Per Katzman

Hyperbaric Oxygen Therapy Facilitates Healing of Chronic Foot Ulcers in Patients With Diabetes

OBJECTIVE Chronic diabetic foot ulcers are a source of major concern for both patients and health care systems. The aim of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) in the management of chronic diabetic foot ulcers. RESEARCH DESIGN AND METHODS The Hyperbaric Oxygen Therapy in Diabetics with Chronic Foot Ulcers (HODFU) study was a randomized, single-center, double-blinded, placebo-controlled clinical trial. The outcomes for the group receiving HBOT were compared with those of the group receiving treatment with hyperbaric air. Treatments were given in a multi-place hyperbaric chamber for 85-min daily (session duration 95 min), five days a week for eight weeks (40 treatment sessions). The study was performed in an ambulatory setting. RESULTS Ninety-four patients with Wagner grade 2, 3, or 4 ulcers, which had been present for >3 months, were studied. In the intention-to-treat analysis, complete healing of the index ulcer was achieved in 37 patients at 1-year of follow-up: 25/48 (52%) in the HBOT group and 12/42 (29%) in the placebo group (P = 0.03). In a sub-analysis of those patients completing >35 HBOT sessions, healing of the index ulcer occurred in 23/38 (61%) in the HBOT group and 10/37 (27%) in the placebo group (P = 0.009). The frequency of adverse events was low. CONCLUSIONS The HODFU study showed that adjunctive treatment with HBOT facilitates healing of chronic foot ulcers in selected patients with diabetes.

Carotid Artery Surgery. Local versus General Anaesthesia as Related to Sympathetic Activity and Cardiovascular Effects

Arterial plasma catecholamines, blood pressure and heart rate were determined in 75 patients before, during and after carotid endarterectomy. Local anaesthesia given as a cervical block with skin infiltration containing 200 micrograms adrenaline was used in 28 patients (LA-group), general anaesthesia (nitrous oxide, fentanyl, isoflurane) with skin infiltration containing 200 micrograms adrenaline in 32 patients (GAs-group) and general anaesthesia without skin infiltration in 15 patients (GAo-group). In the LA-Group plasma noradrenaline (P-NA) levels were significantly higher during anaesthesia and surgery, with an increase from preanaesthesia levels (P less than 0.05). P-NA decreased from a preanaesthesia level in the GAo-group (P less than 0.01) but remained unaltered in the GAs-group. P-NA values in the GAo-group were lower than those of the GAs-group (P less than 0.001) following anaesthesia and surgery. Plasma adrenaline (P-A) increased in the LA- and the GAs-group and decreased in the GAo-group (P less than 0.001) following anaesthesia and surgery. In the LA-group P-A was similar before the skin incision and clamping but higher after declamping as compared to the GAs-group. Before the skin incision and thereafter P-A was lower in the GAo-group as compared to the other groups. There was a positive correlation between plasma catecholamines, on the one hand, and mean blood pressure and heart rate on the other. Two patients in the LA-, eight in the GAs- and seven in the GAo-group showed a hypotensive blood pressure reaction (SBP less than 100 mmHg; LA vs. GAo, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperbaric oxygen therapy improves health-related quality of life in patients with diabetes and chronic foot ulcer

Diabet. Med. 28, 186–190 (2011)

What is the Role of Hyperbaric Oxygen in the Management of Diabetic Foot Disease

Systemic hyperbaric oxygen (HBO) is accomplished when a patient is breathing 100% oxygen in an environment with increased barometric pressure. A typical HBO treatment protocol of diabetic foot ulcer involves 20 to 40 sessions. Treatment is usually given as daily 90- to 120-minute HBO sessions at pressures between 2.0 and 2.5 absolute atmospheres. The wide use of HBO as treatment of diabetic foot ulcers over the past decades has been founded on weak scientific ground (ie, few and small prospective studies with methodologic limitations on top of case series). However, the consistency in positive outcome in these trials evaluating HBO on ulcer healing is noteworthy because these findings are in concert with data from in vitro and physiologic studies supporting the theoretic framework of HBO reversing hypoxia-induced pathology. Two well-designed randomized double-blinded placebo-controlled studies have in recent years put HBO on firmer ground as treatment of a selection of diabetic patients with chronic foot. Some evidence indicates that microvascular parameters such as transcutaneous (partial) oxygen pressure (TcPO2) could be useful in predicting which patients will benefit from therapy. Health economic studies suggest potential cost-effectiveness of HBO. But because these analyses are limited by their deficient primary clinical data, they should be interpreted with caution. Thus, HBO is only indicated in a selected group of patients with chronic diabetic foot ulcers. Several key issues remain to be addressed such as developing robust criteria to determine which patients are likely to benefit and when to start and stop treatment.

Biochemical diagnosis of primary hyperparathyroidism: Analysis of the sensitivity of total and ionized calcium in combination with PTH.

OBJECTIVES To investigate the accuracy of the biochemical diagnosis of primary hyperparathyroidism (pHPT) in a consecutive series of patients with operatively verified disease. DESIGN AND SUBJECTS Four hundred thirty-six patients with pHPT, 340 women and 96 men, were reviewed. Biochemical variables, including total calcium (Ca), ionized calcium (Cai) and PTH were analyzed and registered in a prospective database. RESULTS In the subgroup of patients with more mild hypercalcemia (Ca below 2.70mmol/L) the correlation between Ca and Cai was poor. 19 respectively 18 patients had preoperatively a Ca respectively Cai level within the reference range. Further 35 patients had preoperatively a normal level of PTH. The diagnostic sensitivities, in detecting pHPT, for Ca, Cai and the combination of Ca and Cai were 96%, 96% and 99%. CONCLUSION If calcium and ionized calcium are not used in the diagnostic workup of pHPT some 4% of the patients will be overlooked. We recommend analyzing both Ca and Cai in the diagnostic workup of pHPT.

Cardiovascular prevention before admission reduces mortality following acute myocardial infarction in patients with diabetes

Abstract. Löndahl M, Katzman P, Nilsson A, Ljungdahl L, Prütz K‐G (Helsingborg Hospital, Helsingborg, Sweden). Cardiovascular prevention before admission reduces mortality following acute myocardial infarction in patients with diabetes. J Intern Med 2002; 251: 325–330.

Comments on Margolis et al. Lack of effectiveness of Hyperbaric Oxygen Therapy for the Treatment of Diabetic Foot Ulcer and the Prevention of Amputation

Dear Editors, In a cohort trial recently published in Diabetes Care (1), longitudinal data from NHC (2005–2011) were used to compare diabetic foot ulcer (DFU) healing and amputation rates at 16 weeks in 793 patients receiving hyperbaric oxygen (HBO) therapy with 5466 patients not receiving HBO. Some of the conclusions call for comments. First of all, randomisation is the best available method to reduce selection biases, especially when hard to identify. Also, if study treatment is double-blind, biases linked to patient compliance is reduced. In the present cohort study selection bias cannot be ruled out. Contrarily, all patients were individually selected for HBO treatment based on decisions taken by experienced clinicians. Secondly, HBO has been shown to exert several plausible effects that might enhance ulcer healing. Some are acute, as immediate increase in tissue pO2 during an HBO treatment session had been noted, whereas others such as recruitment of stem/progenitor cells may be fully manifested only after several weeks (2). Therefore, a follow-up period of 16 weeks might be too short to identify the full effect of HBO as indicated by our own findings at 16 weeks (in the randomised placebo-controlled double-blind HODFU-study) showing an ulcer healing rate of less than 15% in the HBO group (3). Thirdly, in the discussion authors rely on the negative ≥1 year healing outcome as reported in the 2012 Cochrane analysis. However, this analysis had reservations about accuracy – that is, between-trial heterogeneity was prominent, inclusion criteria and study designs largely differed – are omitted (4). As cited, Cochrane’s three randomised-controlled trial (RCT)-meta-analysis, including studies by Abidia et al., Duzgun et al. and Löndahl et al., did not show any significant difference between groups (RR in favour of HBO 9·53, P = 0·15). Between-trial heterogeneity was, however, notably enhanced by the low healing rate (0/50) in Duzgun’s control group. Duzgun’s study endpoint was healing without amputation or debridement in the operating room – that is not including healing with debridement, and nine control group patients in fact healed after this. If the latter definition of ulcer healing had been applied throughout Cochrane’s meta-analysis, the between-trial heterogeneity, and thereby possibly the P -values, could have been different. Thus, another recently published meta-analysis including data from RCTs using sham therapy showed improved ulcer healing at 1 year following HBO treatment (odds ratio 2·3; P = 0·03) (5). Fourthly, as compared to above-mentioned double-blind RCTs, differences in inclusion criteria for HBO treatment should be noted, which includes, for example, considerably lower mean ulcer duration. Also, a substantially lower minimum number of HBO sessions was needed for patients to be included in the intention-to-treat cohort analysis. In conclusion, the present cohort trial does not convincingly confirm that HBO is an ineffective tool in the armamentarium of diabetic foot ulcer therapy. We agree with the authors that more well-designed RCTs are needed. In our opinion, only inclusion criteria used in double-blind RCTs should at present serve as practice guidelines in selecting patients for non research HBO treatment.

Antihypertensive efficacy and tolerability of enalapril and slow-release verapamil in essential hypertension: a double-blind, cross-over study.

Abstract. The antihypertensive efficacy and tolerability of enalapril (E) and slow‐release verapamil (V) were compared in a 2‐month double‐blind cross‐over study in 22 patients with mild to moderate essential hypertension. After 1 month, significantly lower systolic (P < 0.01) and diastolic (P < 0.02) blood pressures (BP) were achieved with E, 20 mg d−1, compared with V, 240 mg d−1. After 2 months of treatment, BP reductions were similar after E, 40 mg d−1, and V, 240 mg twice a day. The fall in supine mean BP after 2 months of treatment with V was significantly greater in patients aged ≥ 50 years of age (P = 0.02) (median 18 mmHg) than in patients aged < 50 years (10 mmHg). E showed similar effectiveness in both age groups. Statistical group analysis of a quality‐of‐life questionnaire showed no significant differences between the active drugs and the placebo. It is concluded that E and V are equally effective as antihypertensive agents, and that both drugs are well tolerated.

A case of constrictive pericarditis during cabergoline treatment for hyperprolactinaemia.

OBJECTIVE Treatment with dopamine agonists has been associated with cardiopulmonary fibrotic reactions, predominantly in patients treated for Parkinsons disease. To our knowledge, these reactions have previously not been associated with low-dose cabergoline treatment for hyperprolactinaemia. METHOD A case of constrictive pericarditis in a patient treated with cabergoline for hyperprolactinaemia is presented. The patient has been treated at a county hospital and a university hospital in southern Sweden. RESULTS A 20-year-old woman with a 3-year history of amenorrhoea was referred to the department in 1992. From 2001 to 2005, she was given cabergoline, 0.5-1.5 mg/week. In 2005 a pericardectomy was performed due to fibrotic, constrictive pericarditis. CONCLUSIONS Our present case suggests that constrictive pericarditis may develop even on low-dose cabergoline, which might indicate that this reaction, as opposed to valvular fibrosis, is not mediated by a 5-HT(2B) agonistic mechanism.

Glucose Tolerance and Secretion and Clearance of Insulin during Long Term Felodipine Treatment

ConclusionsGlucose tolerance was unaltered during long term felodipine treatment. Furthermore, felodipine did not affect glucose-stimulated insulin release as the incremental area under the curve for peripheral venous C-peptide, which reflects insulin secretion (Binder & Faber 1985), was unchanged. The decreased incremental area under the curve for insulin during felodipine treatment suggests increased insulin clearance.