Intra-articular injections and articular cartilage metabolism

Summary We studied the effects of repeated intra-articular injections of sterile 140 mM NaCl solution on articular cartilage in adult rabbits. After 20 injections into the knee joints over a period of 4 weeks, chondrocyte glucosaminoglycan synthesis was evenly reduced in all cartilage layers, accompanied by a significant proteoglycan depletion of the matrix which was most marked in the superficial half of the cartilage. These and other changes only partially reversed during a further 4-week period after the injections had been stopped. Our data underline the need for a clear-cut indication for intra-articular injections. The microtrauma caused by injection, in conjunction with the introduction of a carrier solution into the joint, may, at least when repeated at short intervals, lead to measurable damage to the articular cartilage.Recipient of grant no. Ne 308/1-1 from the Deutsche Forschungsgemeinschaft, Bonn, Germany     

Endogenous and recombinant erythropoietin levels decline in human amniotic fluid and fetal plasma in vitro at 37 degrees C.

OBJECTIVE: To determine the in vitro stability of endogenous and recombinant erythropoietin (EPO) incubated at 37 degrees C in amniotic fluid (AF) and fetal plasma. STUDY DESIGN: Endogenous and recombinant EPO in AF, fetal plasma and phosphate buffer were incubated in vitro for 21 days at 37 degrees C. Serial aliquots were analyzed for EPO and the rates of EPO decline were compared within and between groups. RESULTS: Endogenous and recombinant EPO declined significantly in plasma and AF at 37 degrees C. Endogenous EPO displayed a similar linear rate of decline in AF and plasma, with nearly 70% of the initial hormone concentration remaining at 21 days. Recombinant EPO incubated in buffer did not change. CONCLUSIONS: Using the rate of decline in endogenous EPO we observed, EPO levels measured in AF or plasma within 21 days of fetal demise can be extrapolated back to the level likely present at fetal death.     

Plasma Concentrations of Mycophenolic Acid Acyl Glucuronide Are Not Associated with Diarrhea in Renal Transplant Recipients

The aim of this study was to determine whether plasma concentrations of the acyl (AcMPAG) and phenolic (MPAG) glucuronide metabolites of mycophenolic acid (MPA) were related to diarrhoea in renal transplant patients on mycophenolate mofetil (MMF) with cyclosporine (CsA) or tacrolimus (TCL). Blood samples (0, 30, 120 min) were taken at days 3, 10, week 4, months 3, 6 and 12 for determination of MPA, MPAG and AcMPAG. MPA-AUC was estimated using validated algorithms. Two hour AUCs were calculated for MPAG and AcMPAG. Immunosuppressive therapy consisted of CsA/MMF (n= 110) and of TCL/MMF (n= 180). In 70/290 (24%) patients 86 episodes of diarrhoea were recorded during 12 months. Significantly more patients on TCL (31.1%) suffered from diarrhea compared to CsA (12.7%). MMF dose, MPA-AUC and the 2 h AUCs of MPAG and AcMPAG did not differ between patients with and without diarrhoea. Plasma AcMPAG and MPAG concentrations were substantially higher in patients on CsA compared with TCL, while MPA-AUC was lower in the former group. These data support the concept that CsA inhibits the biliary excretion of MPAG and AcMPAG, thereby potentially reducing the risk of intestinal injury through enterohepatic recycling of MPA and its metabolites.     

A questionable parasitic macular cyst

A 60 year old male patient is introduced who developed a loss of vision caused by chorioretinal cystic alteration in the macula of the left eye 9 months after a routine extracapsular cataract surgery with implantation of posterior chamber lens. There existed no other general symptoms, hematologic values and serology were regular. Having discussed literature the diagnosis of solitary Toxocara canis granuloma was produced.     

Case report: Concordant traumatic brainstem contusion delayed diagnosis in a young man with Wilson's disease

Wilson's disease is a hereditary autosomal recessive disorder of copper metabolism. The corresponding gene locus has been localized on the long arm of chromosome 13. Three different clinical variants of the disease can be distinguished: hepato-cerebral, abdominal/hepatic, and central nervous type. The heterogeneity of symptoms can cause problems in differential diagnosis, especially when another concordant disorder can also explain the pathogenesis of symptoms. The case report of a young man who suffered from brainstem contusion demonstrates the possibilities of misinterpretation because presenting symptoms could be attributed either to traumatic brain injury followed by adjustment disorder or Wilson's disease. Clinical signs included leftsided hemiparesis, bilateral gaze direction nystagmus, marked dysarthria with consecutive pervasive mutism, choreo-athetoid movements, spasmodic torticollis and diplopia dependent on gaze direction. Slit lamp examination showed Kayser-Fleischer's corneal ring. EEG- and computer assisted tomography investigations revealed non-specific findings. The patient was treated with D-Penicillamine. Alternative treatment with oral zinc preparations is discussed.

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Zusammenfassung Beim Morbus Wilson handelt es sich um eine autosomal rezessiv vererbte Störung des Kupferstoffwechsels. Der Genort konnte auf dem langen Arm des Chromosoms 13 lokalisiert werden. Klinisch können aufgrund ihrer Symptomatik drei Verlaufsformen (hepato-zerebraler, abdominalhepatischer und zerebraler Typ) unterschieden werden. Die Vielfalt der Symptome kann differentialdiagnostische Schwierigkeiten bereiten. Das Beispiel eines jungen Mannes mit einer traumatischen Hirnstammkontusion zeigt, wie die Diagnose der hepato-lentikulären Erkrankung dadurch erschwert wurde, daß die Pathogenese der Symptome durch die Hirnstammkontusion und darauf folgende Anpassungsstörungen erklärt worden war. Die Symptomatik bestand aus linksseitiger Hemiparese, lateralem Blickrichtungsnystagmus, Dysarthrie mit nachfolgendem universalem Mutismus, choreo-athetodischen Bewegungsstörungen, Torticollis spasmoidicus und blickrichtungsabhängigem Auftreten von Doppelbildern. Bei der Spaltlampenuntersuchung stellte sich der Kayser-Fleischer Ring dar. EEG- und computertomographische Untersuchungen erbrachten nur unspezifische Befunde. Die Behandlung erfolgte mit D-Penicillamin. Die alternative Behandlung mit oraler Gabe von Zinksalzen wird diskutiert.

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Résumé La maladie de Wilson est une affection héréditaire autosomale recessive concernant le métabolisme cuivré. Le locus du gène a été situé sur le bras long du chromosome 13. Du point de vue clinique on distingue trois formes symptomatologiques: le type hepato-cérébral, hepato-abdominal et cérébral. La diversité des signes cliniques peut poser des problèmes de diagnostic différentiel, car d'autres affections peuvent se présenter avec cette même Symptomatologie. Nous rapportons ici l'exemple d'un homme jeune, porteur d'une maladie de Wilson et victime d'une contusion traumatique du tronc cérébral, dont les signes cliniques ainsi que les troubles du comportement pouvaient été autant rapportés à la contusion du tronc cérébral qu'à l'affection métabolique.La Symptomatologie comprenait une hemiparesie gauche, un nystagmus lateralisé, une dysarthrie avec mutisme secondaire universel, des mouvements choréo-athétosiques, un torticolis spasmodique et une diplopie dépendante de la direction du regard. L'examen à la lampe à fente permettait à mettre en evidence un anneau de Kayser Fleischer. L'EEG et le scanner cérébral ne montraient pas d'anomalies specifique.Le traitement a consisté en l'administration de D-Penicillamine. Traitment alternative avec les sels de zinc est discuté.

     

Excess of DD homozygotes in haemodialysed patients with type II diabetes. The Diabetic Nephropathy Study Group

The role of the insertion/deletion polymorphism of the angiotensin- converting enzyme (ACE) gene in the genesis of diabetic nephropathy has been controversial. It has recently been proposed that progression occurs more rapidly in individuals with diabetic and non-diabetic renal disease who are homozygous for the D allele. We studied 658 patients with type II diabetes, 347 without diabetic nephropathy and 311 with various stages of diabetic nephropathy, and determined the I/D polymorphism of the ACE gene. Patients at the extremes of renal risk, i.e. normotensive patients without antihypertensive treatment and without nephropathy (n = 144), vs patients on dialysis (n = 61), differed with respect to genotype (DD 36.8% vs 57.4%; P = 0.007) and allele frequencies (D 0.59 vs 0.76; P < 0.001). In contrast, patients with and without presumed nephropathy as assessed by albuminuria did not differ with respect to DD genotype. In conclusion, in this study, which was limited by sample size, patients with the highest renal risk more frequently had the DD genotype. This would be compatible with a greater risk of (or rate of) progression to end-stage renal failure.      

Quantification of tricuspid insufficiency--comparison of Doppler echocardiography and radionuclide ventriculography]

In 40 patients (pts) (ages 34-83 years) the severity of tricuspid regurgitation (TR) was graded by pulsed Doppler echocardiographic determination of regurgitant jet extension. Mild TR was assessed in seven pts (group I), mode-rate TR in 20 pts (group II), and severe TR in 13 pts (group III). The enddiastolic diameter of the left ventricle as measured by M-mode-echocardiography was 55 +/- 16 mm in group I, 48 +/- 6 mm in group II, and 50 +/- 10 mm in group III. The regurgitant index (RI), i.e., the ratio of left-to-right-ventricular stroke counts (normal range 0.89-1.97) and the time-activity curve over the liver area were measured by equilibrium radionuclide ventriculography (RNV). The RI differed significantly between group I (1.6 +/- 0.5), II (1.0 +/- 0.3), and III (0.8 +/- 0.3) (p less than 0.01). An RI-value below 0.89 as an index of right-ventricular volume overload was found in 14% (group I), 45%, (group II) and 77% (group III). The time-activity curve over the liver area, as graded by count variation in phase with the right atrium from 1 (no count variation) to 4 (typical count variation) showed all grades in groups I and II, but only grade 2 to 4 in group III. The RI resp. the time-activity curve over the liver is a sensitive parameter for the detection of moderate to severe TR. If TR is ascertained, severe regurgitation can be differentiated from mild regurgitation by RNV-derived RI as an index of right-ventricular volume overload.