Diabetes care and pregnancy outcomes for women with pregestational diabetes in Ireland.

AIMS: Pre-gestational diabetes mellitus (PGDM) is associated with adverse outcomes. We aimed to examine pregnancies affected by PGDM; report on these pregnancy outcomes and compare outcomes for patients with type 1 versus type 2 diabetes mellitus; compare our findings to published Irish and United Kingdom (UK) data and identify potential areas for improvement. METHODS: Between 2016 and 2018 information on 679 pregnancies from 415 women with type 1 Diabetes Mellitus and 244 women with type 2 diabetes was analysed. Data was collected on maternal characteristics; pregnancy preparation; glycaemic control; pregnancy related complications; foetal and maternal outcomes; unscheduled hospitalisations; congenital anomalies and perinatal deaths. RESULTS: Only 15.9% of women were adequately prepared for pregnancy. Significant deficits were identified in availability and attendance at pre-pregnancy clinic, use of folic acid, attaining appropriate glycaemic targets and appropriate retinal screening. The majority of pregnancies (n = 567, 83.5%) resulted in a live birth but the large number of infants born large for gestational age (LGA) (n = 280, 49.4%), born prematurely <37 weeks and requiring neonatal intensive care unit (NICU) admission continue to be significant issues. CONCLUSIONS: This retrospective cohort study identifies multiple targets for improvements in the provision of care to women with pre-gestational DM which are likely to translate into better pregnancy outcomes.

An Irish National Diabetes in Pregnancy Audit: aiming for best outcomes for women with diabetes.

AIMS: The purpose of this study was to identify the number of pregnancies affected by pre-gestational diabetes in the Republic of Ireland; to report on pregnancy outcomes and to identify areas for improvement in care delivery and clinical outcomes. METHODS: Healthcare professionals caring for women with pre-gestational diabetes during pregnancy were invited to participate in this retrospective study. Data pertaining to 185 pregnancies in women attending 15 antenatal centres nationally were collected and analysed. Included pregnancies had an estimated date of delivery between 1 January and 31 December 2015. RESULTS: The cohort consisted of 122 (65.9%) women with Type 1 diabetes and 56 (30.3%) women with Type 2 diabetes. The remaining 7 (3.8%) pregnancies were to women with maturity-onset diabetes of the young (MODY) (n = 6) and post-transplant diabetes (n = 1). Overall women were poorly prepared for pregnancy and lapses in specific areas of service delivery including pre-pregnancy care and retinal screening were identified. The majority of pregnancies 156 (84.3%) resulted in a live birth. A total of 103 (65.5%) women had a caesarean delivery and 58 (36.9%) infants were large for gestational age. CONCLUSIONS: This audit identifies clear areas for improvement in delivery of care for women with diabetes in the Republic of Ireland before and during pregnancy.

The use of a portable breath analysis device in monitoring type 1 diabetes patients in a hypoglycaemic clamp: validation with SIFT-MS data.

Monitoring blood glucose concentrations is a necessary but tedious task for people suffering from diabetes. It has been noted that breath in people suffering with diabetes has a different odour and thus it may be possible to use breath analysis to monitor the blood glucose concentration. Here, we evaluate the analysis of breath using a portable device containing a single mixed metal oxide sensor during hypoglycaemic glucose clamps and compare that with the use of SIFT-MS described in previously published work on the same set of patients. Outputs from both devices have been correlated with the concentration of blood glucose in eight volunteers suffering from type 1 diabetes mellitus. The results demonstrate that acetone as measured by SIFT-MS and the sensor output from the breath sensing device both correlate linearly with blood glucose; however, the sensor response and acetone concentrations differ greatly between patients with the same blood glucose. It is therefore unlikely that breath analysis can entirely replace blood glucose testing.

A regional pre-pregnancy care (PPC) programme for women with type 1 and type 2 diabetes.

Unfortunately the risks associated with pregnancy in a woman with Diabetes (Type 1 and Type 2) continue to be high. However these risks can be reduced significantly with pregnancy planning and pre-pregnancy care. We report here the establishment of a regional pre pregnancy service and the interim results of its benefits. Pre pregnancy care is as vital as combined diabetes antenatal care for women with diabetes and must become the norm for this population.

Phase I and pharmacokinetic study of carboplatin and paclitaxel with a biweekly schedule in patients with advanced non-small-cell lung cancer.

PURPOSE: A phase I study was conducted to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of carboplatin in combination with paclitaxel using a biweekly schedule in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: The pharmacokinetics of paclitaxel were determined preliminarily in some patients. The criteria for eligibility for study entry included histologically and/or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable disease. Paclitaxel was given in combination with a fixed dose of carboplatin at an area under the concentration-time curve (AUC) of 3 mg/ml x min, every 2 weeks. The starting dose of paclitaxel was 100 mg/m(2), and the dose was increased in increments of 20 mg/m(2). Three to six patients were allocated to each dose level. RESULTS: A total of 19 patients (11 male and 8 female) with a median age of 61 years (range 43-74 years) and a median ECOG performance status of 0 (range 0-1) were enrolled. The MTD of paclitaxel proved to be 160 mg/m(2), and the DLT was neutropenia, which improved well following treatment with G-CSF. Gastrointestinal toxicity was well tolerated. Of 17 patients who received four cycles or more, 7 (41%; 95% confidence interval 18.4-67.1%) responded to this combination therapy. The pharmacokinetics of paclitaxel did not differ from published data. CONCLUSIONS: The recommended dose for phase II study is paclitaxel 140 mg/m(2) with a carboplatin AUC of 3 mg/ml.min. This biweekly regimen is highly effective and acceptable, and the present data indicate that the regimen may be suitable for use on an outpatient basis.

[pncA gene mutations in clinical isolates of tubercle bacillus by polymerase chain reaction-direct sequencing method: in relationship to pyrazinamide resistance].

We screened clinical isolates of tubercle bacillus for mutations in the pncA gene, which encodes pyrazinamidase (PZase), by polymerase chain reaction (PCR)-direct sequencing method. Sixty-eight strains of tubercle bacillus were isolated from 32 patients with pulmonary tuberculosis. The patients were treated with antituberculous agents including pyrazinamide (PZA) for 2 months. Thirty-two of the 68 strains were isolated from sputum samples collected from the patients before treatment; 29 strains and 7 strains were collected after 1 month and 2 months of treatment, respectively. The pncA genes in these strains, were assessed for mutations by direct sequencing of PCR products using an automated sequencer. Similarly, we examined two clinical isolates (ka567 and minami22) of tubercle bacillus, determined to be deficient in PZase activity by the Wayne method. A PZA-sensitive strain (H37Rv, ATCC27294), and a PZA-resistant strain (H37Rv-PZA-R, ATCC35828) were used as negative and positive controls for mutations in the pncA gene, respectively. None of the 68 strains demonstrated any mutations in the pncA gene; however, the 2 PZase-deficient strains had missense mutations in the pncA gene resulting in an amino acid substitution from His82 to Arg in clone ka567, and from Ala171 to Val in clone minami22.

Changes in intramucosal pH and gut blood flow during whole body heating in a porcine model.

Heat stroke is a syndrome which reduces systemic vascular resistance and cardiac collapse. The gut plays an important role in shock. In hyperthermia, many of the same symptoms as heat stroke may be present, including inhibition of splanchnic vasoconstriction and endotoxemia. Furthermore, both conditions result in shock, in which the gut plays an important role. Detection of insufficient oxygenation of gut tissue, which sustains an earlier and more severe hypoxia, can warn of impending shock and can be performed by monitoring intramucosal pH (pHim). This index is very sensitive to tissue hypoxia and ischemia. In the present study both pHim, using tonometry, and gut blood flow during whole body heating (WBH) in pigs were measured. WBH was achieved by circulating warm water through a vinyl sheet covering the animal. Central venous pressure was maintained by fluid infusion. Body temperature was measured using a thermometer probe inserted into the right jugular vein. Mean arterial pressure, cardiac output and gut blood flow were also measured. pHim was evaluated using a tonometer placed into the midileum lumen. During WBH, cardiac index and mean arterial pressure increased, however systemic vascular resistance decreased. Gut blood flow was either maintained at the normal rate or increased. Intraarterial pH did not change significantly, however pHim significantly decreased from 7.30 at the beginning of WBH to approximately 7.05 after the body temperature reached 42.5 degrees C. These findings suggest that there was reduced oxygen delivery to the tips of the small intestinal villi during regional ischemia following WBH. In conclusion, insufficient tissue oxygen delivery as detected by a reduction in inramucosal pH is an important index in whole body heating.

[Lung cancer with a sarcoid-like reaction in the primary tumor].

An 80-year-old woman was admitted to the hospital because of a nodular lesion in the right upper lobe of the lung. Transbronchial biopsy was performed and adenocarcinoma of the lung was confirmed by pathological examination. The tumor was resected by right upper lobectomy and was found to be a moderately differentiated tubular adenocarcinoma. Numerous non-caseating epithelioid cell granulomas were also found intermingled with the cancer cells. Metastasis was apparent in several regional lymph nodes but no granulomatous lesions were found in any lymph node, regardless of metastasis. These findings were compatible with a "sarcoid-like reaction" because there was no clinical evidence of generalized sarcoidosis or pulmonary mycobacterial infection. Although sarcoid-like reactions are occasionally associated with cancer, formation of an epithelioid cell granuloma inside the primary tumor is very rare. All the reported cases of a sarcoid-like reaction within the primary lung tumor so far were with adenocarcinoma. The sarcoid-like reaction may be a local immune response to the cancer cells.

[The influence of the alcohol and the low protein diet on rat pancreas].

We investigated the influence of alcohol and the low protein diet upon rat pancreas. Rats were separated in four groups, 1) Control diet group (Cont), 2) Alcohol diet group (Al), 3) Low protein diet group (Lp), 4) Low protein and alcohol diet group (Lp+Al). They were fed on isocaloric liquid diet compulsorily through the gastric tube. They were sacrificed 3, 6, 12 weeks after. By the light microscopic observation on the rat pancreas which were fed for 12 weeks, lipid droplets in the acinar cells were observed in all groups other than Cont. Apoptosis was founded in Lp and Lp+Al groups. Protein plugs were observed in all groups, and no relation was found between the plugs and the location of the injured acinar cells. By the electromicroscopic observation, in Lp+Al group, acinar cells were typically injured (ER dilation, atrophic nuclei, mitochondria degeneration, etc.) and mesenchymal cells appeared among acinar cells. These results suggest that alcohol causes pancreatic acinar cell injury directly, and relative low protein diet helps to turn it worse.

[Interleukin-6 and glucocorticosteroid responses to cardiopulmonary bypass].

The responses of interleukin-6 (IL-6), ACTH, cortisol, WBC, CRP to cardiopulmonary bypass (CPB) were studied in 5 patients who underwent elective CABG (N = 4) and AVR (N = 1). IL-6 started to increase from 3 h after the beginning of the operation at which aortic clamp was removed and reached a peak after 4 h at which CPB was withdrawn. ACTH also reached a peak after 4 h. The increase of cortisol started from 2 h when aorta was clamped, which was earlier than that of IL-6. IL-6 and ACTH fell sharply to pre-CPB levels before first postoperative day (1 POD) while cortisol remained high postoperatively. CRP level and WBC counts were maximum at 2 POD. The results suggest that the cortisol response to CPB is not only caused by IL-6, but also by other factors, such as IL-1 and TNF.

[Coagulation changes during liver resection].

Thrombin-antithrombin III complex (TAT) and plasminogen activator inhibitor (PAI) were measured during liver resection surgery in 8 patients. TAT and PAI activities of patients under liver resection were compared with those of 11 patients under resection of esophageal carcinoma. TAT activity increased during liver resection (P < 0.001) and reached 14 times (P < 0.001) of its control value in the recovery room. PAI activity was very stable during operation, but increased to twice (P < 0.01) of its control value in the recovery room. TAT activity of patients after liver surgery in the recovery room was (P < 0.05) more than twice of that of patients after esophageal surgery. We conclude that hypercoagulable state occurred during liver resection to a greater degree compared with that observed with esophageal surgery, and that its cause might be liver resection itself.

Interstitial nephritis associated with glomerulonephritis in a patient with Hashimoto's disease and idiopathic portal hypertension.

A middle-aged women with hypothyroidism, idiopathic portal hypertension and nephrotic syndrome is presented. This unusual clinical appearance could not be explained as SLE by serological examinations. Pathohistological examinations showed "Banti's liver", Hashimoto's thyroiditis and diffuse proliferative glomerulonephritis with severe tubulo-interstitial nephritis. Immunohistochemical studies revealed IgA deposits in glomeruli. Electron microscopic study disclosed peculiar lucent areas of rarefaction with osmiophilic particles in tubular basement membranes. This tubulointerstitial nephritis was considered to be related to the immunological mechanism involving thyroid gland, liver and kidney disorders. This case thus had a clinically rare combination of these three.