Functional diagnosis of early arthroses of the extremities

Patient history and clinical examination are important for the diagnosis of degenerative joint disease. Here the typical statements of a patient suffering from early osteoarthritis are described and, as far as possible, explained. The joint in question must be systematically examined. Furthermore, the neighboring joints and soft-tissue structures, i.e., muscles, tendons etc., should be examined and evaluated with respect to their importance in hindering the functional chain. The neuroreflectory mechanisms involved herein are described.     

Effect of distension on adrenergic innervation of the rat urinary bladder

Summary The effect of distension on adrenergic innervation was investigated in the rat urinary bladder. Bladders were distended for 3 h by forced diuresis and ballon obstruction, and specimens were taken from the bladder dome, body and neck for the demonstration of glyoxylic acid-induced fluorescence of catecholamines. Depletion of catecholamines started after 10 h and was almost complete after 2 days. The fluorescence had recovered part way after 5–7 days and was practically normal after 21 days. Small, intensely fluorescent (SIF) cells in the ganglia continued to leak catecholamines throughout the 21-day study period. The primary clinical success of distension therapy for the treatment of unstable bladder may be at least partly due to a reversible disturbance in the function of the adrenergic nerves, which have an excitatory alpha-adrenergic dominance in such cases, but the persistent leakage from SIF cells raises the question of whether distension causes prolonged disturbances in bladder function.     

Head lice in Israeli children: parents' answers to an epidemiological questionnaire

BACKGROUND: The aim was to determine the influence of the socioeconomic status of the family and the hygienic practices in the home on the prevalence of head lice infestation in children. METHODS: The study was carried out by analyzing the answers to a standardized epidemiological questionnaire given to parents of school children aged 4-17 in Bet Shemesh, a medium-sized urban town 25 km from Jerusalem. RESULTS: Of 3,000 questionnaires distributed, 958 (31.9%) were completed and returned. The majority of the children (72.4%) had been previously infested with lice. Half of them had other family members, mainly brothers and sisters, who had been infested in the past with lice. In 97.5% of the families the mother was responsible for examining the children for lice, and for carrying out treatment when infestation was present. An association was found between presence of lice infestation and mother's education, age of child, and frequency of shampooing, combing, and examination for lice. There was no association between infestation rates and mother's country of origin, crowding in the home, and the sharing of combs, brushes, hats, scarves, towels, and clothes. CONCLUSIONS: There is evidence that the incidence of lice infestation depends on the hygienic practices in the home rather than on the socioeconomic status of the family or sharing of personal articles among family members.     

Neurogenic stress ulceration caused by laparotomy under anesthesia plus restraint. The device of a new rat model

We report herein, a new method devised of producing neurogenic stress ulceration in rats. An experimental subarachnoid hemorrhage (SAH) was produced in rats by injecting 0.2 ml of arterial blood from other rats into the cisterna magna. Three days later, the rats were laparotomized for 1 hour under ether anesthesia, followed by restraint for 3 hours in wakefulness. The SAH rats were found to develop stress ulcers (UL-I) in the glandular stomach, which were significantly (p less than 0.001) more marked than those in non-SAH rats. Measurements were performed on gastric acid secretion, an important aggressive factor. It was found that the SAH rats undergoing the laparotomy-restraint stress showed a more marked increase in gastric acid secretion and a more marked reduction in MBF, than the non-SAH rats. The effects of bilateral vagotomy, upper abdominal sympathectomy and bilateral adrenalectomy were examined, and it was revealed that the SAH rats were under the condition of hyperreactivity both in the sympathetic and parasympathetic systems and, on this basis, the laparotomy-restraint stress caused the stress gastric ulceration. In this rat model, the laparotomy stress was applied under anesthesia and any exposure to low temperatures which may have interfered with blood circulation was avoided.     

Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification of Diet in Renal Disease Study

Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time-consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99mTc-diethylenetriamine-pentaacetic acid (DTPA), 169Yb-DTPA, and 125I-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 125I-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL.min-1.1.73m-2. Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99mTc-DTPA, 169Yb-DTPA, or 125I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects.     

Nafarelin controlled release injectable: theoretical clinical plasma profiles from multiple dosing and from mixtures of microspheres containing 2 per cent, 4 per cent and 7 per cent nafarelin

Nafarelin controlled release injectable (CRI) releases a decapeptide drug for target one month therapy. Nafarelin, a luteinizing hormone releasing hormone agonistic analogue, is microencapsulated in biodegradable poly(lactide-co-glycolide) microspheres and given by intramuscular injection. Clinical data from a human single dose Phase I clinical study are modelled to develop theoretical multiple dose profiles and theoretical single dose profiles from mixtures of two or three formulations. Single dose injections of nafarelin CRI microspheres (4 mg nafarelin) containing 2, 4, or 7 per cent nafarelin all achieve useful plasma drug levels throughout the target 30 day interval. Therapeutic suppression of testosterone levels was observed in all subjects participating in the phase I clinical study. Highest plasma nafarelin levels are achieved in the 0-10 and 20-35 day post-injection intervals. Theoretical multiple dosing profiles generated from the single dose clinical results show significant oscillations in plasma nafarelin levels depending on the particular dosing interval selected. Thirty or forty day dosing intervals yield significant variability in plasma nafarelin levels at steady state; 15 day dosing intervals show less variability. Therapeutic testosterone suppression was observed in the single dose study, so the nafarelin dose per injection can be reduced in multiple dosing therapies. Theoretical plasma nafarelin profiles from certain mixtures of 2 and 4 per cent nafarelin microspheres or 2 and 7 per cent nafarelin microspheres indicate that a 60 day product could be achieved. In general, all three formulations yield their lowest plasma drug levels during the 10-20 day post-injection interval. Therefore any mixture of these formulations will likewise exhibit low plasma drug levels during this interval.     

Altered serum immunoglobulin response to model intestinal antigens during dietary exposure to vomitoxin (deoxynivalenol)

The effect of dietary vomitoxin on the serum IgA and IgG responses to two model intestinal antigens, casein and cholera toxin (CT), were assessed in 4 experimental groups: (1) mice fed casein-based diet, (2) mice fed casein-based diet containing 25 ppm vomitoxin, (3) mice fed casein-based diet and immunized with CT, and (4) mice fed casein-based diet containing 25 ppm vomitoxin and immunized with CT. Unimmunized and CT-immunized mice that were fed vomitoxin exhibited increased levels of total serum IgA relative to matched control animals fed the standard diet. Relative concentrations of casein-specific IgA were greater in both unimmunized mice and CT-immunized mice fed standard diet with vomitoxin than in matched controls fed standard diet only. CT-specific serum IgA in CT-immunized mice was not affected by vomitoxin feeding, but relative levels of CT-specific IgA were higher in unimmunized mice fed vomitoxin than in unimmunized mice fed standard diet. Both casein- and CT-specific serum IgG were depressed in mice fed vomitoxin. Significant differences in total, casein-specific and CT-specific IgA within the intestinal contents were not observed between CT-immunized mice fed vomitoxin and those fed the control diet. The results suggest that vomitoxin altered regulation of the normal immunoglobulin response to intestinal antigens and that this was manifested in the systemic compartment.     

The effect of metronidazole on TPN-associated liver dysfunction in neonates

The effect of metronidazole (MNZ) on hepatic dysfunction associated with total parenteral nutrition (TPN) in neonates was investigated. Neonates receiving TPN for more than 2 weeks were divided into three groups. In group 1, TPN was given alone, in group 2, 25 mg/kg/d of MNZ was administered intravenously for the first 2 weeks of TPN, and in group 3, 50 mg/kg/d of MNZ was given for the first 3 weeks of TPN. Several parameters of liver function tests (LFTs) during the first 4 weeks of TPN were compared among these three groups. There was no significant difference of these parameters between group 1 and group 2. Although there was no significant difference of alkaline phosphatase, gamma-glutamyl transpeptidase, direct bilirubin, and total bile acid between groups 1 and 3, transaminase (glutamic oxaloacetic, glutamic pyruvic) of group 3 remained significantly lower than those of group 1. In conclusion, the administration of MNZ 50 mg/kg/d for 3 weeks, at least, prevented the elevation of transaminase during TPN in neonates, suggesting the possible involvement of intestinal anaerobic flora in the pathogenesis of TPN-associated liver dysfunction.     

Absence of HIV antigens in renal tissue from patients with HIV-associated nephropathy

HIV-associated nephropathy (HIV-N) is considered a distinctive disease, the pathogenesis of which is still undefined. Direct virus-induced renal cell damage has been postulated. The numerous cytolytic ultrastructural changes and a few studies by immunoperoxidase support this hypothesis, but there has been no demonstration of virus by electron-microscopy (EM) or by tissue culture. In seven out of 12 cases with histological characteristics of HIV nephropathy, with proteinuria (five cases) or with nephrotic syndrome (two cases), we tested renal tissue for HIV antigens: core p18 and p25; envelope gp45 and gp110, by means of immunoperoxidase avidin-biotin complex monoclonal antibodies (MoAbs). Light-microscopy (LM) showed in five patients a focal and segmental glomerular sclerosis, and in two a mesangial hyperplasia with vacuolisation of visceral epithelium and protein inclusions. Electron-microscopy, performed in five of seven patients, showed several protein inclusions in podocyte cytoplasm, tubuloreticular inclusions in endothelial cell cytoplasm in all cases, nuclear degranulation of tubular cells in four cases and nuclear bodies in two. HIV antigens by MoAbs on renal tissue were negative in all cases, in both glomeruli and tubules. These results do not confirm the presence of HIV proteins in renal tissue of patients with HIV nephropathy. A possible explanation, apart from no direct HIV in the disease, may be the low viral load in tissues, because of the early phases of renal damage in most cases.     

Uptake of Adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas

Summary Eight patients with malignant gliomas verified on CT scan, received an intravenous injection of 50 mg of Adriamycin R, 24 hours prior to surgical removal of the tumour. Peroperatively, both tumour and surrounding tissue specimens were obtained for determination of the tissue concentrations of Adriamycin and its reduced metabolite Adriamycinol. It was found that Adriamycin could be detected in tumour tissue from all patients. The concentration varied between 0,9 and 4,6 nmol/g tissue. In contrast, Adriamycin could only be detected in surrounding brain tissue from one patient.In anin vitro study a human malignant glioma cell line (U-251 MG) was exposed to various concentrations of Adriamycin for 24 hours. It was found that an intracellular drug concentration above 30 nmol/g cells caused a concentration dependent inhibition of cell growth. Thus, it is likely that the poor effect of Adriamycin on patients with malignant gliomas is due to an ineffective drug accumulation in the tumour tissue.