Determinants of invasive treatment in lower extremity peripheral arterial disease.

OBJECTIVE: Since it is unknown what factors are weighed in a clinician's decision to refer patients with symptomatic lower extremity peripheral arterial disease (PAD) for invasive treatment, we examined the relationship between health status, lesion location, and site variations and invasive treatment referral ≤1 year following diagnosis in patients with PAD. METHODS: This was a prospective observational cohort study on ambulatory patients that presented themselves at two vascular surgery outpatient clinics. A total of 970 patients with new symptoms of PAD or with an exacerbation of existing PAD symptoms that required clinical evaluation and treatment (Rutherford Grade I) were eligible, 884 consented and were included between March 2006 and November 2010. We report on 505 patients in the current study. Prior to patients' initial PAD evaluation, the Short Form-12, Physical Component Scale (PCS) was administered to measure health status. Anatomical lesion location (proximal vs distal) was derived from duplex ultrasounds. PCS scores, lesion location, and site were evaluated as determinants of receiving invasive (endovascular, surgery) vs noninvasive treatment ≤1 year following diagnosis in Poisson regression analyses, adjusting for demographics, ankle-brachial index, and risk factors. RESULTS: Invasive treatment as a first-choice was offered to 167 (33%) patients. While an association between poorer health status and invasive therapy was found in unadjusted analyses (relative risk [RR], 0.98; 95% confidence interval [CI], 0.97-1.00; P = .011), proximal lesion location (RR, 3.66; 95% CI, 2.70-4.96; P < .0001) and site (RR, 1.69; 95% CI, 1.11-2.58; P = .014) were independent predictors of invasive treatment referral in the final model. CONCLUSIONS: One-third of patients were treated invasively following PAD diagnosis. Patients' health status was considered in providers' decision to refer patients for invasive treatment, but having a proximal lesion was the strongest predictor. This study also found some important first indications of site variations in offering invasive treatment among patients with PAD. Future work is needed to further document these variations in care.

Abnormal secretion of insulin and glucagon by the in vitro perfused pancreas of the genetically diabetic Chinese hamster.

Hereditary insulin-deficient diabetes mellitus occurs in certain sublines of nonobese Chinese hamsters. Several characteristics of this syndrome are similar to those seen in insulin-deficient human diabetics. Therefore, to characterize pancreatic islet function, dynamic insulin and glucagon release from normal and nonketotic diabetic hamster pancreases in response to glucose (300 mg/100 ml) and theophylline (10 mM), infused singly and together, was studied in vitro.20-min glucose infusions of normal hamster pancreases caused biphasic insulin release, consisting of a rapid first peak and a gradually rising second phase, similar to that reported for man in vivo. Both phases were significantly reduced in the diabetic pancreases. Theophylline alone stimulated similar nonphasic insulin release in both the normal and the diabetic pancreases. Glucose and theophylline together caused greater insulin release than either stimulant alone in both normals and diabetics; however, the diabetic response was still subnormal. Glucose suppressed glucagon release from normal pancreases; suppression was significantly impaired in diabetics. Theophylline stimulated nonphasic glucagon release in both the normals and diabetics. Glucose partially suppressed the theophylline-stimulated release in both groups.Insulin/glucagon molar ratios of the diabetics were consistently subnormal, although individual hormone levels often overlapped into the normal range. IN SUMMARY, THE PANCREASES OF GENETICALLY DIABETIC CHINESE HAMSTERS PERFUSED IN VITRO SHOWED: (a) decreased first and second phase insulin release in response to glucose-containing stimuli-only partially ameliorated by theophylline-, and (b) impaired suppression of glucagon in response to glucose, resulting in (c) a decreased insulin/glucagon molar ratio. These data support the suggestion that both alpha and beta cells of diabetic pancreases may be insensitive to glucose.

[Guidelines in Dutch mental health institutions for dealing with persons attempting suicide]. / Richtlijnen voor de opvang van suïcidepogers in Nederlandse ggz-instellingen.

BACKGROUND: Attempted suicide is a frequent occurrence, even in mental health institutions (mhis). The World Health Organization strongly supports the development and implementation of guidelines for dealing with cases of attempted suicide in mhis. aim To check on the existence, content and quality of guidelines for dealing with persons attempting suicide within mhis in the Netherlands and to compare these guidelines with those available in university and general hospitals. METHOD: A questionnaire was sent to all mhis. Criteria for assessing the content of existing guidelines were derived from the literature. The quality of the guidelines was then assessed on the basis of the Appraisal of Guidelines for Research and Evaluation (agree), a tool developed to evaluate guideline quality. results Thirty-eight out of 48 (72.2%) psychiatric institutions responded, giving us access to 12 sets of guidelines. The content and quality of these guidelines were compared with the content and quality of the guidelines available in university and general hospitals; there were several differences, but on the whole the mhi-guidelines were better. CONCLUSION: Guidelines were only available in a limited number of mhis. Most of the guidelines were adequate with regard to content, but some of the mhi-guidelines lacked some important elements. The quality of the mhi-guidelines was rather low but nevertheless better that that of the hospital guidelines.

Macrophage p53 deficiency leads to enhanced atherosclerosis in APOE*3-Leiden transgenic mice.

Cell proliferation and cell death (either necrosis or apoptosis) are key processes in the progression of atherosclerosis. The tumor suppressor gene p53 is an essential gene in cell proliferation and cell death and is upregulated in human atherosclerotic plaques, both in smooth muscle cells and in macrophages. In the present study, we investigated the importance of macrophage p53 in the progression of atherosclerosis using bone marrow transplantation in APOE*3-Leiden transgenic mice, an animal model for human-like atherosclerosis. APOE*3-Leiden mice were lethally irradiated and reconstituted with bone marrow derived from either p53-deficient (p53(-/-)) or control (p53(+/+)) donor mice. Reconstitution of mice with p53(-/-) bone marrow did not result in any hemopoietic abnormalities as compared with p53(+/+) transplanted mice. After 12 weeks on an atherogenic diet, APOE*3-Leiden mice reconstituted with p53(-/-) bone marrow showed a significant (P=0.006) 2.3-fold increase in total atherosclerotic lesion area as compared with mice reconstituted with p53(+/+) bone marrow. Although likely a secondary effect of the increased lesion area, p53(-/-) transplanted mice also showed significantly more lesion necrosis (necrotic index, 1.1+/-1.3 versus 0.2+/-0.7; P=0.04) and lesion macrophages (macrophage area, 79.9+/-40.0 versus 39.7+/-27.3x10(3) micrometer(2) per section; P=0.02). These observations coincided with a tendency toward decreased apoptosis (terminal deoxynucleotidyl transferase end-labeling [TUNEL]-positive nuclei going from 0.42+/-0.39 to 0.14+/-0.15%, P=0.071), whereas the number of proliferating cells (5'-bromo-2'-deoxyuridine-positive nuclei) was not affected (3.75+/-0.98 versus 4.77+/-2.30%; P=0.59). These studies indicate that macrophage p53 is important in suppressing the progression of atherosclerosis and identify a novel therapeutic target for regulating plaque stability.

The Chinese hamster as a model for the study of diabetes mellitus.

Selection for and against diabetes and subsequent inbreeding of Chinese hamsters started in 1963. Currently there are six inbred sublines that have greater than 85% incidence of glycosuria and two control inbred nondiabetic sublines that are essentially free of glycosuria. At birth, hamsters from inbred sublines are considered prediabetic. There is phenotypic variation between diabetic sublines. Onset time, incidence of ketonuria, blood glucose, plasma insulin, glucagon and glycohydrolase levels vary from subline to subline, but pancreatic insulin and glucagon levels are consistently low and high, respectively, in all diabetic sublines compared with nondiabetics. Experimental breeding data suggest a minimum of two homozygous recessive genes for diabetes. It is not known if the inbred lines are similar diabetic genotypes, but the probability is high that modifier background genes vary from subline to subline. Chinese hamsters have diabetes ranging from mild to severe. Animals weighing 25 g can excrete up to 75 ml of urine containing 3 g of glucose per day. Fasting blood glucose as high as 500 mg/dl and 10 mumol/ml of beta-hydroxybutyrate have been reported. Gluconeogenesis is elevated, and some glycolytic enzymes are decreased in severe diabetes. Low levels of renal acid glycohydrolase enzymes may contribute to glomerular capillary loop basement membrane thickening in diabetic hamsters. Caloric restriction per se or reduction of dietary fat prevented onset of hyperglycemia and hyperinsulinemia in prediabetics. Morphologic changes have been observed in pancreatic islets, kidney, nerve, blood vessels, eyes, brain, and genito-urinary systems of diabetic Chinese hamsters. Pathogenesis of diabetes in this animal appears to be related to an increased demand for insulin. Initially there is a positive response to this demand by beta cells, but exhaustion occurs. This is followed by a decrease in beta-cell mass and relative or absolute insulin deficiency.

Aging changes in intervertebral discs and spondylosis in Chinese hamsters.

Vertebrae and intervertebral discs of Chinese hamsters, a species of rodents that develop spontaneous diabetes, were investigated for age-linked changes and for the occurrence of spondylosis. Aging changes in the intervertebral discs were similar in diabetic and nondiabetic animals. The incidence of spondylosis was significantly increased and its onset was accelerated in the diabetic animals. The mechanisms operative in the pathogenesis of the lesions and their relation to the human disease are discussed.

Responses to arginine of the perfused pancreas of the genetically diabetic Chinese hamster.

Nonketotic, genetically diabetic Cinese hamsters show subnormal pancreatic insulin release and impaired suppression of glucagon in response to glucose. To study the pancreatic effects of other agents, dynamic insulin and glucagon release was measured from the in vitro perfused pancreases of normal and diabetic Chinese hamsters in response to various combinations of arginine (20mM), glucose (100 or 150 mg. per 100 ml.), and theophylline (10 mM). Theophylline alone caused identical insulin and glucagon release in diabetics and normals. Glucose, alone and in the presence of theophylline, caused subnormal insulin release and less suppression of glucagon release in the diabectics than in the normals. Arginine, in the presence of glucose and theophylline, caused excessive glucagon release but nearly normal insulin release in the diabetics. Arginine, in the absence of glucose or theophylline, caused excessive glucagon release in the diabetics and undetectable insulin release in either diabetics or normals. Pancreatic content after perfusion did not correlate with release during perfusion. Infusion of arginine alone markedly decreased the amount of extractable pancreatic insulin and glucagon. These results indicate that the pancreatic alpha cell of the diabetic Chinese hamster responds excessively to arginine, as is seen in the human diabetic. This defect is not related to acute insulin release or the presence of glucose. Further, these results confirm that the diabetic Chinese hamster's alpha and beta cells respond normally to theophylline, but are relatively insensitive to glucose.

Metabolic and underlying causes of diabetes mellitus.

It is emphasized that animal models should be used to study specific genotypic or phenotypic expressions associated with diabetes rather than assuming a single animal model can reflect diverse forms of the human disease. Diabetic and normal animals are reviewed on the basis of their usefulness as models of genetic, viral, and chemically induced diabetes, including the often associated immune phenomena. Characteristics of spontaneously diabetic animals with and without obesity are also described with an emphasis on both genetics and metabolic derangements. Recommendations for future animal experimentation include: more longitudinal studies evaluating the role of sex, prenatal environment, diet, and viral or chemical attack on B-cell function; characterization of the immune phenomena associated with B-cell lesions (and insulitis) in diabetic and immunologically incompetent lines; clarification of relationships between obesity and islet-cell function with emphasis on the role of fuel metabolism, vitamins, and minerals; and, finally, the development of new models with specific genetic aberrations placed in normal or diabetic lines.

Heterogeneity of stage II glottic carcinoma and its therapeutic implications.

The heterogeneity of glottic carcinoma results in variable loco-regional control probabilities from 40 to 80%. These widely different results may be due to two prognostic parameters of the tumor: the mobility of the vocal cord and the volume of the tumor. On the other hand radiation dose and technique may influence the treatment results. Stringent work-up has been prospectively undertaken in 156 patients with Stage II glottic carcinoma since 1974 through 1983 in the Academic Hospital of the Free University in Amsterdam. Several subgroups were defined from the beginning to indicate one or both of these prognostic factors. All were treated with a high quality accurate radiation therapy program delivering high dose to all patients with worse prognostic factors and even higher dosages to voluminous tumors with impaired mobility of a cord or slowly regressing tumors. The latter was individually judged for each patient towards the end of the treatment period. The loco-regional control probability of around 80% for all the subgroups irrespective of the prognostic factors indicate that the heterogeneity of Stage II glottic cancer may be influenced by high dosages of quality controlled radiotherapy. Thus results hitherto reported in literature may be further improved by the dose-schedules outlined here.

Progression of atherosclerosis at one-year follow-up seen with volumetric intravascular ultrasound in femoropopliteal arteries.

Volume measurements derived from intravascular ultrasound (IVUS) images assessed with an automated contour analysis system are accurate and reproducible. However, it is unknown to what extent plaque volume may change at follow-up. Therefore, the purpose of this longitudinal study is to examine whether IVUS is a sensitive means to identify progression of atherosclerosis and its derived primary end point plaque volume at 1-year follow-up. Patients (n = 11) undergoing percutaneous transluminal angioplasty (PTA) of the femoropopliteal artery were studied with IVUS immediately after PTA in the same session and at 1-year follow-up. Matched, well-identified vascular segments (3 to 4 cm in length), not subjected to PTA, imaged at baseline and after 1-year follow-up, were used for calculation of the longitudinal change in lumen, vessel and plaque volume, and mean plaque thickness. The median length of the selected vascular segments was 4 cm. At follow-up (12+/-2 months) a nonsignificant increase in lumen volume (2.3+/-11%), vessel volume (2.0+/-7.0%), and plaque volume (3.0+/-5.1%) was seen; the mean plaque thickness increase was 2.2+/-5.6%. In conclusion, progression of atherosclerosis implies changes in plaque and vessel volume, resulting in lumen volume change. This observation has important implications for future clinical trials aimed at monitoring the effect of pharmacologic agents on the progression and/or regression of atherosclerosis.

Morphometric evaluation of capillary basement membrane thickness in the quadriceps muscle of diabetic and nondiabetic Chinese hamsters.

Quadriceps muscle capillaries from 19-23 month old genetically diabetic (XA and AC) and nondiabetic (M) subline Chinese hamsters were morphometrically evaluated to determine if capillary basement membrane thickening (CBMT) is a quantifiable complication of diabetes. Significant CBMT was present in the diabetic XA Chinese hamsters (49.37 nm +/- 17.81, p less than 0.007) in comparison with the nondiabetic M hamsters (34.08 nm +/- 9.98). Although there was a trend towards expansion of the muscle capillary basement membranes in the diabetic AC Chinese hamsters, the value was not statistically significant. A nested analysis of variance showed that the greatest source of variation in basement membrane thickness occurred among capillaries within each animal. In addition, a positive correlation (r = 0.62; p less than 0.002) existed between blood glucose levels and CBMT in the XA subline. These data should serve as guidelines for evaluation of antimicrovascular disease compounds which will be tested to determine if they prevent or retard microangiopathy in the diabetic Chinese hamster.

The influence of plasma insulin concentrations on tissue insulin levels in rodents: a study of the diabetic Chinese hamster and the ob/ob mouse.

Immunoreactive insulin was measured in acid-ethanol extracts of kidney, brain, liver, and heart from genetically diabetic Chinese hamsters and their nondiabetic controls and from obese (ob/ob) mice and their thin littermates. Selected samples were filtered on Sephadex G-50 columns and the insulin concentration determined. There was a good correlation between the insulin level measured in the acid-ethanol extracts of tissues and the insulin level after gel filtration, suggesting that the concentration measured in the whole extract is representative of the true insulin content. The present data demonstrate that different extrapancreatic organs contain characteristic amounts of insulin that are often (sometimes several-fold) higher than the insulin level of plasma. The tissue insulin concentrations also exhibit a wide range of values, with occasional high values. The data also show a direct correlation between plasma and kidney insulins but no relationship between plasma and brain insulins and a mixed correlation among plasma and liver and heart insulins.

Primary radiotherapy with surgery in reserve for advanced laryngeal carcinoma. Results and complications.

A retrospective study of a selected group of 58 patients with T3 and T4 squamous cell carcinomas of the larynx presenting between 1974 and 1984 was undertaken. These patients were treated primarily with radical radiotherapy and salvage surgery in reserve. The aim of this study was to examine survival, recurrence rate and the complications after salvage surgery. In 30 patients the tumor was classified as a T3 and in 28 as a T4. In 14 patients (24%) nodal disease in the neck was present prior to the radiotherapy. Follow-up in all patients continued for at least 3 years or until death. Nineteen patients (33%) developed locally recurrent tumor and five (9%) developed nodal metastases to the neck. The recurrence in almost every patient was detected within 2 years after completion of the irradiation. Thirty patients (52%) are alive of whom 29 have no evidence of disease. Of these 30 patients 22 (73%) have their larynx intact and functioning. The 5-year adjusted acturial survival for the whole group of patients is 73%, for the T3N0 group 87% and for the T4N0 group 75%. Patients with nodal disease responded poorly. After salvage surgery severe postoperative complications developed in 37% of the patients. There were no deaths following salvage surgery.

MRI of normal or cancerous laryngeal cartilages: histopathologic correlation.

MRI appearances of laryngeal cartilages, normal or invaded by cancer, are still relatively unfamiliar to most clinicians. Twelve primary laryngeal tumors out of a series of 65 patients which have been investigated by MRI were examined postoperatively by macroscopic and microscopic sectioning of the surgical specimens. Images were obtained with a 0.6 Tesla superconductive system using a solenoid surface coil. The authors emphasize the value of a combined use of T1-weighted and balanced (relatively T2-weighted images with still T1-characteristics) Spin Echo images. T1-weighted images permit differentiation between pathological and normal bone marrow. Balanced images allow separation between nonossified cartilage and tumor tissue. MRI is an additional tool in the diagnostic workup of cartilage invasion by tumor.

Articular cartilage of diabetic Chinese hamsters.

Investigations were carried out in order to determine whether animals with spontaneous diabetes are prone to develop skeletal lesions comparable to those found in diabetic human subjects. The present report deals with the ultrastructure of the cartilage of the hip joint of diabetic Chinese hamsters and nondiabetic control animals. In the diabetic animals, chondrocytes of the femoral head showed atrophy of the endoplasmic reticulum, bizarre mitodhoncria, and huge lipid inclusions, which are changes suggestive of disturbed function.

Morphometric analysis of the vagus nerve in non-diabetic and ketonuric diabetic Chinese hamsters.

Morphometric analysis of axons from the ventral division of the vagus nerve of ketonuric diabetic Chinese hamsters and age-sex matched non-diabetic controls was performed to determine the frequency distribution and numerical and volume density. Myelinated fibres of diabetics displayed a significant reduction in diameter (P less than 0.001) compared with controls, which was correlated inversely with progressive ketonuria (P less than 0.05). The reduced calibre of myelinated fibres was the result of thin myelin sheaths rather than a reduction in axon diameter. A marked decrease in numerical density (P less than 0.05) and volume density (P less than 0.005) was found in the myelinated fibres of diabetics compared with controls. Non-myelinated axons showed a significant shift to smaller diameter (P less than 0.001) in diabetics, which was correlated inversely with duration of ketonuria (P less than 0.05). Numerical density of non-myelinated axons was increased (P less than 0.01) in diabetic hamsters whereas volume density was comparable in diabetic and control animals. These data provide morphological evidence of impairment in the parasympathetic nervous system which may be a major factor underlying previously reported gastrointestinal and pancreatic islet dysfunction in the diabetic Chinese hamster.

Emphysematous cholecystitis.

Emphysematous cholecystitis is an acute inflammation of the gallbladder caused by gas forming bacteria. The diagnosis is easily made on a plain abdominal X-ray showing air in the gallbladder. A fatal case is presented and some aspects of the disease are discussed.

Cartilagenous tumours of the larynx.

A brief review of the literature on cartilagenous tumours of the larynx is presented and their pathology, clinical features and treatment is discussed: Chondromas are rare; Chondrosarcomas can be potentially fatal. Conservative surgical therapy and close follow up is the essential line of treatment for tumours of the cricoid cartilage. Three new cases are presented.

Long-term results of surgical intervention on the temporomandibular joint.

Between 1973-1987, 40 patients (51 joints) underwent 71 surgical procedures on the temporomandibular joint (TMJ). Indications for surgery included painful TM dysfunction, not alleviated by conservative treatment of at least 12 months' duration, or complete anterior disk dislocation not responding to conservative treatment for three to six months. The incidence of surgical treatment in the period 1983-1987 was 4.1% in a group of 679 patients. The mean follow-up is 5.8 years (range 1-15 years). At the follow-up examination (37/51) 72.5% of the treated joints appeared to have an excellent or good result; however, 14/51 joints had one or more reoperations (= 14/40 patients: 35%). The first surgical procedure on the TMJ resulted in an excellent or good result in 29/51 (57%) joints: 6/14 (= 42.9%) high condylectomies; 5/8 (= 62.5%) high condylectomies with a plication procedure; 15/24 (= 62.5%) plication procedure only; 2/2 silastic implants. After one or more reoperations, these figures improved to 10/14 (71%) high condylectomies, 7/8 (87.5%) high condylectomies with a plication procedure, 17/24 (70.8%) plication procedures. Radiographic changes, including flattening of the condyle, lack of condylar contour, erosion, sclerosis, subcondral cysts, and osteophytes were seen in all (16/16) patients in which a high condylectomy was performed. Out of 22 joints in which only a disk repositioning and plication procedure was performed, only 4/22 showed radiographic changes. The radiographic status was not correlated to the clinical picture at the time of the follow-up examination.

A field evaluation of arm prostheses for unilateral amputees.

A post-clinical investigation has been carried out among 42 unilateral amputees who lost their hand due to an accident. The investigation was directed at two main topics of interest. Firstly the amputee, the problems he has to cope with, and the role the prosthesis plays in his life; and secondly the prosthesis, its use and its potential benefits and burdens. The group of amputees consisted of above-elbow and below-elbow amputees. Body powered as well as myoelectric prostheses were represented in the group. Most of the information was obtained during a two-day home visit where a semi-structured interview was conducted, and where a number of daily life activities were observed. The information thus obtained has led to a number of conclusions and recommendations with respect to the rehabilitation of this category of amputees, and with respect to the design criteria of prostheses for unilateral amputees.