Toe temperature versus transcutaneous oxygen tension monitoring during acute circulatory failure

Measurements of toe temperature and transcutaneous PO₂ (P_tcO₂) have been both suggested for non-invasive assessment of peripheral blood flow in acute circulatory failure. The underlying principle of the two methods is that cutaneous vasoconstriction occurs early when tissue perfusion is altered. In 15 patients, we compared the two measurements during cardiogenic shock (27 measurements) or septic shock (29 measurements). Toe-ambiant temperature gradient and P_tcO₂ correlated well together (r=0.66, p(0.001) especially in hyperkinetic septic shock (r=0.79, p(0.001). In cardiogenic shock, toe-ambiant temperature correlated well with cardiac index (r=0.63), stroke index (r=0.64) and oxygen transport (r=0.65), and these correlations were stronger than for P_tcO₂. In septic shock, both techniques were poor indicators of blood flow indexes but P_tcO₂ rather correlated with arterial pressure (r=0.66) and left ventricular work (r=0.66). Trend evaluation of data revealed in cardiogenic shock that the increase in toe temperature usually preceded the increase in P_tcO₂. Since measurement of P_tcO₂ is technically more complicated, correlates less well with standard hemodynamic parameters and later reflects cardiovascular improvement, it has no advantage over measurement of toe temperature in circulatory shock. In cardiogenic shock, measurements of toe temperature can reliably track cardiac output changes. In septic states, however, non-invasive assessment of skin perfusion is of limited interest.     

Antihypertensive effect of beta blockade in renal transplant recipients with or without host kidneys

Host kidneys may contribute considerably to hypertension after renal transplantation. Their role in sustaining hypertension is more prominent if glomerulonephritis (GN) than if interstitial nephritis (IN) is the original renal disease. We compared the antihypertensive effect of beta-blockade in IN (n = 10) and GN (n = 19) hypertensive renal transplant recipients with host kidneys in situ with those who had undergone bilateral nephrectomy (BN, n = 10). Pretreatment blood pressures were comparable in BN, IN, and GN patients, being 165 +/- 6/108 +/- 3, 172 +/- 5/104 +/- 3, and 161 +/- 3/104 +/- 1, mmHg, respectively. Blood pressure did not change on beta-blockade in BN patients, whereas it decreased significantly more (P less than 0.001) in GN than in IN patients, changes of mean arterial pressure being -107 +/- 1.0, -14.9 +/- 1.3, and -6.8 +/- 1.6%, respectively. This failure to respond to beta-blockade in patients without host kidneys may be related to low activity of the renin-angiotensin system or to functional denervation of the grafted kidney. Further investigations of this phenomenon may clarify the mechanism of antihypertensive action of beta-blockade as well as the nature of hypertension after renal transplantation.     

A comparative study on the diagnostic value of prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) in patients with carcinoma of the prostate gland

Serum prostatic-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined simultaneously in 241 patients presented to the Urology Department. The patients consisted of 140 prostatic carcinoma patients (34 newly diagnosed and 106 previously treated) and 101 patients with benign prostatic hypertrophy (BPH). Prostatic acid phosphatase was measured by two different methods, an enzymatic method (PAP-EA, Boehringer) with tartrate inhibition and an immunoenzymetric assay (PAP-IEMA, Hybritech). The concentration of prostatic specific antigen in serum was measured using a recently introduced immunoradiometric assay (PSA-IRMA, Hybritech). Receiver operating characteristic curves were constructed to compare the diagnostic value of the different tests at different cutoff values. The diagnostic efficiencies of the PAP-EA and the PAP-IEMA appeared to be similar. A better diagnostic efficiency for PSA compared to PAP was found independent of the cutoff value. The upper-normal limit of 2.7 micrograms/l for PSA, as suggested by the manufacturer and mentioned in the literature introduces too many false-positive results. We therefore selected 10 micrograms/l as the upper-normal limit for PSA (sensitivity 57%, specificity 88%). Combined sensitivity found for PAP + PSA was 37% with a specificity of 97%. A literature survey is included to allow better comparison with data published elsewhere.     

Cardiovascular effects of caffeine and nifedipine

Because caffeine and nifedipine may have opposing effects on intracellular calcium concentration, a possible interaction between these agents on blood pressure and heart rate was examined. With a randomized, double-blind, crossover design, 10 normal, caffeine-abstaining subjects received caffeine, 300 mg, or placebo followed by nifedipine, 10 mg, or placebo. Caffeine increased blood pressure, whereas nifedipine reduced it and caused a reflex increase in heart rate. With caffeine pretreatment, nifedipine decreased blood pressure significantly more than with placebo pretreatment. However, nifedipine reduced blood pressure to the same absolute level on both the caffeine and placebo pretreatment days. The reflex increase in heart rate after nifedipine was not affected by prior caffeine or placebo administration. Caffeine pretreatment does not alter the cardiovascular responses to nifedipine but the pressor effect of caffeine is completely reversed by subsequent nifedipine administration.     

Chondrocyte-seeded hydroxyapatite for repair of large articular cartilage defects. A pilot study in the goat

The aim of this study was to evaluate the potential for restoration of a large cartilage defect in the goat knee with hydroxyapatite (HA) loaded with chondrocytes. Isolated chondrocytes were suspended in fibrin glue, seeded on top of the HA, and then the composite graft was implanted in the defect. After transplantation, cell behaviour, newly synthesised matrix and the HA–glue interface were assessed histologically after 2, 4, 12, 26 and 52 weeks. Special attention was paid to the incorporation process of HA in the subchondral bone and interactions between this biomaterial and the fibrin-glue–chondrocyte suspension.

Chondrocytes in the glue proved to survive the transplantation procedure and produced new metachromatically stained matrix two weeks after implantation. The glue–cell suspension had penetrated the superficial porous structure of the HA. Four weeks after surgery, islands of hyaline-like cartilage were observed at the HA–glue interface. A layer of fibrous tissue was formed surrounding the HA graft, resulting in a relatively instable fixation of the HA in the defect. This instability of the graft in the defect, possibly together with early weight bearing, resulted in a gradual loss of the newly formed hyaline cartilage-like repair tissue. Progressive resorption of the HA occurred without any sign of active bone remodelling from the host site. One year after surgery part of the defect which extended down to the cancellous bone had been predominantly restored with newly formed lamellar bone. Only small HA remnants were still present at the bottom of the original defect. Resurfacing of the joint had occurred with fibrocartilaginous repair tissue.

The absence of adequate fixation capacity of the HA near the joint space resulted in a relative instability of the graft with progressive resorption. Therefore, HA is not a suitable biomaterial to facilitate the repair of large articular cartilage defects.     

Adverse reactions attributed to sumatriptan

There are several reports on cardiac adverse reactions attributed to the antimigraine drug sumatriptan in the recent literature. In order to assess the frequency and the character of adverse reactions to sumatriptan, a postmarketing cohort study was performed one year after registration of the drug in The Netherlands. With assistance of 86% of the drug dispensing general practitioners in The Netherlands, 1727 patients who had received sumatriptan were traced in July, 1992. Via their general practitioners, a questionnaire about use of sumatriptan, adverse reactions and other medication was sent to the patients in December 1992. During the study period, seven patients were lost to follow-up. Of the 1720 remaining patients, 1202 (70%) responded to the questionnaire, of whom 1187 had actually used sumatriptan. The most frequently reported suspected adverse reactions were paraesthesiae (139 patients, 95% CI 9.9%–13.5%) and dizziness (96 patients, 95% CI 6.5%–9.7%). Chest pain after use of sumatriptan was reported by 94 patients (7.9%, 95% CI 6.4%–9.4%), and according to the close temporal relationship with the intake of sumatriptan and a positive rechallenge, a causal relationship was probable in most of those patients. The frequency of chest pain attributed to sumatriptan was higher in females (9.0% vs 4.6%; relative risk 1.9, 95% CI 1.1–3.4). Age and hypertension were not associated with chest pain attributed to sumatriptan. Dyspnoea attributed to sumatriptan was reported by 26 patients (2.2%), and was associated with obstructive lung disease (relative risk 5.4 95% CI 1.7–16.9). Thus, in view of the high frequency of chest pain after use of sumatriptan and reports in the literature of cardiac disturbances, including myocardial infarction, cautious use of the drug is advised.     

Negative symptoms in schizophrenia: considerations for clinical trials

There is little agreement about the methodology of clinical trials of antipsychotic drugs in patients with negative symptoms. A literature review revealed wide variation in experimental design, rating scales and study duration. This reflects differing views as to the definition and response to treatment of negative symptoms. Some degree of standardization would improve comparability of studies and aid the development of new compounds. Patients included in such studies should have displayed negative symptoms for at least 6 months. Depressive symptoms, positive schizophrenic symptoms and extrapyramidal signs may all influence or be confused with negative symptoms and may respond to treatment; they should be at a low level at baseline and should be measured during the study period. Studies should last at least 8 weeks. Several scales are available for measuring negative symptoms and are reviewed; a global impression score should be used additionally.