A dietary and behavioural programme for the treatment of obesity. A 4-year clinical trial and a long-term posttreatment follow-up

OBJECTIVES: To evaluate weight loss maintenance after 4 years of nonpharmacological, nonsurgical obesity treatment, including a very low calorie diet (VLCD), diet and behavioural support. Furthermore, to assess weight development amongst completers and noncompleters beyond the active 4-year treatment period. DESIGN: Clinical trial. SETTING: Two Swedish county hospitals. SUBJECTS: A total of 113 patients were randomized to a 2-year treatment programme with or without an initial VLCD period. The 87 patients who completed the 2-year programme were offered the chance to continue a support programme for another 2 years. A total of 55 patients completed the entire 4-year programme. INTERVENTIONS: All the patients took part in a comprehensive support programme, including a hypocaloric diet and behavioural support, either as single treatment (non-VLCD group) or following the VLCD period (VLCD group). RESULTS: Significant 4-year weight losses were found in both groups, 7.6 +/- 12.2 kg (VLCD group) and 6.3 +/- 8.5 kg (non-VLCD group), (P < 0.01, n.s. between groups). The completers (n = 55) had maintained a weight loss of 3.3 +/- 10.7 kg (P < 0.05) 8 years after randomization. After 6 years, the noncompleters (n = 58) had gained 3.2 +/- 9.7 kg compared with baseline (P < 0.05). The difference in weight change between completers and non-completers was highly significant (P < 0.01). CONCLUSIONS: Highly significant weight losses can be maintained after a 4-year comprehensive treatment programme, including a hypocaloric diet and behavioural support. An initial VLCD period did not significantly affect the long-term weight loss. The posttreatment long-term weight loss was larger amongst completers than amongst patients who did not complete the treatment.     

High survival in adult patients with acute respiratory distress syndrome treated by extracorporeal membrane oxygenation, minimal sedation, and pressure supported ventilation

OBJECTIVES: To evaluate the results of treatment of severe acute respiratory distress syndrome (ARDS) with extracorporeal membrane oxygenation (ECMO), minimal sedation, and pressure supported ventilation. DESIGN AND SETTING: Observational study in a tertiary referral center, Intensive Care Unit, Astrid Lindgren Children's Hospital at Karolinska Hospital, Stockholm, Sweden. SUBJECTS AND METHODS: Seventeen adult patients with ARDS were treated with venovenous or venoarterial ECMO after failure of conventional therapy. The Murray score of pulmonary injury averaged 3.5 (3.0-4.0) and the mean PaO2/FIO2 ratio was 46 (31-65). A standard ECMO circuit with nonheparinized surfaces was used. The patients were minimally sedated and received pressure-supported ventilation. High inspiratory pressures were avoided and arterial saturation as low as 70% was accepted on venovenous bypass. RESULTS: In one patient a stable bypass could not be established. Among the remaining 16 patients 13 survived (total survival rate 76%) after 3-52 days (mean 15) on bypass. Major surgical procedures were performed in several patients. The cause of death in the three nonsurvivors was intracranial complications leading to total cerebral infarction. CONCLUSION: A high survival rate can be obtained in adult patients with severe ARDS using ECMO and pressure-supported ventilation with minimal sedation. Surgical complications are amenable to surgical treatment during ECMO. Bleeding problems can generally be controlled but require immediate and aggressive approach. It is difficult or impossible to decide when a lung disease is irreversible, and prolonged ECMO treatment may be successful even in the absence of any detectable lung function.     

Origin of carcinoma in secretory endometrium—A study using a whole-organ sectioning technique

Uteri from four patients with endometrial adenocarcinoma and concomitant “functioning” endometrium were examined by a whole-organ sectioning technique. All showed one or several “progesterone-refractory” mucosal areas or polyps, mainly in the tubal recesses. In one patient the adenocarcinoma obviously originated in a fundal polyp, and in the others the tumors could have arisen in mucosal areas not adequately responding to progesterone. These findings do not in fact contradict the “unopposed estrogen” theory of the genesis of endometrial carcinoma.     

Neurological signs are common in patients with urodynamically verified "idiopathic" bladder overactivity

Overactive bladder dysfunction is an expression of defective neuromuscular control of the lower urinary tract. The causes and the way to classify this problem are currently under debate. In some patients the overactive bladder is one sign of a neurological disorder, in so called "idiopathic detrusor instability" the cause is less obvious. That an overactive bladder has a neurogenic cause is a reasonable hypothesis. We made a detailed neurological investigation in 45 patients with idiopathic overactive bladder. Cerebrospinal fluid (CSF) was examined and blood tests for vitamin B(12)and folic acid deficiency were checked, too. In 37 of the 45 patients (82%) pathological signs were observed in the neurological tests. The most common finding was central or peripheral paresis of the legs appearing in 24 patients (53%). Of the 45 patients, eight received a neurological diagnosis, definite or possible MS or dorsal column sensation neuropathy. The results of this study give an indication of the importance of the neurological examination and suggest that neuropathy might not be uncommon in patients with so-called idiopathic detrusor instability. This also invites to reconsideration of the current classification. It is possible that a new classification based on a functional view could provide a better fundament in the search of etiologic and pathogenetic factors and also guide in the selection of the treatment most optimal for the individual patient.     

Gross genomic aberrations in precancers: clinical implications of a long-term follow-up study in oral erythroplakias.

PURPOSE: Gross genomic aberrations are increasingly seen as a cause rather than a consequence of carcinogenesis. Carcinomas may be prevented by systemically acting agents when used in high-risk individuals. If gross genomic aberrations could be shown to be predictive markers in precancers, they could serve as a tool for identifying high-risk individuals to be included in chemopreventive trials. PATIENTS AND METHODS: To investigate the predictive power of gross genomic aberrations in several types of oral premalignancies, we analyzed 57 biopsies from oral erythroplakias of 37 patients, both histologically and for DNA content. DNA content was measured by high-resolution image cytometry, and distribution histograms of DNA content were generated and interpreted according to established protocols. The primary end point was cancer-free survival. RESULTS: Fifty-seven dysplastic oral red lesions from 37 patients were investigated. Forty-one lesions from 25 patients were classified with aberrant DNA content (DNA aneuploidy), of which 23 patients (92%) later developed an oral carcinoma (after a median observation time of 53 months; range, 29 to 79 months). Of 12 patients having altogether 16 lesions with normal DNA content, none developed a carcinoma (median observation time, 98 months; range, 23 to 163 months; P <.001). In multivariate analysis, DNA content was a significant prognostic factor (P <.001), whereas histologic grade, sex, use of tobacco, size and location of lesions, and the presence multiple of lesions were not. CONCLUSION: Gross genomic aberrations are highly predictive for the subsequent occurrence of carcinomas from a wide range of oral premalignancies.