Adequate Wound Healing Research Articles

Zinc Supplementation in Critically Ill Patients: A Key Pharmaconutrient?

The purpose of the present paper is to provide a rationale for zinc supplementation as a potential therapeutic agent in critically ill patients by describing its role in health and disease, conducting a systematic review of current randomized trials in critical care, considering optimum route and dose of administration, and making recommendations for future research. Normal zinc homeostasis is required for a functional immune system, adequate antioxidant capacity, glucose homeostasis, and wound healing. In addition, zinc is a required cofactor for many enzymes, transcription factors, and replication factors. In non-critically ill patients, zinc supplementation has been associated with an improvement in markers of immune function. In critically ill patients, only 4 randomized trials have examined the effect of zinc supplementation on clinical outcomes. When all 4 studies were aggregated, zinc supplementation was associated with a nonsignificant reduction in mortality (relative risk = 0.63, 95% confidence intervals 0.25-1.59, P = .33) and length of stay in intensive care (-0.35 days, -0.85 to 0.15; P = .17). Thus, because of the paucity of clinical data, there is inadequate evidence to recommend the routine use of high-dose zinc supplementation in the critically ill. A first step would be to determine the optimal dose that has a maximal positive effect on underlying inflammatory, immunologic, and metabolic processes yet is safe and tolerated by critically ill patients. Subsequently, large, rigorously designed, randomized trials are required to elucidate the efficacy of such doses of zinc supplementation in this patient population.

The Use of Free Flaps in the Management of Type IIIB Open Calcaneal Fractures

There have been a limited number of reports regarding calcaneal open fractures so far. Thus, the debate regarding treatment is continuing. Type IIIB open calcaneal fractures are often associated with the possibility of chronic osteomyelitis that may cause severe complications, including amputation. Between the years 1990 and 2001, 27 free tissue transfers were performed in 25 patients for reconstruction of soft-tissue defects complicated by calcaneal fracture. All of the patients underwent debridement and bone fixation procedures at the initial operation in the acute phase. Ten patients with comminuted fractures were treated by means of external fixation and 15 patients had intraarticular fractures that required internal fixation in addition to external fixation. After several aggressive debridements, free tissue transfers were performed subacutely for primary wound coverage. Muscle flaps were used in the majority of cases (n = 21). The mean follow-up period was 7 years 8 months. Complete flap survival occurred in 93 percent of flaps. There was one partial and one total flap failure. The overall infection rate was 12 percent (n = 3). Two of these patients were treated successfully and one required partial calcanectomy. In all cases, solid bone union was achieved. However, 72 percent of the patients suffered from pain or degenerative changes. Type IIIB open calcaneal fractures require systematic and meticulous treatment. Free tissue transfer is the essential component of providing healthy tissue for achieving adequate wound healing with reduced infection rates.

Plastic Surgery Reconstruction of the Diabetic Foot

Soft tissue reconstruction of the diabetic foot is a challenge for the perioperative team. Primary closure may not be an option and secondary healing may not be reliable. Therefore, surgery is vital and should be coordinated among a well-functioning multidisciplinary team that specializes in caring for patients with diabetes mellitus. Team members must have expertise in reconstructive surgery to ensure adequate wound healing. This article emphasizes the appropriate timing and staging of surgery, discusses the most common plastic surgery techniques, and underscores the importance of a team approach in the management of diabetic foot wounds.

Ovarian non-Hodgkin′s lymphoma presenting as obstructive jaundice - a case report

To highlight the importance of considering abdominal Lymphoma as a differential diagnosis in the management of obstructive jaundice. A 51 year old female who presented with abdominal swelling associated with features of obstructive jaundice. Significant findings included jaundice on examination, with abdominal ascites. Laparotomy revealed three litres of icteric fluid. There was a huge left ovarian tumour measuring 14 cm x 12 cm. Massive peritoneal seedling involved the whole abdomen and pelvis was noted. Following surgery allowing for adequate wound healing, the patient was placed on appropriate chemotherapy. INVESTIGATION/DIAGNOSIS: Histology of excision biopsy revealed high grade Non-Hodgkins's Lymphoma. Screening for human deficiency virus (HIV) was negative. However the erythrocyte sedimentation rate (ESR) was raised at 92 mm Westergren in the first hour. The liver function tests were deranged with total bilirubin of 274 micromol/l and conjugated bilirubin of 204 micromol. serum Ast and Alt were also significantly raised. Total proteins, urea and electrolytes remained essentially within normal limits. The patient was placed on CHOP combination therapy. She attained remission after four cycles of chemotherapy and was discharged home. Abdominal Non-Hodgkin's Lymphoma should be a strong consideration in the management of obstructive jaundice.

Emerging new drugs for wound repair

Every year, millions of people experience burns, suffer from nonhealing wounds, or have acute wounds that become complicated by infection, dehiscence or problematic scarring. Effective wound treatment requires carefully considered interventions often requiring multiple clinic or hospital visits. The resulting costs of wound care are staggering, and more efficacious and cost-effective therapies are needed to decrease this burden. Unfortunately, the expenses and difficulties encountered in performing clinical trials have led to a relatively slow growth of new treatment options for the wound management. Research efforts attempting to examine wound pathophysiology have been hampered by the lack of an adequate chronic wound healing model, and the complexity of the wound healing cascade has limited attempts at pharmacological modification. As such, currently available wound healing therapies are only partially effective. Therefore, many new therapies are emerging that target various aspects of wound repair and the promise of new therapeutic interventions is on the immediate horizon.

Platelet-induced growth of human fibroblasts is associated with an increased expression of 5-lipoxygenase

Proliferation of fibroblasts is vital for adequate wound healing but is probably also involved in different hyperproliferative disorders such as atherosclerosis and cancer. The regeneration of tissue usually starts with coagulation, involving release of mitogenic and inflammatory factors from activated platelets. This study focuses on the role of eicosanoids in the proliferative effects of platelets on human fibroblasts. We show that the phospholipase A (2) inhibitor 7,7-dimethyl-5,8-eicosadienoic acid (DMDA), the combined cyclooxygenase (COX) and lipoxygenase (LOX) inhibitor 5,8,11,14-eicosatetraynoic acid (ETYA) and the LOX inhibitor 5,8,11-eicosatriynoic acid (ETI) block the platelet-induced proliferation of serum starved subconfluent human fibroblasts. Anti-proliferative effects were also obtained by specific inhibition of 5-LOX with 5,6-dehydro arachidonic acid (5,6-dAA), whereas the 12-LOX inhibitor cinnamyl-3,4-dihydroxy- a -cyanocinnamate (CDC) did not affect the platelet-stimulated growth of fibroblasts. The expression of 5-LOX was analyzed by reverse-transcriptase-mediated PCR (RT-PCR), Western blotting and HPLC. 5-LOX message and protein was detected in fibroblasts but not in platelets. Incubation with platelets markedly increased, already after one hour, the expression of 5-LOX in the fibroblast culture. The increased 5-LOX activity was associated with an elevated level of the 5-LOX metabolite 5-hydroxyeicosatetraenoic acid (5-HETE) reaching its maximum after 1 - 2 hours of co-incubation of fibroblasts and platelets. The 5-HETE production was reduced by the inhibitors DMDA, ETYA and ETI. In conclusion, this study suggests that platelet-stimulated proliferation of fibroblasts is mediated by an increased 5-LOX activity, which supports recent findings indicating a crucial role for this enzyme in proliferative disorders such as atherosclerosis.

Altered fibroblast function following myocardial infarction

Adequate wound healing and scar formation is an essential response to myocardial infarction (MI), and fibroblasts are primary cellular components regulating the process. How fibroblast functions are altered post-MI and to what extent these abnormalities persist in vitro is not well understood. Accordingly, we isolated myocardial fibroblasts from MI and non-MI (remote) regions at 7 days post-MI ( n = 35) and from the free wall and septum of unoperated control C57BL/6 mice ( n = 14). Proliferation was increased 182 ± 28% in MI, but not in remote, fibroblasts compared with unoperated controls ( P = 0.01). Migration decreased 61 ± 8%, adhesion to laminin decreased 79 ± 8%, adhesion to collagen IV increased 196 ± 27%, and collagen synthesis increased 169 ± 24% in fibroblasts isolated from the MI region (all P < 0.05). Migration, adhesion, and collagen synthesis changes were similar in remote fibroblasts, and the phenotypic differences were maintained through passage four. Transforming growth factor β1 (TGFβ1) is a bioactive molecule that has been shown to affect fibroblast function. Stimulation of unoperated control fibroblasts with 10 ng/ml TGFβ 1 increased proliferation 137 ± 7% ( P = 0.03 vs. unstimulated), increased adhesion to collagen IV 149 ± 6% ( P < 0.01), and increased collagen I levels 187 ± 10% ( P = 0.01). TGFβ1 may, therefore, explain some of the changes in post-MI fibroblast phenotype. These data demonstrate for the first time region specific alterations in post-MI fibroblast biology that are maintained in vitro. Additionally, our model provides a novel in vitro template for examining the cellular mechanisms of wound healing and scar formation post-MI.

Salvage of Infected Cartilage Grafts for Nasal Reconstruction With a Through-and-Through Irrigation System

Development of a wound infection after nasal reconstruction can place the entire reconstructive effort in jeopardy. The approach to management in these cases has traditionally entailed wound drainage, removal of involved graft material, and debridement of nonvital tissue. Following adequate wound healing, delayed reconstruction is then performed, with the final result often compromised in form and function. We present a case of a postoperative wound infection following reconstruction of a traumatic nasal deformity utilizing autologous cartilage grafts. Treatment consisted of hospitalization with administration of culture-specific parenteral antibiotics and continuous through-and-through antibiotic irrigation of the wound via an indwelling catheter. The infection was completely eradicated and all cartilage grafts were salvaged utilizing this technique. At 3 years postoperatively, the patient has maintained the shape and quality of her reconstruction, without evidence of recurrent infection.

Expanded mesh connective tissue graft for the treatment of multiple gingival recessions.

The connective tissue graft procedure is an effective method to achieve root coverage. Although multiple sites often need grafting, the palatal mucosa supplies only a limited area of grafting material. The expanded mesh graft provides a method whereby a graft can be stretched to cover a larger area. The aim of this study was to determine the effectiveness and the predictability of expanded mesh connective tissue graft (e-MCTG) in the treatment of multiple gingival recessions. Fifty-two buccal gingival recessions were treated in 10 systemically healthy patients. Fifteen recession treated operation sites with at least three adjacent Miller Class I and/or II recessions were performed. The connective tissue graft obtained from the palatal mucosa was expanded to cover the recipient bed, which was 1.5 times larger than the graft. Clinical measurements recorded at baseline and 12 months postoperatively included gingival recession depth (RD), gingival recession width (RW), percentage root coverage (RC), probing depth (PD), width of keratinized tissue (KT), and clinical attachment level (CAL). Twelve months after surgery, a statistically significant gain in CAL (3.2 +/- 0.8 mm, P < 0.001) and increase in KT (1.2 +/- 0.4, P < 0.001) were assessed. In 80% of the treated sites, 100% RC was achieved (mean 96%). The results of this study demonstrated that the use of e-MCTG technique allowed the treatment of multiple adjacent recessions with adequate wound healing and highly predictable root coverage. This procedure can be applied favorably in treating multiple gingival recessions in one surgery.

Update on topical wound medications

Numerous topical wound medicants are available today. Very few of these products have been tested in the horse. Due to the unique nature of wound healing in the distal limbs of horses (carpus, tarsus and distad), many beneficial effects of these medicants seen in other species and in vitro have not been reproduced in equine limb wounds. There is an abundance of literature regarding topical wound medicants; however, the findings of these studies are quite variable, in general. Many wound care articles have questioned the routine use of topical medications, preferring the concept of moist wound healing in which the body produces all the substrates necessary for adequate wound healing. This article outlines many of the common products that are available to equine practitioners and provides current information regarding their use in wound healing. Unfortunately no product or substrate has been shown to be superior for equine wound management. That being said, the information provided in this article will attempt to provide the practitioner with information necessary to make educated decisions regarding the selection of topical medicants for wound care.

Supplemental perioperative fluid administration increases tissue oxygen pressure

Background. Wound infections are common and serious surgical complications. Wound perfusion delivers oxygen, inflammatory cells, growth factors, and cytokines to injured tissues. Hypoperfused regions experience low oxygen tensions that do not support adequate oxidative killing or wound healing. Clinicians may fail to recognize clinically important hypovolemia because hemodynamic stability and urine output are maintained after peripheral perfusion is compromised. We tested the hypothesis that supplemental fluid administration during and after elective colon resection increases tissue perfusion and tissue oxygen pressure. Methods. Fifty-six patients undergoing colon resection were randomly assigned to conservative (8 mL·kg−1·h−1, n = 26) or aggressive (16 to 18 mL·kg−1·h−1, n = 30) fluid management. Anesthetic technique was standardized. We used 60% nitrous oxide in 40% oxygen. During surgery and postanesthetic recovery, subcutaneous oxygen tension (PsqO2) was measured by using a polarographic sensor implanted subcutaneously into 1 upper arm. Capillary blood flow was evaluated postoperatively with a thermal diffusion system. Data were analyzed with 2-tailed t tests; P value less than.05 was considered statistically significant. Results. Hemodynamic and renal responses were similar in the groups. Intraoperative tissue oxygen tension was significantly greater in patients given supplemental fluid: 81 ± 26 vs 67 ± 18 mm Hg, P =.03. Postoperative PsqO2 (77 ± 26 vs 59 ± 15 mm Hg, P =.009) and capillary blood flow (69 ± 12 vs 53 ± 12, P <.001) were also greater in the supplemental fluid patients. Conclusions. Supplemental perioperative fluid administration significantly increases tissue perfusion and tissue oxygen partial pressure. Optimizing tissue perfusion will require providing more fluid than indicated by normal clinical criteria or use of invasive monitoring to guide treatment. The actual effect of supplemental fluid administration on incidence of wound infection requires further investigation. (Surgery 2003;133:49-55.)

Reconstructed human skin produced in vitro and grafted on athymic mice.

The best alternative to a split-thickness graft for the wound coverage of patients with extensive burns should be in vitro reconstructed autologous skin made of both dermis and epidermis and devoid of exogenous extracellular matrix proteins and synthetic material. We have designed such a reconstructed human skin (rHS) and present here its first in vivo grafting on athymic mice. The rHS was made by culturing newborn or adult keratinocytes on superimposed fibrous sheets obtained after culturing human fibroblasts with ascorbic acid. Ten days after keratinocyte seeding, reconstructed skins were either cultured at the air-liquid interface or grafted on athymic mice. We present the macroscopic, histologic, and phenotypic properties of such tissues in vitro and in vivo after grafting on nude mice. After maturation in vitro, the reconstructed skin exhibited a well-developed human epidermis that expressed differentiated markers and basement membrane proteins. Four days after grafting, a complete take of all grafts was obtained. Histological analysis revealed that the newly generated epidermis of newborn rHS was thicker than that of adult rHS after 4 days but similar 21 days after grafting. The basement membrane components (bullous pemphigoid antigens, laminin, and type IV and VII collagens) were detected at the dermo-epidermal junction, showing a continuous line 4 days after grafting. Ultrastructural studies revealed that the basement membrane was continuous and well organized 21 days after transplantation. The macroscopic aspect of the reconstructed skin revealed a resistant, supple, and elastic tissue. Elastin staining and elastic fibers were detected as a complex network in the rHS that contributes to the good elasticity of this new reconstructed tissue. This new rHS model gives supple and easy to handle skins while demonstrating an adequate wound healing on mice. These results are promising for the development of this skin substitute for permanent coverage of burn wounds.

Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement.

Substances released by platelets during blood clotting are essential participants in events that link hemostasis and angiogenesis and ensure adequate wound healing and tissue injury repair. We assessed the participation of sphingosine 1-phosphate (Sph-1-P), a biologically active phosphorylated lipid growth factor released from activated platelets, in the regulation of endothelial monolayer barrier integrity, which is key to both angiogenesis and vascular homeostasis. Sph-1-P produced rapid, sustained, and dose-dependent increases in transmonolayer electrical resistance (TER) across both human and bovine pulmonary artery and lung microvascular endothelial cells. This substance also reversed barrier dysfunction elicited by the edemagenic agent thrombin. Sph-1-P-mediated barrier enhancement was dependent upon G(ialpha)-receptor coupling to specific members of the endothelial differentiation gene (Edg) family of receptors (Edg-1 and Edg-3), Rho kinase and tyrosine kinase-dependent activation, and actin filament rearrangement. Sph-1-P-enhanced TER occurred in conjunction with Rac GTPase- and p21-associated kinase-dependent endothelial cortical actin assembly with recruitment of the actin filament regulatory protein, cofilin. Platelet-released Sph-1-P, linked to Rac- and Rho-dependent cytoskeletal rearrangement, may act late in angiogenesis to stabilize newly formed vessels, which often display abnormally increased vascular permeability.

Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement

Substances released by platelets during blood clotting are essential participants in events that link hemostasis and angiogenesis and ensure adequate wound healing and tissue injury repair. We assessed the participation of sphingosine 1-phosphate (Sph-1-P), a biologically active phosphorylated lipid growth factor released from activated platelets, in the regulation of endothelial monolayer barrier integrity, which is key to both angiogenesis and vascular homeostasis. Sph-1-P produced rapid, sustained, and dose-dependent increases in transmonolayer electrical resistance (TER) across both human and bovine pulmonary artery and lung microvascular endothelial cells. This substance also reversed barrier dysfunction elicited by the edemagenic agent thrombin. Sph-1-P–mediated barrier enhancement was dependent upon Giα-receptor coupling to specific members of the endothelial differentiation gene (Edg) family of receptors (Edg-1 and Edg-3), Rho kinase and tyrosine kinase-dependent activation, and actin filament rearrangement. Sph-1-P–enhanced TER occurred in conjunction with Rac GTPase- and p21-associated kinase–dependent endothelial cortical actin assembly with recruitment of the actin filament regulatory protein, cofilin. Platelet-released Sph-1-P, linked to Rac- and Rho-dependent cytoskeletal rearrangement, may act late in angiogenesis to stabilize newly formed vessels, which often display abnormally increased vascular permeability.

Does MMP-2 expression and secretion change with increasing serial passage of keratocytes in culture?

The effects of ageing on matrix metalloprotease degradation of the extracellular matrix during corneal wound healing are largely unknown. The following study used an in vitro model of ageing to assess changes in MMP-2 RNA expression and protein secretion. Early passage (EP) EK1.BR keratocyte cultures from 14 to 18 cumulative population doublings (cpds) and late passage (LP) cultures from 40 to 47 cpds were used to isolate protein and mRNA samples. Total protein from EP and LP cultures was measured using the Bradford protein assay. Zymographic analysis of EP and LP samples was carried out to compare MMP-2 activity. Northern blot analysis was used to assess changes in MMP-2 mRNA expression by EP and LP cultures, using a digoxigenin (DIG) based chemiluminescent detection system. LP cultures secreted more total protein per cell. MMP-2 but not MMP-9 activity was detected in keratocyte cultures. Densitometric analysis of zymograms and calculation of MMP-2 activity indicated a significant increase in MMP-2 activity per cell (P<0.05, n=11). No difference was observed in the levels of MMP-2 mRNA expressed by EP and LP cultures. An increase in MMP-2 activity per cell by LP cultures suggests that senescent keratocytes increase their degradative capacity. Similar changes in the keratocyte phenotype within the ageing cornea may alter the balanced response necessary for adequate wound healing and may have implications for the therapeutic use of MMP inhibitors in the eye.

Potential role of growth factors and extracellular matrix in wound healing after laryngotracheal reconstruction

Laryngotracheal reconstruction (LTR) has been used for more than 20 years to treat infants and children with subglottic stenosis. Results after pediatric LTR have been satisfactory; however, approximately 10% of children have recurrent airway narrowing after LTR. The purpose of our study was to determine whether a correlation existed between specific growth factors and extracellular matrix in patients with adequate wound healing capability as compared with patients with poor wound healing capability. Histologic sections from 27 patients who underwent LTR were cut, and immunohistochemical staining was performed for transforming growth factor-β, platelet-derived growth factor, fibronectin, tenascin, transforming growth factor-α, and vascular endothelial growth factor. Results showed that patients with adequate wound healing capability had a positive correlation with vasculature fibronectin, vasculature tenascin, and stromal fibronectin. Patients with poor wound healing capability had a positive correlation with stromal vascular endothelial growth factor. (Otolaryngol Head Neck Surg 2000;122:363-6.)

Potential role of growth factors and extracellular matrix in wound healing after laryngotracheal reconstruction

Laryngotracheal reconstruction (LTR) has been used for more than 20 years to treat infants and children with subglottic stenosis. Results after pediatric LTR have been satisfactory; however, approximately 10% of children have recurrent airway narrowing after LTR. The purpose of our study was to determine whether a correlation existed between specific growth factors and extracellular matrix in patients with adequate wound healing capability as compared with patients with poor wound healing capability. Histologic sections from 27 patients who underwent LTR were cut, and immunohistochemical staining was performed for transforming growth factor-beta, platelet-derived growth factor, fibronectin, tenascin, transforming growth factor-alpha, and vascular endothelial growth factor. Results showed that patients with adequate wound healing capability had a positive correlation with vasculature fibronectin, vasculature tenascin, and stromal fibronectin. Patients with poor wound healing capability had a positive correlation with stromal vascular endothelial growth factor.

Allograft survival prolongation after microsurgical lymphatic reconstruction in a short-term immunosuppressed rat small bowel transplantation model

“It is clear, however, that today's discovery by bacteriologists, immunologists, biochemists, pathologists and other specialists have their origin in the questions raised by early surgical pioneers, whose primary concern was adequate wound coverage and healing.” This quotation by Felix T. Rapaport and plastic surgeon John Marquis Converse represents the early history of transplantation. “It remains there to this day and did him lasting good in many ways.” This statement by Sir Winston Churchill of his donation of a skin allograft to a brother officer in 1899 illustrates an example of allogeneic grafting without immunosuppression. “Their vasculature is established by direct end-to-end anastomosis of some at least of vessels in the graft with the vessels of the bed.” A quotation from Sir Peter Medawar's classic Harvey Lecture of March 21, 1957, describes the importance of vessel connections between the graft and the host to prevent rejection of allografts described by others. “Nature presents us with her protests against removing lymphatics, with her protests against any lymphatic malfunctioning.” Leo Clodius, who spent his career studying lymphatics, opened with these words a congress on lymphology in 1987. He referred later to the clinical lymphedema treatment by plastic and microsurgical operations. These four quotations demonstrate that (1) grafts can be transplanted allogeneically without immunosuppression; (2) they will not be rejected if no connection to the vascular system of the host take place, like in the brain; (3) but will be rejected if vessels of the host shoot up to the allograft; and (4) lymphatics also belong to a vascular system that transports immunological circulating cells. Interestingly, the possibility of microsurgical reconstructions of the lymphatic system is not seen to be necessary in transplantation today. It is unclear why the actual state of the art of microneurolymphovascular transplantation in plastic surgery is not considered in today's transplantation research.

Energy and protein provisions for thermally injured children revisited: an outcome-based approach for determining requirements.

Energy and protein provisions for adequate wound healing and weight maintenance were examined among severely burned children. Actual intakes were documented for 27 patients admitted with a more than 40% total body surface area burn. Mean energy intake over the 4-week study period averaged 140% of the predicted basal metabolic rate (PBMR), and mean protein intake was 2.8 +/- 0.2 grams per kilogram daily. Wound healing progressed satisfactorily in all patients; at 4 weeks, the open wound area (% open) was 20% or less in 22 patients. Average weight at discharge was 88% +/- 2.6% of ideal body weight. Discharge weights were significantly higher (p < 0.05) among patients whose energy intake exceeded PBMR x 1.7 for at least 1 of the study weeks. We suggest that energy intakes approximating PBMR x 1.2 with a minimum of 3 grams of protein per kilogram will support adequate wound healing, whereas higher energy provisions (PBMR x 1.7) will enhance weight status.

Anorectal surgery in human immunodeficiency virus-infected patients. Clinical outcome in relation to immune status.

Anorectal disease is commonly found in human immunodeficiency virus (HIV)-infected patients. The aim of this study was to determine the spectrum of anorectal disease, its surgical treatment, clinical outcome, and its relation to immune status. Medical records of all HIV-infected patients with anorectal pathology that required surgical treatment from January 1984 to January 1994 were retrospectively reviewed. Patients were divided into five different groups: common anorectal pathology (hemorrhoids, polyps, Group A); condylomata acuminata (Group B); perianal sepsis (abscesses, fistulas, Group C); anorectal ulcers (Group D); malignancies (Group E). Eighty-three patients needed 204 surgical consultations (13 percent conservative, 87 percent operative) for 170 anorectal diseases. Fifty-one patients had multiple anorectal pathology. Operative intervention resulted in adequate wound healing and symptom relief in 59 percent of patients, adequate wound healing without relief of symptoms in 24 percent of patients, and disturbed wound healing was related to type of anorectal disease (P < 0.001) and to preoperative CD4(+)-lymphocyte counts (P < 0.01). Disturbed wound healing and most insufficient immune status were encountered in Groups C, D, and E. Within these groups low CD4(+)-lymphocyte counts were a risk factor for disturbed wound healing (P = 0.004). Median postoperative survival was highest (4.7 years) in Group A, lowest (0.6 years) in Groups D and E, and related to type of anorectal disease (P = 0.0001). The spectrum of anorectal disease is complex. Type of anorectal disease is strongly related to immune status, wound healing, and postoperative survival.