Clearance of proteoglycan from joint cavities.

The rate of loss from the synovial cavity of proteoglycan subunit, a major constituent of cartilage, has been measured in rabbits with and without experimental arthritis. The effect of aggregation between proteoglycan and hyaluronic acid upon the rate of elimination has also been investigated. The results indicate that proteoglycan subunit has a clearance half life of around 12 hours in normal joints and that this rate is not significantly altered in the presence of an active synovitis. Neither injection of proteoglycan as an aggregate, nor in a form incapable of aggregation, had any significant effect on clearance rates. These data indicate that loss of proteoglycan from the joint is not retarded by its ability to aggregate with hyaluronic acid in the synovial fluid and, together with measurements of synovial fluid proteoglycan, may enable rates of cartilage breakdown in vivo to be calculated.     

Occlusive disease confined to the right coronary artery: Clinical features, surgical treatment and long-term follow-up in 124 patients

The clinical presentation and surgical results in 124 consecutive patients who underwent aorta to right coronary arterial bypass surgery from January 1970 through June 1977 were reviewed. Preoperatively, 75 percent of the patients were in New York Heart Association functional class III or IV, 9 percent presented with unstable angina and 5 percent had life-threatening ventricular arrhythmias. All patients had high grade occlusive disease confined to the right coronary artery; 34 percent of the patients had associated nonsignificant disease (less than 50 percent intraluminal narrowing) of the left anterior descending or circumflex artery. Left ventricular function was normal in 63 percent and minimally impaired in 37 percent. The operative mortality rate was 1.6 percent. The course of the 122 survivors was followed up for 3.7 years. There were four late deaths, and the 5 year mortality rate was 4.0 percent. Eight patients were reoperated on because of recurrence of symptoms and occlusion of the graft or progression of occlusive disease of the other major coronary arteries, or both. Of the remaining 110 patients, 98 are either in functional class I or II, 60 are taking no cardiovascular medications, 52 are working full time without angina and 73 are asymptomatic. In summary, bypass surgery for isolated right coronary artery disease has a low mortality rate and results in excellent long-term symptomatic improvement.     

Embryo fossilization is a biological process mediated by microbial biofilms

Fossilized embryos with extraordinary cellular preservation appear in the Late Neoproterozoic and Cambrian, coincident with the appearance of animal body fossils. It has been hypothesized that microbial processes are responsible for preservation and mineralization of organic tissues. However, the actions of microbes in preservation of embryos have not been demonstrated experimentally. Here, we show that bacterial biofilms assemble rapidly in dead marine embryos and form remarkable pseudomorphs in which the bacterial biofilm replaces and exquisitely models details of cellular organization and structure. The experimental model was the decay of cleavage stage embryos similar in size and morphology to fossil embryos. The data show that embryo preservation takes place in 3 distinct steps: (i) blockage of autolysis by reducing or anaerobic conditions, (ii) rapid formation of microbial biofilms that consume the embryo but form a replica that retains cell organization and morphology, and (iii) bacterially catalyzed mineralization. Major bacterial taxa in embryo decay biofilms were identified by using 16S rDNA sequencing. Decay processes were similar in different taphonomic conditions, but the composition of bacterial populations depended on specific conditions. Experimental taphonomy generates preservation states similar to those in fossil embryos. The data show how fossilization of soft tissues in sediments can be mediated by bacterial replacement and mineralization, providing a foundation for experimentally creating biofilms from defined microbial species to model fossilization as a biological process.     

Discrimination and abuse in internal medicine residency

OBJECTIVE: To survey the extent to which internal medicine housestaff experience abuse and discrimination in their training. DESIGN: Through a literature review and resident focus groups, we developed a self-administered questionnaire. In this cross-sectional survey, respondents were asked to record the frequency with which they experienced and witnessed different types of abuse and discrimination during residency training, using a 7-point Likert scale. PARTICIPANTS: Internal medicine housestaff in Canada. MEASUREMENTS AND MAIN RESULTS: Of 543 residents in 13 programs participating (84% response rate), 35% were female. Psychological abuse, as reported by attending physicians (68%), patients (79%), and nurses or other health workers (77%), was widespread. Female residents experienced gender discrimination by attending physicians (70%), patients (88%), and nurses (71%); rates for males were 23%, 38%, and 35%, respectively. Females reported being sexually harassed more often than males, by attending physicians (35% vs 4%,p<.01), peers (30% vs 6%,p<.01), and patients (56% vs 18%,p<.01). Physical assault by patients was experienced by 40% of residents. Half of the residents surveyed reported racial discrimination and homophobic remarks in the workplace, perpetrated by all groups of health professionals. CONCLUSIONS: Psychological abuse, gender discrimination, sexual harassment, physical abuse, homophobia, and racial discrimination are prevalent problems during residency training. Housestaff, medical educators, allied health workers, and the public need to work together to address these problems in the training environment. Dr. Cook is a Career Scientist with the Ontario Ministry of Health. For a complete listing, see Appendix A. This study was supported by the Royal College of Physicians and Surgeons of Canada.     

Portal vein thrombosis following endoscopic variceal sclerotherapy

The association between portal vein thrombosis (PVT) and prior endoscopic variceal sclerotherapy has been suggested but remains unproven. The aim of this study was to compare the incidence of PVT in patients who had received sclerotherapy for esophageal variceal hemorrhage to a control group of cirrhotic patients with portal hypertension who had not received sclerotherapy. Doppler ultrasound was used to assess PVT in 48 patients (group 1) who had received sclerotherapy for variceal hemorrhage as well as in 52 patients (group 3) with cirrhosis and portal hypertension who had not received sclerotherapy. Assessment of PVT was made at the time of surgery in 24 patients (group 2) who had received sclerotherapy for variceal hemorrhage, failed therapy, and had portacaval shunt surgery or received liver transplantation for liver failure. One patient had splenectomy for symptoms related to a massively enlarged spleen. The incidence of PVT in group 1 was 10%, in group 2 was 13%, and in group 3 was 10%. The incidence of PVT in the three groups was not significantly different statistically. In this controlled study of patients with cirrhosis and portal hypertension, sclerotherapy does not increase the incidence of PVT.     

Results of colectomy for severe slow transit constipation

PURPOSE: This study assesses the outcome of a standardized operation performed by two surgeons for severe idiopathic slow transit constipation that was resistant to laxative treatment. METHODS: Fifty-nine consecutive patients, 4 men and 55 women, with a mean age of 42.3 years, underwent colectomy with ileorectal anastomosis. Slow colonic transit was demonstrated in each case. Fifty-two patients were available for follow-up, with median time to follow-up being 42 (range, 3–81) months. RESULTS: Median bowel frequency was 4 per 24 hours. Sixty-nine percent had four or less bowel movements daily. Ten percent used antidiarrheal medication regularly. One patient had a stoma for recurrent severe constipation. Mean continence score was 1.8 (on a scale of 0–20); six patients were incontinent, and four of these six had normal preoperative anal manometry. Fourteen patients (27 percent) had difficulty with rectal evacuation. Preoperative defecating proctography was a poor predictor of postoperative evacuation difficulties. Twenty-seven patients (52 percent) had persisting abdominal pain, but there was a significant improvement in the degree of pain (P <0.00001). Forty-seven patients (90 percent) were satisfied with the outcome of the operation (and would elect to have it done again). Dissatisfied patients had recurrent constipation or diarrhea and incontinence. CONCLUSION: Colectomy with ileorectal anastomosis produces a satisfactory functional outcome in the majority of patients undergoing surgery for severe constipation with proven slow colonic transit.Supported by the Division of Surgery and the Colorectal Research Fund.Read at the meeting of the Royal Australasian College of Surgeons, Perth, Australia, May 1995.     

Quality of life in bed partners of patients with obstructive sleep apnea or hypopnea after treatment with continuous positive airway pressure

OBJECTIVE: Obstructive sleep apnea (OSA) has been shown to affect the quality of life (QOL) in patients, and QOL improves after treatment with nasal continuous positive airway pressure (CPAP). However, the effects on the bed partner of the patient with OSA have received little attention. We studied QOL in patients with OSA and their bed partners, and the effect of CPAP therapy on QOL. DESIGN: Fifty-four patients and their bed partners who had been seen for evaluation of OSA, had undergone polysomnography, and subsequently had received treatment with CPAP. Patients and bed partners completed the Epworth sleepiness scale (ESS) and QOL questionnaires before and after the patients' therapy. SETTING: Sleep disorders center in an academic medical center. PARTICIPANTS: Patients with documented OSA and regular bed partners. INTERVENTIONS: Both individuals completed the 36-item short-form health survey (SF-36), the ESS, and the Calgary sleep apnea quality of life index (SAQLI). At about 6 weeks after CPAP therapy, patients and their bed partners completed the same set of questionnaires again. RESULTS: Of the 54 subjects who completed the study, the mean (+/- SD) apnea-hypopnea index was 48.4 +/- 33.3. For the subjects, the mean ESS decreased from 12.9 +/- 4.4 to 7.3 +/- 4.0 (p < 0.001) after treatment with CPAP. For the bed partners, the mean ESS decreased from 7.4 +/- 6.1 to 5.8 +/- 4.7 (p = 0.02). The mean scores on the SAQLI were 4.1 +/- 1.0 for the subjects and 4.5 +/- 1.3 for the bed partners. Following CPAP therapy, the SAQLI increased in the subjects to 4.9 +/- 1.2 (p < 0.001), and in the bed partners to 5.1 +/- 0.9 (p = 0.002). The SF-36 showed positive changes in both the subjects and the bed partners. Significant improvements were observed in the subjects in role-physical, vitality, social functioning, role-emotional, and mental health domains. In the bed partners, significant changes in the SF-36 were observed in role-physical, vitality, social functioning, and mental health domains. CONCLUSION: OSA results in impaired QOL in both the patients and their bed partners. Treatment with CPAP improves QOL, as measured by the SF-36 and the SAQLI.     

Is there a future for liver-assist devices?

Patients with fulminant hepatic failure fall into two categories: those who will not recover without hepatic replacement, and those with severe but potentially reversible liver injury whose livers have the potential to recover and/or regenerate. Liver support systems must provide physiologic support, rendering the patient hemodynamically stable and “bridging” the patient to transplantation, or allowing the native liver to recover and/or regenerate. Recent limited successes with bioartificial liver support for patients with fulminant liver failure are encouraging. However, these preliminary results come without randomization or control groups and without stratification by disease etiology or severity. It is hoped that randomized, controlled trials will answer important questions about the efficacy of these systems.     

Clinical and haematological consequences of recurrent G6PD mutations and a single new mutation causing chronic nonspherocytic haemolytic anaemia

We have determined the causative mutation in 12 cases of glucose-6-phosphate dehydrogenase deficiency associated with chronic non-spherocytic haemolytic anaemia. In 11 of them the mutation we found had been previously reported in unrelated individuals. These mutations comprise seven different missense mutations and a 24 base pair deletion, G6PD Nara, previously found in a Japanese boy. Repeated findings of the same mutations suggests that a limited number of amino acid changes can produce the CNSHA phenotype and be compatible with normal development. The one new mutation we have found, G6PD Serres, is 1082 C → T causing a 361 Ala → Val substitution in the dimer interface where most other severe G6PD mutations are found. Now that several patients with the same mutation have been reported we can compare the resulting clinical phenotypes. For each mutation we find a reasonably consistent clinical picture, ranging from mild (G6PD Clinic) through moderate (G6PD Nashville) to severe (G6PD Beverly Hills and G6PD Nara).     

Lipid response to pioglitazone in diabetic patients: clinical observations from a retrospective chart review

The objective of this study was to determine whether improvements in the lipid profile observed in controlled clinical trials with pioglitazone are seen in the clinical practice setting, and to ascertain the influence of concurrent statin treatment. Charts of 100 consecutive patients with type 2 diabetes (mean age 56.8 years) treated with pioglitazone (45 mg/day) for 2-4 months were retrospectively analyzed for changes in serum lipids, glycemic parameters, and body weight. Subanalyses were performed on the relationship of lipid changes to baseline lipid values and to concurrent statin therapy. Pioglitazone was associated with statistically significant (p < 0.001) changes from baseline in HbA(1C) (mean decrease 1.09%), body weight (mean increase 1.76 kg), HDL cholesterol (HDL-C) levels (mean increase 15.6%), and triglycerides (mean decrease 9.9%). There was an increase (+ 1.09%) in mean individual LDL-C levels from baseline values, but this change was not statistically significant. The greatest absolute and percentage improvements in HDL-C and triglycerides were observed in patients who had the greatest lipid abnormalities at baseline: in patients with baseline HDL-C < 35 mg/dL, mean individual HDL-C values increased by 31% (p < 0.001); in those with baseline triglycerides >399 mg/dL, triglyceride levels decreased by 46% (p < 0.001); and in patients with baseline LDL-C > 129 mg/dL, mean individual LDL-C values decreased by 10.6% (p < 0.001). Subgroup analysis showed similar beneficial changes in HDL-C and triglycerides in patients who were not receiving concurrent statin therapy (n = 48) as in those who were receiving statins (n = 49). This observational study demonstrated that significant improvements in HDL-C and triglyceride levels can be achieved with pioglitazone in the clinical practice setting. The greatest improvements occurred in patients with the worst baseline lipid levels, and benefits were seen regardless of whether patients were receiving concurrent statin therapy.