT and HOMA methods in all groups, which was maintained over the 12-month period. The study included 31 diabetic patients, of whom only 3 required medication following hospital discharge. Conclusion: The changes in insulin resistance seen after gastric bypass, which are responsible for the resolution or improvement of type 2 diabetes occur within 6 days of the surgery, before any appreciable weight loss has occurred. This finding has implications for our understanding of the mechanism of insulin resistance in severely obese patients and is consistent with a humoral mechanism emanating from the GI tract.     

Participatory action research to understand and reduce health disparities

Participatory action research (PAR) is an excellent way to systematically learn about the conditions under which people experience health disparities, what it is like from the perspective of those experiencing such disparities and, even more importantly, how to ameliorate this major public health problem and create a more equitable and effective health care system. This article describes the method of PAR, supports the appropriateness of PAR to learn about and reduce health disparities, and then presents some specific examples of research projects that have employed or are planning to employ PAR. These examples are from the work of several authors of this article, who are members of an interdisciplinary working group that serves as a forum for discussion of issues related to qualitative research methods and facilitates the development of qualitative studies. All of the authors of this article are part of a task force of this working group that is focusing specifically on community outreach with the goal of reducing health disparities within specific communities.     

Some in vitro and in vivo studies of a new angiotensin I-converting enzyme inhibitor [[S-(R*), S*]-1-[(3-acetylthio)-3-benzoyl-2-methylpropionyl]-L-proline] (CL 242,817) in comparison with captopril

Some in vitro and in vivo properties of CL 242,817, a new angiotensin l-converting enzyme (ACE) inhibitor, were studied and compared to those of captopril. In vitro CL 242,817 effectively inhibited rabbit lung ACE (IC50 54.9 nM), angiotensin l (Al)-induced contractions (IC50 0.82 μM), and potentiated bradykinin (BK)-induced contractions (EC50 0.383μM) of the guinea pig ileum. In these systems, CL 242,817 was approximately 3.5, 27, and 96 times less effective than captopril, respectively. In vivo, equimolar oral doses of CL 242,817 (8.36 mg/kg) and captopril (5 mg/kg) were equieffective in inhibiting the pressor responses to intravenously (i.v.) administered angiotensin l (Al) in normotensive rats and dogs. Similar equimolar oral doses of CL 242,817 and captopril were also equieffective in potentiating the depressor responses to i.v. administered BK in the rat. In the anesthetized dog 30 min after dosing, captopril (0.5 mg/kg i.v.) produced significantly greater potentiation of the BK response than a similar dose of CL 242,817. A single 1 mg/kg i.v. dose of Cl 242,817 or captopril effectively lowered mean arterial blood pressure of the aortic-coarcted hypertensive rat (AHR) and markedly inhibited serum ACE activity after 1 hr. Serum from AHR treated with CL 242,817 or captopril exhibited an apparent loss in ACE inhibition upon cold storage. However, the loss of inhibition of ACE activity was faster with captopril than with CL 242,817. Kinetic studies indicate that CL 242,817 is a pure competive inhibitor of ACE with an estimated Ki of 24.3 nM.