The human myotendinous junction: an ultrastructural and 3D analysis study.

The myotendinous junction (MTJ) is a specialized structure in the musculotendinous system, where force is transmitted from muscle to tendon. Animal models have shown that the MTJ takes form of tendon finger-like processes merging with muscle tissue. The human MTJ is largely unknown and has never been described in three dimensions (3D). The aim of this study was to describe the ultrastructure of the human MTJ and render 3D reconstructions. Fourteen subjects (age 25 ± 3 years) with isolated injury of the anterior cruciate ligament (ACL), scheduled for reconstruction with a semitendinosus/gracilis graft were included. Semitendinosus and gracilis tendons were stripped as grafts for the ACL reconstruction. The MTJ was isolated from the grafts and prepared for transmission electron microscopy (TEM) and focused ion beam/scanning electron microscopy. It was possible to isolate recognizable MTJ tissue from all 14 patients. TEM images displayed similarities to observations in animals: Sarcolemmal evaginations observed as finger-like processes from the tendon and endomysium surrounding the muscle fibers, with myofilaments extending from the final Z-line of the muscle fiber merging with the tendon tissue. The 3D reconstruction revealed that tendon made ridge-like protrusions, which interdigitiated with groove-like indentations in the muscle cell.

Non-hematopoietic PAR-2 is essential for matriptase-driven pre-malignant progression and potentiation of ras-mediated squamous cell carcinogenesis.

The membrane-anchored serine protease, matriptase, is consistently dysregulated in a range of human carcinomas, and high matriptase activity correlates with poor prognosis. Furthermore, matriptase is unique among tumor-associated proteases in that epithelial stem cell expression of the protease suffices to induce malignant transformation. Here, we use genetic epistasis analysis to identify proteinase-activated receptor (PAR)-2-dependent inflammatory signaling as an essential component of matriptase-mediated oncogenesis. In cell-based assays, matriptase was a potent activator of PAR-2, and PAR-2 activation by matriptase caused robust induction of nuclear factor (NF)κB through Gαi. Importantly, genetic elimination of PAR-2 from mice completely prevented matriptase-induced pre-malignant progression, including inflammatory cytokine production, inflammatory cell recruitment, epidermal hyperplasia and dermal fibrosis. Selective ablation of PAR-2 from bone marrow-derived cells did not prevent matriptase-driven pre-malignant progression, indicating that matriptase activates keratinocyte stem cell PAR-2 to elicit its pro-inflammatory and pro-tumorigenic effects. When combined with previous studies, our data suggest that dual induction of PAR-2-NFκB inflammatory signaling and PI3K-Akt-mTor survival/proliferative signaling underlies the transforming potential of matriptase and may contribute to pro-tumorigenic signaling in human epithelial carcinogenesis.

Small cerebral aneurysms presenting with symptoms other than rupture.

BACKGROUND: Recent natural history studies have suggested that unruptured intracranial aneurysms smaller than 1 cm have a low risk of rupture. Symptomatic aneurysms may be underrepresented in natural history studies because they are preferentially treated. The authors compared the number of patients with symptoms caused by unruptured intracranial aneurysms smaller than 1 cm treated surgically at their institution with similar patients enrolled in the International Study of Unruptured Intracranial Aneurysms (ISUIA) from their institution over the same time period. METHODS: The records of all unruptured aneurysms treated surgically at the Mayo Clinic from 1980 through 1991 were reviewed. There were 97 patients with 117 unruptured aneurysms smaller than 1 cm by angiography. Aneurysms with a history of rupture or larger than 1 cm on cross-sectional imaging were excluded from analysis. The presence and characteristics of symptoms directly attributable to the aneurysm were recorded. Comparison was made with patients from the Mayo Clinic enrolled in the ISUIA retrospective natural history cohort over the same time period. RESULTS: Of the 97 patients studied, 15 presented with symptoms other than rupture (15.5%). The symptoms were third nerve deficit (seven patients), cerebral ischemia owing to emboli originating from within the aneurysm (five patients), and visual acuity loss (three patients). Eleven other aneurysms had possibly but not definitively caused symptoms; these were considered asymptomatic. No patient from the Mayo Clinic enrolled in the retrospective cohort of the ISUIA had a symptomatic aneurysm smaller than 1 cm on both angiography and cross-sectional imaging. CONCLUSIONS: Unruptured intracranial aneurysms smaller than 1 cm occasionally present with neurologic symptoms. These symptoms are typically owing to mass effect on the second and third cranial nerves or cerebral ischemia as a result of emboli originating from within the aneurysm. Patients with symptomatic unruptured aneurysms less than 1 cm at the Mayo Clinic were preferentially treated. Although existing natural history data may be applied to most unruptured aneurysms, small symptomatic aneurysms may be underrepresented in natural history studies.

Lipoprotein-cholesterol levels in infertile women with luteal phase deficiency.

OBJECTIVE: To determine if reductions in plasma progesterone (P) secretion seen in luteal phase deficiency (LPD) might be because of reduced availability of circulating low-density lipoprotein (LDL) or high-density lipoprotein (HDL), known substrates for corpus luteum P synthesis. DESIGN: We measured plasma lipoproteins in the luteal phase of the menstrual cycle in 39 infertile women. These women were divided into two groups on the basis of endometrial biopsies; the LPD group had biopsies that were greater than or equal to 3 days out-of-phase. SETTING: All participants were recruited from the Reproductive Endocrinology and Infertility Clinic at the University of Washington, an institutional tertiary care center. PATIENTS, PARTICIPANTS: Eighteen women had in-phase and 21 had out-of-phase LPD biopsies. MAIN OUTCOME MEASURE: Lipoprotein levels were obtained in a fasted state on the day of the luteal phase on which the biopsy was performed. RESULTS: No difference in covariates that affect lipoprotein levels such as obesity, age, and alcohol use were observed between the two groups. No significant differences between groups were found for triglycerides, total cholesterol, very low density lipoprotein, LDL, HDL, HDL2, and HDL3 concentrations. However, LPD was associated with a reduction in the extent to which: age and obesity are associated with higher triglycerides; obesity is associated with a lower HDL2; and alcohol is associated with a higher HDL3-cholesterol. CONCLUSIONS: Lipoproteins on average are not different in LPD, suggesting reasons other than a deficient plasma lipoprotein cholesterol source as the explanation for decreased P secretion. A lesser interaction between LDL or HDL and obesity, age, and alcohol in LPD could signify an influence of the altered hormonal milieu of LPD on the way lipoproteins interact with covariates and could lead to differences in lipoproteins between normal and LPD subjects at the extremes of the lipoprotein distribution.

Late patency of long saphenous vein bypass grafts to the anterior and posterior cerebral circulation.

To evaluate the late results and the natural history of long saphenous vein bypass grafts (SVGs) between the extracranial and intracranial circulation, the authors retrospectively analyzed 202 consecutive SVGs performed at the Mayo Clinic from 1979 to 1992. The distal anastomosis was to the vertebrobasilar system in 98 patients and to the carotid artery system in 103 patients. Surgical indications were advanced cerebroocclusive disease in 63% (127 cases), giant aneurysm in 37% (74 cases), and neoplasm in one patient. In 125 patent SVGs follow-up information was obtained for longer than 1 year and in 23 patent SVGs it was over 10 years (maximum 13 years, median 6.5 years). Most of the graft failures (76%) occurred during the 1st year after surgery, with 42% of all graft failures found during the first 24 hours after operation. Late graft attrition occurred in only 10 patients (8%). Cumulative patency at 1 year was 86% +/- 3%, at 5 years 82% +/- 4%, and at 13 years 73% +/- 19%. Neurological worsening at the time of occlusion developed in 72% of patients with early occlusion, whereas 80% of patients with late graft occlusion had no new neurological symptoms. Long-term patency of SVGs for cerebral revascularization appears to be excellent, with an average failure rate of 1% to 1.5% per year following the 1st year after surgery. To minimize early graft thrombosis, meticulous attention must be paid to technical detail.

Ischemic complications of surgery for anterior choroidal artery aneurysms.

OBJECT: Anterior choroidal artery (AChA) aneurysms account for 4% of all intracranial aneurysms. The surgical approach is similar to that for other supraclinoid carotid artery lesions, but surgery may involve a higher risk of debilitating ischemic complications because of the critical territory supplied by the AChA. METHODS: Between 1968 and 1999, 51 AChA aneurysms in 50 patients were treated using craniotomy and clipping at the Mayo Clinic. There were 22 men (44%) and 28 women (56%) whose average age was 53 years (range 27-79 years). Twenty-four AChA aneurysms (47%) had hemorrhaged; nine patients (18%) had subarachnoid hemorrhage from another aneurysm. Three AChA aneurysms (6%) were associated with symptoms other than rupture. Forty-one patients (82%) achieved a Glasgow Outcome Scale (GOS) score of 4 or 5 at long-term follow up. The surgical mortality rate was 4%, and major surgical morbidity (GOS < or = 3) was 10%. Eight patients (16%) had clinically and computerized tomography-demonstrated AChA territory infarcts. Five of these strokes manifested in a delayed fashion 6 to 36 hours after the operation, and progressed from mild to complete deficit over hours. In 41 patients the aneurysm arose from the internal carotid artery adjacent to the AChA, and in nine patients the aneurysm arose directly from the origin of the AChA itself; four of these nine patients had postoperative infarction. CONCLUSIONS: Surgical treatment of AChA aneurysms involves a significant risk of debilitating ischemic complications. Most postoperative strokes occur in a delayed fashion, offering a potential therapeutic window. Patients with aneurysms arising from the AChA itself have an extremely high risk for postoperative stroke.

Patient-administered sequential spirometry in healthy volunteers and patients with alpha 1-antitrypsin deficiency.

The launching of cheap, pocket-sized spirometers, with data storage capability, has made patient-administered sequential spirometry (PASS) an attractive method of monitoring ventilatory capacity. At present, little information is available on the quality of PASS, compared to laboratory spirometry. The aim of this study was to investigate whether patients could perform PASS without loss of reliability and reproducibility as compared with traditional laboratory spirometry. Ten healthy volunteers performed spirometry for 1 month and 10 emphysematous patients with alpha 1-antitrypsin deficiency (type PiZ) performed spirometry twice daily for up to 2 yr. To fulfil Good Clinical Practice criteria on full data documentation, a traditional direct recording spirometer, the Vitalograph R-model, was used. A decompression device was used for calibration and a 3.8% annual drift in volume registration was noted. This drift was largest for the first year. After training, all patients were able to perform unsupervised spirometry, producing technically correct forced expiratory curves. Reproducibility of FEV1 and FVC obtained by PASS was found to be as good as for laboratory spirometry. After adjustment for the diurnal variation, the residual variation of FEV1 was 2.5% (range 1.6-4.2%) for healthy volunteers and 5.6% (range 4.2-7.7%) for emphysematous patients. Forced vital capacity showed the same pattern. In conclusion, PASS is possible in highly motivated individuals without loss of reliability and reproducibility when compared to laboratory spirometry.

Folk remedies and child abuse: a review with emphasis on caida de mollera and its relationship to shaken baby syndrome.

OBJECTIVE: There were two objectives: first, to make the reader familiar with folk remedies that might be confused with child abuse; second, to challenge the idea existing in the literature that treatment for the Hispanic folk illness caida de mollera can cause the injuries seen in the shaken baby syndrome. METHOD: Literature review and analysis with case application were used. RESULTS: A wide variety of folk remedies with potential for confusion with child abuse were found to exist, and were described. Treatment for caida de mollera was found to consist of a number of gentle, nonviolent maneuvers quite different from the violent shaking believed to cause shaken baby syndrome. CONCLUSIONS: Familiarity with folk remedies will help differentiate them from child abuse. The child protection community would benefit from realizing that treatment for caida de mollera is an improbable cause of shaken baby syndrome injuries.

Role of estrogen in avian osteoporosis.

One of the difficulties associated with commercial layer production is the development of osteoporosis in hens late in the production cycle. In light of this fact and because of hens' unique requirements for Ca, many studies have focused on the regulation of Ca and the role of estrogen in this process. The time course of estrogen synthesis over the productive life of hens has been well documented; increased circulating estrogen accompanies the onset of sexual maturity while decreases signal a decline in egg production prior to a molt. Numbers of estrogen receptors decrease with age in numerous tissues. The parallel changes in calcium-regulating proteins, primarily Calbindin D28K, and in the ability of duodenal cells to transport Ca, are thought to occur as a result of the changes in estrogen, and are also reversible by the molt process. In addition to the traditional model of estrogen action, evidence now exists for a possible nongenomic action of estrogen via membrane-bound receptors, demonstrated by extremely rapid surges of ionized Ca in chicken granulosa cells in response to 17beta-estradiol. Estrogen receptors have also been discovered in duodenal tissue, and tamoxifen, which binds to the estrogen receptor, has been shown to cause a rapid increase in Ca transport in the duodenum. In addition, recent evidence also suggests that mineralization of bone per se may not explain entirely the etiology of osteoporosis in the hen but that changes in the collagen matrix may contribute through decreases in bone elasticity. Taken together, these studies suggest that changes in estrogen synthesis and estrogen receptor populations may underlie the age-related changes in avian bone. As with postmenopausal women, dietary Ca and vitamin D are of limited benefit as remedies for osteoporosis in the hen.

Western immunoblotting in avian shell gland sample immunoblotting methods.

Avian shell gland tissue was subjected to Western blot analysis using anti-human estrogen receptor-alpha antibody H222. Initial attempts to obtain consistent, high-quality blots were unsuccessful because, as it turned out, excessive lipid in tissue preparations interfered with protein separation. Incremental additions of acetone eventually proved to be the critical step in solubilizing lipids and allowing consistent separation of bands on gels. A detailed description of the methodology is presented.

Exogenous estrogen boosts circulating estradiol concentrations and calcium uptake by duodenal tissue in heat-stressed hens.

In the hen, heat stress (HS) disrupts shell calcification and reproductive processes, including hormone synthesis and egg production. Two studies were conducted to investigate palliative effects of exogenous estrogen or dietary vitamin D3 on Ca homeostasis and reproductive physiology during HS. Study 1: Hy-Line W36 hens were randomly assigned to thermoneutral (TN) or HS treatments and to 1 of 7 estrogen treatments: zero (control) or one Compudose 200 implant given 1, 2, 3, 8, 9, or 10 d before onset of HS. With no implant, HS reduced plasma estradiol (E2) and total Ca absorbed (CaT) by duodenal cells (P < 0.05). In TN hens with implants, plasma E2 tripled within 24 h (P < 0.05) and remained elevated (P < 0.05) through d 9. In HS hens with implants, plasma E2 rose 6-fold (P < 0.05) to equal TN+E2 concentrations and remained elevated through d 10. In TN and HS hens with implants, the rate of Ca absorption (CaTR) and CaT increased dramatically; the responses were quadratic and essentially identical. Study 2: Hy-Line W36 hens were provided diets formulated either according to NRC requirements (NRC, 1994), or with the addition of 22,000 IU/kg vitamin D3 (+VD hens). A 24-h HS episode was imposed 2 wk after initiation of the dietary regimen. Duodenal samples were collected for Ca absorption assays after the 24-h HS episode. Both CaTR and CaT in +VD hens were approximately 3-fold higher than in hens in the NVD group (P = 0.102). The results lead to the conclusion that exogenous estrogen, high levels of dietary vitamin D, or both, before a HS episode, are efficacious in alleviating at least some of the effects of HS and should be further investigated.

Estrogen receptor-alpha populations change with age in commercial laying hens.

Older hens in production lay larger but fewer eggs than younger birds, and the incidence of soft and broken shells is greater in older hens than younger. These changes are attributable at least in part to changing hormone profiles and diminished ability of the hen to transport calcium at the duodenum. In further exploration of this relationship, a study was conducted with three ages of Hy-Line W-36 birds: prelay pullets (PL; 19 wk, 0% production), peak-production hens (PP; 29 wk, approximately 93% production), and late-stage hens (LS; 71 wk, approximately 80% production). Hens from the PP and LS groups were palpated for presence of an egg in the shell gland; hens were then euthanized and tissues (kidney, shell gland, hypothalamus) were removed for quantification of estrogen receptor-alpha (ERalpha) populations via immunocytochemical and Western blot analyses. Localization of ERalpha by immunostaining in the shell gland showed differences among age groups; however, no differences were noted in localization of ERalpha between age groups in the kidney and hypothalamus. In both the kidney and the shell gland there was a decrease in the amount of ERalpha, as detected by immunoblotting, in the LS hens compared to PL and PP birds (P < 0.05). The results suggest that failure of calcium regulating mechanisms with age may be mediated at least in part through the reduced populations of estrogen receptors in certain critical tissues.

Cutting healthcare costs. Can physicians make a difference?

Information about healthcare "bargains" is easy to obtain. Physicians who take the time to familiarize themselves with costs in their hospitals and clinics can help reduce charges for tests and drugs and can avoid wasteful use of supplies and misuse of staff time that can lead to additional charges. Education is effective in fighting rising healthcare costs, but efforts need to be ongoing if patients and medical institutions are to benefit in the long run.

Mycoplasma hyosynoviae in joints with arthritis in abattoir baconers.

The occurrence of Mycoplasma hyosynoviae in synovial fluid of baconers with chronic arthritis was studied at an abattoir. Cultural examination of synovial fluid samples from diseased tarsal joints of 50 animals from 42 herds yielded M. hyosynoviae in 10 cases from 8 herds. Streptococci were found in 6 cases from 6 other herds. M. hyosynoviae antigen was found in 1 of 47 of the samples, and antibody to the mycoplasma was found in 14 of 40 of the samples by ELISA test. The presence of M. hyosynoviae in a joint was usually accompanied by the corresponding antibody. In joints with streptococcal infection antibody to M. hyosynoviae could not be found.

[Cytomegalovirus infection. A review]. / Cytomegalovirus-infektion. En oversigt.

Once considered to be an infrequent cause of human disease, human cytomegalovirus (CMV) is now recognized as being one of the most common congenital infections leading to birth defects, and furthermore, it is a common opportunistic infection associated with serious illness and death in immunocompromised patients. CMV has been assigned to the herpes family of viruses. It is an enveloped DNA virus. About 50%-60% of Danish blood donors have anti-CMV. This figure is dependent on age, race, socioeconomic status, sexual behaviour and geographical area. Patients exhibiting symptoms and signs of primary or reactivated CMV infection should be further evaluated with appropriate laboratory tests, as treatment of CMV disease with antiviral chemotherapy such as ganciclovir or foscarnet, has proven to be effective.

[Allergy and bronchial reactivity in children and adolescents from Copenhagen]. / Allergi og bronkial reaktivitet hos børn og unge fra København.

The relationship between bronchial responsiveness and the results of a skin prick test was studied in 527 children and adolescents from Copenhagen. All participants completed a questionnaire concerning birth weight, breastfeeding, month of birth, month of examination, allergic symptoms in themselves or their parents. Furthermore, skin prick test reactivity to nine common aero-allergens, lung function, serum IgE, and bronchial responsiveness to histamine and exercise were measured. A total of 158 (30%) subjects showed signs of allergy (defined as a positive reaction to the skin prick test), of whom 53 (10%) subjects had positive skin reactivity and 105 subjects had moderate skin reactivity; 366 (70%) subjects had no signs of allergic disease as measured by the pride test. The most important marker for the degree of bronchial responsiveness was asthma (p < 0.001), month of examination (p < 0.01) and allergy (skin reactivity to one or more allergens) (p < 0.05). Furthermore, the degree of bronchial responsiveness to inhaled histamine was significantly related to a history of asthma in two first degree relatives (p < 0.01) and the skin reactivity to house-dust mites (p < 0.01), whereas the degree of bronchial responsiveness to exercise was significantly associated with the level of serum IgE (p < 0.05), month of birth (p < 0.001) and birth weight (p < 0.05). In conclusion, allergy is an important risk factor for the presence of increased degree of bronchial responsiveness to inhaled histamine and to exercise.

Bacteraemia as a result of Campylobacter species: a population-based study of epidemiology and clinical risk factors.

Invasive disease as a result of Campylobacter is rarely reported. We reviewed 46 cases of blood stream infection with Campylobacter in a Danish population with complete follow-up. The incidence was 2.9 per 1 million person-years with a peak incidence in the age group above 80 years. In the population, the ratio of notified bacteraemia/enteritis patients with Campylobacter infection was 0.004. Patients with bacteraemia were older and had higher comorbidity, e.g. alcoholism, immunosuppression, previous gastrointestinal surgery or HIV infection. We found 26% of blood isolates resistant to ciprofloxacin. The length of hospitalization was significantly longer in bacteraemia patients, whereas the outcome was favourable with 28-day mortality of 4% in bacteraemia patients and 1% in enteritis patients. None of the bacteraemia patients relapsed within 365-day follow-up.