Multi-institutional competing risks analysis of distant brain failure and salvage patterns after upfront radiosurgery without whole brain radiotherapy for brain metastasis.

Background: In this study, we use a competing risks analysis to assess factors predictive of early-salvage whole brain radiotherapy (WBRT) and early death after upfront stereotactic radiosurgery (SRS) alone for brain metastases in an attempt to identify populations that benefit less from upfront SRS. Patients and methods: Patients from eight academic centers were treated with SRS for brain metastasis. Competing risks analysis was carried out for distant brain failure (DBF) versus death prior to DBF as well as for salvage SRS versus salvage WBRT versus death prior to salvage. Linear regression was used to determine predictors of the number of brain metastases at initial DBF (nDBF). Results: A total of 2657 patients were treated with upfront SRS alone. Multivariate analysis (MVA) identified an increased hazard of DBF associated with increasing number of brain metastases (P < 0.001), lowest SRS dose received (P < 0.001), and melanoma histology (P < 0.001), while there was a decreased hazard of DBF associated with increasing age (P < 0.001), KPS < 70 (P < 0.001), and progressive systemic disease (P = 0.004). MVA for first salvage SRS versus WBRT versus death prior to salvage revealed an increased hazard of first salvage WBRT seen with increasing number of brain metastases (P < 0.001) and a decreased hazard with widespread systemic disease (P = 0.002) and increasing age (P < 0.001). Variables associated with nDBF included age (P = 0.02), systemic disease status (P = 0.03), melanoma histology (P = 0.05), and initial number of brain metastases (P < 0.001). Conclusions: Patients with a higher initial number of brain metastases were more likely to experience DBF, have a higher nDBF, and receive early-salvage WBRT, while patients who were older, had lower KPS, or had more systemic disease were more likely to experience death prior to DBF or salvage WBRT.

Differential locomotor activity responses to day-time light intensity in juvenile and adult solitary Cape mole-rats, Georychus capensis (Rodentia: Bathyergidae).

The Cape mole-rat (Georychus capensis) is a solitary, strictly subterranean rodent that is responsive to light and entrains to photic cues despite having a reduced visual system. Circadian entrainment is maintained throughout life, but age can alter the amplitude of the response and re-entrainment time. Mole-rats are long-lived for their size which raises questions regarding the robustness of their circadian rhythms and how impacts their locomotor activity rhythms. The locomotor activity rhythms of juvenile and adult Cape mole-rats were investigated. They were exposed to pre-experimental and post-experimental control cycles under fluorescent lights, six 12 h light:12 h dark cycles of decreasing intensities and a constant dark cycle (DD). All animals exhibited more activity during the dark phases of all light regimes. Juveniles were more active than adults and displayed more variable activity during both the light and dark phases. Adults exhibited relatively stable levels of activity under all experimental conditions, whereas juvenile activity decreased as the light intensity was reduced. The amplitude of Cape mole-rat rhythms was consistently low, but similar across light regimes and between adults and juveniles. Cape mole-rats have functional circadian systems, are primarily nocturnal and respond differentially to light intensity depending on their age. Light intensity does not affect the locomotor activity responses of Cape mole-rats in a predictable manner, and could indicate more complex interactions with light wavelengths. The circadian systems of juveniles appear to be more sensitive than those of adults, although the mechanism of the light response remains unclear.

Breast cancer in the lower jaw after reconstructive surgery with a pectoralis major myocutaneous flap (PMMC) -- a case report.

For head and neck as well as for oromaxillofacial surgery, the use of the pectoralis major myocutaneous (PMMC) flap is a standard reconstructive technique after radical surgery for cancers in this region. We report to our knowledge for the first development of breast cancer in the PMMC flap in a 79 year old patient, who had undergone several operations in the past for recurring squamous cell carcinoma of the jaw. The occurrence of a secondary malignancy within the donor tissue after flap transfer is rare, but especially in the case of transferred breast tissue and the currently high incidence of breast cancer theoretically possible. Therefore preoperative screening mammography seems advisable to exclude a preexisting breast cancer in female patients undergoing such reconstruction surgery. Therapy for breast cancer under these circumstances is individual and consists of radical tumor resection followed by radiation if applicable and a standard systemic therapeutic regimen on the background of the patients individual prognosis due to the primary cancer.

Necrotizing fasciitis: microbiological characteristics and predictors of postoperative outcome.

OBJECTIVE: Necrotizing fasciitis is a life threatening soft-tissue infection with a high morbidity and mortality. Prompt treatment based on extensive surgical debridement and antibiotic therapies are the therapeutic principles. METHODS: The medical records of patients with necrotizing fasciitis (n = 26) from 1996 to 2005 were retrospectively analyzed. RESULTS: The localization of necrotizing fasciitis was most commonly the trunk (42.3 %). Type I polymicrobial infection was the dominating infection. The involvement of anaerobic bacteria was associated with an increase in the number of surgical revisions (p = 0.005). Length of postoperative intensive care unit stay, duration of postoperative ventilation and mortality were significantly increased in the ASA IV-V group. Computed tomography displayed only a limited significance as diagnostic tool for initial diagnosis. CONCLUSIONS: In severe cases the combination of necrotic skin and soft tissue gas facilitates the correct diagnosis, which should than be followed by immediate - and most often - repeated debridement. If anaerobes are isolated an early and aggressive second look is necessary.

[Giant condyloma of the penis with malignant transformation associated with lichen sclerosus et atrophicus]. / Riesenkondylom des Penis mit maligner Transformation bei vorbestehendem Lichen sclerosus et atrophicus.

A 72-year old patient presented with a 6 months history of a rapidly growing tumor of the glans and foreskin. He had a long history of phimosis with lichen sclerosus et atrophicus-like lesions on the foreskin which had not been treated. The rest of the personal, family and sexual history was unremarkable. Treatment consists of circumcision and tumor excision. Histopathology confirmed a squamous cell carcinoma within a giant condyloma with a concomitant lichen sclerosus et atrophicus. CT- and ultrasound scans showed no metastases. Giant condylomas are a rare sexually transmitted disease usually caused by human papilloma virus subtypes 6, 11, but also by 16 and 18 among others. They are expansive, cauliflower-like destructive lesions that most frequently affect the anogenital region. In about 30 percent a giant condyloma progresses into a squamous cell carcinoma. Therapy of choice is the histopathologically controlled excision. Recurrences are often seen, so the patients should be monitored frequently after therapy.

Diffusion Characteristics of Pediatric Diffuse Midline Gliomas with Histone H3-K27M Mutation Using Apparent Diffusion Coefficient Histogram Analysis.

BACKGROUND AND PURPOSE: Diffuse midline gliomas with histone H3 K27M mutation are biologically aggressive tumors with poor prognosis defined as a new diagnostic entity in the 2016 World Health Organization Classification of Tumors of the Central Nervous System. There are no qualitative imaging differences (enhancement, border, or central necrosis) between histone H3 wildtype and H3 K27M-mutant diffuse midline gliomas. Herein, we evaluated the utility of diffusion-weighted imaging to distinguish H3 K27M-mutant from histone H3 wildtype diffuse midline gliomas. MATERIALS AND METHODS: We identified 31 pediatric patients (younger than 21 years of age) with diffuse gliomas centered in midline structures that had undergone assessment for histone H3 K27M mutation. We measured ADC within these tumors using a voxel-based 3D whole-tumor measurement method. RESULTS: Our cohort included 18 infratentorial and 13 supratentorial diffuse gliomas centered in midline structures. Twenty-three (74%) tumors carried H3-K27M mutations. There was no difference in ADC histogram parameters (mean, median, minimum, maximum, percentiles) between mutant and wild-type tumors. Subgroup analysis based on tumor location also did not identify a difference in histogram descriptive statistics. Patients who survived <1 year after diagnosis had lower median ADC (1.10 × 10-3mm2/s; 95% CI, 0.90-1.30) compared with patients who survived >1 year (1.46 × 10-3mm2/s; 95% CI, 1.19-1.67; P < .06). Average ADC values for diffuse midline gliomas were 1.28 × 10-3mm2/s (95% CI, 1.21-1.34) and 0.86 × 10-3mm2/s (95% CI, 0.69-1.01) for hemispheric glioblastomas with P < .05. CONCLUSIONS: Although no statistically significant difference in diffusion characteristics was found between H3-K27M mutant and H3 wildtype diffuse midline gliomas, lower diffusivity corresponds to a lower survival rate at 1 year after diagnosis. These findings can have an impact on the anticipated clinical course for this patient population and offer providers and families guidance on clinical outcomes.

Dermoid cyst of the parotid gland--a case report and brief review of the literature.

There is controversy over the frequency of dermoid cysts in the head and neck area. Some authors report that they are common, whereas others say that only 7% of such cysts occur in the head and neck area. In either case, they are extremely rare in the parotid gland. When PubMed is searched for 'dermoid cyst of the parotid gland', only 11 articles are listed. Only four of the articles written in English are case reports of dermoid cysts of the parotid gland. Due to the rarity of descriptions and the considerable diversity of swellings of the parotid gland diagnosis is difficult. Visualizing options like computed tomography, magnetic resonance imaging and ultrasound cannot give a conclusive preoperative diagnosis. This case report shows the challenges in diagnosis and gives a short review of the literature.

Impact of Neuroradiology-Based Peer Review on Head and Neck Radiotherapy Target Delineation.

BACKGROUND AND PURPOSE: While standard guidelines assist in target delineation for head and neck radiation therapy planning, the complex anatomy, varying patterns of spread, unusual or advanced presentations, and high risk of treatment-related toxicities produce continuous interpretive challenges. In 2007, we instituted weekly treatment planning quality assurance rounds as a joint enterprise of head and neck radiation oncology and neuroradiology. Here we describe its impact on head and neck radiation therapy target delineation. MATERIALS AND METHODS: For 7 months, treatment planning quality assurance included 80 cases of definitive (48%) or postoperative (52%) head and neck radiation therapy. The planning CT and associated target volumes were reviewed in comparison with diagnostic imaging studies. Alterations were catalogued. RESULTS: Of the 80 cases, 44 (55%) were altered, and of these, 61% had clinically significant changes resulting in exclusion or inclusion of a distinct area or structure. Reasons for alteration included the following: gross or extant tumor, 26/44 (59%); elective or postoperative coverage, 25/44 (57%); lymph nodes, 13/44 (30%); bone, 7/44 (16%); skull base, 7/44 (16%); normal organs, 5/44 (11%); perineural, 3/44 (7%); distant metastasis, 2/44 (5%); and eye, 1/44 (2%). Gross tumor changes ranged from 0.5% to 133.64%, with a median change in volume of 5.95 mm3 (7.86%). Volumes were more likely to be increased (73%) than decreased (27%). CONCLUSIONS: A collaborative approach to head and neck treatment planning quality assurance has an impact. Cases likely to have challenging patterns of infiltrative, intracranial, nodal, orbital, or perineural spread warrant intensive imaging-based review in collaboration with a diagnostic neuroradiologist.

Comparison of clinical couse and sequential electrophysiological tests in diabetics with symptomatic polyneuropathy and its implications for clinical trials.

The use of electrophysiological (EP) tests as the primary basis for determining outcome in clinical trials of therapy for symptomatic diabetic polyneuropathy, and the frequently short duration of such trials, is based on assumptions at variance with the pathology and natural history of this disorder and with the evidence that the commonly employed EP tests predominantly reflect the status of the large myelinated nerve fibers. The course of painful, distal symmetrical, primarily sensory polyneuropathy was studied in nine chronic diabetics, aged 21--59 yr, selected for the absence of other forms of diabetic neuropathy, other causes of neuropathy, and other significant illness. All were treated with modifications of diet, insulin, and a daily multivitamin tablet, and, on a randomized basis, also received either placebo or myo-inositol tablets. Initially, and after 2, 4, and 6 mo, a standardized questionnaire was used to assess symptoms, and a standardized neurological examination and battery of EP tests were performed. A minimum of 6 mo was found necessary to assess the clinical course of this syndrome. Clinical improvement occurred in both legs and arms in four patients, as judged by improvement both in symptoms and in the extent of deficits in pinprick and temperature perception; abnormalities in sensory modalities mediated by large myelinated fibers, however, were generally unaltered after 6 mo. A nonuniform distribution of abnormal EP tests of sensory components of the commonly studied nerves of the leg and arm was demonstrated in the study group at the outset, and clinical improvement was not accompanied by evidence of any consistent pattern of improvement in the initially abnormal EP tests. A significant fraction of chronic diabetics with painful, distal symmetrical, primarily sensory polyneuropathy selected by standard criteria appear to have potential for clinical improvement over 6 mo, but primarily in sensory modalities that make it inappropriate to use the common EP tests as the primary basis of judging outcome.

Diabetic glycemic control and retinal blood flow.

The effect of strict glycemic control on retinal volumetric blood flow rate (Q) was investigated in 13 insulin-dependent diabetic patients with laser Doppler velocimetry and monochromatic fundus photography. Strict glycemic control was achieved by glucose monitoring and four daily insulin injections. Q was determined in a major retinal vein at baseline and then 5 days, 2 mo, and 6 mo after the institution of strict control. Level of retinopathy was assessed from stereocolor fundus photographs taken at baseline and 6 mo. After 6 mo of strict diabetic control, five eyes demonstrated progression (P) by one or more retinopathy levels, and eight eyes showed no progression (NP). At 5 days, there was a significant decrease in Q of 1.4 +/- 0.9 microliters/min (P less than 0.005) in NP eyes and a nonsignificant increase in Q of 1.2 +/- 1.7 microliters/min in P eyes. Changes in Q from baseline observed at 5 days were strongly correlated with changes in retinopathy level at 6 mo (r = 0.79, P less than 0.005). No significant changes in Q from baseline were observed at 2 and 6 mo. A lack of decrease in Q at 5 days was associated with the progression of retinopathy that occurs in some patients after the institution of strict glycemic control and may serve as a predictor for progression of retinopathy.

Evaluation of new rapid office test for microalbuminuria and its comparison to fully quantitative radioimmunoassay.

A novel enzyme-linked immunosorbent assay (ELISA [Dialbumin]) for rapid office measurement of microalbuminuria was evaluated and its performance compared with that of a commercially available radioimmunoassay (double-antibody albumin). Urine samples containing between 0.75 and 1800 micrograms/ml of albumin were obtained from 31 diabetic patients and assayed by both methods. A comparison of the paired values obtained from the two methods gave a correlation coefficient of greater than 0.99. The Dialbumin assay, which used detachable eight-well strips (1 strip/sample), 10-min incubation, tap water wash, and a 2-min color development step, was read on both an ELISA reader and a hand-held analytical device (Acc-U-Dial) designed specifically for this test. The findings of this study indicate that the Dialbumin assay, used in conjunction with the Acc-U-Dial device, affords a rapid, convenient, and sensitive method for quantitative determination of a broad range (0.3-1280 micrograms/ml) of urinary albumin levels in the office setting.

GM-CSF activates regenerative epidermal growth and stimulates keratinocyte proliferation in human skin in vivo.

Granulocyte/macrophage-colony-stimulating factor (GM-CSF), an immunomodulator of hematopoietic cells, has also been shown to stimulate human keratinocyte proliferation in vitro and speed healing of wounds in the skin of lepromatous leprosy patients. In this study we have examined the in vivo effects of recombinant human GM-CSF on epidermal keratinocyte proliferation and on expression of proteins marking regenerative epidermal growth. Skin biopsies from GM-CSF injected cutaneous sites were obtained between 1 and 6 d following administration of 7.5 or 15 micrograms of the growth factor. Activation of keratinocyte proliferation, quantified as the expression of the Ki67+ nuclear antigen, was noted 1 d following GM-CSF administration. A regenerative epidermal phenotype, demonstrated by immunohistochemical staining of cellular proteins involucrin, filaggrin, and keratin 16, was similarly noted as early as 1 d following GM-CSF injection. This phenotype persisted as late as 6 d post-injection. These results suggest that GM-CSF injection into human skin induces keratinocyte proliferation as well as regenerative differentiation of the epidermis. To date no other cytokine has been shown to be mitogenic for human keratinocytes both in vivo and in vitro or to alter keratinocyte differentiation along the "alternate" or regenerative pathway.

Comparison of fixed-ratio versus variable-ratio regular and NPH semisynthetic human insulin in insulin-requiring diabetic patients.

The efficacy and safety of a fixed combination of semisynthetic human insulin (Novolin) providing a 70:30 ratio of NPH to regular insulin versus a varying ratio of semisynthetic human insulin, regular and NPH (control group), were compared in adult insulin-dependent and noninsulin-dependent diabetic patients whose glycemic control had been stable on customized split-mix regimens of animal insulin. Seventy-eight patients were enrolled, of whom 72 were evaluated for efficacy of the respective regimens. Although the baseline fasting serum glucose concentrations were significantly higher in the fixed-ratio group than in the control group, mean serum glucose and glycosylated hemoglobin values throughout the 12 weeks of experimental treatment were not significantly different between groups. The mean serum glucose and glycosylated hemoglobin values in the fixed-ratio group also did not differ significantly from baseline; however, statistically significant increases were observed in the control group at weeks 4 and 8, but not at week 12. Total daily insulin dosages were comparable between the two groups, and body weight did not change significantly in either group. At the end of the study, the investigators judged 90% of the patients in the fixed-ratio group and 88% of the patients in the control group to be either improved or unchanged with respect to glycemic control. The frequency of hypoglycemic episodes and other clinical events did not change significantly from baseline in either group or differ significantly between the two groups at any time. The results of this study suggest that stable diabetic patients receiving animal insulin can safely be transferred to semisynthetic human insulin and that the majority of patients can maintain acceptable glycemic control with a fixed 70:30 ratio of NPH to regular semisynthetic human insulin.

Lymphoid myelofibrosis associated with high grade B cell lymphoma of the liver: morphological, cytogenetic, and clinical features.

Severe pancytopenia associated with moderate hepatosplenomegaly, increased serum lactic dehydrogenase (LDH) levels, and hypogammaglobulinemia were found in a young male patient. Bone marrow histology showed extensive fibrosis, hypoplasia of erythro- and granulocytopoiesis, and hyperplasia of megakaryocytopoiesis associated with histiocytic fat cell phagocytosis and infiltration of abnormal lymphocytes, compatible with lymphoid myelofibrosis. Striking chromosomal aberrations indicating karyotype evolution were also demonstrated by cytogenetic analyses (47, XY, +3 / 47, XY, +3, 1p+ / 46, XO, +3, 1p+, -Y). The clinical course was characterized by cyclic febrile episodes accompanied by excessive increase of serum LDH levels and leukocyte counts, and decrease of platelet counts, followed by spontaneous regression. Further diagnostic procedures, including two liver biopsies and computed tomography, did not detect any manifestation of lymphoma. Eventually, the patient developed rapidly progressive, lethal pulmonary aspergillosis. At autopsy, high grade B cell lymphoma of the liver was found. In this case, the lymphoid myelofibrosis seen on bone marrow biopsy may be considered as a manifestation of "discordant" bone marrow histology related to high grade lymphoma. With respect to the cyclic clinical course, a possible role of apoptotic mechanisms in the physiopathology of this disorder is reviewed.

Therapeutic strategy of papillary cystic and solid neoplasm (PCSN): a rare non-endocrine tumor of the pancreas in children.

Papillary-cystic and solid neoplasm (PCSN) are rare tumors. Two personal observations and a review of the literature are presented with a total of 44 pediatric patients in addition to a total of 67 published cases in the review of Cohen (Pediatr. Surg. Int. 6 (1991) 128) and Snadjauf (Eur. J. Pediatr. Surg. 9 (1999) 416). Overall, PCSN shows a clear predominance in females and only occasionally occurs in males. Typically they grow to a large tumor mass with minimal symptoms. Their histologic and immunocytologic characteristics cause diagnostic difficulties, especially on frozen sections of small biopsies. The tumors are assumed to origin from pluripotent stem cells and present as tumors of low malignancy with a favorable prognosis. Nevertheless 10 children have been reported to develop metastases, 5 have demonstrated an invasive growth pattern and 4 local recurrence. But only two of the 111 pediatric cases have died from their tumor burden. Treatment of choice is a complete surgical resection, which is true for the primary tumor and for metastases as well as local recurrences. In our 2 patients one had spleen-conserving left pancreatic resection and one mesopancreatectomy with roux-en-y-reconstruction leading to long-term cure. Adjuvant therapy in curative resected patients is unnecessary and does not appear to improve prognosis.

The effect of tibial lengthening using the Ilizarov method on the cartilage and the menisci of the knee joint.

In order to investigate possible acute damage to the knee joint cartilage and the menisci during tibial lengthening, sixteen young beagle dogs underwent 30% lengthening of the right tibia of 2.5 cm by callus distraction at a distraction rate of twice 0.5 mm per day. A further four dogs comprised the control group with fixator and osteotomy but without lengthening. After a distraction period of 25 days half the dogs were killed (group A) while the other half (eight dogs with limb lengthening and two dogs without) were killed after a further period of 25 days (group B). At the end of the study, the menisci were removed together with three cartilage-bone cylinders from both femoral condyles from the weight-bearing zones as well as from the corresponding tibial condyles. Serial sections from the menisci were stained with haematoxylin and eosin (H&E) and Elastica van Gieson. Sections of the cartilage-bone cylinders were stained with H&E and safranin-O. Cartilage thickness was measured and the glycosaminoglycan content of the joint cartilage was determined using microspectrophotometry. None of the histological preparations obtained from the untreated and distracted sides showed any signs of damage to the cartilage or to the menisci. There were no significant differences between cartilage thickness and proteoglycan content of the untreated side and the lengthened side. Thus, tibial lengthening using the llizarov method does not appear to cause acute damage to the cartilage of the knee joint or to the menisci.

Early occurrence of an adenocarcinoma after allogeneic bone marrow transplantation in a patient with AML.

Several reports have showed an increased risk of secondary malignancies after bone marrow transplantation (BMT), especially after total body irradiation (TBI). We report on a 39-year-old female who underwent BMT with a matched unrelated donor because of acute myeloid leukemia in second complete remission. Previously, the patient received chemotherapy for induction, consolidation, maintenance and reinduction after diagnosis of relapse. Conditioning regimen consisted of cyclophosphamide and TBI. MTX and CSA was administered for GvHD prophylaxis. Engraftment was confirmed on day 28. Within 6 months following BMT, no complication occurred. Continuous complete remission was demonstrated by repeated bone marrow smears. On day 300 the patient complained of chest pain and dyspnea. X-ray and CT-scan showed thickening of the pleura and pleural effusion. A pleuracarcinosis was diagnosed by cytologic examination of a pleural aspirate. By an open thoracotomy a disseminated inoperable disease became apparent. Diagnosis of an adenocarcinoma was confirmed by histologic examination. The patient died 2 months later due to disseminated tumour in complete remission of AML. Solid tumours are rare as secondary malignancies after BMT. Usually the neoplasmas are late events occurring more than 10 years after BMT. In this case predisposing factors such as genetic disposition, long-term smoking, intensive pretransplant chemotherapy, TBI and immunosuppression may have lead to the early secondary malignancy.

FTY720 prolongs clear corneal allograft survival with a differential effect on different lymphocyte populations.

BACKGROUND: FTY720 is a potent immunomodulator with unique effects on lymphocyte homing and has recently proved to be safe and effective in renal transplantation in man. The authors investigated the potency of FTY720 in inhibiting allograft rejection in the rat model of orthotopic allogeneic penetrating keratoplasty. METHODS: Penetrating keratoplasties were performed using Fisher rats as donors and Lewis rats as recipients or donors: group 1 (n = 10), allogeneic control; group 2 (n = 10), Lewis/Lewis syngeneic control; group 3 (n = 9), mycophenolate mofetile (MMF) 40 mg/kg; group 4 (n = 10), FTY720 1.2 mg/kg; group 5 (n = 8), FTY720 0.3 mg/kg. Four animals from each group were sacrificed for immunohistological evaluation on day 14. Medication in the therapy groups was given for 18 days. RESULTS: The mean (SD) rejection free graft survival time was 11.3 (0.8) days for the allogeneic control (group 1), 24.6 (2.5) days for group 3 (MMF), 44.5 (5.7) days for group 4 (FTY720 1.2 mg/kg), and 35.3 (5.7) days for group 5 (FTY720 0.3 mg/kg) (p<0.05). The allogeneic control showed a dense infiltration with CD4+, CD8+, CD161+ (NK-cells), CD25+ (IL2 receptor), and macrophages. In the therapy groups the density of infiltrating CD4+, CD8+, CD161+ (NK-cells), and CD25+ (IL2 receptor) cells was notably reduced compared with the allogeneic control (p<0.05). In group 5 however, the reduction of infiltration by CD4+ cells was higher than the reduction of infiltration by CD8+ (p<0.05) and CD161+ (NK) cells. DISCUSSION: Oral immunosuppression with FTY720 significantly prolongs corneal allograft survival in this transplant model. The results suggest that FTY720 has a different effect on certain lymphocyte populations. CD4+ cells seem to be more affected than CD8+ cells and NK-cells.

Strict control of glycaemia: effects on blood flow in the large retinal vessels and in the macular microcirculation.

AIMS: The purpose of this study was to investigate the effect of instituting strict diabetic glycaemic control on the retinal macular microcirculation and to compare this effect with that observed in the main retinal veins. METHODS: In 28 insulin dependent diabetic patients with poor glycaemic control a regimen of strict diabetic control, consisting of four daily insulin injections was instituted and maintained for 6 months. Retinal haemodynamics were investigated in the macular microcirculation by the blue field simulation technique and in the major retinal veins by a combination of bidirectional laser Doppler velocimetry and monochromatic fundus photography. Progression of diabetic retinopathy was assessed from fundus photographs taken at baseline and at the end of the study. RESULTS: Institution of strict diabetic control resulted in a significant increase in leucocyte velocity in the macular circulation (p = 0.013). No significant difference in this increase was observed between eyes that showed progression (n = 8) and no progression (n = 20) of retinopathy during the study. Significant correlations were found between relative changes over time of blood flow measured in the main retinal veins and relative changes of leucocyte velocity determined in the macular microcirculation at 2 months (p = 0.008) and 6 months (p = 0.001) but not at 5 days (p = 0.49). In the eight eyes that showed progression of retinopathy, the product of leucocyte velocity and density at baseline was significantly higher than normal (p < 0.05). During the length of this study, this product was also significantly higher in the eight eyes that showed retinopathy progression than in the 20 eyes that did not show progression (p = 0.005). CONCLUSION: Our results suggest that increased flow in the macular microcirculation may be associated with progression of retinopathy, thus supporting the hypothesis that increased blood flow may play a role in the development of diabetic microangiopathy. Although there are correlations between the changes detected in the macular microcirculation and those measured in the main retinal vessels, there are also differences which need to be further investigated in order to better understand pathogenetic mechanisms.

Strict metabolic control and retinal blood flow in diabetes mellitus.

The effects of strict diabetic control on retinal haemodynamics were studied to elucidate whether such effects are associated with retinopathy changes. In 28 patients with poorly controlled insulin dependent diabetes mellitus and non-proliferative retinopathy, retinal haemodynamics were investigated at baseline, 5 days, 2 months, and 6 months after the institution of strict diabetic control using the bidirectional laser Doppler velocimetry technique and monochromatic fundus photography. Changes in retinal blood flow measured in a major retinal vein (Q) on the fifth day of strict diabetic control correlated significantly with changes in retinopathy level observed at the end of the 6 months of this study (rank correlation 0.65, p < 0.01). On the fifth day of strict diabetic control, 16 out of 20 eyes that showed no progression (NP) of retinopathy at the end of the study had decreases in Q, whereas six out of eight eyes that showed progression (P) had increases in Q. The difference in these changes in Q between P and NP eyes was statistically significant (one way analysis of variance, p = 0.001). No significant changes in Q were detected at 2 months or 6 months. Following the institution of strict diabetic control, no significant changes in time were detected in the regulatory response to 100% oxygen breathing characterised as the percentage decrease in Q at 4-6 minutes of oxygen breathing (analysis of variance, p = 0.36). Changes in Q following institution of strict diabetic control are associated with progression of retinopathy. Measurements described in this study may help identify diabetic patients at risk of progression when their metabolic control is improved.