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Abstract: Spark's nevus is a particular type of melanocytic nevus, with histology that shows features of both Spitz and Clark nevus. Detailed dermoscopic features in a series of Spark nevi have not been described yet. We performed a monocentric retrospective observational study on 20 lesions of Spark nevus excised from 19 patients (M:F = 10:9; mean age: 37,6 years), reviewed by 5 experts in dermoscopy and 2 dermatopathologists. A histologic review confirmed that Spark nevi were mostly symmetric (80%), well circumscribed (100%), mainly compound (65%) melanocytic lesions with either epithelioid (55%) or spitzoid (45%) cell morphology and bridging of the nests (100%). Spark nevi were more frequently found on the trunk (85%) in patients with a history of sunburns in childhood (84%), with skin phototype III (79%), and with high nevus count (>100 nevi, 7 patients (36%)). On dermoscopy, we observed different general patterns: multicomponent (40%), reticular-globular-homogeneous (15%), globular homogeneous (15%), reticular (15%), reticular-globular (5%), homogeneous (5%), and globular (5%). Spark nevi showed frequently dermoscopic asymmetry (63%), brown color (90%) with areas of central hyperpigmentation (41%) and peripheral hypopigmentation (28%), atypical pigment network (48%), irregular globules (42%), irregular dots (31%), irregular blotches (16%), blue-whitish veil (13%), peripheral island (25%), irregular hyperpigmented areas (12%), and regression (33%). BRAF mutation was present in 7 of the 10 analyzed cases (70%); all these cases presented a history of evolution. In conclusion, Spark nevi occur on the trunk of young adults with high nevus count and history of sunburns; dermoscopic features are protean, often atypical and suspicious of melanoma., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Spitz tumors are notoriously characterized by a high propensity to nodal involvement with a morphologically malignant (intraparenchymal) pattern but with little or no tendency toward further spread. We describe a case of spindle cell Spitz neoplasm removed from the thigh in a 34-year-old woman and initially diagnosed as "Spitzoid melanoma;" the sentinel node was characterized by a morphologically benign pattern of nodal involvement, with prevailingly capsular and septal aggregated of melanocytes showing the same cytomorphological features as the cutaneous tumor. Both the cutaneous and the nodal tumor were strongly ROS1-positive on immunohistochemistry; rearrangement of the ROS1 gene was confirmed with fluorescence in situ hybridization on the cutaneous tumor. The clonal relationship between the cutaneous and the nodal capsular/trabecular tumor, as established by their morphological and immunophenotypical resemblance, underlines the existence of a morphologically benign pattern of spread of Spitz neoplasms, as also suggested by the occurrence of eruptive Spitz nevi., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Although hypothermia is independently associated with an increased mortality in trauma patients, it might be an effective therapeutic approach for otherwise lethal hemorrhage. The effect of hypothermia on microcirculation, however, has been poorly studied in this setting. Our goal was to characterize the effects of hypothermia on microcirculation in normal conditions and in severe hemorrhagic shock., Methods: In anesthetized and mechanically ventilated sheep, we measured cardiac output (CO), renal blood flow (RBF), and systemic and renal O2 consumption (VO2). Cortical renal, intestinal villi, and sublingual microcirculation was assessed by IDF-videomicroscopy. After basal measurements, sheep were assigned to hypothermia (n = 12) and normothermia (n = 12) groups. Central temperature was reduced to ∼34°C and maintained at baseline in each group, respectively. Measurements were repeated after 1 h of hemodynamic stable conditions and 1 h of severe hemorrhagic shock., Results: In conditions of hemodynamic stability, the hypothermia group showed lower CO, RBF, and systemic and renal VO2 than the normothermia group. Red blood cell velocity was also lower in renal, villi, and sublingual microvascular beds (836 ± 195 vs. 1,066 ± 162, 916 ± 105 vs. 1051 ± 41, and 970 ± 182 vs. 1,102 ± 49 μm/s, respectively; P < 0.0001 for all). In hemorrhagic shock, most of the microvascular variables were similarly compromised in both the groups. In hypo- and normothermia groups, the percentage of reduction in perfused vascular density was higher in renal than in intestinal and sublingual microcirculation (66 ± 31 vs. 31 ± 23 and 15 ± 15%, and 78 ± 26 vs. 32 ± 37 and 18 ± 21%, P < 0.01 for both)., Conclusions: This is the first experimental study assessing the effect of systemic hypothermia on microcirculation in severe hemorrhagic shock. The main finding was that hypothermia did not hamper additionally the microcirculatory derangements induced by hemorrhagic shock. In addition, renal microcirculation was more susceptible to hemorrhagic shock than villi and sublingual microcirculation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by the Shock Society.)

Purpose: To evaluate the clinical outcomes after implantation of a new 320°-arc length Ferrara intrastromal corneal ring segment (320-ICRS) in eyes of patients with keratoconus., Methods: A multicentric nonrandomized study was conducted in which a new 320-ICRS was placed in 138 eyes of 130 patients with keratoconus. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), keratometry, corneal volume, asphericity, lines of vision gain/loss, and vectorial analysis were assessed preoperatively and at the final follow-up visit after the procedure., Results: The mean follow-up time was 6.2 ± 3.3 (SD) months (range 3-12 months). Mean UDVA improved from 20/250 to 20/60. Mean CDVA improved from 20/100 to 20/40. Mean Q improved from -1.12 ± 0.49 preoperatively to -0.28 ± 0.51 postoperatively (P < 0.001). Mean corneal volume increased from 56.2 ± 4.28 mm preoperatively to 57.6 ± 4.74 postoperatively (P < 0.001). Mean Km reduced from 53.3 ± 5.5 D preoperatively to 47.8 ± 4.6 D postoperatively (P < 0.001). The change in UDVA, CDVA, and topographic astigmatism was statistically significant (P < 0.0001)., Conclusions: The 320-ICRS can efficiently and safely improve visual acuity in keratoconus, modifying the corneal shape to a more physiologic, aspheric shape.

The occurrence of pseudolymphomatous infiltrates in cutaneous lupus erythematosus (cLE) is described mainly in lupus panniculitis and lupus tumidus/lymphocytic infiltration of the skin (Jessner-Kanof). We collected 15 cases of pseudolymphomatous cLE other than lupus panniculitis and lupus tumidus (M:F = 4:11; age range: 23-79 years; mean age: 50.9 years; median age: 57 years). Of the 15 cases, 9 (60%) were characterized by dense nodular infiltrates. Three cases (20%) showed an angiocentric pattern with cytological atypia of lymphoid cells; 2 cases (13.3%) showed a band-like infiltrate mimicking mycosis fungoides, and 1 case had mixed features of the band-like and angiocentric patterns. Clues to the histopathological diagnosis of cLE were presence of interface dermatitis, clusters of plasmacytoid dendritic cells, and dermal mucin deposition. Our study shows that the spectrum of pseudolymphomatous presentations of cLE is broader than previously described, including band-like cases that may be misconstrued as mycosis fungoides, and angiocentric cases that may be misinterpreted as an aggressive lymphoma. Recognition of such cases is possible only on careful clinicopathologic correlation and requires a high level of histopathological suspicion to allow a correct diagnosis and the proper management of the patients.

Cold-associated perniosis of the thighs ("equestrian cold panniculitis") is an unusual and still enigmatic entity. The authors retrieved 6 cases for a re-evaluation of their clinicopathologic features and for an immunohistochemical assessment with antibodies anti-CD3, anti-CD20, and anti-CD123. All patients were women, aged 17-45 years. One of them had elevated antinuclear antibody titers. Available anamnestic data confirmed the triggering role of prolonged/intermittent exposure to cold (not necessarily for equestrian activities). The lesions affected the thighs, with a preferential, although not exclusive involvement of the upper lateral surface. The histopathological pattern was perivascular, superficial, and deep, extending toward the superficial fat lobules, with lymphocytic vasculitis and mucin deposition; clumps of CD123 cells were found in 4 of 6 cases. Cold-associated perniosis of the thighs cannot be considered as a panniculitis. The histopathological features considerably overlap with perniosis at other sites of the body and with chilblain lupus erythematosus.

Although conventional histopathological examination is the undisputable mainstay for the diagnosis of melanocytic skin neoplasms, fluorescence in situ hybridization (FISH) has the potential to provide important information to morphologically challenging cases. The standard melanoma FISH test targeting RREB1 (6p25), MYB (6q23), CCND1 (11q13), and centromere 6 is an effective compromise between cost, technical complexity, and sensitivity. The authors use the standard FISH-positivity as a tie-breaker for challenging melanocytic neoplasms mainly in a non-Spitzoid morphologic context because the currently available test leaves several unresolved issues: namely, a relatively low diagnostic accuracy in morphologically ambiguous melanocytic neoplasms; a relatively low sensitivity and specificity in Spitzoid neoplasms; and the occurrence of false positives due to tetraploidy in Spitz nevi and in nevi with an atypical epithelioid component. Under investigation is currently a new melanoma probe cocktail targeting RREB1 (6p25), C-MYC (8q24), CDKN2A (9p21), and CCND1 (11q13). However, CDKN2A is a significant parameter only if lost in homozygosis, and this complicates the interpretation of the results. Furthermore, the new melanoma probe cocktail has been tested on cases of atypical Spitzoid proliferations with fatal outcomes which at present are too few to allow definite conclusions. The authors propose the implementation of a FISH algorithm (standard 4-probe test followed by either C-MYC or CDKN2A/centromere 9) to assist the histopathological diagnosis and minimize the technical problems. Nevertheless, because the diagnostic accuracy of the FISH technique is far from being absolute, the overall clinicopathological context must always guide the decision-making process about the management of morphobiologically ambiguous melanocytic proliferations.

Family presence during resuscitation (FPDR) has been an ongoing topic of discussion in many hospital emergency departments throughout the United States. With the current emphasis promoting patient- and family-centered care, families are now exercising their right to be present at the bedside during resuscitation. With or without a policy, there is continued resistance to allow families to remain with their loved ones during resuscitation. The purpose of this study was to evaluate if an evidence-based educational intervention would increase physicians' and nurses' knowledge, attitudes, and compliance with allowing FPDR. This quasi-experimental study evaluated 30 attending physicians' and 65 registered nurses' knowledge of an existing family presence policy and their attitudes toward family presence post-educational intervention in an emergency department setting. Compliance of family presence was observed for 2 months pre- and post-educational intervention. Results show that most physicians and nurses either were not sure or were not aware that there was an existing written policy. The study demonstrated that nurses agree more than physicians that the option of FPDR is a patient/family right. The results also showed that the educational intervention had no effect on the physicians and nurses attitudes for FPDR, but it did change behaviors. Of the events involving professionals who were exposed to the educational intervention, family members were present 87.5% of the time. In contrast, only 23% of the events involving professionals who did not receive the educational intervention had families present. Ongoing staff education will heighten awareness to FPDR, make the staff more comfortable with families being present, and will presumably continue to increase invitations for FPDR.

Teno Torque virus, member of the family of Anelloviridae, has been associated with many autoimmune diseases such as idiopathic hepatitis, systemic lupus erythematosus, and multiple sclerosis. Its viral load tends to be higher in the bone marrow and in tissues with high turnover rate. We report here a case of an 11-month-old infant affected by acute myeloid leukemia who underwent hematopoietic stem cell transplantation, and after 6 months had autoimmune hepatitis and atopic dermatitis. Extremely high-cytokine IP-10 and eotaxin levels were found in her sera, and serological tests and RT-PCR for viruses showed positive results exclusively for Teno Torque virus.

A case of a pneumomediastinum mimicking a pericarditis in a boy with an occult perforation due to ulcerative colitis is reported. Pneumomediastinum is a rare complication of severe attacks of ulcerative colitis, with or without the previous development of a toxic megacolon, that should be considered in the differential diagnosis.

Acquired long QT syndrome (LQTS) is a disorder of cardiac repolarization most often due to specific drugs, hypokalemia, or hypomagnesemia that may precipitate torsade de pointes and cause sudden cardiac death. Common presentations of the LQTS are palpitations, presyncope, syncope, cardiac arrest, and seizures. An abnormal 12-lead electrocardiogram obtained while the patient is at rest is the key to diagnosis. The occurrence of drug-induced LQTS is unpredictable in any given individual, but a common observation is that most patients have at least 1 identifiable risk factor in addition to drug exposure. The cornerstone of the management of acquired LQTS includes the identification and discontinuation of any precipitating drug and the correction of metabolic abnormalities, such as hypokalemia or hypomagnesemia. Most of the episodes of torsade de pointes are short-lived and terminate spontaneously. We propose a management protocol that could be useful for the daily practice in the emergency pediatric department to reduce the risk of acquired QT prolongation.

Granuloma annulare (GA) is characterized histopathologically by 3 patterns: necrobiotic granuloma, interstitial incomplete form and, rarely, sarcoidal or tuberculoid granuloma. The amount of lymphoid infiltrate in GA is usually limited. We describe 10 cases of GA with prominent "pseudolymphomatous" lymphoid infiltrates mimicking cutaneous lymphoid hyperplasia. Patients were 6 males and 4 females (mean age 49.9 years, median age 47 years, age range 25-70). Lesions were localized to a limited area of the body (n = 6), or involved the entire trunk (n = 3), or were generalized (n = 1). The correct clinical diagnosis of GA was provided only in 30% of the cases. In all cases, histopathologic features were characterized by dense, nodular, superficial, and deep infiltrates of lymphocytes. Immunohistology revealed predominance of T lymphocytes in 7 of 7 tested cases. This "pseudolymphomatous" variant of GA represents a pitfall in the histopathologic diagnosis of the disease and may be misinterpreted as other types of cutaneous lymphoproliferative disorders.

Purpose of Review: Tuberculosis (TB) remains a global emergency and continues to kill 1.4 million people every year. The interaction between noncommunicable and infectious diseases like TB has important implications with regard to the attainment of the Millennium Development Goals (MDGs). Smoking, diabetes mellitus, anti-TNFα drugs and other immunosuppressive therapies are well known major risk factors associated with TB. The purpose of this review is to summarize the recent literature on these risk factors and interventions that reduce the risk., Recent Findings: Mathematical models and aggregate data from the field show that smoking, diabetes and anti-TNFα drugs independently increase the risk of developing active TB. There is consensus on the great need for screening for active TB disease in patients with these conditions and targeted preventive interventions through a combined multidisciplinary approach., Summary: Smoking, diabetes mellitus, anti-TNFα drugs and new immunosuppressive treatments represent important common risk factors for TB. A high degree of clinical awareness of the possibility of TB should be considered in patients with these risk factors, and active screening and prevention should be undertaken. Further operational research is needed to optimize screening for latent Mycobacterium tuberculosis infection, instituting preventive intervention measures.

Objective: Hexavalent chromium (Cr(VI)) compounds are widely found in different working environments. These compounds can cause apoptosis in human cells, but the mechanisms underlying chromium-induced apoptosis are not clear. A marker of apoptosis is the exposure of phosphatidylserine on cell membrane and the modification of phosphatidylserine metabolism. The aim of this study was to verify whether chromium could cause phosphatidylserine exposure and modification of its metabolism in human lymphoblastic leukemia cell line (MOLT-4)., Methods: Phosphatidylserine exposure was evaluated by annexin V binding whereas phosphatidylserine metabolism was studied measuring the incorporation of [³H]serine., Results: Cell treatment with Cr(VI) increases phosphatidylserine exposure and cell apoptosis, but decreases the incorporation of [³H]serine into phosphatidylserine in a dose- and time-dependent manner., Conclusions: The Cr(VI)-induced apoptosis also through modification of phosphatidylserine exposure and metabolism.

A 58-year-old white woman with stasis dermatitis developed a solitary, slowly growing keratotic nodule of the dorsum of the foot. The excision biopsy specimen of this lesion showed a biphasic pattern of eccrine syringofibroadenoma and clear cell acanthoma. Such a previously unreported association is neither necessarily by chance nor necessarily a collision. Because a reactive histogenesis has been postulated for both eccrine syringofibroadenoma and clear cell acanthoma, this case could represent a morphologically biphasic pattern of epidermal and ductal hyperplasia as a consequence of the stasis-induced chronic inflammation coupled with the footwear-induced chronic trauma.

We present a case of interstitial mycosis fungoides showing pseudodovascular clefts with "free-floating" collagen fibers surrounded by neoplastic T lymphocytes. Such a finding further expands the histopathologic spectrum of mycosis fungoides and could be taken into account in its differential diagnosis from granuloma annulare, inflammatory morphea, and interstitial granulomatous drug reaction.

We describe 3 cases of desmoplastic nevus with special emphasis on some repetitive dermoscopic and histopathologic features, which-if confirmed on larger series-could allow to identify desmoplastic nevus as a specific clinicopathologic entity within the spectrum of acquired melanocytic nevi.

Objective: To test the hypothesis that persistent villi hypoperfusion explains intramucosal acidosis after endotoxemic shock resuscitation., Design: Controlled experimental study., Setting: University-based research laboratory., Subjects: A total of 14 anesthetized, mechanically ventilated sheep., Interventions: Sheep were randomly assigned to endotoxin (n = 7) or control groups (n = 7). The endotoxin group received 5 microg/kg endotoxin, followed by 4 microg x kg(-1) x hr(-1) for 150 mins. After 60 mins of shock, hydroxyethylstarch resuscitation was given to normalize oxygen transport for an additional 90 mins., Measurements and Main Results: Endotoxin infusion decreased mean arterial blood pressure, cardiac output, and superior mesenteric artery blood flow (96 +/- 10 vs. 51 +/- 20 mm Hg, 145 +/- 30 vs. 90 +/- 30 mL x min(-1) x kg(-1), and 643 +/- 203 vs. 317 +/- 93 mL x min(-1) x kg(-1), respectively; p < .05 vs. basal), whereas it increased intramucosal-arterial PCO2 (deltaPCO2) and arterial lactate (3 +/- 3 vs. 14 +/- 8 mm Hg, and 1.5 +/- 0.5 vs. 3.7 +/- 1.3 mmol/L; p < .05). Sublingual, and serosal and mucosal intestinal microvascular flow indexes, and the percentage of perfused ileal villi were reduced (3.0 +/- 0.1 vs. 2.3 +/- 0.4, 3.2 +/- 0.2 vs. 2.4 +/- 0.6, 3.0 +/- 0.0 vs. 2.0 +/- 0.2, and 98% +/- 3% vs. 76% +/- 10%; p < .05). Resuscitation normalized mean arterial blood pressure (92 +/- 13 mm Hg), cardiac output (165 +/- 32 mL x min(-1) x kg(-1)), superior mesenteric artery blood flow (683 +/- 192 mL x min(-1) x kg(-1)), and sublingual and serosal intestinal microvascular flow indexes (2.8 +/- 0.5 and 3.5 +/- 0.7). Nevertheless, deltaPCO2, lactate, mucosal intestinal microvascular flow indexes, and percentage of perfused ileal villi remained altered (10 +/- 6 mm Hg, 3.7 +/- 0.9 mmol/L, 2.3 +/- 0.4, and 78% +/- 11%; p < .05)., Conclusions: In this model of endotoxemia, fluid resuscitation corrected both serosal intestinal and sublingual microcirculation but was unable to restore intestinal mucosal perfusion. Intramucosal acidosis might be due to persistent villi hypoperfusion.

The histopathologic diagnosis of cutaneous tuberculosis (CTB) is often troublesome, because there are several other entities (tuberculids, demodicidosis, granulomatous rosacea, and acne agminata) that may display granulomatous inflammation with caseation necrosis. The current study describes four cases of granulomatous disease of the face. The final diagnosis (assessed on the basis of the clinical response to therapy) was CTB in three cases and granulomatous rosacea in one case. Histologically, epithelioid granulomas were a constant feature; in one case of CTB, they displayed a palisading (granuloma annulare-like) arrangement. Caseation necrosis was a prominent feature only in the case of granulomatous rosacea. Routinely processed biopsy specimens were evaluated with nested polymerase chain reaction (nPCR) for Mycobacterium tuberculosis (MBT) DNA. The correlation between nPCR results and clinical outcome was less than optimal; in fact, one case showed an excellent clinical response to the antituberculous drug therapy despite the absence of MBT DNA amplification. In granulomatous diseases of the face, the importance of evaluating not only nPCR but the overall clinicopathologic picture so as to avoid diagnostic misinterpretations is emphasized.

A combination of molecular genotyping and protein biochemistry methods was used to assess the HLA-A, -B, -C genotyping and expression of six tumor cell lines. Four cell lines had been previously HLA typed by conventional serologic methods. Two could not be typed by serology because deficient in the surface expression of HLA-A, -B, -C molecules. As shown herein, all the 25 alleles carried by the six tested cell lines were typed at the DNA level. In addition, discrepancies between the previous serologic and the present DNA typing results were detected in 9 of the 21 tested serologic specificities. Typing at the protein level by isoelectric focusing and allele-specific monoclonal antibodies confirmed the DNA typing data. Our results exemplify the limits of the serologic typing procedures and demonstrate that molecular methods are highly desirable to conduct functional experiments and identify HLA losses in neoplastic cells at single allele level.

A 70-year-old Italian man with a history of squamous cell carcinoma of the lung presented with a nodular skin eruption. He had traveled extensively in India and Sri Lanka. The nodules were well demarcated and measured up to 3.5 cm in diameter. Histologically, there was a proliferation of spindled and polygonal cells with focal and relatively inconspicuous cytoplasmic vacuolation. A macrophage-monocyte lineage for the cells was confirmed by paraffin section immunohistochemistry, using the monoclonal antibodies anti-CD45, MAC-387, KP-1, UCHL-1, MT-1, L26, and MB2. Infiltrating borders, extension of the lesion into the subcutis, and involvement of small dermal nerves and eccrine glands initially suggested the possibility of a "histiocytic" neoplasm of indeterminate biological potential. However, air-dried and Giemsa-stained material from a fine-needle aspirate of one cutaneous nodule showed needle-shaped intracellular "negative images," and acid-fast stains revealed a large number of intracytoplasmic bacilli in virtually all of the vacuolated lesional cells. Furthermore, a second skin nodule that was excised 3 weeks after initial presentation showed the typical morphology of lepromatous leprosy. The clinicopathologic features of this case demonstrated several similarities with those of so-called "histoid" leprosy. Unusual morphologic variants of leprosy need to be considered in the interpretation of unusual "histiocytic" infiltrates in order to avoid a mistaken diagnosis of neoplasia, regardless of the geographic locale in which the patient is evaluated.

Thirty-four patients with previously untreated advanced non-small-cell lung cancer were treated with a combination of polychemotherapy and recombinant interferon. Chemotherapy consisted of cyclophosphamide, 400 mg/m2, epidoxorubicin, 50 mg/m2, and cisplatin, 40 mg/m2 (CAP) i.v. on day 4; recombinant alpha 2b interferon (r alpha 2b IFN) was given i.m. daily at the dose of 3-5 MU from days 1 to 7. The treatment was repeated every 4 weeks. In the 32 eligible patients the overall response rate was 19.3% (95% C.L. 7.4-37.4%). Non-hematologic toxicity consisted formerly in flulike symptoms and fatigue complained of by 37.5% and 31.2% of patients, respectively, and vomiting reported in 68.7% of patients; grade III-IV myelotoxicity was observed in 12.5% of cases. In no case was the toxicity life threatening. The median overall actuarial survival and progression-free survival were 37 and 20 weeks, respectively. This study indicates that the combination of CAP chemotherapy and r alpha IFN is feasible and active in the treatment of advanced non-small-cell lung cancer.

Three immunizations yielding cross reacting anti-HL-A antibodies were followed for 1 year or more. The specificities of the antisera obtained at different times were determined from their reactivity against a selected cell panel. Each antiserum was titrated against cells presenting different degrees of cross reaction. An extensive absorption study of each antiserum, diluted to one cytotoxic unit, was also performed. The data obtained suggest that the cross reactivity pattern in each response is rather rigidly established from the beginning and that it has little chance to vary even after secondary stimulation from the same donor.

A radioimmunoassay procedure is described by which peripheral blood lymphocytes can be typed for HLA-DR specificities. The major advantages of this method are the following: simple and reproducible procedure, no need for B lymphocyte separation, no need for optimal viability, and no need for preabsorption of antisera with platelets. This method will find an application in the genetic and biochemical analysis of the HLA complex, and in the clinical tests of Ia antigens for diagnostic or prognostic purposes and in retrospective transplant studies.

A standardized procedure is proposed for deliberate immunizations against human major histocompatibility complex determinants. The data presented demonstrate its effectiveness and, by using a number of necessary precautions, this procedure has proven to be very safe. The following points are especially important: (1) exclusive utilization of regular blood donors as immunizers; (3) use of whole blood as an immunizing agent; and (3) use of small immunizing stimuli rather than large transfusions. This procedure can be recommended for the production of monospecific anti-HLA antisera and it may be useful if and when a deliberate transfusion policy for prospective kidney recipients is adopted.