Missense mutation of the last nucleotide of exon 1 (G->C) of beta globin gene not only leads to undetectable mutant peptide and transcript but also interferes with the expression of wild allele.

Hemoglobin Monroe (beta globin G->C, codon 30) is a missense mutation. We could not detect either the mutant peptide or transcript in reticulocyte-enriched preparation and in expanded erythroid progenitor cells. By quantitative gene expression assay beta globin mRNA was found to be reduced by more than 70% in all heterozygous subjects with different haplotypes. We conclude that this mutation also interferes with expression of wild type allele.

Familial polycythemia caused by a novel mutation in the beta globin gene: essential role of P50 in evaluation of familial polycythemia.

Two polycythemic subjects from a family with multiple polycythemic subjects were evaluated. Estimation of oxygen affinity of Hb from venous blood gas parameters (P50) revealed low P50 suggesting a high affinity Hb variant. Further work up, which included beta globin gene sequencing, revealed a novel mutation changing a codon to the previously reported high affinity Hb - Hb Johnstown (beta 109 Val->Leu). Polycythemic subjects with high affinity Hb variant are asymptomatic with normal life expectancy. Their differentiation from polycythemia vera (PV) is crucial to avoid therapy which is otherwise reserved for PV patients. We provide an electronic version (in Microsoft excel program) of a previously reported mathematical formula for rapid calculation of P50 from venous blood gases. Estimation of P50 is an essential initial step in the evaluation of a subject with personal and family history of polycythemia.

Aggressive management of potential penetrating cardiac injuries.

Since 1970 all patients admitted with penetrating injuries near the cardiac silhouette are transferred immediately to the operating room for resuscitation and evaluation for immediate thoracotomy. The clinical courses of 10 patients with penetrating cardiac injuries treated between 1962 and 1969 were analyzed and compared with those of 33 patients who presented between 1970 and 1977 and were managed more aggressively. Since the institution of this more aggressive policy, overall survival has improved from 20% to 67%. In patients arriving in the emergency room with signs of viability, survival increased from 29% to 76%. Of 53 patients with injuries in the area of the cardiac silhouette, 33 (62%) actually sustained cardiac injury. The high probability of cardiac injury in patients with external wounds in the silhouette and the improved survival rate seen with aggressive surgical therapy justifies the change to this policy.

Nutritional deficiencies and nutritional support therapy in geriatric cancer patients.

Nutritional deficits and their correction were studied in 45 cancer patients (age range, 60--86 years) who were undergoing various modalities of cancer therapy. Their nutritional status was maintained with a variety of commercially available special diets, and serum albumin concentrations were sequentially determined in order to gauge the efficacy of the nutritional support. Serum albumin levels were preserved when nutritional support was employed in surgical therapy. However, patients undergoing palliative chemotherapy or radiotherapy responded only to adequate levels of the standard hospital diet with or without supplements of special enteral diets. In the survivors, albumin levels were maintained; in the nonsurvivors, albumin levels decreased. This group of older patients tolerated nutritional support therapy, especially when it was carefully monitored. Satisfactory nutritional therapy can be achieved by use of appropriate enteral formulas. The method lends itself to adequate management in the outpatient or nursing-home situation during certain phases of cancer.

Plasma amino acid and serum unesterified fatty acid deficits and the effect of nutritional support in chemotherapy treatment.

The deficits in plasma amino acids and serum unesterified fatty acids of cancer patients undergoing chemotherapy and/or radiation therapy were studied to delineate the special requirements of the patients and efficacy of our nutritional therapy. Seven general surgery patients and 13 patients treated by the Head-Neck Service had baseline levels measured as part of their nutritional evaluation prior to surgical treatment of their cancers. Fifteen chemotherapy outpatients maintained on their regular diets had fasting levels analyzed. Twenty-six patients who were admitted for their therapy had their intake of the regular hospital diet supplemented with a low-residue enteral diet formula (Vivonex High Nitrogen Diet); parenteral nutrition was used only if their oral intake was totally inadequate. Baseline and sequential measurements were made of plasma amino acid and serum unesterified fatty acid levels by gas liquid chromatographic techniques. Before operation the patients had normal levels of amino acids except for a significant deficiency of threonine and glycine observed in patients with head-neck tumors. Outpatients with and without hepatic metastases had significantly depressed levels of the essential amino acids valine, leucine, threonine, and methionine and the nonessential amino acids serine, glycine, and proline. The baseline levels of the patients admitted for treatment had similar deficiencies except for more evidence of lysine deficiency. Patients supported with total parenteral nutrition had rapid elevation of the amino acid levels. The patients whose intake was supplemented with the oral diets had improvement in their amino acid levels, but the deficiency in the leucine and threonine fractions persisted up to 4 weeks of therapy. Although the lysine levels were normal when first analyzed, significant differences developed in the patients without hepatic metastases after the start of chemotherapy with return to normal only after chemotherapy was discontinued. Fatty acid levels were not significantly different between the cancer groups except for preoperative elevated oleic acid levels noted in the general surgery tumor group; there were no deficiencies in the essential fatty acids. These studies indicate a need for enteral formulas with adequate branched-chain amino acids and enrichment with threonine and lysine for supplementing the nutrition of the cancer patient who is undergoing chemotherapy.

Two-dimensional phase unwrapping using a minimum spanning tree algorithm.

Phase unwrapping refers to the determination of phase from modulo 2pi data, some of which may not be reliable. In 2D, this is equivalent to confining the support of the phase function to one or more arbitrarily shaped regions. A phase unwrapping algorithm is presented which works for 2D data known only within a set of nonconnected regions with possibly nonconvex boundaries. The algorithm includes the following steps: segmentation to identify connectivity, phase unwrapping within each segment using a Taylor series expansion, phase unwrapping between disconnected segments along an optimum path, and filling of phase information voids. The optimum path for intersegment unwrapping is determined by a minimum spanning tree algorithm. Although the algorithm is applicable to any 2D data, the main application addressed is magnetic resonance imaging (MRI) where phase maps are useful.

Infectious enteritis after intestinal transplantation: incidence, timing, and outcome.

AIM: To review the incidence, timing, and outcome of infectious enteritis after intestinal transplantation (IT). METHOD: A retrospective review of all patients undergoing IT at a single institution between 1991 and 2003 was analyze with standard statistical tools. RESULTS: Among 33 IT recipients, 13 (39%) developed 20 culture- or biopsy-proven episodes of infectious enteritis. The recipient demographics were 77% men and median age 2.6 years. Infections were diagnosed at a median of 76 days (32 to 1800) after IT. There were 14 viral (CMV one, rotavirus eight, adenovirus four, EBV one, three bacterial (Clostridium difficile), and three other infections (Giardia lamblia one, cryptosporidium two). Complete resolution was achieved in 17 (94%) infectious after appropriate antimicrobial or conservative therapy. Interestingly, there were six rejection episodes following infectious enteritis. Grafts were lost to rejection after rotaviral enteritis (n = 1) and adenoviral enteritis misdiagnosed as rejection (n = 1). Patient and graft survival were not adversely affected by infections. CONCLUSIONS: Infectious enteritis occurs frequently after IT. Viral agents are the cause in two-thirds of cases. With supportive care and appropriate treatment, resolution is possible in the majority of cases. Differentiating rejection and infection by histopathology can be difficult.

3,5-Pyrazoledicarboxylic acid monohydrate

In the title compound, C(5)H(4)N(2)O(4).H(2)O, the 3, 5-pyrazoledicarboxylic acid (H(3)pdc) molecules are joined into one-dimensional chains by O-H.O and N-H.O hydrogen bonds, with distances of 2.671 (2) and 2.776 (2) A, respectively. The one-dimensional chains form a three-dimensional structure via O-H.OW and OW-HW.N hydrogen bonds, with distances of 2.597 (3) and 2.780 (3) A, respectively. In addition to the potential for forming open-channel frameworks, access to the six coordination atoms of H(3)pdc can be directly controlled by varying the pH of the reaction environment, allowing further control over the design and synthesis of novel coordination polymers using various metal centers.

Long-term low dose interferon alpha-2b in the treatment of chronic hepatitis B in multi-ethnic patients in Hawaii.

The antiviral and immunomodulatory effects of interferon were assessed in the treatment of chronic hepatitis B in multi-ethnic patients to prevent viral replication and chronic liver damage. Five million units of recombinant interferon alpha-2b were administered three times a week for 48 weeks to a group of 18 chronic active hepatitis B patients. A complete response was defined as seroconversion to anti-HBe and/or loss of HBe antigen. Seroconversion to anti-HBe in 5 of 12 (42%) chronic active hepatitis B patients occurred after 48 weeks of therapy. HBV-DNA decreased to undetectable levels in 8 of 12 (67%) patients. This chronic low-dose interferon administration regimen demonstrated responses comparable to other studies.

The immunologic staging of chronic active hepatitis B patients in Hawaii.

The hepatitis B antigen/antibody levels and natural killer cell activity status of chronic hepatitis B patients identified by the Hawaii State Department of Health were evaluated to select chronically infected hepatitis B patients for interferon therapy and to determine possible immunodeficiencies. The presence of hepatitis Be antigen denotes active replication of the virus. Ninety-five patients were studied: 17/95 (18%) had chronic active hepatitis B, 71/95 (75%) were hepatitis B carriers and 7/95 (7%) had seroconverted. NK activity to the erythroleukemia K562 cell and virus-infected HSV-1 cell of the chronic active and carrier population (P < .05) were lower than that of the control population and those who had spontaneously seroconverted. Of this population 18% were identified with active viral infection and would be candidates for interferon therapy.

Interferon alpha-2b in the treatment of chronic hepatitis C: early experience.

The antiviral and immunomodulatory effects of interferon were assessed in the treatment of chronic Hepatitis C in multi-ethnic patients to prevent viral replication and chronic liver damage. Three million units of recombinant interferon alpha-2b were administered three times a week for 48 weeks to a group of 9 active Hepatitis C patients. A clinical response was defined as normalization of serum ALT values. Serum was frozen and stored for Hepatitis C viral assays. Four patients normalized their liver functions. When viral levels were measured only two patients had unmeasurable levels of HCV RNA after treatment. Therapeutic results were observed and much work needs to be done to improve therapy because a serious epidemic is predicted for the future.