Ultrastructural Pathology of Murine Cytomegalovirus Infection in Cultured Mouse Nervous System Tissue

Mouse spinal cord-ganglia cultures were innoculated with murine cytomegalo-virus 14 days after explantation. Intranuclear virus was first observed 4 days after infection. The viruses, which occurred in four forms, were observed in increasing numbers during the ensuing 4 days. Differences were noted in the relative prevalence of certain of these forms in older as compared to younger cultures. This suggests that variations in virus form are related to virus maturation. Cytoplasmic viruses were occasionally observed, but their site of origin is not certain. A variety of cytoplasmic inclusions were seen, particularly in the older cultures. It seems likely that they represent specific cell responses to the presence of the virus. They were not observed in the control cultures, even though some of the latter did show severe degenerative changes.     

Duchenne muscular dystrophy and idiopathic hyperCKemia segregating in a family

A 7-month-old boy with gross motor delay and failure to thrive presented with rhabdomyolysis following an acute asthmatic episode. During hospitalization an electrocardiographic conversion to a Wolff-Parkinson-White type 1 (WPW) pattern took place. Duchenne muscular dystrophy (DMD) was suspected based on elevated creatine kinase (CK) serum levels, muscle biopsy, and family history. The diagnosis was confirmed by molecular analysis, which documented a deletion corresponding to cDNA probe 1-2a in the dystrophin gene, in the propositus and in an affected male cousin of his mother. “Idiopathic” hyperCKemia was found in the propositus, his father, and 5 of his relatives. We suggest that the unusually early and severe manifestations of DMD in this patient may be related to the coincidental inheritance of the maternal DMD gene and of a paternal gene, causing hyperCKemia. © 1995 Wiley-Liss, Inc.     

Transcriptional profiling of target of RNAIII-activating protein, a master regulator of staphylococcal virulence

Staphylococcus aureus is a gram-positive bacterium that is part of the normal healthy flora but that can become virulent and cause infections by producing biofilms and toxins. The production of virulence factors is regulated by cell-cell communication (quorum sensing) through the histidine phosphorylation of target of RNAIII-activating protein (TRAP), which is a 21-kDa protein that is highly conserved among staphylococci. Using microarray analysis, we show here that the expression and phosphorylation of TRAP upregulate the expression of most, if not all, toxins known to date, as well as their global regulator agr. In addition, we show here that the expression and phosphorylation of TRAP are also necessary for the expression of genes known to be necessary for the survival of the bacteria in a biofilm, like arc, pyr, and ure. TRAP is thus demonstrated to be a master regulator of staphylococcal pathogenesis.     

Atrial sympathetic and parasympathetic nerve sprouting and hyperinnervation induced by subthreshold electrical stimulation of the left stellate ganglion in normal dogs

BACKGROUND: Subthreshold electrical stimulation of the left stellate ganglion (LSG) can induce nerve sprouting and sympathetic hyperinnervation in canine ventricles. It is unclear whether a similar neural plasticity involving both sympathetic and parasympathetic innervation also exists in the atria. METHODS AND RESULTS: We applied subthreshold electrical stimulation at 20 Hz (0.45 ms pulse width) or 5 Hz (1.9 ms pulse width) to the LSG in 6 normal mongrel dogs. After 41+/-9 days, the hearts were harvested and the right and left atrium stained for synaptophysin (SYN), growth-associated protein 43 (GAP43), sympathetic nerve markers tyrosine hydroxylase (TH), and parasympathetic marker choline acetyltransferase (ChAT). Tissues from 6 additional healthy dogs were used as controls. The hearts from dogs with LSG electrical stimulation had a higher density of nerve structures immunopositive to the SYN, GAP43, TH, and ChAT (P<.01) in both right and left atria. Nerve density was equal in right and left atria. There were more TH-positive nerve structures than ChAT-positive nerve structures (P<.01) for both right and left atria. No atrial arrhythmia was observed at the second surgery. CONCLUSIONS: Continuous subthreshold electrical stimulation to the LSG induces both sympathetic and parasympathetic hyperinnervation in both right and left atria in normal dogs.     

Antibiotic Administration in Patients Undergoing Common Surgical Procedures in a Community Teaching Hospital: The Chaos Continues

The influence of recently published guidelines by the Surgical Infection Society (SIS) on current surgical practice are not well documented. The appropriateness of antibiotic administration in a cohort of surgical patients undergoing elective and emergency surgery in a department of surgery in an urban, community-based, private, 560-bed teaching hospital was retrospectively reviewed. The following were the criteria defining administration as appropriate as modified from SIS guidelines: Prophylactic use: (1) started prior to operation; (2) spectrum appropriate to the specific operation; (3) duration ≤ 24 hours. Therapeutic use: (1) started prior to operation; (2) spectrum appropriate to pathology; (3) Duration ≤ 24 hours for contamination or “resectable” infection and ≤ 5 days for established infection in the absence of clinical evidence of persisting infection. Any switchover from an appropriate agent to another appropriate or inappropriate agent in the same patient in the absence of microbiologic or clinical indication was considered inappropriate administration. We reviewed the charts of 211 randomly selected patients who underwent elective (n= 132) or emergency (n= 79) procedures during 1996. The operations included gastrectomy (n= 22), appendectomy (n= 27), open (n= 5) or laparoscopic (n= 27) cholecystectomy, colectomy (n= 28), hysterectomy (n= 8), laparotomy for intestinal obstruction (n= 11), mastectomy (n= 26), and ventral hernia repair (n= 37). A total of 17 antibiotics were used for prophylaxis and 21 for therapy. In 156 patients (74%) the administration was considered inappropriate. Eight patients in the inappropriate group developed diarrhea (two cases of Clostridium difficile-induced colitis) compared to two cases of diarrhea in the appropriate group (nonsignificant). The average duration of administration after elective and emergency operations was 3.3 and 5.7 days, respectively. The total expense for excessive duration of administration was $18,533. Many surgeons are not familiar with the spectrum of antimicrobials and often do not distinguish between prophylactic and therapeutic administration. Antibiotic usage in current surgical practice is often inappropriate, excessive, and chaotic.     

Planned reoperations and open management in critical intra-abdominal infections: Prospective experience in 52 cases

Open management and planned relaparotomies in the treatment of critical abdominal infections have recently generated interest and hope. Most studies which examine the value of these therapeutic modalities are retrospective and include poorly stratified groups of patients. Since 1985, we have consistently applied these aggressive methods of treatment in all patients presenting with ultra-abdominal infections belonging to the following groups: I) diffuse postoperative peritonitis (29 cases); II) diffuse fecal peritonitis (14 cases); and III) infected pancreatic necrosis (9 cases). The overall mortality rate was 44%; it was 55%, 14% and 56%, respectively, in the 3 groups. The abdomen was closed between reoperations in 21 patients who required an average of 1.7 relaparotomies; the mortality in this group was 24%. Thirty-one patients, who required an average of 3.8 relaparotomies, were managed with the open method resulting in a mortality of 58%. Multiple organ failure was the cause of death in 87% of the patients. We conclude that planned relaparotomies may have been beneficial in group II. The value of open management in patients belonging to groups I and III remains unproven. The mechanical-surgical answers to severe forms of peritonitis may have reached their limit.

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Resumen El manejo de abdomen abierto (laparostomía) con relaparotomías planeadas en el tratamiento de infecciones abdominales críticas ha generado reciente interés y esperanza. La mayoía de los estudios destinados a valorar estas modalidades terapéuticas han sido de carácter retrospectivo y basados en grupos de pacientes pobremente estratificados. A partir de 1985 el autor ha aplicado en forma consistente estos agresivos métodos de terapia en la totalidad de los pacientes con infecciones intraabdominales, clasificados en los siguientes grupos: I — Peritonitis postoperatoria difusa (29 casos); II — Peritonitis fecal difusa (14 casos); y III — necrosis pancréatica infectada (9 casos). La tasa global de mortalidad fue 44%; correspondió a 55%, 14% y 56%, respectivamente, en los 3 grupos. El abdomen fue cerrado entre reoperaciones en 21 pacientes que requirieron un promedio de 1.7 relaparotomías; la mortalidad en este grupo fue de 24%. Treinta y un pacientes que requirieron un promedio de 3.8 relapatomías fueron manejados mediante el método abierto, con una mortalidad de 58%. La falla orgánica múltiple fue la causa de muerte en 87% de las muertes. Nuestra conclusión es que las relaparotomías planeadas pueden ser beneficiosas en el grupo II; su valor no queda demostrado en pacientes de los grupos I y III. Las soluciones de tipo quirúrgico mecánico pueden haber llegado a su límite de beneficio en las formas severas de peritonitis.

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Résumé La technique de ventre ouvert avec des laparotomies répétées dans le traitement des infections abdominales graves est une méthode thérapeutique d'intérêt et d'espoir récent. La plupart des études concernant cette modalité thérapeutique souffrent d'être rétrospectives et d'être inhomogènes quant aux type de patients inclus. Depuis 1985, l'auteur a appliqué cette technique chez tous les patients ayant une infection abdominale qui se répartissaient dans les groupes suivants: I — péritonite diffuse postopératoire (29 cas), II — péritonite diffuse fécale (14 cas), III — nécrose pancréatite infectée (9 cas). La mortalité globale a été de 44%; elle a été de 55%, 14% et 56%, respectivement, dans les groupes I, II et III. Chez 21 patients qui ont nécessaité une moyenne de 1.7 relaparotomies, l'abdomen était fermé entre les réopérations (réouverture planifiée). La mortalité dans ce groupe a été de 24%. Chez les 31 patients qui ont nécessité une moyenne de 3.8 relaparotomies, l'abdomen a été laissé ouvert entre les explorations successives avec une mortalité de 58%. La défaillance polyviscérale était la cause de mortalité dans 87% des cas. La réouverture planifiée a pu être bénéfique dans le groupe II, mais sa valeur reste à démontrer dans les groupes I et III. Les moyens mécaniques ont peut-être atteint leur apogée dans le traitement des péritonites sévères.

     

Use of photodynamic therapy in the palliation of massive advanced rectal cancer

Photodynamic therapy (PDT) is a relatively new form of cancer therapy utilizing a photosensitizer such as hematoporphyrin derivative. We conducted a pilot study to determine the efficacy of its use in palliating advanced rectal cancer, to determine toxicity, and to establish objective outcome criteria. Six patients with very advanced, usually recurrent rectal cancer were treated with PDT after being photosensitized with Photofrin II^®. A protocol was established to measure clinical and radiologic response to therapy. A new intraluminal delivery system was incorporated. Five patients had both clinical and radiologic responses to therapy. In two patients we observed such significant responses that they cannot be accounted for on a photobiologic basis alone. One patient developed a significant sunburn after discharge. There was no major toxicity of bleeding or sepsis even at maximum doses (200 J/cm²). We are confident that PDT has a role to play in rectal cancer and speculate as to future applications.     

Comparison of postoperative complications following radical and modified radical mastectomy

A retrospective study was carried out by reviewing the files of 100 patients who had undergone radical mastectomy and 100 patients who had undergone modified radical mastectomy from 1966 to 1975 for the purpose of comparing early and late complications. In each group, 80 patients were involved in long-term follow-up. Immediate postoperative complications—notably seromas, wound infection, and flap necrosis—were found to be considerably fewer following modified radical mastectomy. There was also a significantly lower incidence of late complications, such as limb edema and recurrent infection, after modified radical mastectomy. Since the cure rates achieved by the two radical mastectomy procedures appear to be similar, it is concluded that modified radical mastectomy is the procedure of choice in stages I and II cancer of the breast.

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Résumé Nous avons relevé les dossiers de 100 patientes traitées par mammectomie radicale conventionelle et de 100 patientes traitées par mammectomie radicale modifiée et avons comparé les complications post-opératoires observées dans les 2 groupes. Toutes les patientes furent opérées entre 1966 et 1975. Dans chaque groupe, nous avions un recul suffisant chez 80 patientes pour évaluer les résultats à long terme. Les complications post-opératoires, immédiates (sérÔmes, infections de plaie, nécrose de greffe cutanée) ou tardives (lymphoedème du bras, infections à répétition), furent beaucoup plus rares après mammectomie radicale modifiée. Etant donné que les taux de guérison obtenus avec ces 2 opérations semblent Être les mÊmes, nous en concluons que la mammectomie radicale modifiée est l'opération de choix pour traiter les cancers du sein au stade I et II.