Biomedical subjects
Publications and source records attributed to R Mani.
There are instances when chronic disease states manifest as microvascular disturbances of the skin. Objective assessment of these disturbances would permit a better understanding of the causative factors and, in certain circumstances, influence decisions of clinical management. Recent advances in technology that permit such assessment non-invasively are evaluated in this review.
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Skin oxygen tension (TcPO2) was measured at 43 degrees C on patients (n = 27) with venous ulcers. Measurements were made at ulcer edge and proximally on the same limb for control. Similar measurements were also made on healthy volunteers (n = 14) in the medial aspects of the distal third of the legs. TcPO2 at ulcer edge was significantly lower (P = 0.001) than control values which in turn were lower than that measured on healthy volunteers. TcPO2 reflects skin nutrition. While low TcPO2 at ulcer edges might be the result of pericapillary barriers to oxygen transport, the control values measured on apparently normal skin suggest the need for further studies.
The laser Doppler flowmeter (LDF), which measures changes in cutaneous blood flow, and the transcutaneous oxygen electrode which measures cutaneous perfusion, were used to study reflex changes in the microcirculation of the shoulder in 38 patients with frozen shoulder and 10 normal controls. In all controls and 22 patients with frozen shoulder, a normal LDF response to inspiration/expiration was observed. In 16 patients with frozen shoulder, LDF responses were either unilaterally or bilaterally absent. Comparison between the two patient groups showed a significant association (chi 2 = 6.43, P less than 0.02) between abnormality of response and the persistence of pain. TcPO2 was in the normal range in all patients and controls. These findings suggest that the LDF together with the TcPO2 may be a useful method of studying the skin microcirculation over the shoulder.
In this double-blind study we have investigated the vascular effects of prostaglandin, (PG) D2, in normal skin and compared these effects with histamine and the initial PGD2 metabolite 9 alpha, 11 beta-PGF2. In eight healthy subjects the vascular response to intradermal injections of histamine, PGD2, a combination of histamine and PGD2, and 9 alpha,11 beta-PGF2, was assessed by measurement of the weal and flare area. Histamine caused dose-related increases in weal area (P less than 0.01). The weal response due to PGD2 was greater than saline control only at a dose of 71.0 and 710 nmol (P less than 0.05). Because of the small size of the weal produced by PGD2 when compared with histamine, it was not possible to determine their relative potencies. Histamine and PGD2 caused dose-related increases in flare area (P less than 0.05), and when compared at a response level of 10 cm2 and 15 cm2, histamine was 45 and 251 (P less than 0.01) times more potent than PGD2 in molar terms. Weal and flare responses due to 9 alpha,11 beta-PGF2 were similar to those observed with the equimolar concentration of PGD2. The weal and flare responses when PGD2 and histamine when combined were not significantly different from that predicted by a purely additive effect. We conclude that histamine is likely to be an important mediator contributing towards increased vascular permeability and vasodilatation following immunological activation of skin mast cells in vivo, while PGD2 and its metabolite 9 alpha, 11 beta-PGF2 play only a minor role.
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The efficacy and tolerability of the dihydropyridine derivative nisoldipine was assessed in 36 patients with primary Raynaud's phenomenon. Nisoldipine was given at doses of 5 mg and 10 mg daily for one month each in a placebo controlled double-blind cross-over trial. There was no subjective improvement in symptoms or changes in resting finger blood flow, platelet aggregability or red cell deformability after nisoldipine. The incidence of unwanted effects was similar to that previously described with nifedipine, suggesting that plasma concentrations of nisoldipine were sufficient to cause pharmacodynamic effects. Nisoldipine, in contrast to nifedipine is ineffective in the treatment of primary Raynaud's phenomen when given in a dose of up to 10 mg/day.
The use of laser Doppler flowmetry (LDF) in determining changes in cutaneous blood flow following intradermal injection of histamine has been investigated in this double-blind study. In eight subjects blood flow (LDF) and weal-and-flare area (planimetry) were measured at regular intervals for 1 hr following 50-microliter injections of different concentrations of histamine (6.5 X 10(-5)-6.5 X 10(-3)M) and saline. The mean maximum increase in LDF values over the flare was at least nine-fold greater than the baseline values for all three concentrations of histamine injected. When the LDF values observed at different sites were integrated to obtain the 'LDF response' it was possible to demonstrate concentration-related increases in blood flow and to differentiate clearly between the different concentrations of histamine and saline for up to 30 min after injection. During this period, the repeatability and the time course of the LDF response was comparable with that of the flare area. These studies suggest that the noninvasive technique of LDF is a sensitive and reproducible method for quantifying the changes in cutaneous blood flow that occurs for the first 30 min after intradermal injection of histamine.
Using skin-surface sensors, transcutaneous oxygen tension (TcPo2) has been measured at the edges of ulcers and at control sites proximal to wounds on the same legs. TcPo2 at 43 degrees C at the edges of venous ulcers was found to be significantly different (P less than 0.003) from that of arterial and mixed arteriovenous ulcers (P less than 0.05) respectively. TcPo2 on healed skin was higher than at any wound edge. At this temperature TcPo2 was also found to be significantly different (P less than 0.001) on the intact skin of patients with venous disease when compared with measurements at identical sites on healthy controls. In the same group, these TcPo2 values increased with dependency. By contrast, at 37 degrees C TcPo2 was no different between groups (P less than 0.10), nor did it alter with position. This protocol adopted for investigating ulcers enables a quantitative distinction to be made between ulcers of different aetiologies. The differences in TcPo2 between different ulcers and healed skin support the fibrin cuff mechanism which has been suggested as the cause of venous ulceration.
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To define the natural history of the asymptomatic, nonstenotic, ulcerative lesion involving the carotid artery bifurcation, the arteriograms and clinical course of 67 patients with 72 asymptomatic ulcerative lesions of the carotid artery were reviewed. The angiographic appearance of ulceration was classified into three groups: minimal (group A), large (group B), and compound (group C). Using life-table methods, the clinical course of these patients was compared between groups and was also compared to a nonrandomized surgically treated group of patients with nonstenotic ulcerative lesions in whom operation was performed for hemispheric or monocular symptoms. There were no significant (P greater than .1) differences in mortality, but the differences in stroke incidence was highly significant (P less than .001). The annual stroke rate, averaged over seven years, was 0.4% per year for group A, 1.47% per year for the surgically treated group, and 12.5% per year for groups B and C. The data indicate that group A ulcers have a benign prognosis, in noticeable contrast to group B and C ulcers which incur a high risk for subsequent stroke.
Wounds that are slow to heal are poorly understood. Clinicians and researchers have attempted to predict treatment outcomes from simple physical measurements without, as yet, understanding the pathogenesis or the role of complications on chronic wounds. Laboratory studies on tissues from biopsies and wound fluids are essential. These must be associated with carefully conducted physiological measurements before, the significance of measurements in wound healing is established.
During the surgical treatment of head and neck cancers the surgeon may have to face the problem of deciding what measures to adopt when the tissue at the margin of the surgical sections proves histologically to be cancerous. Many factors may influence the decision for supplementary therapy; among these, of primary importance are stage and site of the tumor, the effectiveness of non surgical therapy, and the psychophysical status of the patient. In order to better consider this problem a retrospective study, limited to laryngeal surgery, and a review of the literature have been carried out. Review of the patients undergoing surgery from 1972 to 1988 has revealed that histological examination of section margins during or after laryngeal surgery was performed in 56 cases: 10 stripping vocal cords, 11 cordectomies, 2 frontolateral laryngectomies, 2 hemilaryngectomies, 20 horizontal supraglottic laryngectomies, 10 total laryngectomies and 1 subtotal laryngectomy with cricohyoidopexis. The margin was negative in 35 cases while tumor lesions of various types were present in 21 cases. An invasive tumor was present in 14 patients and in 7 an 'in situ' tumor or premalignant diskeratosis was found. A policy of abstention was adopted in all but one of the cases. All cases of 'in situ' cancer and of invasive premalignant change were grouped together as they have in common base membrane integrity and the fact that the second lesion is to be considered precancerous. The following results were obtained: in 14 cases of invasive cancer at the section margin there were 8 recurrences (57.1%) 4 after total laryngectomy; 6 patients showed no evidence of disease (NED) after from 3 to 7 years. In the 7 cases of 'in situ' cancer and premalignant lesions at the surgical margin, 4 showed recurrence (57%) and of these 2 underwent surgery. The 3 other cases have been NED for 3 to 5 years. On the other hand, even in the group of 35 margin free patients 8 developed recurrences (22.3%) and of these 3 underwent surgery and 1 radiotherapy. It appears evident that in conservative surgery of the larynx the presence of tumor cells at the surgical margin does not necessarily lead to a recurrence; such recurrences vary from 18% to 60% depending on the study. Nonetheless, it is certain that a real possibility of recovery exists in 50% of these patients. It is, however, impossible to specify which patient manifesting a positive margin actually runs the risk of developing a recurrence.(ABSTRACT TRUNCATED AT 400 WORDS)