Conjunctivitis as a sign of persistent SARS-COV-2 infection? An observational study and report of late symptoms.

PURPOSE: To investigate if symptomatic conjunctivitis during the recovery phase of the disease could be associated to a persistent presence of SARS-CoV-2 in the upper respiratory tract. Secondary end points were to analyze the presence of SARS-CoV-2 in the conjunctiva of ocular symptomatic patients and to record the presence of ocular disturbances at this point of the disease. METHODS: An observational study including consecutive COVID19 patients treated at Humanitas Clinical and Research Hospital who were attending for nasopharyngeal swab to confirm the resolution of SARS-CoV-2 infection and end of isolation. We examined 129 consecutive patients from May to June 2020. The primary end point was to determine if symptomatic conjunctivitis at this point of the disease could be associated to a persistent presence of SARS-CoV-2 in the upper respiratory tract. Secondary end points were to analyze the presence of SARS-CoV-2 in the conjunctiva of ocular symptomatic patients and to record the presence of ocular disturbances at this point of the disease. RESULTS: One hundred twenty eight patients were included, 9.38% had conjunctivitis, none resulted positive to conjunctival PCR swab test, while two of them had positive nasopharyngeal result. Mean time elapsed since the first COVID-19 positive swab to the time of examination was 6 weeks ( ± 3). The only significant association was the presence of conjunctivitis with older age (65.3 ± 12.7 vs 56.7 + 13.5. p = 0.046). Nasopharyngeal swab resulted positive in 22 patients (17.19%). While 88 patients (68.2%) did not have any ocular complain during their COVID19 disease. The 40 patients (31.8%) reporting ocular disturbances complained about: redness (25.43%), tearing (19.53%), burning (18.35%), foreign body sensation (17.18%), itching (15.62%), and discharge (12.5%). CONCLUSION: This study showed that late conjunctivitis cannot be considered as a marker of persistent infection when patients are sent to confirm the resolution of SARS-CoV-2 infection.

Fine organization of Bombyx mori fibroin heavy chain gene.

The complete sequence of the Bombyx mori fibroin gene has been determined by means of combining a shotgun sequencing strategy with physical map-based sequencing procedures. It consists of two exons (67 and 15 750 bp, respectively) and one intron (971 bp). The fibroin coding sequence presents a spectacular organization, with a highly repetitive and G-rich (approximately 45%) core flanked by non-repetitive 5' and 3' ends. This repetitive core is composed of alternate arrays of 12 repetitive and 11 amorphous domains. The sequences of the amorphous domains are evolutionarily conserved and the repetitive domains differ from each other in length by a variety of tandem repeats of subdomains of approximately 208 bp which are reminiscent of the repetitive nucleosome organization. A typical composition of a subdomain is a cluster of repetitive units, Ua, followed by a cluster of units, Ub, (with a Ua:Ub ratio of 2:1) flanked by conserved boundary elements at the 3' end. Moreover some repeats are also perfectly conserved at the peptide level indicating that the evolutionary pressure is not identical along the sequence. A tentative model for the constitution and evolution of this unusual gene is discussed.

Cloning and sequencing of the gene coding for topoisomerase I from the extremely thermophilic eubacterium, Thermotoga maritima.

A 2767 bp fragment containing a gene coding for a topoisomerase I from the extremely thermophilic eubacterium Thermotoga maritima (Tm TopA) has been cloned and sequenced. The protein is composed of 633 amino acids with a calculated molecular mass of 72,695 Da. It shares significant similarity with the topoisomerases I of mesophilic eubacteria. The highest score is obtained with Bacillus subtilis (44% identity); in particular, T. maritima and B. subtilis possess an insertion of 7-8 amino acids in the vicinity of the active site, that is absent in topoisomerases of other organisms. A specific feature of T. maritima topoisomerase I is its low cysteine content compared to its mesophilic homologs. It contains 5 cysteine residues, of which 4 could constitute a zinc finger motif. Finally, analysis of the regions flanking the gene reveals that Tm TopA is surrounded by two other ORFs, suggesting the occurrence of a polycistronic transcriptional unit.

SAV, an archaebacterial gene with extensive homology to a family of highly conserved eukaryotic ATPases.

Nucleotide sequencing of a region of the hyperthermophilic archaebacterium Sulfolobus acidocaldarius allowed us to identify an open reading frame of 780 amino acids strikingly similar to a family of eukaryotic ATPases, involved in a variety of biological functions. Sequence analysis of the predicted polypeptide revealed 63 to 66% similarity with S. cerevisiae CDC 48p and its related genes in amphibians (p97ATPase) and mammals (Valosin Containing Protein, VCP), all possibly involved in the regulation of the cell cycle. The finding of an archaebacterial equivalent of these proteins with a high degree of similarity suggests that it represents the same gene in these various species. The new archaebacterial ORF, called SAV (S. acidocaldarius VCP-like) exhibited the usual signature of all members of the family, a highly conserved domain of about 200 amino acids, which is duplicated. Thus, apart from the VCP-like proteins, SAV also appeared similar, although less clearly, to other ATPases, members of the family, involved in vesicle-mediated transport (NSF, Sec18p), peroxysome assembly (PAS1p), and gene expression in yeast (SUG1p) and in human immunodeficiency virus (TBP-1). Finally, the discovery of the archaebacterial gene could enlighten not only the evolutionary relationships between the members of this complex ATPase family, but also the cellular function of these proteins, that is presently obscure.

Autonomic nervous system dysfunction associated with HIV infection in intravenous heroin users.

OBJECTIVE: To evaluate the presence of autonomic nervous system (ANS) involvement in HIV-positive drug users. DESIGN: We investigated 37 HIV-positive (and 18 HIV-negative controls) intravenous heroin users who were without symptoms and signs of autonomic or peripheral neuropathy. METHODS: The patients were clinically and immunologically assessed and subjected to a battery of five cardiovascular reflex function tests. RESULTS: The tests revealed ANS involvement in 22 HIV-positive subjects but only in one HIV-negative subject. Immunoglobulin (Ig) G and C1q immune complex levels were significantly higher in HIV-positive subjects with severe cardiovascular reflex function tests alteration compared to those with normal tests. In a follow-up of 17 HIV-positive subjects, nine presented deteriorated reflexes in the tests and higher IgG immune complex levels. CONCLUSIONS: The results confirm that, by using sufficiently sensitive tests, signs of preclinical autonomic neuropathy can frequently be found in HIV-positive intravenous heroin users, as previously observed in homosexual patients, and suggest the existence of an HIV-related autoimmune pathogenesis. Early diagnosis of ANS involvement could be important, since the presence of autonomic dysfunction could increase the risk of cardiorespiratory arrest during invasive procedures.

The nature of the last universal ancestor and the root of the tree of life, still open questions.

The nature of the last universal ancestor to all extent cellular organisms and the rooting of the universal tree of life are fundamental questions which can now be addressed by molecular evolutionists. Several scenarios have been proposed during the last years, based on the phylogenies of ribosomal RNA and of duplicated proteins, which suggest that the last universal ancestor was either an RNA progenote or an hyperthermophilic prokaryote. We discuss these hypotheses in the light of new data on the evolution of DNA metabolizing enzymes and of contradictions between different protein phylogenies. We conclude that the last universal ancestor was a member of the DNA world already containing several DNA polymerases and DNA topoisomerases. Furthermore, we criticize current data which suggest that the rooting of the universal tree of life is located in the eubacterial branch and we conclude that both rooting the universal tree and the nature of the last universal ancestor are still open questions.

A BAC library and paired-PCR approach to mapping and completing the genome sequence of Sulfolobus solfataricus P2.

The original strategy used in the Sulfolobus solfataricus genome project was to sequence non overlapping, or minimally overlapping, cosmid or lambda inserts without constructing a physical map. However, after only about two thirds of the genome sequence was completed, this approach became counter-productive because there was a high sequence bias in the cosmid and lambda libraries. Therefore, a new approach was devised for linking the sequenced regions which may be generally applicable. BAC libraries were constructed and terminal sequences of the clones were determined and used for both end mapping and PCR screening. The PCR approaches included a novel chromosome walking method termed "paired-PCR". 21 gaps were filled by BAC end sequence analyses and 6 gaps were filled by PCR including three large ones by paired-PCR. The complete map revealed that 0.9 Mb remained to be sequenced and 34 BAC clones were selected for walking over small gaps and preparing template libraries for larger ones. It is concluded that an optimal strategy for sequencing microorganism genomes involves construction of a high-resolution physical map by BAC end analyses, PCR screening and paired-PCR chromosome walking after about half the genome sequence has been accumulated.

Immunological patterns during regular intensive training in athletes: quantification and evaluation of a preventive pharmacological approach.

The effects of regular intensive exercise training on immune system homeostasis and the potential value of treatment with an immunostimulating agent were assessed in this randomized, double-blind, placebo-controlled, parallel-group study. A total of 60 athletes were studied over a 3-month period of regular intensive physical activity. After 1 and 3 months there were significant decreases in the immunoglobulin levels in the whole athlete population compared with baseline values. Specifically there were significant decreases in immunoglobulin M and immunoglobulin G (G1 and G2 subclasses). There was also a significant decrease in natural killer cells and a slight but significant increase in B and T lymphocytes. In the thymomodulin-treated group, unlike the placebo group, there was no significant decrease in the immunoglobulin G2 subclass and there was a significant increase in the T-helper cell subpopulation. The clinical relevance of these immunological findings should be evaluated in larger clinical and epidemiological studies.

[Richter's syndrome. Presentation of a rare variant with regression of chronic lymphatic leukemia and review of the literature]. / Sindrome di Richter. Presentazione di una rara variante con regressione della leucemia linfatica cronica e revisione della letteratura.

The incidence of a lymphoreticular system malignancy in patients with chronic lymphocytic leukemia (CLL), Richter's syndrome (RS), is 3.3 to 10.6%. In 89 cases in the literature, the second neoplasm was either reticulum cell sarcoma or large cell diffuse histiocytic lymphoma (DHL), and there were 61 cases of Hodgkin's disease (HD). In a few cases the lymphoma was simultaneously diagnosed, for other cases an association with preexisting CLL was reported. Appearance of lymphoma was associated with leukemia regression for only 4 patients with DHL and 3 with HD. We report one case of B-lymphocyte CLL with macroglobulinemia, treated with melphalan and prednisone, in which DHL developed and the hematologic and histologic signs of CLL and of paraproteinemia remissed. Such patients might constitute a subgroup or a variant of RS. Since the non-Hodgkin malignant lymphomas (NHML) are considered to be monoclonal neoplastic expansion of the B-cell or T-cell lymphocytes, and since in some cases it has been proved that the proliferative cell clone was the same as that of the initial lymphoproliferative disease, RS could be a dedifferentiation or a transformation of CLL, resulting in an aggressive clinical course. The inclusion in this syndrome of CLL cases associated with HD is still controversial. Many of these cases could be giant cell pleomorphic lymphomas, while, on the contrary, in typical cases this association might be merely fortuitous.

[A case of oral localization of Crohn's disease. Review of the literature]. / Un caso di localizzazione orale del morbo di Crohn. Rassegna della letteratura.

A case of Crohn's disease with specific tonsillar, pharyngeal and laryngeal lesions is presented. The unusualness of this site was clear from the literature. Stress is laid on the ubiquity of lesions indicative of the systemic nature of the disease. The intestinal lesions contain a viral agent that can be transmitted to animals.

[A case of pure erythroblastic aplasia effectively treated with immunosuppressive drugs]. / Un caso di aplasia eritroblastica pura efficacemente trattato con immunosoppressori.

A case of PRCA, refractory to corticosteroids and androgenes is reported. The patient presented persistent remission when treated with Cyclophosphamide. The review of the cases treated with immunosuppressive drugs proves that this treatment is effective and emphasizes the probable autoimmune pathogenesis of PRCA.

[Palliative cholangiojejunostomy on the duct of hepatic segment III. Our experience]. / Colangiodigiunostomia palliativa sul dotto del 3o segmento epatico. La nostra esperienza.

BACKGROUND: Aim of the paper is to prove that indications for cholangiojejunostomy, in cases when a mean and long term palliation may be expected, are better than those offered by the use of prostheses, without the well known and early bile duct complications. METHODS: Between 1984 and 1995, 12 patients with obstructive jaundice due to malignancy at the hepatic hilum were treated by segment III Roux-en-y or omega cholangiojejunostomy. In 1 patient with no communication between right and left lobe of the liver, biliary-enteric bypass to segment VI duct was also undertaken; in another with neoplastic stenosis of pylorus gastrojejunostomy was performed. Seven patients had carcinoma of the gallbladder, three hilar cholangiocarcinoma, one gastric carcinoma and one recurrent pancreatic carcinoma. RESULTS: There were two postoperative deaths, one for myocardial infarction and one for biliary peritonitis. Six patients had complications: four biliary fistulas with spontaneous resolution and two wound infections. Seven of the ten surviving patients experienced complete resolution of jaundice for at least 4 months. The mean survival of surviving patients was 9.7 months. Nine patients developed recurrent jaundice. CONCLUSIONS: Segment III cholangiojejunostomy is a good palliative treatment in most patients with malignant hilar obstruction.

[Cholecystolithotomy with cholecystojejunostomy as surgical solution for cholelithiasis in portal hypertension caused by hepatic cirrhosis]. / La colecistolitotomia con colecistodigiunostomia come soluzione chirurgica della colelitiasi nella ipertensione portale da cirrosi epatica.

Cholecystolithotomy and cholecystojejunostomy has been carried out on 11 patients with severe hypertension from cirrhosis. The indications were frequently recurring attacks of biliary cholic or acute cholecystitis at onset. There was 1 postoperative death from cardiac infarction and only minor in-hospital morbidity. None of the remaining patients has to date developed post-cholecystojejunostomy sequelae. Except the case of extensive inflammation on gangrena, this procedure appears to be a safe and definitive operation, alternative to subtotal cholecystectomy.

[Role of total parenteral nutrition in the treatment of ulcerous colitis]. / Il ruolo della nutrizione parenterale totale nel trattamento della colite ulcerosa.

Reference is made to the literature and personal experience in an assessment of the rôle of total parenteral nutrition in ulcerative colitis. An estimate is made of the position of this form of treatment with respect to conventional medical and surgical management, and its influence on the natural course of the disease. The results observed in 6 patients treated in this way are reported and the treatment protocol employed for the management of ulcerative colitis in a surgical department is described.

[Surgical treatment of perforated duodenal ulcer. Review of 36 cases]. / Il trattamento chirurgico dell'ulcera duodenale perforata. Revisione di 36 casi.

Results obtained in the surgical management of 36 cases of perforated duodenal ulcer treated between January 1976 and November 1979 are presented. A choice was made between three methods (suturing, excision plus pyloroplasty and truncular vagotomy, and Péan-Billroth resection and reconstruction) in the light of the duration of the disease, the extent of the duodenal alterations, and the concomitance of serious disorders. No account was taken of age, the time elapsed between perforation and treatment, or the extent of peritoneal reaction.

[A case of pulmonary aspergillosis effectively treated with itraconazole. Possible interaction of the antimycotic agent with hydroquinidine]. / Un caso di aspergillosi polmonare trattato efficacemente con itraconazolo. Possibile interferenza dell'antimicotico con la idrochinidina.

This study describes a case of pulmonary aspergilloma in a neutropenic patient affected with myelodysplastic syndrome. It reports the therapeutic efficacy of itraconazole, emphasizing in particular the possible interaction with quinidine, with QT prolongation--at ECG--disappeared after quinidine withdrawal.

Terlipressin-induced metabolic acidosis.

Vasopressin and its analogue terlipressin are potent vasoconstrictors which reduce mesenteric blood flow and have been used in the therapy of variceal hemorrhage. This vasoconstrictor effect applies on vascular beds throughout the body. Since in literature vasopressin is rarely described to determine lactic acidosis, we report of a patient in whom a severe metabolic (probably lactic) acidosis appeared, associated with terlipressin administration for bleeding esophageal varices. By exclusion, the temporal sequence with terlipressin therapy, the contemporary increase of arterial blood pressure and autoptic data in the case presented make likely a diagnosis of terlipressin-induced lactic acidosis. Because of the seriousness of metabolic acidosis observed in our patient we suggest a careful monitoring of acid-base parameters in patients under treatment with vasopressin analogues.

[Hospital pseudo-infections caused by Mycobacterium gordonae]. / Pseudoinfezioni ospedaliere da Mycobacterium gordonae.

Sputum specimens from 15 patients with respiratory disease were reported to have positive cultures for Mycobacterium gordonae, an organism generally considered to be non-pathogenic for man. None showed typical radiological changes for mycobacteriosis. Mycobacterium gordonae was also isolated from some components of the aerosol therapy instrument. Because aerosol therapy was used for 4 patients only, we were not able to establish whether the Mycobacterium gordonae was only a colonizer. We suggest that its isolation in culture must be evaluated in an adequate clinical context before concluding that it is pathogenic.

[Still's disease in adults: diagnostic problems]. / Malattia di Still dell'adulto: problemi diagnostici.

Still's disease is a seronegative arthritis of children which, in a limited number of cases, can affect adults. The diagnosis of adult-onset Still's disease is characterized by high fever, arthritis and negative serologic tests for rheumatoid factor and antinuclear antibodies and by at least two minor symptoms (leukocytosis, evanescent rash, serositis, hepato- or splenomegaly, and lympho-adenopathy). Since many diseases present analogous manifestations and the adult-onset Still's disease is generally diagnosed by exclusion, we report two patients, aged 26 and 39, with Still's disease, the former with a classic clinical feature, the latter with a clinical feature characterized by severe hepatic abnormalities. The determination of histocompatibility antigens can be useful because some of them (HLA-DR4 in case 1 and HLA-DRw6 in case 2) are frequently associated with the adult-onset Still's disease. The role of anti-inflammatory therapy (acetylsalicylic acid, indomethacin, steroids) must be emphasized, whose efficacy can constitute the pathognomonic element on which the diagnosis of adult-onset Still's disease can be based in a proper clinical pattern.

[Transitory efficacy of potassium perchlorate in hypothyroidism caused by amiodarone]. / Transitoria efficacia del perclorato di potassio nell'ipotiroidismo da amiodarone.

We report a case of a patient with hypothyroidism due to amiodarone. The short-term administration (1 g/die for 10 days) of potassium perchlorate (KClO4) led to normalization of serum thyroid hormone concentrations and marked reduction of thyrotropic hormone. The reduction of KClO4 (400 mg/die) and its following withdrawal led to reappearance of hypothyroidism signs. No side-effects or toxic reactions occurred during KClO4 therapy. This anion competitively inhibits thyroid iodide transport, reducing intrathyroidal iodide content and removing thyroid hormone synthesis inhibition. We suggest KClO4 therapy when amiodarone-associated hypothyroidism impairs a pre-existent cardiac disease and when a quick restoration of euthyroidism is necessary. Nevertheless, we emphasize that its effect can be transitory in cases of short-term treatment or low doses.