Engraftment of bone marrow cells into normal unprepared hosts: effects of 5-fluorouracil and cell cycle status

Bone marrow from animals treated with 5-fluorouracil (5FU) competes equally with normal marrow when assessed in vivo in an irradiated mouse, but shows markedly defective engraftment when transplanted into noncytoablated hosts. Using Southern Blot analysis and a Y-chromosome specific probe, we determined the level of engraftment of male donor cells in the bone marrow, spleen, and thymus of unprepared female hosts. We have confirmed the defective engraftment of marrow harvested 6 days after 5FU (FU-6) and transplanted into unprepared hosts and shown that this defect is transient; by 35 days after 5FU (FU-35), engraftment has returned to levels seen with normal marrow. FU-6 marrow represents an actively cycling population of stem cells, and we hypothesize that the cycle status of the stem cell may relate to its capacity to engraft in the nonirradiated host. Accordingly, we have evaluated the cycle status of engrafting normal and FU-6 marrow into normal hosts using an in vivo hydroxyurea technique. We have shown that those cells engrafting from normal marrow and over 70% of the cells engrafting from FU-6 marrow were quiescent, demonstrating no killing with hydroxyurea. We have also used fluorescent in situ hybridization (FISH) analysis with a Y-chromosome probe and demonstrated that normal and post-5FU engraftment patterns in peripheral blood were similar to those seen in bone marrow, spleen, and thymus. Altogether these data indicate that cells engrafting in normal, unprepared hosts are dormant, and the defect that occurs after 5FU is concomitant with the induction of these cells to transit the cell cycle.     

Subcutaneous panniculitis complicating pancreatic acinar cell carcinoma

Acinar cell carcinoma of the pancreas is rare and can occur with the unusual presentation of arthritis and panniculitis that mimic erythema nodosum. We report a case and review the available literature regarding this rare condition of erythema nodosum and panniculitis associated with bilateral ankle and feet pain, which has rendered the patient virtually wheelchair‐bound.     

Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.     

Refrigerated storage of lyophilized and rehydrated, lyophilized human red cells

Human red cells (RBCs) were collected in CPDA-1 and then freeze-dried in lyoprotective solution. The lyophilized RBCs were then stored at -20 degrees C for 7 days. At the end of the storage period, the lyophilized RBCs were rehydrated and washed in dextrose saline. The washed, reconstituted, lyophilized RBCs were resuspended in final wash solutions of ADSOL, CPDA-1, or a special additive solution containing glucose, citrate, phosphate, adenine, and mannitol, and then they were stored at 4 degrees C for an additional 7 days. The main purpose of this study was to determine whether human RBCs can be lyophilized in such a manner that normal metabolic, rheologic, and cellular properties are maintained during rehydration and subsequent storage in standard blood bank preservative solutions. Our results show that reconstituted, lyophilized RBCs maintained levels of ATP, 2,3 DPG, lactate, and cellular properties that are equal to or better than those in control nonlyophilized RBCs stored for a comparable period in CPDA-1. Reconstituted, lyophilized RBCs stored at 4 degrees C after rehydration also show better maintenance of ATP, 2,3 DPG, and lactate than do control RBCs stored in the same preservative solutions for comparable periods.     

White cell subsets in apheresis and filtered platelet concentrates

BACKGROUND: White cell (WBC)-reduced platelet concentrates (PCs) are defined by their absolute WBC count, a criterion which provides no information regarding the various WBC subsets contained in the PC. These heterogeneous cells are known to mediate different physiologic and pathophysiologic functions and account for distinct adverse transfusion responses. This study describes a method which allows the detection and quantification of these subsets and characterizes their presence in a variety of platelet components. STUDY DESIGN AND METHODS: Random-donor pooled PCs (RD PCs) and single-donor apheresis PCs (SD PCs) were studied. RD PCs consisting of 6 units of 2- to 3-day old PCs were randomly assigned to be filtered with one of four WBC-reduction filters from three different manufacturers (n=34). The residual WBCs were pelleted by centrifugation and isolated on a density gradient. The various WBC subsets were quantified by flow cytometry in unfiltered and filtered PCs using fluorescence and two-angle light scatter. SD PCs obtained with two manufacturer's systems and three processing protocols (n=30) were studied in like manner. RESULTS: WBC counts for non-WBC- reduced PCs averaged 3 × 10(8) in RD PCs and ranged from 8.6 to 9.6 × 10(6) per SD PC. Residual WBC counts in filtered PCs ranged from 2.3 × 10(4) to 2.2 × 10(5) and those in WBC-reduced SD PCs averaged 2.2 × 10(5) per unit. The data demonstrate significant phenotypic differences among PCs produced with various procedures. All SD PCs and two of four filtered RD PCs contained five WBC populations including granulocytes and monocytes, while RD PCs filtered with the remaining manufacturer's devices contained only lymphocytes. CONCLUSION: The data confirm that distinct phenotypic differences exist among PCs prepared with different devices and/or procedures. It is suggested that as for non-generic pharmaceuticals, the clinical benefits of these various PCs should be individually proved.     

Is interval from an initial biopsy a significant predictor of prostate cancer at repeat biopsies?

BACKGROUND: Currently, there are no clear criteria for indicating repeat biopsies in patients with negative results at an initial biopsy of the prostate. The aim of the present study is to determine the clinical and pathological parameters which predict prostate cancer at repeat biopsies with special attention to the interval between biopsies in addition to prostate specific antigen (PSA) and its derivatives. METHODS: We reviewed 100 patients who underwent an initial biopsy that proved negative for prostate cancer and required repeat biopsies between November 1996 and November 2003. Clinical parameters such as age, PSA and its derivatives, interval between biopsies, number of cores taken and initial biopsy histology were analyzed. RESULTS: In total, 31 patients (31.0%) were found to have prostate cancer, 18 (25.7%) of 70 patients by the second biopsy and 13 (46.4%) of 28 patients by the third biopsy. Two patients underwent the fourth biopsy, which revealed no prostate cancer. The patients with a positive biopsy had a significantly longer interval between the biopsies than the patients with a negative biopsy (P=0.0036). Furthermore, in both univariate and multivariate logistic regression analysis, only the interval between the biopsies proved to be an independent predictor of positive results at repeat biopsies (P=0.0094 and 0.0019). CONCLUSIONS: Only the biopsy interval was a significant predictor of prostate cancer at repeat biopsies in both univariate and multivariate analysis.     

Homozygous α-thalassaemia: clinical presentation, diagnosis and management. A review of 46 cases

Summary. Forty-six hydropic infants with homozygous α-thalassaemia born during a period of 10 years have been reviewed. The incidence was 1: 1550 total births, and accounted for 81% of all non-immune hydrops. The male to female ratio was 1: 1.4. There was increased incidence of anaemia, pregnancy induced hypertension, antepartum haemorrhage, malpresentation, prematurity, fetal distress, difficult vaginal delivery, caesarean section, retained placenta. postpartum haemorrhage and congenital abnormalities. Antenatal diagnosis by DNA hybridization with subsequent abortion of the affected fetuses is the best method to decrease maternal morbidity and to reduce the incidence of hydrops fetalis in couples at risk. For those with no previous history, but with early onset hypertension and/or polyhydramnios, sonography is useful in making an earlier diagnosis, and in reducing avoidable morbidity, because DNA analysis can be done before caesarean section and aggressive neonatal management is instituted.     

Antidiabetic and haematological effect of aqueous extract of stem bark of Afzelia africana (Smith) on streptozotocin-induced diabetic Wistar rats

Objective

To investigate the antidiabetic properties of aqueous extract of stem bark of Afzelia africana (A. africana) and its beneficial effect on haematological parameters in streptozotocin induced diabetic rats.

Methods

A total of 30 rats including 24 diabetic and 6 normal rats were used for this study. Diabetes was induced in male Wistar rats by intraperitoneal injection of streptozotocin. After being confirmed diabetic, animals were orally treated with distilled water or extracts at 100 or 200 mg/kg body weight daily for 10 days. The haematological parameters including red blood and white blood cells and their functional indices were evaluated in diabetic treated groups compared with the controls.

Results

The extract significantly reduced the blood glucose levels while the best result was obtained at 200 mg/kg body weight. The feed and water intake in diabetic rats were significantly reduced while weight loss was minimized at both dosages. Similarly, the levels of red blood, white blood cells and their functional indices were significantly improved after extract administration at both doses.

Conclusions

It can be concluded that the aqueous extract of bark of A. africana possesses antihyperglycemic properties. In addition, the extract can prevent various complications of diabetes and improve some haematological parameters. Further experimental investigation is needed to exploit its relevant therapeutic effect to substantiate its ethnomedicinal usage.     

Upper gastrointestinal endoscopy findings in Mbale Regional Referral Hospital,Eastern Uganda: a 10-year retrospective analysis

BackgroundEndoscopy is required for formal diagnosis of many upper gastrointestinal (UGI) conditions including oesophageal cancer (OC). There is a paucity of data on endoscopy findings in East Africa as access to testing is challenging for patients. We describe the findings of 10 years of UGI endoscopy in Mbale Regional Referral Hospital (MRRH).MethodRecords of patients that underwent UGI endoscopy in MRRH, November 2009 – March 2019 were retrospectively analysed. Indication, macroscopic findings, histology and patient demographics were retrieved. Sub-group analyses were performed on those with a histological diagnosis of oesophageal cancer.Results833 eligible patients received single UGI procedures during the study period. Mean age was 54.8 years, range 16-93 years and 56.9% of patients were male. The main indication was dysphagia (42%) and the most common findings OC (34%) and gastritis (28%). 151 patients had histologically proven OC with a median age of 60 years and a 2:1 male to female ratio. 145/151 (96%) of samples tested revealed squamous cell carcinoma (SCC).ConclusionThose undergoing endoscopy in MRRH are most commonly male patients presenting in their 5th decade with dysphagia. There is a high proportion of significant findings including gastritis, peptic ulcer disease, and oesophageal cancer.