Blood supply of the tibialis anterior tendon

Injection techniques and immunohistochemical methods (antibodies against laminin) were performed to uncover the vascular pattern of the human tibialis anterior tendon with regard to spontaneous rupture of this tendon. Proximally, the blood supply of the tibialis anterior tendon mainly arises from the anterior tibial artery. Distally, the tendon is supplied by branches of the medial tarsal artery. Blood vessels enter the peritenon via vinculae from the posterior side. From the peritenon, the blood vessels penetrate the tendon and anastomose with a longitudinally orientated intratendinous network. Compared with the surrounding peritenon, the number of vessels in the tendon substance is greatly reduced. The distribution of blood vessels within the anterior tibial tendon is not homogenous. The posterior part of the tendon has a complete vascular network that extends from the musculotendinous junction to the insertion at the bone. In the anterior half of the tendon, there is an avascular zone between 45 and 67 mm in length. The location of the avascular zone correlates well with the location of the most frequent site of spontaneous rupture of the tibialis anterior tendon reported in the literature. Hypovascularity has to be considered as an etiological cofactor for spontaneous rupture of the tibialis anterior tendon.     

Semen quality and reproductive hormones before and after orchiectomy in men with testicular cancer

PURPOSE: We clarify the impact of removal of the tumor bearing testis on semen quality and reproductive hormones in men with testicular cancer. MATERIALS AND METHODS: Semen quality and levels of reproductive hormones were investigated in 48 men before and after orchiectomy for testicular cancer. Semen analysis was done in 35 of these men and hormone analyses were done in 47. The hormone data of patients with (14) or without (33) elevated values of human chorionic gonadotropin (HCG) were analyzed separately. RESULTS: Median sperm concentration and total sperm count decreased from 17 x 10(6)/ml. (range 0 to 117) and 39 x 10(6) (0 to 433), respectively, before to 7 x 10(6)/ml. (0 to 69) and 30 x 10(6) (0 to 200), respectively, after orchiectomy. After orchiectomy sperm concentration was decreased in 30 of 35 men (p = 0.001) and azoospermia developed in 3 (9%). In men without detectable HCG median follicle-stimulating hormone levels increased (p <0.001) from 5.7 IU/l. (range 0.01 to 30) before to 10.0 IU/l. (4.6 to 48) after orchiectomy in 33 of 33 patients. Median inhibin B significantly decreased (p = 0.003) from 108 pg./l. (range 60 to 193) before to 95 pg./l. (less than 20 to 141) after orchiectomy. Median luteinizing hormone increased significantly from 3.1 IU/l. (range 1.1 to 9.9) before to 5.2 IU/l. (2.1 to 27) after treatment (p <0.001). Testosterone and sex hormone-binding globulin did not change significantly after orchiectomy. Patients with detectable serum HCG before orchiectomy had a considerable increase in follicle-stimulating hormone after orchiectomy, and a concomitant decrease in testosterone and estradiol. CONCLUSIONS: Semen quality was poor at diagnosis and deteriorated further after orchiectomy compared with pretreatment values. Our findings indicate that in some patients the most appropriate time for cryopreservation of semen is before orchiectomy. Androgen production was maintained by increased luteinizing hormone stimulation after orchiectomy.     

Review of 1028 bulbar eviscerations and enucleations. Changes in aetiology and frequency over a 20-year period.

PURPOSE: To evaluate possible changes in aetiology and frequency of bulbar eviscerations and enucleations. METHODS: A total of 1028 cases from three two-year periods: 1975-76, 1985-86 and 1995-96 collected by the Eye Pathology Institute were reviewed. RESULTS: A significant decrease (p<0.001) in number of enucleations was observed from 358 in 1975-76 to 214 in 1995-96, corresponding to an almost equivalent increase in number of eviscerations from 5 in 1975-76 to 83 in 1995-96. The total number of eye removals decreased significantly (p<0.01) over the last two periods from 368 in 1985-86 to 296 in 1995-96. This was primarily caused by a decrease in the number of glaucoma-related enucleations from 32.7% in 1975-76 to 15.0% in 1995-96. The reduction in number was not fully balanced by the increase in glaucoma-related eviscerations. CONCLUSION: Over the last 20 years there has been a change in choice of operation from enucleation to evisceration.     

Characterization of the procoagulant chain derived from human high molecular weight kininogen (Fitzgerald factor) by human tissue kallikrein

Human high molecular weight kininogen (HMWK), a single-chain protein with mol wt 120,000, is cleaved by human urinary kallikrein (HUK) to release kinin from within a disulfide loop and form a two-chain protein that retains all the procoagulant activity of the native molecule. Cleavage of HMWK by HUK is associated with a reduction in size to mol wt 115,000, as assessed by SDS-PAGE of unreduced protein, whereas the two chains of the reduced protein present together as a single broad band with mol wt 64,000. The 64,000 chain with procoagulant activity was chromatographically separated from the nonfunctional chain of similar size. The homogeneous procoagulant chain had an amino acid composition similar to that of smaller procoagulant ("light") chains isolated by others upon cleavage of HMWK with plasma kallikrein and elicited an antiserum that was monospecific by Ouchterlony analysis and inhibited the procoagulant function of HMWK. Thus, the limited proteolysis of HMWK by HUK has permitted, for the first time, the isolation of a stable procoagulant chain that is equal in size to the nonfunctional chain. The common terminology of "heavy" and "light" chain for kinin-free kininogen obtained with plasma kallikrein reflects the continued degradation of the procoagulant carboxyterminal chain and is not appropriate for the initial two-chain product formed when kinin is released from HMWK. It is proposed that the initial cleavage products of HMWK be designated the A-chain, the B-fragment, and the C- chain, representing the amino-terminal chain, the released vasoactive peptide containing the bradykinin sequence, and the carboxy-terminal procoagulant chain, respectively. Thus, intact HMWK would contain, in sequence, A, B, and C regions.     

Multiple-dose pharmacokinetics of epirubicin at four different dose levels: studies in patients with metastatic breast cancer

Summary Pharmacokinetic analysis of epirubicin and its metabolites epirubicinol and 7-deoxy-13-dihydro-epirubicinol aglycone during the first and the fourth courses of treatment was performed in 78 patients with metastatic breast cancer. The patients were treated every 3 weeks with epirubicin given as 10-min i.v. infusions at four different dose levels: 40, 60, 90 and 135 mg/m². In most cases (76 of 78 cases), plasma concentration-time curves fitted to a three-compartmental pharmacokinetic model. The terminal half-life of epirubicin was independent of dose and duration of treatment. Large interindividual differences were demonstrated (meant _1/2, 21.6±7.9 h; range, 10.6–69 h;n=110). In two subjects, extremely long half-lives and high serum bilirubin concentrations indicated impaired liver function. No correlation was found between the half-life and levels of liver alanine aminotransferase (ALAT) or serum creatinine. The metabolite epirubicinol appeared quickly after epirubicin administration and its half-lives were shorter than that of the parent compound (meant _1/2, 18.1±4.8 h; range, 8.2–38.4 h;n=105).Formation of the aglycone metabolite was delayed and the half-life of this metabolite was shorter than that of epirubicin (meant _1/2, 13±4.6 h; range, 2.7–29 h;n=104). The AUC of epirubicin and the total AUC (drug and metabolites) were linearly proportional to the dose, with the former value constituting two-thirds of the latter. A correlation was found between AUC and the plasma concentration of epirubicin at two time points (2 and 24 h after administration). The proposed model was AUC=9.44×c ₂+62.5×c ₂₄+157.7 (r=0.953).This work was supported by the Lundbeck Foundation, the Michaelsen Foundation and Farmitalia Carlo Erba Ltd.     

Integrating providers into quality improvement: a pilot project at one hospital

Brigham and Women's Hospital initiated a study of the quality of care centering on self-reporting of potential medical injuries by providers. The goal of the study is to decrease the incidence of such injuries through a continuous quality methodology that integrates providers into the identification phase and incorporates all hospital employees in the development of new practices. This article provides an overview of the investigation methodology and discusses the conceptual relationships between clinical epidemiological analyses and industrial quality improvement.     

Steady-state kinetics of imipramine in patients

Steady-state plasma level kinetics were studied in 76 patients given imipramine (IP) 150 to 225 mg/day for 2–5 weeks. IP was given in three divided doses at 8.00 a.m., 1.00 p.m. and 5.00 p.m. Plasma concentrations of IP and its active metabolite desipramine (DMI) were determined by quantitative in situ thin-layer chromatography. The plasma levels of IP and DMI showed pronounced flucutations throughout the day with a ratio of about 2 between highest and lowest level. Patients with steady-state levels of IP and/or DMI below 50 g/l reached this within 1 week of treatment. Patients with higher steady-state levels reached steady-state concentrations within 2–3 weeks. There were some intraindividual fluctuations in plasma levels from week to week after steady state had been reached (coefficient of variation: 10–20%). Interindividually, the steady-state levels corrected to a dose of 3.5 mg/kg per day varied considerably: IP: 6–356 g/l, DMI: 24–659 g/l and IP+DMI: 58–809 g/l. The steady-state plasma levels showed a skew distribution that became normal by logarithmic transformation. The IP/DMI ratio ranged from 0.07 to 5.5 with a median value of 0.47. Compared to data from amitriptyline treated patients the IP/DMI ratios had significantly lower median value and larger variation than the corresponding plasma level ratios of amitriptyline/nortriptyline. Several statistically significant differences in steady-state levels between age groups were found. For IP: Women aged 30–39 had lower levels than women aged 20–29, 40–49, and 50–59, and men aged 50–59 and 60–65; men aged 30–39 had lower levels than men aged 60–65. For DMI: Women aged 30–39 had lower levels than women aged 50–59.     

The Safety of Atovaquone/Proguanil in Long-Term Malaria Prophylaxis of Nonimmune Adults

Background Data on the long-term safety of atovaquone/proguanil in nonimmune travelers are limited.
Methods An open-label study, involving 300 Danish soldiers stationed in Eritrea for 6 months was initiated. The subjects self-reported their symptoms on a post-travel questionnaire. The study compared the symptoms of compliers and noncompliers.
Results No serious adverse events occurred. Diarrhea, stomach pain, headache, cough, and loss of appetite were the most common symptoms reported. No case of Plasmodium falciparum malaria occurred.
Conclusions Atovaquone/proguanil was safe and well tolerated in this group of long-term nonimmune travelers.