Patellofemoral joint: kinematic MR imaging to assess tracking abnormalities

The patellofemoral joint was imaged with magnetic resonance (MR) in the axial plane while the knee was positioned from 0 degrees to 32 degrees of flexion (nine positions). These multiple sequential images obtained within the early phases of flexion of the knee were viewed in a "cine-loop" format, producing a kinematic study that clearly demonstrated the relationship of the patella to the trochlear groove. Four healthy subjects and one patient with known bilateral subluxing patellae were studied. The preliminary results suggest that kinematic MR imaging of the patellofemoral joint is potentially useful for the evaluation of patellar tracking abnormalities.     

A model of spatial localization and its application to strabismus

Visually guided, spatially oriented behavior involves an ongoing integration of signals regarding the loci of the retinal images and the position and orientation of the eye. In the strabismic this requires an altered spatial metric resulting from a functional readaptation to avoid confusion and diplopia. A comparator mechanism for evaluating these two signals is presented. A case report using "disruptive" therapeutic procedures that deliberately alter the strabismic's visual-postural control system is presented. A treatment plan for altering the anomalous binocular link, a characteristic of the well adapted strabismic, is described and related to the comparator mechanism.     

Malakoplakia of the adrenal gland.

The clinical and pathological features of a case of malakoplakia of the adrenal gland occurring in a woman with Escherichia coli infection are described. This lesion mimicked a neoplasm, the true diagnosis only being revealed by histological examination. The light and electron microscopic features are described and it is suggested that malakoplakia is due to an abnormal macrophage response to E coli infection.     

Growth hormone benefits children with 18q deletions

Most individuals with constitutional deletions of chromosome 18q have developmental delays, dysmyelination of the brain, and growth failure due to growth hormone deficiency. We monitored the effects of growth hormone treatment by evaluating 23 individuals for changes in growth, nonverbal intelligence quotient (nIQ), and quantitative brain MRI changes. Over an average of 37 months, the treated group of 13 children had an average nIQ increase of 17 points, an increase in height standard deviation score of 1.7, and significant change in T1 relaxation times in the caudate and frontal white matter. Cognitive changes of this magnitude are clinically significant and are anticipated to have an effect on the long-term outcomes for the treated individuals.     

Randomized, open-label study of the impact of two doses of subcutaneous recombinant interleukin-2 on viral burden in patients with HIV-1 infection and CD4+ cell counts of > or = 300/mm3: CPCRA 059

The effect of intermittent courses of recombinant interleukin-2 (rIL-2) on HIV-1 load in patients receiving combination antiretroviral therapy remains uncertain. CPCRA 059 was an open-label, randomized, multicenter trial in which 511 patients with HIV-1 infection and CD4+ cell counts of > or = 300/mm3 who were receiving antiretroviral therapy were assigned to receive no rIL-2 (255 patients [controls]) or subcutaneous rIL-2 in dosages of 4.5 MIU (130) or 7.5 MIU (126) twice daily for 5-day courses every 8 weeks to maintain CD4+ cell counts that were twice the baseline value or > or = 1,000/mm3. The primary objective of this study was to compare the effects of the two doses of rIL-2 and no rIL-2 on viral load and CD4+ cell counts over 12 months. There was no difference in the following viral load measurements between the rIL-2 treatment groups and the control treatment group: percentage of patients with viral loads of <50 copies/mL at 12 months (p =.55), time to viral load of > or = 50 copies/mL for patients who had baseline viral loads of <50 copies/mL (p =.35), and change in viral load from baseline for patients who had viral loads of > or = 50 copies/mL at baseline (p =.63). At each follow-up visit, the change in CD4+ cell count from baseline was significantly greater in the rIL-2 treatment groups than in the control treatment group, with a mean difference of 251/mm3 at month 12 (95% confidence interval, 207-295; p <.0001). No unanticipated adverse experiences were seen in this trial, to our knowledge the largest randomized evaluation of rIL-2 treatment conducted to date.     

Action of gold salts in some inflammatory and immunological models

Several gold salts were compared in kaolin-induced rat paw oedema, u.v. erythema in guinea pigs, delayed type hypersensitivity and humoral immunity in mice, and adjuvant-induced arthritis in the rat. In the latter the additional parameters of serum gold and copper levels and lysosomal enzyme activity were determined. In addition, the in vitro inhibition of several lysosomal enzymes derived from mouse macrophages was studied. The gold compounds examined were aurothiomalate, aurothioglucose, triethylphosphine gold chloride (SK & F 36914) and its glucopyranoside derivative (SK & F D-39162), triphenylphosphine gold chloride and sodium gold chloride dihydrate.SK & F 36914 and SK & F D-39162 had significant activity after oral dosage upon paw kaolin and u.v. erythema in rats and guinea pigs, respectively. Gastric swelling also occurred.In Wistar rats, adjuvant arthritis was little affected by the gold salts but in the Lewis rats there was suppression. In both strains there was less elevation in serum copper levels with treatment by SK & F 36914 and SK & F D-39162, but not by aurothiomalate.None of the compounds had any measurable effect on delayed hypersensitivity or humoral antibody levels in mice.The in vitro activities of cathepsin B₁ and cathepsin D were inhibited by all the gold compounds. Reactivity of gold dependent on compound solubility and the nature of the gold ligand.Considerable differences exist between the profiles of activity for the different gold salts evaluated.These observations indicate that some gold salts do possess anti-inflammatory activity with a potency similar to that of indomethacin.     

102T/C polymorphism of serotonin receptor type 2A gene is not associated with schizophrenia in either Chinese or British populations

Several pieces of evidence implicate serotonin receptors in the aetiology of schizophrenia, and recently a number of studies have reported a genetic association between the 102T/C polymorphism of serotonin receptor type 2A gene and schizophrenia. Unfortunately a number of failures to replicate these positive associations in both Caucasian and Chinese populations have also been reported. We have examined the 102T/C polymorphism by PCR amplification and restriction analysis of DNA from: 202 schizophrenics and 202 controls from Shanghai; 112 schizophrenics and 224 parents from Chengdu, Cina; and 253 schizophrenics and 244 controls from the the UK. We find no evidence of association or transmission disequilibrium between the 102T/C polymorphism and schizophrenia in any of the groups we have examined. We conclude that either the original positive reports occurred by chance or any effect must be minimal, and urge caution in interpreting small positive results derived using data from different centres.     

Cathepsin-D expression in cervical carcinoma and its prognostic significance

An immunohistochemical study was made of cathepsin-D protein expression in each of the three main types of uterine cervical carcinoma (squamous carcinoma, adenosquamous carcinoma and adenocarcinoma) with particular reference to lymph node status and prognosis. Of the 61 cases, 54.1% showed cytoplasmic staining in more than 2.5% of tumour cells counted. Cathepsin-D expression was significantly higher in adenocarcinoma (mean -3.128) than in squamous carcinoma and adenosquamous carcinoma (mean –3.709,P=0.047 using logit transformation). Cathepsin-D had no prognostic value in any of the three tumour types. No relationship was found between cathepsin-D staining and lymph node status and there was no advantage in adding cathepsin-D values to lymph node status. These results suggest that immunostaining for cathepsin-D protein expression is unlikely to be of use as a prognostic marker.     

Voltage-dependent, pertussis toxin insensitive inhibition of calcium currents by histamine in bovine adrenal chromaffin cells

Histamine is a known secretagogue in adrenal chromaffin cells. Activation of G-protein linked H(1) receptors stimulates phospholipase C, which generates inositol trisphosphate leading to release of intracellular calcium stores and stimulation of calcium influx through store operated and other channels. This calcium leads to the release of catecholamines. In chromaffin cells, the main physiological trigger for catecholamine release is calcium influx through voltage-gated calcium channels (I(Ca)). Therefore, these channels are important targets for the regulation of secretion. In particular N- and P/Q-type I(Ca) are subject to inhibition by transmitter/hormone receptor activation of heterotrimeric G-proteins. However, the direct effect of histamine on I(Ca) in chromaffin cells is unknown. This paper reports that histamine inhibited I(Ca) in cultured bovine adrenal chromaffin cells and this response was blocked by the H(1) antagonist mepyramine. With high levels of calcium buffering in the patch pipette solution (10 mM EGTA), histamine slowed the activation kinetics and inhibited the amplitude of I(Ca). A conditioning prepulse to +100 mV reversed the kinetic slowing and partially relieved the inhibition. These features are characteristic of a membrane delimited, voltage-dependent pathway which is thought to involve direct binding of G-protein betagamma subunits to the Ca channels. However, unlike virtually every other example of this type of inhibition, the response to histamine was not blocked by pretreating the cells with pertussis toxin (PTX). The voltage-dependent, PTX insensitive inhibition produced by histamine was modest compared with the PTX sensitive inhibition produced by ATP (28% vs. 53%). When histamine and ATP were applied concomitantly there was no additivity of the inhibition beyond that produced by ATP alone (even though the agonists appear to activate distinct G-proteins) suggesting that the inhibition produced by ATP is maximal. When experiments were carried out under conditions of low levels of calcium buffering in the patch pipette solution (0.1 mM EGTA), histamine inhibited I(Ca) in some cells using an entirely voltage insensitive pathway. We demonstrate that activation of PTX insensitive G-proteins (most likely Gq) by H(1) receptors inhibits I(Ca). This may represent a mechanism by which histamine exerts inhibitory (in addition to previously identified stimulatory) effects on catecholamine release.